FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hsu, C Rosenberg, SA Morgan, RA AF Hsu, Cary Rosenberg, Steven A. Morgan, Richard A. TI Clonal Expansion of a CD8+T Cell Clone after Retroviral Transduction of Mature T Lymphocytes with the IL-15 Gene SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Hsu, Cary; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 979 BP S376 EP S377 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502376 ER PT J AU Hu, JQ Ferris, A Krause, A Donahue, RE Hughes, SH Dunbar, CE AF Hu, Jingqiong Ferris, Andrea Krause, Allen Donahue, Robert E. Hughes, Stephen H. Dunbar, Cynthia E. TI Avian Sarcoma Leukosis Virus Vectors Can Transduce Rhesus Macaque HSCs and Result in a Potentially Safer Integration Profile SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Hu, Jingqiong; Krause, Allen; Donahue, Robert E.; Dunbar, Cynthia E.] Lung Inst, Mol Hematopoiesis Sect, Hematol Branch, Bethesda, MD USA. [Ferris, Andrea; Hughes, Stephen H.] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 732 BP S283 EP S283 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502131 ER PT J AU Jones, S Hsu, C Morgan, R Rosenberg, S AF Jones, Stephanie Hsu, Cary Morgan, Richard Rosenberg, Steven TI Genetic Engineering of an Immortal Human CD8+T Cell Line SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Jones, Stephanie; Hsu, Cary; Morgan, Richard; Rosenberg, Steven] NIH, Surg Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 767 BP S297 EP S297 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502166 ER PT J AU Kachapati, K Sachdeva, G Arya, S AF Kachapati, Kritika Sachdeva, Geetanjali Arya, Suresh TI Chimeric Lentiviral Vectors with Safety Insurance SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Kachapati, Kritika; Sachdeva, Geetanjali; Arya, Suresh] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Arya, Suresh] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 471 BP S182 EP S183 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501395 ER PT J AU Kawai, T Choi, U Cardwell, L Deravin, SS Naumann, N Whiting-Theobald, NL Linton, GF Brenner, S Murphy, PM Malech, HL AF Kawai, Toshinao Choi, Uimook Cardwell, Lanise Deravin, Suk See Naumann, Nora Whiting-Theobald, Narda L. Linton, Gilda F. Brenner, Sebastian Murphy, Philip M. Malech, Harry L. TI WHIM Syndrome Type Myelokathexis In Vivo in the NOD/SCID Mouse Model Following Transplant of Healthy Human Stem Cells Transduced with C-Terminus Truncated CXCR4 SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Kawai, Toshinao; Choi, Uimook; Cardwell, Lanise; Deravin, Suk See; Naumann, Nora; Whiting-Theobald, Narda L.; Linton, Gilda F.; Brenner, Sebastian; Murphy, Philip M.; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Brenner, Sebastian] Tech Univ Dresden, Dept Pediat, Univ Clin Carl Gustav Carus, Dresden, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 664 BP S256 EP S256 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502064 ER PT J AU Keiser, NW Maminishkis, A Bennicelli, JL Miller, SS Bennett, J AF Keiser, Nicholas W. Maminishkis, Arvydas Bennicelli, Jeannette L. Miller, Sheldon S. Bennett, Jean TI AAV-Mediated Somatic Gene Transfer as an Approach To Delineate Pathogenic Mechanisms in an Autosomal Dominant Blindness Disorder Resembling Age-Related Macular Degeneration (AMD) SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Keiser, Nicholas W.; Bennicelli, Jeannette L.; Bennett, Jean] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA. [Maminishkis, Arvydas; Miller, Sheldon S.] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 886 BP S341 EP S341 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502284 ER PT J AU Morrison, BJ Tagaya, Y Steel, JC Mannan, P Waldmann, TA Morris, JC Sakai, Y AF Morrison, Brian J. Tagaya, Yutaka Steel, Jason C. Mannan, Poonam Waldmann, Thomas A. Morris, John C. Sakai, Yoshio TI Adenoviral-Mediated Interleukin-15 Receptor-alpha Gene Therapy of Murine Breast Cancer SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Morrison, Brian J.; Tagaya, Yutaka; Steel, Jason C.; Mannan, Poonam; Waldmann, Thomas A.; Morris, John C.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Sakai, Yoshio] Kanazawa Univ, Grad Sch Med Sci, Dept Canc Gene Regulat, Kanazawa, Ishikawa, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 429 BP S165 EP S165 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501353 ER PT J AU Naumann, N De Ravin, SS Moayeri, M Choi, U Ikeda, Y Malech, HL AF Naumann, Nora De Ravin, Suk See Moayeri, Morvarid Choi, Uimook Ikeda, Yasuhiro Malech, Harry L. TI Evaluation of Factors Influencing the Production Titers of SIV-Derived Lentiviral Vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Naumann, Nora; De Ravin, Suk See; Moayeri, Morvarid; Choi, Uimook; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Ikeda, Yasuhiro] Windeyer Inst, Div Infect & Immun, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 468 BP S181 EP S181 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501392 ER PT J AU Naumann, N Choi, U De Ravin, SS Moayeri, M Lantz, L Cardwell-Miller, L Malech, HL AF Naumann, Nora Choi, Uimook De Ravin, Suk See Moayeri, Morvarid Lantz, Larry Cardwell-Miller, Lanise Malech, Harry L. TI SIV-Derived Lentiviral Vectors Pseudotyped with Modified RD114 Envelope and Containing Mutant MGMT Efficiently Transduce Human CD34+PBSCs and Allow Selection SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Naumann, Nora; Choi, Uimook; De Ravin, Suk See; Moayeri, Morvarid; Cardwell-Miller, Lanise; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Lantz, Larry] NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 671 BP S259 EP S259 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502071 ER PT J AU Negrete, A Urabe, MU Kotin, RM AF Negrete, Alejandro Urabe, Masashi Urabe Kotin, Robert M. TI Advances in Large-Scale Production of Recombinant Adeno-Associated Vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Negrete, Alejandro; Kotin, Robert M.] Natl Harth Lung & Blood Inst, NIH, Bethesda, MD USA. [Urabe, Masashi Urabe] Jichi Med Sch, Minami Kawachi, Tochigi 32904, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 505 BP S195 EP S195 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501429 ER PT J AU Nienhuis, AW Gray, JT Vayda, S Cline, A Evans-Galea, MV Bodine, DM AF Nienhuis, Arthur W. Gray, John T. Vayda, Serena Cline, Amanda Evans-Galea, Marguerite V. Bodine, David M. TI Evidence for Correction of Mutations in the c-Kit Gene by rAAV Mediated Gene Targeting in W/W-v Mice SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Nienhuis, Arthur W.; Gray, John T.; Evans-Galea, Marguerite V.] St Jude Childrens Reserach Hosp, Memphis, TN USA. [Vayda, Serena; Cline, Amanda; Bodine, David M.] NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 68 BP S29 EP S29 DI 10.1016/j.ymthe.2006.08.084 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933500069 ER PT J AU Otsu, M Nakajima, S Kida, M Maeyama, Y Toita, N Hatano, N Kawamura, N Kobayashi, R Tatsuzawa, O Onodera, M Candotti, F Bali, P Hershfield, MS Sakiyama, Y Ariga, T AF Otsu, Makoto Nakajima, Satoru Kida, Miyuki Maeyama, Yoshihiro Toita, Nariaki Hatano, Norikazu Kawamura, Nobuaki Kobayashi, Ryouji Tatsuzawa, Osamu Onodera, Masafumi Candotti, Fabio Bali, Pawan Hershfield, Michael S. Sakiyama, Yukio Ariga, Tadashi TI Stem Cell Gene Therapy with No Pre-Conditioning for the ADA-Deficiency Patients Leads to Generalized Detoxification and Delayed, but Steady Hematological Reconstitution SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Otsu, Makoto; Nakajima, Satoru; Kida, Miyuki; Maeyama, Yoshihiro; Toita, Nariaki; Hatano, Norikazu; Kawamura, Nobuaki; Kobayashi, Ryouji; Sakiyama, Yukio; Ariga, Tadashi] Hokkaido Univ, Grad Sch Med, Dept Pediat, Sapporo, Hokkaido, Japan. [Tatsuzawa, Osamu] Natl Ctr Child Hlth & Dev, Tokyo, Japan. [Onodera, Masafumi] Univ Tsukuba, Dept Hematol, Tsukuba, Ibaraki, Japan. [Candotti, Fabio] NIH, GMBB, Bethesda, MD 20892 USA. [Bali, Pawan; Hershfield, Michael S.] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 1088 BP S418 EP S418 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502485 ER PT J AU Puttaraju, M Wang, J Remaley, AT Brewer, BH Garcia-Blanco, MA McGarrity, GJ AF Puttaraju, Madaiah Wang, Jun Remaley, Alan T. Brewer, Bryan H., Jr. Garcia-Blanco, Mariano A. McGarrity, Gerard J. TI Spliceosome Mediated RNA Trans-Splicing To Increase Blood Levels of Apolipoprotein A-I and High Density Lipoproteins SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Puttaraju, Madaiah; Garcia-Blanco, Mariano A.; McGarrity, Gerard J.] Intronn Inc, Dyslipidemia, Gaithersburg, MD USA. [Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA. [Brewer, Bryan H., Jr.] Washington Hosp Ctr, MedStar Res Inst, Washington, DC 20010 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 867 BP S334 EP S334 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502265 ER PT J AU Ryser, MF Gentsch, M Ugarte, F Malech, HL Brenner, S AF Ryser, Martin F. Gentsch, Marcus Ugarte, Fernando Malech, Harry L. Brenner, Sebastian TI mRNA Transfection Results in Efficient Overexpression of Transgenes in Leukemic Cell Lines and Hematopoietic Stem Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Ryser, Martin F.; Gentsch, Marcus; Ugarte, Fernando; Brenner, Sebastian] Univ Clin Dresden, Dept Pediat, Dresden, Germany. [Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 514 BP S198 EP S198 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501438 ER PT J AU Ryu, BY Gray, JT Bodine, DM Nienhuis, AW AF Ryu, Byoung Y. Gray, John T. Bodine, David M. Nienhuis, Arthur W. TI Activation of the LMO2 Gene in Human Lymphoid Cells by rAAV-Mediated Targeted Insertion of a Single LTR Expression Cassette into the First Intron SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Ryu, Byoung Y.; Gray, John T.; Nienhuis, Arthur W.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Bodine, David M.] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 102 BP S42 EP S42 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501026 ER PT J AU Schmidt, M Voutetakis, A Afione, S Zheng, CY Chiorini, JA AF Schmidt, Michael Voutetakis, Antonis Afione, Sandra Zheng, Changyu Chiorini, John A. TI AAV12, Isolated from Vervet Monkey, Has Unique Tropism and Biological as Well as Neutralization Properties SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Schmidt, Michael; Voutetakis, Antonis; Afione, Sandra; Zheng, Changyu; Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 745 BP S288 EP S288 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502144 ER PT J AU Steel, JC Morrison, BJ Mannan, P Prince, GA Yim, KC Miles, BK Wildner, O Morris, JC AF Steel, Jason C. Morrison, Brian J. Mannan, Poonam Prince, Gregory A. Yim, Kevin C. Miles, Brian K. Wildner, Oliver Morris, John C. TI Syngeneic Cotton Rat Cancer Model for Replicating Adenoviral Vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Steel, Jason C.; Morrison, Brian J.; Mannan, Poonam; Morris, John C.] NCI, Metab Branch, Canc Gene Therapy Sect, Bethesda, MD 20892 USA. [Prince, Gregory A.; Yim, Kevin C.; Miles, Brian K.] Vir Syst, Rockville, MD USA. [Wildner, Oliver] Ruhr Univ Bochum, Bochum, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 322 BP S123 EP S123 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501246 ER PT J AU Therrien, JP Tock, CL Vogel, JC AF Therrien, Jean-Philippe Tock, Christine L. Vogel, Jonathan C. TI Development of Human Skin Gene Therapy for Systemic In Vivo Delivery of Atrial Natriuretic Peptide (ANP) To Treat Hypertension SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Therrien, Jean-Philippe; Tock, Christine L.; Vogel, Jonathan C.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 875 BP S337 EP S337 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502273 ER PT J AU Voutetakis, A Zheng, C Chiorini, JA Schmidt, M Afione, S Metzger, M Dunbar, C Donahue, RE Baum, BJ AF Voutetakis, A. Zheng, C. Chiorini, J. A. Schmidt, M. Afione, S. Metzger, M. Dunbar, C. Donahue, R. E. Baum, B. J. TI Administration of rAAV2 and rAAV5 to the Parotid Gland of Non-Human Primates SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Voutetakis, A.; Zheng, C.; Chiorini, J. A.; Schmidt, M.; Afione, S.; Baum, B. J.] NIDCR, GTTB, NIH, Bethesda, MD USA. [Metzger, M.; Dunbar, C.; Donahue, R. E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 674 BP S260 EP S260 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502074 ER PT J AU Weller, ML Maki, CJ Stone, IM Poulsen, DJ AF Weller, Melodie L. Maki, Christopher J. Stone, Ida M. Poulsen, David J. TI Selective Targeting of GABAergic Neurons Using rAAV: The Potential Role of EAAC1 in Seizure Susceptibility SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Weller, Melodie L.; Maki, Christopher J.; Stone, Ida M.; Poulsen, David J.] Univ Montana, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA. [Weller, Melodie L.; Poulsen, David J.] Univ Montana, COBRE Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 894 BP S344 EP S345 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502292 ER PT J AU Wu, XL He, WJ Burgess, SM Clark, RA Li, SL AF Wu, Xiaolin He, Weijing Burgess, Shawn M. Clark, Robert A. Li, Senlin TI Lentiviral Vector Integration in Mouse Bone Marrow Stem Cells Undergoing Gene Therapy SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 UTHSCSA, San Antonio, TX USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 358 BP S136 EP S136 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501282 ER PT J AU Zhao, YB Zheng, ZL Cohen, CJ Rosenberg, SA Morgan, RA AF Zhao, Yangbing Zheng, Zhili Cohen, Cyrille J. Rosenberg, Steven A. Morgan, Richard A. TI Recognition of Tumor Antigens by In Vitro Developed T Cells from Hematopoietic Stem Cells Retrovirally Transduced with TCR Genes SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Zhao, Yangbing; Zheng, Zhili; Cohen, Cyrille J.; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 454 BP S175 EP S175 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501378 ER PT J AU Zheng, CY Baum, BJ AF Zheng, Changyu Baum, Bruce J. TI Effect on Expression of Including Binding Sites for the ELAV-Like Proteins HuD and HuR in Transgene Cassettes SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Zheng, Changyu; Baum, Bruce J.] NIDCR, GTTB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 1006 BP S387 EP S388 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502403 ER PT J AU Zhou, BY Ye, ZH Gao, P Cheng, LZ AF Zhou, Betty Y. Ye, Zhaohui Gao, Peter Cheng, Linzhao TI Inducible and Reversible Transgene Expression in Human Stem Cells Stably Transduced by Novel Lentiviral Vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Zhou, Betty Y.; Ye, Zhaohui; Cheng, Linzhao] Johns Hopkins Univ, Inst Cell Engn, Baltimore, MD USA. [Gao, Peter] NINDS, Neurooncol Branch, NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 100 BP S41 EP S41 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501024 ER PT J AU Fu, HQ Wang, LX Lin, CM Singhania, S Bouhassira, EE Aladjem, MI AF Fu, HQ Wang, LX Lin, CM Singhania, S Bouhassira, EE Aladjem, MI TI Preventing gene silencing with human replicators SO NATURE BIOTECHNOLOGY LA English DT Article ID BETA-GLOBIN LOCUS; DNA-REPLICATION; CONTROL REGION; ORIGIN; INITIATION; METHYLATION; EXPRESSION; CHROMATIN; CELLS; INACTIVATION AB Transcriptional silencing, one of the major impediments to gene therapy in humans, is often accompanied by replication during late S-phase. We report that transcriptional silencing and late replication were prevented by DNA sequences that can initiate DNA replication (replicators). When replicators were included in silencing-prone transgenes, they did not undergo transcriptional silencing, replicated early and maintained histone acetylation patterns characteristic of euchromatin. A mutant replicator, which could not initiate replication, could not prevent gene silencing and replicated late when included in identical transgenes and inserted at identical locations. These observations suggest that replicators introduce epigenetic chromatin changes that facilitate initiation of DNA replication and affect gene silencing. Inclusion of functional replicators in gene therapy vectors may provide a tool for stabilizing gene expression patterns. C1 NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA. RP Aladjem, MI (reprint author), NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. EM aladjemm@mail.nih.gov RI Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 FU Intramural NIH HHS; NHLBI NIH HHS [P01 HL55435]; NIDDK NIH HHS [R01 DK56845] NR 35 TC 29 Z9 29 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 2006 VL 24 IS 5 BP 572 EP 576 DI 10.1038/nbt1202 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 039TX UT WOS:000237331300033 PM 16604060 ER PT J AU Hinshaw, JE AF Hinshaw, JE TI Filling the GAP for dynamin SO NATURE CELL BIOLOGY LA English DT Editorial Material ID RECEPTOR-MEDIATED ENDOCYTOSIS; PHOSPHOLIPASE-D; CONSTRICTION; DOMAIN AB Endocytosis in eukaryotic cells involves numerous specialized protein complexes and lipid domains. One particularly intriguing protein is dynamin, a large GTPase that is very different from other GTPases. Now, phospholipase D has been identified as surprising regulator of dynamin's GTPase activity. C1 NIDDK, Lab Cell Biochem & Biol, NIH, Rockville, MD 20852 USA. RP Hinshaw, JE (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, 8 Ctr Dr, Rockville, MD 20852 USA. EM jennyh@helix.nih.gov NR 8 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAY PY 2006 VL 8 IS 5 BP 432 EP 433 DI 10.1038/ncb0506-432 PG 2 WC Cell Biology SC Cell Biology GA 039IO UT WOS:000237299400005 PM 16691207 ER PT J AU Blair-Levy, JM AF Blair-Levy, JM TI Carbonated apatite-induced arthropathy: a consideration in cases of polyarthritis SO NATURE CLINICAL PRACTICE RHEUMATOLOGY LA English DT Article DE atomic force microscopy; basic calcium phosphates; carbonated apatite; crystal-induced arthritis; electron microprobe ID BASIC CALCIUM-PHOSPHATE; SYNOVIAL-FLUID; CRYSTAL DEPOSITION; IDENTIFICATION; INFLAMMATION; FIBROBLASTS; MITOGENESIS; INDUCTION; ARTHRITIS; DISEASE AB Background A 79-year-old woman was referred for evaluation of her painful and swollen joints. She had a medical history of congestive heart failure, renal insufficiency and peptic ulcer disease. For the past 3 years she had experienced recurrent bouts of debilitating arthritis, lasting approximately 3-4 weeks at a time. The symptoms were most severe in the hands and knees, where the joints were warm, swollen and tender. During each flare-up, the patient was housebound and required therapeutic dosing of nonsteroidal anti-inflammatory drugs and codeine to control joint pain. Investigations Physical examination, fine-detailed radiographs of the hands, standing radiographs of the knees, arthrocentesis including cell count and gram stain, compensated polarized light microscopy, alizarin-red staining, X-ray diffraction, scanning and transmission electron microscopy with energy dispersive spectrometry, electron microprobe analysis with energy dispersive spectrometry, Fourier transform infrared spectroscopy, and atomic force microscopy. Diagnosis Carbonated-substituted apatite arthropathy. Management Both knees were aspirated and large volumes of a straw-colored synovial fluid was removed. The knees were injected with corticosteroid, resulting in excellent symptomatic response. C1 NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Blair-Levy, JM (reprint author), 9 Ctr Dr,Bldg 9-B1E10 MC 0903, Bethesda, MD 20892 USA. EM blairj1@mail.nih.gov NR 21 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8382 J9 NAT CLIN PRACT RHEUM JI Nat. Clin. Pract. Rheumatol. PD MAY PY 2006 VL 2 IS 5 BP 278 EP 283 DI 10.1038/ncprheum0174 PG 6 WC Rheumatology; Social Issues SC Rheumatology; Social Issues GA 036SO UT WOS:000237095900007 PM 16932701 ER PT J AU Staton, TL Habtezion, A Winslow, MM Sato, T Love, PE Butcher, EC AF Staton, TL Habtezion, A Winslow, MM Sato, T Love, PE Butcher, EC TI CD8(+) recent thymic emigrants home to and efficiently repopulate the small intestine epithelium SO NATURE IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; INTRAEPITHELIAL LYMPHOCYTES; RHODAMINE ISOTHIOCYANATE; MUCOSAL LYMPHOCYTES; EXCISION CIRCLES; LYMPHOID ORGANS; DENDRITIC CELLS; GUT EPITHELIUM; IN-VIVO; MICE AB Prevailing knowledge dictates that naive ab T cells require activation in lymphoid tissues before differentiating into effector or memory T cells capable of trafficking to nonlymphoid tissues. Here we demonstrate that CD8(+) recent thymic emigrants (RTEs) migrated directly into the small intestine. CCR9, CCL25 and alpha(4)beta(7) integrin were required for gut entry of CD8(+) RTEs. After T cell receptor stimulation, intestinal CD8+ RTEs proliferated and acquired a surface phenotype resembling that of intraepithelial lymphocytes. CD8(+) RTEs efficiently populated the gut of lymphotoxin-alpha-deficient mice, which lack lymphoid organs. These studies challenge the present understanding of naive alpha beta T cell trafficking and suggest that RTEs may be involved in maintaining a diverse immune repertoire at mucosal surfaces. C1 Stanford Univ, Sch Med, Program Immunol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Pathol, Lab Immunol & Vasc Biol, Stanford, CA 94305 USA. Vet Affairs Palo Alto Hlth Care Syst, Ctr Mol Biol & Med, Palo Alto, CA 94304 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Butcher, EC (reprint author), Stanford Univ, Sch Med, Program Immunol, Stanford, CA 94305 USA. EM ebutcher@stanford.edu FU NIAID NIH HHS [T32 AI007290, AI47822]; NIDDK NIH HHS [DK56339, DK07056, DK060000]; NIGMS NIH HHS [GM37734] NR 49 TC 63 Z9 66 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2006 VL 7 IS 5 BP 482 EP 488 DI 10.1038/ni1319 PG 7 WC Immunology SC Immunology GA 035NT UT WOS:000237008800013 PM 16582913 ER PT J AU Plant, K Pelkey, KA Bortolotto, ZA Morita, D Terashima, A McBain, CJ Collingridge, GL Isaac, JTR AF Plant, K Pelkey, KA Bortolotto, ZA Morita, D Terashima, A McBain, CJ Collingridge, GL Isaac, JTR TI Transient incorporation of native GluR2-lacking AMPA receptors during hippocampal long-term potentiation SO NATURE NEUROSCIENCE LA English DT Article ID CALCIUM-PERMEABLE AMPA; SUBUNIT COMPOSITION; PYRAMIDAL NEURONS; RECTIFICATION; SWITCH; TRAFFICKING; SYNAPSES; SUBTYPE; BLOCK; LTP AB Postnatal glutamatergic principal neuron synapses are typically presumed to express only calcium-impermeable (CI), GluR2-containing AMPARs under physiological conditions. Here, however, we demonstrate that long-term potentiation (LTP) in CA1 hippocampal pyramidal neurons causes rapid incorporation of GluR2-lackingcalcium-permeable (CP)AMPARs: CP-AMPARs are present transiently, being replaced by GluR2-containing AMPARs similar to 25 min after LTP induction. Thus, CP-AMPARs are physiologically expressed at CA1 pyramidal cell synapses during LTP, and may be required for LTP consolidation. C1 Univ Bristol, Sch Med Sci, MRC, Ctr Synapt Plast, Bristol BS8 1TD, Avon, England. NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. NINDS, Dev Synapt Plast Unit, NIH, Bethesda, MD 20892 USA. RP Isaac, JTR (reprint author), Univ Bristol, Sch Med Sci, MRC, Ctr Synapt Plast, Bristol BS8 1TD, Avon, England. EM isaacj@ninds.nih.gov RI Collingridge, Graham/C-4605-2015 OI Collingridge, Graham/0000-0002-9572-5359 FU Intramural NIH HHS; Medical Research Council [G9532377]; Wellcome Trust NR 15 TC 268 Z9 281 U1 2 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2006 VL 9 IS 5 BP 602 EP 604 DI 10.1038/nn1678 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 040YI UT WOS:000237417200008 PM 16582904 ER PT J AU Gattinoni, L Powell, DJ Rosenberg, SA Restifo, NP AF Gattinoni, L Powell, DJ Rosenberg, SA Restifo, NP TI Adoptive immunotherapy for cancer: building on success SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID CD8(+) T-CELLS; VERSUS-HOST-DISEASE; TUMOR-INFILTRATING LYMPHOCYTES; TOTAL-BODY IRRADIATION; NATURAL-KILLER-CELLS; IN-VIVO PERSISTENCE; LONG-TERM SURVIVAL; METASTATIC MELANOMA; TRANSFER THERAPY; ANTITUMOR IMMUNITY AB Adoptive cell transfer after host preconditioning by lymphodepletion represents an important advance in cancer immunotherapy. Here, we describe how a lymphopaenic environment enables tumour-reactive T cells to destroy large burdens of metastatic tumour and how the state of differentiation of the adoptively transferred T cells can affect the outcome of treatment. We also discuss how the translation of these new findings might further improve the efficacy of adoptive cell transfer through the use of vaccines, haematopoietic-stem-cell transplantation, modified preconditioning regimens, and alternative methods for the generation and selection of the T cells to be transferred. C1 NCI, Mark O Hatfield Clin Res Ctr, NIH, Bethesda, MD 20892 USA. RP Gattinoni, L (reprint author), NCI, Mark O Hatfield Clin Res Ctr, NIH, Room 3-5762,10 Ctr Dr, Bethesda, MD 20892 USA. EM gattinol@mail.nih.gov; restifo@nih.gov RI Gattinoni, Luca/A-2281-2008; Restifo, Nicholas/A-5713-2008; OI Gattinoni, Luca/0000-0003-2239-3282; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 141 TC 541 Z9 570 U1 7 U2 76 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD MAY PY 2006 VL 6 IS 5 BP 383 EP 393 DI 10.1038/nri1842 PG 11 WC Immunology SC Immunology GA 036UI UT WOS:000237100800012 PM 16622476 ER PT J AU Meyer-Lindenberg, A Mervis, CB Berman, KF AF Meyer-Lindenberg, A Mervis, CB Berman, KF TI Neural mechanisms in Williams syndrome: a unique window to genetic influences on cognition and behaviour SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID SUPRAVALVULAR AORTIC STENOSIS; BEUREN-SYNDROME DELETION; SYNDROME CRITICAL REGION; SOCIAL-BEHAVIOR; CHROMOSOME 7Q11.23; FUNCTIONAL NEUROANATOMY; VISUOSPATIAL COGNITION; TRANSCRIPTION FACTOR; MENTAL-RETARDATION; ADAPTIVE-BEHAVIOR AB Williams syndrome, a rare disorder caused by hemizygous microdeletion of about 28 genes on chromosome 7q11.23, has long intrigued neuroscientists with its unique combination of striking behavioural abnormalities, such as hypersociability, and characteristic neurocognitive profile. Williams syndrome, therefore, raises fundamental questions about the neural mechanisms of social behaviour, the modularity of mind and brain development, and provides a privileged setting to understand genetic influences on complex brain functions in a 'bottom-up' way. We review recent advances in uncovering the functional and structural neural substrates of Williams syndrome that provide an emerging understanding of how these are related to dissociable genetic contributions characterized both in special participant populations and animal models. C1 NIMH, Unit Syst Neurosci Psychiat, DHHS, NIH, Bethesda, MD 20892 USA. NIMH, Neuroimaging Core Facil, DHHS, NIH, Bethesda, MD 20892 USA. NIMH, Genes Cognit & Psychosis Program, DHHS, NIH, Bethesda, MD 20892 USA. NIMH, Sect Integrat Neuroimaging, DHHS, NIH, Bethesda, MD 20892 USA. Univ Louisville, Dept Psychol & Brain Sci, Neurodev Sci Lab, Louisville, KY 40292 USA. RP Meyer-Lindenberg, A (reprint author), NIMH, Unit Syst Neurosci Psychiat, DHHS, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM andreasml@nih.gov OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 FU Intramural NIH HHS; NINDS NIH HHS [R01 NS035102] NR 169 TC 200 Z9 208 U1 8 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD MAY PY 2006 VL 7 IS 5 BP 380 EP 393 DI 10.1038/nrn1906 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 036LM UT WOS:000237072600016 PM 16760918 ER PT J AU Wan, XL Shen, N Mendoza, A Khanna, C Helman, LJ AF Wan, Xiaolin Shen, Na Mendoza, Arnulfo Khanna, Chand Helman, Lee J. TI CCl-779 inhibits rhabdomyosarcoma xenograft growth by an antiangiogenic mechanism linked to the targeting of mTOR/Hif-1 alpha/VEGF signaling SO NEOPLASIA LA English DT Article DE CCl-779; mTOR; Hif-1 alpha; VEGF; rhabdomyosarcoma xenografts ID SOFT-TISSUE SARCOMA; P70 S6 KINASE; TUMOR-GROWTH; CANCER-THERAPY; CELL-GROWTH; FACTOR-II; RAPAMYCIN; ANGIOGENESIS; PATHWAY; EXPRESSION AB Angiogenesis is one of the critical steps in tumor growth and metastasis. The goal of this study was to evaluate whether the antitumor activity of CCI-779 is related to antiangiogenic effects in vivo in tumors of mice bearing human rhabdomyosarcoma (RMS) xenografts. We now demonstrate that CCI-779 rapidly inhibits mTOR activity, as indicated by S6 reduction and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation in two xenograft models of RMS within 24 hours of treatment. Treatment with a single 20-mg/kg dose of CCI-779 suppressed S6 phosphorylation for more than 72 hours and 4E-BP1 phosphorylation for more than 96 hours. Based on these data, an intermittent treatment schedule (every 3 days for 30 days) was chosen and displayed a significant suppression of both tumor growth and mTOR signaling. Western blot analysis and immunohistochemical studies demonstrated that the antitumor activity of CCI-779 was associated with antiangiogenesis, as indicated by impaired levels of hypoxia-inducible factor-1 alpha (Hif-1 alpha) and vascular endothelial growth factor (VEGF) protein expression and by decreased microvessel density in Rh30 and RD xenografts. Together, these data suggest that CCI-779 inhibits human RMS xenograft growth by an antiangiogenic mechanism associated with the targeting of mTOR/Hif-1 alpha/VEGF signaling. C1 NCI, Mol Oncol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Wan, XL (reprint author), NCI, Mol Oncol Sect, Pediat Oncol Branch, NIH, Bldg 10,Room CRC-1W-3750, Bethesda, MD 20892 USA. EM xiaolinw@mail.nih.gov FU Intramural NIH HHS NR 47 TC 107 Z9 116 U1 0 U2 4 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD MAY PY 2006 VL 8 IS 5 BP 394 EP 401 DI 10.1593/neo.05820 PG 8 WC Oncology SC Oncology GA 067DX UT WOS:000239283000007 PM 16790088 ER PT J AU Momeni, P Cairns, NJ Perry, RH Bigio, EH Gearing, M Singleton, AB Hardy, J AF Momeni, Parastoo Cairns, Nigel J. Perry, Robert H. Bigio, Eileen H. Gearing, Marla Singleton, Andrew B. Hardy, John TI Mutation analysis of patients with neuronal intermediate filament inclusion disease (NIFID) SO NEUROBIOLOGY OF AGING LA English DT Article DE Frontotemporal dementia; Neural aggregates; Mutation analysis; Neurofilament light chain (NFL); Neurofilament medium chain (NFM); Neurofilament; heavy chain (NFH); Super oxide dismutase 1 (SOD1); alpha-Internexin; NUDEL AB Abnormal neuronal aggregates of alpha-internexin and the three neurofilament (NF) subunits, NFL, NFM, and NFH have recently been identified as the signature lesions of neuronal intermediate filament (IF) inclusion disease (NIFID), a novel neurological disease of early onset with a variable clinical phenotype including frontotemporal dementia, pyramidal and extrapyramidal signs. In other neurodegenerative diseases in which protein aggregates contribute to disease pathogenesis, mutations in the encoding protein cause the hereditary variant of the disease. To determine the molecular genetic contribution to this disease we performed a mutation analysis of all type IV neuronal IF, SOD1 and NUDEL genes in cases of NIFID and unaffected control cases. We found no pathogenic variants. (C) 2005 Elsevier Inc. All rights reserved. C1 [Momeni, Parastoo; Singleton, Andrew B.; Hardy, John] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Cairns, Nigel J.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Perry, Robert H.] Newcastle Gen Hosp, Dept Neuropathol, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. [Bigio, Eileen H.] Northwestern Univ, Sch Med, Dept Neuropathol, Chicago, IL USA. [Gearing, Marla] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. RP Momeni, P (reprint author), NIA, Neurogenet Lab, Porter Neurosci Bldg,Bldg 35,Room 1A1010,35 Conve, Bethesda, MD 20892 USA. EM momeni@mail.nih.gov RI Singleton, Andrew/C-3010-2009 NR 12 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY PY 2006 VL 27 IS 5 AR 778.e1 DI 10.1016/j.neurobiolaging.2005.03.030 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA V28CF UT WOS:000208658200004 PM 16005115 ER PT J AU Malkani, R D'Souza, I Gwinn-Hardy, K Scheenberg, GD Hardya, J Momeni, P AF Malkani, R D'Souza, I Gwinn-Hardy, K Scheenberg, GD Hardya, J Momeni, P TI A MAPT mutation in a regulatory element upstream of exon 10 causes frontotemporal dementia SO NEUROBIOLOGY OF DISEASE LA English DT Article DE MAPT; frontotemporal dementia; splicing ID TAU; CHROMOSOME-17; ASSOCIATION; EXPRESSION; GENE AB We report here the genetic analysis of a newly ascertained kindred in which frontotemporal dementia occurs in an apparent autosomal dominant fashion, and in which a novel MAPT gene mutation cosegregates with disease. Sequencing the MAPT gene in affected individuals revealed a change in intron 9. This finding supports earlier studies on the effect of a splice-accepting element in inclusion of exon 10 in the MAPT transcript. This mutation sheds light on a novel mechanism by which over-expression of 4-repeat tau leads to disease. Based on our current findings, we propose a novel mechanism by which intronic mutations can lead to frontotemporal dementia. (c) 2005 Elsevier Inc. All rights reserved. C1 Natl Inst Aging, Lab Neurogenet, Bethesda, MD 20892 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. Natl Inst Neurol Disorders & Stroke, Neurogenet Cluster, Bethesda, MD 20892 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. RP Momeni, P (reprint author), Natl Inst Aging, Lab Neurogenet, Porter Neurosci Bldg,35,Convent Dr, Bethesda, MD 20892 USA. EM momeni@mail.nih.gov RI Gwinn, Katrina/C-2508-2009; Hardy, John/C-2451-2009 FU Intramural NIH HHS; Medical Research Council [G0701075]; NIA NIH HHS [R01 AG1176] NR 9 TC 19 Z9 20 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD MAY PY 2006 VL 22 IS 2 BP 401 EP 403 DI 10.1016/j.nbd.2005.12.001 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 040KS UT WOS:000237378000019 PM 16503405 ER PT J AU Betarbet, R Canet-Aviles, RA Sherer, TB Mastroberardino, PG McLendon, C Kim, JH Lund, S Na, HM Taylor, G Bence, NF Kopito, R Seo, BB Yagi, T Klinefelter, G Cookson, MR Greenamyre, JT AF Betarbet, R Canet-Aviles, RA Sherer, TB Mastroberardino, PG McLendon, C Kim, JH Lund, S Na, HM Taylor, G Bence, NF Kopito, R Seo, BB Yagi, T Klinefelter, G Cookson, MR Greenamyre, JT TI Intersecting pathways to neurodegeneration in Parkinson's disease: Effects of the pesticide rotenone on DJ-1, alpha-synuclein, and the ubiquitin-proteasome system SO NEUROBIOLOGY OF DISEASE LA English DT Article DE mitochondria; oxidative stress; pesticide; proteasomal dysfunction; alpha-tocopherol ID OXIDOREDUCTASE NDI1 GENE; MITOCHONDRIAL COMPLEX-I; SUBSTANTIA-NIGRA; OXIDATIVE STRESS; SACCHAROMYCES-CEREVISIAE; 20S PROTEASOME; PROTEIN LIGASE; ANIMAL-MODELS; UP-REGULATION; LEWY BODIES AB Sporadic Parkinson's disease (PD) is most likely caused by a combination of environmental exposures and genetic susceptibilities, although there are rare monogenic forms of the disease. Mitochondrial impairment at complex I, oxidative stress, alpha-synuclein aggregation, and dysfunctional protein degradation, have been implicated in PD pathogenesis, but how they are related to each other is unclear. To further evaluated PD pathogenesis here, we used in vivo and in vitro models of chronic low-grade complex I inhibition with the pesticide rotenone. Chronic rotenone exposure in vivo caused oxidative modification of DJ-1, accumulation of alpha-synuclein, and proteasomal impairment. Interestingly, the effects become more regionally restricted such that systemic complex I inhibition eventually results in highly selective degeneration of the nigrostriatal pathway. DJ-1 modifications, alpha-synuclein accumulation, and proteasomal dysfunction were also seen in vitro and these effects could be prevented with et-tocopherol. Thus, chronic exposure to a pesticide and mitochondrial toxin brings into play three systems, DJ-1, alpha-synuclein, and the ubiquitin-proteasome system, and implies that mitochondrial dysfunction and oxidative stress link environmental and genetic forms of the disease. (c) 2005 Elsevier Inc. All rights reserved. C1 Emory Univ, Ctr Neurodegerat Dis, Atlanta, GA 30322 USA. NIA, Lab Neurogenet, Bethesda, MD 20892 USA. Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. Scripps Res Inst, Dept Mol & Expt Med, Div Biochem, La Jolla, CA 92037 USA. US EPA, ORD, NHEERL, Reprod Toxicol Div, Res Triangle Pk, NC 27711 USA. Univ Pittsburgh, Pittsburgh Inst Neurodegenerat Dis, Pittsburgh, PA 15213 USA. RP Betarbet, R (reprint author), Emory Univ, Ctr Neurodegerat Dis, Whitehead Biomed Res Bldg 615 Michael St, Atlanta, GA 30322 USA. EM rbetarb@emory.edu RI Greenamyre, J. Timothy/B-4049-2011; Mastroberardino, Pier /D-5623-2009 FU NIEHS NIH HHS [ES012068] NR 78 TC 173 Z9 181 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD MAY PY 2006 VL 22 IS 2 BP 404 EP 420 DI 10.1016/j.nbd.2005.12.003 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 040KS UT WOS:000237378000020 PM 16439141 ER PT J AU Yin, HH Zhuang, XX Balleine, BW AF Yin, HH Zhuang, XX Balleine, BW TI Instrumental learning in hyperdopaminergic mice SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Article DE dopamine; dopamine transporter; learning; instrumental conditioning; operant; inhibitory control ID MIDBRAIN DOPAMINE NEURONS; DORSOLATERAL STRIATUM; DORSOMEDIAL STRIATUM; DOUBLE DISSOCIATION; NUCLEUS-ACCUMBENS; HABIT FORMATION; MEMORY-SYSTEMS; REWARD SIGNAL; WATER MAZE; LESIONS AB In two experiments we investigated the effects of elevated dopaminergic tone on instrumental learning and performance using dopamine transporter knockdown (DAT KD) mice. In Experiment 1, we showed that both DAT KD mice and wild-type controls were similarly sensitive to outcome devaluation induced by sensory specific satiety, indicating normal action-outcome learning in both groups. In Experiment 2, we used a Pavlovian-to-instrumental transfer procedure to assess the potentiation of instrumental responding by Pavlovian conditional stimuli (CS). Although during the Pavlovian training phase the DAT KID mice entered the food magazine more frequently in the absence of the CS, when tested later both groups showed outcome-selective PIT. These results suggest that the elevated dopaminergic tone reduced the selectivity of stimulus control over conditioned behavior, but did not affect instrumental learning. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Chicago, Dept Neurobiol Pharmacol & Physiol, Chicago, IL 60637 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90092 USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90092 USA. RP Yin, HH (reprint author), NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, Bethesda, MD 20892 USA. EM yinh@mail.nih.gov FU NIMH NIH HHS [MH56446, MH66216] NR 38 TC 37 Z9 37 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 1074-7427 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD MAY PY 2006 VL 85 IS 3 BP 283 EP 288 DI 10.1016/j.nlm.2005.12.001 PG 6 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 041DN UT WOS:000237433700010 PM 16423542 ER PT J AU Baker, PE Kearney, JA Gong, B Merriam, AP Kuhn, DE Porter, JD Rafael-Fortney, JA AF Baker, PE Kearney, JA Gong, B Merriam, AP Kuhn, DE Porter, JD Rafael-Fortney, JA TI Analysis of gene expression differences between utrophin/dystrophin-deficient vs mdx skeletal muscles reveals a specific upregulation of slow muscle genes in limb muscles SO NEUROGENETICS LA English DT Article DE muscular dystrophy; dystrophin; Myh7; Myl2; myosin heavy chain; myosin light chain ID DUCHENNE MUSCULAR-DYSTROPHY; MICE LACKING UTROPHIN; HEAVY-CHAIN GENE; NEUROMUSCULAR-JUNCTION; BETA-DYSTROGLYCAN; PROTEIN COMPLEX; BINDING-SITE; F-ACTIN; MOUSE; MUTATION AB Dystrophin deficiency leads to the progressive muscle wasting disease Duchenne muscular dystrophy (DMD). Dystrophin-deficient mdx mice are characterized by skeletal muscle weakness and degeneration but they appear outwardly normal in contrast to DMD patients. Mice lacking both dystrophin and the dystrophin homolog utrophin [double knockout (dko)] have muscle degeneration similar to mdx mice, but they display clinical features similar to DMD patients. Dko limb muscles also lack postsynaptic membrane folding and display fiber-type abnormalities including an abundance of phenotypically oxidative muscle fibers. Extraocular muscles, which are spared in mdx mice, show a significant pathology in dko mice. In this study, microarray analysis was used to characterize gene expression differences between mdx and dko tibialis anterior and extraocular skeletal muscles in an effort to understand the phenotypic differences between these two dystrophic mouse models. Analysis of gene expression differences showed that upregulation of slow muscle genes specifically characterizes dko limb muscle and suggests that upregulation of these genes may directly account for the more severe phenotype of dko mice. To investigate whether any upregulation of slow genes is retained in vitro, independent of postsynaptic membrane abnormalities, we derived mdx and dko primary myogenic cultures and analyzed the expression of Myh7 and Myl2. Real-time reverse transcriptase-polymerase chain reaction analysis demonstrates that transcription of these slow genes is also upregulated in dko vs mdx myotubes. This data suggests that at least part of the fiber-type abnormality is due directly to the combined absence of utrophin and dystrophin and is not an indirect effect of the postsynaptic membrane abnormalities. C1 Ohio State Univ, Coll Med, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. NINDS, NSC, Bethesda, MD USA. RP Rafael-Fortney, JA (reprint author), Ohio State Univ, Coll Med, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. EM rafael-fortney.1@osu.edu RI Rafael-Fortney, Jill/E-3909-2011 FU NEI NIH HHS [R01 EY12779]; NIAMS NIH HHS [AR47034-S] NR 52 TC 16 Z9 17 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1364-6745 J9 NEUROGENETICS JI Neurogenetics PD MAY PY 2006 VL 7 IS 2 BP 81 EP 91 DI 10.1007/s10048-006-0031-7 PG 11 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA 039RX UT WOS:000237325600002 PM 16525850 ER PT J AU Hartley, SW Scher, AI Korf, ESC White, LR Launer, LJ AF Hartley, SW Scher, AI Korf, ESC White, LR Launer, LJ TI Analysis and validation of automated skull stripping tools: A validation study based on 296 MR images from the Honolulu Asia aging study SO NEUROIMAGE LA English DT Article ID BRAIN EXTRACTION; CARDIOVASCULAR-HEALTH; ALZHEIMERS-DISEASE; SEGMENTATION; CONSORTIUM AB As population-based epidemiologic studies may acquire images from thousands of subjects, automated image post-processing is needed. However, error in these methods may be biased and related to subject characteristics relevant to the research question. Here, we compare two automated methods of brain extraction against manually segmented images and evaluate whether method accuracy is associated with subject demographic and health characteristics. MRI data (n = 296) are from the Honolulu Asia Aging Study, a population-based study of elderly Japanese-American men. The intracranial space was manually outlined on the axial proton density sequence by a single operator. The brain was extracted automatically using BET (Brain Extraction Tool) and BSE (Brain Surface Extractor) on axial proton density images. Total intracranial volume was calculated for the manually segmented images (ticvM), the BET segmented images (ticvBET) and the BSE segmented images (ticvBSE). Mean ticvBSE was closer to that of ticvM, but ticvBET was more highly correlated with ticvM than ticvBSE. BSE had significant over (positive error) and underestimated (negative error) ticv, but net error was relatively low. BET had large positive and very low negative error. Method accuracy, measured in percent positive and negative error, varied slightly with age, head circumference, presence of the apolipoprotein e epsilon 4 polymorphism, subcortical and cortical infracts and enlarged ventricles. This epidemiologic approach to the assessment of potential bias in image post-processing tasks shows both skull-stripping programs performed well in this large image dataset when compared to manually segmented images. Although method accuracy was statistically associated with some subject characteristics, the extent of the misclassification (in terms of percent of brain volume) was small. (c) 2005 Elsevier Inc. All rights reserved. C1 Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. Vrije Univ Amsterdam, Med Ctr, Dept Neurol & Alzheimer Ctr, Amsterdam, Netherlands. Pacific Hlth Res Inst, Honolulu, HI 96813 USA. RP Scher, AI (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, 4201 Jones Bridge Rd, Bethesda, MD 20814 USA. EM ascher@usuhs.mil FU Intramural NIH HHS NR 20 TC 29 Z9 29 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 1 PY 2006 VL 30 IS 4 BP 1179 EP 1186 DI 10.1016/j.neuroimage.2005.10.043 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 043LB UT WOS:000237601500011 PM 16376107 ER PT J AU Lee, L Friston, K Horwitz, B AF Lee, L Friston, K Horwitz, B TI Large-scale neural models and dynamic causal modelling SO NEUROIMAGE LA English DT Article DE dynamic causal modelling; fMRI; large-scale neural model; validation ID FUNCTIONAL CONNECTIVITY; HUMAN BRAIN; FMRI; CORTEX AB Dynamic causal modelling (DCM) is a method for estimating and making inferences about the coupling among small numbers of brain areas, and the influence of experimental manipulations on that coupling [Friston, K.J., Harrison, L., Penny, W., 2003. Dynamic causal modelling. Neuroimage 19, 1273-1302]. Large-scale neural modelling aims to construct neurobiologically grounded computational models with emergent behaviours that inform our understanding of neuronal systems. One such model has been used to simulate region-specific BOLD time-series [Horwitz, B., Friston, K.J., Taylor, J.G., 2000. Neural modeling and functional brain imaging: an overview. Neural Netw. 13, 829-846]. DCM was used to make inferences about effective connectivity using data generated by a model implementing a visual delayed match-to-sample task [Tagamets, M.A., Horwitz, B., 1998. Integrating electrophysiological and anatomical experimental data to create a large-scale model that simulates a delayed match-to-sample human brain imaging study. Cereb. Cortex 8, 310-320]. The aim was to explore the validity of inferences made using DCM about the connectivity structure and task-dependent modulatory effects, in a system with a known connectivity structure. We also examined the effects of misspecifying regions of interest. Models with hierarchical connectivity and reciprocal connections were examined using DCM and Bayesian Model Comparison [Penny, W.D., Stephan, K.E., Mechelli, A., Friston, K.J., 2004. Comparing dynamic causal models. Neuroimage 22, 1157-1172]. This approach revealed strong evidence for those models with correctly specified anatomical connectivity. Furthermore, Bayesian model comparison favoured those models when bilinear effects corresponded to their implementation in the neural model. These findings generalised to an extended model with two additional areas and reentrant circuits. The conditional uncertainty of coupling parameter estimates increased in proportion to the number of incorrectly specified regions. These results highlight the role of neural models in establishing the validity of estimation and inference schemes. Specifically, Bayesian model comparison confirms the validity of DCM in relation to a well-characterised and comprehensive neuronal model. (c) 2005 Elsevier Inc. All rights reserved. C1 Wellcome Dept Imaging Neurosci, London WC1N 3BG, England. Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modelling Sect, NIH, Bethesda, MD 20892 USA. RP Friston, K (reprint author), Wellcome Dept Imaging Neurosci, 12 Queen Sq, London WC1N 3BG, England. EM k.friston@fil.ion.ucl.ac.uk RI Friston, Karl/D-9230-2011 OI Friston, Karl/0000-0001-7984-8909 FU Intramural NIH HHS; Wellcome Trust NR 15 TC 58 Z9 61 U1 1 U2 10 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 MAY 1 PY 2006 VL 30 IS 4 BP 1243 EP 1254 DI 10.1016/j.neuroimage.2005.11.007 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 043LB UT WOS:000237601500017 PM 16387513 ER PT J AU Luo, QA Nakic, M Wheatley, T Richell, R Martin, A Blair, RJR AF Luo, QA Nakic, M Wheatley, T Richell, R Martin, A Blair, RJR TI The neural basis of implicit moral attitude - An IAT study using event-related fMRI SO NEUROIMAGE LA English DT Article DE moral attitude; IAT; emotion; Amygdala; ventrolateral PFC; medial OFC ID ANTERIOR CINGULATE CORTEX; HUMAN PREFRONTAL CORTEX; FUNCTIONAL MRI; ORBITOFRONTAL CORTEX; DECISION-MAKING; INTERFERENCE TASK; COGNITIVE CONTROL; ASSOCIATION TEST; COUNTING STROOP; ERROR-DETECTION AB Recent models of morality have suggested the importance of affect-based automatic moral attitudes in moral reasoning. However, previous investigations of moral reasoning have frequently relied upon explicit measures that are susceptible to voluntary control. To investigate participant's automatic moral attitudes, we used a morality Implicit Association Test (IAT). Participants rated the legality of visually depicted legal and illegal behaviors of two different intensity levels (e.g., high intensity illegal = interpersonal violence; low intensity illegal = vandalism) both when the target concept (e.g., illegal) was behaviorally paired with an associated attribute (e.g., bad; congruent condition) or an unassociated attribute (e.g., good; incongruent condition). Behaviorally, an IAT effect was shown; RTs were faster in the congruent rather than incongruent conditions. At the neural level, implicit moral attitude, as indexed by increased BOLD response as a function of stimulus intensity, was associated with increased activation in the right amygdala and the ventromedial orbitofrontal cortex. In addition, performance on incongruent trials relative to congruent trials was associated with increased activity in the right ventrolateral prefrontal cortex (BA 47), left subgenual cingulate gyrus (BA 25), bilateral premotor cortex (BA 6) and the left caudate. The functional contributions of these regions in moral reasoning are discussed. Published by Elsevier Inc. C1 NIMH, Unit Affect Cognit Neurosci Mood & Anxiety Progra, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, Unit Affect Cognit Neurosci Mood & Anxiety Progra, Dept Hlth & Human Serv, 15K N Dr,Room 206,MSC 2670, Bethesda, MD 20892 USA. EM James.Blair@mail.nih.gov RI martin, alex/B-6176-2009 NR 84 TC 88 Z9 96 U1 10 U2 42 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 MAY 1 PY 2006 VL 30 IS 4 BP 1449 EP 1457 DI 10.1016/j.ncuroimage.2005.11.005 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 043LB UT WOS:000237601500036 PM 16418007 ER PT J AU Taylor, JL Bishop, C Ullrich, T Rice, KC Walker, PD AF Taylor, JL Bishop, C Ullrich, T Rice, KC Walker, PD TI Serotonin 2A receptor antagonist treatment reduces dopamine D1 receptor-mediated rotational behavior but not L-DOPA-induced abnormal involuntary movements in the unilateral dopamine-depleted rat SO NEUROPHARMACOLOGY LA English DT Article DE Parkinson's disease; dyskinesia; supersensitivity; M100907; D1 receptor; D2 receptor ID PREPROTACHYKININ MESSENGER-RNA; LEVODOPA-INDUCED DYSKINESIA; PARKINSONS-DISEASE; 5-HT2A RECEPTOR; 6-HYDROXYDOPAMINE-LESIONED RATS; GENE-EXPRESSION; NUCLEUS-ACCUMBENS; MDL 100907; IN-VIVO; STRIATUM AB Previous experiments have demonstrated that serotonin (5-HT) 2A receptor antagonists suppress hyperkinetic behaviors associated with dopamine (DA) D1 receptor supersensitivity in rats with 6-hydroxydopamine (6-OHDA) lesions. Since L-DOPA induced dyskinesia (LID) may be mediated by oversensitive D1-mediated signaling, the present study examined the effects of the selective 5-HT2A antagonist M100907 on LID behaviors in DA-depleted rats. Adult male Sprague-Dawley rats with unilateral 6-OHDA lesions received daily L-DOPA treatments to produce dyskinetic behaviors as measured by abnormal involuntary movements (AIMS) testing. In these animals, M100907 (0.01, 0.1 or 1.0 mg/kg. ip) given 30 min before L-DOPA did not alter the appearance or intensity of AIMS behaviors. Because L-DOPA induced AIMS in rats are dependent upon D1 and D2 receptor activation, a second study was performed to determine if M100907 could suppress D1- or D2-mediated rotational behaviors. Contralateral rotations induced by the D1 agonist SKF82958 were significantly reduced by pre-treatment with M100907. However. M100907 was ineffective in reducing rotations induced by the D2 agonist quinpirole. The finding that M 100907 suppresses rotations induced by D1. but not D2, agonists may provide a partial explanation for the lack of effect of a selective 5-HT2A antagonist on L-DOPA-induced AIMs behaviors. (c) 2005 Elsevier Ltd. All rights reserved. C1 Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Cellular & Clin Neurobiol Program, Detroit, MI 48201 USA. NIDDK, Med Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Walker, PD (reprint author), Wayne State Univ, Sch Med, Dept Anat & Cell Biol, 540 E Canfield Ave, Detroit, MI 48201 USA. EM pdwalker@med.wayne.edu FU NINDS NIH HHS [NS39013] NR 62 TC 26 Z9 26 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD MAY PY 2006 VL 50 IS 6 BP 761 EP 768 DI 10.1016/j.neuropharm.2005.12.004 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 043LY UT WOS:000237603800014 PM 16434065 ER PT J AU Mitchell, DGV Fine, C Richell, RA Newman, C Lumsden, J Blair, KS Blair, RJR AF Mitchell, D. G. V. Fine, C. Richell, R. A. Newman, C. Lumsden, J. Blair, K. S. Blair, R. J. R. TI Instrumental learning and relearning in individuals with psychopathy and in patients with lesions involving the amygdala or orbitofrontal cortex SO NEUROPSYCHOLOGY LA English DT Article DE instrumental learning; psychopathy; acquired sociopathy; amygdala lesion; orbitofrontal cortex lesion ID PREFRONTAL CORTEX; PASSIVE-AVOIDANCE; CONDITIONED REINFORCEMENT; BASOLATERAL AMYGDALA; EXCITOTOXIC LESIONS; ANTISOCIAL-BEHAVIOR; DOUBLE DISSOCIATION; FACIAL EXPRESSIONS; NEURAL MECHANISMS; RESPONSE REVERSAL AB Previous work has shown that individuals with psychopathy are impaired on some forms of associative learning, particularly stimulus-reinforcement learning (Blair et al., 2004; Newman & Kosson, 1986). Animal work suggests that the acquisition of stimulus-reinforcement associations requires the amygdala (Baxter & Murray, 2002). Individuals with psychopathy also show impoverished reversal learning (Mitchell, Colledge, Leonard, & Blair, 2002). Reversal learning is supported by the ventrolateral and orbitofrontal cortex (Rolls, 2004). In this paper we present experiments investigating stimulus-reinforcement learning and relearning in patients with lesions of the orbitofrontal cortex or amygdala, and individuals with developmental psychopathy without known trauma. The results are interpreted with reference to current neurocognitive models of stimulus-reinforcement learning, relearning, and developmental psychopathy. C1 NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Melbourne, Dept Philosophy, Parkville, Vic 3052, Australia. Hammersmith Hosp, Psychiat Grp, MRC, Clin Sci Ctr,Imperial Coll, London, England. UCL, Dept Psychol, London, England. Broadmoor Hosp, Dept Neurophysiol, Crowthorne, Berks, England. RP Mitchell, DGV (reprint author), NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, 15K N Dr,Room 206,MSC 2670, Bethesda, MD 20892 USA. EM mitchelld@mail.nih.gov OI , Cordelia/0000-0001-6413-4372 FU Intramural NIH HHS NR 74 TC 26 Z9 27 U1 10 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD MAY PY 2006 VL 20 IS 3 BP 280 EP 289 DI 10.1037/0894-4105.20.3.280 PG 10 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 047UN UT WOS:000237904300003 PM 16719621 ER PT J AU Sokolov, BP Cadet, JL AF Sokolov, BP Cadet, JL TI Methamphetamine causes alterations in the MAP kinase-related pathways in the brains of mice that display increased aggressiveness SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE proteomics; violence; drug abuse; psychiatric disorders ID GENE-EXPRESSION; BIPOLAR DISORDER; CONDUCT DISORDER; AMPHETAMINE ABUSE; SIGNALING PATHWAY; LITHIUM-CARBONATE; EVOKED AGGRESSION; YOUTH VIOLENCE; PUBLIC-HEALTH; BEHAVIOR AB Aggressive behaviors have been reported in patients who suffer from some psychiatric disorders, and are common in methamphetamine (METH) abusers. Herein, we report that multiple (but not single) injections of METH significantly increased aggressiveness in male CD-1 mice. This increase in aggressiveness was not secondary to METH-induced hyperactivity. Analysis of protein expression using antibody microarrays and Western blotting revealed differential changes in MAP kinase-related pathways after multiple and single METH injections. There were statistically significant (p < 0.05) decreases in MEK1, Erk2p, GSK3 alpha, 14-3-3e, and MEK7 in the striata of mice after multiple injections of METH. MEK1 was significantly decreased also after a single injection of METH, but to a much lesser degree than after multiple injections of METH. In the frontal cortex, there was a statistically significant decrease in GSK3a after multiple (but not single) injections of METH. These findings suggest that alterations in MAP kinase-related pathways in the prefronto-striatal circuitries might be involved in the manifestation of aggressive behaviors in mice. C1 NIDA, Mol Neuropsychiat Branch, NIH, US Dept HHS, Baltimore, MD 21224 USA. RP Sokolov, BP (reprint author), NIDA, Mol Neuropsychiat Branch, NIH, US Dept HHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Bsokolov@intra.nida.nih.gov FU Intramural NIH HHS NR 75 TC 30 Z9 32 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2006 VL 31 IS 5 BP 956 EP 966 DI 10.1038/sj.npp.1300891 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 033XY UT WOS:000236889500007 PM 16192988 ER PT J AU Dow-Edwards, DL Benveniste, H Behnke, M Bandstra, ES Singer, LT Hurd, YL Stanford, LR AF Dow-Edwards, DL Benveniste, H Behnke, M Bandstra, ES Singer, LT Hurd, YL Stanford, LR TI Neuroimaging of prenatal drug exposure SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Review ID RECEPTOR MESSENGER-RNA; PERINATAL DELTA(9)-TETRAHYDROCANNABINOL EXPOSURE; MAGNETIC-RESONANCE SPECTROSCOPY; POSITRON EMISSION TOMOGRAPHY; UTERO COCAINE EXPOSURE; CANNABINOID RECEPTOR; RAT-BRAIN; MARIJUANA USE; IN-UTERO; CORPUS-CALLOSUM C1 Suny Downstate Med Ctr, Dept Physiol & Pharmacol, Brooklyn, NY 11203 USA. Dept Med, Brookhaven Natl Lab, New York, NY USA. Univ Florida, Coll Med, Dept Pediat, Gainesville, FL USA. Univ Miami, Sch Med, Dept Pediat, Miami, FL USA. Case Western Reserve Univ, Univ Hosp Cleveland, Cleveland, OH 44106 USA. Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden. Natl Inst Drug Abuse, Bethesda, MD USA. RP Dow-Edwards, DL (reprint author), Suny Downstate Med Ctr, Dept Physiol & Pharmacol, 450 Clarkson Ave,Box 29, Brooklyn, NY 11203 USA. EM diana.dow-edwards@downstate.edu NR 103 TC 23 Z9 23 U1 4 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2006 VL 28 IS 3 BP 386 EP 402 DI 10.1016/j.ntt.2006.03.003 PG 17 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 056JW UT WOS:000238519900008 PM 16832875 ER PT J AU Sager, PR AF Sager, PR TI Mercury levels in Argentine newborns and infants after receipt of routine vaccines containing thimerosal SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2006 VL 28 IS 3 BP 426 EP 426 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 056JW UT WOS:000238519900054 ER PT J AU Berman, RF Lawler, C Harry, GJ AF Berman, RF Lawler, C Harry, GJ TI Effects of neonatal thimerosal exposure in SJL mice on measures of sensory gating, anxiety and sociability SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract C1 Univ Calif Davis, Davis, CA 95616 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2006 VL 28 IS 3 BP 427 EP 427 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 056JW UT WOS:000238519900057 ER PT J AU Harry, GJ Mouton, P Lawler, C Berman, R AF Harry, GJ Mouton, P Lawler, C Berman, R TI Hippocampal morphology - effects of litter and neonatal thimerosal exposure in SJL/J mice SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract C1 Univ Calif Davis, Davis, CA 95616 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Stereol Resource Ctr Inc, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2006 VL 28 IS 3 BP 427 EP 427 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 056JW UT WOS:000238519900058 ER PT J AU de Zwart, JA van Gelderen, P Golay, X Ikonomidou, VN Duyn, JH AF de Zwart, JA van Gelderen, P Golay, X Ikonomidou, VN Duyn, JH TI Accelerated parallel imaging for functional imaging of the human brain SO NMR IN BIOMEDICINE LA English DT Review DE parallel imaging; fMRI; rapid imaging; echo-planar imaging; geometrical distortions; SENSE; SMASH ID SPATIAL HARMONICS SMASH; TO-NOISE RATIO; ACOUSTIC NOISE; HIGH-RESOLUTION; BOLD FMRI; SENSE-EPI; SIMULTANEOUS ACQUISITION; FIELD INHOMOGENEITIES; PRESTO-SENSE; TIME-SERIES AB Accelerated parallel imaging (PI) techniques have recently been applied to functional imaging experiments of the human brain in order to improve the performance of commonly used single-shot techniques like echo-planar imaging (EPI). Potential benefits of PI-fMRI include the reduction of geometrical distortions due to off-resonance signals, the reduction of signal-loss in areas with substantial signal inhomogeneity, increases of the spatial and temporal resolution of the fMR1 experiment and reduction of gradient acoustic noise. Although PI generally leads to a substantial decrease in image signal-to-noise ratio (SNR), its effect on the temporal stability of the signal, which ultimately determines fMRI performance, is only partially determined by image SNR. Therefore, the penalty for using PI is generally not as severe as the SNR reduction. The majority of problems related to single-shot techniques become more severe at an increased magnetic field strength, making PI an important tool in achieving the full potential of fMRI at high field. Copyright (C) 2006 John Wiley & Sons, Ltd. C1 NINDS, Adv MRI Sect, LFMI, NIH, Bethesda, MD 20892 USA. Natl Inst Neurosci, Dept Neuroradiol, Singapore, Singapore. RP de Zwart, JA (reprint author), NINDS, Adv MRI Sect, LFMI, NIH, Bldg 10,Rm B1D-726,MSC 1065,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Jacco.deZwart@nih.gov RI Golay, Xavier/B-2834-2009; Duyn, Jozef/F-2483-2010; OI Golay, Xavier/0000-0002-6447-4446 NR 96 TC 38 Z9 38 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD MAY PY 2006 VL 19 IS 3 BP 342 EP 351 DI 10.1002/nbm.1043 PG 10 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 050KL UT WOS:000238086200006 PM 16705634 ER PT J AU Kellman, P McVeigh, ER AF Kellman, P McVeigh, ER TI Phased array ghost elimination SO NMR IN BIOMEDICINE LA English DT Article DE PAGE; SENSE; TSENSE; ghost cancellation; phased array; parallel imaging; cardiac imaging; EPI ID ECHO; REDUCTION; ARTIFACTS; SSFP AB Parallel imaging may be applied to cancel ghosts caused by a variety of distortion mechanisms, including distortions such as off-resonance or local flow, which are space variant. Phased array combining coefficients may be calculated that null ghost artifacts at known locations based on a constrained optimization, which optimizes SNR subject to the nulling constraint. The resultant phased array ghost elimination (PAGE) technique is similar to the method known as sensitivity encoding (SENSE) used for accelerated imaging; however, in this formulation is applied to full field-of-view (FOV) images. The phased array method for ghost elimination may result in greater flexibility in designing acquisition strategies. For example, in multi-shot EPI applications ghosts are typically mitigated by the use of an interleaved phase encode acquisition order. An alternative strategy is to use a sequential, non-interleaved phase encode order and cancel the resultant ghosts using PAGE parallel imaging. Cancellation of ghosts by means of phased array processing makes sequential, non-interleaved phase encode acquisition order practical, and permits a reduction in repetition time, TR, by eliminating the need for echo-shifting. Sequential, non-interleaved phase encode order has benefits of reduced distortion due to off-resonance, in-plane flow and EPI delay misalignment. Furthermore, the use of EPI with PAGE has inherent fat-water separation and has been used to provide off-resonance correction using a technique referred to as lipid elimination with an echo-shifting N/2-ghost acquisition (LEENA), and may further generalized using the multi-point Dixon method. Other applications of PAGE include cancelling ghosts which arise due to amplitude or phase variation during the approach to steady state. Parallel imaging requires estimates of the complex coil sensitivities. In vivo estimates may be derived by temporally varying the phase encode ordering to obtain a full k-space dataset in a scheme similar to the autocalibrating TSENSE method. This scheme is a generalization of the UNFOLD method used for removing aliasing in undersampled acquisitions. The more general scheme may be used to modulate each EPI ghost image to a separate temporal frequency as described in this paper. Copyright (C) 2006 John Wiley & Sons, Ltd. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Kellman, P (reprint author), NHLBI, Cardiac Energet Lab, NIH, 10 Ctr Dr,MSC-1061, Bldg 10,RM B1D 416, Bethesda, MD 20892 USA. EM kellman@nih.gov FU Intramural NIH HHS [Z01 HL004608-08] NR 23 TC 13 Z9 13 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD MAY PY 2006 VL 19 IS 3 BP 352 EP 361 DI 10.1002/nbm.1044 PG 10 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 050KL UT WOS:000238086200007 PM 16705636 ER PT J AU Chong, HS Milenic, DE Garmestani, K Brady, ED Arora, H Pfiester, C Brechbiel, MW AF Chong, HS Milenic, DE Garmestani, K Brady, ED Arora, H Pfiester, C Brechbiel, MW TI In vitro and in vivo evaluation of novel ligands for radioimmunotherapy SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE radioimmunotherapy; chelates radiolabeled with Lu-177, Y-90, Pb-212, and Bi-213; biodistribution; serum stability; PIP-DTPA ID BIFUNCTIONAL CHELATING-AGENTS; MONOCLONAL-ANTIBODY; LANTHANIDE COMPLEXES; STABILITY; RADIONUCLIDES; ACID; BIODISTRIBUTION; DTPA; CANCER; Y-90 AB Novel ligands cis-2,6-bis[N,N-bis(carboxymethyl)aminomethyl]-1-piperidineacetic acid (PIP-DTPA), cis-[(1R,11S)-6,9,15-Tris-carboxymethyl-3,6,9,15 -tetraazabicyclo[9.3.1]pentadec-3-yl] -acetic acid (PIP-DOTA), cis-{2,7-bis-[bis-earboxymethyl-amino)-methyl]-azepan-1-yl} -acetic acid (AZEP-DTPA), [2-(4,7 -bis-carboxymethyl-[1,4,7]triazacyclononan-1-yl-ethyl]-2-carbonylmethyl-amino]-tetraacetic acid (NETA) and {4-carboxymethyl-7-[2-(carboxymethylamino)-ethyl]-perhydro-1,4,7-triazonin-1-yl}-acetic acid (NPTA) are investigated as potential chelators of (LU)-L-177, Y-90, Pb-212 and Bi-213 for radioimmunotherapy (RIT). The new ligands are radiolabeled with Lu-177, Y-86/88/90 Pb-203 and Bi-205/6, and in vitro stability and in vivo stability of the radiolabeled complexes are assessed in human serum and athymic mice, respectively. In vitro studies indicate that all radiolabeled complexes with the exception of Y-90-AZEP-DTPA are stable in serum for 5-11 days. All new ligands examined herein are found to tightly hold Lu-177 in vivo. Piperidine-backboned DTPA (PIP-DTPA) complexes radiolabeled with all radioisotopes examined display excellent in vivo stability, that is, excretion without dissociation. The azepane-backboned DTPA derivative, AZEP-DTPA, appears ineffective in binding all but Lu-177 in vivo. NETA and NPTA radiolabeled with Y-86 or Lu-177 exhibit rapid blood clearance and low organ uptakes. Significant accretion in the kidney, femur and/or liver is observed with Pb-203-labeled AZEP-DTPA, PIP-DOTA and NPTA. Both Pb-203-PIP-DOTA and Bi-205/6-PIP-DOTA result in moderate to high renal accumulation of radioactivity. NETA exhibits improved renal accumulation with respect to PIP-DOTA for Bi-201/6 but also shows significant liver uptake. Of all ligands studied, only PIP-DTPA appears to effectively bind Pb-201 and Bi-205/6 in vivo. PIP-DTPA, PIP-DOTA, NETA and NPTA all show strong evidence of rapid blood clearance and low organ uptake for Lu-177 and Y-90. Serum stability and in vivo biodistribution results suggest PIP-DTPA as a potential chelating agent with broad applicability for use ill Lu-177, Y-90, Pb-212 and Bi-213 RIT. (c) 2006 Elsevier Inc. All rights reserved. C1 IIT, Div Chem, Biol Chem & Phys Sci Dept, Chicago, IL 60616 USA. NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Chong, HS (reprint author), IIT, Div Chem, Biol Chem & Phys Sci Dept, Chicago, IL 60616 USA. EM chong@iit.edu FU Intramural NIH HHS NR 33 TC 24 Z9 25 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD MAY PY 2006 VL 33 IS 4 BP 459 EP 467 DI 10.1016/j.nucmedbio.2006.03.004 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 051DZ UT WOS:000238142400003 PM 16720237 ER PT J AU Talanov, VS Garmestani, K Regino, CAS Milenic, DE Plascjak, PS Waldmann, TA Brechbiel, MW AF Talanov, VS Garmestani, K Regino, CAS Milenic, DE Plascjak, PS Waldmann, TA Brechbiel, MW TI Preparation and in vivo evaluation of a novel stabilized linker for At-211 labeling of protein SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE At-211; astatine; SAPS; SPEMS; methyl-SAPS; radioimmunotherapy; monoclonal antibody; alpha-particle ID MONOCLONAL-ANTIBODY THERAPY; T-CELL LEUKEMIA; TISSUE DISTRIBUTION; ANTI-CD20 ANTIBODY; RADIOIMMUNOTHERAPY; LYMPHOMA; I-131; BIODISTRIBUTION; STREPTAVIDIN; RADIOTHERAPY AB Significant improvement of in vivo stability of At-211-labeled radioimmunoconjugates achieved upon employment of a recently reported new linker, succinimidyl AT-2-(4-[At-211]astatophenethyl)succinamate (SAPS), prompted additional studies of its chemistry. The At-211 radiolabeling of succinimidyl N-2-(4-tributylstannylphenethyl)succinamate (1) was noted to decline after storage at -15 degrees C for greater than 6 months. Compound I was found to degrade via a ring closure reaction with the fort-nation of N-2-(4-tributylstannylphenethyl)succinimide (3), and a modified procedure for the preparation of I was developed. The N-methyl structural analog of 1, succinimidyl N-2-(4-tributylstanylphenethyl)-N-methyl succinamate (SPEMS), was synthesized to investigate the possibility of improving the stability of reagent-protein linkage chemistry. Radiolabeling of SPEMS with At-211 generates succinimidyl N-2-(4-[(211)-At]lastatophenethyl)-N-methyl succinamate (Methyl-SAPS), with yields being consistent for greater than 1 year. Radiolabelings of 1 and SPEMS with I-125 generated succinimydyl N-2-(4-[I-125]iodophenethyl)succinamate (SIPS) and succinimidyl N-2-(4-[ 121 I]iodoplienethyl)-N-methyl succinamate (Methyl-SIPS), respectively, and showed no decline in yields. Methyl-SAPS, SAPS, Methyl-SIPS and SIPS were conjugated to Herceptin for a comparative assessment in LS-174T xenograft-bearing mice. The conjugates of Herceptin with Methyl-SAPS or Methyl-SIPS demonstrated immunoreactivity equivalent to if not superior to the SAPS and SIPS paired analogs. The in vivo studies also revealed that the N-methyl modification resulted in a superior statinated product. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Nucl Med, Bethesda, MD 20892 USA. RP Talanov, VS (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM vstalanov@msrce.howard.edu; martinwb@mail.nih.gov FU Intramural NIH HHS NR 33 TC 11 Z9 17 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD MAY PY 2006 VL 33 IS 4 BP 469 EP 480 DI 10.1016/j.nucmedbio.2006.03.001 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 051DZ UT WOS:000238142400004 PM 16720238 ER PT J AU Meigs, JB Dupuis, J Liu, CY O'Donnell, CJ Fox, CS Kathiresan, S Gabriel, SB Larson, MG Yang, Q Herbert, AG Wilson, PWF Feng, DL Tofler, GH Cupples, LA AF Meigs, James B. Dupuis, Josee Liu, Chunyu O'Donnell, Christopher J. Fox, Caroline S. Kathiresan, Sekar Gabriel, Stacey B. Larson, Martin G. Yang, Qiong Herbert, Alan G. Wilson, Peter W. F. Feng, DaLi Tofler, Geoffrey H. Cupples, L. Adrienne TI PAI-1 gene 4G/5G polymorphism and risk of type 2 diabetes in a population-based sample SO OBESITY LA English DT Article DE type 2 diabetes; insulin; genetics; risk factors; longitudinal study ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; INSULIN-RESISTANCE ATHEROSCLEROSIS; ENDOTHELIAL DYSFUNCTION; PROMOTER; ASSOCIATION; HISPANICS; MELLITUS; PROTEINS; GENOTYPE; DISEASE AB Elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) increase risk for type 2 diabetes. The PAI-1 4G/5G polymorphism is a major genetic determinant of plasma PAI-1 levels, with 4G/4G homozygotes having elevated PAI-1 levels relative to 5G allele carriers. These observations suggest the hypothesis that the PAI-1 4G/5G polymorphism could be a genetic risk factor for diabetes. We tested this hypothesis among 2169 participants of the Framingham Offspring Study followed for seven examinations over 26 years for 216 cases of type 2 diabetes. PAI-1 4G/4G homozygotes (genotype frequency, 27.4%) were not at significantly (p > 0.05) increased risk of incident diabetes compared with 5G allele carriers and did not have elevated levels of diabetes-related quantitative traits including BMI, fasting plasma glucose, or fasting insulin. In proportional hazards regression models accounting for correlation among siblings, with the 5G/5G genotype as the referent, the hazard ratio for incident diabetes for 4G/5G carriers was 0.93 (95% confidence interval, 0.68 to 1.28) and for 4G/4G carriers was 1.20 (95% confidence interval, 0.83 to 1.92). Results were not altered by further adjustment for sex or levels of BMI, triglycerides, or PAI-1. We conclude that the PAI-1 4G/5G polymorphism is not an important genetic, risk factor for type 2 diabetes in this community-based sample. Elevated PAI-1 levels may be associated with an increased risk for diabetes as a marker for underlying endothelial dysfunction rather than by a direct effect of genetically mediated elevated levels. C1 Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. Med Univ S Carolina, Dept Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. Mayo Clin, Div Cardiol, Rochester, MN USA. Royal N Shore Hosp, Dept Cardiol, Sydney, NSW, Australia. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org RI Yang, Qiong/G-5438-2014 FU NHLBI NIH HHS [R01 HL48157, N01-HC-25195, R01 HL76784] NR 25 TC 15 Z9 16 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBESITY JI Obesity PD MAY PY 2006 VL 14 IS 5 BP 753 EP 758 DI 10.1038/oby.2006.85 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 066SF UT WOS:000239249700002 PM 16855181 ER PT J AU Ackerman, A Thornton, JC Wang, J Pierson, RN Horlick, M AF Ackerman, Alexandra Thornton, John C. Wang, Jack Pierson, Richard N., Jr. Horlick, Mary TI Sex difference in the effect of puberty on the relationship between fat mass and bone mass in 926 healthy subjects, 6 to 18 years old SO OBESITY LA English DT Article DE body composition; bone mass; DXA; puberty; ethnicity ID X-RAY ABSORPTIOMETRY; BODY-COMPOSITION; MINERAL DENSITY; PREPUBERTAL CHILDREN; FOREARM FRACTURES; OBESE CHILDREN; GENDER-DIFFERENCES; LEAN TISSUE; ADOLESCENTS; GIRLS AB Objective: Understanding factors influencing bone mineral accrual is critical to optimize peak bone mass during childhood. The epidemic of pediatric obesity and reported higher incident of fracture risk in obese children led us to study the influence of fat mass on bone mineral content (BMC) in children. Research Methods and Procedures: Height; weight; pubertal stage; and BMC, non-bone fat-free mass (nbFFM), and fat mass (FM) by DXA were obtained in a multiethnic group of healthy children (444 girls/482 boys; 6 to 18 years old) recruited in the New York metropolitan area. Regression techniques were used to explore the relationship between BMC and FM, with age, height, nbFFM, pubertal stage, sex, and ethnicity as covariates. Results: Because there were significant sex interactions, separate regression analyses were performed for girls and boys. Although ln(nbFFM) was the greatest predictor of ln(BMC), ln(FM) was also a significant predictor in prepubertal boys and all girls but not in pubertal boys. This effect was independent of ethnicity. Discussion: FM was a determinant of BMC in all girls but in only prepubertal boys. Our study confirms nbFFM as the greatest predictor of BMC but is the first to find a sex difference in the effect of puberty on the relationship of FM to BMC. Our results suggest that, in two individuals of the same sex and weight, the one with greater fat mass will have lower BMC, especially pubertal boys. The implications of these findings for achievement of optimal peak bone mass in a pediatric population with an unprecedented incidence of overweight and "overfat" status remain to be seen. C1 St Lukes Roosevelt Hosp, Body Composit Unit, New York, NY USA. Columbia Univ, Childrens Hosp New York Presbyterian, New York, NY USA. RP Horlick, M (reprint author), NIDDKD, 6707 Democracy Blvd,Room 679, Bethesda, MD 20892 USA. EM horlickm@niddk.nih.gov FU NIDDK NIH HHS [DK37352] NR 48 TC 41 Z9 42 U1 1 U2 5 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBESITY JI Obesity PD MAY PY 2006 VL 14 IS 5 BP 819 EP 825 DI 10.1038/oby.2006.95 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 066SF UT WOS:000239249700012 PM 16855191 ER PT J AU Hoffman, MK Vahratian, A Sciscione, AC Troendle, JF Zhang, J AF Hoffman, Matthew K. Vahratian, Anjel Sciscione, Anthony C. Troendle, James F. Zhang, Jun TI Comparison of Labor progression between induced and noninduced multiparous women SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 02-07, 2004 CL NEW ORLEANS, LA SP Soc Maternal Fetal Med ID ELECTIVE INDUCTION; CESAREAN DELIVERY; NULLIPAROUS WOMEN; FOLEY CATHETER; GRAPHICOSTATISTICAL ANALYSIS; MISOPROSTOL; RISK; TERM; TRIAL AB OBJECTIVE: The incidence of labor induction is rising rapidly in the United States. Among multiparas, labor is often followed with traditional labor curves derived from noninduced pregnancies. We sought to determine how labor progression of multiparous women who presented in spontaneous labor differed from those who were electively induced with and from those induced without preinduction cervical ripening. METHODS: We analyzed data on all low-risk multiparous women with an elective induction or spontaneous onset of labor between 37(+0) and 4011 weeks of gestation from January 2002 to March 2004 at a single institution. The median duration of labor by each centimeter of cervical dilatation and the risk of cesarean delivery were computed for 61 women with preinduction cervical ripening and oxytocin induction, 735 women with oxytocin induction, and 1,885 women with a spontaneous onset of labor. An intracervical Foley catheter was used to ripen the cervix. RESULTS: Those women who experienced electively induced labor without cervical ripening had a shorter active phase of labor than did those admitted in spontaneous labor (99 minutes in induced labor versus 161 minutes in spontaneous labor, P < .001). However, the cesarean delivery rate was elevated in the induction group (3.9% versus 2.3%, P < .05). Women who underwent preinduction cervical ripening also had a shorter active phase than those admitted in spontaneous labor (109 minutes versus 161 minutes, P = .01). CONCLUSION: The pattern of labor progression differs for women with an electively induced labor without cervical ripening compared with those who present with spontaneous onset of labor. C1 Christiana Care Hlth Serv, Dept Obstet & Gynecol, Newark, DE 19718 USA. NICHHD, Div Epidemiol Stat & Prevent Res, US Dept Hlth & Human Serv, NIH, Bethesda, MD USA. Drexel Univ, Coll Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. RP Hoffman, MK (reprint author), Christiana Care Hlth Serv, Dept Obstet & Gynecol, 4755 Ogletown Stanton Rd, Newark, DE 19718 USA. EM Mhoffman@Christianacare.org FU Intramural NIH HHS NR 23 TC 33 Z9 34 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2006 VL 107 IS 5 BP 1029 EP 1034 DI 10.1097/01.AOG.0000210528.32940.c6 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 095GP UT WOS:000241296500010 PM 16648407 ER PT J AU Higgins, RD Spong, CY AF Higgins, Rosemary D. Spong, Catherine Y. TI Therapy for hypoxic ischemic encephalopathy: A cool idea and hypoxic ischemic encephalopathy and hypothermia: A critical look - Reply SO OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 NICHHD, Pregnancy & Perinatol Branch, Ctr Dev Biol, Bethesda, MD 20892 USA. RP Higgins, RD (reprint author), NICHHD, Pregnancy & Perinatol Branch, Ctr Dev Biol, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2006 VL 107 IS 5 BP 1169 EP 1170 DI 10.1097/01.AOG.0000218105.79328.cb PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 095GP UT WOS:000241296500033 ER PT J AU Furuta, T Hayward, RL Meng, LH Takemura, H Aune, GJ Bonner, WM Aladjem, MI Kohn, KW Pommier, Y AF Furuta, T Hayward, RL Meng, LH Takemura, H Aune, GJ Bonner, WM Aladjem, MI Kohn, KW Pommier, Y TI P21(CDKN1A) allows the repair of replication-mediated DNA double-strand breaks induced by topoisomerase I and is inactivated by the checkpoint kinase inhibitor 7-hydroxystaurosporine SO ONCOGENE LA English DT Article DE UCN-01 (7-hydroxystaurosporine); p21; p53; gamma H2AX; camptothecin; cell cycle; DNA repair; DNA double-strand break ID CELL-CYCLE ARREST; HISTONE H2AX PHOSPHORYLATION; HUMAN COLON-CARCINOMA; S-PHASE CHECKPOINT; DAMAGE CHECKPOINT; CANCER-CELLS; CLEAVAGE COMPLEXES; PROTEIN-KINASE; GENOMIC INSTABILITY; SIGNALING PATHWAY AB This study provides evidence for the importance of p21(CDKN1A) for the repair of replication- mediated DNA double- strand breaks ( DSBs) induced by topoisomerase I. We report that defects of p21(CDKN1A) and p53 enhance camptothecin- induced histone H2AX phosphorylation ( gamma H2AX), a marker for DNA DSBs. In human colon carcinoma HCT116 cells with wild- type ( wt) p53, gamma H2AX reverses after camptothecin removal. By contrast, gamma H2AX increases after camptothecin removal in HCT116 cells deficient for p53 ( p53-/-) or p21(CDKN1A) ( p21-/-) as the cells reach the late- S and G2 phases. Since p21-/- cells exhibit similar S- phase arrest as wt cells in response to camptothecin and aphidicolin does not abrogate the enhanced gamma H2AX formation in p21-/- cells, we conclude that enhanced gamma H2AX formation in p21-/- cells is not due to re- replication. The cell cycle checkpoint abrogator and Chk1/ Chk2 inhibitor 7- hydroxystaurosporine ( UCN- 01) also increases camptothecin- induced gamma H2AX formation and inhibits camptothecin- induced p21(CDKN1A) upregulation in HCT116 wt cells. TUNEL ( terminal deoxynucleotidyl transferase ( TdT)- mediated dUTP- biotin nick end labeling) assays demonstrate that gamma H2AX formation in late S and G2 cells following CPT treatment corresponds to DNA breaks. However, these breaks are not related to apoptotic DNA fragmentation. We propose that p21(CDKN1A) prevents the collapse of replication forks damaged by stabilized topoisomerase I cleavage complexes. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 5060, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Aune, Gregory/I-5895-2015; Aladjem, Mirit/G-2169-2010 OI Aune, Gregory/0000-0002-2750-6461; Aladjem, Mirit/0000-0002-1875-3110 FU Intramural NIH HHS NR 79 TC 31 Z9 32 U1 0 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 MAY PY 2006 VL 25 IS 20 BP 2839 EP 2849 DI 10.1038/sj.onc.120931 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 041IN UT WOS:000237448200002 PM 16407843 ER PT J AU Tarassoff, CP Arlen, PM Gulley, JL AF Tarassoff, Christopher P. Arlen, Philip M. Gulley, James L. TI Therapeutic vaccines for prostate cancer SO ONCOLOGIST LA English DT Review DE prostate cancer; whole-tumor cell vaccines; dendritic cells; poxvirus vaccines; PSA ID T-CELL RESPONSES; COLONY-STIMULATING FACTOR; PHASE-I TRIAL; PERIPHERAL LYMPHOID ORGANS; ANTIGEN-PRESENTING CELLS; DENDRITIC CELLS; TUMOR-CELLS; RADICAL PROSTATECTOMY; MEMBRANE ANTIGEN; IMMUNE-RESPONSES AB Prostate cancer is the most common, noncutaneous cancer for men in the U.S., leading to more than 30,000 deaths a year. Vaccines for prostate cancer, which for several years have been shown to generate immunologic responses, are beginning to show significant clinical promise. At present, numerous therapeutic options are being investigated, including autologous and allogeneic whole-tumor cell vaccines, dendritic cell vaccines, and poxvirus-based vaccines. Advances in basic immunology have translated into new, more complex therapeutic strategies. The findings from current trials and the demonstrated potential to combine vaccines with conventional therapies herald a promising future for the treatment of prostate cancer. This review highlights recent advances and clinical trials in immunotherapy for prostate cancer, along with current thoughts on immunologic and clinical monitoring of these trials. C1 NCI, Clin Immunotherapy Grp, Tumor Immunol & Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, Clin Immunotherapy Grp, Tumor Immunol & Biol Lab, Ctr Canc Res,NIH, 10 Ctr Dr,MSC 1750,Bldg 10,Room 5B52, Bethesda, MD 20892 USA. EM GulleyJ@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS NR 102 TC 25 Z9 25 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD MAY PY 2006 VL 11 IS 5 BP 451 EP 462 DI 10.1634/theoncologist.11-5-451 PG 12 WC Oncology SC Oncology GA 085TM UT WOS:000240627300004 PM 16720845 ER PT J AU Ali, IU Xiao, Z Malone, W Smith, M Conrads, TP Veenstra, TD Greenwald, P Luke, BT McLarty, JW AF Ali, IU Xiao, Z Malone, W Smith, M Conrads, TP Veenstra, TD Greenwald, P Luke, BT McLarty, JW TI Plasma proteomic profiling: Search for lung cancer diagnostic and early detection markers SO ONCOLOGY REPORTS LA English DT Article DE lung cancer; surface-enhanced laser desorption ionization time-of-flight mass spectrometry; plasma proteomic profiling; diagnostic/early detection markers ID TYLER ASBESTOS WORKERS; MASS-SPECTROMETRY; PATTERNS AB Environmental and occupational exposure to asbestos is among the established risk factors for lung cancer, the leading cause of cancer-related deaths in the United States. This link between exposure to asbestos and the excessive death rate from lung cancer was evident in a study of former workers of an asbestos pipe insulation manufacturing plant in Tyler, TX. We performed comparative proteomic profiling of plasma samples that were collected from nine patients within 12 months before death and their age-, race- and exposure-matched disease-free controls on strong anion exchange chips using surface-enhanced laser desorption ionization time-of-flight mass spectrometry. A distance-dependent K-nearest neighbor (KNN) classification algorithm identified spectral features of m/z values 7558.9 and 15103.0 that were able to distinguish lung cancer patients from disease-free individuals with high sensitivity and specificity. The high correlation between the intensities of these two peaks (r=0.987) strongly suggests that they are the doubly and singly charged ions of the same protein product. Examination of these proteomic markers in the plasma samples of subjects from > 5 years before death from lung cancer suggested that they are related to the early development of lung cancer. Validation of these biomarkers would have significant implications for the early detection of lung cancer and better management of high-risk patients. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Lab Canc Prevent, Ctr Canc Res, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21702 USA. Louisiana State Univ, Hlth Sci Ctr, Feist Weiller Canc Ctr, Shreveport, LA 71105 USA. RP Ali, IU (reprint author), NCI, Div Canc Prevent, Bethesda, MD 20892 USA. EM alii@mail.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 19 TC 5 Z9 9 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD MAY PY 2006 VL 15 IS 5 BP 1367 EP 1372 PG 6 WC Oncology SC Oncology GA 034AB UT WOS:000236895200042 PM 16596212 ER PT J AU Zhang, Z Fan, J Becker, KG Graff, RD Lee, GM Francomano, CA AF Zhang, Z Fan, J Becker, KG Graff, RD Lee, GM Francomano, CA TI Comparison of gene expression profile between human chondrons and chondrocytes: a cDNA microarray study SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE cartilage; chondrocytes; chondrons; extracellular matrix; osteoarthritis ID HEAT-SHOCK PROTEINS; ARTICULAR-CARTILAGE; PERICELLULAR MICROENVIRONMENT; MESSENGER-RNA; ULTRASTRUCTURAL ANALYSIS; HYDROSTATIC-PRESSURE; VI COLLAGEN; MATRIX; AGAROSE; PROTEOGLYCANS AB Objective: The chondron is a basic unit of articular cartilage that includes the chondrocyte and its pericellular matrix (PCM). This current study was designed to investigate the effects of the chondron PCM on the gene expression profile of chondrocytes. Design: Chondrons and chondrocytes were enzymatically isolated from human articular cartilage, and maintained in pellet culture. Pellets of chondrons or chondrocytes were collected at days 1, 3 and 5 for cDNA microarray analysis. Results: In comparison with chondrocytes alone, chondrons had 258 genes, in a broad range of functional categories, either up- or downregulated at the three time points tested. At day 1, 26 genes were significantly upregulated in chondrons and four downregulated in comparison to chondrocytes. At day 3, the number of upregulated chondron genes was 97 and the number downregulated was 43. By day 5, there were more downregulated genes (56) than upregulated genes (32) in chondrons. Upregulation of a group of heat shock proteins (HSPA1A, HSPA2 and HSPA8) in chondrons was validated by real time reverse transcription polymerase chain reaction (RT-PCR). Genes related to chondrocyte hypertrophy and dedifferentiation such as SSP1 and DCN were downregulated in chondrons as compared to the expression in chondrocytes. Conclusion: The presence of the PCM in chondrons has a profound influence on chondrocyte gene expression. Upregulation of the heat shock protein 70 may contribute to the robustness and active matrix production of chondrons. The intact PCM may further stabilize the phenotype of chondrocytes within chondrons. (c) 2005 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Div Clin Immunol & Allergy, Baltimore, MD USA. NIA, NIH, Intramural Res Program, Baltimore, MD 21224 USA. Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC USA. RP Zhang, Z (reprint author), Johns Hopkins Univ, Dept Biomed Engn, 3400 N Charles St,Clark Hall 102, Baltimore, MD 21218 USA. EM zhangzj@jhu.edu OI Becker, Kevin/0000-0002-6794-6656 FU Intramural NIH HHS; NIAMS NIH HHS [AR43883] NR 33 TC 17 Z9 18 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD MAY PY 2006 VL 14 IS 5 BP 449 EP 459 DI 10.1016/j.joca.2005.11.008 PG 11 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 046VZ UT WOS:000237840500008 PM 16414292 ER PT J AU Cooney, MA Louis, GMB Sun, WY Rice, MM Klebanoff, MA AF Cooney, MA Louis, GMB Sun, WY Rice, MM Klebanoff, MA TI Is conception delay a risk factor for reduced gestation or birthweight? SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE time to conception; time to pregnancy; subfertility; birthweight; preterm; small-for-gestational-age ID EARLY-PREGNANCY LOSS; TIME-TO-PREGNANCY; LONG-TERM RECALL; QUESTIONNAIRE; FECUNDABILITY; INFERTILITY; POPULATION; VALIDITY; HISTORY; WOMEN AB Previous studies have suggested an association between delays in conception and adverse perinatal outcomes, specifically, low birthweight and preterm birth. We investigated the relationship between conception delay (defined as > 6 months to become pregnant) and three perinatal outcomes: low birthweight (LBW; < 2500 g), preterm birth (PTB; < 37 weeks), and small-for-gestational-age (SGA; < 10th percentile weight for given gestational age) using data from the Collaborative Perinatal Project. The study cohort was limited to pregnancies with a known time-to-pregnancy (n = 8465; 15%). Generalised estimating equations were used to estimate odds ratios (OR) and 95% confidence intervals [CI] for risk of adverse perinatal outcomes accounting for the clustering of pregnancy outcomes for women with more than one pregnancy. After adjusting for confounders, all ORs were close to the null (LBW, OR = 1.01; 95% CI = 0.86, 1.20), (PTB, OR = 1.10; 95% CI = 0.95, 1.27), (SGA, OR = 1.06; 95% CI = 0.91, 1.25). Thus, we found no evidence to support an adverse relationship between conception delay and decrements in gestation or birthweight among this select sample of fertile women, even after varying the cut-point for defining conception delay. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Rockville, MD USA. George Washington Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Washington, DC 20052 USA. EM cooneyma@mail.nih.gov OI Buck Louis, Germaine/0000-0002-1774-4490 NR 28 TC 7 Z9 8 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD MAY PY 2006 VL 20 IS 3 BP 201 EP 209 DI 10.1111/j.1365-3016.2006.00712.x PG 9 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 030ZB UT WOS:000236672800003 PM 16629694 ER PT J AU Mellemkjaer, L Hasle, H Gridley, G Johansen, C Kjaer, SK Frederiksen, K Olsen, JH AF Mellemkjaer, L Hasle, H Gridley, G Johansen, C Kjaer, SK Frederiksen, K Olsen, JH TI Risk of cancer in children with the diagnosis immaturity at birth SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE childhood cancer; CNS tumours; preterm; newborn X-rays ID CHILDHOOD BRAIN-TUMORS; YOUNG-CHILDREN; REPRODUCTIVE HISTORY; MALIGNANT NEOPLASMS; IONIZING-RADIATION; PREGNANCY; LEUKEMIA; ASSOCIATION; WEIGHT; CLASSIFICATION AB Cancer risk in children born before term has been assessed in a large number of case-control studies but very rarely in cohort studies. We carried out a cohort study of 35 178 children with the diagnosis immaturity at birth in the Hospital Discharge Register during 1977-89. The children were followed for cancer in the Danish Cancer Registry until 1994 and comparisons were made with incidence rates for all children in Denmark. The 64 observed cases of childhood cancer in the cohort corresponded closely to the expected number {standardised incidence ratio (SIR) = 1.03; [95% confidence interval (CI) 0.80, 1.32]}. The only cancer site with an observed number that deviated significantly from the expected number was central nervous system (CNS) tumours (26 cases observed; SIR = 1.57; [95% CI 1.02, 2.30]) in particular medulloblastoma (9 cases observed; SIR = 3.1; [95% CI 1.4, 5.9]). In a nested case-control study of the CNS tumours, we found that more cases than controls had been exposed to diagnostic X-rays, but the result was not significant. Surprisingly, for those born before term, the risk of CNS tumours increased with increasing gestational age in the nested case-control data. Our results are in line with previous evidence that children born before term are not at increased risk for childhood cancer in general. An explanation behind the excess of CNS tumours could not be identified, but the effect of diagnostic X-rays in newborns may deserve further attention. C1 Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen O, Denmark. Aarhus Univ Hosp Skejby, Dept Paediat, Aarhus, Denmark. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Mellemkjaer, L (reprint author), Danish Canc Soc, Inst Canc Epidemiol, Strandblvd 49, DK-2100 Copenhagen O, Denmark. EM lene@cancer.dk FU NCI NIH HHS [N01-CP-61111] NR 42 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD MAY PY 2006 VL 20 IS 3 BP 231 EP 237 DI 10.1111/j.1365-3016.2006.00717.x PG 7 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 030ZB UT WOS:000236672800006 PM 16629697 ER PT J AU Gropman, AL Duncan, WC Smith, ACM AF Gropman, AL Duncan, WC Smith, ACM TI Neurologic and developmental features of the Smith-Magenis syndrome (del 17p11.2) SO PEDIATRIC NEUROLOGY LA English DT Review ID CONTIGUOUS-GENE SYNDROME; IN-SITU HYBRIDIZATION; SLEEP-WAKE PATTERNS; DELETION SYNDROME; CIRCADIAN-RHYTHM; CHILDREN; MELATONIN; INFANTS; RAI1; DEL(17)(P11.2) AB The Smith-Magenis syndrome is a rare, complex multisystemic disorder featuring, mental retardation and multiple congenital anomalies caused by a heterozygous interstitial deletion of chromosome 17p11.2. The phenotype of Smith-Magenis syndrome is characterized by a distinct pattern of features including infantile hypotonia, generalized complacency and lethargy in infancy, minor skeletal (brachycephaly, brachydactyly) and craniofacial features, ocular abnormalities, middle ear and laryngeal abnormalities including hoarse voice, as well as marked early expressive speech and language delays, psychomotor and growth retardation, and a 24-hour sleep disturbance. A striking neurobehavioral pattern of stereotypies, hyperactivity, polyembolokoilamania, onychotillomania, maladaptive and self-injurious and aggressive behavior is observed with increasing age. The diagnosis of Smith-Magenis syndrome is based upon the clinical recognition of a constellation of physical, developmental, and behavioral features in combination with a sleep disorder characterized by inverted circadian rhythm of melatonin secretion. Many of the features of Smith-Magenis syndrome are subtle in infancy and early childhood, and become more recognizable with advancing age. Infants are described as looking "cherubic" with a Down syndrome-like appearance, whereas with age the facial appearance is that of relative prognathism. Early diagnosis requires awareness of the often subtle clinical and neurobehavioral phenotype of the infant period. Speech delay with or without hearing loss is common. Most children are diagnosed in mid-childhood when the features of the disorder are most recognizable and striking. While improvements in cytogenetic analysis help to bring cases to clinical recognition at an earlier age, this review seeks to increase clinical awareness about Smith-Magenis syndrome by presenting the salient features observed at different ages including descriptions of the neurologic and behavioral features. Detailed review of the circadian rhythm disturbance unique to Smith-Magenis syndrome is presented. Suggestions for management of the behavioral and sleep difficulties are discussed in the context of the authors' personal experience in the setting of an ongoing Smith-Magenis syndrome natural history study. (c) 2006 by Elsevier Inc. All rights reserved. C1 Georgetown Univ, Ctr Med, Dept Pediat, Washington, DC 20007 USA. Georgetown Univ, Ctr Med, Dept Genet & Metab, Washington, DC 20007 USA. Georgetown Univ, Ctr Med, Dept Neurol, Washington, DC 20007 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disorders Program, Washington, DC 20032 USA. Georgetown Univ, Dept Oncol, Washington, DC 20032 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Gropman, AL (reprint author), Georgetown Univ, Ctr Med, Dept Pediat, 3800 Reservoir Rd,NW 2PHC, Washington, DC 20007 USA. EM ag334@georgetown.edu RI SMITH, ANN C.M./C-1122-2008 FU Intramural NIH HHS NR 61 TC 54 Z9 59 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD MAY PY 2006 VL 34 IS 5 BP 337 EP 350 DI 10.1016/j.pediatrneurol.2005.08.018 PG 14 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 043XR UT WOS:000237636700001 PM 16647992 ER PT J AU Lee, BH Stoll, BJ McDonald, SA Higgins, RD AF Lee, BH Stoll, BJ McDonald, SA Higgins, RD CA Natl I Child Hlth Human Dev TI Adverse neonatal outcomes associated with antenatal dexamethasone versus antenatal betamethasone SO PEDIATRICS LA English DT Article DE antenatal glucocorticoids; dexamethasone; betamethasone; neonatal morbidity; neonatal mortality ID BIRTH-WEIGHT INFANTS; PERIVENTRICULAR LEUKOMALACIA; PREMATURE-INFANTS; GLUCOCORTICOID TREATMENT; RESPIRATORY-DISTRESS; FETAL MATURATION; CONTROLLED TRIAL; PRETERM INFANTS; CEREBRAL-PALSY; RISK-FACTORS AB OBJECTIVE. Antenatal dexamethasone and betamethasone may not be equally efficacious in the prevention of adverse neonatal outcomes. We compared the risks of periventricular leukomalacia ( PVL), intraventricular hemorrhage ( IVH), retinopathy of prematurity ( ROP), and neonatal death among very low birth weight infants who were exposed to dexamethasone, betamethasone, or neither steroid. METHODS. Infants ( 401 - 1500 g) in the National Institute of Child Health and Human Development Neonatal Research Network were studied. Multivariate logistic regression analyses compared the 3 groups with regard to PVL, IVH, ROP, and neonatal death, adjusting for network center and selected covariates. RESULTS. A total of 3600 infants met entry criteria. Compared with no antenatal steroids, there were trends for a reduced risk for PVL associated with dexamethasone and betamethasone but no difference in risk between dexamethasone and betamethasone. Dexamethasone reduced the risk for IVH and severe IVH, compared with no antenatal steroid exposure. Betamethasone reduced the risk for IVH, severe IVH, and neonatal death, compared with no antenatal steroids. Compared with betamethasone, dexamethasone had a statistically significant increased risk for neonatal death. There were trends for greater risks associated with dexamethasone compared with betamethasone for IVH and severe ROP. CONCLUSIONS. Betamethasone was associated with a reduced risk for neonatal death, with trends of decreased risk for other adverse neonatal outcomes, compared with dexamethasone. It may be in the best interest of neonates to receive betamethasone rather than dexamethasone when available. C1 Emory Univ, Sch Med, Div Neonatal Perinatal Med, Atlanta, GA 30322 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NICHHD, Washington, DC USA. RP Lee, BH (reprint author), Emory Univ, Sch Med, Div Neonatal Perinatal Med, 2015 Uppergate Dr, Atlanta, GA 30322 USA. EM ben_lee@oz.ped.emory.edu FU NICHD NIH HHS [U10 HD27904, U10 HD21364, U10 HD21373, U10 HD21385, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD34216, U10 HD36790, U10 HD40461, U10 HD40492, U10 HD40521, U10 HD40689] NR 36 TC 58 Z9 66 U1 0 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 2006 VL 117 IS 5 BP 1503 EP 1510 DI 10.1542/peds.2005-1749 PG 8 WC Pediatrics SC Pediatrics GA 038GO UT WOS:000237207300035 PM 16651303 ER PT J AU Botkin, JR Clayton, EW Fost, NC Burke, W Murray, TH Baily, MA Wilfond, B Berg, A Ross, LF AF Botkin, JR Clayton, EW Fost, NC Burke, W Murray, TH Baily, MA Wilfond, B Berg, A Ross, LF TI Newborn screening technology: Proceed with caution SO PEDIATRICS LA English DT Editorial Material ID TANDEM MASS-SPECTROMETRY; INBORN-ERRORS; CYSTIC-FIBROSIS; METABOLISM; PHENYLKETONURIA; PROGRAMS; ETHICS; POLICY; TESTS C1 Univ Utah, Dept Pediat & Med Eth, Salt Lake City, UT 84112 USA. Vanderbilt Univ, Dept Genet & Hlth Policy, Nashville, TN USA. Vanderbilt Univ, Dept Pediat, Nashville, TN USA. Vanderbilt Univ, Dept Law, Nashville, TN USA. Univ Wisconsin, Dept Pediat, Sch Med, Madison, WI 53706 USA. Univ Wisconsin, Dept Med Hist, Sch Med, Madison, WI 53706 USA. Univ Wisconsin, Dept Bieth, Sch Med, Madison, WI 53706 USA. Univ Washington, Dept Med Hist & Eth, Seattle, WA 98195 USA. Univ Washington, Dept Family Med, Seattle, WA 98195 USA. NIH, Natl Human Genome Res Ins, Bioeth & Social Policy Unit, Social & Behav Res Branch,Clin Ctr, Bethesda, MD USA. NIH, Ctr Clin, Genet Sect, Dept Clin Eth, Bethesda, MD USA. Hastings Ctr, Garrison, NY USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. Univ Chicago, MacLean Ctr Clin Med Eth, Chicago, IL 60637 USA. RP Botkin, JR (reprint author), Res Adm Bldg,75 S 2000 E 108, Salt Lake City, UT 84112 USA. EM jeffrey.botkin@hsc.utah.edu OI Clayton, Ellen/0000-0002-0308-4110 FU NHGRI NIH HHS [1 R01 HG02579] NR 37 TC 96 Z9 97 U1 1 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 2006 VL 117 IS 5 BP 1793 EP 1799 DI 10.1542/peds.2005-2547 PG 7 WC Pediatrics SC Pediatrics GA 038GO UT WOS:000237207300070 PM 16651338 ER PT J AU Alexander, D van Dyck, PC AF Alexander, D van Dyck, PC TI A vision of the future of newborn screening SO PEDIATRICS LA English DT Article DE newborn screening; recommendations AB In 40 years, newborn screening has evolved to become a standard component of preventive public health. Despite its widespread acceptance, efforts need to be made to overcome some significant problems. There is inequity in the conditions for which states screen routinely, and many conditions that could be screened for are not, for economic or logistic reasons. Existing (tandem mass spectrometry) and potential ( DNA microarray) technologies could be developed and put in place to correct these existing shortcomings. To do so will require investment in the technologies, combined with public and professional education and provision of a high-quality, accessible system for confirmation of diagnoses, family counseling, initiation of treatment, and the opportunity to participate in research to develop new or improved therapies. C1 NIH, Bethesda, MD 20892 USA. US Hlth Resources & Serv Adm, Rockville, MD 20857 USA. RP Alexander, D (reprint author), NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 3 TC 49 Z9 50 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 2006 VL 117 IS 5 SU S BP S350 EP S354 DI 10.1542/peds.2005-2633O PG 5 WC Pediatrics SC Pediatrics GA 038GR UT WOS:000237207600015 PM 16735262 ER PT J AU Yang, HYT Iadarola, MJ AF Yang, HYT Iadarola, MJ TI Modulatory roles of the NPFF system in pain mechanisms at the spinal level SO PEPTIDES LA English DT Review DE NPFF; RF-NH2 peptides; NPFF receptor; nociception; inflammation; spinal level ID PROLACTIN-RELEASING PEPTIDE; NEUROPEPTIDE-FF RECEPTORS; PROTEIN-COUPLED RECEPTOR; CENTRAL-NERVOUS-SYSTEM; MAMMALIAN FMRF-NH2-LIKE PEPTIDE; HUMAN CEREBROSPINAL-FLUID; REDUCES FOOD-INTAKE; RAT-BRAIN; MASS-SPECTROMETRY; ION CHANNELS AB The possible roles of the NPFF system in pain processing are summarized from the viewpoints of (1) biological activities of NPFF, (2) anatomical distribution of NPFF and its receptor(s) and (3) the regulation of NPFF and receptor(s) in animal models of pain. NPFF and NPFF analogues were found to have analgesic, pronociceptive and morphine modulating activities. Since the isolation of NPFF, several other RF-NH2 peptides have been identified and some of them were found to have nociceptive or morphine modulating activity. Depending on the pharmacological doses and locations of administration, NPFF may exhibit the biological activities of other structurally related RF-NH2 peptides thus complicating NPFF bioactivity studies and their interpretation. Acid sensing ion channels were found to respond to RF-NH2 peptides including NPFF, raising the possibility that interaction of NPFF and acid sensing ion channels can modulate nociceptive activity. NPFF and NPFF receptor mRNAs are highly expressed and localized in the superficial layers of the dorsal cord, the two genes are also in dorsal root ganglia though at much lower level. The spinal NPFF system is up-regulated by peripheral inflammation in the rat. Furthermore, immunohistochemically, NPFF receptor 2-protein was demonstrated to be increased in the primary afferents in the spinal cord of rats with peripheral inflammation. Regulation and localization of spinal NPFF systems, taken together with the analgesic bioactivity of intrathecally administered NPFF, strongly suggest involvement of spinal NPFF system in pain processing. (c) 2006 Elsevier Inc. All rights reserved. C1 Natl Inst Dent & Craniofacial Res, Neuronal Gene Express Sect, Pain & Neurosensory Mechan Branch, NIH, Bethesda, MD 20892 USA. RP Yang, HYT (reprint author), Natl Inst Dent & Craniofacial Res, Neuronal Gene Express Sect, Pain & Neurosensory Mechan Branch, NIH, Bldg 49,Room 1A07,49 Convent Dr,MSC 4410, Bethesda, MD 20892 USA. EM hyang@dir.nidcr.nih.gov FU Intramural NIH HHS NR 76 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD MAY PY 2006 VL 27 IS 5 BP 943 EP 952 DI 10.1016/j.peptides.2005.06.030 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 045WE UT WOS:000237772600002 PM 16443306 ER PT J AU Jhamandas, K Milne, B Sutak, M Gouarderes, C Zajac, JM Yang, HYT AF Jhamandas, K Milne, B Sutak, M Gouarderes, C Zajac, JM Yang, HYT TI Facilitation of spinal morphine analgesia in normal and morphine tolerant animals by neuropeptide SF and related peptides SO PEPTIDES LA English DT Article DE spinal morphine; neuropeptide SF; analgesia; tolerance ID FF-RELATED PEPTIDES; PHARMACOLOGICAL CHARACTERIZATION; AUTORADIOGRAPHIC DISTRIBUTION; RAT; RECEPTORS; PAIN; IDENTIFICATION; NPFF1; ANTINOCICEPTION; MODULATION AB Neuropeptide FF and related synthetic amidated peptides have been shown to elicit sustained anti-nociceptive responses and potently augment spinal anti-nociceptive actions of spinal morphine in tests of thermal and mechanical nociception. Recent studies have described the occurrence of another octapeptide, neuropeptide SF (NPSF) in the spinal cord and the cerebrospinal fluid and demonstrated its affinity for the NPFF receptors. This study examined the effects of NPSF and two putative precursor peptides, EFW-NPSF and NPAF, on the spinal actions of morphine in normal and opioid tolerant rats using the tailflick and pawpressure tests. In normal rats, NPSF demonstrated weak intrinsic activity but sub-effective doses of the peptide significantly increased the magnitude and duration of spinal morphine anti-nociception in both tests. A low-dose of NPSF also augmented the spinal actions of a delta receptor agonist, deltorphin. The morphine-potentiating effect of NPSF was shared by EFW-NPSF and the octadecapeptide NPAF In animal rendered tolerant by continuous intrathecal infusion of morphine for 6 days, low dose NPSF itself elicited a significant anti-nociceptive response and potently increased morphine-induced response in both tests. In animals made tolerant by repeated injections of intrathecal morphine, administration of NPSF, EFW-NPSF, and NPAF with morphine reversed the loss of the anti-nociceptive effect and restored the agonist potency. The results demonstrate that in normal animals NPSF and related peptides exert strong potentiating effect on morphine anti-nociception at the spinal level and in tolerant animals these agents can reverse the loss of morphine potency. (c) 2006 Elsevier Inc. All rights reserved. C1 Queens Univ, Fac Hlth Sci, Dept Pharmacol & Toxicol, Kingston, ON K7L 3N6, Canada. Queens Univ, Fac Hlth Sci, Dept Anesthesiol, Kingston, ON K7L 3N6, Canada. CNRS, Inst Pharmacol & Biol Struct, UMR 5089, F-31077 Toulouse, France. NIDCR, Neuronal Gene Express Sect, Pain & Neurosurg Mechan Branch, NIH, Bethesda, MD 20892 USA. RP Jhamandas, K (reprint author), Queens Univ, Fac Hlth Sci, Dept Pharmacol & Toxicol, Kingston, ON K7L 3N6, Canada. EM jhamanda@post.queensu.ca RI Zajac, jean-marie/E-5129-2010 NR 39 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD MAY PY 2006 VL 27 IS 5 BP 953 EP 963 DI 10.1016/j.peptides.2005.09.017 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 045WE UT WOS:000237772600003 PM 16515821 ER PT J AU Nikolic, D Li, YM Chadwick, LR van Breemen, RB AF Nikolic, D Li, YM Chadwick, LR van Breemen, RB TI In vitro studies of intestinal permeability and hepatic and intestinal metabolism of 8-prenylnaringenin, a potent phytoestrogen from hops (Humulus lupulus L.) SO PHARMACEUTICAL RESEARCH LA English DT Article DE Caco-2 cells; hops; liquid chromatography-mass spectrometry (LC-MS); metabolism; natural products; 8-prenylnaringenin ID HUMAN LIVER-MICROSOMES; CACO-2 CELL MONOLAYERS; UDP-GLUCURONOSYLTRANSFERASES; FLAVONOID CHRYSIN; SUBSTRATE-SPECIFICITY; ESTROGENIC ACTIVITY; EXPORT PUMP; GLUCURONIDATION; IDENTIFICATION; INDUCTION AB The absorption potential and metabolism of 8-prenylnaringenin (8-PN) from hops (Humulus lupulus L.) were investigated. 8-PN is a potent estrogen with the potential to be used for the relief of menopausal symptoms in women. Monolayers of the human intestinal epithelial cancer cell line Caco-2 and human hepatocytes were incubated with 8-PN to model its intestinal absorption and hepatic metabolism, respectively. The apparent permeability coefficients for 8-PN in the apical-to-basolateral and basolateral-to-apical directions of a Caco-2 monolayer were 5.2 +/- 0.7 x 10(-5) and 4.9 +/- 0.5 x 10(-5) cm/s, respectively, indicating good intestinal absorption via passive diffusion. Both glucuronide and sulfate conjugates of 8-PN were detected in the Caco-2 cell incubations. The 4'-O-glucuronide was the predominant Caco-2 cell metabolite, followed by 7-O-sulfate and 4'-O-sulfate. Both phase I and phase II metabolites of 8-PN were formed by human hepatocytes. The 7-O-glucuronide was the most abundant hepatocyte metabolite, and no sulfate conjugates were detected. Incubations with various cDNA-expressed UDP-glucuronosyltransferases indicated that the isozymes UGT1A1, UGT1A6, UGT1A8, and UGT1A9 were responsible for glucuronidation of 8-PN. Although orally administered 8-PN should be readily absorbed from the intestine, its bioavailability should be reduced significantly by intestinal and hepatic metabolism. C1 Univ Illinois, Dept Med Chem & Pharmacognosy, UIC, NIH,Ctr Bot Dietary Supplements Res,Coll Pharm, Chicago, IL 60612 USA. RP van Breemen, RB (reprint author), Univ Illinois, Dept Med Chem & Pharmacognosy, UIC, NIH,Ctr Bot Dietary Supplements Res,Coll Pharm, 833 S Wood St, Chicago, IL 60612 USA. EM breemen@uic.edu FU NCCIH NIH HHS [P50AT00155, P50 AT000155, P50 AT000155-070001] NR 30 TC 25 Z9 27 U1 1 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES JI Pharm. Res. PD MAY PY 2006 VL 23 IS 5 BP 864 EP 872 DI 10.1007/s11095-006-9902-8 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 044KZ UT WOS:000237672600002 PM 16715376 ER PT J AU Simon, R Wang, SJ AF Simon, R Wang, SJ TI Use of genomic signatures in therapeutics development in oncology and other diseases SO PHARMACOGENOMICS JOURNAL LA English DT Article DE clinical trial; gene expression; genomic signature; oncology; study design; validation ID HLA-B REGION; LUNG-CANCER; GENETIC-VARIATIONS; MICROARRAY DATA; BREAST-CANCER; HYPERSENSITIVITY; ASSOCIATION; ABACAVIR; CLASSIFICATION; CHEMOTHERAPY AB Pharmacogenomics is the science of determining how the benefits and adverse effects of a drug vary among a target population of patients based on genomic features of the patient's germ line and diseased tissue. By identifying those patients who are most likely to respond while eliminating serious adverse effects, the therapeutic index of a drug can be substantially increased. This may facilitate demonstrating the effectiveness of the drug and may avoid subsequent problems due to serious adverse events. Our objective here is to provide clinical trial designs and analysis strategies for the utilization of genomic signatures as classifiers for patient stratification or patient selection in therapeutics development. We review methods for the development of genomic signature classifiers of treatment outcome in high-dimensional settings, where the number of variables available for prediction far exceeds the number of cases. The split-sample and cross-validation methods for obtaining estimates of prediction accuracy in developmental studies are described. We present clinical trial designs for utilizing genomic signature classifiers in therapeutics development. The purpose of the classifier is to facilitate the identification of groups of patients with a high probability of benefiting from it and avoiding serious adverse events. We distinguish exploratory analysis during the development of the genomic classifier from prospective planning and rigorous testing of therapeutic hypotheses in studies that utilize the genomic classifier in therapeutics development. We discuss a variety of clinical trial designs including those utilizing specimen collection and assay prospectively for newly accrued patients and those involving a prospectively planned analysis of archived specimens from a previously conducted clinical trial. Our discussion of the development and use of classifiers of efficacy is mostly focused on applications in oncology using classifiers based on biomarkers measured in tumors. Some of the same considerations apply, however, to development of efficacy and safety classifiers in nononcologic diseases based on single-nucleotide germline polymorphisms. C1 NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. US FDA, CDER, Off Biostat, Off Pharmacoepidemiol & Stat Sci, Rockville, MD 20857 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, MSC 7434,9000 Rockville Pike, Bethesda, MD 20892 USA. EM rsimon@nih.gov NR 25 TC 60 Z9 64 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD MAY PY 2006 VL 6 IS 3 BP 166 EP 173 DI 10.1038/sj.tpj.6500349 PG 8 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 045OM UT WOS:000237751400004 PM 16415922 ER PT J AU Young, R Batkai, S Dukat, M Glennon, RA AF Young, Richard Batkai, Sandor Dukat, Malgorzata Glennon, Richard A. TI TDIQ (5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline) exhibits anxiolytic-like activity in a marble-burying assay in mice SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE noradrenergic; Alzheimer's disease; dementia; drug abuse; insomnia; norepinephrine; obsessive-compulsive disorder (OCD); panic disorder; post-traumatic stress disorder (PTSD); premenstrual syndrome (PMS); sundowning ID SOCIAL-INTERACTION TEST; LOCUS-COERULEUS; SPIROIMIDAZOLINE AGONIST; STIMULUS PROPERTIES; HIGHLY POTENT; BINDING-SITES; CLONIDINE; RECEPTOR; ANXIETY; RAT AB Numerous studies have suggested that the central alpha(2)-adrenergic receptor system may exert an important role in some types of human anxiety. The anxiolytic-like activity and potential side effect-like activities of the novel and purported alpha(2)-adrenergic compound TDIQ (5,6,7,8-1,3-dioxolo[4,5-g] isoquinoline) were compared to those of the anxiolytic drugs diazepam and buspirone, and the nonselective alpha(2)-adrenergic agent clonidine. Anxiolytic-like behavior was assessed in an object (marble)-burying assay, a selective test for the evaluation of known anxiolytics and identification of putative antianxiety compounds, that used mice housed either alone or in groups (5/cage). The rodents' antianxiety-like effect was defined as dose-related increases in the number of marbles that remained uncovered in their bedding material without concomitant disruption of their motor activities. Rotarod and inclined screen procedures were employed as potential indicators of side effects. An additional test monitored the heart rate (HR) and blood pressure (BP) of mice after the intravenous (IV) administration of doses of TDIQ. The reference compounds inhibited marble-burying behavior in a dose-related manner and produced various degrees of impairment in the side effect tests. TDIQ also inhibited object burying and displayed a wide separation between doses that produced anxiolytic-like activity and doses that produced some, if any, disruption of coordinated movement and/or motor activity. Moreover, the IV administration of TDIQ, up to 10 mg/kg, produced negligible effects on the HR and BP of mice. TDIQ could be a lead candidate for a new type of structural compound in the treatment of certain forms of anxiety. (c) 2006 Elsevier Inc. All rights reserved. C1 Virginia Commonwealth Univ, Sch Pharm, Dept Med Chem, Richmond, VA 23298 USA. NIAAA, Lab Physiol Studies, NIMH, Bethesda, MD 20892 USA. RP Young, R (reprint author), Virginia Commonwealth Univ, Sch Pharm, Dept Med Chem, 410 N 12th St, Richmond, VA 23298 USA. EM ryoung@vcu.edu RI Batkai, Sandor/G-3889-2010; Batkai, Sandor/H-7983-2014 NR 45 TC 9 Z9 9 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAY PY 2006 VL 84 IS 1 BP 62 EP 73 DI 10.1016/j.pbb.2006.04.006 PG 12 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 066IR UT WOS:000239223400009 PM 16750844 ER PT J AU Young, R Rothman, RB Rangisetty, JB Partilla, JS Dukat, M Glennon, RA AF Young, Richard Rothman, Richard B. Rangisetty, Jagadeesh B. Partilla, John S. Dukat, Malgorzata Glennon, Richard A. TI TDIQ (5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline) inhibits the consumption of "snacks" in mice SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE alpha(2)-noradrenergic; anxiety; binge eating; eating disorders; feeding behavior; hypothalamus; monoamines; obesity; paraventricular nucleus ID FEEDING-BEHAVIOR; PARAVENTRICULAR NUCLEUS; NEUROPEPTIDE-Y; RAT HYPOTHALAMUS; LEPTIN RECEPTOR; OBESE-PATIENTS; NOREPINEPHRINE; CLONIDINE; RELEASE; YOHIMBINE AB There is considerable evidence that alpha(2)-adrenergic receptor activity exerts a pivotal role in initiation of feeding behavior. The appetite suppressant and monoamine release effects of TDIQ (5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline), a putative selective alpha(2)-adrenergic compound, were compared to those of fenfluramine, a reference drug that produces an anorectic effect via presynaptic release and reuptake inhibition of serotonin. The drugs were administered to two groups of mice that had learned to consume either sweet milk or chocolate pellets (i.e. "snacks") during the low-activity/reduced-feeding "light" portion of their light/dark cycle. The selectivity of the drugs to suppress the consumption of snacks was determined by comparing doses of each drug that inhibited the animals' consumption of snacks to doses of each drug that have been shown, or were shown, to impact the motor (i.e. locomotor, rotarod, and inclined-screen side effect-like tests) or conditioned taste aversion (CTA) behavior of mice. An evaluation of TDIQ as a releaser of monoamines was determined in rodent brain synaptosomes. The administration of TDIQ or fenfluramine inhibited the consumption of the snacks, and a comparison of their ED50 doses indicated that TDIQ is about 3 times more potent than fenfluramine (1.3 mg/kg vs. 4.2 mg/kg, respectively) in the sweet milk test and almost equipotent to fenfluramine (19.4 mg/kg vs. 18.4 mg/ kg, respectively) in the chocolate pellet assay. The selectivity of the appetite suppressant effect of TDIQ was differentiated from that of fenfluramine on the basis that TDIQ exhibited a wide separation between its dose-response effects that suppressed snack consumption and its minimal effects in tests that measured behavioral impairment. Moreover, TDIQ was distinguished from fenfluramine in that it displayed very low potencies as a presynaptic releaser of monoamines. Finally, TDIQ (0.3 mg/kg-30.0 mg/kg) did not induce a conditioned taste aversion. TDIQ may represent a novel chemical entity that exhibits a significantly favorable therapeutic-like (i.e. appetite suppressant) effect to side effect-like ratio. (c) 2006 Elsevier Inc. All rights reserved. C1 Virginia Commonwealth Univ, Sch Pharm, Dept Med Chem, Richmond, VA 23298 USA. NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Young, R (reprint author), Virginia Commonwealth Univ, Sch Pharm, Dept Med Chem, Box 540,410 N 12th St, Richmond, VA 23298 USA. EM ryoung@vcu.edu NR 61 TC 2 Z9 2 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAY PY 2006 VL 84 IS 1 BP 74 EP 83 DI 10.1016/j.pbb.2006.04.007 PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 066IR UT WOS:000239223400010 PM 16750261 ER PT J AU Fox, MA Stevenson, GW Rice, KC Riley, AL AF Fox, Meredith A. Stevenson, Glenn W. Rice, Kenner C. Riley, Anthony L. TI Naloxone, not proglumide or MK-801, alters effects of morphine preexposure on morphine-induced taste aversions SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE taste aversion; UCS preexposure; tolerance; morphine; proglumide; MK-801; naloxone; NMDA; CCK ID CONDITIONED PLACE PREFERENCE; RECEPTOR ANTAGONIST MK-801; MU-OPIOID RECEPTOR; CHOLECYSTOKININ OCTAPEPTIDE; PRE-EXPOSURE; NAIVE MICE; RATS; TOLERANCE; WITHDRAWAL; ACQUISITION AB Both cholecystokinin (CCK) antagonists and N-methyl-D-aspartate (NMDA) antagonists block or reduce the development of morphine tolerance in several analgesic assays. The present experiments were performed to assess the ability of the CCK antagonist proglumide and the NMDA antagonist MK-801 to affect tolerance to the aversive properties of morphine as indexed by conditioned taste aversion (CTA) learning. Specifically, male Sprague-Dawley rats were exposed to either vehicle or morphine (5 mg/kg) in combination with either proglumide (5 mg/kg; Experiment 1), MK-801 (0.1 mg/kg; Experiment 2) or naloxone (1, 3.2 mg/kg; Experiment 3). Saccharin was then presented and was followed by an injection of either vehicle or morphine (10 mg/kg). Animals preexposed to and conditioned with morphine acquired an attenuated morphine-induced aversion to saccharin. While neither proglumide nor MK-801 had an effect on this attenuation, naloxone blocked the effects of morphine preexposure, suggesting that neither CCK nor NMDA may be involved in the aversive effects of morphine (or their modulation by drug exposure). That the attenuating effects of morphine preexposure on a morphine-induced CTA can be blocked suggests that the weakening of the aversive effects of morphine with chronic use can be prevented, an effect that may have implications for overall drug acceptability. (c) 2006 Elsevier Inc. All rights reserved. C1 NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Univ New England, Dept Psychol, Biddeford, ME 04005 USA. Univ New England, Dept Pharmacol, Biddeford, ME 04005 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. American Univ, Dept Psychol, Psychopharmacol Lab, Washington, DC 20016 USA. RP Fox, MA (reprint author), NIMH, Clin Sci Lab, NIH, Bldg 10,Room 3D41, Bethesda, MD 20892 USA. EM mfox@mail.nih.gov NR 74 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAY PY 2006 VL 84 IS 1 BP 169 EP 177 DI 10.1016/j.pbb.2006.05.003 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 066IR UT WOS:000239223400022 PM 16777201 ER PT J AU Nakai, K Moffen, AG Chignell, CF AF Nakai, K Moffen, AG Chignell, CF TI An in vivo study of free radicals generated in murine skin by protoporphyrin IX and visible light SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID SPIN-RESONANCE DETECTION; MICE; SPECTROSCOPY; ADDUCTS AB Lipids extracted from the skin of C57BL/6J mice injected subcutaneously with alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) and exposed to topical protoporphyrin IX (PPIX) and visible light had significantly higher levels of POBN spin adducts compared with dark PPIX exposed or vehicle-treated controls. Computer analysis of the POBN adduct electron paramagnetic (spin) resonance (EPR) spectra indicated that two radical species were present in each extract, one of which was a lipid-derived carbon-centered adduct (1, a(N) = 14.8 G and a(H) = 2.6 G), whereas the other (2, a(N) = 13.8 G and a(H) = 1.8 G) was probably oxygen centered. Adduct 2 was present in greater proportion in lipids extracted from PPIX/light-exposed mice compared with dark or vehicle-treated controls. These findings suggest that PPIX/light generates free radicals in mouse skin, thus providing a radical mechanism for PPIX-induced photosensitivity. Our approach may be useful for the detection of free radicals generated by other skin photosensitizers and may also provide a means for testing putative skin-protecting agents. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Chignell, CF (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM chignell@niehs.nih.gov FU Intramural NIH HHS [Z01 ES050046-29] NR 19 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAY-JUN PY 2006 VL 82 IS 3 BP 738 EP 740 DI 10.1562/2006-01-30-RA-787 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 053RS UT WOS:000238323300018 PM 16522136 ER PT J AU Duncan, T Wiggert, B Whittaker, N Darrow, R Organisciak, DT AF Duncan, T Wiggert, B Whittaker, N Darrow, R Organisciak, DT TI Effect of visible light on normal and P23H-3 Transgenic rat retinas: Characterization of a novel retinoic acid derivative present in the P23H-3 retina SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID PHOTORECEPTOR DEGENERATION; RHODOPSIN MUTATIONS; OUTER SEGMENTS; INDUCED DAMAGE; PIGMENTOSA; SUSCEPTIBILITY; MODEL; MICE; DEHYDROGENASE; INCREASES AB Transgenic rats with the P23H mutation in rhodopsin exhibit increased susceptibility to light damage, compared with normal animals. It is known that light-induced retinal damage requires repetitive bleaching of rhodopsin and that photoreceptor cell loss is by apoptosis; however, the underlying molecular mechanism(s) leading to photoreceptor cell death are still unknown. Photoproducts, such as all-trans retinal or other retinoid metabolites, released by the extensive bleaching of rhodopsin could lead to activation of degenerative processes, especially in animals genetically predisposed to retinal degenerations. Using wild-type and transgenic rats carrying the P23H opsin mutation, we evaluated the effects of acute intense visible light on retinoid content, type and distribution in ocular tissues. Rats were exposed to green light (480-590 nm) for 0, 5, 10, 30 and 120 min. Following light treatment, rats were sacrificed and neural retinas were dissected free of the retinal pigment epithelium. Retinoids were extracted from retinal tissues and then subjected to HPLC and mass spectral analysis. We found that the light exposure affected relative levels of retinoids in the neural retina and retinal pigment epithelium of wild-type and P23H rat eyes similarly. In the P23H rat retina but not the wild-type rat retina, we found a retinoic acid-like compound with an absorbance maximum of 357 nm and a mass of 304 daltons. Production of this retinoic acid-like compound in transgenic rats is influenced by the age of the animals and the duration of light exposure. It is possible that this unique retinoid may be involved in the process of light-induced retinal degeneration. C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. Wright State Univ, Sch Med, Petticrew Res Lab, Dept Biochem & Mol Biol, Dayton, OH 45435 USA. RP Wiggert, B (reprint author), NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM wiggertb@nei.nih.gov FU Intramural NIH HHS; NEI NIH HHS [EY01959] NR 32 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAY-JUN PY 2006 VL 82 IS 3 BP 741 EP 745 DI 10.1562/2005-10-05-RA-712 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 053RS UT WOS:000238323300019 PM 16336041 ER PT J AU Argyrakis, P Weiss, GH AF Argyrakis, P Weiss, GH TI A first-passage time problem for many random walkers SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article DE membrane channels; lattice random walks AB The passage of ions through membrane channels plays an important role in many fields of biology. An earlier paper [M. Boguna, A.M. Berezhkovskii, G.H. Weiss, Phys. Rev. E 62 (2000) 3250] developed a toy model for statistical properties of the Occupancy of a single site by different numbers of lattice random walkers chosen from an infinite set. It was assumed there that the residence time in one Sojourn at the origin differed from the residence time of points elsewhere. In this paper we derive some properties of the corresponding first-passage time to the Occupancy of the special site by k(> 1) random walkers in one or two dimensions. Results of our study were obtained from an extensive set of Simulations. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Thessaloniki, Dept Phys, GR-54124 Thessaloniki, Greece. NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Argyrakis, P (reprint author), Univ Thessaloniki, Dept Phys, GR-54124 Thessaloniki, Greece. EM panos@physics.auth.gr NR 7 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD MAY 1 PY 2006 VL 363 IS 2 BP 343 EP 347 DI 10.1016/j.physa.2005.08.087 PG 5 WC Physics, Multidisciplinary SC Physics GA 028XU UT WOS:000236522900018 ER PT J AU Sakurai, N Nakagawa-Goto, K Ito, J Sakurai, Y Nakanishi, Y Bastow, KF Cragg, G Lee, KH AF Sakurai, Nobuko Nakagawa-Goto, Kyoko Ito, Junko Sakurai, Yojiro Nakanishi, Yuka Bastow, Kenneth F. Cragg, Gordon Lee, Kuo-Hslung TI Cytotoxic Alangium alkaloids from Alangium longiflorum SO PHYTOCHEMISTRY LA English DT Article DE Alangium longiflorum; Alangiaceae; cytotoxic activity; 10-O-demethylcephaeline; 10-O-demethylisocephaeline ID TETRAHYDROISOQUINOLINE-MONOTERPENE; LAMARCKII; NSC-33669; AGENT AB Seven alkaloids (1-7) were isolated from the stem bark of Alangium longiflorum. Compound 1, (-)-10-O-demethylisocephaeline, was isolated for the first time as a naturally occurring product from a plant source. All structures were elucidated by detailed spectroscopic analysis. Biological evaluation showed that 2, 10-O-demethylcephaeline, exhibited potent cytotoxic activity against human lung carcinoma (A549) and breast adenocarcinoma (MCF-7) with ED50 values of 0.013 and 0.062 mu M, respectively. The stereoisomer 1 was less potent than 2, and related compounds with different hydroxy/methoxy substitution patterns were also less potent or inactive. Thus, compound 2 merits attention as a cytotoxic lead for further study. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ N Carolina, Sch Pharm, Nat Prod Lab, Chapel Hill, NC 27599 USA. NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. RP Lee, KH (reprint author), Univ N Carolina, Sch Pharm, Nat Prod Lab, 315 Beard Hall,CB 7360, Chapel Hill, NC 27599 USA. EM khlee@une.edu RI GOTO, Kyoko/D-8389-2015 OI GOTO, Kyoko/0000-0002-1642-6538 FU NCI NIH HHS [CA-17625] NR 11 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9422 J9 PHYTOCHEMISTRY JI Phytochemistry PD MAY PY 2006 VL 67 IS 9 BP 894 EP 897 DI 10.1016/j.phytochem.2006.01.009 PG 4 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA 043KQ UT WOS:000237600300008 PM 16530796 ER PT J AU O'Meara, WP Smith, DL McKenzie, FE AF O'Meara, Wendy Prudhomme Smith, David L. McKenzie, F. Ellis TI Potential impact of intermittent preventive treatment (IPT) on spread of drug-resistant malaria SO PLOS MEDICINE LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; PLACEBO-CONTROLLED TRIAL; ELIMINATION HALF-LIFE; PYRIMETHAMINE-SULFADOXINE; TRANSMISSION; INTENSITY; CHILDREN; TANZANIA; MODEL; EPIDEMIOLOGY AB Background Treatment of asymptomatic individuals, regardless of their malaria infection status, with regularly spaced therapeutic doses of antimalarial drugs has been proposed as a method for reducing malaria morbidity and mortality. This strategy, called intermittent preventive treatment OPT), is currently employed for pregnant women and is being studied for infants OPTO as well. As with any drug-based intervention strategy, it is important to understand how implementation may affect the spread of drug-resistant parasites. This is a difficult issue to address experimentally because of the limited size and duration of IPTi trials as well as the intractability of distinguishing the spread of resistance due to conventional treatment of malaria episodes versus that due to IPTi when the same drug is used in both contexts. Methods and Findings Using a mathematical model, we evaluated the possible impact of treating individuals with antimalarial drugs at regular intervals regardless of their infection status. We translated individual treatment strategies and drug pharmacokinetics into parasite population dynamic effects and show that immunity, treatment rate, drug decay kinetics, and presumptive treatment rate are important factors in the spread of drug-resistant parasites. Our model predicts that partially resistant parasites are more likely to spread in low-transmission areas, but fully resistant parasites are more likely to spread under conditions of high transmission, which is consistent with some epidemiological observations. We were also able to distinguish between spread of resistance due to treatment of symptomatic infections and that due to IPTi. We showed that IPTi could accelerate the spread of resistant parasites, but this effect was only likely to be significant in areas of low or unstable transmission. Conclusions The results presented here demonstrate the importance of considering both the half-life of a drug and the existing level of resistance when choosing a drug for IPTi. Drugs to which little or no resistance exists are not advisable for IPT in high-transmission areas, but IPTi is not likely to significantly impact the spread of highly resistant parasites in areas where partial resistance is already established. IPTi is more likely to accelerate the spread of resistance in high-transmission areas than is IPT in adults (i.e., pregnant women). C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP O'Meara, WP (reprint author), NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. EM prudhomw@mail.nih.gov RI Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 FU Intramural NIH HHS [Z99 TW999999] NR 32 TC 44 Z9 45 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD MAY PY 2006 VL 3 IS 5 BP 633 EP 642 AR e141 DI 10.1371/journal.pmed.0030141 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 057VS UT WOS:000238623900018 PM 16573365 ER PT J AU Wendler, D Emanuel, EJ AF Wendler, David Emanuel, Ezekiel J. TI Mistrust among minorities and the trustworthiness of medicine - Authors' reply SO PLOS MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM DWendler@cc.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD MAY PY 2006 VL 3 IS 5 BP 702 EP 702 AR e245 DI 10.1371/journal.pmed.0030245 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 057VS UT WOS:000238623900030 ER PT J AU Custer, MC Risinger, JI Hoover, S Simpson, RM Patterson, T Barrett, JC AF Custer, MC Risinger, JI Hoover, S Simpson, RM Patterson, T Barrett, JC TI Characterization of an antibody that can detect the Kai1/CD82 murine metastasis suppressor SO PROSTATE LA English DT Article DE KAI1; CD82; tetraspanins ID SYNCYTIUM FORMATION; PROSTATE-CANCER; DOWN-REGULATION; INCLUDING CD9; CELL LINES; EXPRESSION; KAI1; PROTEIN; IDENTIFICATION; SUPERFAMILY AB BACKGROUND. Kai1, also known as CD82, is a member of the tetraspanin family (TM4SF). The human homolog, KAI1, is an activation antigen of T-cells and is a metastasis suppressor for prostate and other cancers. Little is known about the mouse protein because of the lack of antibody reagents. METHODS. Peptide immunized rabbits were used to generate polyclonal antibody to Kai1. The antibody was analyzed using immunoblotting, flow cytometry, and immunohistochemistry. RESULTS. This antibody specifically recognizes murine Kai1 protein, crossreacts with rat Kai1 but not with human KAI1 The normal tissue distribution of this protein in mice is shown to be similar to that of the human homolog. Interestingly, mouse prostatic epithelium showed differential expression within the lobes. CONCLUSION. This antibody, the first described that can specifically detect murine Kai1/CD82, should be very useful in addressing the mechanism of action of Kai1 in metastatic suppression. C1 NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. NCI, CCR, Mol Pathol Unit, NIH, Bethesda, MD 20892 USA. RP Custer, MC (reprint author), NCI, Lab Biosyst & Canc, NIH, 37 Convent Dr,Room 5046 MSC-4264, Bethesda, MD 20892 USA. EM custema@mail.nih.gov FU Intramural NIH HHS NR 21 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD MAY 1 PY 2006 VL 66 IS 6 BP 567 EP 577 DI 10.1002/pros.20386 PG 11 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 031RN UT WOS:000236721800001 PM 16372335 ER PT J AU Giomarelli, B Schumacher, KM Taylor, TE Sowder, RC Hartley, JL McMahon, JB Mori, T AF Giomarelli, B Schumacher, KM Taylor, TE Sowder, RC Hartley, JL McMahon, JB Mori, T TI Recombinant production of anti-HIV protein, griffithsin, by auto-induction in a fermentor culture SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE griffithsin; GRFT; lectin; anti-HIV; recombinant expression; E. coli; auto-induction; cyanovirin; CV-N; scytovirin ID ESCHERICHIA-COLI; MICROBICIDE DEVELOPMENT; INACTIVATING PROTEIN; CYANOVIRIN-N; PURIFICATION AB Griffithsin (GRFT) is a novel anti-HIV protein isolated from the red alga Griffithia sp. The potent anti-viral activity of GRFT against both laboratory and primary isolates of HIV at picomolar concentrations makes this protein an attractive candidate microbicide to prevent sexual transmission of HIV. Here, we describe the recombinant production and purification of a biologically active hexa-histidine-tagged GRFT (His-GRFT) from Escherichia coli. To facilitate a large-scale production of recombinant His-GRFT, we tested different expression conditions to optimize the expression in the cytoplasm of E coli to increase the overall production of soluble His-GRFT. Attempts to express His-GRFT in shake flask cultures resulted in a modest yield of soluble His-GRFT, with a large accumulation of the protein in inclusion bodies. The use of a fermenter and of a rich, auto-inducing medium allowed the total amount of His-GRFT per liter to be increased by about 45-fold, with approximately 70% of the protein expressed in the soluble fraction. N-terminal sequencing and MALDI-TOF analyses of the recombinant His-GRFT confirmed that the initial methionine residue was cleaved off. Recombinant His-GRFT showed equivalent activity with natural GRFT,. both in respect to gp120-binding characteristics as well as anti-HIV activity. Size-exclusion chromatography analysis showed that both native GRFT and recombinant His-GRFT existed as homodimers in solution. The expression system described in this work provides a basis for the mass production of GRIFT to allow further studies of the protein and investigation of therapeutic and preventive strategies against HIV. Published by Elsevier Inc. C1 NCI, Mol Targets Dev Program, Canc Res Ctr, Frederick, MD 21702 USA. NCI, Werner H Kirsten Student Internship Program, Canc Res Ctr, Frederick, MD 21702 USA. SAIC, Res Technol Program, Prot Express Lab, Frederick, MD 21702 USA. SAIC, AIDS Vaccine Program, Frederick, MD 21702 USA. RP Mori, T (reprint author), Takeda Pharmaceut Co Ltd, Div Pharmaceut Res, Biomed Res Labs, Yodogawa Ku, 2-17-85,Jusohonmachi, Osaka 5328686, Japan. EM mori@nciferf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 14 TC 35 Z9 38 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 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD MAY PY 2006 VL 47 IS 1 BP 194 EP 202 DI 10.1016/j.pep.2005.10.014 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 043MC UT WOS:000237604200024 PM 16300962 ER PT J AU Josic, D Brown, MK Huang, F Lim, YP Rucevic, M Clifton, JG Hixson, DC AF Josic, D Brown, MK Huang, F Lim, YP Rucevic, M Clifton, JG Hixson, DC TI Proteomic characterization of inter-alpha inhibitor proteins from human plasma SO PROTEOMICS LA English DT Article DE biomarkers; diagnostic and therapeutic agents; inter-alpha inhibitor proteins; proteomic characterization ID CLOTTING FACTOR-IX; TRYPSIN-INHIBITOR; HEAVY-CHAINS; OVARIAN-CANCER; LIGHT-CHAIN; IN-VIVO; FAMILY; BIKUNIN; SEPSIS; GLYCOSAMINOGLYCAN AB inter-alpha inhibitor proteins (IaIp) are a family of structurally related serine protease inhibitors found in relatively high concentrations in human plasma. Recent studies have implicated a role for IaIp in sepsis, and have demonstrated their potential as biomarkers in sepsis and cancer. For characterization of isolated IaI proteins and contaminating proteins during the last steps of the purification process, SELDI-TOF MS and HPLC-ESI-MS/MS were used. After separation by SDSPAGE or 2-DE, polypeptide bands of 80, 125 and 250 kDa were excised from gels and digested by trypsin. The tryptic peptides were analyzed by both MS methods. The main contamination during the purification process, a band of 80 kDa, contains mainly IaIp heavy chain (HC) H3. HC H1 and H2 were also found in this band. In addition, some vitamin K-dependent clotting factors and inhibitors and other plasma proteins were identified. The 125-kDa band, representing the pre-alpha inhibitor, was found to contain both bikunin and HC H3. The presence of other HC H1, H2 and the recently described HC H4 was also detected by SELDI-TOF MS. The presence of HC H1, H2, and H3 in the 125-kDa band was confirmed by ESI-MS/MS, but not the presence of the H4. Three polypeptides, H1 and H2 together with bikunin, were identified in the 250-kDa band, representing the ITI, by both MS techniques. Once again, the presence of H4 was detected in this band only by SELDI-TOF MS, but the number of corresponding peptides was still not sufficient for final identification of this polypeptide. The importance of the application of proteomic methods for the proper evaluation of therapeutic drugs based on human plasma is discussed. C1 Rhode Isl Hosp, COBRE, Ctr Canc Res Dev, Proteom Core, Providence, RI 02904 USA. Rhode Isl Hosp, Dept Med, Div Med Oncol, Providence, RI 02903 USA. RP Josic, D (reprint author), Rhode Isl Hosp, COBRE, Ctr Canc Res Dev, Proteom Core, 1 Hoppin St,Coro W 4, Providence, RI 02904 USA. EM djuro_josic@brown.edu FU NCRR NIH HHS [P20RR017695] NR 41 TC 37 Z9 38 U1 0 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD MAY PY 2006 VL 6 IS 9 BP 2874 EP 2885 DI 10.1002/pmic.200500563 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 045WN UT WOS:000237773500021 PM 16596706 ER PT J AU Orvisky, E Drake, SK Martin, BM Abdel-Hamid, M Ressom, HW Varghese, RS An, YM Saha, D Hortin, GL Loffredo, CA Goldman, R AF Orvisky, E Drake, SK Martin, BM Abdel-Hamid, M Ressom, HW Varghese, RS An, YM Saha, D Hortin, GL Loffredo, CA Goldman, R TI Enrichment of low molecular weight fraction of serum for MS analysis of peptides associated with hepatocellular carcinoma SO PROTEOMICS LA English DT Article DE biomarker; fibrinopeptide A; hepatocellular carcinoma; MALDI-TOF MS; serum ID MASS-SPECTROMETRY; BIOMARKER DISCOVERY; CANCER-DETECTION; MICROARRAY DATA; HEPATITIS-C; PROTEOMICS; TOF; PROTEINS; ELECTROPHORESIS; IDENTIFICATION AB A challenging aspect of biomarker discovery in serum is the interference of abundant proteins with identification of disease-related proteins and peptides. This study describes enrichment of serum by denaturing ultrafiltration, which enables an efficient profiling and identification of peptides up to 5 kDa. We consistently detect several hundred peptide-peaks in MALDI-TOF and SELDI-TOF spectra of enriched serum. The sample preparation is fast and reproducible with an average CV for all 276 peaks in the MALDI-TOF spectrum of 11%. Compared to unenriched serum, the number of peaks in enriched spectra is 4 times higher at an S/N ratio of 5 and 20 times higher at an S/N ratio of 10. To demonstrate utility of the methods, we compared 20 enriched sera of patients with hepatocellular carcinoma (HCC) and 20 age-matched controls using MALDI-TOF. The comparison of 332 peaks at p < 0.001 identified 45 differentially abundant peaks that classified HCC with 90% accuracy in this small pilot study. Direct TOF/TOF sequencing of the most abundant peptide matches with high probability des-Ala-fibrinopeptide A. This study shows that enrichment of the low molecular weight fraction of serum facilitates an efficient discovery of peptides that could serve as biomarkers for detection of HCC as well as other diseases. C1 Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA. NIH, Dept Lab Med, Clin Chem Serv, Bethesda, MD 20892 USA. NIMH, Unit Mol Struct, LNT, NIH, Bethesda, MD 20892 USA. NHTMRI, Viral Hepatitis Res Lab, Cairo, Egypt. RP Goldman, R (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, LCCC Room S183,3970 Reservoir Rd NW, Washington, DC 20057 USA. EM rg26@georgetown.edu RI Varghese, Rency/A-8770-2012 FU NIEHS NIH HHS [1R21ES011958-01A1] NR 41 TC 92 Z9 103 U1 0 U2 15 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD MAY PY 2006 VL 6 IS 9 BP 2895 EP 2902 DI 10.1002/pmic.200500443 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 045WN UT WOS:000237773500023 PM 16586431 ER PT J AU Klouckova, I Hrncirova, P Mechref, Y Arnold, RJ Li, TK McBride, WJ Novotny, MV AF Klouckova, I Hrncirova, P Mechref, Y Arnold, RJ Li, TK McBride, WJ Novotny, MV TI Changes in liver protein abundance in inbred alcohol-preferring rats due to chronic alcohol exposure, as measured through a proteomics approach SO PROTEOMICS LA English DT Article DE alcohol dependency; LC-MS/MS; rat liver; two-dimensional gel electrophoresis ID CHRONIC ETHANOL TREATMENT; ANIMAL-MODELS; FATTY LIVER; METABOLISM; DISEASE; ACETALDEHYDE; DEHYDROGENASE; CONSUMPTION; DRINKING; SYSTEM AB This study compares the total liver proteome of inbred alcohol-preferring line (iP) rats exposed to alcohol with iP rats without alcohol experience. Rat liver proteins were extracted using a threestep procedure. Each of the three solutions solubilizes a different set of proteins. The extracted proteins were separated by 2-DE. Scanned gels of two sample groups, alcohol-exposed iP and alcohol-naive iP, were compared, revealing many protein spots with significantly higher or lower densities. These spots were cut from the gel, destained, and subjected to trypsin digestion and subsequent identification by LC-MS/MS. Twenty-four individual rats, 12 alcohol-naive, and 12 alcohol-exposed, were used in this study. Two groups, each containing six naive and six exposed animals, were created for statistical comparison. For the first group, 64 spots were observed to have statistically significant intensity differences upon alcohol exposure across all three extracts while 118 such spots were found in the second group. There were 113 unique proteins in both groups together. The majority of these proteins were enzymes. Significant changes are observed for three major metabolic pathways: glycolysis, gluconeogenesis, and fatty acid P-oxidation. In addition, enzymes involved in protein synthesis and antioxidant activity show significant changes in abundance in response to alcohol exposure. C1 Indiana Univ, Dept Chem, Bloomington, IN 47405 USA. NIAAA, NIH, Bethesda, MD USA. Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. RP Novotny, MV (reprint author), Indiana Univ, Dept Chem, 800 E Kirkwood Ave, Bloomington, IN 47405 USA. EM novotny@indiana.edu OI Mechref, Yehia/0000-0002-6661-6073 NR 52 TC 19 Z9 20 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD MAY PY 2006 VL 6 IS 10 BP 3060 EP 3074 DI 10.1002/pmic.200500725 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 049IT UT WOS:000238010400013 PM 16619309 ER PT J AU Le, AD Funk, D Harding, S Juzytsch, W Fletcher, PJ Shaham, Y AF Le, AD Funk, D Harding, S Juzytsch, W Fletcher, PJ Shaham, Y TI Effects of dexfenfluramine and 5-HT3 receptor antagonists on stress-induced reinstatement of alcohol seeking in rats SO PSYCHOPHARMACOLOGY LA English DT Review DE 5-hydroxytryptamine; reinstatement; footshock; 5-HT3 receptors; relapse; stress ID CORTICOTROPIN-RELEASING-FACTOR; DORSAL RAPHE NUCLEUS; VOLUNTARY ETHANOL-CONSUMPTION; COCAINE-INDUCED REINSTATEMENT; CONDITIONED PLACE PREFERENCE; INDUCED RELAPSE; 5-HYDROXYINDOLEACETIC ACID; DRUG SEEKING; EXTRACELLULAR DOPAMINE; INDIVIDUAL-DIFFERENCES AB Rationale and objectives: We previously found that systemic injections of the 5-HT uptake blocker fluoxetine attenuate intermittent footshock stress-induced reinstatement of alcohol seeking in rats, while inhibition of 5-HT neurons in the median raphe induces reinstatement of alcohol seeking. In this study, we further explored the role of 5-HT in footshock stress-induced reinstatement of alcohol seeking by determining the effects of the 5-HT releaser and reuptake blocker dexfenfluramine, and the 5-HT receptor antagonists ondansetron and tropisetron, which decrease alcohol self-administration and anxiety-like responses in rats, on this reinstatement. Methods: Different groups of male Wistar rats were trained to self-administer alcohol (12% v/v) for 28-31 days (1 h/day, 0.19 ml per alcohol delivery) and then their lever responding for alcohol was extinguished over 9-10 days. Subsequently, the effect of systemic injections of vehicle or dexfenfluramine (0.25 or 0.5 mg/kg, i.p), ondansetron (0.001, 0.01, or 0.1 mg/kg, i.p), or tropisetron (0.001, 0.01, and 0.1 mg/kg, i.p) on reinstatement induced by 10 min of intermittent footshock (0.8 mA) was determined. Results: Systemic injections of dexfenfluramine, ondansetron or tropisetron attenuated footshock-induced reinstatement of alcohol seeking. Injections of dexfenfluramine, ondansetron, or tropisetron had no effect on extinguished lever responding in the absence of footshock. Conclusions: The present results provide additional support for the hypothesis that brain 5-HT systems are involved in stress-induced reinstatement of alcohol seeking. The neuronal mechanisms that potentially mediate the unexpected observation that both stimulation of 5-HT release and blockade of 5-HT3 receptors attenuate footshock-induced reinstatement are discussed. C1 Ctr Addict & Mental Hlth, Dept Neurosci, Toronto, ON M5S 2S1, Canada. Univ Toronto, Dept Pharmacol, Toronto, ON, Canada. Univ Toronto, Dept Psychiat, Toronto, ON, Canada. Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD USA. RP Le, AD (reprint author), Ctr Addict & Mental Hlth, Dept Neurosci, 33 Russell St, Toronto, ON M5S 2S1, Canada. EM Anh_Le@camh.net RI shaham, yavin/G-1306-2014 FU NIAAA NIH HHS [AA13108] NR 114 TC 29 Z9 29 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2006 VL 186 IS 1 BP 82 EP 92 DI 10.1007/s00213-006-0346-y PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 035EL UT WOS:000236982900010 PM 16521030 ER PT J AU Schmidt, KF Febo, M Shen, Q Luo, F Sicard, KM Ferris, CF Stein, EA Duong, TQ AF Schmidt, KF Febo, M Shen, Q Luo, F Sicard, KM Ferris, CF Stein, EA Duong, TQ TI Hemodynamic and metabolic changes induced by cocaine in anesthetized rat observed with multimodal functional MRI SO PSYCHOPHARMACOLOGY LA English DT Article DE multimodal imaging; CMRO2; BOLD; CBF; pharmacological fMRI; biophysical model; arterial spin labeling; hypercapnic calibration ID CEREBRAL-BLOOD-FLOW; OXYGEN-CONSUMPTION; FOREPAW STIMULATION; NEURAL ACTIVITY; OXIDATIVE-METABOLISM; RELATIVE CMRO2; IN-VIVO; BRAIN; ACTIVATION; BOLD AB Rationale: Physiological changes (such as heart rate and respiration rate) associated with strong pharmacological stimuli could change the blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) mapping signals, independent of neural activity. Objectives: This study investigates whether the physiological changes per se associated with systemic cocaine administration (1 mg/kg) contaminate the BOLD fMRI signals by measuring BOLD and cerebral blood flow (CBF) fMRI and estimating the cerebral metabolic rate of oxygen (CMRO2) changes. Materials and methods: BOLD and CBF fMRI was performed, and changes in CMRO2 were estimated using the BOLD biophysical model. Results: After systemic cocaine administration, blood pressure, heart rate, and respiration rate increased, fMRI signals remained elevated after physiological parameters had returned to baseline. Cocaine induced changes in the BOLD signal within regions of the reward pathway that were heterogeneous and ranged from -1.2 to 5.4%, and negative changes in BOLD were observed along the cortical surface. Changes in CBF and estimated CMRO2 were heterogeneous and positive throughout the brain, ranging from 14 to 150% and 10 to 55%, respectively. Conclusions: This study demonstrates a valuable tool to investigate the physiological and biophysical basis of drug action on the central nervous system, offering the means to distinguish the physiological from neural sources of the BOLD fMRI signal. C1 Emory Univ, Yerkes Imaging Ctr, Atlanta, GA 30329 USA. Univ Massachusetts, Ctr Comparat Neuroimaging, Worcester, MA 01605 USA. Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, Baltimore, MD USA. RP Duong, TQ (reprint author), Emory Univ, Yerkes Imaging Ctr, 954 Gatewood Rd, Atlanta, GA 30329 USA. EM tduong@emory.edu RI Duong, Timothy/B-8525-2008; Stein, Elliot/C-7349-2008; Shen, Qiang/B-8784-2008; Febo, Marcelo/G-5718-2011; OI Shen, Qiang/0000-0002-4287-3403; Febo, Marcelo/0000-0001-8981-4163 FU NIDA NIH HHS [R01 DA013517, R01DA13517]; NINDS NIH HHS [R01 NS045879, R01 NS045879-01A1, R01 NS045879-02, R01 NS045879-03, R01 NS045879-04, R01 NS045879-05, R01 NS045879-06] NR 46 TC 38 Z9 39 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2006 VL 185 IS 4 BP 479 EP 486 DI 10.1007/s00213-006-0319-1 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 028OP UT WOS:000236497900009 PM 16550388 ER PT J AU Shepard, JD Chuang, DT Shaham, Y Morales, M AF Shepard, JD Chuang, DT Shaham, Y Morales, M TI Effect of methamphetamine self-administration on tyrosine hydroxylase and dopamine transporter levels in mesolimbic and nigrostriatal dopamine pathways of the rat SO PSYCHOPHARMACOLOGY LA English DT Article DE tyrosine hydroxylase; dopamine transporter; neurotoxicity; ventral tegmental area; substantia nigra; forced abstinence ID STRESS-INDUCED REINSTATEMENT; VENTRAL TEGMENTAL AREA; COCAINE-SEEKING; NORADRENERGIC MECHANISMS; INDUCED NEUROTOXICITY; EXTINCTION BEHAVIOR; NUCLEUS-ACCUMBENS; HEROIN SEEKING; TIME-COURSE; WITHDRAWAL AB Rationale and objectives: Many studies have examined the effect of experimenter-delivered methamphetamine on the mesolimbic and nigrostriatal dopamine pathways. In contrast, little is known about the effect of methamphetamine self-administration on these neuronal pathways. We studied the effect of methamphetamine self-administration on two key regulators of dopamine transmission, tyrosine hydroxylase (TH), and dopamine transporter (DAT), in components of the mesolimbic and nigrostriatal dopamine pathways. Methods: Rats self-administered methamphetamine (0.1 mg/kg per infusion, fixed-ratio-1 reinforcement schedule) or saline (control condition) for 9 h/day over 10 days. The brains of these rats were collected after 1 or 30 days of forced abstinence and the expression levels of TH and DAT were assayed by in situ, hybridization and western blot. Results: TH mRNA and protein levels were increased in the ventral tegmental area (VTA, the cell body region of the mesolimbic dopamine system) and the substantia nigra pars compacta (SNC, the cell body region of the nigrostriatal dopamine system) after 1 day, but not 30 days, of forced abstinence from methamphetamine. In contrast, methamphetamine self-administration had no effect on TH protein levels in dopaminergic terminals located in the nucleus accumbens and caudate-putamen. In addition, methamphetamine self-administration had no effect on DAT mRNA levels in the VTA. Conclusions: Results suggest that extended daily access to self-administered methamphetamine results in a transient, short-lasting effect on mesolimbic and nigrostriatal dopamine neurons of the rat brain. C1 NIDA, Cellular Neurobiol Res Branch, IRP, NIH, Baltimore, MD 21224 USA. Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD USA. RP Morales, M (reprint author), NIDA, Cellular Neurobiol Res Branch, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mmorales@intra.nida.nih.gov RI shaham, yavin/G-1306-2014 FU Intramural NIH HHS NR 54 TC 37 Z9 37 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2006 VL 185 IS 4 BP 505 EP 513 DI 10.1007/s00213-006-0316-4 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 028OP UT WOS:000236497900012 PM 16555063 ER PT J AU Graham, JJ Lederman, RJ Dick, AJ AF Graham, John J. Lederman, Robert J. Dick, Alexander J. TI Magnetic resonance imaging and its role in myocardial regenerative therapy SO REGENERATIVE MEDICINE LA English DT Review DE magnetic resonance imaging; myocardium; regenerative therapy ID MESENCHYMAL STEM-CELLS; PASSIVE CATHETER TRACKING; CONGESTIVE-HEART-FAILURE; CONTRAST ENHANCEMENT; GD-DTPA; PROGENITOR CELLS; INFARCTION; MRI; TRANSPLANTATION; VOLUME AB There has been extensive interest recently in cardiac stem cell therapy. Current research has been hampered by differences in cell type, methods of delivery and efficacy evaluation. In this article we review the use of magnetic resonance imaging in this growing area and argue that it is well suited to all areas of myocardial regeneration: from patient identification, through cell delivery and tracking of appropriately labeled cells, to evaluation of therapeutic effect, Potential future advances are discussed including magnetic resonance imaging-guided intervention suites and the use of higher field strength magnets for cell tracking. C1 Sunnybrook Hlth Sci Ctr, Div Cardiol, Toronto, ON M4N 3M5, Canada. NHLBI, Cardiovasc Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Dick, AJ (reprint author), Sunnybrook Hlth Sci Ctr, Div Cardiol, D380,2075 Bawview Ave, Toronto, ON M4N 3M5, Canada. EM Alexander.Dick@sunnybrook.ca OI lederman, robert/0000-0003-1202-6673 NR 68 TC 4 Z9 6 U1 1 U2 3 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0751 J9 REGEN MED JI Regen. Med. PD MAY PY 2006 VL 1 IS 3 BP 347 EP 355 DI 10.2217/17460751.1.3.347 PG 9 WC Cell & Tissue Engineering; Engineering, Biomedical SC Cell Biology; Engineering GA 142UF UT WOS:000244675000014 PM 17465788 ER PT J AU Kim, H Csaky, KG Gravlin, L Yuan, P Lutz, RJ Bungay, PM Tansey, G De Monasterio, F Potti, GK Grimes, G Robinson, MR AF Kim, Hyuncheol Csaky, Karl G. Gravlin, Luisa Yuan, Peng Lutz, Robert J. Bungay, Peter M. Tansey, Ginger De Monasterio, Francisco Potti, Gopal K. Grimes, George Robinson, Michael R. TI Safety and pharmacokinetics of a preservative-free triamcinolone acetonide formulation for intravitreal administration SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article ID CYSTOID MACULAR EDEMA; ACCIDENTAL INTRAOCULAR INJECTION; HYDROXYPROPYL METHYLCELLULOSE; NONINFECTIOUS ENDOPHTHALMITIS; ANAPHYLACTIC SHOCK; TOXICITY; HYPERSENSITIVITY; DEGENERATION; CLEARANCE AB Purpose: The safety and pharmacokinetics of a triamcinolone acetonide (TA) preservative-free (TA-PF) formulation were investigated after intravitreal administration in rabbits. Methods: A TA-PF formulation was prepared as a sterile 40-mg/mL or 160-mg/mL suspension in single-use vials by adding TA powder to 0.5% hydroxypropyl methylcellulose in normal saline. TA-PF (4-mg and 16-mg doses) and Kenalog (Bristol-Myers-Squibb, Princeton, NJ) (4-mg dose) were injected into the vitreous of separate groups of rabbits, and drug levels were measured in the vitreous over time with HPLC. Ocular toxicology (clinical examination, serial electroretinography, and histopathologic analysis) was evaluated in a separate group of animals after intravitreal TA-PF injection. Results: The half-lives of the injection amount in the vitreous, 4-mg TA-PF, 16-mg TA-PF, and 4-mg Kenalog, were found to be 24 days, 39 days, and 23 days, respectively. There were no signs of toxicities by clinical examination after TA-PF injection. Serial electroretinograms of rabbits receiving either 4-mg or 16-mg intravitreal TA-PF injections remained normal over time. Histopathologic analysis showed normal ocular tissues in animals receiving either 4-mg or 16-mg intravitreal TA-PF injections. Conclusion: The half-life of TA in the vitreous after a 4-mg injection of either TA-PF or Kenalog was comparable. A 16-mg dose of TA-PF produced a long vitreous half-life, and this may be of clinical benefit in patients requiring 6 months of drug exposure in the eye for a chronic disease. C1 NEI, NIH, Bethesda, MD 20892 USA. NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. RP Robinson, MR (reprint author), Allergan Pharmaceut Inc, 2525 Dupont Dr,Mail Code T2-4A, Irvine, CA 92612 USA. EM Robinson-Michael@Allergan.com FU Intramural NIH HHS NR 48 TC 36 Z9 40 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD MAY-JUN PY 2006 VL 26 IS 5 BP 523 EP 530 DI 10.1097/00006982-200605000-00005 PG 8 WC Ophthalmology SC Ophthalmology GA 100QZ UT WOS:000241685000005 PM 16770258 ER PT J AU Sirimaharaj, M Robinson, MR Zhu, M Csaky, KG Donovan, B Sutter, F Gillies, MC AF Sirimaharaj, Maytinee Robinson, Michael R. Zhu, Meidong Csaky, Karl G. Donovan, Basil Sutter, Florian Gillies, Mark C. TI Intravitreal injection of triamcinolone acetonide for immune recovery uveitis SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; CYTOMEGALOVIRUS RETINITIS; CUSHINGS-SYNDROME; FLUTICASONE; AIDS C1 Univ Sydney, Dept Clin Ophthalmol, Save Sight Inst, Sydney, NSW 2001, Australia. NEI, Bethesda, MD 20892 USA. Sydney Hosp, Sydney Sexual Hlth Ctr, Sydney, NSW, Australia. Univ Sydney, Sch Publ Hlth, Sydney, NSW 2001, Australia. RP Gillies, MC (reprint author), Univ Sydney, Dept Clin Ophthalmol, Sydney Eye Hosp, GPOB 4337, Sydney, NSW 2001, Australia. EM mark@eye.usyd.edu.au RI gillies, mark/B-3242-2012 NR 8 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD MAY-JUN PY 2006 VL 26 IS 5 BP 578 EP 580 DI 10.1097/00006982-200605000-00013 PG 3 WC Ophthalmology SC Ophthalmology GA 100QZ UT WOS:000241685000013 PM 16770266 ER PT J AU Xing, GQ Zhang, L Russell, S Post, R AF Xing, GQ Zhang, L Russell, S Post, R TI Reduction of dopamine-related transcription factors Nurr1 and NGFI-B in the prefrontal cortex in schizophrenia and bipolar disorders SO SCHIZOPHRENIA RESEARCH LA English DT Article DE dopaminergic; transcription factor; schizophrenia; affective illness; prefrontal cortex; cell density; maturation; GFAP ID ORPHAN NUCLEAR RECEPTOR; TYROSINE-HYDROXYLASE GENE; FIBRILLARY ACIDIC PROTEIN; FACTOR-INDUCIBLE-B; NEUROPATHOLOGY-CONSORTIUM; MESSENGER-RNA; MORPHOMETRIC ANALYSIS; DEPRESSIVE DISORDER; NEURONAL DENSITY; PROGENITOR CELLS AB Abnormal cortical and subcortical dopaminergic activities are among the most consistent neuropathological findings in schizophrenia. The molecular mechanisms remain unspecified. NGFI-B and Nurr1 are two closely related transcription factors involved in dopaminergic cell differentiation, maturation, and apoptosis. NGFI-B knockout mice show attenuated behavioral response to dopamine receptor agonists, whereas Nurr1 knockout disrupts midbrain dopaminergic neuron development. To further understand the role of Nurr1 and NGFI-B in schizophrenia and bipolar disorders, we measured Nurr1 and NGFI-B mRNA in the prefrontal cortex Brodmann's areas 9 (BA 9) and BA 46 by in situ hybridization, and the protein levels in BA 9 by Western blotting, of patients with schizophrenia, major depression, and bipolar disorders, and non-psychiatric control subjects (n = 15 per group). NGFI-B mRNA (P < 0.05) and protein (P < 0.01) were significantly lower in patients with schizophrenia (BA9), and NGFI-B mRNA was lower in bipolar disorder (BA 9 and BA 46) than in the controls. In the deep cortical layers of BA 46, Nurr1 mRNA was significantly (P < 0.05) lower in patients with bipolar disorder and schizophrenia than in the controls. Nurr1 protein in BA 9 was significantly lower in major depression (P < 0.05) and lower at a trend level in schizophrenia (P=0.056) than in the controls. These data show a deficient prefrontal NGFI-13 and Nurr1 expression in schizophrenia and bipolar disorder. Further study may elucidate if and how these deficiencies could be associated with abnormal dopaminergic functions seen in both illnesses. (c) 2005 Elsevier B.V. All rights reserved. C1 Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Xing, GQ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Psychiat, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM gxing@usuhs.mil NR 68 TC 48 Z9 50 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2006 VL 84 IS 1 BP 36 EP 56 DI 10.1016/j.schres.2005.11.006 PG 21 WC Psychiatry SC Psychiatry GA 051KP UT WOS:000238160300005 PM 16631355 ER PT J AU Feld, JJ Heathcote, EJ AF Feld, JJ Heathcote, EJ TI Hepatitis B e antigen-positive chronic hepatitis B: Natural history and treatment SO SEMINARS IN LIVER DISEASE LA English DT Review DE immunotolerant state; HBeAg seroconversion; pegylated interferon; nucleos(t)ide therapies; drug resistance; risk factors; severe hepatitis B ID TERM-FOLLOW-UP; HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATOCELLULAR-CARCINOMA; INTERFERON THERAPY; LAMIVUDINE THERAPY; GENOTYPE-C; HBEAG SEROCONVERSION; ADEFOVIR DIPIVOXIL; ACUTE EXACERBATION; PEGYLATED INTERFERON-ALPHA-2B AB The natural history of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is very heterogeneous. Age at acquisition is a major factor in determining the natural history of chronic infection. The vigor of the host immune response to the virus, viral factors (genotype, core promoter mutations, and duration of viral replication) as well as exogenous factors (alcohol, immune suppression) all influence the severity of disease. The goal of antiviral therapy is HBeAg seroconversion, and preferably HB surface Ag seroconversion as this latter end-point is associated with sustained immune control and the halting of disease progression. Although peginterferon is now considered as the first line of therapy for HBeAg-positive chronic hepatitis B, in most cases there are circumstances where nucleos(t)ide analogues are indicated (e.g., decompensated liver disease) for those requiring cancer chemotherapy/other immunosuppressive agents and for those with contraindications to interferon. The major challenge for the clinician using these agents is the emergence of antiviral drug resistance. Long-term immune control of viral replication is key to improving patient outcome. C1 Toronto Western Hosp, Univ Hlth Network, Toronto, ON M5T 2S8, Canada. NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Heathcote, EJ (reprint author), Toronto Western Hosp, Univ Hlth Network, 399 Bathurst St,6B Fell Pavil,Room 154, Toronto, ON M5T 2S8, Canada. NR 82 TC 23 Z9 25 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0272-8087 EI 1098-8971 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD MAY PY 2006 VL 26 IS 2 BP 116 EP 129 DI 10.1055/s-2006-939750 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 040CT UT WOS:000237357300005 PM 16673290 ER PT J AU Cecchi, F Debolini, P Lova, RM Macchi, C Bandinelli, S Bartali, B Lauretani, F Benvenuti, E Hicks, G Ferrucci, L AF Cecchi, F Debolini, P Lova, RM Macchi, C Bandinelli, S Bartali, B Lauretani, F Benvenuti, E Hicks, G Ferrucci, L TI Epidemiology of back pain in a representative cohort of Italian persons 65 years of age and older - The InCHIANTI study SO SPINE LA English DT Article DE back pain; elderly; epidemiology ID LOWER-LIMBS; HEALTH; POPULATION; PREVALENCE; DISABILITY; SYMPTOMS; ASSOCIATION; STRENGTH; MOBILITY; OUTCOMES AB Study Design. Clinico-epidemiologic study in the Chianti area (Tuscany, Italy). Objectives. To describe prevalence and correlates of back pain in a representative sample of the population. Summary of Background Data. Back pain is common in old age and is related to functional limitations, but back pain characteristics and correlates in older adults, which may be targeted by specific interventions, are still under-investigated. Methods. A total of 1,299 persons aged 65 or older were selected from the city registry of Greve in Chianti and Bagno a Ripoli; 1,008 (565 women; 443 men) were included in this analysis. Back pain in the past 12 months was ascertained using a questionnaire. Potential correlates of back pain were identified in age- and sex-adjusted regression analyses, and their independent association with back pain was tested in a multivariate model. Results. The prevalence of frequent back pain was 31.5%. Back pain was reported less often by men and the very old, was primarily located in the dorsolumbar and lumbar spine, was moderate in intensity and mainly elicited by carrying, lifting, and pushing heavy objects. Among participants who reported frequent back pain, 76.3% had no back pain-related impairments; 7.4% of the overall study population had back pain-related functional limitation. Back pain participants were significantly more likely to report difficulty in heavy household chores, carrying a shopping bag, cutting toenails, and using public transportation. Limited trunk extension, depression, low levels of prior-year physical activity, and hip, knee, and foot pain were independent correlates of back pain. Conclusions. Frequent back pain is highly prevalent in the older population and is often associated with conditions that are potentially reversible. C1 NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. Fdn Don Carlo Gnocchi, Inst Recovery & Care Sci Character, Ctr S Maria Ulivi, Florence, Italy. Local Hlth Unit, Florence, Italy. Tuscany Reg Hlth Agcy, Florence, Italy. Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. Univ Maryland, Dept Phys Therapy & Rehabil Sci, Dept Epidemiol & Prevent Med, Sch Med, Baltimore, MD 21201 USA. RP Ferrucci, L (reprint author), NIA, Clin Res Branch, Longitudinal Studies Sect, ASTRA Unit,Harbor Hosp, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Lauretani, Fulvio/K-5115-2016 OI Lauretani, Fulvio/0000-0002-5287-9972 FU Intramural NIH HHS [Z99 AG999999] NR 39 TC 49 Z9 54 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD MAY 1 PY 2006 VL 31 IS 10 BP 1149 EP 1155 DI 10.1097/01.brs.0000216606.24142.e1 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 040EP UT WOS:000237362100014 PM 16648752 ER PT J AU Peila, R White, LR Masaki, K Petrovitch, H Launer, LJ AF Peila, R White, LR Masaki, K Petrovitch, H Launer, LJ TI Reducing the risk of dementia efficacy of long-term treatment of hypertension SO STROKE LA English DT Article DE dementia; hypertension; treatment ID ISOLATED SYSTOLIC HYPERTENSION; JAPANESE-AMERICAN MEN; BLOOD-PRESSURE; COGNITIVE FUNCTION; ANTIHYPERTENSIVE TREATMENT; CEREBROVASCULAR-DISEASE; OLDER PATIENTS; TRIAL; PREVENTION; ADULTS AB Background and Purpose-The efficacy of treating older persons for hypertension remains controversial. Although clinical trials suggest no short-term harm, or some benefits, there are little data on the effect on cognitive function of long-term antihypertensive treatment. We evaluated the risk of dementia and cognitive decline associated with duration of antihypertensive treatment. Methods-Data are from the Honolulu Asia Aging Study on Japanese American men followed since 1965. The subjects included in this analysis were hypertensive from midlife and dementia-free in 1991 (mean age 76.7 years). In 1991, 1994 and 1997, global cognitive function was assessed with the Cognitive Abilities Screening Instrument (ASI) and dementia by a standardized examination using international criteria. The sample was grouped by treatment duration (never-treated hypertensives (TH), <= 5 years, 5 to 12 years, > 12 years). Normote nsive subjects up to 1991 were included in the analysis as a control group. Results-For each additional year of treatment there was a reduction in the risk of incident dementia ( hazard ratio [HR] = 0.94, 95% CI, 0.89 to 0.99). The risk for dementia in subjects with > 12 years of treatment was lower compared to NTH (HR for dementia = 0.40; 95% CI, 0.22 to 0.75 and for Alzheimer disease HR = 0.35; 95% CI, 0.16 to 0.78) and was similar to the normotensives. Nondemented subjects with 5 to 12 years of treatment had lower yearly CASI decline compared to NTH. Conclusions-Results suggest that in hypertensive men, the duration of the antihypertensive treatment is associated with a reduced risk for dementia and cognitive decline. C1 NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. Pacific Hlth Res Inst, Honolulu, HI USA. Univ Hawaii Manoa, Dept Geriatr Med, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Peila, R (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, Room 3C-309 Gateway Bldg,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM peilar@mail.nih.gov FU NHLBI NIH HHS [N01-HC-0-5102]; NIA NIH HHS [N01-AG-4-2149, UO1-AG-0-9349-03] NR 36 TC 95 Z9 100 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2006 VL 37 IS 5 BP 1165 EP 1170 DI 10.1161/01.STR.0000217653.01615.93 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 036EN UT WOS:000237053900017 PM 16601212 ER PT J AU Howard, G Prineas, R Moy, C Cushman, M Kellum, M Temple, E Graham, A Howard, V AF Howard, G Prineas, R Moy, C Cushman, M Kellum, M Temple, E Graham, A Howard, V TI Racial and geographic differences in awareness, treatment, and control of hypertension - The REasons for geographic and racial differences in stroke study SO STROKE LA English DT Article DE geography; hypertension; racial differences ID SOUTHEASTERN UNITED-STATES; MORTALITY; PREVALENCE; DESIGN AB Background and Purpose-Stroke mortality is higher in the "Stroke Belt" and among blacks in the United States. Because hypertension is the leading risk factor for stroke, hypertension management (raising awareness, increasing treatment, and improving control) may reduce these disparities. Methods-Hypertension awareness, treatment, and control were measured in the REasons for Geographic And Racial Differences in Stroke study, a national population-based cohort of black and white participants > 45 years of age. At the time of this report, 11 701 had been enrolled. Racial differences and geographic differences (between the Stroke Belt and other regions of the United States) were described. Results-Black participants were more aware than whites of their hypertension (odds ratio [OR], 1.31; 95% CI, 1.07 to 1.59) and more likely to be on treatment if aware of their diagnosis (OR, 1.69; 95% CI, 1.40 to 2.05), but among those treated for hypertension, they were less likely than whites to have their blood pressure controlled (OR, 0.73; 95% CI, 0.64 to 0.83). There was no evidence of a difference between the Stroke Belt and other regions in awareness of hypertension (OR, 0.95; 95% CI, 0.79 to 1.14), but there was a trend for better treatment (OR, 1.15; 95% CI, 0.97 to 1.37) and control (OR, 1.11; 95% CI, 0.98 to 1.30) in the Stroke Belt region. Conclusions-These findings suggest that interventions to improve blood pressure control among blacks are promising to reduce the racial disparity in stroke mortality. The lack of substantial geographic differences in hypertension awareness and the trend toward better treatment and control in the Stroke Belt suggest that differences in hypertension management may not be a major contributor to the geographic disparity in stroke mortality. C1 Univ Alabama, Dept Biostat, Sch Publ Hlth, Birmingham, AL 35294 USA. Univ Alabama, Dept Epidemiol, Sch Publ Hlth, Birmingham, AL 35294 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. NINDS, NIH, Bethesda, MD 20892 USA. Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA. Examinat Management Serv Inc, Dallas, TX USA. RP Howard, G (reprint author), Univ Alabama, Dept Biostat, Sch Publ Hlth, Ryals Bldg,1665 Univ Blvd, Birmingham, AL 35294 USA. EM ghoward@uab.edu FU NINDS NIH HHS [NS 041588] NR 19 TC 127 Z9 128 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2006 VL 37 IS 5 BP 1171 EP 1178 DI 10.1161/01.STR.0000217222.09978.ce PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 036EN UT WOS:000237053900018 PM 16556884 ER PT J AU Furlan, AJ Eyding, D Albers, GW Al-Rawi, Y Lees, KR Rowley, HA Sachara, C Soehngen, M Warach, S Hacke, W AF Furlan, AJ Eyding, D Albers, GW Al-Rawi, Y Lees, KR Rowley, HA Sachara, C Soehngen, M Warach, S Hacke, W CA DEDAS Investigators TI Dose escalation of desmoteplase for acute ischemic stroke (DEDAS) - Evidence of safety and efficacy 3 to 9 hours after stroke onset SO STROKE LA English DT Article DE desmoteplase; stroke; thrombolytic therapy ID TISSUE-PLASMINOGEN ACTIVATOR; PERFUSION MRI; THROMBOLYSIS; DIFFUSION AB Background and Purpose-Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents. This study evaluated safety and efficacy of intravenous (IV) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke. Methods-DEDAS was a placebo-controlled, double-blind, randomized, dose-escalation study investigating doses of 90 mu g/kg and 125 mu g/kg desmoteplase. Eligibility criteria included baseline National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch. The safety end point was the rate of symptomatic intracranial hemorrhage. Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days. The primary analyses were intent-to-treat. Before unblinding, a target population, excluding patients violating specific MRI criteria, was defined. Results-Thirty-seven patients were randomized and received treatment (intent-to-treat; placebo: n= 8; 90 mu g/kg: n = 14; 125 mu g/kg: n = 15). No symptomatic intracranial hemorrhage occurred. Reperfusion was achieved in 37.5% (95% CI [8.5; 75.5]) of placebo patients, 18.2% (2.3; 51.8) of patients treated with 90 mu g/kg desmoteplase, and 53.3% (26.6; 78.7) of patients treated with 125 mu g/kg desmoteplase. Good clinical outcome at 90 days occurred in 25.0% (3.2; 65.1) treated with placebo, 28.6% (8.4; 58.1) treated with 90 mu g/kg desmoteplase and 60.0% (32.3; 83.7) treated with 125 mu g/ kg desmoteplase. In the target population (n = 25), the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 mu g/kg desmoteplase (P = 0.022). Conclusions-Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe. At a dose of 125 mu g/kg desmoteplase appeared to improve clinical outcome, especially in patients fulfilling all MRI criteria. The results of DEDAS generally support the results of its predecessor study, Desmoteplase in Acute Ischemic Stroke (DIAS). C1 Cleveland Clin, Dept Neurol, Cleveland, OH 44195 USA. PAION Deutschland GmbH, Aachen, Germany. Stanford Stroke Ctr, Palo Alto, CA USA. Univ Glasgow, Western Infirm, Dept Med & Therapeut, Glasgow G11 6NT, Lanark, Scotland. Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA. ClinRes GmbH, Cologne, Germany. NINDS, Bethesda, MD 20892 USA. Univ Heidelberg, Dept Neurol, Heidelberg, Germany. RP Furlan, AJ (reprint author), Cleveland Clin, Dept Neurol, S91,9500 Euclid Ave, Cleveland, OH 44195 USA. EM furlana@ccf.org NR 12 TC 356 Z9 377 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2006 VL 37 IS 5 BP 1227 EP 1231 DI 10.1161/01.STR.0000217403.66996.6d PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 036EN UT WOS:000237053900028 PM 16574922 ER PT J AU Zhou, J Pavel, J Macova, M Yu, ZX Imboden, H Ge, L Nishioku, T Dou, JT Delgiacco, E Saavedra, JM AF Zhou, J Pavel, J Macova, M Yu, ZX Imboden, H Ge, L Nishioku, T Dou, JT Delgiacco, E Saavedra, JM TI AT(1) receptor blockade regulates the local angiotensin II system in cerebral microvessels from spontaneously hypertensive rats SO STROKE LA English DT Article DE circulation; endothelial cells; hypertension; renin-angiotensin system ID GENE-DISRUPTED MICE; BRAIN MICROVESSELS; CONVERTING ENZYME; ENDOTHELIAL-CELLS; EXPRESSION; LOCALIZATION; RESPONSES; ISCHEMIA; KIDNEY; RENIN AB Background and Purpose-Blockade of angiotensin II AT(1) receptors in cerebral microvessels protects against brain ischemia and inflammation. In this study, we tried to clarify the presence and regulation of the local renin-angiotensin system (RAS) in brain microvessels in hypertension. Methods-Spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) controls were treated with an AT1 receptor antagonist (candesartan, 0.3 mg/ kg per day) via subcutaneous osmotic minipumps for 4 weeks. The expression and localization of RAS components and the effect of AT1 receptor blockade were assessed by Affymetrix microarray, qRT-PCR, Western blots, immunohistochemistry and immunofluorescence. Results-We found transcripts of most of RAS components in our microarray database, and confirmed their expression by qRT-PCR. Angiotensinogen (Aogen), angiotensin-converting enzyme (ACE) and AT(1) receptors were localized to the endothelium. There was no evidence of AT(2) receptor localization in the microvascular endothelium. In SHR, (pro) renin receptor mRNA and AT(1) receptor mRNA and protein expression were higher, whereas Aogen, ACE mRNA and AT(2) receptor mRNA and protein expression were lower than in WKY rats. Candesartan treatment increased Aogen, ACE and AT(2) receptor in SHR, and increased ACE and decreased Aogen in WKY rats, without affecting the (pro) renin and AT(1) receptors. Conclusions-Increased (pro) renin and AT(1) receptor expression in SHR substantiates the importance of the local RAS overdrive in the cerebrovascular pathophysiology in hypertension. AT(1) receptor blockade and increased AT(2) receptor stimulation after administration of candesartan may contribute to the protection against brain ischemia and inflammation. C1 NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NHLBI, Pathol Core, Bethesda, MD 20892 USA. Univ Bern, Inst Cell Biol, Bern, Switzerland. RP Zhou, J (reprint author), NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM jinzhou@mail.nih.gov FU Intramural NIH HHS NR 31 TC 59 Z9 65 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2006 VL 37 IS 5 BP 1271 EP 1276 DI 10.1161/01.STR.0000217404.64352.d7 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 036EN UT WOS:000237053900036 PM 16601219 ER PT J AU Jagoda, EM Lang, LX Tokugawa, J Simmons, A Ma, Y Contoreggi, C Kiesewetter, D Eckelman, WC AF Jagoda, EM Lang, LX Tokugawa, J Simmons, A Ma, Y Contoreggi, C Kiesewetter, D Eckelman, WC TI Development of 5-HT1A receptor radioligands to determine receptor density and changes in endogenous 5-HT SO SYNAPSE LA English DT Article DE 5-HT1A receptors; 5-HT; FPWAY; PET ID IN-VIVO MICRODIALYSIS; BLOOD-BRAIN-BARRIER; URETHANE ANESTHESIA; PHYSIOPHARMACOLOGICAL INVESTIGATIONS; SEROTONIN RECEPTORS; C-11 WAY-100635; P-GLYCOPROTEIN; KNOCKOUT MICE; BINDING; PET AB [F-18]FCWAY and [F-18]FPWAY, analogues of the high affinity 5-HT1A receptor (5-HT1AR) antagonist WAY100635, were evaluated in rodents as potential radiopharmaceuticals for determining 5-HT1AR density and changes in receptor occupancy due to changes in endogenous serotonin (5-HT) levels. The in vivo hippocampus specific binding ratio [(hippocampus(uptakde)/cerebellum(uptake))-1] of [F-18]FPWAY was decreased to 32% of the ratio of [18 F]FCWAY, indicating that [18F]FPWAY has lower affinity than [F-18]FCWAY. The 5-HT1AR selectivity of [(1)8F]FPWAY was confirmed using ex vivo autoradiography studies with 5-HT1AR knockout, heterozygous, and wildtype mice. Pre- or post-treatment of awake rodents in tissue dissection studies with paroxetine had no effect on hippocampal binding of [F-18]FCWAY or [F-18]FPWAY compared to controls, indicating neither tracer was sensitive to changes in endogenous 5-HT. In mouse ex vivo autoradiography studies in which awake mice were treated with fenfluramine following the [F-18]FPWAY, a significant decrease was not observed in the hippocampus specific binding ratios. In rat dissection studies with fenfluramine administered following [F-18]FPWAY or [F-18]FBWAY ([F-18]-MPPF) in awake or urethane-anesthetized rats, no significant differences in the specific binding ratios of the hippocampus were observed compared to their respective controls. [F-18]FPWAY and [F-18]FBWAY uptakes in all brain regions were increased variably in the anesthetized group (with the greatest increase in the hippocampus) vs. the awake group, but were decreased in the fen-fluralmine-treated anesthetized group vs. the anesthetized group. These data are best explained by changes in blood flow caused by urethane and fenfluramine, which varies from region to region in the brain. C1 NIH, Warren G Magnuson Clin Ctr, PET, Bethesda, MD 20892 USA. NIDA, IRP, NIH, Baltimore, MD 21224 USA. RP Jagoda, EM (reprint author), NIH, Warren G Magnuson Clin Ctr, PET, Bld 10 Rm 1C495,10 Ctr Dr MSC 1180, Bethesda, MD 20892 USA. EM ejagoda@mail.nih.gov NR 42 TC 17 Z9 18 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD MAY PY 2006 VL 59 IS 6 BP 330 EP 341 DI 10.1002/syn.20246 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 025XY UT WOS:000236302100002 PM 16440292 ER PT J AU Nemukhin, AV Topol, IA Cachau, RE Burt, SK AF Nemukhin, AV Topol, IA Cachau, RE Burt, SK TI On the nature of oxoiron (IV) intermediate in dioxygen activation by non-heme enzymes SO THEORETICAL CHEMISTRY ACCOUNTS LA English DT Article DE quantum chemical modeling; non-heme iron enzymes; biomimetic complexes; oxoiron intermediates ID ALPHA-KETOGLUTARATE DIOXYGENASE; ELECTRONIC-STRUCTURE; CYTOCHROME-P450 ENZYMES; OXYGEN ACTIVATION; IRON OXYGENASES; MECHANISM; COMPLEX; CLEAVAGE; TAURINE; WATER AB We discuss electronic properties of the molecular systems with the short distance Fe-O unit, which are presumably formed as reaction intermediates during oxygen activation by non-heme enzymes. By performing an analysis of electronic densities in terms of multiconfigurational expansions of wavefunctions with localized orbitals the electronic properties of the Fe-O moiety in two model complexes are compared. The first one refers to the enzymatic intermediate, and the second biomimetic complex models a synthetic compound [Fe(O)(TMC)(NCCH3)](OTf)(2) with a terminal Fe-O unit, which is experimentally characterized as the Fe(IV)=O species. We show that the orbital pictures of the FeO unit in both model complexes share common features. According to these simulations, the non-heme enzymatic intermediates may be assigned to the systems with the oxidation state of Fe between III and IV, as recently proposed for the TauD enzyme in experimental spectroscopic studies. C1 NCI, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119992, Russia. Russian Acad Sci, Inst Biochem Phys, Moscow 119997, Russia. RP Topol, IA (reprint author), NCI, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. EM topol@ncifcrf.gov RI Nemukhin, Alexander/P-9662-2015 NR 36 TC 8 Z9 8 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1432-881X J9 THEOR CHEM ACC JI Theor. Chem. Acc. PD MAY PY 2006 VL 115 IS 5 BP 348 EP 353 DI 10.1007/s00214-005-0047-3 PG 6 WC Chemistry, Physical SC Chemistry GA 042WY UT WOS:000237562500002 ER PT J AU Nwosu, BU Gourgiotis, L Gershengorn, MC Neumann, S AF Nwosu, BU Gourgiotis, L Gershengorn, MC Neumann, S TI A novel activating mutation in transmembrane helix 6 of the thyrotropin receptor as cause of hereditary nonautoimmune hyperthyroidism SO THYROID LA English DT Article ID NON-AUTOIMMUNE HYPERTHYROIDISM; TSH RECEPTOR; GERMLINE MUTATIONS; THYROID-CARCINOMA; CYCLIC-AMP; GENE; PREVALENCE; PHENOTYPE; DISEASES; PHOSPHATIDYLINOSITOL AB Constitutively-activating germline mutations of the thyrotropin receptor (TSHR) gene are very rare and are considered the cause of hereditary nonautoimmune hyperthyroidism. We describe four affected individuals from a Caucasian family: a mother and her three children, and an unaffected father. The mother and her first two children presented in a similar manner: lifelong histories of heat intolerance, hyperactivity, fast heart rate, reduced energy, increased appetite, and scrawny build. They all developed goiter in childhood and showed a suppressed TSH and elevated thyroxine (T-4). The last child, a 12-year-old female, presented with no clinical symptoms or palpable neck mass, but with a suppressed TSH, elevated T-4 and thyromegaly detected by ultrasound. Mutation analysis of the TSHR gene in all family members revealed a novel heterozygous germline mutation resulting in the substitution of phenylalanine (TTC) by serine (TCC) at codon 631 in transmembrane helix 6 in the mother and all three children. Functional characterization of this germline mutation showed constitutive activation of the G(s)-mediated cyclic adenosine monophosphate (cAMP) pathway, which controls thyroid hormone production and thyroid growth. Molecular characterization of F631S demonstrates that this activating mutation plays a key role in the development of hereditary hyperthyroidism in this family although the timing of onset of clinical manifestations in the subjects may depend on other, as yet unidentified, factors. C1 NIDDK, NIH, CEB, Bethesda, MD 20892 USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. RP Neumann, S (reprint author), NIDDK, NIH, CEB, 50 South Dr, Bethesda, MD 20892 USA. EM susannen@intra.niddk.nih.gov NR 41 TC 25 Z9 26 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAY PY 2006 VL 16 IS 5 BP 505 EP 512 DI 10.1089/thy.2006.16.505 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 055IM UT WOS:000238443500013 PM 16756474 ER PT J AU Kojima, C Qu, W Waalkes, MP Himeno, S Sakurai, T AF Kojima, C Qu, W Waalkes, MP Himeno, S Sakurai, T TI Chronic exposure to methylated arsenicals stimulates arsenic excretion pathways and induces arsenic tolerance in rat liver cells SO TOXICOLOGICAL SCIENCES LA English DT Article DE arsenic; monomethylarsonic acid; dimethylarsinic acid; glutathione; multidrug resistance-associated proteins; tolerance ID MALE F344 RATS; DIMETHYLARSINIC ACID; MONOMETHYLARSONIC ACID; CELLULAR GLUTATHIONE; REDUCED GLUTATHIONE; TRIOXIDE AS2O3; TRANSPORT; CARCINOGENICITY; CYTOLETHALITY; MACROPHAGES AB Although inorganic arsenicals are toxic and carcinogenic in humans, inorganic arsenite has recently emerged as a highly effective chemotherapeutic agent for acute promyelocytic leukemia (APL). Inorganic arsenicals are enzymatically methylated to monomethylarsonic acid (MMAsV), dimethylarsinic acid (DMAsV), and trimethylarsine oxide ((TMAsO)-O-V) in mammals. We examined the effects of chronic exposure to methylated arsenicals on arsenic tolerance by using rat normal liver TRL 1215 cells. TRL 1215 cells were exposed for 20 weeks to MMAsV, DMAsV, or (TMAsO)-O-V at levels that produced submicromolar cellular concentrations of arsenic. On chronic exposure to these methylated arsenicals, the cells acquired tolerance to acute arsenic cytolethality. Cellular arsenic uptake was reduced in these cells compared to passage-matched control cells. The long-term arsenic exposure increased glutathione S-transferase (GST) activity and cellular glutathione (GSH) levels. Glutathione S-transferase, multidrug resistance-associated proteins (Mrps; efflux transporters encoded by Mrp genes), and P-glycoprotein [P-gp; efflux transporter encoded by multidrug resistance gene (MDR)] had also increased in these cells at the transcript and protein levels. The depletion of cellular GSH and the inhibition of Mrps and P-gp functions increased cellular arsenic uptake and reduced arsenic tolerance in these cells. These results indicate that chronic exposure to methylated arsenicals induces a generalized arsenic tolerance that is caused by increased arsenic excretion. Because accumulation of methylated arsenicals may occur in patients with chronic arsenic poisoning and arsenic-treated APL patients, this study may provide important information regarding chronic arsenic poisoning and the latent risk of developing multidrug resistance in APL therapy using inorganic arsenite. C1 Tokushima Bunri Univ, Fac Pharmaceut Sci, Lab Mol Nutr & Toxicol, Tokushima 7708514, Japan. NIEHS, Inorgan Carcinogenesis Sect, Lab Comparat Carcinogenesis,NCI, NIH, Res Triangle Pk, NC 27709 USA. RP Sakurai, T (reprint author), Tokushima Bunri Univ, Fac Pharmaceut Sci, Lab Mol Nutr & Toxicol, Yamashiro Cho, Tokushima 7708514, Japan. EM teruaki@ph.bunri-u.ac.jp FU Intramural NIH HHS NR 40 TC 25 Z9 31 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2006 VL 91 IS 1 BP 70 EP 81 DI 10.1093/toxsci/kfj117 PG 12 WC Toxicology SC Toxicology GA 032WX UT WOS:000236808200009 PM 16436460 ER PT J AU Stroncek, DF Jett, BW Tudisco, C Byrne, K Leitman, SF AF Stroncek, DF Jett, BW Tudisco, C Byrne, K Leitman, SF TI Measuring the pH of platelet concentrates - Reply SO TRANSFUSION LA English DT Letter C1 NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Stroncek, DF (reprint author), NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. EM dstroncek@cc.nih.gov NR 2 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2006 VL 46 IS 5 BP 872 EP 872 DI 10.1111/j.1537-2995.2006.00812.x PG 1 WC Hematology SC Hematology GA 036TK UT WOS:000237098200030 ER PT J AU Shah, BH Catt, KJ AF Shah, BH Catt, KJ TI TACE-dependent EGF receptor activation in angiotensin-II-induced kidney disease SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article ID EPIDERMAL GROWTH-FACTOR; CARDIAC-HYPERTROPHY; HB-EGF; METALLOPROTEINASE; TRANSACTIVATION; THERAPY; INHIBITORS; EXPRESSION; FAMILY AB Angiotensin II (Ang 11) has been implicated in the development of cardiovascular disorders and chronic kidney disease (CKD). Ang 11 causes renal lesions through the activation of tumor necrosis factor (TNF)-alpha-converting enzyme (TACE, also called a disintegrin and a metalloproteinase domain 17) and the release of transforming growth factor (TGF)-alpha, which binds to and activates the epidermal growth factor receptor. Renal lesions such as glomerulosclerosis, tubular atrophy, fibrosis, mononuclear cell infiltration and proteinuria following chronic Ang 11 infusion are substantially reduced in mice lacking TGF-alpha and those given a specific TACE inhibitor. These findings indicate that the selective inhibition of renal TACE could have therapeutic potential in the treatment of CKD. C1 NICHHD, Sect Hormonal Regulat, NIH, Bethesda, MD 20892 USA. RP Shah, BH (reprint author), NICHHD, Sect Hormonal Regulat, NIH, Bethesda, MD 20892 USA. EM shahb@mail.nih.gov FU Intramural NIH HHS NR 17 TC 34 Z9 35 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAY PY 2006 VL 27 IS 5 BP 235 EP 237 DI 10.1016/j.tips.2006.03.010 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 049JS UT WOS:000238013000001 PM 16600387 ER PT J AU Weinstein, LS Chen, M Xie, T Liu, J AF Weinstein, LS Chen, M Xie, T Liu, J TI Genetic diseases associated with heterotrimeric G proteins SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID PSEUDOHYPOPARATHYROIDISM TYPE IB; STIMULATORY G-PROTEIN; STATIONARY NIGHT BLINDNESS; IMPRINTING CONTROL ELEMENT; AUTONOMIC NERVOUS-SYSTEM; ALPHA-SUBUNIT G(S)ALPHA; GNAS1 GENE; BETA-3 SUBUNIT; T393C POLYMORPHISM; ACTIVATING MUTATIONS AB Heterotrimeric G proteins couple receptors for diverse extracellular signals to effector enzymes or ion channels. Each G protein comprises a specific a-subunit and a tightly bound beta gamma dimer. Several human disorders that result from genetic G-protein abnormalities involve the imprinted GNAS gene, which encodes G(s)alpha, the ubiquitously expressed a-subunit that couples receptors to adenylyl cyclase and cAMP generation. Loss-of-function and gain-of-function mutations, in addition to imprinting defects, of this gene lead to diverse clinical phenotypes. Mutations of GNAT1 and GNAT2 which encode the retinal G proteins (transducins), are rare causes of specific congenital visual defects. Common polymorphisms of the GNAS and GNB3 (which encodes G beta(3) genes have been associated with multigenic disorders (e.g. hypertension and metabolic syndrome). To date, no other G proteins have been implicated directly in human disease. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Weinstein, LS (reprint author), NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov OI Weinstein, Lee/0000-0002-1899-5152 FU Intramural NIH HHS [ZIA DK043302-16] NR 79 TC 68 Z9 70 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAY PY 2006 VL 27 IS 5 BP 260 EP 266 DI 10.1016/j.tips.2006.03.005 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 049JS UT WOS:000238013000007 PM 16600389 ER PT J AU Soto, E Richani, K Goncalves, LF Devers, P Espinoza, J Lee, W Treadwell, MC Romero, R AF Soto, E Richani, K Goncalves, LF Devers, P Espinoza, J Lee, W Treadwell, MC Romero, R TI Three-dimensional ultrasound in the prenatal diagnosis of cleidocranial dysplasia associated with B-cell immunodeficiency SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE clavicular fracture; clavicular pseudoarthrosis; cleidocranial dysplasia; high-resolution; hypomineralization; three-dimensional; widened fontanelles; 3D ID OSTEOGENESIS IMPERFECTA; SONOGRAPHIC DIAGNOSIS; ALKALINE-PHOSPHATASE; HYPOPHOSPHATASIA; DYSOSTOSIS; BONE; GENE; MUTATIONS AB A patient with a singleton pregnancy was referred for three-dimensional ultrasonography (3DUS) at 18 + 3 weeks for suspected hypomineralization of the skull bones and absence of the nasal bones. Three-dimensional rendered images of the fetal skull revealed widening of the coronal sutures, absence of the squamous portion of the temporal bone, and absence of the occipital bone, except for two areas of ossification. In addition, a fractured right clavicle was identified. The remainder of the fetal anatomy was normal and biometry was appropriate for gestational age. Genetic amniocentesis revealed a 46,XX fetal karyotype. Family history was Positive for a 5-year-old sibling with an open anterior fontanelle. Cleidocranial dysplasia was suspected. A female neonate was delivered by elective repeat Cesarean section at 40 + 3 weeks of gestation without complications and discharged home 3 days after delivery. Prenatal diagnosis was confirmed by physical and radiological evaluation. The infant died at 8 weeks of age due to respiratory syncytial virus pneumonia secondary to B-cell deficiency. RUNX2 mutations were not detected by molecular analysis. There are three relevant aspects to this case: (1) clear visualization of the widened fontanelles and hypomineralized occipital bones was possible with the use of 3DUS; (2) a clavicular fracture was identified in utero with combined high-resolution two-dimensional and 3DUS; and (3) although absence of the nasal bones is most commonly observed in fetuses with chromosomal disorders (e.g. trisomy 21 and trisomy 18), a careful examination of the skeleton should be considered in fetuses with absent nasal bones and a normal karyotype. Copyright (c) 2006 ISUOG. Published by John Wiley Sons, Ltd. C1 Wayne State Univ, Hutzel Womens Hosp, NICHD, NIH,DHHS,Perinatol Res Branch,Dept Obstet & Gynec, Detroit, MI 48201 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, NIH,DHHS,Perinatol Res Branch,Dept Obstet & Gynec, 3990 John R,Box 4, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov FU Intramural NIH HHS NR 26 TC 5 Z9 5 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD MAY PY 2006 VL 27 IS 5 BP 574 EP 579 DI 10.1002/uog.2770 PG 6 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 045CL UT WOS:000237720100018 PM 16619383 ER PT J AU Cox, MC Dahut, WL Figg, WD AF Cox, MC Dahut, WL Figg, WD TI The use of thalidomide in androgen-independent prostate cancer SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Urologic-Oncology CY MAY, 2005 CL San Antonio, TX SP Soc Urol Oncol DE angiogenesis; prostate cancer; hormones; thalidomide; oncology ID NECROSIS-FACTOR-ALPHA; PHASE-II TRIAL; TUMOR ANGIOGENESIS; CARCINOMA; DOCETAXEL; MITOXANTRONE; METASTASIS; PREDNISONE; INHIBITOR; GROWTH AB More than 200,000 men will be diagnosed with prostate cancer during the year 2006. Approximately 20% to 30% of these cases may develop advanced disease, for which there currently is no cure. Although therapy for this disease has improved significantly over the past few years, with docetaxel treatment showing improved survival times in metastatic disease, there remains the need for improved treatment options. Dr. Folkman put forth the idea of angiogenesis in 1971, and, since that time, researchers have been trying to determine the best possible way to inhibit blood vessel formation. This review summarizes the use of thalidomide in androgen-independent prostate cancer and the results of trials conducted at the National Cancer Institute. Published by Elsevier Inc. C1 NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 27 TC 12 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD MAY-JUN PY 2006 VL 24 IS 3 BP 246 EP 249 DI 10.1016/j.urolonc.2005.11.020 PG 4 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 048KA UT WOS:000237944800014 PM 16678058 ER PT J AU Macy, RJ Nurius, PS Norris, J AF Macy, RJ Nurius, PS Norris, J TI Responding in their best interests - Contextualizing women's coping with acquaintance sexual aggression SO VIOLENCE AGAINST WOMEN LA English DT Article DE coping; prevention; sexual aggression ID ALCOHOL-CONSUMPTION; SITUATIONAL FACTORS; EXPERIENCES SURVEY; RAPE; RESISTANCE; ASSAULT; VICTIMIZATION; THREAT; RISK; REVICTIMIZATION AB Using an investigation of 202 college women who completed a survey about coping with sexual aggression from a known male assailant, the authors examined assailant behaviors, along with women's victimization history, alcohol use, positive relationship expectancies, and sexual assertiveness, to clarify how these factors shape women's responses to acquaintance sexual aggression. Multivariate regression analyses showed that these factors and assailant actions accounted uniquely and Cumulatively for women's responding. Rape avoidance and resistance training programs can benefit by using a two-pronged approach: by targeting factors that impede and promote women's assertion and by helping women anticipate and respond to assailant actions. C1 Univ N Carolina, Sch Social Work, Chapel Hill, NC 27599 USA. Univ Washington, Sch Social Work, NIMH, Prevent Res Training Program, Seattle, WA 98195 USA. RP Macy, RJ (reprint author), Univ N Carolina, Sch Social Work, Chapel Hill, NC 27599 USA. FU NIMH NIH HHS [MH 53702, 5 T32 MH20010] NR 39 TC 31 Z9 31 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-8012 J9 VIOLENCE AGAINST WOM JI Violence Against Women PD MAY PY 2006 VL 12 IS 5 BP 478 EP 500 DI 10.1177/1077801206288104 PG 23 WC Women's Studies SC Women's Studies GA 038CC UT WOS:000237194900005 PM 16617172 ER PT J AU Chin, H Choi, SH Jang, YS Cho, SM Kim, HS Lee, JH Jeong, SW Kim, IK Kim, GJ Kwon, OJ AF Chin, H Choi, SH Jang, YS Cho, SM Kim, HS Lee, JH Jeong, SW Kim, IK Kim, GJ Kwon, OJ TI Protein kinase A-dependent phosphorylation of B/K protein SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Article DE calcium signaling; phosphorylation; protein kinase A; vasopressin ID PUTATIVE TARGET PROTEIN; RAT-BRAIN; CA2+-DEPENDENT EXOCYTOSIS; NEUROTRANSMITTER RELEASE; SYNAPTIC-TRANSMISSION; BRAIN/KIDNEY PROTEIN; SYNAPTOTAGMIN-I; PC12 CELLS; C2 DOMAINS; EXPRESSION AB We have previously isolated a novel protein "B/K" that contains two C2-like domains. Here, we report the isolatioin and mRNA distribution of a human B/K isoform, and protein kinase A (PKA)-dependent phosphorylation of the B/K protein. The 1.5 kb human B/K cDNA clone exhibits 89% and 97% identities with rat B/K in the sequences of nucleotide and amino acid, respectively. Human B/K isoform encodes a 474 amino acid protein and shows structural features similar to the rat counterpart including two C2 domains, three consensus sequences for PKA, absence of a transmembrane region, and conservation of the N-terminal cysteine cluster. On Northern and dot blot analyses, a 3.0 kb B/K transcript was abundantly present in human brain, kidney, and prostate. Among the brain regions, strong signals were observed in the frontal and temporal lobes, the hippocampus, the hypothalamus, the amygdala, the substantia nigra, and the pituitary. Recombinant B/K proteins containing three consensus sites for PKA was very efficiently phosphorylated in vitro by PKA catalytic subunit. B/K protein which was overexpressed in LLC-PK1 cells was also strongly phosphorylated in vivo by vasopressin analog DDAVP, and PKA-specific inhibitor H89 as well as type 2 vasopressin receptor antagonist specifically suppressed DDAVP-induced B/K phosphorylation. These results suggest that B/K proteins play a role as potential substrates for PKA in the area where they are expressed. C1 Catholic Univ Korea, Dept Biochem, Coll Med, Seoul 137701, South Korea. NEI, NIH, Bethesda, MD 20892 USA. Princeton Univ, Princeton, NJ 08544 USA. RP Kwon, OJ (reprint author), Catholic Univ Korea, Dept Biochem, Coll Med, Seoul 137701, South Korea. EM ojkwon@catholic.ac.kr NR 40 TC 6 Z9 7 U1 0 U2 1 PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY PI SEOUL PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1226-3613 J9 EXP MOL MED JI Exp. Mol. Med. PD APR 30 PY 2006 VL 38 IS 2 BP 144 EP 152 PG 9 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 043FZ UT WOS:000237586700005 PM 16672768 ER PT J AU Daddario-DiCaprio, KM Geisbert, TW Stroher, U Geisbert, JB Grolla, A Fritz, EA Fernando, L Kagan, E Jahrling, PB Hensley, LE Jones, SM Feldmann, H AF Daddario-DiCaprio, KM Geisbert, TW Stroher, U Geisbert, JB Grolla, A Fritz, EA Fernando, L Kagan, E Jahrling, PB Hensley, LE Jones, SM Feldmann, H TI Postexposure protection against Marburg haemorrhagic fever with recombinant vesicular stomatitis virus vectors in non-human primates: an efficacy assessment SO LANCET LA English DT Article ID REPLICATION-COMPETENT; INFLUENZA-VIRUS; DEFICIENT MICE; GUINEA-PIGS; INFECTION; MONKEYS; VACCINATION; DISEASE; EBOLA; GLYCOPROTEINS AB Background Effective countermeasures are urgently needed to prevent and treat infections caused by highly pathogenic and biological threat agents such as Marburg virus (MARV). We aimed to test the efficacy of a replication-competent vaccine based on attenuated recombinant vesicular stomatitis virus (rVSV), as a postexposure treatment for MARV haemorrhagic fever. Methods We used a rhesus macaque model of MARV haemorrhagic fever that produced 100% lethality. We administered rVSV vectors expressing the MARV Musoke strain glycoprotein to five macaques 20-30 min after a high-dose lethal injection of homologous MARV. Three animals were MARV-positive controls and received nonspecific rVSV vectors. We tested for viraemia, undertook analyses for haematology and serum biochemistry, and measured humoral and cellular immune responses. Findings All five rhesus monkeys that were treated with the rVSV MARV vectors as a postexposure treatment survived a high-dose lethal challenge of MARV for at least 80 days. None of these five animals developed clinical symptoms consistent with MARV haemorrhagic fever. All the control animals developed fulminant disease and succumbed to the MARV challenge by day 12. MARV disease in the controls was indicated by: high titres of MARV (10(3)-10(5) plaque-forming units per mL); development of leucocytosis with concurrent neutrophilia at end-stage disease; and possible damage to the liver, kidney, and pancreas. Interpretation Postexposure protection against MARV in non-human primates provides a paradigm for the treatment of MARV haemorrhagic fever. indeed, these data suggest that rVSV-based filoviral vaccines might not only have potential as preventive vaccines, but also could be equally useful for postexposure treatment of filoviral infections. C1 USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Publ Hlth Agcy Canada, Special Pathogens Program, Natl Microbiol Lab, Winnipeg, MB, Canada. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. Univ Manitoba, Dept Immunol, Winnipeg, MB, Canada. NIAID, Integrated Res Facil, NIH, Bethesda, MD 20892 USA. RP Geisbert, TW (reprint author), USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. EM tom.geisbert@amedd.army.mil NR 35 TC 103 Z9 109 U1 1 U2 5 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 29 PY 2006 VL 367 IS 9520 BP 1399 EP 1404 DI 10.1016/S0140-6736(06)68546-2 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 038CI UT WOS:000237195600027 PM 16650649 ER PT J AU Chattopadhyay, MK Tabor, CW Tabor, H AF Chattopadhyay, MK Tabor, CW Tabor, H TI Methylthioadenosine and polyamine biosynthesis in a Saccharomyces cerevisiae meu1 Delta mutant SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE methionine; methylthioadenosine; methionine salvage pathway; polyamines; spermidine; spermine; yeast ID MURINE LYMPHOMA-CELLS; S-ADENOSYLMETHIONINE; ORNITHINE-DECARBOXYLASE; SPERMIDINE SYNTHASE; METHIONINE SYNTHESIS; PHOSPHORYLASE; 5'-METHYLTHIOADENOSINE; METABOLISM; DEFICIENT; 5'-DEOXY-5'-METHYLTHIOADENOSINE AB As part of our studies on polyamine biosynthesis in yeast, the metabolism of methylthioadenosine was studied in a mutant that lacks methylthioadenosine phosphorylase (meuI Delta). The nucleoside accumulates in this mutant and is mainly excreted into the culture medium. Intracellular accumulation of the nucleoside is enough to account for the inhibition of spermidine synthase and thus to indirectly regulate the polyamine content of the meu1 Delta cells. By comparing the results with this mutant with a meu1 Delta spe2 Delta mutant that cannot synthesize spermidine or spermine, we showed that > 98%, of methylthioadenosine is produced as a by product of polyamine synthesis (i.e., from decarboxylated S-adenosylmethionine). In contrast, in MEW SPE2(+) cells methylthioadenosine does not accumulate and is metabolized through the methionine salvage pathway. Using a metI5 Delta mutant we show that this pathway (i.e., involving polyamine biosynthesis and methylthioadenosine metabolism) is a significant factor in the metabolism of methionine, accounting for 15% of the added methionine. Published by Elsevier Inc. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Tabor, H (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 223, Bethesda, MD 20892 USA. EM tabor@helix.nih.gov FU Intramural NIH HHS NR 32 TC 12 Z9 13 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 28 PY 2006 VL 343 IS 1 BP 203 EP 207 DI 10.1016/j.bbrc.2006.02.144 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 030UC UT WOS:000236659300029 PM 16530730 ER PT J AU Wang, WS Huang, XR Canlas, E Oka, K Truong, LD Deng, CX Bhowmick, NA Ju, WJ Bottinger, EP Lan, HY AF Wang, WS Huang, XR Canlas, E Oka, K Truong, LD Deng, CX Bhowmick, NA Ju, WJ Bottinger, EP Lan, HY TI Essential role of Smad3 in angiotensin II-induced vascular fibrosis SO CIRCULATION RESEARCH LA English DT Article DE angiotensin; TGF-beta; Smads; vascular fibrosis ID GROWTH-FACTOR-BETA; SMOOTH-MUSCLE-CELLS; TGF-BETA; TARGETED DISRUPTION; GLOMERULAR FIBROSIS; DERMAL FIBROBLASTS; CROSS-TALK; RECEPTOR; MECHANISM; KINASE AB Angiotensin II (Ang II) plays a pivotal role in vascular fibrosis, which leads to serious complications in hypertension and diabetes. However, the underlying signaling mechanisms are largely unclear. In hypertensive patients, we found that arteriosclerosis was associated with the activation of Smad2/3. This observation was further investigated in vitro by stimulating mouse primary aorta vascular smooth muscle cells (VSMCs) with Ang II. There were several novel findings. First, Ang II was able to activate an early Smad signaling pathway directly at 15 to 30 minutes. This was extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase ( MAPK) dependent but transforming growth factor-beta (TGF-beta) independent because Ang II-induced Smad signaling was blocked by addition of ERK1/2 inhibitor and by dominant-negative (DN) ERK1/2 but not by DN-TGF-beta receptor II (T beta RII) or conditional deletion of T beta RII. Second, Ang II was also able to activate the late Smad2/3 signaling pathway at 24 hours, which was TGF-beta dependent because it was blocked by the anti-TGF-beta antibody and DN-T beta RII. Finally, activation of Smad3 but not Smad2 was a key and necessary mechanism of Ang II-induced vascular fibrosis because Ang II induced Smad3/4 promoter activities and collagen matrix expression was abolished in VSMCs null for Smad3 but not Smad2. Thus, we concluded that Ang II induces vascular fibrosis via both TGF-beta-dependent and ERK1/2 MAPK-dependent Smad signaling pathways. Activation of Smad3 but not Smad2 is a key mechanism by which Ang II mediates arteriosclerosis. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. Natl Canc Inst, Genet Dev & Dis Branch, NIH, Bethesda, MD USA. Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. CUNY Mt Sinai Sch Med, Dept Med, Div Renal, New York, NY 10029 USA. RP Lan, HY (reprint author), Baylor Coll Med, Dept Med Nephrol, Alkek N520,1 Baylor Plaza, Houston, TX 77030 USA. EM hlan@bcm.tmc.edu RI deng, chuxia/N-6713-2016; Lan, hui/C-9734-2015 OI Lan, hui/0000-0003-4283-9755 FU NHLBI NIH HHS [R01 HL076661, R01HL076661]; NIDDK NIH HHS [P50 DK064233, P50DK-064233, R01 DK060043, R01 DK062828, R01DK062828] NR 32 TC 126 Z9 139 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 28 PY 2006 VL 98 IS 8 BP 1032 EP 1039 DI 10.1161/01.RES.0000218782.52610.dc PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 037AO UT WOS:000237119300010 PM 16556868 ER PT J AU Garcia, AD Otero, J Lebowitz, J Schuck, P Moss, B AF Garcia, AD Otero, J Lebowitz, J Schuck, P Moss, B TI Quaternary structure and cleavage specificity of a poxvirus Holliday junction resolvase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VACCINIA VIRUS-DNA; SIZE-DISTRIBUTION ANALYSIS; ESCHERICHIA-COLI; IN-VITRO; LINEAR MINICHROMOSOMES; CONCATEMER JUNCTIONS; RUVC PROTEIN; ANALYTICAL ULTRACENTRIFUGATION; SACCHAROMYCES-CEREVISIAE; HAIRPIN TERMINI AB Recently, poxviruses were found to encode a protein with signature motifs present in the RuvC family of Holliday junction ( HJ) resolvases, which have a key role in homologous recombination in bacteria. The vaccinia virus homolog A22 specifically cleaved synthetic HJ DNA in vitro and was required for the in vivo resolution of viral DNA concatemers into unit-length genomes with hairpin telomeres. It was of interest to further characterize a poxvirus resolvase in view of the low sequence similarity with RuvC, the absence of virus-encoded RuvA and RuvB to interact with, and the different functions of the viral and bacterial resolvases. Because purified A22 aggregated severely, studies were carried out with maltose-binding protein fused to A22 as well as to RuvC. Using gel filtration, chemical cross-linking, analytical ultracentrifugation, and light scattering, we demonstrated that A22 and RuvC are homodimers in solution. Furthermore, the dimeric form of the resolvase associated with HJ DNA, presumably facilitating the symmetrical cleavage of such structures. Like RuvC, A22 symmetrically cleaved fixed HJ junctions as well as junctions allowing strand mobility. Unlike RuvC and other members of the family, however, the poxvirus enzyme exhibited little cleavage sequence specificity. Structural and enzymatic similarities of poxvirus, bacterial, and fungal mitochondrial HJ resolvases are consistent with their predicted evolutionary relationship based on sequence analysis. The absence of a homologous resolvase in mammalian cells makes these microbial enzymes excellent potential therapeutic targets. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM bmoss@nih.gov OI Schuck, Peter/0000-0002-8859-6966 NR 50 TC 12 Z9 13 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 28 PY 2006 VL 281 IS 17 BP 11618 EP 11626 DI 10.1074/jbc.M600182200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 035GH UT WOS:000236988100025 PM 16513635 ER PT J AU Smyth, JT Lemonnier, L Vazquez, G Bird, GS Putney, JW AF Smyth, JT Lemonnier, L Vazquez, G Bird, GS Putney, JW TI Dissociation of regulated trafficking of TRPC3 channels to the plasma membrane from their activation by phospholipase C SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CA2+-PERMEABLE CATION CHANNEL; INOSITOL TRISPHOSPHATE RECEPTOR; PROTEIN-COUPLED RECEPTOR; CAPACITATIVE CA2+ ENTRY; TRANSIENT RECEPTOR; FUNCTIONAL EXPRESSION; SIGNALING MECHANISM; STORE DEPLETION; B-LYMPHOCYTES; KINASE-C AB Regulated translocation of canonical transient receptor potential ( TRPC) proteins to the plasma membrane has been proposed as a mechanism of their activation. By using total internal reflection fluorescence microscopy (TIRFM), we monitored green fluorescent protein-labeled TRPC3 (TRPC3-GFP) movement to the plasma membrane in HEK293 cells stably expressing this fusion protein. We observed no increase in TRPC3-GFP TIRFM in response to the muscarinic receptor agonist methacholine or the synthetic diacylglycerol, 1-oleoyl-2-acetyl-sn-glycerol, despite activation of TRPC3 by these agents. We did, however, observe a TIRFM response to epidermal growth factor (EGF). This TIRFM response to EGF was accompanied by increased Ba2+ entry and TRPC3 currents. However, 1-oleoyl-2-acetyl-sn-glycerol-induced TRPC3 activity was not increased. TIRFM also increased in response to Gd3+, a competitive inhibitor of TRPC3 channels. This may be indicative of constitutive trafficking of TRPC3, with Gd3+ acting to "trap" cycling TRPC3 molecules in the plasma membrane. Consistent with this interpretation, TRPC3-expressing cells exhibited large variance in membrane capacitance, and this variance was decreased by both Gd3+ and EGF. These results indicate the following: (i) trafficking of TRPC3 may play a role in regulating the concentration of channels in the plasma membrane but is not involved in activation through the phospholipase C pathway; (ii) TRPC3 undergoes constitutive cyclical trafficking in the plasma membrane, and the mechanism by which growth factors increase the number of plasma membrane channels may involve stabilizing them in the plasma membrane. C1 NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS NR 44 TC 43 Z9 44 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 28 PY 2006 VL 281 IS 17 BP 11712 EP 11720 DI 10.1074/jbc.M510541200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 035GH UT WOS:000236988100035 PM 16522635 ER PT J AU Bampi, C Bibillo, A Wendeler, M Divita, G Gorelick, RJ Le Grice, SFJ Darlix, JL AF Bampi, C Bibillo, A Wendeler, M Divita, G Gorelick, RJ Le Grice, SFJ Darlix, JL TI Nucleotide excision repair and template-independent addition by HIV-1 reverse transcriptase in the presence of nucleocapsid protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DNA STRAND TRANSFER; RNASE-H ACTIVITY; IN-VITRO; VIRAL-DNA; 3'-AZIDO-3'-DEOXYTHYMIDINE AZT; CDNA INTEGRATION; MUTATION-RATE; LIFE-CYCLE; HOT-SPOT AB During HIV replication, reverse transcriptase (RT), assisted by the nucleocapsid protein (NC), converts the genomic RNA into proviral DNA. This process appears to be the major source of genetic variability, as RT can misincorporate nucleotides during minus and plus strand DNA synthesis. To investigate nucleotide addition or substitution by RT, we set up in vitro models containing HIV-1 RNA, cDNA, NC, and various RTs. We used the wild type RT and azidothymidine- and didanosine-resistant RTs, because they represent the major forms of resistant RTs selected in patients undergoing therapies. Results show that all RTs can add nucleotides in a non-template fashion at the cDNA 3'end, a reaction stimulated by NC. Nucleotide substitutions were examined using in vitro systems where 3'-mutated cDNAs were extended by RT on an HIV-1 RNA template. With NC, RT extension of the mutated cDNAs was efficient, and surprisingly, mutations were frequently corrected. These results suggest for the first time that RT has excision-repair activity that is triggered by NC. Chaperoning of RT by NC might be explained by the fact that NC stabilizes an RT-DNA binary complex. In conclusion, RT-NC interactions appear to play critical roles in HIV-1 variability. C1 Ecole Normale Super Lyon, LaboRetro, INSERM, U412,Unite Virol Humaine,Inst Federat Rech 128, F-69364 Lyon 07, France. NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. Ctr Rech Biochim Macromol, CNRS, Format Rech Evolut 2593, F-36293 Montpellier 05, France. NCI, AIDS Vaccine Program, Sci Applicat Int Corp Frederick Inc, NIH, Frederick, MD 21702 USA. RP Darlix, JL (reprint author), Ecole Normale Super Lyon, LaboRetro, INSERM, U412,Unite Virol Humaine,Inst Federat Rech 128, 46 Allee Italie, F-69364 Lyon 07, France. EM Jean-Luc.Darlix@ens-lyon.fr FU NCI NIH HHS [N01-CO-12400] NR 50 TC 27 Z9 28 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 28 PY 2006 VL 281 IS 17 BP 11736 EP 11743 DI 10.1074/jbc.M600290200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 035GH UT WOS:000236988100038 PM 16500895 ER PT J AU Liu, Y Belkina, NV Graham, C Shaw, S AF Liu, Y Belkina, NV Graham, C Shaw, S TI Independence of protein kinase C-delta activity from activation loop phosphorylation - Structural basis and altered functions in cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CATALYTIC SUBUNIT; PKC-DELTA; PEPTIDE SPECIFICITY; CRYSTAL-STRUCTURE; CK2; DETERMINANTS; APOPTOSIS; ISOTYPES; SEGMENT; SERINE AB Activation loop phosphorylation plays critical regulatory roles for many kinases. Unlike other protein kinase Cs ( PKC), PKC-delta does not require phosphorylation of its activation loop ( Thr-507) for in vitro activity. We investigated the structural basis for this unusual capacity and its relevance to PKC-delta function in intact cells. Mutational analysis demonstrated that activity without Thr- 507 phosphorylation depends on 20 residues N-terminal to the kinase domain and a pair of phenylalanines ( Phe-500/Phe-527) unique to PKC-delta in/near the activation loop. Molecular modeling demonstrated that these elements stabilize the activation loop by forming a hydrophobic chain of interactions from the C-lobe to activation loop to N- terminal ( helical) extension. In cells PKC-delta mediates both apoptosis and transcription regulation. We found that the T507A mutant of the PKC-delta kinase domain resembled the corresponding wild type in mediating apoptosis in transfected HEK293T cells. But the T507A mutant was completely defective in AP-1 and NF-kappa B reporter assays. A novel assay in which the kinase domain of PKC-delta and its substrate ( a fusion protein of PKC substrate peptide with green fluorescent protein) were co-targeted to lipid rafts revealed a major substrate-selective defect of the T507A mutant in phosphorylating the substrate in cells. In vitro analysis showed strong product inhibition on the T507A mutant with particular substrates whose characteristics suggest it contributes to the substrate selective defect of the PKC-delta T507A mutant in cells. Thus, activation loop phosphorylation of PKC-delta may regulate its function in cells in a novel way. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Shaw, S (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM sshaw@nih.gov FU Intramural NIH HHS NR 32 TC 28 Z9 28 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 28 PY 2006 VL 281 IS 17 BP 12102 EP 12111 DI 10.1074/jbc.M600508200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 035GH UT WOS:000236988100080 PM 16505477 ER PT J AU Madziva, MT Birnbaumer, M AF Madziva, MT Birnbaumer, M TI A role for ADP-ribosylation factor 6 in the processing of G-protein-coupled receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID V2 VASOPRESSIN RECEPTOR; NEPHROGENIC DIABETES-INSIPIDUS; PLASMA-MEMBRANE; WILD-TYPE; ARF6; CELLS; ENDOCYTOSIS; PHOSPHORYLATION; GLYCOSYLATION; GTPASE AB After agonist-induced internalization, the vasopressin V-2 receptor (V2R) does not recycle to the plasma membrane. The ADP-ribosylation factor (ARF) proteins initiate vesicular intracellular traffic by promoting the recruitment of adaptor proteins; thus, we sought to determine whether ARF6 could promote V2R recycling. Neither the agonist-induced internalization nor the recycling of the V2R was regulated by ARF6, but a constitutively active mutant of ARF6 reduced cell-surface V(2)Rs 10-fold in the absence of agonist treatment. Visualization of the ARF6 mutant-expressing cells revealed a vacuolar-staining pattern of the V2R instead of the normal plasma-membrane expression. Analysis of V2R maturation revealed that reduced cell-surface expression was due to the diminished ability of the newly synthesized receptor to migrate from the endoplasmic reticulum to the Golgi network. The same mechanism affected processing of the V1aR and acetylcholine M2 receptors. Therefore, ARF6 controls the exit of the V-2 and other receptors from the endoplasmic reticulum in addition to its established role in the trafficking of plasma-membrane-derived vesicles. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Birnbaumer, M (reprint author), NIEHS, Lab Signal Transduct, NIH, MD F1-10, Res Triangle Pk, NC 27709 USA. EM birnbau2@niehs.nih.gov NR 34 TC 15 Z9 15 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 28 PY 2006 VL 281 IS 17 BP 12178 EP 12186 DI 10.1074/jbc.M601357200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 035GH UT WOS:000236988100088 PM 16497672 ER PT J AU Semsey, S Virnik, K Adhya, S AF Semsey, S Virnik, K Adhya, S TI Three-stage regulation of the amphibolic gal operon: From repressosome to GaIR-free DNA SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE transcription; repression; protein-protein interaction; DNA looping; D-galactose metabolism ID RNA-POLYMERASE CONTACT; ESCHERICHIA-COLI; TRANSCRIPTION; REPRESSION; HU; BINDING; PROTEIN; PROMOTERS; COMPLEX; INHIBITION AB The gal operon of Escherichia coli is negatively 'regulated by the Gal repressosome, a higher order nucleoprotein complex containing a DNA loop that encompasses two gal promoters. In the repressosome structure, Gal repressor (GaIR) dimers are bound to the two operator sites, flanking the promoter region, thus generating a DNA loop. The DNA loop is stabilized by binding of the architectural HU protein to the apex of the loop, and negative supercoiling. The gal promoters are also regulated in opposite directions by GaIR without DNA looping. The repressosome-mediated as well as looping-independent transcription regulation of the two promoters is lifted in the presence of the inducer D-galactose. We tested the effect Of D-galactose on various DNA-protein and protein-protein interactions of different regulatory complexes and on transcription repression in vitro. We found that the inducer breaks up the repressosome with clear intermediates in a concentration-dependent manner. The sequential disassembly generates different stages of regulation of the gal operon. The D-galactose-dependent switch from one stage of regulation to another satisfies the amphibolic requirement of the gal operon. Published by Elsevier Ltd. C1 NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Adhya, S (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM sadhya@helix.nih.gov RI Semsey, Szabolcs/L-6329-2013 FU Intramural NIH HHS NR 33 TC 37 Z9 38 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 28 PY 2006 VL 358 IS 2 BP 355 EP 363 DI 10.1016/j.jmb.2006.02.022 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 037LY UT WOS:000237149600002 PM 16524589 ER PT J AU Babu, MM Teichmann, SA Aravind, L AF Babu, MM Teichmann, SA Aravind, L TI Evolutionary dynamics of prokaryotic transcriptional regulatory networks SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE transcriptional regulatory network; evolution; network; network motif; regulation ID ESCHERICHIA-COLI; THIAMIN BIOSYNTHESIS; PROTEIN-INTERACTION; COMPLEX NETWORKS; GENOMIC ANALYSIS; GENE CIRCUITS; BACTERIA; MOTIFS; CONSERVATION; ORGANIZATION AB The structure of complex transcriptional regulatory networks has been studied extensively in certain model organisms. However, the evolutionary dynamics of these networks across organisms, which would reveal important principles of adaptive regulatory changes, are poorly understood. We use the known transcriptional regulatory network of Escherichia Coll to analyse the conservation patterns of this network across 175 prokaryotic genomes, and predict components of the regulatory networks for these organisms. We observe that transcription factors are typically less conserved than their target genes and evolve independently of them, with different organisms evolving distinct repertoires of transcription factors responding to specific signals. We show that prokaryotic transcriptional regulatory networks have evolved principally through widespread tinkering of transcriptional interactions at the local level by embedding orthologous genes in different types of regulatory motifs. Different transcription factors have emerged independently as dominant regulatory hubs in various organisms, suggesting that they have convergently acquired similar network structures approximating a scale-free topology. We note that organisms with similar lifestyles across a wide phylogenetic range tend to conserve equivalent interactions and network motifs. Thus, organism-specific optimal network designs appear to have evolved due to selection for specific transcription factors and transcriptional interactions, allowing responses to prevalent environmental stimuli. The methods for biological network analysis introduced here can be applied generally to study other networks, and these predictions can be used to guide specific experiments. Published by Elsevier Ltd. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. RP Babu, MM (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM madanm@mrc-lmb.cam.ac.uk; aravind@ncbi.nlm.nih.gov OI Teichmann, Sarah/0000-0002-6294-6366 NR 60 TC 171 Z9 176 U1 0 U2 8 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD APR 28 PY 2006 VL 358 IS 2 BP 614 EP 633 DI 10.1016/j.jmb.2006.02.019 PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 037LY UT WOS:000237149600023 ER PT J AU Bishop, JM Varmus, H AF Bishop, JM Varmus, H TI Re-aim blame for NIH's hard times SO SCIENCE LA English DT Editorial Material C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NIH, Bethesda, MD 20892 USA. RP Bishop, JM (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 9 Z9 9 U1 0 U2 1 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 28 PY 2006 VL 312 IS 5773 BP 499 EP 499 DI 10.1126/science.1128904 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 039HN UT WOS:000237296700001 PM 16645053 ER PT J AU Wang, HY Owens, JD Shih, JH Li, MC Bonner, RF Mushinski, JF AF Wang, Hongyang Owens, James D. Shih, Joanna H. Li, Ming-Chung Bonner, Robert F. Mushinski, J. Frederic TI Histological staining methods preparatory to laser capture microdissection significantly affect the integrity of the cellular RNA SO BMC GENOMICS LA English DT Article ID GENE-EXPRESSION; CDNA MICROARRAYS; CELLS; AMPLIFICATION; SECTIONS; TISSUES AB Background: Gene expression profiling by microarray analysis of cells enriched by laser capture microdissection (LCM) faces several technical challenges. Frozen sections yield higher quality RNA than paraffin-imbedded sections, but even with frozen sections, the staining methods used for histological identification of cells of interest could still damage the mRNA in the cells. To study the contribution of staining methods to degradation of results from gene expression profiling of LCM samples, we subjected pellets of the mouse plasma cell tumor cell line TEPC 1165 to direct RNA extraction and to parallel frozen sectioning for LCM and subsequent RNA extraction. We used microarray hybridization analysis to compare gene expression profiles of RNA from cell pellets with gene expression profiles of RNA from frozen sections that had been stained with hematoxylin and eosin (H&E), Nissl Stain (NS), and for immunofluorescence ( IF) as well as with the plasma cell-revealing methyl green pyronin (MGP) stain. All RNAs were amplified with two rounds of T7-based in vitro transcription and analyzed by two-color expression analysis on 10-K cDNA microarrays. Results: The MGP-stained samples showed the least introduction of mRNA loss, followed by H&E and immunofluorescence. Nissl staining was significantly more detrimental to gene expression profiles, presumably owing to an aqueous step in which RNA may have been damaged by endogenous or exogenous RNAases. Conclusion: RNA damage can occur during the staining steps preparatory to laser capture microdissection, with the consequence of loss of representation of certain genes in microarray hybridization analysis. Inclusion of RNAase inhibitor in aqueous staining solutions appears to be important in protecting RNA from loss of gene transcripts. C1 NCI, Genet Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. Emmes Corp, Rockville, MD 20850 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Univ Virginia, Dept Internal Med, Div Rheumatol & Immunol, Charlottesville, VA 22906 USA. NIH, Bethesda, MD 20892 USA. RP Mushinski, JF (reprint author), NCI, Genet Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM hw4f@virginia.edu; jow@helix.nih.gov; jshih@mail.nih.gov; limingch@helix.nih.gov; bonner@helix.nih.gov; jm8p@nih.gov RI Bonner, Robert/C-6783-2015 FU Intramural NIH HHS NR 24 TC 40 Z9 42 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD APR 27 PY 2006 VL 7 AR 97 DI 10.1186/1471-2164-7-97 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 068AG UT WOS:000239343400001 PM 16643667 ER PT J AU Iwahara, J Clore, GM AF Iwahara, J Clore, GM TI Detecting transient intermediates in macromolecular binding by paramagnetic NMR SO NATURE LA English DT Article ID HOMEODOMAIN-DNA COMPLEX; RELAXATION ENHANCEMENT; ANTENNAPEDIA HOMEODOMAIN; ASSOCIATION; PROTEINS; REFINEMENT; RATES AB Macromolecular complex formation is governed by two opposing constraints of specificity and speed(1,2). Kinetic(3-6) and theoretical considerations suggest that significant rate enhancement can be achieved either by reducing the dimensionality of the search process(1,7) or by the creation of a short-range attractive potential around the target site(2). This implies the existence of transient intermediates involving non-specific binding modes. Here we show that intermolecular paramagnetic relaxation enhancement (PRE) provides a means of directly detecting the presence of, and investigating the nature of, low population transient intermediates under equilibrium conditions. Applying this approach, we characterize the search process whereby a sequence-specific transcription factor (the homeodomain of HOXD9) binds to non-cognate DNA sites as a means of enhancing the rate of specific association. The PRE data in the fast exchange regime reveal the presence of transient intermediates formed in a stochastic manner at non-cognate sites whose structure is similar to that of the specific complex. Two distinct search processes involving intra- as well as intermolecular translocations can be delineated. The intermolecular PRE method is general and can be readily applied to investigations of transient intermediates in many other macromolecular binding processes. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, 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; Iwahara, Junji/0000-0003-4732-2173 FU Intramural NIH HHS NR 27 TC 235 Z9 236 U1 5 U2 53 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 27 PY 2006 VL 440 IS 7088 BP 1227 EP 1230 DI 10.1038/nature04673 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 036OG UT WOS:000237080000053 PM 16642002 ER PT J AU Bock, NA Kovacevic, N Lipina, TV Roder, JC Ackerman, SL Henkelman, RM AF Bock, NA Kovacevic, N Lipina, TV Roder, JC Ackerman, SL Henkelman, RM TI In vivo magnetic resonance imaging and semiautomated image analysis extend the brain phenotype for cdf/cdf mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE mice; imaging; cytoarchitecture; cerebellum; hippocampus; inferior colliculus ID DEFICIENT FOLIA CDF; RESOLUTION 3D MRI; MOUSE-BRAIN; REGISTRATION; CEREBELLAR; VALIDATION; MICROSCOPY AB Magnetic resonance imaging and computer image analysis in human clinical studies effectively identify abnormal neuroanatomy in disease populations. As more mouse models of neurological disorders are discovered, such an approach may prove useful for translational studies. Here, we demonstrate the effectiveness of a similar strategy for mouse neuroscience studies by phenotyping mice with the cerebellar deficient folia (cdf) mutation. Using in vivo multiple-mouse magnetic resonance imaging for increased throughput, we imaged groups of cdf mutant, heterozygous, and wild-type mice and made an atlas-based segmentation of the structures in 15 individual brains. We then performed computer automated volume measurements on the structures. We found a reduced cerebellar volume in the cdf mutants, which was expected, but we also found a new phenotype in the inferior colliculus and the olfactory bulbs. Subsequent local histology revealed additional cytoarchitectural abnormalities in the olfactory bulbs. This demonstrates the utility of anatomical magnetic resonance imaging and semiautomated image analysis for detecting abnormal neuroarchitecture in mutant mice. C1 Hosp Sick Children, Mouse Imaging Ctr, Toronto, ON M5G 1X8, Canada. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Jackson Lab, Bar Harbor, ME 04609 USA. Howard Hughes Med Inst, Bar Harbor, ME 04609 USA. RP Bock, NA (reprint author), NINDS, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr,Bldg 10,Room B1D109, Bethesda, MD 20892 USA. EM bockn@mail.nih.gov RI Roder, John/G-6468-2013; Henkelman, Mark/F-3662-2011; Lipina, Tatiana/G-9148-2014 FU NINDS NIH HHS [NS35900] NR 22 TC 42 Z9 42 U1 1 U2 4 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 26 PY 2006 VL 26 IS 17 BP 4455 EP 4459 DI 10.1523/JNEUROSCI.5438-05.2006 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 039AK UT WOS:000237271400002 PM 16641223 ER PT J AU Yao, YN Mayer, ML AF Yao, YN Mayer, ML TI Characterization of a soluble ligand binding domain of the NMDA receptor regulatory subunit NR3A SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glutamate receptor; NMDA; gating; antagonist; agonist; proteolysis ID GLUTAMATE-RECEPTOR; NR1 SUBUNIT; SURFACE EXPRESSION; CRYSTAL-STRUCTURES; D-SERINE; GLYCINE; ACTIVATION; MECHANISMS; FAMILY; BRAIN AB NR3A is expressed widely in the developing CNS of mammals. Coassembly of NR3A with NR1 and NR2 modifies NMDA receptormediated responses, reducing calcium permeability and single- channel conductance. The ligand binding properties of NR3A are unknown but shape the role NR3A plays when incorporated into NMDA receptors. Here, a soluble NR3A ligand binding domain ( NR3A S1S2) was constructed based on amino acid sequence alignments with other glutamate receptor ion channels and is expressed in Escherichia coli. After purification by affinity, gel filtration, and ion exchange chromatography, NR3A S1S2 behaves as a monomer even at a concentration of 20 mg/ml, as determined by size-exclusion chromatography and dynamic light scattering. NR3A S1S2 has very high affinity for glycine with an apparent dissociation constant (K-d) of 40nM, 650- fold less than the Kd for NR1. Glutamate, which binds to NR2 subunits, also binds to NR3A, but with very low affinity (K-d = 9.6mM); in contrast, binding of glutamate to NR1 was not detectable even at a 300 mM concentration. The antagonist binding profiles of NR3A and NR1 also show striking differences. 6-Cyano-2,3-dihydroxy-7nitro- quinoxaline ( CNQX), and its analog CGP78608, bind to NR3A S1S2 with low micromolar affinity, whereas for NR1, the affinity of CGP78608 increases 1000-fold compared with CNQX. Other high-affinity NR1 antagonists also show very weak binding to NR3A. Proteolysis protection experiments reveal that CNQX and CGP78608 bind to and stabilize domain 1 of NR3A S1S2 but increase proteolysis of domain 2, indicating that they produce conformational changes distinct from those induced by glycine and D-serine. C1 NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Mayer, ML (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,Dept Hlth & Human Serv, Bldg 35,Room 3B1002,35 Lincoln Dr, Bethesda, MD 20892 USA. EM mayerm@mail.nih.gov RI Mayer, Mark/H-5500-2013 FU Intramural NIH HHS NR 32 TC 53 Z9 61 U1 0 U2 4 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 26 PY 2006 VL 26 IS 17 BP 4559 EP 4566 DI 10.1523/JNEUROSCI.0560-06.2006 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 039AK UT WOS:000237271400014 PM 16641235 ER PT J AU Ichise, M Vines, DC Gura, T Anderson, GM Suomi, SJ Higley, JD Innis, RB AF Ichise, M Vines, DC Gura, T Anderson, GM Suomi, SJ Higley, JD Innis, RB TI Effects of early life stress on [C-11] DASB positron emission tomography imaging of serotonin transporters in adolescent peer- and mother-reared rhesus monkeys SO JOURNAL OF NEUROSCIENCE LA English DT Article DE positron emission tomography; serotonin transporter; early life stress; aggression; peer-reared rhesus monkey; impulse control ID NONHUMAN PRIMATE MODEL; 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; STRIATAL DOPAMINE TRANSPORTER; EXCESSIVE ALCOHOL-CONSUMPTION; DIMINISHED SOCIAL COMPETENCE; H-3 PAROXETINE BINDING; CEREBROSPINAL-FLUID; HEALTHY HUMANS; IN-VITRO; BRAIN AB Peer-reared (PR) rhesus monkeys with early maternal separation later exhibit aggressiveness, impaired impulse control, alcohol abuse, and low CSF 5-hydroxyindoleacetic acid. This study compared regional brain serotonin transporter (SERT) binding between nine PR and seven mother-reared rhesus monkeys with [C-11] DASB positron emission tomography (PET) imaging. Parametric images of binding potential (BP) (which is proportional to B-max/K-D, in which B-max is transporter density and K-D is dissociation constant) and relative blood flow (R-1) were generated by the two-parameter multilinear reference tissue model. R1 images were used for coregistration and normalization of PET parametric data to the magnetic resonance imaging template space. Group BP differences were analyzed voxelwise by Student's t test in SPM2. Region of interest-based parameter values were also calculated to obtain the magnitude of regional BP differences between the two groups. For the PR group, SERT BP was decreased by 10 - 23% across a range of brain areas consisting of the raphe, thalamus, hypothalamus, caudate and putamen, globus pallidum, anterior cingulate gyrus, and medial temporal regions, including amygdala and hippocampus (cluster-level corrected p = 0.002). For the latter three regions, BP was decreased in the right hemisphere. These results agree with the hypothesis that early maternal deprivation affects the development of the serotonergic system and suggest that decreased serotonergic innervations in the critical brain regions may explain some of the behavioral and biochemical abnormalities in PR monkeys. C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, Primate Unit, Div Intramural Clin & Biol Res, Poolesville, MD 20837 USA. Yale Univ, Sch Med, Dept Child Psychiat & Lab Med, New Haven, CT 06510 USA. NICHD, Comparat Ethol Lab, Natl Inst Hlth Anim Ctr, Poolesville, MD 20837 USA. RP Ichise, M (reprint author), Brigham & Womens Hosp, 75 Francis St,ASBI-L1-037-E, Boston, MA 02115 USA. EM michise@partners.org FU Intramural NIH HHS NR 45 TC 87 Z9 87 U1 2 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 26 PY 2006 VL 26 IS 17 BP 4638 EP 4643 DI 10.1523/JNEUROSCI.5199-05.2006 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 039AK UT WOS:000237271400023 PM 16641244 ER PT J AU Polgar, O Ozvegy-Laczka, C Robey, RW Morisaki, K Okada, M Tamaki, A Koblos, G Elkind, NB Ward, Y Dean, M Sarkadi, B Bates, SE AF Polgar, O Ozvegy-Laczka, C Robey, RW Morisaki, K Okada, M Tamaki, A Koblos, G Elkind, NB Ward, Y Dean, M Sarkadi, B Bates, SE TI Mutational studies of G553 in TM5 of ABCG2: A residue potentially involved in dimerization SO BIOCHEMISTRY LA English DT Article ID CANCER RESISTANCE PROTEIN; HUMAN MULTIDRUG TRANSPORTER; INSECT CELLS; ESCHERICHIA-COLI; EXPRESSION; IDENTIFICATION; TRAFFICKING; MEMBRANE; HOMOLOG; SURFACE AB ABCG2 is an ATP-binding cassette half-transporter conferring resistance to chemotherapeutic agents such as mitoxantrone, irinotecan, and flavopiridol. With its one trans membrane and one ATP-binding domain, ABCG2 is thought to homodimerize for function. One conserved region potentially involved in dimerization is a three-amino acid sequence in transmembrane segment 5 (residues 552-554). Mutations in the corresponding residues in the Drosophila white protein (an orthologue of ABCG2) are thought to disrupt heterodimerization. We substituted glycine 553 with leucine (G553L) followed by stable transfection in HEK 293 cells. The mutant was not detectable on the cell surface, and markedly reduced protein expression levels were observed by immunoblotting. A deficiency in N-linked glycosylation was suggested by a reduction in molecular mass compared to that of the 72 kDa wild-type ABCG2. Similar results were observed with the G553E mutant. Confocal microscopy demonstrated mostly ER localization of the G553L mutant in HEK 293 cells, even when coexpressed with the wild-type protein. Despite its altered localization, the G553L and G553E mutants were cross-linked using amine-reactive cross-linkers with multiple arm lengths, suggesting that the monomers are in the proximity of each other but are unable to complete normal trafficking. Interestingly, when expressed in Sf9 insect cells, G553L moves to the cell membrane but is unable to hydrolyze ATP or transport the Hoechst dye. Still, when coexpressed, the mutant interferes with the Hoechst transport activity of the wild-type protein. These data show that glycine 553 is important for protein trafficking and are consistent with, but do not yet prove, its involvement in ABCG2 homodimerization. C1 NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Hungarian Acad Sci, Inst Haematol & Immunol, Membrane Res Grp, Natl Med Ctr, H-1113 Budapest, Hungary. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Natl Canc Inst Frederick, Lab Genom Divers, Human Genet Sect, Ft Detrick, MD 21702 USA. RP Bates, SE (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 13N240, Bethesda, MD 20892 USA. EM sebates@helix.nih.gov RI Dean, Michael/G-8172-2012; Sarkadi, Balazs/I-5024-2013 OI Dean, Michael/0000-0003-2234-0631; FU Intramural NIH HHS [Z01 BC010622-04] NR 40 TC 27 Z9 27 U1 0 U2 6 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 25 PY 2006 VL 45 IS 16 BP 5251 EP 5260 DI 10.1021/bi0521590 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 036CV UT WOS:000237049400017 PM 16618113 ER PT J AU Liu, YZ Gao, LQ Gelman, IH AF Liu, YZ Gao, LQ Gelman, IH TI SSeCKS/Gravin/AKAP12 attenuates expression of proliferative and angiogenic genes during suppression of v-Src-induced oncogenesis SO BMC CANCER LA English DT Article ID PROTEIN-KINASE-C; ENDOTHELIAL GROWTH-FACTOR; BREAST-CANCER CELLS; LUNG-CANCER; CYTOSKELETAL ARCHITECTURE; INSULIN-RESISTANCE; TUMOR PROGRESSION; PRECURSOR LESIONS; PROSTATE-CANCER; OVER-EXPRESSION AB Background: SSeCKS is a major protein kinase C substrate with kinase scaffolding and metastasis-suppressor activity whose expression is severely downregulated in Src- and Ras-transformed fibroblast and epithelial cells and in human prostate, breast, and gastric cancers. We previously used NIH3T3 cells with tetracycline-regulated SSeCKS expression plus a temperature-sensitive v-Src allele to show that SSeCKS re-expression inhibited parameters of v-Src-induced oncogenic growth without attenuating in vivo Src kinase activity. Methods: We use cDNA microarrays and semi-quantitative RT-PCR analysis to identify changes in gene expression correlating with i) SSeCKS expression in the absence of v-Src activity, ii) activation of v-Src activity alone, and iii) SSeCKS re-expression in the presence of active v-Src. Results: SSeCKS re-expression resulted in the attenuation of critical Src- induced proliferative and pro-angiogenic gene expression including Afp, Hif-1 alpha, Cdc20a and Pdgfr-beta, and conversely, SSeCKS induced several cell cycle regulatory genes such as Ptpn11, Gadd45a, Ptplad1, Cdkn2d (p19), and Rbbp7. Conclusion: Our data provide further evidence that SSeCKS can suppress Src- induced oncogenesis by modulating gene expression downstream of Src kinase activity. C1 Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. NIH, Mucosal Immunol Unit, Bethesda, MD 20892 USA. RP Gelman, IH (reprint author), Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. EM yoliu@mail.nih.gov; lingqiu.gao@roswellpark.org; irwin.gelman@roswellpark.org FU NCI NIH HHS [R55 CA094108, 2P30 CA016056, CA94108, P30 CA016056, R01 CA094108] NR 73 TC 21 Z9 22 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD APR 25 PY 2006 VL 6 AR 105 DI 10.1186/1471-2407-6-105 PG 12 WC Oncology SC Oncology GA 043ZS UT WOS:000237642300001 PM 16638134 ER PT J AU Velmurugan, D Rajakannan, V Gayathri, D Banumathi, S Yamane, T Dauter, Z Dauter, M Sekar, K AF Velmurugan, D Rajakannan, V Gayathri, D Banumathi, S Yamane, T Dauter, Z Dauter, M Sekar, K TI Ab initio structure determination of the triple mutant (K53,56,121M) of bovine pancreatic phospholipase A(2) at atomic and high resolution using ACORN SO CURRENT SCIENCE LA English DT Article DE ab initio phasing; ACORN; bovine pancreatic phospholipase A(2); triple mutant ID X-RAY; MACROMOLECULAR STRUCTURES; ANOMALOUS SCATTERING; CRYSTAL-STRUCTURE; SMALL PROTEIN; REFINEMENT; SUBSTRUCTURE; ROLES; SNB AB Atomic resolution (0.97 angstrom) data were collected for the triple mutant (K53,56,121M) of bovine pancreatic phospholipase A(2) at 100 K and data extending to LOA resolution were used for the present study. Accuracy of the data at high resolution allowed the structure to be solved using the program ACORN, with a random single-atom start in an ab initio manner. The phases obtained from ACORN are of good quality and revealed most of the amino acid residues. Single wavelength Anomalous Diffraction (SAD) data were also used to locate the position of the sulphurs and ACORN was run with these atomic positions as a source of phasing in- formation. The effect of truncating the data to 1.4 and 1.45 angstrom for input to ACORN is also examined. Larger fragments are required to trigger successful phase refinement at these lower resolutions. C1 Indian Inst Sci, Bioinformat Ctr, Bangalore 560012, Karnataka, India. Indian Inst Sci, Supercomp Educ & Res Ctr, Bangalore 560012, Karnataka, India. Univ Madras, Dept Crystallog & Biophys, Madras 600025, Tamil Nadu, India. NCI, Synchrotron Radiat Res Sect, Upton, NY 11973 USA. Brookhaven Natl Lab, Upton, NY 11973 USA. Nagoya Univ, Dept Biotechnol & Biomat Sci, Grad Sch Engn, Nagoya, Aichi 4648603, Japan. Brookhaven Natl Lab, Basic Res Program, SAIC Frederick Inc, Upton, NY 11973 USA. RP Sekar, K (reprint author), Indian Inst Sci, Bioinformat Ctr, Bangalore 560012, Karnataka, India. EM sekar@physics.iisc.ernet.in NR 26 TC 2 Z9 2 U1 0 U2 2 PU INDIAN ACAD SCIENCES PI BANGALORE PA C V RAMAN AVENUE, SADASHIVANAGAR, P B #8005, BANGALORE 560 080, INDIA SN 0011-3891 J9 CURR SCI INDIA JI Curr. Sci. PD APR 25 PY 2006 VL 90 IS 8 BP 1091 EP 1099 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 039XN UT WOS:000237341800016 ER PT J AU Snapp, EL Sharma, A Lippincott-Schwartz, J Hegde, RS AF Snapp, EL Sharma, A Lippincott-Schwartz, J Hegde, RS TI Monitoring chaperone engagement of substrates in the endoplasmic reticulum of live cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE castanospermine; fluorescence loss in photobleaching; fluorescence recovery after photobleaching; pactamycin; puromycin ID GREEN FLUORESCENT PROTEIN; QUALITY-CONTROL; IN-VIVO; CALRETICULIN; CALNEXIN; GLYCOPROTEINS; RETENTION; DYNAMICS; BIP; TRANSLOCATION AB The folding environment in the endoplasmic reticulum (ER) depends on multiple abundant chaperones that function together to accommodate a range of substrates. The ways in which substrate engagement shapes either specific chaperone dynamics or general ER attributes in vivo remain unknown. In this study, we have evaluated how changes in substrate flux through the ER influence the diffusion of both the lectin chaperone calreticulin and an inert reporter of ER crowdedness. During acute changes in substrate load, the inert probe revealed no changes in ER organization, despite significant changes in calreticulin dynamics. By contrast, inhibition of the lectin chaperone system caused rapid changes in the ER environment that could be reversed over time by easing new substrate burden. Our findings provide insight into the normal organization and dynamics of an ER chaperone and characterize the capacity of the ER to maintain homeostasis during acute changes in chaperone activity and availability. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA. RP Snapp, EL (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, 18 Lib Dr,Bldg 18,Room 101, Bethesda, MD 20892 USA. EM esnapp@aecom.yu.edu OI Hegde, Ramanujan/0000-0001-8338-852X FU NIDDK NIH HHS [R21 DK074650, R21 DK074650-02] NR 45 TC 62 Z9 64 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 25 PY 2006 VL 103 IS 17 BP 6536 EP 6541 DI 10.1073/pnas.0510657103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 037MM UT WOS:000237151000023 PM 16617114 ER PT J AU Covassin, LD Villefranc, JA Kacergis, MC Weinstein, BM Lawson, ND AF Covassin, LD Villefranc, JA Kacergis, MC Weinstein, BM Lawson, ND TI Distinct genetic interactions between multiple Vegf receptors are required for development of different blood vessel types in zebrafish SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE differentiation; endothelial ID ENDOTHELIAL-GROWTH-FACTOR; VASCULAR DEVELOPMENT; TYROSINE KINASE; SIGNALING PATHWAYS; ANGIOGENESIS; FLT-1; LIGAND; MICE; VASCULOGENESIS; HEMATOPOIESIS AB Recent evidence indicates a specific role for vascular endothelial growth factor a (Vegfa) during artery development in both zebrafish and mouse embryos, whereas less is known about signals that govern vein formation. In zebrafish, loss of vegfa blocks segmental artery formation and reduces artery-specific gene expression, whereas veins are largely unaffected. Here, we describe a mutation in the zebrafish vegf receptor-2 homolog, kdra, which eliminates its kinase activity and leads to specific defects in artery development. We further find that Flt4, a receptor for Vegfc, cooperates with Kdr during artery morphogenesis, but not differentiation. We also identify an additional zebrafish vegfr-2 ortholog, referred to as kdrb, which can partially compensate for loss of kdra but is dispensable for vascular development in wild-type embryos. interestingly, we find that these Vegf receptors are also required for formation of veins but in distinct genetic interactions that differ from those required for artery development. Taken together, our results indicate that formation of arteries and veins in the embryo is governed in part by different Vegf receptor combinations and suggest a genetic mechanism for generating blood vessel diversity during vertebrate development. C1 Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. NICHHD, Genet Mol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Lawson, ND (reprint author), Univ Massachusetts, Sch Med, Program Gene Funct & Express, Lazare Res Bldg,Room 617,364 Plantat St, Worcester, MA 01605 USA. EM nathan.lawson@umassmed.edu FU NCI NIH HHS [R01 CA107454, R01CA107454] NR 41 TC 142 Z9 150 U1 2 U2 9 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 25 PY 2006 VL 103 IS 17 BP 6554 EP 6559 DI 10.1073/pnas.0506886103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 037MM UT WOS:000237151000026 PM 16617120 ER PT J AU Das, H Kumar, A Lin, ZY Patinol, WD Hwang, PM Feinberg, MW Majumder, PK Jain, MK AF Das, H Kumar, A Lin, ZY Patinol, WD Hwang, PM Feinberg, MW Majumder, PK Jain, MK TI Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE inflammation; transcription; transcriptional factor; NF-kappa B; activator protein 1 ID NF-KAPPA-B; T-CELL QUIESCENCE; TRANSCRIPTION FACTOR; IN-VIVO; BETA-THALASSEMIA; FACTOR EKLF; INFLAMMATION; GENE; ATHEROSCLEROSIS; INHIBITION AB The mechanisms regulating activation of monocytes remain incompletely understood. Herein we provide evidence that Kruppel-like factor 2 (KLF2) inhibits proinflammatory activation of monocytes. In vitro, KLF2 expression in monocytes is reduced by cytokine activation or differentiation. Consistent with this observation, KLF2 expression in circulating monocytes is reduced in patients with chronic inflammatory conditions such as coronary artery disease. Adenoviral overexpression of KLF2 inhibits the LPS-mediated induction of proinflammatory factors, cytokines, and chemokines and reduces phagocytosis. Conversely, short interfering RNA-mediated reduction in KLF2 increased inflammatory gene expression. Reconstitution of immunodeficient mice with KLF2-overexpressing monocytes significantly reduced carrageenan-induced acute paw edema formation. Mechanistically, KLF2 inhibits the transcriptional activity of both NF-kappa B and activator protein 1, in part by means of recruitment of transcriptional coactivator p300/CBP-associated factor. These observations identify KLF2 as a novel negative regulator of monocytic activation. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Program Cardiovasc Transcript Biol,Cardiovasc Div, Boston, MA 02115 USA. NHLBI, NIH, Bethesda, MD 20824 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jain, MK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Program Cardiovasc Transcript Biol,Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM mjain@rics.bwh.harvard.edu FU NHLBI NIH HHS [HL69477, HL72952, HL67755, F32 HL078183, HL75427, HL76754, K08 HL067755, P01 HL048743, P01 HL48743, R01 HL069477, F32 HL78183, R01 HL072952, R01 HL075427, R01 HL076754] NR 29 TC 108 Z9 116 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 25 PY 2006 VL 103 IS 17 BP 6653 EP 6658 DI 10.1073/pnas.0508235103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 037MM UT WOS:000237151000043 PM 16617118 ER PT J AU Law, AJ Lipska, BK Weickert, CS Hyde, TM Straub, RE Hashimoto, R Harrison, PJ Kleinman, JE Weinberger, DR AF Law, AJ Lipska, BK Weickert, CS Hyde, TM Straub, RE Hashimoto, R Harrison, PJ Kleinman, JE Weinberger, DR TI Neuregulin 1 transcripts are differentially expressed in schizophrenia and regulated by 5 ' SNPs associated with the disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genetics; mRNA; human postmortem brain; hippocampus; ErbB ID FAMILY-BASED ASSOCIATION; AT-RISK HAPLOTYPE; GENE-EXPRESSION; SUSCEPTIBILITY GENES; PREFRONTAL CORTEX; BIPOLAR DISORDER; NO ASSOCIATION; MUTANT MICE; LINKAGE; GENOME AB Genetic variation in neuregulin 1 (NRG1) is associated with schizophrenia. The disease-associated SNIPS are noncoding, and their functional implications remain unknown. We hypothesized that differential expression of the NRG1 gene explains its association to the disease. We examined four of the disease-associated SNIPS that make up the original risk haplotype in the 5' upstream region of the gene for their effects on mRNA abundance of NRG1 types I-IV in human postmortem hippocampus. Diagnostic comparisons revealed a 34% increase in type I mRNA in schizophrenia and an interaction of diagnosis and genotype (SNP8NRG221132) on this transcript. Of potentially greater interest, a single SNP within the risk haplotype (SNP8NRG243177) and a 22-kb block of this core haplotype are associated with mRNA expression for the novel type IV isoform in patients and controls. Bioinformatic promoter analyses indicate that both SNIPS lead to a gain/loss of putative binding sites for three transcription factors, serum response factor, myelin transcription factor-1, and High Mobility Group Box Protein-1. These data implicate variation in isoform expression as a molecular mechanism for the genetic association of NRG1 with schizophrenia. C1 Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Law, AJ (reprint author), Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. EM amanda.law@psych.ox.ac.uk RI Shannon Weickert, Cynthia/G-3171-2011; Law, Amanda/G-6372-2012; Hashimoto, Ryota/P-8572-2014; Lipska, Barbara/E-4569-2017; OI Hashimoto, Ryota/0000-0002-5941-4238; Law, Amanda/0000-0002-2574-1564 NR 42 TC 265 Z9 281 U1 2 U2 9 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 25 PY 2006 VL 103 IS 17 BP 6747 EP 6752 DI 10.1073/pnas.0602002103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 037MM UT WOS:000237151000059 PM 16618933 ER PT J AU Sharp, JS Nelson, S Brown, D Tomer, KB AF Sharp, JS Nelson, S Brown, D Tomer, KB TI Structural characterization of the E2 glycoprotein from Sindbis by lysine biotinylation and LC-MS/MS SO VIROLOGY LA English DT Article DE Sindbis; mass spectrometry; surface labeling; Alphavirus; glycoprotein ID MASS-SPECTROMETRY; SURFACE-TOPOLOGY; LOW PH; VIRUS; CELLS; MEMBRANE; RECEPTOR; E1; ALPHAVIRUSES; PROTEINS AB Sindbis is an Alphavirus capable of infecting and replicating in both vertebrate and invertebrate hosts. Mature Sindbis virus particles consist of an inner capsid surrounded by a host-derived lipid bilayer, which in turn is surrounded by a protein shell consisting of the E1 and E2 glycoproteins. While a homolog of the E1 glycoprotein has been structurally characterized, the amount of structural data on the E2 glycoprotein is considerably less. In this study, the organization of the E2 glycoprotein was probed by surface biotinylation of intact virions. The virus remained fully infectious, demonstrating that the biotinylation did not alter the topology of the proteins involved in infection. Seven sites of modification were identified in the E2 glycoprotein (K70, K76, K97, K131, K149, K202, and K235), while one site of modification in the E1 glycoprotein (K16) was identified, confirming that the E1 protein is almost completely buried in the virus structure. (c) 2005 Elsevier Inc. All rights reserved. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Mol & Struct Biochem, Raleigh, NC 27695 USA. RP Sharp, JS (reprint author), NIEHS, Struct Biol Lab, POB 12233,111 TW Alexander Dr,MD F0-04, Res Triangle Pk, NC 27709 USA. EM sharp1@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 FU Intramural NIH HHS NR 23 TC 11 Z9 12 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 25 PY 2006 VL 348 IS 1 BP 216 EP 223 DI 10.1016/j.virol.2005.12.020 PG 8 WC Virology SC Virology GA 039WH UT WOS:000237338000019 PM 16443253 ER PT J AU Brust, D Polis, M Davey, R Hahn, B Bacharach, S Whatley, M Fauci, AS Carrasquillo, JA AF Brust, D Polis, M Davey, R Hahn, B Bacharach, S Whatley, M Fauci, AS Carrasquillo, JA TI Fluorodeoxyglucose imaging in healthy subjects with HIV infection: impact of disease stage and therapy on pattern of nodal activation SO AIDS LA English DT Article DE F-18; fluorodeoxyglucose; HAART; HIV; positron emission tomography ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; POSITRON-EMISSION-TOMOGRAPHY; VIRAL SUPPRESSION; LYMPH-NODES; T-CELLS; LYMPHOCYTES; DYNAMICS; PLASMA; TURNOVER AB Objectives: Nodal uptake in areas of lymphocyte activation can be visualized using fluorodeoxyglucose. Various patterns of fluorodeoxyglucose accumulation in HIV-positive patients have been described previously and hypothesized potentially to represent regions of active HIV replication or nodal activation. We evaluated the utility of fluorodeoxyglucose scanning as a tool to study HIV pathogenesis. Design: We evaluated fluorodeoxyglucose biodistribution visually and quantitatively in HIV-negative individuals and various groups of HIV-infected patients to determine the impact on the pattern of nodal activation of HIV infection, the stage of HIV infection and degree of viremia, and HAART. In addition, we attempted to image anatomical site(s) of ongoing HIV replication in patients with suppressed HIV viremia on HAART, but subsequently discontinued HAART. Method: We performed fluorodeoxyglucose imaging on five groups: HIV-negative, HIV-positive individuals with early infection, HIV-positive patients with advanced disease, HIV-positive patients with suppressed viral loads, and HIV-positive patients who stopped HAART. Results: Healthy HIV patients with suppressed viral loads and HIV-negative individuals had no or little fluorodeoxyglucose nodal accumulation or any other hypermetabolic areas, whereas viremic individuals with early and advanced HIV had increased fluorodeoxyglucose in the peripheral nodes, indicating that fluorodeoxyglucose potentially identifies areas of HIV replication. Fluorodeoxyglucose biodistribution was similar between early and advanced-stage disease. Four of five patients taken off HAART had negative baseline scans but developed nodal uptake and increases in viral loads. Conclusion: Abnormal fluorodeoxyglucose accumulation occurs in the nodes of individuals with detectable viral loads. Interruption of effective HAART results in the activation of previously quiescent nodal areas. (c) 2006 Lippincott Williams & Wilkins C1 NIH, Warren G Magnuson Clin Ctr, Natl Inst Allergy & Infect Dis, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. RP Carrasquillo, JA (reprint author), 10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA. EM jcarrasquillo@cc.nih.gov RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 37 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 24 PY 2006 VL 20 IS 7 BP 985 EP 993 DI 10.1097/01.aids.0000222070.52996.76 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 043BV UT WOS:000237575200005 PM 16603850 ER PT J AU Townsley, CA Major, P Siu, LL Dancey, J Chen, E Pond, GR Nicklee, T Ho, J Hedley, D Tsao, M Moore, MJ Oza, AM AF Townsley, CA Major, P Siu, LL Dancey, J Chen, E Pond, GR Nicklee, T Ho, J Hedley, D Tsao, M Moore, MJ Oza, AM TI Phase II study of erlotinib (OSI-774) in patients with metastatic colorectal cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE clinical trial; erlotinib; colorectal cancer; EGFR; correlative markers; phase II ID EPIDERMAL-GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; FACTOR RECEPTOR; MULTICENTER; MUTATIONS; GEFITINIB; FLUOROURACIL; MALIGNANCIES; LEUCOVORIN AB Erlotinib (Tarceva (TM), OSI-774), a potent epidermal growth factor receptor tyrosine kinase inhibitor (EGFR), was evaluated in a phase II study to assess its activity in patients with metastatic colorectal cancer. In all, 38 patients with metastatic colorectal cancer were treated with erlotinib at a continuous daily oral dose of 150 mg. Radiological evaluation was carried out every 8 weeks and tumour biopsies were performed before treatment and on day 8. Of 31 evaluable patients, 19 (61%) had progressive disease and 12 (39%) had stable disease (s.d.). The median time to progression for those patients having s.d. was 123 days (range 108-329 days). The most common adverse events were rash in 34 patients and diarrhoea in 23 patients. Correlative studies were conducted to investigate the effect of erlotinib on downstream signalling. Tumour tissue correlations were based on usable tissue from eight match paired tumour samples pre- and on therapy, and showed a statistically significant decrease in the median intensity of both pEGFR (P = 0.008) and phospho-extracellular signal-regulated kinase (ERK) (P = 0.008) a week after commencement of treatment. No other statistically significant change in tumour markers was observed. Erlotinib was well tolerated with the most common toxicities being rash and diarrhoea. More than one-third of evaluable patients had s.d. for a minimum of 8 weeks. Correlative studies showed a reduction in phosphorylated EGFR and ERK in tumour tissue post-treatment. C1 Univ Toronto, Univ Hlth Network, Princess Margaret Hosp Consortium Phase 2, Dept Haematol & Med Oncol, Toronto, ON M5G 2M9, Canada. Natl Canc Inst, Canc Therapy Evaluat Program, Rockville, MD USA. RP Oza, AM (reprint author), Univ Toronto, Univ Hlth Network, Princess Margaret Hosp Consortium Phase 2, Dept Haematol & Med Oncol, 610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM amit.oza@uhn.on.ca FU NCI NIH HHS [N01-CM-17107] NR 32 TC 87 Z9 89 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD APR 24 PY 2006 VL 94 IS 8 BP 1136 EP 1143 DI 10.1038/sj.bjc.6603055 PG 8 WC Oncology SC Oncology GA 034EG UT WOS:000236910300008 PM 16570047 ER PT J AU Adighibe, O Micklem, K Campo, L Ferguson, M Harris, A Pozos, R Gatter, K Pezzella, F AF Adighibe, O Micklem, K Campo, L Ferguson, M Harris, A Pozos, R Gatter, K Pezzella, F TI Is nonangiogenesis a novel pathway for cancer progression? A study using 3-dimensional tumour reconstructions SO BRITISH JOURNAL OF CANCER LA English DT Article DE lung cancer; angiogenesis; 3D reconstruction ID ANGIOGENESIS; GROWTH AB The nonangiogenic lung tumour is characterized by neoplastic cells co-opting the pre-existent vasculature and filling the alveoli space. 3-Dimensional reconstruction of the tumour reveals that this particular tumour progresses without neovascularization and there is no major destruction of the lung's architectural integrity. C1 Univ Oxford, John Radcliffe Hosp, Canc Res UK Tumour Pathol Grp, Nuffield Dept,Clin Lab Sci, Oxford OX3 9DU, England. NIA, NIH, Lab Neurogenet, Bethesda, MD 20892 USA. Churchill Hosp, Canc Res UK Med Oncol Unit, Oxford OX3 7LJ, England. San Diego State Univ, San Diego, CA 92182 USA. NIH, Minor Int Res Training Program, Div Int Training & Res, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Pezzella, F (reprint author), Univ Oxford, John Radcliffe Hosp, Canc Res UK Tumour Pathol Grp, Nuffield Dept,Clin Lab Sci, Oxford OX3 9DU, England. EM Francesco.pezzella@cancer.org.uk OI Harris, Adrian/0000-0003-1376-8409 FU FIC NIH HHS [5T37TW00067-07, T37 TW000067] NR 13 TC 10 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD APR 24 PY 2006 VL 94 IS 8 BP 1176 EP 1179 DI 10.1038/sj.bjc.6603039 PG 4 WC Oncology SC Oncology GA 034EG UT WOS:000236910300013 PM 16622442 ER PT J AU Frescas, D Mavrakis, M Lorenz, H DeLotto, R Lippincott-Schwartz, J AF Frescas, D Mavrakis, M Lorenz, H DeLotto, R Lippincott-Schwartz, J TI The secretory membrane system in the Drosophila syncytial blastoderm embryo exists as functionally compartmentalized units around individual nuclei SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM; LIVING CELLS; FLUORESCENT PROTEIN; MEIOTIC MATURATION; GOLGI-APPARATUS; MESSENGER-RNAS; EGG CORTEX; ACTIVATION; CELLULARIZATION; DYNAMICS AB Drosophila melanogaster embryogenesis begins with 13 nuclear division cycles within a syncytium. This produces > 6,000 nuclei that, during the next division cycle, become encased in plasma membrane in the process known as cellularization. In this study, we investigate how the secretory membrane system becomes equally apportioned among the thousands of syncytial nuclei in preparation for cellularization. Upon nuclear arrival at the cortex, the endoplasmic reticulum ( ER) and Golgi were found to segregate among nuclei, with each nucleus becoming surrounded by a single ER/Golgi membrane system separate from adjacent ones. The nuclear-associated units of ER and Golgi across the syncytial blastoderm produced secretory products that were delivered to the plasma membrane in a spatially restricted fashion across the embryo. This occurred in the absence of plasma membrane boundaries between nuclei and was dependent on centrosome-derived microtubules. The emergence of secretory membranes that compartmentalized around individual nuclei in the syncytial blastoderm is likely to ensure that secretory organelles are equivalently partitioned among nuclei at cellularization and could play an important role in the establishment of localized gene and protein expression patterns within the early embryo. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Copenhagen, Inst Mol Biol & Physiol, Dept Genet, DK-1353 Copenhagen K, Denmark. RP Lippincott-Schwartz, J (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM jlippin@helix.nih.gov FU Intramural NIH HHS NR 49 TC 37 Z9 39 U1 0 U2 2 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 24 PY 2006 VL 173 IS 2 BP 219 EP 230 DI 10.1083/jcb.200601156 PG 12 WC Cell Biology SC Cell Biology GA 036FC UT WOS:000237055500013 PM 16636144 ER PT J AU Esteban, PF Yoon, HY Becker, J Dorsey, SG Caprari, P Palko, ME Coppola, V Saragovi, HU Randazzo, PA Tessarollo, L AF Esteban, PF Yoon, HY Becker, J Dorsey, SG Caprari, P Palko, ME Coppola, V Saragovi, HU Randazzo, PA Tessarollo, L TI A kinase-deficient TrkC receptor isoform activates Arf6-Rac1 signaling through the scaffold protein tamalin SO JOURNAL OF CELL BIOLOGY LA English DT Article ID METABOTROPIC GLUTAMATE RECEPTORS; CORTICAL DENDRITIC GROWTH; EXCHANGE FACTOR; NEURONAL DEVELOPMENT; ACTIN CYTOSKELETON; PLASMA-MEMBRANE; RAT TRKC; ARF6; CELLS; NEUROTROPHINS AB Neurotrophins play an essential role in mammalian development. Most of their functions have been attributed to activation of the kinase-active Trk receptors and the p75 neurotrophin receptor. Truncated Trk receptor isoforms lacking the kinase domain are abundantly expressed during development and in the adult; however, their function and signaling capacity is largely unknown. We show that the neurotrophin-3 (NT3) TrkCT1-truncated receptor binds to the scaffold protein tamalin in a ligand-dependent manner. Moreover, NT3 initiation of this complex leads to activation of the Rac1 GTPase through adenosine diphosphate-ribosylation factor 6 (Arf6). At the cellular level, NT3 binding to TrkCT1-tamalin induces Arf6 translocation to the membrane, which in turn causes membrane ruffling and the formation of cellular protrusions. Thus, our data identify a new signaling pathway elicited by the kinase-deficient TrkCT1 receptor. Moreover, we establish NT3 as an upstream regulator of Arf6. C1 NCI, Neural Dev Grp, Mouse Canc Genet Program, Frederick, MD 21702 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada. RP Tessarollo, L (reprint author), NCI, Neural Dev Grp, Mouse Canc Genet Program, Frederick, MD 21702 USA. EM tessarol@ncifcrf.gov RI Coppola, Vincenzo/E-2917-2011 OI Coppola, Vincenzo/0000-0001-6163-1779 FU Intramural NIH HHS; NCI NIH HHS [R01 CA082642, CA82642] NR 41 TC 53 Z9 55 U1 0 U2 2 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 24 PY 2006 VL 173 IS 2 BP 291 EP 299 DI 10.1083/jcb.200512013 PG 9 WC Cell Biology SC Cell Biology GA 036FC UT WOS:000237055500019 PM 16636148 ER PT J AU Husain, FT McKinney, CM Horwitz, B AF Husain, FT McKinney, CM Horwitz, B TI Frontal cortex functional connectivity changes during sound categorization SO NEUROREPORT LA English DT Article DE auditory; categorization; functional magnetic resonance imaging; human; inferior frontal gyrus; speech; superior temporal gyrus ID WORKING-MEMORY; IDENTIFICATION; PERCEPTION; ACTIVATION; LANGUAGE; STIMULI; SPEECH; TIME; FMRI AB Using functional connectivity analysis of functional magnetic resonance imaging data, we investigated the role of the inferior frontal gyrus in categorization of simple sounds. We found stronger functional connectivity between left inferior frontal gyrus and auditory processing areas in the temporal cortex during categorization of speech (vowels, syllables) and nonspeech (tones, combinations of tones and sweeps) sounds relative to an auditory discrimination task; the hemispheric lateralization varied depending on the speech-like properties of the sounds. Our results attest to the importance of interactions between temporal cortex and left inferior frontal gyrus in sound categorization. Further, we found different functional connectivity patterns between left inferior frontal gyrus and other brain regions implicated in categorization of syllables compared with other stimuli, reflecting the greater facility for categorization of syllables. (c) 2006 Lippincott Williams & Wilkins. C1 NIH, Brain Imaging & Modeling Sect, Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. RP Husain, FT (reprint author), NIH, Brain Imaging & Modeling Sect, Natl Inst Deafness & Other Commun Disorders, Bldg 10,Rm 8S235-E,9000 Rockville Pike, Bethesda, MD 20892 USA. EM husainf@nidcd.nih.gov FU Intramural NIH HHS NR 19 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 24 PY 2006 VL 17 IS 6 BP 617 EP 621 DI 10.1097/00001756-200604240-00012 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 042LK UT WOS:000237529300012 PM 16603922 ER PT J AU Chen, JH Bian, XW Yao, XH Gong, WH Hu, JY Chen, KQ Iribarren, P Zhao, W Zhou, XD AF Chen, JH Bian, XW Yao, XH Gong, WH Hu, JY Chen, KQ Iribarren, P Zhao, W Zhou, XD TI Nordy, a synthetic lipoxygenase inhibitor, inhibits the expression of formylpeptide receptor and induces differentiation of malignant glioma cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE nordihydroguaiaretic acid; Nordy; glioma; formylpeptide receptor ID FORMYL PEPTIDE RECEPTOR; NORDIHYDROGUAIARETIC ACID; HUMAN-NEUTROPHILS; ESCHERICHIA-COLI; MEDICAL PROGRESS; ARACHIDONIC-ACID; BRAIN-TUMORS; IN-VIVO; GROWTH; CANCER AB We recently found that formylpeptide receptor (FPR), a G-protein-coupled receptor that mediates chemotaxis of phagocytic leukocytes induced by bacterial peptide N-formyl-methionyl-leucyl-phenylalanine is expressed by malignant human glioma cells and promotes tumor growth and angiogenesis. In this study, we examined the effect of Nordy, a novel chiral lipoxygenase inhibitor which was synthesized based on the structure of a natural nordihydroguaiaretic acid, on the expression of FPR by human glioblastoma cells. We found that FPR was expressed at the protein level by highly malignant human glioma cell lines U87 and BT325, and a rat glioma cell line C6. The expression level of FPR was correlated with the degree of the malignancy of tumor cells. The poorly differentiated glioma cell line U87 expressed the highest level of FPR. In U87 glioma cells, the expression of FPR was attenuated at the protein level by Nordy treatment for 48 (P < 0.05). Nordy did not affect FPR mRNA expression in U87 cells. In addition, Nordy treatment seemed to promote glioma cell differentiation, as evidenced by their reduced expression of vimentin and increased expression of GFAP. Our results suggest that Nordy was capable of reducing the level of malignancy of glioma cells. (c) 2006 Elsevier Inc. All rights reserved. C1 Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing 400038, Peoples R China. Third Mil Med Univ, Southwest Hosp, Dept Pharm, Chongqing 400038, Peoples R China. NCI Frederick, Canc Res Ctr, Mol Immunoregulat Lab, Ft Detrick, MD 21702 USA. NCI Frederick, SAIC, Basic Res Program, Ft Detrick, MD 21702 USA. Third Mil Med Univ, Div Basic Med Sci, Dept Pharm, Chongqing 400038, Peoples R China. RP Bian, XW (reprint author), Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing 400038, Peoples R China. EM bianxiuwu@263.net RI Bian, Xiuwu/F-1569-2011; Bian, Xiu-wu/D-4736-2017 OI Bian, Xiu-wu/0000-0003-4383-0197 NR 38 TC 16 Z9 24 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 21 PY 2006 VL 342 IS 4 BP 1368 EP 1374 DI 10.1016/j.bbrc.2006.02.113 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 026DE UT WOS:000236316100054 PM 16516855 ER PT J AU Cariou, B van Harmelen, K Duran-Sandoval, D van Dijk, TH Grefhorst, A Abdelkarim, M Caron, S Torpier, G Fruchart, JC Gonzalez, FJ Kuipers, F Staels, B AF Cariou, B van Harmelen, K Duran-Sandoval, D van Dijk, TH Grefhorst, A Abdelkarim, M Caron, S Torpier, G Fruchart, JC Gonzalez, FJ Kuipers, F Staels, B TI The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 3-PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE-1; HEPATIC CARBOHYDRATE-METABOLISM; BILE-ACID; DIABETES-MELLITUS; 3T3-L1 ADIPOCYTES; DEFICIENT MICE; FXR; ACTIVATION; RESISTANCE; EXPRESSION AB The farnesoid X receptor (FXR) is a bile acid (BA)-activated nuclear receptor that plays a major role in the regulation of BA and lipid metabolism. Recently, several studies have suggested a potential role of FXR in the control of hepatic carbohydrate metabolism, but its contribution to the maintenance of peripheral glucose homeostasis remains to be established. FXR-deficient mice display decreased adipose tissue mass, lower serum leptin concentrations, and elevated plasma free fatty acid levels. Glucose and insulin tolerance tests revealed that FXR deficiency is associated with impaired glucose tolerance and insulin resistance. Moreover, whole-body glucose disposal during a hyperinsulinemic euglycemic clamp is decreased in FXR-deficient mice. In parallel, FXR deficiency alters distal insulin signaling, as reflected by decreased insulin-dependent Akt phosphorylation in both white adipose tissue and skeletal muscle. Whereas FXR is not expressed in skeletal muscle, it was detected at a low level in white adipose tissue in vivo and induced during adipocyte differentiation in vitro. Moreover, mouse embryonic fibroblasts derived from FXR-deficient mice displayed impaired adipocyte differentiation, identifying a direct role for FXR in adipocyte function. Treatment of differentiated 3T3-L1 adipocytes with the FXR-specific synthetic agonist GW4064 enhanced insulin signaling and insulin-stimulated glucose uptake. Finally, treatment with GW4064 improved insulin resistance in genetically obese ob/ob mice in vivo. Although the underlying molecular mechanisms remain to be unraveled, these results clearly identify a novel role of FXR in the regulation of peripheral insulin sensitivity and adipocyte function. This unexpected function of FXR opens new perspectives for the treatment of type 2 diabetes. C1 Inst Pasteur, Dept Atherosclerose, F-59019 Lille, France. INSERM, U545, F-59019 Lille, France. Univ Lille 2, F-59006 Lille, France. Univ Groningen, Med Ctr, Pediat Lab, Ctr Liver Digest & Metab Dis, NL-9700 RB Groningen, Netherlands. NCI, Lab Metab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Staels, B (reprint author), Inst Pasteur, Dept Atherosclerose, F-59019 Lille, France. EM bart.staels@pasteur-lille.fr OI Staels, Bart/0000-0002-3784-1503 NR 39 TC 242 Z9 256 U1 2 U2 11 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 21 PY 2006 VL 281 IS 16 BP 11039 EP 11049 DI 10.1074/jbc.M510258200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 033BV UT WOS:000236822200045 PM 16446356 ER PT J AU He, LS Wu, XL Siegel, R Lipsky, PE AF He, LS Wu, XL Siegel, R Lipsky, PE TI TRAF6 regulates cell fate decisions by inducing caspase 8-dependent apoptosis and the activation of NF-kappa B. SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESONANCE ENERGY-TRANSFER; RECEPTOR-ASSOCIATED KINASE; LIVING CELLS; INTERLEUKIN-1 RECEPTOR; PROTEASOME INHIBITORS; CASPASE ACTIVITY; FLOW-CYTOMETRY; PROTEIN; DEATH; MEDIATE AB Tumor necrosis factor receptor-associated factor 6 (TRAF6) functions as an adaptor, positively regulating the NF-kappa B pathway. Here we report a new function of human TRAF6, the direct stimulation of apoptosis. The mechanism of apoptosis induction results from the capacity of human TRAF6 to interact and activate caspase 8. Both the C-terminal TRAF domain of human TRAF6, which directly interacts with the death effector domain of pro-caspase 8, and the N-terminal RING domain, which is required for activation of caspase 8, are necessary for the induction of apoptosis. The role of endogenous TRAF6 in regulating apoptosis was confirmed by extinguishing TRAF6 expression with specific small-hairpin RNA that resulted in diminished spontaneous apoptosis and resistance to induced apoptosis. In contrast to the human molecule, murine TRAF6 displayed less ability to induce apoptosis and a greater capacity to stimulate NF-kappa B activity. Human and murine TRAF6 are similar except in the region between zinc finger 5 and the TRAF domains. Reciprocal transfer of this connecting region completely exchanged the ability of human and murine TRAF6 to induce apoptosis and activate NF-kappa B. Unique regions of TRAF6 therefore play an important role in determining cell fate. C1 NIAMS, Flow Cytometry Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. NIAMS, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP He, LS (reprint author), NIAMS, Flow Cytometry Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. EM Liusheng.He@Stjude.org RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 NR 40 TC 24 Z9 29 U1 1 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 21 PY 2006 VL 281 IS 16 BP 11235 EP 11249 DI 10.1074/jbc.M508779200 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 033BV UT WOS:000236822200067 PM 16436380 ER PT J AU Yamasaki, E Wada, A Kumatori, A Nakagawa, I Funao, J Nakayama, M Hisatsune, J Kimura, M Moss, J Hirayama, T AF Yamasaki, E Wada, A Kumatori, A Nakagawa, I Funao, J Nakayama, M Hisatsune, J Kimura, M Moss, J Hirayama, T TI Helicobacter pylori vacuolating cytotoxin induces activation of the proapoptotic proteins Bax and Bak, leading to cytochrome C release and cell death, independent of vacuolation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPITHELIAL-CELLS; LIPID-BILAYERS; CANCER-CELLS; VACA TOXIN; APOPTOSIS; INDUCTION; EXPRESSION; INFECTION; PATHWAY; DOMAIN AB Helicobacter pylori vacuolating cytotoxin, VacA, which causes vacuolation of gastric epithelial cells and other types of cultured cells, is known to stimulate apoptosis via a mitochondria-dependent pathway. In the present study, we examined the mechanisms of VacA-induced mitochondrial damage. Intracellular VacA localization was monitored by immunostaining and confocal microscopy; in AZ-521 cells in which cytochrome c release was stimulated, most of VacA was localized to vacuoles rather than mitochondria. VacA reduced the membrane potential of isolated mitochondria without inducing cytochrome c release, suggesting that it did not act directly to induce cytochrome c release from mitochondria and that in intact cells, VacA-induced cytochrome c release involved apoptosis-related factor(s), such as a proapoptotic Bcl-2 family protein. In agreement, flow cytometric analyses using antibodies specific for activated Bax revealed that intracellular Bax was activated by VacA in a concentration- and time-dependent manner. Using active form-specific antibodies, we also observed that the Bcl-2 family protein, Bak, was activated. By confocal microscopy, Bax and Bak were activated in AZ-521 cells in which cytochrome c release was induced by VacA. In addition, small interfering RNA-induced silencing of the bax gene resulted in reduction of VacA-stimulated cytochrome c release, consistent with a contribution of VacA-induced Bax activation to cytochrome c release. NH4Cl enhanced both VacA-induced vacuolation and Bax activation, whereas Bax activation was not inhibited by bafilomycin A1, which inhibited vacuolation caused by VacA. These results suggest that VacA acts through different signaling pathways to induce apoptosis via Bax activation, independent of vacuolation. C1 Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528523, Japan. Japan Sci & Technol Corp, PRESTO, Saitama 3320012, Japan. Chiba Inst Technol, Fac Risk & Crisis Management, Dept Disaster Prevent Syst, Div Med Sci, Chiba 2880025, Japan. Osaka Univ, Grad Sch Dent, Dept Oral & Mol Microbiol, Suita, Osaka 5650871, Japan. Okayama Univ, Sch Med, Fac Hlth Sci, Dept Med Technol, Okayama 7008558, Japan. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Wada, A (reprint author), Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528523, Japan. EM a-wada@net.nagasaki-u.ac.jp FU Intramural NIH HHS NR 51 TC 85 Z9 93 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 21 PY 2006 VL 281 IS 16 BP 11250 EP 11259 DI 10.1074/jbc.M509404200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 033BV UT WOS:000236822200068 PM 16436379 ER PT J AU Kaus, S Castellone, MD Bedell, VM Konar, M Gutkind, JS Ramchandran, R AF Kaus, S Castellone, MD Bedell, VM Konar, M Gutkind, JS Ramchandran, R TI Robo4 signaling in endothelial cells implies attraction guidance mechanisms SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAGIC ROUNDABOUT; AXON GUIDANCE; RHO-GTPASES; SLIT; ZEBRAFISH; RECEPTORS; MIGRATION; PROTEINS; ANGIOGENESIS; CDC42 AB Roundabouts (robo) are cell-surface receptors that mediate repulsive signaling mechanisms at the central nervous system midline. However, robos may also mediate attraction mechanisms in the context of vascular development. Here, we have performed structure-function analysis of roundabout4 (Robo4), the predominant robo expressed in embryonic zebrafish vasculature and found by gain of function approaches in vitro that Robo4 activates Cdc42 and Rac1 Rho GTPases in endothelial cells. Indeed, complementary robo4 gene knockdown approaches in zebrafish embryos show lower amounts of active Cdc42 and Rac1 and angioblasts isolated from these knockdown embryos search actively for directionality and guidance cues. Furthermore, Robo4-expressing endothelial cells show morphology and phenotype, characteristic of Rho GTPase activation. Taken together, this study suggests that Robo4 mediates attraction-signaling mechanisms through Rho GTPases in vertebrate vascular guidance. C1 NIH, Pathol Lab, NCI, Rockville, MD 20850 USA. NIDCR, Cell Growth Regulat Sect, Oral & Pharyngeal Canc Branch, NIH, Rockville, MD 20850 USA. RP Ramchandran, R (reprint author), NIH, Pathol Lab, NCI, Key W Facil,Room 320,9610 Med Ctr Dr, Rockville, MD 20850 USA. EM ramchanr@mail.nih.gov RI Gutkind, J. Silvio/A-1053-2009; Xiao, Yang/B-5668-2012; OI CASTELLONE, MARIADOMENICA/0000-0003-0507-8037 NR 36 TC 0 Z9 0 U1 0 U2 6 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 21 PY 2006 VL 281 IS 16 BP 11347 EP 11356 DI 10.1074/jbc.M508853200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 033BV UT WOS:000236822200077 ER PT J AU Ren, JW Kan, A Leong, SH Ooi, LLPJ Jeang, KT Chong, SS Kon, OL Lee, CGL AF Ren, JW Kan, A Leong, SH Ooi, LLPJ Jeang, KT Chong, SS Kon, OL Lee, CGL TI FAT10 plays a role in the regulation of chromosomal stability SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UBIQUITIN-LIKE PROTEIN; SPINDLE ASSEMBLY CHECKPOINT; NECROSIS-FACTOR-ALPHA; MITOTIC CHECKPOINT; COLORECTAL-CANCER; MAD2; EXPRESSION; CELLS; GENE; INSTABILITY AB Aneuploidy is a key process in tumorigenesis. Dysfunction of the mitotic spindle checkpoint proteins has been implicated as a cause of aneuploidy in cells. We have previously reported that FAT10, a member of the ubiquitin-like modifier family of proteins, is overexpressed in several gastrointestinal and gynecological cancers. Here we show that FAT10 interacts with MAD2, a spindle checkpoint protein, during mitosis. Notably, we show that localization of MAD2 at the kinetochore during the prometaphase stage of the cell cycle was greatly reduced in FAT10-overexpressing cells. Furthermore, compared with parental HCT116 cells, fewer mitotic cells were observed after double thymidine-synchronized FAT10-overexpressing cells were released into nocodazole for more than 4 h. Nonetheless, when these double thymidine-treated cells were released into media, a similar number of G(1) parental and FAT10-overexpressing HCT116 cells was observed throughout the 10-h time course. Additionally, more nocodazole-treated FAT10-overexpressing cells escape mitotic controls and are multinucleate compared with parental cells. Significantly, we observed a higher degree of variability in chromosome number in cells overexpressing FAT10. Hence, our data suggest that high levels of FAT10 protein in cells lead to increased mitotic nondisjunction and chromosome instability, and this effect is mediated by an abbreviated mitotic phase and the reduction in the kinetochore localization of MAD2 during the prometaphase stage of the cell cycle. C1 Natl Canc Ctr, Div Med Sci, Singapore 169610, Singapore. Natl Canc Ctr, Dept Surg Oncol, Singapore 169610, Singapore. Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117597, Singapore. Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pediat, Singapore 117597, Singapore. Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Obstet & Gynecol, Singapore 117597, Singapore. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA. RP Lee, CGL (reprint author), Natl Canc Ctr, Div Med Sci, Level 6,Lab 5,11 Hosp Dr, Singapore 169610, Singapore. EM bchleec@nus.edu.sg RI Jeang, Kuan-Teh/A-2424-2008; Chong, Samuel/D-8098-2015 NR 35 TC 52 Z9 61 U1 1 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 21 PY 2006 VL 281 IS 16 BP 11413 EP 11421 DI 10.1074/jbc.M507218200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 033BV UT WOS:000236822200084 PM 16495226 ER PT J AU Berezhkovskii, AM Weiss, GH AF Berezhkovskii, AM Weiss, GH TI Diffusion in multilayer media: Transient behavior of the lateral diffusion coefficient SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID SURFACES AB A general formalism for treating lateral diffusion in a multilayer medium is developed. The formalism is based on the relation between the lateral diffusion and the distribution of the cumulative residence time, which the diffusing particle spends in different layers. We exploit this fact to derive general expressions which give the global and local time-dependent diffusion coefficients in terms of the average cumulative times spent by the particle in different layers and the probabilities of finding the particle in different layers, respectively. These expressions are used to generalize two recently obtained results: (a) A solution for the short-time behavior of the lateral diffusion coefficient in two layers separated by a permeable membrane obtained by a perturbation theory is extended to the entire range of time. (b) A solution for the time-dependent diffusion coefficient of a ligand, which repeatedly dissociates and rebinds to sites on a planar surface, obtained under the assumption that the medium above the surface is infinite, is generalized to allow for the medium layer of finite thickness. For the latter problem we derive an expression for the Fourier-Laplace transform of the propagator in terms of the double Laplace transform of the probability density of the cumulative residence time spent by the ligand in the medium layer. C1 Natl Inst Hlth, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Berezhkovskii, AM (reprint author), Karpov Inst Phys Chem, Vorontsovo Pole 10, Moscow 103064, Russia. EM berezh@mail.nih.gov FU Intramural NIH HHS NR 11 TC 4 Z9 4 U1 0 U2 0 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 2006 VL 124 IS 15 AR 154710 DI 10.1063/1.2188394 PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 034ZN UT WOS:000236969500044 PM 16674254 ER PT J AU Gopich, IV Szabo, A AF Gopich, IV Szabo, A TI Theory of the statistics of kinetic transitions with application to single-molecule enzyme catalysis SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID RESONANCE ENERGY-TRANSFER; PROTEIN CONFORMATIONAL DYNAMICS; TRANSFER CONFOCAL MICROSCOPY; FLUORESCENCE SPECTROSCOPY; COUNTING STATISTICS; PHOTON STATISTICS; TIME; TRAJECTORIES; PEPTIDES; DISORDER AB Single-molecule spectroscopy can monitor transitions between two microscopic states when these transitions are associated with the emission of photons. A general formalism is developed for obtaining the statistics of such transitions from a microscopic model when the dynamics is described by master or rate equations or their continuum analog, multidimensional reaction-diffusion equations. The focus is on the distribution of the number of transitions during a fixed observation time, the distribution of times between transitions, and the corresponding correlation functions. It is shown how these quantities are related to each other and how they can be explicitly calculated in a straightforward way for both immobile and diffusing molecules. Our formalism reduces to renewal theory when the monitored transitions either go to or originate from a single state. The influence of dynamics slow compared with the time between monitored transitions is treated in a simple way, and the probability distributions are expressed in terms of Mandel-type formulas. The formalism is illustrated by a detailed analysis of the statistics of catalytic turnovers of enzymes. When the rates of conformational changes are slower than the catalytic rates which are in turn slower than the binding relaxation rate, (1) the mean number of turnovers is shown to have the classical Michaelis-Menten form, (2) the correlation function of the number of turnovers is a direct measure of the time scale of catalytic rate fluctuations, and (3) the distribution of the time between consecutive turnovers is determined by the steady-state distribution. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Gopich, IV (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM gopich@nih.gov RI Szabo, Attila/H-3867-2012 FU Intramural NIH HHS NR 71 TC 105 Z9 106 U1 3 U2 34 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 2006 VL 124 IS 15 AR 154712 DI 10.1063/1.2180770 PG 21 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 034ZN UT WOS:000236969500046 PM 16674256 ER PT J AU Yanagida, A Shoji, A Shibusawa, Y Shindo, H Tagashira, M Ikeda, M Ito, Y AF Yanagida, A Shoji, A Shibusawa, Y Shindo, H Tagashira, M Ikeda, M Ito, Y TI Analytical separation of tea catechins and food-related polyphenols by high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE tea; catechin; thearubigin; polyphenol; counter-current chromatography ID SIZE-EXCLUSION CHROMATOGRAPHY; BLACK TEA; CAPILLARY-ELECTROPHORESIS; LIQUID-CHROMATOGRAPHY; INDIVIDUAL CATECHINS; APPLE PROCYANIDINS; MASS-SPECTROMETRY; GREEN TEA; THEARUBIGINS; THEAFLAVINS AB High-speed counter-current chromatography (HSCCC) using the type-J coil planet centrifuge was applied to compositional analysis of tea catechins and separation of other food-related polyphenols. The HSCCC separation of nine different standard compounds and those from extracts of commercial tea leaves was performed with a two-phase solvent system composed of tert-butyl methyl ether-acetonitrile-0.1% aqueous trifluoroacetic acid (TFA) (2:23, v/v/v) by eluting the upper organic phase at a flow rate of 2 ml/min. The main compounds in the extract of non-fermented green tea were found to be monomeric catechins, their galloylated esters and caffeine. In addition to these compounds, oxidized pigments, such as hydrophobic theaflavins (TFs) and polar thearubigins (TRs) were also separated and detected from the extracts of semi-fermented oolong tea and fermented black tea. Furthermore, several food-related polyphenols, such as condensed catechin oligomers (procyanidins), phenolic acids and flavonol glycosides were clearly separated under the same HSCCC condition. These separation profiles of HSCCC provide useful information about the hydrophobic diversity of these bioactive polyphenols present in various types of teas and food products. (c) 2005 Elsevier B.V. All rights reserved. C1 Tokyo Univ Pharm & Life Sci, Div Struct Biol & Analyt Sci, Sch Pharm, Hachioji, Tokyo 1920392, Japan. Asahi Brewery Co Ltd, Fundamental Res Lab, Ibaraki 3020106, Japan. Natl Heart & Lung Inst, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Yanagida, A (reprint author), Tokyo Univ Pharm & Life Sci, Div Struct Biol & Analyt Sci, Sch Pharm, 1432-1 Horinouchi, Hachioji, Tokyo 1920392, Japan. EM yanagida@ps.toyaku.ac.jp NR 31 TC 62 Z9 66 U1 2 U2 29 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 21 PY 2006 VL 1112 IS 1-2 BP 195 EP 201 DI 10.1016/j.chroma.2005.09.086 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 034RC UT WOS:000236947300019 PM 16239007 ER PT J AU He, K Pauli, GF Zheng, B Wang, HK Bai, NS Peng, TS Roller, M Zheng, QY AF He, K Pauli, GF Zheng, B Wang, HK Bai, NS Peng, TS Roller, M Zheng, QY TI Cimicifuga species identification by high performance liquid chromatography-photodiode array/mass spectrometric/evaporative light scattering detection for quality control of black cohosh products SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE black cohosh; Cimicifuga; cimigenol arabinoside; cimifugin; species identification; botanical standardization ID TRITERPENE GLYCOSIDES; ACID-DERIVATIVES; RACEMOSA; CONSTITUENTS; RHIZOMA; MEDICINE; EXTRACTS; ESTERS; LC/MS; L. AB Black cohosh has become one of the most important herbal products in the US dietary supplements market. It is manufactured from roots and rhizomes of Cimicifuga racemosa (Ranunculaceae). Botanical identification of the raw starting material is a key step in the quality control of black cohosh preparations. The present report summarizes a fingerprinting approach based on high performance liquid chromatography-photodiode array/mass spectrometric/evaporative light scattering detection (HPLC-PDA/MS/ELSD) that has been developed and validated using a total of 10 Cimicifuga species. These include three North American species, Cimicifuga racemosa, Cimicifuga americana, Cimicifuga rubifolia, and seven Asian species, Cimicifuga acerina, Cimicifuga biternat, Cimicifuga dahurica, Cimicifuga heracleifolia, Cimicifuga japonica, Cimicifuga foetida, and Cimicifuga simplex. The chemotaxonomic distinctiveness of the HPLC fingerprints allows identification of all 10 Cimicifuga species. The triterpene glycoside cimigenol-3-O-arabinoside (3), cimifugin (12), and cimifugin-3-O-glucoside (18) were determined to be suitable species-specific markers for the distinction of C. racemosa from the other Cimicifuga species. In addition to identification, the fingerprint method provided insight into chemical interconversion processes occurring between the diverse triterpene glycosides contained in black cohosh. The reported method has proven its usefulness in the botanical standardization and quality control of black cohosh products. (c) 2006 Published by Elsevier B.V. C1 Naturex Pure World Bot Inc, Dept Res & Dev, S Hackensack, NJ 07606 USA. Univ Illinois, Coll Pharm, UIC, NIH,Ctr Bot Dietary Supplements Res,PCRPS, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. AndroSci Corp, San Diego, CA 92121 USA. RP Zheng, QY (reprint author), 6 Fox Hill Dr, Wayne, NJ 07470 USA. EM qyzheng@aol.com OI Pauli, Guido/0000-0003-1022-4326 FU NCCIH NIH HHS [P50 AT000155-070001, P50 AT000155, P50 AT00155] NR 36 TC 60 Z9 65 U1 3 U2 21 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 21 PY 2006 VL 1112 IS 1-2 BP 241 EP 254 DI 10.1016/j.chroma.2006.01.004 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 034RC UT WOS:000236947300025 PM 16515793 ER PT J AU Natarajan, K Hicks, A Mans, J Robinson, H Guan, RJ Mariuzza, RA Margulies, DH AF Natarajan, K Hicks, A Mans, J Robinson, H Guan, RJ Mariuzza, RA Margulies, DH TI Crystal structure of the murine cytomegalovirus MHC-I homolog m144 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE X-ray structure; MHC-Iv; immunoevasin; NK recognition; viral virulence ID NATURAL-KILLER-CELLS; RECEPTOR LY49A; PEPTIDE ANTIGENS; INFECTED CELLS; COMPLEX; MOLECULES; LIGAND; RECOGNITION; GENE; BETA(2)-MICROGLOBULIN AB Large DNA viruses of the herpesvirus family produce proteins that mimic host MHC-I molecules as part of their immunoevasive strategy. The m144 glycoprotein, expressed by murine cytomegalovirus, is thought to be an MHC-I homolog whose expression prolongs viral survival in vivo by preventing natural killer cell activation. To explore the structural basis of this m144 function, we have determined the three-dimensional structure of an m.144/beta 2-microglobulin (beta 2m) complex at 1.9 angstrom resolution. This structure reveals the canonical features of MHC-I molecules including readily identifiable alpha 1, alpha.2, and alpha 3 domains. A unique disulfide bond links the alpha 1 helix to the beta-sheet floor, explaining the known thermal stability of m144. Close juxtaposition of the alpha 1 and alpha 2 helices and the lack of critical residues that normally contribute to anchoring the peptide N and C termini eliminates peptide binding. A region of 13 amino acid residues, corresponding to the amino-terminal portion of the alpha 2 helix, is missing in the electron density map, suggesting an area of structural flexibility that may be involved in ligand binding. Published by Elsevier Ltd. C1 NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Witwatersrand, ZA-2050 Wits, South Africa. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, WM Keck Lab Struct Biol, Rockville, MD 20850 USA. RP Margulies, DH (reprint author), NIAID, Mol Biol Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM dhm@nih.gov RI Margulies, David/H-7089-2013; OI Mans, Janet/0000-0001-6721-1177; Margulies, David/0000-0001-8530-7375 FU Intramural NIH HHS; NIAID NIH HHS [AI 47990, R01 AI047990, R01 AI047990-08] NR 72 TC 27 Z9 27 U1 0 U2 0 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 21 PY 2006 VL 358 IS 1 BP 157 EP 171 DI 10.1016/j.jmb.2006.01.068 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 033SX UT WOS:000236870700014 PM 16500675 ER PT J AU Kuiken, T Holmes, EC McCauley, J Rimmelzwaan, GF Williams, CS Grenfell, BT AF Kuiken, T Holmes, EC McCauley, J Rimmelzwaan, GF Williams, CS Grenfell, BT TI Host species barriers to influenza virus infections SO SCIENCE LA English DT Editorial Material ID ACUTE RESPIRATORY SYNDROME; RNA VIRUS; H5N1; DISEASE; TRANSMISSION; EVOLUTION; FITNESS; EPIDEMIOLOGY; DETERMINANTS; EMERGENCE C1 Erasmus Med Ctr, Dept Virol, NL-3015 GE Rotterdam, Netherlands. Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. Inst Anim Hlth, Comp Lab, Newbury RG20 7NN, Berks, England. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Kuiken, T (reprint author), Erasmus Med Ctr, Dept Virol, NL-3015 GE Rotterdam, Netherlands. EM t.kuiken@erasmusmc.nl OI Holmes, Edward/0000-0001-9596-3552 NR 38 TC 203 Z9 219 U1 2 U2 36 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 21 PY 2006 VL 312 IS 5772 BP 394 EP 397 DI 10.1126/science.1122818 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 034OZ UT WOS:000236941800038 PM 16627737 ER PT J AU Viboud, C Bjornstad, ON Smith, DL Simonsen, L Miller, MA Grenfell, BT AF Viboud, C Bjornstad, ON Smith, DL Simonsen, L Miller, MA Grenfell, BT TI Synchrony, waves, and spatial hierarchies in the spread of influenza SO SCIENCE LA English DT Article ID PANDEMIC INFLUENZA; DYNAMICS; POPULATION; MORTALITY; IMPACT; MODEL; TRANSMISSION; EPIDEMICS; EVOLUTION; PATTERNS AB Quantifying long-range dissemination of infectious diseases is a key issue in their dynamics and control. Here, we use influenza-related mortality data to analyze the between-state progression of interpandemic influenza in the United States over the past 30 years. Outbreaks show hierarchical spatial spread evidenced by higher pairwise synchrony between more populous states. Seasons with higher influenza mortality are associated with higher disease transmission and more rapid spread than are mild ones. The regional spread of infection correlates more closely with rates of movement of people to and from their workplaces (workflows) than with geographical distance. Workflows are described in turn by a gravity model, with a rapid decay of commuting up to around 100 km and a long tail of rare longer range flow. A simple epidemiological model, based on the gravity formulation, captures the observed increase of influenza spatial synchrony with transmissibility; high transmission allows influenza to spread rapidly beyond local spatial constraints. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Penn State Univ, Dept Entomol, University Pk, PA 16802 USA. Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. NIAID, NIH, Bethesda, MD 20818 USA. RP Viboud, C (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM viboudc@mail.nih.gov RI Bjornstad, Ottar/I-4518-2012; Smith, David/L-8850-2013; OI Smith, David/0000-0003-4367-3849; Simonsen, Lone/0000-0003-1535-8526 NR 29 TC 326 Z9 333 U1 4 U2 55 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 21 PY 2006 VL 312 IS 5772 BP 447 EP 451 DI 10.1126/science.1125237 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 034OZ UT WOS:000236941800053 PM 16574822 ER PT J AU Mandal, DM Sorant, AJM Atwood, LD Wilson, AF Bailey-Wilson, JE AF Mandal, DM Sorant, AJM Atwood, LD Wilson, AF Bailey-Wilson, JE TI Allele frequency misspecification: effect on power and Type I error of model-dependent linkage analysis of quantitative traits under random ascertainment SO BMC GENETICS LA English DT Article ID LIKELIHOOD AB Background: Studies of model-based linkage analysis show that trait or marker model misspecification leads to decreasing power or increasing Type I error rate. An increase in Type I error rate is seen when marker related parameters (e.g., allele frequencies) are misspecified and ascertainment is through the trait, but lod-score methods are expected to be robust when ascertainment is random ( as is often the case in linkage studies of quantitative traits). In previous studies, the power of lod-score linkage analysis using the "correct" generating model for the trait was found to increase when the marker allele frequencies were misspecified and parental data were missing. An investigation of Type I error rates, conducted in the absence of parental genotype data and with misspecification of marker allele frequencies, showed that an inflation in Type I error rate was the cause of at least part of this apparent increased power. To investigate whether the observed inflation in Type I error rate in model-based LOD score linkage was due to sampling variation, the trait model was estimated from each sample using REGCHUNT, an automated segregation analysis program used to fit models by maximum likelihood using many different sets of initial parameter estimates. Results: The Type I error rates observed using the trait models generated by REGCHUNT were usually closer to the nominal levels than those obtained when assuming the generating trait model. Conclusion: This suggests that the observed inflation of Type I error upon misspecification of marker allele frequencies is at least partially due to sampling variation. Thus, with missing parental genotype data, lod-score linkage is not as robust to misspecification of marker allele frequencies as has been commonly thought. C1 Louisiana State Univ, Hlth Sci Ctr, Dept Genet, New Orleans, LA 70112 USA. NHGRI, NIH, Baltimore, MD USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Mandal, DM (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Genet, 533 Bolivar St,CSRB 6-16, New Orleans, LA 70112 USA. EM dmanda@lsuhsc.edu; ajms@mail.nih.gov; lda@bu.edu; afw@mail.nih.gov; jebw@mail.nih.gov RI Wilson, Alexander/C-2320-2009; OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU Intramural NIH HHS; NCRR NIH HHS [P41 RR003655, RR03655]; NHGRI NIH HHS [N01HG65404] NR 16 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD APR 20 PY 2006 VL 7 AR 21 DI 10.1186/1471-2156-7-21 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 050YT UT WOS:000238127700001 PM 16618369 ER PT J AU Kaufmann, M Hortobagyi, GN Goldhirsch, A Scholl, S Makris, A Valagussa, P Blohmer, JU Eiermann, W Jackesz, R Jonat, W Lebeau, A Loibl, S Miller, W Seeber, S Semiglazov, V Smith, R Souchon, R Stearns, V Untch, M von Minckwitz, G AF Kaufmann, M Hortobagyi, GN Goldhirsch, A Scholl, S Makris, A Valagussa, P Blohmer, JU Eiermann, W Jackesz, R Jonat, W Lebeau, A Loibl, S Miller, W Seeber, S Semiglazov, V Smith, R Souchon, R Stearns, V Untch, M von Minckwitz, G TI Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: An update SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SURGICAL ADJUVANT BREAST; PATHOLOGICAL COMPLETE RESPONSE; PROJECT PROTOCOL B-27; SENTINEL NODE BIOPSY; RANDOMIZED-TRIAL; PREOPERATIVE CHEMOTHERAPY; INDUCTION CHEMOTHERAPY; CONSERVING SURGERY; FACTOR SUPPORT; TRASTUZUMAB T AB Neoadjuvant (primary systemic) treatment is the standard treatment for locally advanced breast cancer and a standard option for primary operable disease. Because of new treatments and new understandings of breast cancer, however, recommendations published in 2003 regarding neoadjuvant treatment for operable disease required updating. Therefore, a second international panel of representatives of a number of breast cancer clinical research groups was convened in September 2004 to update these recommendations. As part of this effort, data published to date were reviewed critically and indications for neoadjuvant treatment were newly defined. C1 Univ Frankfurt, D-6000 Frankfurt, Germany. St Gertrauden, Berlin, Germany. Krankenhaus Roten Kreuz, Frauenklin, Munich, Germany. Univ Munich, Inst Pathol, D-8000 Munich, Germany. Univ Hosp, Kiel, Germany. Tumorzentrum, Essen, Germany. Allgemeines Krankenhaus Hagen, Hagen, Germany. German Breast Grp, Neu Isenburg Frankfurt, Germany. European Sch Oncol, Milan, Italy. Ist Nazl Tumori, I-20133 Milan, Italy. Inst Curie, Paris, France. Mt Vernon Hosp, Northwood HA6 2RN, Middx, England. Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland. Univ Edinburgh, Edinburgh, Midlothian, Scotland. Univ Klin Chirurg, Vienna, Austria. NN Petrov Oncol Res Inst, St Petersburg, Russia. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Kaufmann, M (reprint author), Univ Frankfurt Klinikum, Dept Obstet & Gynecol, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. EM M.Kaufmann@em.uni-frankfurt.de RI Jonat, Walter/E-3024-2010; OI Semiglazov, Vladimir/0000-0003-0077-9619 NR 62 TC 315 Z9 349 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2006 VL 24 IS 12 BP 1940 EP 1949 DI 10.1200/JCO.200502.6187 PG 10 WC Oncology SC Oncology GA 037CM UT WOS:000237124300025 PM 16622270 ER PT J AU Tsurutani, J Ballas, MS Dennis, PA AF Tsurutani, J Ballas, MS Dennis, PA TI Overestimating the influence of the 1999 WHO classification of lung tumors on survival in bronchioloalveloar carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID POSITRON-EMISSION-TOMOGRAPHY; CANCER; IMPACT C1 NCI, Ctr Canc Res, Canc Therapeut Branch, Bethesda, MD 20892 USA. RP Tsurutani, J (reprint author), NCI, Ctr Canc Res, Canc Therapeut Branch, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2006 VL 24 IS 12 BP 1963 EP 1963 DI 10.1200/JCO.2005.05.1318 PG 1 WC Oncology SC Oncology GA 037CM UT WOS:000237124300036 PM 16622278 ER PT J AU Tripathi, P Madan, R Chougnet, C Divanovic, S Ma, XJ Wahl, LM Gajewski, T Karp, CL Hildeman, DA AF Tripathi, P Madan, R Chougnet, C Divanovic, S Ma, XJ Wahl, LM Gajewski, T Karp, CL Hildeman, DA TI An adenoviral vector for probing promoter activity in primary immune cells SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE T cell; macrophage; dendritic cell; transcription; promoter ID NF-KAPPA-B; FACTOR-ALPHA PRODUCTION; MEDIATED GENE DELIVERY; T-CELLS; DENDRITIC CELLS; IN-VIVO; INTERFERON-GAMMA; TRANSGENIC MICE; HUMAN MONOCYTES; MACROPHAGES AB Functional analysis of the DNA regulatory regions that control gene expression has largely been performed through transient transfection of promoter-reporter constructs into transformed cells. However, transformed cells are often poor models of primary cells. To directly analyze DNA regulatory regions in primary cells, we generated a novel adenoviral luciferase reporter-vector, pShuttle-luciferase-GFP (pSLUG) that contains a promoterless luciferase cassette (with an upstream cloning site) for probing promoter activity, and a GFP expression cassette that allows for the identification of transduced cells. Recombinant adenoviruses generated front this vector can transduce a wide range of primary immune cells with high efficiency, including human macrophages. dendritic cells and T cells; and mouse T cells transgenic for the coxsackie and adenoviral receptor (CAR). In primary T cells, we show inducible nuclear factor of activated T cells (NF-AT) activity using a recombinant pSLUG adenovirus containing a consensus NF-AT promoter. We further show inducible IL-12/23 p40 promoter activity in primary macrophages and dendritic cells using a recombinant pSLUG adenovirus containing the proximal human IL-12/23 p40 promoter. The pSLUG system promises to be a powerful tool for the analysis of DNA regulatory regions in diverse types of primary immune cells. (c) 2006 Elsevier B.V. All rights reserved. C1 Childrens Hosp, Med Ctr, Dept Pediat, Div Immunobiol, Cincinnati, OH 45229 USA. Univ Cincinnati, Coll Med, Cincinnati, OH 45229 USA. Childrens Hosp, Med Ctr, Div Mol Immunol, Cincinnati, OH 45229 USA. Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. Natl Inst Dent & Craniofacial Res, Immunopathol Sect, Bethesda, MD 20892 USA. Univ Chicago, Dept Med, Ben May Inst Canc Res, Chicago, IL 60637 USA. RP Hildeman, DA (reprint author), Childrens Hosp, Med Ctr, Dept Pediat, Div Immunobiol, MLC 7038,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM David.Hildeman@cchmc.org RI Hildeman, David/I-4884-2015; OI Hildeman, David/0000-0002-0421-8483; Karp, Christopher/0000-0002-0832-2659 FU NCI NIH HHS [R01 CA100223-01A1, R01 CA100223]; NIAID NIH HHS [R01 AI057753, R01 AI056927, AI057753, AI056927, R56 AI057753]; NIDDK NIH HHS [R01 DK056415, DK56415]; NINDS NIH HHS [NS39435, R01 NS039435] NR 38 TC 2 Z9 2 U1 1 U2 4 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 2006 VL 311 IS 1-2 BP 19 EP 30 DI 10.1016/j.jim.2006.01.009 PG 12 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 042KQ UT WOS:000237527200003 PM 16563424 ER PT J AU Yang, XY Chen, E Jiang, HG Hartmann, WK Mitra, G Hecht, T Soman, G AF Yang, XY Chen, E Jiang, HG Hartmann, WK Mitra, G Hecht, T Soman, G TI Development of a quantitative cell-based ELISA, for a humanized anti-IL-2/IL-15 receptor beta antibody (HuMik beta(1)), and correlation with functional activity using an antigen-transfected murine cell line SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE IL-2/IL-15R beta; antibody; HuMik beta(1); CbELISA; IL-15; proliferation; assay validation ID IL-2 RECEPTOR; INTERLEUKIN-2 RECEPTOR; AUTOIMMUNE-DISEASES; ALPHA-CHAIN; PHASE-I; SYSTEM; TARGET; TRANSPLANTATION; IMMUNOTHERAPY; INVOLVEMENT AB The HuMi beta(1), humanized IgG1 monoclonal antibody directed toward the IL-2/IL-15 receptor beta-chain (CD 122), inhibits the actions of the inflammatory cytokine IL-15, and may be useful for immunotherapy of an array of autoimmune disorders as well as diseases associated with the retrovirus human T-cell lymphotrophic virus 1 (HTLV-1). In order to facilitate the production of material for clinical investigation, we developed a cell-based ELISA (CbELISA) for measuring the binding activity, as if potential biological activity marker, of the HuMik beta(1) monoclonal antibody to a transfected 32D mouse cell line (32D beta) expressing IL-2R beta antigen on the cell surface. There is specific binding of HuMik beta(1) to the transfected cell line, titrating out in the concentration range of 1-1000ng/ml. Under identical conditions. there was no binding of HuMik beta(1) to the parent cell line 32D. Satisfactory binding curves with HuMik beta(1) were obtained with 32D beta cells grown between 3 and 19 passages in culture and at sced densities of 2 x 10(5) - 4 x 10(6) cells/well. The binding was specific for Mik beta antibodies recognizing the IL-2/IL-15 receptor beta subunit as demonstrated by binding of HuMik beta(1), Mik beta(2), and Mik beta(3) antibodies, and lack of binding of irrelevant humanized and chimeric antibodies and isotype-matched human IgG1 to the 32D beta cell. Also, the human IgG1 and irrelevant humanized and chimeric antibodies did not interfere with the HuMik beta(1) binding. The assay could detect changes in binding activity of HuMik beta(1) antibody under stressful conditions (heat and low pH) and the results paralleled the effect of stress oil the physicochemical characteristics. More importantly, the binding activity shows in apparent correlation to inhibition of IL-15-induced proliferation of 32D beta cells with HuMik beta(1). In conclusion, the cell-based ELISA method represents a simple, reproducible accurate quantitative assay for monitoring HuMik beta(1) activity and could be used as a potency marker assay for monitoring the lot-lot consistency and functional stability of HuMik beta(1) product. (c) 2006 Elsevier B.V. All rights reserved. C1 NCI, Bioanalyt Dev Lab, Biopharmaceut Dev Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Biol Resource Branch, Frederick, MD 21702 USA. RP Soman, G (reprint author), NCI, Bioanalyt Dev Lab, Biopharmaceut Dev Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM somang@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 25 TC 6 Z9 6 U1 0 U2 2 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 2006 VL 311 IS 1-2 BP 71 EP 80 DI 10.1016/j.jim.2006.01.014 PG 10 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 042KQ UT WOS:000237527200007 PM 16564055 ER PT J AU Takala, SL Smith, DL Stine, OC Coulibaly, D Thera, MA Doumbo, OK Plowe, CV AF Takala, SL Smith, DL Stine, OC Coulibaly, D Thera, MA Doumbo, OK Plowe, CV TI A high-throughput method for quantifying alleles and haplotypes of the malaria vaccine candidate Plasmodium falciparum merozoite surface protein-1 19 kDa SO MALARIA JOURNAL LA English DT Article ID LINKAGE-DISEQUILIBRIUM; SEQUENCE DIVERSITY; NATURAL-SELECTION; DNA POOLS; MSP-1; FREQUENCIES; PARASITE; POLYMORPHISM; ANTIGEN; PYROSEQUENCING(TM) AB Background: Malaria vaccine efficacy may be compromised if the frequency of non-target alleles increases following vaccination with a genetically polymorphic target. Methods are needed to monitor genetic diversity in polymorphic vaccine antigens, but determining which genetic variants of such antigens are present in infected individuals is complicated by the frequent occurrence of mixed infections. Methods: Pyrosequencing was used to determine allele frequencies at each of six single nucleotide polymorphisms in the Plasmodium falciparum blood-stage vaccine antigen merozoite surface protein 1 19 kDa (MSP-1(19)) in field samples from a vaccine-testing site in Mali. Mixtures of MSP-1(19) clones were created to validate a haplotype-estimating algorithm that uses maximum likelihood methods to determine the most probable combination of haplotypes given the allele frequencies for an infection and the haplotypes known to be circulating in the population. Results: Fourteen unique MSP-1(19) haplotypes were identified among 351 genotyped infections. After adjustment to a standard curve, Pyrosequencing provided accurate and precise estimates of allele frequencies in mixed infections. The haplotype-estimating algorithm provided accurate estimates of haplotypes in mixed infections containing up to three haplotypes. Based on the MSP-1(19) locus, approximately 90% of the 351 infections contained two or fewer haplotypes. Conclusion: Pyrosequencing in conjunction with a haplotype-estimating algorithm provides accurate estimates of haplotypes present in infections with up to 3 haplotypes, and can be used to monitor genetic diversity in parasite populations prior to and following introduction of MSP-1-based malaria vaccines. C1 Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. Univ Bamako, Malaria Res & Training Ctr, Bamako, Mali. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. RP Plowe, CV (reprint author), Univ Maryland, Sch Med, Ctr Vaccine Dev, 685 W Baltimore St,HSFI-480, Baltimore, MD 21201 USA. EM stakala@medicine.umaryland.edu; smitdave@helix.nih.gov; ostin001@umaryland.edu; drissac@yahoo.fr; mthera@mrtcbko.org; okd@mrtcbko.org; cplowe@medicine.umaryland.edu RI Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 FU NIAID NIH HHS [N01AI85346] NR 26 TC 25 Z9 25 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD APR 20 PY 2006 VL 5 AR 31 DI 10.1186/1475-2875-5-31 PG 10 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 043AX UT WOS:000237572800001 PM 16626494 ER PT J AU Nakazawa, K AF Nakazawa, K TI Inducible and cell-type restricted manipulation in the entorhinal cortex SO NEURON LA English DT Editorial Material ID MEDIAL TEMPORAL-LOBE; REMOTE SPATIAL MEMORY; HIPPOCAMPAL-LESIONS; RETROGRADE-AMNESIA; RAT; PLACES; DAMAGE AB The entorhinal cortex functions as the gateway to the hippocampal formation. However, its role in formation and consolidation of hippocampus-dependent memory remains relatively unexplored. In this issue of Neuron, Yasuda and Mayford report an elegant cell-type restricted inducible transgenic mouse overexpressing a mutant form of CaM kinase II selectively in superficial layers of medial entorhinal cortex and its upstream regions. These animals display a selective spatial memory deficit during the immediate posttraining period as well as during acquisition in the Morris water maze. Similar to the hippocampus, this time-limited involvement of entorhinal cortex in spatial memory processing suggests a crucial role for hippocampal-entorhinal circuitry in spatial memory formation. C1 NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Nakazawa, K (reprint author), NIMH, Intramural Res Program, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. RI Nakazawa, Kazutoshi/J-6195-2015 OI Nakazawa, Kazutoshi/0000-0001-5699-9093 NR 18 TC 2 Z9 2 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 20 PY 2006 VL 50 IS 2 BP 183 EP 185 DI 10.1016/j.neuron.2006.04.007 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 037VW UT WOS:000237176700005 PM 16630829 ER PT J AU Simonsen, L Taylor, RJ Kapikian, AZ AF Simonsen, L Taylor, RJ Kapikian, AZ TI Rotavirus vaccines SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID INTUSSUSCEPTION; EFFICACY; SAFETY C1 NIAID, Bethesda, MD 20892 USA. RP Simonsen, L (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM lsimonsen@mail.nih.gov OI Simonsen, Lone/0000-0003-1535-8526 NR 4 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 20 PY 2006 VL 354 IS 16 BP 1748 EP 1748 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 033ZP UT WOS:000236893900017 ER PT J AU Daw, MI Bannister, NV Isaac, JTR AF Daw, MI Bannister, NV Isaac, JTR TI Rapid, activity-dependent plasticity in timing precision in neonatal barrel cortex SO JOURNAL OF NEUROSCIENCE LA English DT Article DE development; glutamate; kainate receptor; AMPA receptor; long-term potentiation; spike timing ID LONG-TERM POTENTIATION; THALAMOCORTICAL SYNAPSES; SOMATOSENSORY CORTEX; PYRAMIDAL CELLS; AMPA RECEPTORS; FEEDFORWARD INHIBITION; SYNAPTIC MODIFICATION; KAINATE RECEPTORS; STIMULUS LOCATION; TRANSMISSION AB Developing neuronal networks acquire the ability to precisely time events, a key feature required for information processing. In the barrel cortex, encoding of information requires a high-precision temporal code with a resolution of similar to 5 ms; however, it is not known what process drives the maturation in timing precision. Here, we report that long-term potentiation (LTP) at thalamocortical synapses in the neonatal layer IV barrel cortex produces a dramatic improvement in the timing of neuronal output and synaptic input. LTP strongly reduces the latency and variability of synaptically evoked action potentials, improving the fidelity of timing to within that predicted to be required for adult sensory processing. Such changes in timing also occur during development in the neonate. LTP also reduces the summation of EPSPs shortening the window for coincidence detection for synaptic input. In contrast to these reliable effects, LTP produced only a modest and variable change in synaptic efficacy. Thus, our findings suggest that the primary role of this form of neonatal LTP is for the acquisition of timing precision and the refinement of coincidence detection, rather than an increase in synaptic strength. Therefore, neonatal thalamocortical LTP may be a critical prerequisite for the maturation of information processing in the barrel cortex. C1 NINDS, NIH, Bethesda, MD 20892 USA. Univ Bristol, Sch Med Sci, Dept Anat, MRC,Ctr Synapt Plast, Bristol BS8 1TD, Avon, England. RP Isaac, JTR (reprint author), NINDS, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM isaacj@ninds.nih.gov OI Daw, Michael/0000-0002-8374-5977 FU Intramural NIH HHS; Wellcome Trust NR 47 TC 27 Z9 28 U1 0 U2 0 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 19 PY 2006 VL 26 IS 16 BP 4178 EP 4187 DI 10.1523/JNEUROSCI.0150-06.2006 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 034ET UT WOS:000236912100004 PM 16624938 ER PT J AU McAlonan, K Cavanaugh, J Wurtz, RH AF McAlonan, K Cavanaugh, J Wurtz, RH TI Attentional modulation of thalamic reticular neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE attention; thalamus; visual; thalamic reticular nucleus; macaque; extracellular recordings ID LATERAL GENICULATE-NUCLEUS; NIGRA PARS RETICULATA; PRIMARY VISUAL-CORTEX; PULVINAR NUCLEI; ORGANIZATION; ACTIVATION; RESPONSES; COMPLEX; INVITRO; GALAGO AB The major pathway for visual information reaching cerebral cortex is through the lateral geniculate nucleus (LGN) of the thalamus. Acting on this vital relay is another thalamic nucleus, the thalamic reticular nucleus (TRN). This nucleus receives topographically organized collaterals from both thalamus and cortex and sends similarly organized projections back to thalamus. The inputs to the TRN are excitatory, but the output back to the thalamic relay is inhibitory, providing an ideal organization for modulating visual activity during early processing. This functional architecture led Crick in 1984 to hypothesize that TRN serves to direct a searchlight of attention to different regions of the topographic map; however, despite the substantial influence of this hypothesis, the activity of TRN neurons has never been determined during an attention task. We have determined the nature of the response of visual TRN neurons in awake monkeys, and the modulation of that response as the monkeys shifted attention between visual and auditory stimuli. Visual TRN neurons had a strong (194 spikes/s) and fast (25 ms latency) transient increase of activity to spots of light falling in their receptive fields, as well as high background firing rate (45 spikes/s). When attention shifted to the spots of light, the amplitude of the transient visual response typically increased, whereas other neuronal response characteristics remained unchanged. Thus, as predicted previously, TRN activity is modified by shifts of visual attention, and these attentional changes could influence visual processing in LGN via the inhibitory connections back to the thalamus. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20982 USA. RP McAlonan, K (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50,49 Convent Dr, Bethesda, MD 20982 USA. EM km@nei.nih.gov FU Intramural NIH HHS NR 32 TC 94 Z9 95 U1 1 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 19 PY 2006 VL 26 IS 16 BP 4444 EP 4450 DI 10.1523/JNEUROSCI.5602-05.2006 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 034ET UT WOS:000236912100030 PM 16624964 ER PT J AU Korzhnev, DM Bezsonova, I Evanics, F Taulier, N Zhou, Z Bai, YW Chalikian, TV Prosser, RS Kay, LE AF Korzhnev, DM Bezsonova, I Evanics, F Taulier, N Zhou, Z Bai, YW Chalikian, TV Prosser, RS Kay, LE TI Probing the transition state ensemble of a protein folding reaction by pressure-dependent NMR relaxation dispersion SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; 4-HELIX BUNDLE PROTEIN; HYDROGEN-EXCHANGE; APOCYTOCHROME B(562); UNFOLDED STATES; VOLUME CHANGES; CYTOCHROME-C; N-15 NMR; COMPRESSIBILITY; DYNAMICS AB The F61A/A90G mutant of a redesigned form of apocytochrome b(562) folds by an apparent two-state mechanism. We have used the pressure dependence of N-15 NMR relaxation dispersion rate profiles to study the changes in volumetric parameters that accompany the folding reaction of this protein at 45 degrees C. The experiments were performed under conditions where the folding/unfolding equilibrium could be studied at each pressure without addition of denaturants. The exquisite sensitivity of the methodology to small changes in folding/unfolding rates facilitated the use of relatively low-pressure values (between 1 and 270 bar) so that pressure-induced changes to the unfolded state ensemble could be minimized. A volume change for unfolding of -81 mL/mol is measured (at 1 bar), a factor of 1.4 larger (in absolute value) than the volume difference between the transition state ensemble (TSE) and the unfolded state. Notably, the changes in the free energy difference between folded and unfolded states and in the activation free energy for folding were not linear with pressure. Thus, the difference in the isothermal compressibility upon unfolding (-0.11 mL mol(-1) bar(-1)) and, for the first time, the compressibility of the TSE relative to the unfolded state (0.15 mL mol(-1) bar(-1)) could be calculated. The results argue for a TSE that is collapsed but loosely packed relative to the folded state and significantly hydrated, suggesting that the release of water occurs after the rate-limiting step in protein folding. The notion of a collapsed and hydrated TSE is consistent with expectations based on earlier temperature-dependent folding studies, showing that the barrier to folding at 45 degrees C is entropic (Choy, W. Y.; Zhou, Z.; Bai, Y.; Kay, L. E. J Am. Chem. Soc. 2005, 127, 5066-5072). C1 Univ Toronto, Dept Med Genet, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Chem, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Pharmaceut Sci, Leslie Dan Fac Pharm, Toronto, ON M5S 2S2, Canada. NCI, Biochem Lab, Bethesda, MD 20892 USA. RP Kay, LE (reprint author), Univ Toronto, Dept Med Genet, Toronto, ON M5S 1A8, Canada. EM kay@pound.med.utoronto.ca RI Taulier, Nicolas/C-5793-2008; Taulier, Nicolas/C-3965-2011 OI Taulier, Nicolas/0000-0003-1017-1068 FU Intramural NIH HHS NR 37 TC 26 Z9 27 U1 1 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 19 PY 2006 VL 128 IS 15 BP 5262 EP 5269 DI 10.1021/ja0601540 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 034GN UT WOS:000236917200059 PM 16608362 ER PT J AU Baker, SG AF Baker, SG TI Surrogate endpoints: Wishful thinking or reality? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CLINICAL-TRIALS; VALIDATION; CRITERIA C1 NCI, EPN 3131, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, EPN 3131, 6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA. EM sbl6i@nih.gov NR 10 TC 31 Z9 31 U1 0 U2 2 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 19 PY 2006 VL 98 IS 8 BP 502 EP 503 DI 10.1093/jnci/djj153 PG 2 WC Oncology SC Oncology GA 043UO UT WOS:000237627900001 PM 16622112 ER PT J AU Rowland, JH Yancik, R AF Rowland, JH Yancik, R TI Cancer survivorship: The interface of aging, comorbidity, and quality care SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID TEACHABLE MOMENT; RECOMMENDATIONS; PERSPECTIVES; DIAGNOSIS; HEALTH C1 NCI, Div Canc Control & Populat Sci, Off Canc Survivorship, Bethesda, MD 20892 USA. NIA, Bethesda, MD 20892 USA. RP Rowland, JH (reprint author), NCI, Div Canc Control & Populat Sci, Off Canc Survivorship, 6130 Execut Blvd,Ste 4089, Bethesda, MD 20892 USA. EM rowland@mail.nih.gov NR 15 TC 38 Z9 40 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 19 PY 2006 VL 98 IS 8 BP 504 EP 505 DI 10.1093/jnci/djj154 PG 2 WC Oncology SC Oncology GA 043UO UT WOS:000237627900002 PM 16622113 ER PT J AU Thompson, IM Ankerst, DP Chi, C Goodman, PJ Tangen, CM Lucia, MS Feng, ZD Parnes, HL Coltman, CA AF Thompson, IM Ankerst, DP Chi, C Goodman, PJ Tangen, CM Lucia, MS Feng, ZD Parnes, HL Coltman, CA TI Assessing prostate cancer risk: Results from the prostate cancer prevention trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MEN; ANTIGEN; LEVEL; NG/ML AB Prostate-specific antigen (PSA) testing is the primary method used to diagnose prostate cancer in the United States. Methods to integrate other risk factors associated with prostate cancer into individualized risk prediction are needed. We used prostate biopsy data from men who participated in the Prostate Cancer Prevention Trial (PCPT) to develop a predictive model of prostate cancer. Methods: We included 5519 men from the placebo group of the PCPT who underwent prostate biopsy., had at least one PSA measurement and a digital rectal examination (DRE) performed during the year before the biopsy, and had at least two PSA measurements performed during the 3 years before the prostate biopsy. Logistic regression was used to model the risk of prostate cancer and high-grade disease associated with age at biopsy, race, family history of prostate cancer, PSA level, PSA velocity, DRE result, and previous prostate biopsy. Risk equations were created from the estimated logistic regression models. All statistical tests were two-sided. Results: A total of 1211 (21.9%) men were diagnosed with prostate cancer by prostate biopsy. Variables that predicted prostate cancer included higher PSA level, positive family history of prostate cancer, and abnormal DRE result, whereas a previous negative prostate biopsy was associated with reduced risk. Neither age at biopsy nor PSA velocity contributed independent prognostic information. Higher PSA level, abnormal DRE result, older age at biopsy, and African American race were predictive for high-grade disease (Gleason score >= 7) whereas a previous negative prostate biopsy reduced this risk. Conclusions: This predictive model allows an individualized assessment of prostate cancer risk and risk of high-grade disease for men who undergo a prostate biopsy. C1 Univ Texas, Hlth Sci Ctr, Dept Urol, UTHSCSA, San Antonio, TX 78229 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Colorado, Denver, CO 80202 USA. NCI, Div Canc Prevent, Bethesda, MD USA. SW Oncol Grp, San Antonio, TX USA. RP Thompson, IM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Urol, UTHSCSA, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM thompsoni@uthscsa.edu FU NCI NIH HHS [CA35178, 5UO1CA86402-04, CA37429, CA45808] NR 10 TC 506 Z9 523 U1 6 U2 22 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 19 PY 2006 VL 98 IS 8 BP 529 EP 534 DI 10.1093/jnci/djj131 PG 6 WC Oncology SC Oncology GA 043UO UT WOS:000237627900010 PM 16622122 ER PT J AU Max, MB Wu, TX Atlas, SJ Edwards, RR Haythornthwaite, JA Bollettino, AF Hipp, HS McKnight, CD Osman, IA Crawford, EN Pao, M Nejim, J Kingman, A Aisen, DC Scully, MA Keller, RB Goldman, D Belfer, I AF Max, Mitchell B. Wu, Tianxia Atlas, Steven J. Edwards, Robert R. Haythornthwaite, Jennifer A. Bollettino, Antonella F. Hipp, Heather S. McKnight, Colin D. Osman, Inge A. Crawford, Erin N. Pao, Maryland Nejim, Jemiel Kingman, Albert Aisen, Daniel C. Scully, Michele A. Keller, Robert B. Goldman, David Belfer, Inna TI A clinical genetic method to identify mechanisms by which pain causes depression and anxiety SO MOLECULAR PAIN LA English DT Article ID MAINE LUMBAR SPINE; RISK-FACTORS; NONSURGICAL MANAGEMENT; PSYCHIATRIC-DISORDERS; PERSISTENT PAIN; DISC HERNIATION; RECEPTOR GENE; PRIMARY-CARE; BACK-PAIN; POLYMORPHISM AB Background: Pain patients are often depressed and anxious, and benefit less from psychotropic drugs than pain-free patients. We hypothesize that this partial resistance is due to the unique neurochemical contribution to mood by afferent pain projections through the spino-parabrachial-hypothalamic-amygdalar systems and their projections to other mood-mediating systems. New psychotropic drugs for pain patients might target molecules in such brain systems. We propose a method to prioritize molecular targets by studying polymorphic genes in cohorts of patients undergoing surgical procedures associated with a variable pain relief response. We seek molecules that show a significant statistical interaction between ( 1) the amount of surgical pain relief, and ( 2) the alleles of the gene, on depression and anxiety during the first postoperative year. Results: We collected DNA from 280 patients with sciatica due to a lumbar disc herniation, 162 treated surgically and 118 non-surgically, who had been followed for 10 years in the Maine Lumbar Spine Study, a large, prospective, observational study. In patients whose pain was reduced > 25% by surgery, symptoms of depression and anxiety, assessed with the SF-36 Mental Health Scale, improved briskly at the first postoperative measurement. In patients with little or no surgical pain reduction, mood scores stayed about the same on average. There was large inter-individual variability at each level of residual pain. Polymorphisms in three pre-specified pain-mood candidate genes, catechol-O-methyl transferase (COMT), serotonin transporter, and brain-derived neurotrophic factor (BDNF) were not associated with late postoperative mood or with a pain-gene interaction on mood. Although the sample size did not provide enough power to persuasively search through a larger number of genes, an exploratory survey of 25 other genes provides illustrations of pain-gene interactions on postoperative mood - the mu opioid receptor for short-term effects of acute sciatica on mood, and the galanin- 2 receptor for effects of unrelieved post-discectomy pain on mood one year after surgery. Conclusion: Genomic analysis of longitudinal studies of pain, depression, and anxiety in patients undergoing pain-relieving surgery may help to identify molecules through which pain alters mood. Detection of alleles with modest-sized effects will require larger cohorts. C1 Natl Inst Dent & Craniofacial Res, Clin Pain Res Sect, Div Intramural Res, NIH,DHHS, Bethesda, MD USA. Natl Inst Dent & Craniofacial Res, Stat Core, Div Populat & Hlth Promot Sci, NIH,DHHS, Bethesda, MD USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Serv,Gen Med Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Serv,Clin Epidemiol Unit, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. NIMH, Off Clin Director, NIH, DHHS, Bethesda, MD 20892 USA. NIAAA, Neurogenet Lab, NIH, DHHS, Rockville, MD 20852 USA. Howard Hughes Med Inst, Bethesda, MD 20817 USA. Maine Spine & Rehabil, Portland, ME USA. RP Max, MB (reprint author), Natl Inst Dent & Craniofacial Res, Clin Pain Res Sect, Div Intramural Res, NIH,DHHS, Bethesda, MD USA. EM mm77k@nih.gov; wuti@mail.nih.gov; satlas@partners.org; redwar10@jhmi.edu; jhayth1@jhmi.edu; bollettinoa@nidcr.nih.gov; hs_hipp@yahoo.com; mcknightc@ohsu.edu; osmani@mail.nih.gov; crawforde@mail.nih.gov; paom@mail.nih.gov; nejimj@mail.nih.gov; kingmana@mail.nih.gov; chicken1@gmail.com; mascully7@aol.com; rbkeller@wildblue.net; dgneuro@mail.nih.gov; ibelfer@mail.nih.gov RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU AHRQ HHS [HS-09804, HS-06344, HS-08194, R01 HS009804]; Intramural NIH HHS; NIAAA NIH HHS [Z01 AA000301]; NIAMS NIH HHS [K23 AR051315, P60 AR048094]; NIDCR NIH HHS [Z01 DE000366]; NINDS NIH HHS [K24 NS002225, K24 NS02225] NR 50 TC 36 Z9 39 U1 3 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-8069 J9 MOL PAIN JI Mol. Pain PD APR 19 PY 2006 VL 2 AR 14 DI 10.1186/1744-8069-2-14 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 165AV UT WOS:000246277100001 PM 16623937 ER PT J AU Smith-Bindman, R Miglioretti, DL Lurie, N Abraham, L Barbash, RB Strzelczyk, J Dignan, M Barlow, WE Beasley, CM Kerlikowske, K AF Smith-Bindman, R Miglioretti, DL Lurie, N Abraham, L Barbash, RB Strzelczyk, J Dignan, M Barlow, WE Beasley, CM Kerlikowske, K TI Does utilization of screening mammography explain racial and ethnic differences in breast cancer? SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID WHITE WOMEN; BLACK-WOMEN; SOCIOECONOMIC-FACTORS; CARCINOMA SURVIVAL; AMERICAN WOMEN; UNITED-STATES; RACE; DIAGNOSIS; STAGE; DISPARITIES AB Background: Reasons for persistent differences in breast cancer mortality rates among various racial and ethnic groups have been difficult to ascertain. Objective: To determine reasons for disparities in breast cancer outcomes across racial and ethnic groups. Design: Prospective cohort. Setting: The authors pooled data from 7 mammography registries that participate in the National Cancer Institute-funded'Breast Cancer Surveillance Consortium. Cancer diagnoses were ascertained through linkage with pathology databases; Surveillance, Epidemiology, and End Results programs; and state tumor registries. Participants: 1010515 women 40 years of age and older who had at least 1 mammogram between 1996 and 2002; 17558 of these women had diagnosed breast cancer. Measurements: Patterns of mammography and the probability of inadequate mammography screening were examined. The authors evaluated whether overall and advanced cancer rates were similar across racial and ethnic groups and whether these rates were affected by the use of mammography. Results: African-American, Hispanic, Asian, and Native American women were more likely than white women to have received inadequate mammographic screening (relative risk, 1.2 [95% Cl, 1.2 to 1.2], 1.3 [Cl, 1.2 to 1.3], 1.4 [Cl, 1.3 to 1.4], and 1.2 [Cl, 1.1 to 1.2) respectively). African-American women were more likely than white, Asian, and Native American women to have large, advanced-stage, high-grade, and lymph node-positive tumors of the breast. The observed differences in advanced cancer rates between African American and white women were attenuated or eliminated after the cohort was stratified by screening history. Among women who were previously screened at intervals of 4 to 41 months, African -American women were no more likely to have large, advanced-stage tumors or lymph node involvement than white women with the same screening history. African-American women had higher rates of high-grade tumors than white women regardless of screening history. The lower rates of advanced cancer among Asian and Native American women persisted when the cohort was stratified by mammography history. Limitations: Results are based on a cohort of women who had received mammographic evaluations. Conclusions: African-American women are less likely to receive adequate mammographic screening than white women, which may explain the higher prevalence of advanced breast tumors among African-American women. Tumor characteristics may also contribute to differences in cancer outcomes because African-American women have higher-grade tumors than white women regardless of screening. These results suggest that adherence to recommended mammography screening intervals may reduce breast cancer mortality rates. C1 Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94115 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA. RAND Corp, Arlington, VA USA. NCI, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Kentucky, Prevent Res Ctr, Lexington, KY USA. Canc Res & Biostat, Seattle, WA USA. Univ N Carolina, Pembroke, NC USA. RP Smith-Bindman, R (reprint author), Univ Calif San Francisco, Dept Radiol, 1600 Divisadero St, San Francisco, CA 94115 USA. EM Rebecca.Smith-Bindman@Radiology.UCSF.edu FU NCI NIH HHS [U01CA69976, U01CA70013, U01CA86082, U01CA63740, U01CA63736, U01CA63731, U01CA86076, U01CA70040, K07 CA86032] NR 49 TC 181 Z9 185 U1 2 U2 5 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 18 PY 2006 VL 144 IS 8 BP 541 EP 553 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 035QZ UT WOS:000237017900001 PM 16618951 ER PT J AU Augustyn, KE Wojtuszewski, K Hawkins, ME Knutson, JR Mukerji, I AF Augustyn, KE Wojtuszewski, K Hawkins, ME Knutson, JR Mukerji, I TI Examination of the premelting transition of DNA A-tracts using a fluorescent adenosine analogue SO BIOCHEMISTRY LA English DT Article ID PTERIDINE NUCLEOSIDE ANALOGS; SEQUENCE-DIRECTED CURVATURE; RESONANCE ENERGY-TRANSFER; MINOR-GROOVE; CIRCULAR-DICHROISM; ADENINE TRACT; HU BINDING; BENT DNA; THERMODYNAMICS; DUPLEX AB The fluorescent adenosine analogue 4-amino-8-(2-deoxy-beta-D-ribofuranosyl)-5'-O-dimethoxytrityl-6-methyl-7(8H)-pteridone (6MAP) has been used to perforin residue specific analyses of DNA A-tracts during the premelting transition. DNA A-tracts, which exhibit sequence-induced curvature, adopt a B-DNA conformation as a function of increasing temperature. Fluorescence melting curves indicate that 6MAP is a more sensitive reporter of the premelting transition than UV absorption spectroscopy. Further, residue specific fluorescence analyses of A-tract and control duplexes reveal that some of the conformational changes associated with the premelting transition occur within A-tract regions. Analyses of the energetics of the premelting transition indicate that ApA steps make a larger enthalpic contribution to the premelting transition than ApT steps. To explore the effect of cations on the premelting transition, fluorescence melts were performed in the presence of NH4+, Mg2+, and low (0.05 M) and high (0.5 M) concentrations of Na+. These studies show that the fluorescence intensity changes associated with the premelting transition are sensitive to cation type and concentration and are larger and more pronounced in the presence of 0.5 M Na+, NH4+, and Mg2+. incorporation of 6MAP into longer duplexes containing phased A-tracts shows that the local environment of adenosines in phased A-tracts is similar to that of individual A-tracts. Fluorescence quenching results indicate that ApA and ApT steps within A-tracts are less solvent exposed than their counterparts in control sequence isomers, possibly because of the narrowed minor groove of A-tract sequences. C1 Wesleyan Univ, Dept Mol Biol & Biochem, Mol Biophys Program, Middletown, CT 06459 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, Opt Spect Sect, NIH, Bethesda, MD 20892 USA. RP Mukerji, I (reprint author), Wesleyan Univ, Dept Mol Biol & Biochem, Mol Biophys Program, Middletown, CT 06459 USA. EM imukerji@wesleyan.edu FU Intramural NIH HHS; NIGMS NIH HHS [GM08271] NR 51 TC 22 Z9 22 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 18 PY 2006 VL 45 IS 15 BP 5039 EP 5047 DI 10.1021/bi0518343 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 034TE UT WOS:000236952700034 PM 16605272 ER PT J AU Aletras, AH Tilak, GS Natanzon, A Hsu, LY Gonzalez, FM Hoyt, RF Arai, AE AF Aletras, AH Tilak, GS Natanzon, A Hsu, LY Gonzalez, FM Hoyt, RF Arai, AE TI Retrospective determination of the area at risk for reperfused acute myocardial infarction with T2-weighted cardiac magnetic resonance imaging - Histopathological and displacement encoding with stimulated echoes (DENSE) functional validations SO CIRCULATION LA English DT Article DE contractility; edema; magnetic resonance imaging; myocardial infarction; myocardial strain ID AUTOMATED FEATURE ANALYSIS; DELAYED ENHANCEMENT MRI; BLOOD-FLOW; GD-DTPA; IRREVERSIBLE INJURY; INVERSION-RECOVERY; SIZING ALGORITHM; RELAXATION-TIMES; GADOLINIUM-DTPA; CONTRAST AGENT AB Background - The aim of this study was to determine whether edema imaging by T2-weighted cardiac magnetic resonance (CMR) imaging could retrospectively delineate the area at risk in reperfused myocardial infarction. We hypothesized that the size of the area at risk during a transient occlusion would be similar to the T2-weighted hyperintense region observed 2 days later, that the T2- weighted hyperintense myocardium would show partial functional recovery after 2 months, and that the T2 abnormality would resolve over 2 months. Methods and Results - Seventeen dogs underwent a 90-minute coronary artery occlusion, followed by reperfusion. The area at risk, as measured with microspheres ( 9 animals), was comparable to the size of the hyperintense zone on T2- weighted images 2 days later (43.4 +/- 3.3% versus 43.0 +/- 3.4% of the left ventricle; P = NS), and the 2 measures correlated ( R = 0.84). The infarcted zone was significantly smaller (23.1 +/- 3.7; both P < 0.001). To test whether the hyperintense myocardium would exhibit partial functional recovery over time, 8 animals were imaged on day 2 and 2 months later. Systolic strain was mapped with displacement encoding with stimulated echoes. Edema, as detected by a hyperintense zone on T2- weighted images, resolved, and regional radial systolic strain partially improved from 4.9 +/- 0.7 to 13.1 +/- 1.5 ( P = 0.001) over 2 months. Conclusions - These findings are consistent with the premise that the T2 abnormality depicts the area at risk, a zone of reversibly and irreversibly injured myocardium associated with reperfused subendocardial infarctions. The persistence of postischemic edema allows T2-weighted CMR to delineate the area at risk 2 days after reperfused myocardial infarction. C1 NHLBI, NIH, US Dept HHS, Bethesda, MD 20892 USA. Mt Sinai Sch Med, New York, NY USA. RP Arai, AE (reprint author), NHLBI, NIH, US Dept HHS, Bldg 10,Room B1D416,MSC 1061, Bethesda, MD 20892 USA. EM AraiA@nhlbi.nih.gov OI Aletras, Anthony/0000-0002-3786-3817 FU Intramural NIH HHS NR 35 TC 322 Z9 328 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 18 PY 2006 VL 113 IS 15 BP 1865 EP 1870 DI 10.1161/CIRCULATIONAHA.105.576025 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 033QX UT WOS:000236865100011 PM 16606793 ER PT J AU Kim, JA Montagnani, M Koh, KK Quon, MJ AF Kim, JA Montagnani, M Koh, KK Quon, MJ TI Reciprocal relationships between insulin resistance and endothelial dysfunction - Molecular and pathophysiological mechanisms SO CIRCULATION LA English DT Review DE diabetes mellitus; endothelium; hypertension; insulin ID NITRIC-OXIDE SYNTHASE; PROTEIN-KINASE-C; MUSCLE GLUCOSE-UPTAKE; NF-KAPPA-B; SPONTANEOUSLY HYPERTENSIVE-RATS; NECROSIS-FACTOR-ALPHA; TYPE-2 DIABETES-MELLITUS; RECEPTOR-ASSOCIATED KINASE; RENIN-ANGIOTENSIN SYSTEM; MULTIPLE SERINE KINASES AB Endothelial dysfunction contributes to cardiovascular diseases, including hypertension, atherosclerosis, and coronary artery disease, which are also characterized by insulin resistance. Insulin resistance is a hallmark of metabolic disorders, including type 2 diabetes mellitus and obesity, which are also characterized by endothelial dysfunction. Metabolic actions of insulin to promote glucose disposal are augmented by vascular actions of insulin in endothelium to stimulate production of the vasodilator nitric oxide (NO). Indeed, NO-dependent increases in blood flow to skeletal muscle account for 25% to 40% of the increase in glucose uptake in response to insulin stimulation. Phosphatidylinositol 3-kinase-dependent insulin-signaling pathways in endothelium related to production of NO share striking similarities with metabolic pathways in skeletal muscle that promote glucose uptake. Other distinct nonmetabolic branches of insulin-signaling pathways regulate secretion of the vasoconstrictor endothelin-1 in endothelium. Metabolic insulin resistance is characterized by pathway-specific impairment in phosphatidylinositol 3-kinase - dependent signaling, which in endothelium may cause imbalance between production of NO and secretion of endothelin-1, leading to decreased blood flow, which worsens insulin resistance. Therapeutic interventions in animal models and human studies have demonstrated that improving endothelial function ameliorates insulin resistance, whereas improving insulin sensitivity ameliorates endothelial dysfunction. Taken together, cellular, physiological, clinical, and epidemiological studies strongly support a reciprocal relationship between endothelial dysfunction and insulin resistance that helps to link cardiovascular and metabolic diseases. In the present review, we discuss pathophysiological mechanisms, including inflammatory processes, that couple endothelial dysfunction with insulin resistance and emphasize important therapeutic implications. C1 NCCAM, Diabet Unit, NIH, Bethesda, MD 20892 USA. Univ Bari, Sch Med, Dept Pharmacol & Human Physiol, Pharmacol Sect, Bari, Italy. Gachon Med Sch, Gil Heart Ctr, Div Cardiol, Inchon, South Korea. RP Quon, MJ (reprint author), NCCAM, Diabet Unit, NIH, 10 Ctr Dr,Bldg 10,Room 6C-205, Bethesda, MD 20892 USA. EM quonm@nih.gov RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; montagnani, monica/0000-0002-5697-8185; Quon , Michael /0000-0002-5289-3707 FU Intramural NIH HHS NR 183 TC 774 Z9 839 U1 9 U2 77 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD APR 18 PY 2006 VL 113 IS 15 BP 1888 EP 1904 DI 10.1161/CIRCULATIONAHA.105.563213 PG 17 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 033QX UT WOS:000236865100014 PM 16618833 ER PT J AU Minton, AP AF Minton, AP TI Macromolecular crowding SO CURRENT BIOLOGY LA English DT Editorial Material C1 NIDDKD, Lab Biochem & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Minton, AP (reprint author), NIDDKD, Lab Biochem & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA. EM minton@helix.nih.gov NR 4 TC 65 Z9 66 U1 0 U2 17 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 18 PY 2006 VL 16 IS 8 BP R269 EP R271 DI 10.1016/j.cub.2006.03.047 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 036CD UT WOS:000237047600005 PM 16631567 ER PT J AU Zimmerberg, J AF Zimmerberg, J TI Membrane biophysics SO CURRENT BIOLOGY LA English DT Editorial Material ID HYDRATION FORCES; SPECTROSCOPY; TRANSITION; ELECTRON; VESICLES; BILAYERS; PROTEIN; FUSION; LIQUID; LIPIDS C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Zimmerberg, J (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. EM joshz@helix.nih.gov NR 30 TC 13 Z9 13 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 18 PY 2006 VL 16 IS 8 BP R272 EP R276 DI 10.1016/j.cub.2006.03.050 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 036CD UT WOS:000237047600007 PM 16631568 ER PT J AU Butler, J Rodondi, N Zhu, YW Figaro, K Fazio, S Vaughan, DE Satterfield, S Newman, AB Goodpaster, B Bauer, DC Holvoet, P Harris, TB de Rekeneire, N Rubin, S Ding, JZ Kritchevsky, SB AF Butler, J Rodondi, N Zhu, YW Figaro, K Fazio, S Vaughan, DE Satterfield, S Newman, AB Goodpaster, B Bauer, DC Holvoet, P Harris, TB de Rekeneire, N Rubin, S Ding, JZ Kritchevsky, SB CA Hlth ABC Study TI Metabolic syndrome and the risk of cardiovascular disease in older adults SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-HEART-DISEASE; INSULIN-RESISTANCE; UNITED-STATES; MORTALITY; FAILURE; HEALTH; CHOLESTEROL; POPULATION; PREVALENCE AB OBJECTIVES The Purpose of this study was to assess whether metabolic syndrome (MetSyn) predicts a higher risk for cardiovascular events in older adults. BACKGROUND The importance of MetSyn as a risk factor has not previously focused on older adults and deserves further study. METHODS We Studied the impact of MetSyn (38% prevalence) on outcomes in 3,035 participants in the Health, Aging, and Body Composition (Health ABC) study (51% women, 42% black, ages 70 to 79 years). RESULTS During a 6-year follow-up, there were 434 deaths overall, 472 coronary events (CE), 213 myocardial infarctions (MI), and 231 heart failure (HF) hospital stays; 59% of the subjects had at least one hospital stay. Coronary events, MI, HF, and overall hospital stays occurred significantly more in subjects with MetSyn (19.9% vs. 12.9% for CE, 9.1% vs. 5.7% for MI, 10.0% vs. 6.1% for HF, and 63.1% vs. 56.1% for overall hospital stay; all p < 0.001). No significant differences in overall mortality was seen; however, there was a trend toward higher cardiovascular mortality (51% vs. 3.8%, p = 0.067) and coronary mortality (4.5% vs. 3.2%, p = 0.051) in patients with MetSyn. After adjusting for baseline characteristics, patients with MetSyn were at a significantly higher risk for CE (hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.28 to 1.91.), MI (HR 1.51, 95% CI 1.12 to 2.05), and HF hospital stay (HR 1.49, 95% CI 1.10 to 2.00). Women and whites with MetSyn had a higher coronary mortality rate. The CE rate was higher among subjects with diabetes and with MetSyn; those with both had the highest risk. CONCLUSIONS Overall, subjects over 70 years are at high risk for cardiovascular events; MetSyn in this group is associated with a significantly greater risk. C1 Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Div Cardiol, Dept Biostat, Nashville, TN 37232 USA. Vanderbilt Univ, Div Gen Internal Med, Nashville, TN 37232 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN 38163 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Catholic Univ Louvain, Ctr Expt Surg & Anesthesiol, B-3000 Louvain, Belgium. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Sticht Ctr Aging, Sch Med, Winston Salem, NC 27109 USA. RP Butler, J (reprint author), Vanderbilt Univ, Med Ctr, Div Cardiol, Dept Biostat, 383 PRB, Nashville, TN 37232 USA. EM javed.butler@vanderbilt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIDDK NIH HHS [DK26657-24] NR 23 TC 105 Z9 108 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 18 PY 2006 VL 47 IS 8 BP 1595 EP 1602 DI 10.1016/j.jacc.2005.12.046 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 033AR UT WOS:000236819000013 PM 16630996 ER PT J AU Roberts, MR Srinivas, M Forrest, D de Escobar, GM Reh, TA AF Roberts, MR Srinivas, M Forrest, D de Escobar, GM Reh, TA TI Making the gradient: Thyroid hormone regulates cone opsin expression in the developing mouse retina SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE photoreceptor; retinal development; nuclear hormone receptor ID X-RECEPTOR-GAMMA; BRAIN-DEVELOPMENT; PHOTORECEPTOR DIFFERENTIATION; TRANSGENE EXPRESSION; ORGAN-CULTURE; BETA-RECEPTOR; BLUE OPSIN; GENE; FETAL; RAT AB Most mammals have two types of cone photoreceptors, which contain either medium wavelength (M) or short wavelength (S) opsin. The number and spatial organization of cone types varies dramatically among species, presumably to fine-tune the retina for different visual environments. In the mouse, S- and M-opsin are expressed in an opposing dorsal-ventral gradient. We previously reported that cone opsin patterning requires thyroid hormone beta 2, a nuclear hormone receptor that regulates transcription in conjunction with its ligand, thyroid hormone (TH). Here we show that exogenous TH inhibits S-opsin expression, but activates M-opsin expression. Binding of endogenous TH to TR beta 2 is required to inhibit S-opsin and to activate M-opsin. TH is symmetrically distributed in the retina at birth as S-opsin expression begins, but becomes elevated in the dorsal retina at the time of M-opsin onset (postnatal day 10). Our results show that TH is a critical regulator of both S-opsin and M-opsin, and suggest that a TH gradient may play a role in establishing the gradient of M-opsin. These results also suggest that the ratio and patterning of cone types may be determined by TH availability during retinal development. C1 Univ Washington, Grad Program Neurobiol & Behav, Seattle, WA 98195 USA. Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. NIDDK, NIH, Bethesda, MD 20892 USA. CSIC, Inst Invest Biomed, E-28029 Madrid, Spain. Univ Autonoma Madrid, E-28029 Madrid, Spain. RP Reh, TA (reprint author), Univ Washington, Grad Program Neurobiol & Behav, Box 357420, Seattle, WA 98195 USA. EM tomreh@u.washington.edu FU Intramural NIH HHS; NEI NIH HHS [T32 EY007031, T32EY07031]; NINDS NIH HHS [NS28308, R01 NS028308] NR 56 TC 119 Z9 119 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 18 PY 2006 VL 103 IS 16 BP 6218 EP 6223 DI 10.1073/pnas.0509981103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 035KF UT WOS:000236999000030 PM 16606843 ER PT J AU Meyer-Lindenberg, A Buckholtz, JW Kolachana, B Hariri, AR Pezawas, L Blasi, G Wabnitz, A Honea, R Verchinski, B Callicott, JH Egan, M Mattay, V Weinberger, DR AF Meyer-Lindenberg, A Buckholtz, JW Kolachana, B Hariri, AR Pezawas, L Blasi, G Wabnitz, A Honea, R Verchinski, B Callicott, JH Egan, M Mattay, V Weinberger, DR TI Neural mechanisms of genetic risk for impulsivity and violence in humans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE aggression; antisocial; functional MRI; monoamine oxidase A; serotonin ID MONOAMINE-OXIDASE-A; FUNCTIONAL POLYMORPHISM; AMYGDALA INTERACTIONS; ORBITOFRONTAL CORTEX; ANTISOCIAL BEHAVIORS; AGGRESSIVE-BEHAVIOR; BRAIN ACTIVITY; SEROTONIN; PROMOTER; GENOTYPE AB Neurobiological factors contributing to violence in humans remain poorly understood. One approach to this question is examining allelic variation in the X-linked monoamine oxidase A (MAOA) gene, previously associated with impulsive aggression in animals and humans. Here, we have studied the impact of a common functional polymorphism in MAOA on brain structure and function assessed with MRI in a large sample of healthy human volunteers. We show that the low expression variant, associated with increased risk of violent behavior, predicted pronounced limbic volume reductions and hyperresponsive amygdala during emotional arousal, with diminished reactivity of regulatory prefrontal regions, compared with the high expression allele. In men, the low expression allele is also associated with changes in orbitofrontal volume, amygdala and hippocampus hyperreactivity during aversive recall, and impaired cingulate activation during cognitive inhibition. Our data identify differences in limbic circuitry for emotion regulation and cognitive control that may be involved in the association of MAOA with impulsive aggression, suggest neural systems-level effects of X-inactivation in human brain, and point toward potential targets for a biological approach toward violence. C1 US Dept HHS, Unit Syst Neurosci Psychiat, NIMH, NIH, Bethesda, MD 20892 USA. US Dept HHS, Neuroimaging Core Facil, NIMH, NIH, Bethesda, MD 20892 USA. US Dept HHS, Clin Brain Disorders Branch, NIMH, Genes Cognit & Psychosis Program,NIH, Bethesda, MD 20892 USA. RP Meyer-Lindenberg, A (reprint author), US Dept HHS, Unit Syst Neurosci Psychiat, NIMH, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM andreasml@nih.gov RI Hariri, Ahmad/D-5761-2011; Buckholtz, Joshua /E-7299-2010; Callicott, Joseph/C-9102-2009; OI Buckholtz, Joshua /0000-0002-9418-8686; Callicott, Joseph/0000-0003-1298-3334; Pezawas, Lukas/0000-0002-1329-6352; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 FU Intramural NIH HHS NR 48 TC 441 Z9 455 U1 8 U2 89 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 18 PY 2006 VL 103 IS 16 BP 6269 EP 6274 DI 10.1073/pnas.0511311103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 035KF UT WOS:000236999000039 PM 16569698 ER PT J AU Tato, CM Laurence, A O'Shea, JJ AF Tato, CM Laurence, A O'Shea, JJ TI Helper T cell differentiation enters a new era: Le Roi est mort; vive le Roi! SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID KLEBSIELLA-PNEUMONIAE; CUTTING EDGE; IL-23; IL-17; INTERLEUKIN-17; CYTOKINES; RESPONSES; DISTINCT; FAMILY; ROLES AB In the dark ages of T cell biology, we considered two fates for differentiated CD4(+) T cells: T helper (Th)1 and Th2 cells. Now we know that the reality is much more complex and interesting. The newest Th cell subset produces the cytokine IL-17. New evidence shows that the IL-17-related cytokine IL-25 is essential for Th2 responses in two infectious disease models. C1 NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Tato, CM (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. EM tatoc@mail.nih.gov RI Laurence, Arian/A-8770-2009 OI Laurence, Arian/0000-0003-0942-8292 NR 28 TC 38 Z9 47 U1 2 U2 3 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 17 PY 2006 VL 203 IS 4 BP 809 EP 812 DI 10.1084/jem.20060522 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 036FH UT WOS:000237056000003 PM 16606679 ER PT J AU Grajewski, RS Silver, PB Agarwal, RK Su, SB Chan, CC Liou, GI Caspi, RR AF Grajewski, RS Silver, PB Agarwal, RK Su, SB Chan, CC Liou, GI Caspi, RR TI Endogenous IRBP can be dispensable for generation of natural CD4(+) CD25(+) regulatory T cells that protect from IRBP-induced retinal autoimmunity SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID BINDING PROTEIN; UVEITIS; RECEPTORS; ANTIGEN; SELF; ENCEPHALOMYELITIS; IDENTIFICATION; MECHANISMS; TOLERANCE; SELECTION AB Susceptibility to experimental autoimmune uveitis (EAU), a model for human uveitis induced in mice with the retinal antigen interphotoreceptor retinoid-binding protein (IRBP), is controlled by "natural" CD4(+)CD25(+) regulatory T (T reg) cells. To examine whether endogenous expression of IRBP is necessary to generate these T reg cells, we studied responses of IRBP knockout (KO) versus wild-type (WT) mice. Unexpectedly, not only WT but also IRBP KO mice immunized with a uveitogenic regimen of IRBP in complete Freund's adjuvant (CFA) exhibited CD25(+) regulatory cells that could be depleted by PC61 treatment, which suppressed development of uveitogenic effector T cells and decreased immunological responses to IRBP. These EAU-relevant T reg cells were not IRBP specific, as their activity was not present in IRBP KO mice immunized with IRBP in incomplete Freund's adjuvant (IFA), lacking mycobacteria (whereas the same mice exhibited normal T reg cell activity to retinal arrestin in IFA). We propose that mycobacterial components in CFA activate T reg cells of other specificities to inhibit generation of IRBP-specific effector T cells in a bystander fashion, indicating that effective T reg cells can be antigen nonspecific. Our data also provide the first evidence that generation of specific T reg cells to a native autoantigen in a mouse with a diverse T cell repertoire requires a cognate interaction. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov OI Caspi, Rachel/0000-0002-7140-7671 FU Intramural NIH HHS; NEI NIH HHS [EY03829] NR 25 TC 49 Z9 54 U1 0 U2 0 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 17 PY 2006 VL 203 IS 4 BP 851 EP 856 DI 10.1084/jem.20050429 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 036FH UT WOS:000237056000010 PM 16585264 ER PT J AU Xie, CP Alcaide, P Geisbrecht, BV Schneider, D Herrmann, M Preissner, KT Luscinskas, FW Chavakis, T AF Xie, CP Alcaide, P Geisbrecht, BV Schneider, D Herrmann, M Preissner, KT Luscinskas, FW Chavakis, T TI Suppression of experimental autoimmune encephalomyelitis by extracellular adherence protein of Staphylococcus aureus SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; MULTIPLE-SCLEROSIS; TRANSENDOTHELIAL MIGRATION; IN-VIVO; VASCULAR ENDOTHELIUM; T-LYMPHOCYTES; ADHESION; CELLS; EXPRESSION AB Multiple sclerosis ( MS) is a devastating inflammatory disorder of the central nervous system (CNS). A major hallmark of MS is the infiltration of T cells reactive against myelin components. T cell infiltration is mediated by the interaction of integrins of the beta 1 and beta 2 family expressed by lymphocytes with their endothelial counter-receptors, vascular cell adhesion molecule 1 and intercellular adhesion molecule (ICAM)-1, respectively. We have reported previously that extracellular adherence protein (Eap) of Staphylococcus aureus exerts antiinflammatory activities by interacting with ICAM-1 and blocking beta 2-integrin-dependent neutrophil recruitment. Here, we report that Eap inhibits experimental autoimmune encephalomyelitis (EAE) in mice. In vitro, Eap reduced adhesion of peripheral blood T cells to immobilized ICAM-1 as well as their adhesion and transmigration of TNF-activated human endothelium under static and shear flow conditions. These inhibitory effects were corroborated in two mouse models of inflammation. In a delayed-type hypersensitivity model, both T cell infiltration and the corresponding tissue edema were significantly reduced by Eap. In addition, Eap administration prevented the development of EAE and markedly decreased infiltration of inflammatory cells into the CNS. Strikingly, intervention with Eap after the onset of EAE suppressed the disease. Collectively, our findings indicate that Eap represents an attractive treatment for autoimmune neuroinflammatory disorders such as MS. C1 NCI, Expt Immunol Branch, NCI, Bethesda, MD 20892 USA. Univ Heidelberg, Dept Internal Med 1, D-69120 Heidelberg, Germany. Univ Missouri, Sch Biol Sci, Div Cell Biol & Biophys, Kansas City, MO 64110 USA. Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Saarland Hosp, Inst Med Microbiol & Hyg, D-66421 Homburg, Germany. Univ Giessen, Sch Med, Inst Biochem, D-35392 Giessen, Germany. RP Chavakis, T (reprint author), NCI, Expt Immunol Branch, NCI, Bethesda, MD 20892 USA. EM chavakist@mail.nih.gov RI Herrmann, Mathias/B-6475-2013 FU Intramural NIH HHS; NHLBI NIH HHS [HL36028, HL53393, HL56985, P01 HL036028, P50 HL056985] NR 42 TC 32 Z9 34 U1 0 U2 1 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 17 PY 2006 VL 203 IS 4 BP 985 EP 994 DI 10.1084/jem.20051681 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 036FH UT WOS:000237056000023 PM 16585266 ER PT J AU Small, A Ilev, I Chernomordik, V Gandjbakhche, A AF Small, A Ilev, I Chernomordik, V Gandjbakhche, A TI Enhancing diffraction-limited images using properties of the point spread function SO OPTICS EXPRESS LA English DT Article ID DIFFERENTIAL CONFOCAL MICROSCOPY; RESOLUTION; IMPLEMENTATION; ILLUMINATION; CONTRAST AB We propose an algorithm to enhance diffraction-limited images based on pixel-to-pixel correlations introduced by the finite width of the Point Spread Function (PSF). We simulate diffraction-limited images of point sources by convolving the PSF of a diffraction-limited lens with simulated images, and enhance the blurred images with our algorithm. Our algorithm reduces the PSF width, increases the contrast, and reveals structure on a length scale half of that resolvable in the unenhanced image. Our enhanced images compare favorably with images enhanced by conventional Tikhonov regularization. (c) 2006 Optical Society of America. C1 NICHHD, Sect Biomed Stochast Phys, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. US FDA, Off Sci & Engn Labs, Rockville, MD 20851 USA. RP Small, A (reprint author), NICHHD, Sect Biomed Stochast Phys, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. EM smallalex@mail.nih.gov NR 16 TC 4 Z9 4 U1 1 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD APR 17 PY 2006 VL 14 IS 8 BP 3193 EP 3203 DI 10.1364/OE.14.003193 PG 11 WC Optics SC Optics GA 037KD UT WOS:000237144700011 PM 19516461 ER PT J AU Cantor, KP AF Cantor, KP TI Feasibility of conducting human studies to address bromate risks SO TOXICOLOGY LA English DT Article DE bromate; epidemiology; 8-hydroxydeoxyguanosine; 8-hydroxyguanine; occupational studies ID OXIDATIVE DNA-DAMAGE; HOGG1 SER326CYS POLYMORPHISM; INCREASED URINARY-EXCRETION; LUNG-CANCER SUSCEPTIBILITY; BODY-MASS INDEX; POTASSIUM BROMATE; VITAMIN-E; SER(326)CYS POLYMORPHISM; CELL-PROLIFERATION; PROSTATE-CANCER AB Findings from epidemiologic studies have been important in evaluating risk of exposure to many contaminants in drinking water. In the case of bromate, a byproduct of ozone disinfection of water, it is unlikely that observational studies of populations exposed to bromate in drinking water will be as revealing as studies of other contaminants, unless risks are much higher than predicted from laboratory studies of rodents. Occupational exposure to bromate has occurred in the flour milling and baking industries, as well as in chemical production of potassium bromate, used as a flour additive. The feasibility of a cohort study of bromate-exposed workers should be evaluated by studying the conditions and levels of exposure in these occupational settings. Bromate exposure causes oxidative damage to guanine bases of DNA, producing 8-hydroxy-guanine (8-OH-Gua), which is excised by 8-oxoguanosine glycosylase (OGGl) and excreted in the urine. Polymorphic variants of OGGl in human populations have been associated with elevated cancer risk. 8-OH-Gua and 8-hydroxy-deoxyguanosine (8-OHdG) have been used as biomarkers of oxidative damage in many human studies, and it would be feasible to employ these indicators in controlled clinical experimental settings to see if exposure to bromate in water at levels close to the maximum contaminant level influences urinary levels of excretion, and if so, to help quantify the level of oxidative damage. Such a study could fill an important data gap by providing human data to help estimate the carcinogenic risk from this exposure. (c) 2005 Aww Research Foundation. Published by Elsevier Ireland Ltd. All rights reserved. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. RP Cantor, KP (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Pl S, Bethesda, MD 20892 USA. EM cantork@nih.gov FU Intramural NIH HHS NR 68 TC 8 Z9 8 U1 0 U2 0 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 17 PY 2006 VL 221 IS 2-3 BP 197 EP 204 DI 10.1016/j.tox.2005.11.009 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 036BU UT WOS:000237046700011 PM 16352386 ER PT J AU Chen, HL Schernhammer, E Schwarzschild, MA Ascherio, A AF Chen, HL Schernhammer, E Schwarzschild, MA Ascherio, A TI A prospective study of night shift work, sleep duration, and risk of Parkinson's disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; Parkinson disease; sleep; sleep disorders; circadian rhythm ID URIC-ACID LEVELS; NURSES HEALTH; WOMEN; MELATONIN; STRESS; SERUM; DEPRESSION; DISORDERS; ANXIETY; CANCER AB The authors prospectively investigated whether working rotating night shifts was associated with the risk of Parkinson's disease among 84,794 female nurses who reported years of night shift work in 1988 (the US Nurses' Health Study). After 975,912 person-years of follow-up (1988-2000), 181 incident Parkinson's disease cases were documented. Compared with nurses who never worked rotating night shifts, those with 15 years or more of night shift work had a 50% lower risk of Parkinson's disease after adjustment for age and smoking (95% confidence interval: 0.26, 0.97; p(trend) = 0.01). Sleep duration was positively associated with Parkinson's disease risk: The relative risk was 1.84 (95% confidence interval: 0.99, 3.42) when comparing nurses who reported 9 or more hours of sleep per day with those who slept 6 hours or less (p(trend) = 0.005). These data suggest that working night shifts may be protective against Parkinson's disease or that low tolerance for night shift work is an early marker of Parkinson's disease. Conversely, habitual longer sleep duration may be an earlier marker of Parkinson's disease. Because of the novelty and the exploratory nature of these findings, confirmation is needed. C1 NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, NIH, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM chenh2@niehs.nih.gov OI Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS; NCI NIH HHS [CA87969]; NINDS NIH HHS [NS35624, NS48468] NR 29 TC 30 Z9 33 U1 0 U2 10 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 2006 VL 163 IS 8 BP 726 EP 730 DI 10.1093/aje/kwj096 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 030DE UT WOS:000236612700006 PM 16495472 ER PT J AU Farr, SL Cai, JW Savitz, DA Sandler, DP Hoppin, JA Cooper, GS AF Farr, SL Cai, JW Savitz, DA Sandler, DP Hoppin, JA Cooper, GS TI Pesticide exposure and timing of menopause - The agricultural health study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE agriculture; endocrine disruptors; fertility; hormone antagonists; hormones; menopause; ovary; pesticides ID FEMALE SPRAGUE-DAWLEY; LIFE-STYLE FACTORS; NATURAL MENOPAUSE; CARBON-TETRACHLORIDE; THYROID-FUNCTION; ORGANOCHLORINE PESTICIDES; MENSTRUAL-CYCLE; IN-VITRO; PUBERTAL DEVELOPMENT; ESTROGENIC ACTIVITY AB Age at menopause has implications for fertility and risk of hormonally related chronic diseases. Some pesticides disrupt reproductive hormones or are toxic to the ovary, but little is known about the association between pesticide exposure and timing of menopause. Cox proportional hazards modeling was used to examine the association between use of pesticides and age at menopause among 8,038 women living and working on farms in Iowa and North Carolina. Premenopausal women aged 35-55 years were followed from enrollment (1993-1997) to the date of their last menstrual period, or their follow-up interview (1999-2003) if still premenopausal. Women who experienced surgical menopause were censored at the date of surgery. Approximately 62% of the women reported ever mixing or applying pesticides; women who had never used pesticides were the comparison group for all analyses. After control for age, smoking status, and past use of oral contraceptives, the median time to menopause increased by approximately 3 months for women who used pesticides (hazard ratio = 0.87, 95% confidence interval: 0.78, 0.97) and by approximately 5 months for women who used hormonally active pesticides (hazard ratio = 0.77, 95% confidence interval: 0.65, 0.92). Pesticide use may be associated with a later age at menopause. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. CUNY Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA. RP Farr, SL (reprint author), 4770 Buford Highway,MS K-34, Atlanta, GA 30341 USA. EM bwa0@cdc.gov OI Sandler, Dale/0000-0002-6776-0018 FU NIEHS NIH HHS [5-T32-ES07018] NR 99 TC 18 Z9 18 U1 1 U2 5 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 2006 VL 163 IS 8 BP 731 EP 742 DI 10.1093/aje/kwj099 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 030DE UT WOS:000236612700007 PM 16495469 ER PT J AU Ling, SM Xue, QL Simonsick, EM Tian, J Bandeen-Roche, K Fried, LP Bathon, JM AF Ling, SM Xue, QL Simonsick, EM Tian, J Bandeen-Roche, K Fried, LP Bathon, JM TI Transitions to mobility difficulty associated with lower extremity osteoarthritis in high functioning older women: Longitudinal data from the Women's Health and Aging Study II SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE osteoarthritis; obesity; mobility; function; disability; women ID BODY-MASS INDEX; KNEE OSTEOARTHRITIS; MUSCLE STRENGTH; US ADULTS; NHANES-I; DISABILITY; PAIN; ARTHRITIS; OBESITY; HIP AB Objective. To assess the impact of lower extremity osteoarthritis (OA) on transitions to mobility difficulty, and to assess the influence of pain, excess weight, and quadriceps strength on these transitions. Methods. We analyzed longitudinal data acquired from 199 participants in the Women's Health and Aging Study II (ages 70-79 years) who initially reported no lower extremity limitation (e.g., difficulty walking one-quarter mile) or difficulty in activities of daily living (ADL; e.g., transferring). Prevalent lower extremity OA was determined from validated algorithms encompassing multiple data sources. Markov transition models were created to analyze the first transition from no difficulty at baseline to lower extremity limitations, ADL difficulty, or both 18, 36, and 72 months later. Results. Compared with women without OA (n = 140), a higher proportion of women with lower extremity OA (n = 59) initially reported pain on most days and more severe pain while walking (P < 0.05). Women with OA were also heavier, with a higher proportion being obese or overweight (P < 0.001). Lower extremity OA, higher body mass index, and lower knee extensor strength independently increased the risk of transition to combined lower extremity and ADL difficulty first over 72 months. Conclusion. Lower extremity OA increased the likelihood of developing difficulty in both lower extremity tasks and ADL over 72 months in a cohort of initially high functioning older women. Two modifiable factors, higher relative weight and lower knee extensor strength, substantially impacted these transitions, and therefore warrant increased attention in the management of lower extremity OA. C1 NIA, Intramural Res Program, Clin Res Branch, Baltimore, MD 21225 USA. Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD 21218 USA. RP Ling, SM (reprint author), NIA ASTRA, Clin Res Branch, 3001 S Hanover St, Baltimore, MD 21225 USA. EM lingsh@grc.nia.nih.gov FU Intramural NIH HHS; NCRR NIH HHS [RR 00722]; NIA NIH HHS [P30 AG 021334, R01 AG 11703-01A1] NR 50 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 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD APR 15 PY 2006 VL 55 IS 2 BP 256 EP 263 DI 10.1002/art.21858 PG 8 WC Rheumatology SC Rheumatology GA 033EV UT WOS:000236830400014 PM 16583416 ER PT J AU Merikangas, K AF Merikangas, K TI What does a short form of the serotonin transporter really signify for major depression? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety 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 15 PY 2006 VL 59 IS 8 SU S MA 4 BP 2S EP 2S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300006 ER PT J AU Sokolov, BP Kleinman, JE Uhl, GR Goldman, D AF Sokolov, BP Kleinman, JE Uhl, GR Goldman, D TI Allele specific gene expression. Emerging clues for understanding complex genetics in mental disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIDA, NIH, DHHS, Baltimore, MD USA. NIMH, Sect Neuropathol, CBDB, IRP,GCAP,NIH, Bethesda, MD 20892 USA. NIAAA, Neurogenet Lab, 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 15 PY 2006 VL 59 IS 8 SU S MA 6 BP 2S EP 2S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300008 ER PT J AU Weinberger, DR AF Weinberger, DR TI Genetic risk factors for schizophrenia: Finding the next therapeutic targets SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, NIH, Intramural Res 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 15 PY 2006 VL 59 IS 8 SU S MA 5 BP 2S EP 2S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300007 ER PT J AU Neumeister, A Mathew, SJ Hasler, G Ding, YS AF Neumeister, A Mathew, SJ Hasler, G Ding, YS TI Novel perspectives on the role of noradrenaline in depression and PTSD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Yale Univ, Sch Med, New Haven, CT 06520 USA. Mt Sinai Sch Med, New York, NY USA. NIMH, Bethesda, MD 20892 USA. RI Hasler, Gregor/E-4845-2012 OI Hasler, Gregor/0000-0002-8311-0138 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 15 PY 2006 VL 59 IS 8 SU S MA 7 BP 3S EP 3S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300009 ER PT J AU Maeng, S Creson, T Gould, T Zarate, C Chen, G Manji, HK AF Maeng, S Creson, T Gould, T Zarate, C Chen, G Manji, HK TI Preclinical evidence that NMDA antagonism induces rapid and sustained antidepressant effects SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 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 15 PY 2006 VL 59 IS 8 SU S MA 19 BP 7S EP 7S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300021 ER PT J AU Vythilingam, M AF Vythilingam, M TI Enhanced amygdala activation during passive avoidance learning in post-traumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Bethesda, MD 20892 USA. NIH, 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 15 PY 2006 VL 59 IS 8 SU S MA 25 BP 9S EP 9S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300027 ER PT J AU Manji, H AF Manji, H TI Mitochondria play an integral role in the treatment of bipolar disorder: Implications for the development of novel therapeutics SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 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 15 PY 2006 VL 59 IS 8 SU S MA 30 BP 10S EP 10S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300032 ER PT J AU Drevets, WC AF Drevets, WC TI Imaging 5-HT1A receptor in mood and anxiety disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, 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 15 PY 2006 VL 59 IS 8 SU S MA 33 BP 11S EP 11S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300035 ER PT J AU Innis, RB AF Innis, RB TI PET radioligands for the 5-HT1A receptor: Rapid removal from brain via p-gp efflux pump and effects of defluorination SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, 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 15 PY 2006 VL 59 IS 8 SU S MA 32 BP 11S EP 11S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300034 ER PT J AU Weinberger, DR AF Weinberger, DR TI Cognitive genetics and schizophrenia susceptibility genes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, NIH, Inramural Res 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 15 PY 2006 VL 59 IS 8 SU S MA 38 BP 13S EP 13S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300040 ER PT J AU Zarate, CA Singh, J Carlson, PJ Brutsche, N Ameli, R Luckenbaugh, D Charney, DS Manji, HK AF Zarate, CA Singh, J Carlson, PJ Brutsche, N Ameli, R Luckenbaugh, D Charney, DS Manji, HK TI Rapid and relatively sustained antidepressant effects with a single intravenous dose of an NMDA antagonist in treatment-resistant major depression: A double-blind, placebo-controlled trial SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Mood Anxiety Disorders Program, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 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 15 PY 2006 VL 59 IS 8 SU S MA 115 BP 36S EP 36S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300117 ER PT J AU Tunbridge, EM Ren-Patterson, R Li, Z Apud, J Egan, M Kolachana, B Harrison, PJ Sei, Y Weinberger, DR AF Tunbridge, EM Ren-Patterson, R Li, Z Apud, J Egan, M Kolachana, B Harrison, PJ Sei, Y Weinberger, DR TI COMT inhibition enhances neuregulin-induced cell migration in B lymphoblasts SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Oxford, Dept Psychiat, Oxford, England. NIMH, Clin Brain Disorders Branch, 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 15 PY 2006 VL 59 IS 8 SU S MA 142 BP 44S EP 44S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300144 ER PT J AU Marques, AH Solis, AC Lotufo, R Ross, J Prado, EBA Dominguez, W Lotufo-Neto, F AF Marques, AH Solis, AC Lotufo, R Ross, J Prado, EBA Dominguez, W Lotufo-Neto, F TI Major depressive disorder and chronic periodontitis: Clinical and immunological evaluation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Sao Paulo, Dept Psychiat, Sao Paulo, Brazil. Univ Sao Paulo, Dept Stomatol, Sao Paulo, Brazil. NIH, Bethesda, MD 20892 USA. RI marques, andrea/H-5297-2012; Lotufo-Neto, Francisco/D-3982-2014 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 15 PY 2006 VL 59 IS 8 SU S MA 163 BP 50S EP 51S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300165 ER PT J AU Sokolov, BP Cadet, JL AF Sokolov, BP Cadet, JL TI Distinct changes in protein expression and phosphorylation after chronic and single injections of methampthetamine SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIDA, NIH, DHHS, 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 15 PY 2006 VL 59 IS 8 SU S MA 166 BP 51S EP 51S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300168 ER PT J AU Neumeister, A Henry, S Geraci, M Herscovitch, P Charney, DS Drevets, WC AF Neumeister, A Henry, S Geraci, M Herscovitch, P Charney, DS Drevets, WC TI Resting rCBF differences between panic disorder patients and controls SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Yale Univ, Sch Med, West Haven, CT 06516 USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIMH, PET Ctr, Bethesda, MD 20892 USA. Mt Sinai Sch Med, New York, NY 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 15 PY 2006 VL 59 IS 8 SU S MA 188 BP 59S EP 59S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300190 ER PT J AU Buzas, B Malhotra, AK Lencz, T Hodgkinson, CA DeRosse, P Kane, J Caycedo, D Max, MM Manji, HK Goldman, D AF Buzas, B Malhotra, AK Lencz, T Hodgkinson, CA DeRosse, P Kane, J Caycedo, D Max, MM Manji, HK Goldman, D TI SOD2 haplotype predicts MnSOD expression level and increases risk of schizophrenia three-fold SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA. Zucker Hillside Hosp, Glen Oaks, NY USA. NIAAA, Neurogenet Lab, Rockville, MD USA. NIDCR, Pain & Neurosensory Mechan Branch, 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 15 PY 2006 VL 59 IS 8 SU S MA 201 BP 63S EP 63S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300203 ER PT J AU Feder, A Southwick, SM Goetz, RR Mathew, SJ Smith, LM Smith, ELP Waldeck, T Moore, J Hain, R Charneyl, DS Vythilingam, M AF Feder, A Southwick, SM Goetz, RR Mathew, SJ Smith, LM Smith, ELP Waldeck, T Moore, J Hain, R Charneyl, DS Vythilingam, M TI Posttraumatic growth in Vietnam prisoners of war SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Mt Sinai Sch Med, New York, NY USA. Yale Univ, New Haven, CT USA. Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA. Robert E Mitchell Ctr, Pensacola, FL 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 15 PY 2006 VL 59 IS 8 SU S MA 206 BP 64S EP 65S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300208 ER PT J AU Finger, E Marsh, A Sims, C Kosson, D Reid, M Mitchell, D Pine, D Blair, J AF Finger, E Marsh, A Sims, C Kosson, D Reid, M Mitchell, D Pine, D Blair, J TI Altered neural activation during probabilistic response reversal in children with psychopathic traits SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA. Rosalind Franklin Univ Med & Sci, Dept Psychol, Chicago, IL 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 15 PY 2006 VL 59 IS 8 SU S MA 229 BP 71S EP 72S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300231 ER PT J AU Leow, AD Lu, A Lee, AD Gogtay, N Rapoport, JL Toga, AW Thompson, PM AF Leow, AD Lu, A Lee, AD Gogtay, N Rapoport, JL Toga, AW Thompson, PM TI Tensor-based mophometry reveals growth pattern abnormalities in childhood-onset schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Calif Los Angeles, Sch Med, Lab Neuro Imaging, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Inst Neuropsychiat, Los Angeles, CA USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008 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 15 PY 2006 VL 59 IS 8 SU S MA 247 BP 77S EP 77S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300249 ER PT J AU Law, AJ Weinberger, DR Kleinman, JE Weickert, CS AF Law, AJ Weinberger, DR Kleinman, JE Weickert, CS TI ErbB4 splice variant expression is altered in schizophrenia and related to disease associated SNPs in the ErbB4 gene SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Oxford, Oxford, England. NIMH, Clin Brain Disorders Branch, Bethesda, MD USA. RI Law, Amanda/G-6372-2012 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 15 PY 2006 VL 59 IS 8 SU S MA 282 BP 88S EP 88S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300284 ER PT J AU Chung, JD Krupin, AS Grundt, P Newman, AH Hammer, RP AF Chung, JD Krupin, AS Grundt, P Newman, AH Hammer, RP TI Recovery of sensorimotor gating is blocked by selective D3-receptor antagonist pretreatment in rats SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Tufts Univ, Sch Med, Boston, MA 02111 USA. NIDA, IRP, Med Chem Sect, NIH, 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 15 PY 2006 VL 59 IS 8 SU S MA 286 BP 89S EP 90S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300288 ER PT J AU Gould, TD AF Gould, TD TI Lithium and amphetamine: Endophenotypes, mouse strain differences and transgenic models SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, 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 15 PY 2006 VL 59 IS 8 SU S MA 304 BP 95S EP 95S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300306 ER PT J AU Hu, XZ Rush, AJ Charney, DS Wilson, AF Sorant, AJM Papanicolaou, GJ Fava, M Madhukar, MH Wisniewski, S Laje, G Buervenich, S McMahon, FJ Manji, H Lipsky, RH AF Hu, XZ Rush, AJ Charney, DS Wilson, AF Sorant, AJM Papanicolaou, GJ Fava, M Madhukar, MH Wisniewski, S Laje, G Buervenich, S McMahon, FJ Manji, H Lipsky, RH TI Serotonin transporter promoter polymorphism predicting increased transcription is associated with tolerability to citalopram treatment in the STAR*D effectiveness trial SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Mt Sinai Hosp, Albert Einstein Sch Med, New York, NY 10029 USA. NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA USA. NIMH, Mol Pathophysiol Lab, Mood & Anxiety Program, NIH, Bethesda, MD 20892 USA. NIAAA, Mol Genet Sect, Neurogenet Lab, 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 15 PY 2006 VL 59 IS 8 SU S MA 315 BP 97S EP 97S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300311 ER PT J AU Miller, JM Oquendo, MA Ogden, RT Hu, X Goldman, D Huang, YY Mann, JJ Parsey, RV AF Miller, JM Oquendo, MA Ogden, RT Hu, X Goldman, D Huang, YY Mann, JJ Parsey, RV TI Brain serotonin transporter and serotonin transporter polymorphism genotype predict one year remission from major depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 CUNY City Coll, Coll Phys & Surg, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. NIAAA, Neurogenet Lab, NIH, Bethesda, MD 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 15 PY 2006 VL 59 IS 8 SU S MA 317 BP 98S EP 98S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300313 ER PT J AU Goldman, D Hu, X Kennedy, J Murphy, D AF Goldman, D Hu, X Kennedy, J Murphy, D TI Linkage of gain-of-function serotonin transporter alleles to obsessive compulsive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Clarke Inst, Toronto, ON, Canada. NIAAA, Rockville, MD 20852 USA. 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 15 PY 2006 VL 59 IS 8 SU S MA 322 BP 99S EP 100S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300318 ER PT J AU Lipska, BK AF Lipska, BK TI Molecules interacting with DISC1 are differentially expressed in schizophrenia and regulated by SNPs associated with the disease SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 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 15 PY 2006 VL 59 IS 8 SU S MA 321 BP 99S EP 99S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300317 ER PT J AU Lipska, BK AF Lipska, BK TI DISC1: Three distinct pools and their implication in major mental illnesses SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 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 15 PY 2006 VL 59 IS 8 SU S MA 320 BP 99S EP 99S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300316 ER PT J AU Barr, CS Lopez, JF Thompson, R Higley, JD AF Barr, CS Lopez, JF Thompson, R Higley, JD TI Studies of the interaction between the serotonin transporter gene promoter polymorphism (rh5-HTTLPR) and early adversity in rhesus macaques SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIAAA, NIH, Poolesville, MD USA. Univ Michigan, Ann Arbor, MI 48109 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 15 PY 2006 VL 59 IS 8 SU S MA 323 BP 100S EP 100S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300319 ER PT J AU Siever, L Frankle, WG Ducci, F New, AS Goodman, M Goldman, D Gelernter, J Hu, XZ Abi-Dargham, A Laruelle, M AF Siever, L Frankle, WG Ducci, F New, AS Goodman, M Goldman, D Gelernter, J Hu, XZ Abi-Dargham, A Laruelle, M TI The serotonin transporter binding and genotypes in impulsive personality disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Mt Sinai Sch Med, Bronx VA Med Ctr, New York, NY USA. Columbia Univ, New York State Psychiat Inst, New York, NY USA. NIAAA, NIH, Rockville, MD 20852 USA. Yale Univ, W Haven VAMC, West Haven, CT 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 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 324 BP 100S EP 100S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300320 ER PT J AU McMahon, FJ AF McMahon, FJ TI A candidate gene association study of outcome after citalopram treatment SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Genet Basis Mood & Anxiety Disorders,Mood & Anxie, 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 15 PY 2006 VL 59 IS 8 SU S MA 340 BP 105S EP 105S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300336 ER PT J AU Manji, HK Hasler, G Drevets, WC Gould, TD Gottesman, II AF Manji, HK Hasler, G Drevets, WC Gould, TD Gottesman, II TI Toward constructing an endophenotype strategy for bipolar disorders: Overlap with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Bethesda, MD 20892 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. RI G, I/D-8042-2011; Gottesman, Irving/B-9303-2011; 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 15 PY 2006 VL 59 IS 8 SU S MA 343 BP 106S EP 106S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300339 ER PT J AU Innis, RB Fujita, M AF Innis, RB Fujita, M TI PET imaging of cAMP phosphodiesterase4 with R-[C-11]Rolipram SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, 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 15 PY 2006 VL 59 IS 8 SU S MA 349 BP 107S EP 107S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300345 ER PT J AU Insel, T AF Insel, T TI Inportance of innovation in neuroscience research SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 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 15 PY 2006 VL 59 IS 8 SU S MA 350 BP 108S EP 108S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300346 ER PT J AU Casanova, MF Giedd, J Rumsey, J Mannheim, G AF Casanova, MF Giedd, J Rumsey, J Mannheim, G TI A negative study on the gyrification index in patients with autism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Louisville, Louisville, KY 40292 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Clin Neurosci Branch, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 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 15 PY 2006 VL 59 IS 8 SU S MA 359 BP 110S EP 110S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300355 ER PT J AU Cadet, JL Better, W Schroder, C Herning, RI AF Cadet, JL Better, W Schroder, C Herning, RI TI The EEG of marijuana abusers: Relationships between increased EEG alpha activity in frontal sites and inability to stay abstinent for a month on an inpatient research unit SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIDA, Mol Neuropsychiat Branch, Baltimore, 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 15 PY 2006 VL 59 IS 8 SU S MA 401 BP 123S EP 123S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300397 ER PT J AU Miller, JM Oquendo, MA Ogden, RT Hu, XZ Goldman, D Huang, YY Mann, JJ Parsey, RV AF Miller, JM Oquendo, MA Ogden, RT Hu, XZ Goldman, D Huang, YY Mann, JJ Parsey, RV TI Brain serotonin transporter and serotonin transporter polymorphism genotype predict one year remission from major depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Columbia Univ, Coll Phys & Surg, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. NIAAA, Neurogenet Lab, 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 15 PY 2006 VL 59 IS 8 SU S MA 406 BP 125S EP 125S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300402 ER PT J AU O'Donnell, KC Einat, H Picchini, AM Schloesser, R Manji, HK Gould, TD AF O'Donnell, KC Einat, H Picchini, AM Schloesser, R Manji, HK Gould, TD TI Modulation by lithium of amphetamine-induced behaviors: Relevance of beta-catenin SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Lab Mol Pathophysiol, Bethesda, MD 20892 USA. Univ Minnesota, Dept Pharm Practice & Pharmaceut Sci, Duluth, MI USA. Columbia Coll Phys & Surg, Dept Pharmacol, 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 15 PY 2006 VL 59 IS 8 SU S MA 421 BP 130S EP 130S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300417 ER PT J AU Tavares, JT Clark, L Cannon, DM Erickson, K Drevets, WC Sahakian, BJ AF Tavares, JT Clark, L Cannon, DM Erickson, K Drevets, WC Sahakian, BJ TI Neuropsychological function in unmedicated unipolar and bipolar depressed subjects SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Cambridge, Wolfson Brain Imaging Ctr, Cambridge, England. Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. NIMH, NIH, Bethesda, MD 20892 USA. Univ Cambridge, Dept Psychiat, Cambridge, England. 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 15 PY 2006 VL 59 IS 8 SU S MA 430 BP 133S EP 133S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301007 ER PT J AU Lissek, S Levenson, J McDowell, DJ Johnson, LL Levine, J Pine, DS Grillon, C AF Lissek, S Levenson, J McDowell, DJ Johnson, LL Levine, J Pine, DS Grillon, C TI Using socially relevant conditioned and unconditioned stimuli to examine the associative learning components of social anxiety disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RI Lissek, Shmuel/B-6577-2008; Levenson, Jessica/O-5448-2015 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 15 PY 2006 VL 59 IS 8 SU S MA 436 BP 134S EP 135S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301013 ER PT J AU Du, J Wei, YL Wang, Y Falke, C Engle, S Chen, J Zhou, RL Chen, JS Yuan, PX Manji, H AF Du, J Wei, YL Wang, Y Falke, C Engle, S Chen, J Zhou, RL Chen, JS Yuan, PX Manji, H TI Glucocorticoid receptors (GR) trafficking into mitochondria: The role in regulating mitochondrial function under chronic stress SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. NIMH, LMP, NIH, Gaithersburg, MD USA. NIMH, CBDB, NIH, Gaithersburg, 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 15 PY 2006 VL 59 IS 8 SU S MA 438 BP 135S EP 135S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301015 ER PT J AU Moral, JR Holmes, MK Cumba, DR Luckenbaugh, DA Zarate, CA Manji, HK AF Moral, JR Holmes, MK Cumba, DR Luckenbaugh, DA Zarate, CA Manji, HK TI Development of the severity index of psychosocial and environmental stress SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 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 15 PY 2006 VL 59 IS 8 SU S MA 454 BP 140S EP 140S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301031 ER PT J AU Kling, MA Csako, G Alesci, S Luckenbaugh, DA Costello, R Bonne, O Manji, H Charney, DS Gold, PW Neumeister, A AF Kling, MA Csako, G Alesci, S Luckenbaugh, DA Costello, R Bonne, O Manji, H Charney, DS Gold, PW Neumeister, A TI Decreased serum transferrin (TRF), a negative acute phase protein, in unmedicated remitted major depressive disorder (MDD) patients: Further evidence for a persistent pro-inflammatory state in MDD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Hadassah Hebrew Univ, Med Ctr, Dept Psychiat, Jerusalem, Israel. Mt Sinai Sch Med, New York, NY USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. W Haven VA Med Ctr, Psychiat Serv, West Haven, CT 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 15 PY 2006 VL 59 IS 8 SU S MA 484 BP 149S EP 149S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301061 ER PT J AU Song, J Chen, J Du, J Liu, G Lipska, BK Weinberger, DR AF Song, J Chen, J Du, J Liu, G Lipska, BK Weinberger, DR TI shRNA-mediated silencing of catechol-O-methyltransferase in stable cell lines SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, CBDB, NIH, Bethesda, MD 20892 USA. NIMH, Mol Pathophysiol 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 15 PY 2006 VL 59 IS 8 SU S MA 509 BP 157S EP 157S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301086 ER PT J AU Leow, AD Lu, A Lee, AD Gogtay, N Rapoport, JL Toga, AW Thompson, PM AF Leow, AD Lu, A Lee, AD Gogtay, N Rapoport, JL Toga, AW Thompson, PM TI Tensor-based mophometry reveals growth pattern abnormalities in childhood-onset schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Calif Los Angeles, Sch Med, Lab Neuro Imaging, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Inst Neuropsychiat, Los Angeles, CA USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008; Leow, Alex/K-3236-2014 OI Leow, Alex/0000-0002-5660-8651 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 15 PY 2006 VL 59 IS 8 SU S MA 528 BP 162S EP 162S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301105 ER PT J AU Blair, K Shaywitz, J Geraci, M Vythilingam, M Jones, M McCaffrey, D Charney, DS Drevets, W Pine, D Blair, J AF Blair, K Shaywitz, J Geraci, M Vythilingam, M Jones, M McCaffrey, D Charney, DS Drevets, W Pine, D Blair, J TI Association between amygdala hyperactivity, and prefrontal hypoactivity to fearful faces and severity of social anxiety in social anxiety disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, NIH, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 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 15 PY 2006 VL 59 IS 8 SU S MA 545 BP 167S EP 168S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301122 ER PT J AU Carlson, PJ Neumeister, A Geraci, M Kaplan, J Nugent, A Luckenbaugh, D Pine, D Charney, DS Drevets, WC AF Carlson, PJ Neumeister, A Geraci, M Kaplan, J Nugent, A Luckenbaugh, D Pine, D Charney, DS Drevets, WC TI Noradrenergic mechanisms in panic disorder: Behavioral, autonomic, and neurophysiological correlates of a yohimbine challenge SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA. Yale Univ, Sch Med, New Haven, CT USA. 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 15 PY 2006 VL 59 IS 8 SU S MA 542 BP 167S EP 167S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301119 ER PT J AU Kling, MA Csako, G Alesci, S Costel, R Luckenbaugh, DA Bonne, O Manji, H Charney, DS Gold, PW Neumeister, A AF Kling, MA Csako, G Alesci, S Costel, R Luckenbaugh, DA Bonne, O Manji, H Charney, DS Gold, PW Neumeister, A TI Selective decrease in serum immunoglobulin (Ig)A but not IgG or IgM levels in unmedicated, remitted patients with major depressive disorder: Pathophysiologic implications SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Ctr Clin, Bethesda, MD USA. NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD USA. Hebrew Univ Jerusalem, Hadassah Med Ctr, Dept Psychiat, Jerusalem, Israel. Mt Sinai Sch Med, Off Dean, New York, NY 10029 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. W Haven VA Med Ctr, Psychiat Serv, West Haven, CT 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 15 PY 2006 VL 59 IS 8 SU S MA 558 BP 171S EP 172S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301135 ER PT J AU Winslow, JT Noble, PL Hertzberg, K Myers, KM Davis, M AF Winslow, JT Noble, PL Hertzberg, K Myers, KM Davis, M TI Fear inhibition in rhesus monkeys: Evidence for an objective measure SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, IRP, Non Human Primate Core, NIH, Bethesda, MD 20892 USA. Emory Univ, Yerkes Natl Primate Ctr, Atlanta, GA 30322 USA. Emory Univ, Ctr Behav Neurosci, Dept Psychiat, Atlanta, GA 30322 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 15 PY 2006 VL 59 IS 8 SU S MA 574 BP 176S EP 176S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301151 ER PT J AU Berman, KF Silbersweig, D Goldstein, JM AF Berman, KF Silbersweig, D Goldstein, JM TI Menstrual cycle-related mood disorders: Is there a distinct neurobiology? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIH, Bethesda, MD 20892 USA. Cornell Univ, New York, NY 10021 USA. Harvard Univ, Sch Med, Boston, MA 02115 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 15 PY 2006 VL 59 IS 8 SU S MA 597 BP 183S EP 183S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301169 ER PT J AU Furey, M Drevets, W AF Furey, M Drevets, W TI The antidepressant effects and cognitive impact of antimuscarinic agents in mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 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 15 PY 2006 VL 59 IS 8 SU S MA 607 BP 186S EP 186S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301179 ER PT J AU Wang, ZW Gilbert, DL Sallee, FR Wassermann, EM Zhang, J White, C AF Wang, ZW Gilbert, DL Sallee, FR Wassermann, EM Zhang, J White, C TI Dopamine transporter genotypes influence on ADHD medication effects on cortical inhibition SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH USA. Cincinnati VA Med Ctr, Hlth Care Line, Cincinnati, OH USA. Cincinnati Children Hosp, Med Ctr, Dept Neurol, Cincinnati, OH USA. NINDS, Brain Stimulat Unit, 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 15 PY 2006 VL 59 IS 8 SU S MA 609 BP 186S EP 187S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301181 ER PT J AU Zarate, CA AF Zarate, CA TI Robust, rapid and relatively sustained antidepressant effects with a single-dose of an NMDA antagonist in treatment-resistant major depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 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 15 PY 2006 VL 59 IS 8 SU S MA 606 BP 186S EP 186S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301178 ER PT J AU Lencz, T Lipsky, RH DeRosse, P Burdick, KE Jaeger, J Kane, JM Goldman, D Malhotra, AK AF Lencz, T Lipsky, RH DeRosse, P Burdick, KE Jaeger, J Kane, JM Goldman, D Malhotra, AK TI Schizoaffective disorder at the crossroads of affective disorders and schizophrenia: Molecular classification using BDNF haplotypes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Zucker Hillside Hosp, Dept Psychiat Res, Glen Oaks, NY USA. Montefiore Med Ctr, Albert Einstein Coll Med, Dept Psychiat, Bronx, NY 10467 USA. Natl Inst Alcohol Abuse & Alcoholism, Neurogenet Lab, Bethesda, MD 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 15 PY 2006 VL 59 IS 8 SU S MA 619 BP 190S EP 190S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301191 ER PT J AU Weinberger, DR Goldberg, T Egan, M Callicott, J Straub, R AF Weinberger, DR Goldberg, T Egan, M Callicott, J Straub, R TI Dysbindin: Relationship to cognitive factors and IQ SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, NIH, Intramural Res 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 15 PY 2006 VL 59 IS 8 SU S MA 624 BP 191S EP 191S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301196 ER PT J AU Pine, D AF Pine, D TI fMRI studies of attention dysfunction in pediatric anxiety disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Intramural 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 15 PY 2006 VL 59 IS 8 SU S MA 625 BP 192S EP 192S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301197 ER PT J AU Rogawski, MA AF Rogawski, MA TI Neurosteroids in seizure disorders and depression and the development of neurosteroid analogs SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NINDS, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 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 15 PY 2006 VL 59 IS 8 SU S MA 631 BP 193S EP 193S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301203 ER PT J AU Rubinow, DR Schmidt, PJ Bloch, M Daly, RC Khinel, K Smith, MJ AF Rubinow, DR Schmidt, PJ Bloch, M Daly, RC Khinel, K Smith, MJ TI Neurosteroids in the pathogenesis and treatment of affective disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Bethesda, MD 20892 USA. Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel. Royal Coll Surgeons, Dublin, Ireland. NINDS, 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 15 PY 2006 VL 59 IS 8 SU S MA 629 BP 193S EP 193S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301201 ER PT J AU Goldman, D Schwartz, L Albaugh, B Virkkunen, M Enoch, MA AF Goldman, D Schwartz, L Albaugh, B Virkkunen, M Enoch, MA TI COMT: Contrasting mechanisms for addictions risk SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIAAA, Rockville, MD 20852 USA. Univ Helsinki, FIN-00014 Helsinki, Finland. 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 15 PY 2006 VL 59 IS 8 SU S MA 638 BP 195S EP 196S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301210 ER PT J AU Higley, JD Barr, C Newman, T AF Higley, JD Barr, C Newman, T TI Choose your parents well: Gene X environment interactions leading to pathological developmental pathways SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIAAA, Sect Study Primate Models Psychopathol, LCTS, 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 15 PY 2006 VL 59 IS 8 SU S MA 637 BP 195S EP 195S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301209 ER PT J AU Alesci, S Listwak, SJ Gold, PW AF Alesci, S Listwak, SJ Gold, PW TI Role of pro-inflammatory mechanisms in the increased risk for cardiovascular disease and bone loss in mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 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 15 PY 2006 VL 59 IS 8 SU S MA 656 BP 200S EP 201S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301228 ER PT J AU Kling, MA Yasuhara, K Martinez, PE Ronsaville, DS Gold, PW AF Kling, MA Yasuhara, K Martinez, PE Ronsaville, DS Gold, PW TI Decreased bone mineral density in major depressive disorder: When does it occur? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Bethesda, MD 20892 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 15 PY 2006 VL 59 IS 8 SU S MA 657 BP 201S EP 201S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301229 ER PT J AU DeRosse, P Hodgkinson, CA Lencz, T Burdick, KE Kane, JM Goldman, D Malhotra, AK AF DeRosse, P Hodgkinson, CA Lencz, T Burdick, KE Kane, JM Goldman, D Malhotra, AK TI Disrupted in schizophrenia 1 (DISC1) genotype and positive symptoms in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Zucker Hillside Hosp, N Shore Long Isl Jewish Hlth Syst, Glen Oaks, NY USA. NIAAA, Neurogenet Lab, 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 15 PY 2006 VL 59 IS 8 SU S MA 718 BP 219S EP 219S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301290 ER PT J AU Casanova, MF El-Zehiry, N Giedd, J Rumsey, J Farag, A AF Casanova, MF El-Zehiry, N Giedd, J Rumsey, J Farag, A TI White matter parcellation in dyslexia reveals a significant diminution of the outer (Radiate) compartment SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Louisville, Comp Vis & Image Proc Lab, Louisville, KY 40292 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 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 15 PY 2006 VL 59 IS 8 SU S MA 731 BP 223S EP 223S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301303 ER PT J AU Duncko, R Brundage, S Graap, K Kling, MA Gold, PW AF Duncko, R Brundage, S Graap, K Kling, MA Gold, PW TI Virtual reality job interview in stuttering subjects: Relationships between communication apprehension, stuttering and endocrine activity SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. George Washington Univ, Dept Speech & Hearing Sci, Washington, DC USA. Better Inc, Decatur, GA 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 15 PY 2006 VL 59 IS 8 SU S MA 750 BP 229S EP 229S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301322 ER PT J AU Lissek, S McDowell, DJ Baas, JMP Cornwell, BR Pine, DS Grillon, C AF Lissek, S McDowell, DJ Baas, JMP Cornwell, BR Pine, DS Grillon, C TI The ability to regulate emotionally-potentiated startle to unpleasant pictures is moderated by levels of state and trait anxiety SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Utrecht, Dept Psychon, Utrecht, Netherlands. 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 15 PY 2006 VL 59 IS 8 SU S MA 756 BP 231S EP 231S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301328 ER PT J AU Goldberg, T Iudicello, J Egan, M Straub, R Elvevaag, B Weinberger, D AF Goldberg, T Iudicello, J Egan, M Straub, R Elvevaag, B Weinberger, D TI BDNF Val66met polymorphism strongly affects memories, but not false memories SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Hillside Zucker, Glen Oaks, NY USA. Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY USA. NIMH, 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 15 PY 2006 VL 59 IS 8 SU S MA 758 BP 232S EP 232S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301330 ER PT J AU Szeszko, PR Hodgkinson, CA Robinson, D Bilder, RM Lencz, T Burdick, KE Kane, JM Ashtari, M Goldman, D Malhotra, AK AF Szeszko, PR Hodgkinson, CA Robinson, D Bilder, RM Lencz, T Burdick, KE Kane, JM Ashtari, M Goldman, D Malhotra, AK TI DISC1 Leu607Phe polymorphism and frontal grey matter volume in first-episode schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Zucker Hillside Hosp, Glen Oaks, NY USA. NIAAA, Rockville, MD 20852 USA. N Shore LIJ Hlth Syst, New Hyde Pk, NY USA. RI Bilder, Robert/A-8894-2008 OI Bilder, Robert/0000-0001-5085-7852 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 15 PY 2006 VL 59 IS 8 SU S MA 760 BP 232S EP 232S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301332 ER PT J AU Hu, XZ Zhou, ZFZ Lipsky, RH Greenberg, BD Richter, MA Kennedy, JL Murphy, D Goldman, D AF Hu, XZ Zhou, ZFZ Lipsky, RH Greenberg, BD Richter, MA Kennedy, JL Murphy, D Goldman, D TI Further evidence for association of serotonin transporter gene with obsessive-compulsive disorder: Role of the 3 ' region SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIAAA, LNG, NIH, Rockville, MD 20852 USA. Butler Hosp, Providence, RI 02906 USA. Ctr Addict & Hlth, Dept Psychiat, Toronto, SK, Canada. NIMH, Clin Sci 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 15 PY 2006 VL 59 IS 8 SU S MA 778 BP 238S EP 238S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301350 ER PT J AU Grodofsky, SR Marenco, S Siuta, M Kippenhan, S Kohn, P Mervis, CB Morris, CA Pierpaoli, C Meyer-Lindenberg, A Berman, KF AF Grodofsky, SR Marenco, S Siuta, M Kippenhan, S Kohn, P Mervis, CB Morris, CA Pierpaoli, C Meyer-Lindenberg, A Berman, KF TI Diffusion tensor imaging (DTI) tractography in Williams syndrome (WS): Preliminary findings SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, NIH, Bethesda, MD 20892 USA. Univ Louisville, Louisville, KY 40292 USA. Univ Nevada, Sch Med, Las Vegas, NV 89154 USA. RI Marenco, Stefano/A-2409-2008; Pierpaoli, Carlo/E-1672-2011 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 15 PY 2006 VL 59 IS 8 SU S MA 790 BP 241S EP 241S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301362 ER PT J AU Ward, SE Perlman, WR Miranda-Angulo, AL Kleinman, JE Weickert, CS AF Ward, SE Perlman, WR Miranda-Angulo, AL Kleinman, JE Weickert, CS TI Association between ESR1 genetic variation and ER alpha mRNA expression in patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, 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 15 PY 2006 VL 59 IS 8 SU S MA 788 BP 241S EP 241S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301360 ER PT J AU Gould, NF Holmes, K Luckenbaugh, DA Manji, HK Zarate, CA Ameli, R AF Gould, NF Holmes, K Luckenbaugh, DA Manji, HK Zarate, CA Ameli, R TI Assessment of anhedonia in depressed patients and healthy controls: Examining the validity of a modified Snaith-Hamilton pleasure scale SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Mol Pathophysiol Lab, Rockville, MD 20857 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 15 PY 2006 VL 59 IS 8 SU S MA 793 BP 242S EP 242S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301365 ER PT J AU Carlson, PJ Kling, MA Bain, E Alesci, S Lambert, G Esler, M Gold, PW Drevets, WC AF Carlson, PJ Kling, MA Bain, E Alesci, S Lambert, G Esler, M Gold, PW Drevets, WC TI Elevated overnight plasma norepinephrine in actively depressed unipolar and bipolar patients: Relation to overnight dihydroxyphenylglycol (DHPG) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. Baker Heart Inst, Melbourne, Vic, Australia. RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 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 15 PY 2006 VL 59 IS 8 SU S MA 805 BP 246S EP 246S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301377 ER PT J AU Mitkus, SN Hyde, TM Caruso, M Sarges, P Kleinman, JE Lipska, BK AF Mitkus, SN Hyde, TM Caruso, M Sarges, P Kleinman, JE Lipska, BK TI Post-mortem analysis of myelin-associated gene expression in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 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 15 PY 2006 VL 59 IS 8 SU S MA 816 BP 249S EP 249S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301388 ER PT J AU Yuan, PX Li, XX Engel, S Du, J Chen, G Manji, HK AF Yuan, PX Li, XX Engel, S Du, J Chen, G Manji, HK TI Bcl-2: a key mediator of the therapeutic effects of antidepressants SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, Mol Pathophysiol Lab, 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 15 PY 2006 VL 59 IS 8 SU S MA 814 BP 249S EP 249S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301386 ER PT J AU Newman, TK Barr, CS Suomi, SJ Higley, JD Goldman, D AF Newman, TK Barr, CS Suomi, SJ Higley, JD Goldman, D TI Multiple, novel polymorphisms in the rhesus macaque DRD4 gene promoter are associated with impulsive and aggressive behavior SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIAAA, Lab Clin & Translat Studies, Poolesville, MD USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. Natl Inst Child Hlth & Dev, Comparat Ethol Lab, Poolesville, MD 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 15 PY 2006 VL 59 IS 8 SU S MA 821 BP 251S EP 251S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301393 ER PT J AU Creson, T Du, J Chen, G Manji, HK AF Creson, T Du, J Chen, G Manji, HK TI Behavioral evidence for the involvement of hippocampal GluR1 AMPA receptor trafficking in the pathophysiology and treatment mechanisms of mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIMH, NIH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Res Program, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 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 15 PY 2006 VL 59 IS 8 SU S MA 835 BP 255S EP 255S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301407 ER PT J AU Voon, V Krack, P Lang, AE Lozano, AM Dujardin, K Dambrosia, J Tamma, F Thobois, S Schupbach, M Speelman, JD Samanta, J Herzog, J Ardouin, CA Kubu, C Moro, E AF Voon, V Krack, P Lang, AE Lozano, AM Dujardin, K Dambrosia, J Tamma, F Thobois, S Schupbach, M Speelman, JD Samanta, J Herzog, J Ardouin, CA Kubu, C Moro, E TI Frequency and risk factors for suicidal outcomes following subthalamic deep brain stimulation surgery for Parkinson's disease: A Multicenter retrospective survey SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Natl Inst Hlth, Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. Univ Grenoble, Grenoble, France. Hop Salengro, Lille, France. Univ Milan, Milan, Italy. Pierre Wertheimer Neurol Hosp, Lyon, France. Hop La Pitie Salpetriere, Paris, France. Univ Amsterdam, Amsterdam, Netherlands. Banner Good Samaritan, Phoenix, AZ USA. Univ Kiel, Kiel, Germany. Cleveland Clin, Cleveland, OH 44106 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 15 PY 2006 VL 59 IS 8 SU S MA 860 BP 263S EP 263S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301432 ER PT J AU Yoshikawa, E Matsuoka, Y Yamasue, H Inagaki, M Nakano, T Akechi, T Kobayakawa, M Fujimori, M Nakaya, N Akizuki, N Imoto, S Murakami, K Kasai, K Uchitomi, Y AF Yoshikawa, E Matsuoka, Y Yamasue, H Inagaki, M Nakano, T Akechi, T Kobayakawa, M Fujimori, M Nakaya, N Akizuki, N Imoto, S Murakami, K Kasai, K Uchitomi, Y TI Prefrontal cortex and amygdala volume in first minor or major depressive episode after cancer diagnosis SO BIOLOGICAL PSYCHIATRY LA English DT Article DE depressive disorder; magnetic resonance imaging; voxel-based morphometry (VBM); prefrontal cortex (PFC); amygdala ID VOXEL-BASED MORPHOMETRY; EMOTIONAL INFORMATION; FMRI; REDUCTION; MRI; INDIVIDUALS; DISORDERS; SURVIVORS; DISEASE AB Background: Major and minor depressive episodes in cancer patients are frequent and are frequently seen as the first depressive episode in a patient's life. However, the neurological basis of these depressive episodes remains largely unknown. Methods: Subjects were 51 breast cancer survivors (BCS) who has no history of any depressive episode before the cancer diagnosis (11 BCS with a history of a first minor depressive episode after cancer diagnosis, 11 BCS with a history of a first major depressive episode after cancer diagnosis, and 29 BCS with no history of any depressive episode after cancer diagnosis). We analyzed the prefrontal cortex (PFC) and amygdala volumes in a 1.5-Tesla Magnetic Resonance Imaging scanner. We characterized the structural correlates of depression using two conmplementary approaches. The first was voxel-based morphometry (VBM) that allowed us to scan the entire brain for reactive gray matter deficit. The second was classsical volumetry focussing on amygdala. Results: Voxel-based morphometry revealed no brain region, including PFC, for which volume was significantly different among the three groups. There wee trend-level differences in the left amygdala volume in the manual tracing method among the three groups. The left amygdala volumes in the subjects with a first minor and /or major depressive episode were significantly smaller than in those with no history of any depressive episode. Conclusion: It might be suggested that amygdala volume was associated with first minor and/or major depressive episode after cancer diagnosis. C1 Natl Canc Ctr, Res Inst E, PsychoOncol Div, Kashiwa, Chiba 2778577, Japan. Nippon Med Coll, Div Psychiat, Tokyo 113, Japan. NIMH, Adult Mental Hlth Div, Natl Ctr Neurol & Psychiat Japan, Tokyo, Japan. Univ Tokyo, Grad Sch Med, Dept Neuropsychiat, Tokyo, Japan. Natl Canc Ctr, Div Psychiat, Tokyo, Japan. Nagoya City Univ, Sch Med, Dept Psychiat, Nagoya, Aichi 467, Japan. Natl Canc Ctr Hosp E, Div Psychiat, Chiba, Japan. Natl Canc Ctr Hosp E, Div Breast Surg, Chiba, Japan. Natl Canc Ctr Hosp E, Dept Radiol, Chiba, Japan. NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Uchitomi, Y (reprint author), Natl Canc Ctr, Res Inst E, PsychoOncol Div, 6-5-1,Kashiwanoha, Kashiwa, Chiba 2778577, Japan. EM yuchitom@east.ncc.go.jp NR 32 TC 23 Z9 26 U1 2 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 15 PY 2006 VL 59 IS 8 BP 707 EP 712 DI 10.1016/j.biopsych.2005.08.018 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 031HN UT WOS:000236695400006 PM 16213471 ER PT J AU Rasooly, A AF Rasooly, A TI Moving biosensors to point-of-care cancer diagnostics SO BIOSENSORS & BIOELECTRONICS LA English DT Editorial Material DE cancer diagnostics; biosensors; point-of-care testing; molecular signatures; ligands; microfluidics; lab-on-a-chip ID SURFACE-PLASMON RESONANCE; IDENTIFICATION C1 NCI, NIH, CDP, Rockville, MD 20852 USA. US FDA, Div Biol Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Rasooly, A (reprint author), NCI, NIH, CDP, 6130 Execut Blvd EPN,Room 6035A, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov NR 15 TC 17 Z9 17 U1 2 U2 15 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD APR 15 PY 2006 VL 21 IS 10 BP 1847 EP 1850 DI 10.1016/j.bios.2006.02.001 PG 4 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA 032EG UT WOS:000236756100001 PM 16556495 ER PT J AU Rasooly, A Jacobson, J AF Rasooly, A Jacobson, J TI Development of biosensors for cancer clinical testing SO BIOSENSORS & BIOELECTRONICS LA English DT Article DE cancer diagnostics; biosensors; point of care testing; molecular signatures; ligands ID PARAFFIN-EMBEDDED TISSUES; POLYMERASE-CHAIN-REACTION; IMMUNOMAGNETIC CELL ENRICHMENT; IMMUNOCYTOCHEMISTRY IN-VITRO; SURFACE-PLASMON RESONANCE; RT-PCR ANALYSIS; BREAST-CANCER; PROMOTER HYPERMETHYLATION; TUMOR-CELLS; BONE-MARROW AB Biosensors are devices that combine a biochemical recognition/binding element (ligand) with a signal conversion unit (transducer). Biosensors are already used for several clinical applications, for example for electrochemical measurement of blood glucose concentrations. Application of biosensors in cancer clinical testing has several potential advantages over other clinical analysis methods including increased assay speed and flexibility, capability for multi-target analyses, automation, reduced costs of diagnostic testing and a potential to bring molecular diagnostic assays to community health care systems and to underserved populations. They have the potential for facilitating Point of Care Testing (POCT), where state-of-the-art molecular analysis is carried out without requiring a state-of-the-art laboratory. However, not many biosensors have been developed for cancer-related testing. One major challenge in harnessing the potential of biosensors is that cancer is a very complex set of diseases. Tumors vary widely in etiology and pathogenesis. Oncologists rely heavily on histological characterization of tumors and a few biomarkers that have demonstrated clinical utility to aid in patient management decisions. New genomic and proteomic molecular tools are being used to profile tumors and produce "molecular signatures." These signatures include genetic and epigenetic signatures, changes in gene expression, protein profiles and post-translational modifications of proteins. These molecular signatures provide new opportunities for utilizing biosensors. Biosensors have enormous potential to deliver the promise of new molecular diagnostic strategies to patients. This article describes some of the basic elements of cancer biology and cancer biomarkers relevant for the development of biosensors for cancer clinical testing, along with the challenges in using this approach. (c) 2006 Elsevier B.V. All rights reserved. C1 NCI, NIH, CDP, Rockville, MD 20852 USA. US FDA, Div Biol Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Rasooly, A (reprint author), NCI, NIH, CDP, 6130 Execut Blvd EPN,6035A, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov NR 100 TC 99 Z9 101 U1 3 U2 46 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD APR 15 PY 2006 VL 21 IS 10 BP 1851 EP 1858 DI 10.1016/j.bios.2005.01.003 PG 8 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA 032EG UT WOS:000236756100002 PM 16458498 ER PT J AU Soper, SA Brown, K Ellington, A Frazier, B Garcia-Manero, G Gau, V Gutman, SI Hayes, DF Korte, B Landers, JL Larson, D Ligler, F Majumdar, A Mascini, M Nolte, D Rosenzweig, Z Wang, J Wilson, D AF Soper, SA Brown, K Ellington, A Frazier, B Garcia-Manero, G Gau, V Gutman, SI Hayes, DF Korte, B Landers, JL Larson, D Ligler, F Majumdar, A Mascini, M Nolte, D Rosenzweig, Z Wang, J Wilson, D TI Point-of-care biosensor systems for cancer diagnostics/prognostics SO BIOSENSORS & BIOELECTRONICS LA English DT Article DE biosensors; cancer; point-of-care ID QUARTZ-CRYSTAL-MICROBALANCE; POLYMERASE-CHAIN-REACTION; LABEL-FREE DETECTION; RESONANCE IMAGING MEASUREMENTS; PHAGE-DISPLAYED LIBRARY; ACOUSTIC-WAVE SENSOR; NANOIMPRINT LITHOGRAPHY; PIEZOELECTRIC BIOSENSOR; MICROFLUIDIC CHIPS; POLY(METHYL METHACRYLATE) AB With the growing number of fatalities resulting from the 100 or so cancer-related diseases, new enabling tools are required to provide extensive molecular profiles of patients to guide the clinician in making viable diagnosis and prognosis. Unfortunately with cancer-related diseases, there is not one molecular marker that can provide sufficient information to assist the clinician in making effective prognoses or even diagnoses. Indeed, large panels of markers must typically be evaluated that cut across several different classes (mutations in certain gene fragments-DNA; over/underexpression of gene activity as monitored by messenger RNAs; the amount of proteins present in serum or circulating tumor cells). The classical biosensor format (dipstick approach for monitoring the presence of a single element) is viewed as a valuable tool in many bioassays, but possesses numerous limitations in cancer due primarily to the single element nature of these sensing platforms. As such, if biosensors are to become valuable tools in the arsenal of the clinician to manage cancer patients, new formats are required. This review seeks to provide an overview of the current thinking on molecular profiling for diagnosis and prognosis of cancers and also, provide insight into the current state-of-the-art in the biosensor field and new strategies that must be considered to bring this important technology into the cancer field. (c) 2006 Elsevier B.V. All rights reserved. C1 Louisiana State Univ, Baton Rouge, LA 70803 USA. Univ Texas, SW Med Ctr, Dallas, TX 75235 USA. Univ Texas, Austin, TX 78712 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. US FDA, Rockville, MD 20857 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NIH, Bethesda, MD 20892 USA. Univ Virginia, Charlottesville, VA 22903 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Univ Florence, Florence, Italy. Purdue Univ, W Lafayette, IN 47907 USA. Univ New Orleans, New Orleans, LA 70148 USA. Arizona State Univ, Tempe, AZ 85287 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Soper, SA (reprint author), Louisiana State Univ, Baton Rouge, LA 70803 USA. EM chsope@lsu.edu RI Wang, Joseph/C-6175-2011 NR 96 TC 158 Z9 161 U1 11 U2 118 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD APR 15 PY 2006 VL 21 IS 10 BP 1932 EP 1942 DI 10.1016/j.bios.2006.01.006 PG 11 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA 032EG UT WOS:000236756100013 PM 16473506 ER PT J AU Ting-De Ravin, SS Kennedy, DR Naumann, N Kennedy, JS Choi, U Hartnett, BJ Linton, GF Whiting-Theobald, NL Moore, PF Vernau, W Malech, HL Felsburg, PJ AF Ting-De Ravin, SS Kennedy, DR Naumann, N Kennedy, JS Choi, U Hartnett, BJ Linton, GF Whiting-Theobald, NL Moore, PF Vernau, W Malech, HL Felsburg, PJ TI Correction of canine X-linked severe combined immunodeficiency by in vivo retroviral gene therapy SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; BONE-MARROW; PROGENITOR CELLS; CD34(+) CELLS; CORD BLOOD; VECTORS; DOGS; EXPRESSION; TRANSPLANTATION; TRANSDUCTION AB X-linked severe combined immunodeficiency (XSCID) is characterized by profound immunodeficiency and early mortality, the only potential cure being hematopoietic stem cell (HSC) transplantation or gene therapy. Current clinical gene therapy protocols targeting HSCs are based upon ex vivo gene transfer, potentially limited by the adequacy of HSC harvest, transduction efficiencies of repopulating HSCs, and the potential loss of their engraftment potential during ex vivo culture. We demonstrate an important proof of principle by showing achievement of durable immune reconstitution in XSCID dogs following intravenous injection of concentrated RD114-pseudotyped retrovirus vector encoding the corrective gene, the interleukin-2 receptor gamma chain (gamma c). In 3 of 4 dogs treated, normalization of numbers and function of T cells were observed. Two long-term-surviving animals (16 and 18 months) showed significant marking of B lymphocytes and myeloid cells, normalization of IgG levels, and protective humoral immune response to immunization. There were no adverse effects from in vivo gene therapy, and in one dog that reached sexual maturity, sparing of gonadal tissue from gene transfer was demonstrated. This is the first demonstration that in vivo gene therapy targeting HSCs can restore both cellular and humoral immunity in a large-animal model of a fatal immunodeficiency. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Vet Med, Dept Clin Studies, Philadelphia, PA 19104 USA. Univ Calif Davis, Sch Vet Med, Davis, CA 95616 USA. RP Ting-De Ravin, SS (reprint author), NIAID, Host Def Lab, NIH, Bldg 10-CRC,Room 5-3750,10 Ctr Dr, Bethesda, MD 20892 USA. EM sderavin@niaid.nih.gov FU Intramural NIH HHS; NIAID NIH HHS [R01 AI 43745] NR 45 TC 24 Z9 25 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2006 VL 107 IS 8 BP 3091 EP 3097 DI 10.1182/blood-2005-104057 PG 7 WC Hematology SC Hematology GA 033FY UT WOS:000236833500022 PM 16384923 ER PT J AU Belyakov, IM Kuznetsov, VA Kelsall, B Klinman, D Moniuszko, M Lemon, M Markham, PD Pal, R Clements, JD Lewis, MG Strober, W Franchini, GA Berzofsky, JA AF Belyakov, IM Kuznetsov, VA Kelsall, B Klinman, D Moniuszko, M Lemon, M Markham, PD Pal, R Clements, JD Lewis, MG Strober, W Franchini, GA Berzofsky, JA TI Impact of vaccine-induced mucosal high-avidity CD8(+)CTLs in delay of AIDS viral dissemination from mucosa SO BLOOD LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; CYTOTOXIC T-LYMPHOCYTES; MAJOR HISTOCOMPATIBILITY COMPLEX; I MOLECULE MAMU-A-ASTERISK-01; COLONY-STIMULATING FACTOR; INFECTED RHESUS MACAQUES; CELL RESPONSES; GASTROINTESTINAL-TRACT; PROTECTIVE IMMUNITY; SELECTIVE INDUCTION AB Natural HIV transmission occurs through mucosa, but it is debated whether mucosal cytotoxic T lymphocytes (CTLs) can prevent or reduce dissemination from the initial mucosal site to the systemic circulation. Also, the role of CTL avidity in mucosal AIDS viral transmission is unknown. To address these questions, we used delay in acute-phase peak viremia after intrarectal challenge as an indicator of systemic dissemination. We found that a peptide-prime/poxviral boost vaccine inducing high levels of high-avidity mucosal CTLs can have an impact on dissemination of intrarectally administered pathogenic SHIV-ku2 in macaques and that such protection correlates better with mucosal than with systemic CTLs and particularly with levels of high-avidity mucosal CTLs. C1 NCI, Vaccine Branch, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Gen Inst Singapore, Div Informat & Math Sci, Singapore, Singapore. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Adv Biosci Labs, Kensington, MD USA. Tulane Univ, Dept Microbiol & Immunol, Sch Med, New Orleans, LA 70118 USA. So Res Inst, Frederick, MD USA. RP Belyakov, IM (reprint author), NCI, Vaccine Branch, Bldg 10,Rm 6B-12, Bethesda, MD 20892 USA. EM belyakov@mail.nih.gov NR 56 TC 105 Z9 107 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 15 PY 2006 VL 107 IS 8 BP 3258 EP 3264 DI 10.1182/blood-2005-11-4374 PG 7 WC Hematology SC Hematology GA 033FY UT WOS:000236833500044 PM 16373659 ER PT J AU Karadag, A Zhou, M Croucher, PI AF Karadag, A Zhou, M Croucher, PI TI ADAM-9 (MDC-9/meltrin-gamma), a member of the a disintegrin and metalloproteinase family, regulates myeloma-cell-induced interleukin-6 production in osteoblasts by direct interaction with the alpha(v)beta(5) integrin SO BLOOD LA English DT Article ID HUMAN MULTIPLE-MYELOMA; SPERM-EGG FUSION; FERTILIN-BETA; ALPHA(6)BETA(1) INTEGRIN; BONE DESTRUCTION; TNF-ALPHA; P38 MAPK; ADHESION; RECEPTOR; DOMAIN AB ADAM-9, a member of the a disintegrin and metalloproteinase family, contains both metalloproteinase and disintegrin domains. Myeloma cell lines express ADAM-9; however, its function and role in the pathophysiology of multiple myeloma is unknown. The aim of this study was to establish whether primary myeloma cells express ADAM-9, whether ADAM-9 regulates IL-6 production in human osteoblasts (hOBs), whether ADAM-9 interacts with specific integrin heterodimers, and the identity of downstream signaling path-ways. Primary myeloma cells demonstrated increased expression of ADAM-9 (P < .01). ADAM-9 promoted a 5-fold increase in IL-6, but not IL-1 beta mRNA, and a dose- and time-dependent increase in IL-6 production by hOBs (P < .01). IL-6 induction was inhibited by an antibody to the alpha(v)beta(5) integrin (P < .01) but not by antibodies to other integrin heterodimers. ADAM-9 was shown to bind directly to the alpha(v)beta(5) integrin on hOBs. Antibodies to ADAM-9 and a.,05 integrin inhibited myeloma cell-induced IL-6 production by hOBs (P < .01). Furthermore, inhibitors of p38 MAPK and cPLA(2), but not NF-kappa B and JAK2, signaling pathways inhibited ADAM-9-induced IL-6 production by hOBs (P < .01). These data demonstrate that ADAM-9, expressed by myeloma cells, stimulates IL-6 production in hOBs by binding the alpha(v)beta(5) integrin. This may have important consequences for the growth and survival of myeloma cells in bone. C1 Univ Sheffield, Sch Med, Div Clin Sci, Acad Unit Bone Biol, Sheffield S10 2RX, S Yorkshire, England. NIH, Craniofacial & Skeletal Dis Branch, Natl Inst Dent & Carniofacial Res, Dept Hlth & Human Serv, Bethesda, MD USA. Adnan Menderes Univ, Fac Med, Dept Biochem, Aydin, Turkey. RP Croucher, PI (reprint author), Univ Sheffield, Sch Med, Div Clin Sci, Acad Unit Bone Biol, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England. EM a.karadag@sheffield.ac.uk; p.croucher@sheffield.ac.uk FU Intramural NIH HHS NR 42 TC 20 Z9 21 U1 3 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 2006 VL 107 IS 8 BP 3271 EP 3278 DI 10.1182/blood-2005-09-3830 PG 8 WC Hematology SC Hematology GA 033FY UT WOS:000236833500046 PM 16373656 ER PT J AU Catalano, A Caprari, P Moretti, S Faronato, M Tamagnone, L Procopio, A AF Catalano, A Caprari, P Moretti, S Faronato, M Tamagnone, L Procopio, A TI Semaphorin-3A is expressed by tumor cells and alters T-cell signal transduction and function SO BLOOD LA English DT Article ID NEUROPILIN-1; RECEPTORS; CANCER; PLEXINS; GROWTH; RAP1; LYMPHOCYTES; ACTIVATION; INHIBITION; CONTRIBUTE AB An important aspect of tumor progression is the ability of cancer cells to escape detection and clearance by the immune system. Recent studies suggest that several tumors express soluble factors interfering with the immune response. Here, we show that semaphorin-3A (Sema3A), a secreted member of the semaphorin family involved in axonal guidance, organogenesis, and angiogenesis, is highly expressed in several tumor cells. Conditioned media of Sema-3A-transfected COS-7 cells or human recombinant Sema-3A inhibited primary human T-cell proliferation and cytokines production under anti-CD3 plus anti-CD28 stimulating conditions. Sema-3A also inhibited the activation of nonspecific cytotoxic activity in mixed lymphocyte culture (MLC), as measured against K-562 cells. In contrast, suppression of Sema-3A in tumor cells with a small interfering RNA (sIRNA) augmented T-cell activation. The inhibitory effect of Sema-3A in T cells is mediated by blockade of Ras/mitogenactivated protein kinase (MAPK) signaling pathway. The presence of Sema-3A increased the activation of the Ras family small GTPase Rap1 and introduction of the dominant-negative mutant of Rap1 (Rap1N17) blunted the Immunoinhibitory effects of Sema-3A. These results suggest that Sema-3A inhibits primary T-cell activation and imply that it can contribute to the T-cell dysfunction in the tumor microenvironment. C1 Polytech Univ Marche, Dept Mol Pathol & Innovat Therapies, Ancona, Italy. INRCA IRCCS, Ctr Cytol, Ancona, Italy. NCI, Neural Dev Grp, Mouse Canc Genet Program, Frederick, MD 21701 USA. Univ Turin, Inst Canc Res & Treatment, Candiolo, Italy. RP Catalano, A (reprint author), Politecn Marche, Dipartimento Patol Mol, Via Ranieri, I-60131 Ancona, Italy. EM catgfp@yahoo.it NR 39 TC 82 Z9 88 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 15 PY 2006 VL 107 IS 8 BP 3321 EP 3329 DI 10.1182/blood-2005-06-2445 PG 9 WC Hematology SC Hematology GA 033FY UT WOS:000236833500052 PM 16380453 ER PT J AU Bhargava, R Chen, BY Klimstra, DS Saltz, LB Hedvat, C Tang, LH Gerald, W Teruya-Feldstein, J Paty, PB Qin, J Shia, J AF Bhargava, R Chen, BY Klimstra, DS Saltz, LB Hedvat, C Tang, LH Gerald, W Teruya-Feldstein, J Paty, PB Qin, J Shia, J TI Comparison of two antibodies for immunohistochemical evaluation of epidermal growth factor receptor expression in colorectal carcinomas, adenomas, and normal mucosa SO CANCER LA English DT Article DE epidermal growth factor receptor; colon carcinoma; immunohistochemistry; Ventana clone 31G7 antibody; PharmDx kit Dako antibody ID MONOCLONAL-ANTIBODY; CANCER; CETUXIMAB; EGFR; SECTIONS; THERAPY; KINASE; TARGET; TUMORS AB BACKGROUND. Immunohistochemical staining for epidermal growth factor receptor (EGFR) has been used as a criterion for the selection of patients with colon cancer for anti-EGFR therapy. Two antibodies, the PharmDx kit and the 31G7 clone, are used commonly for immunohistochemistry by various laboratories. No comparative studies on the performance of these 2 antibodies are available. METHODS. FGFR status was evaluated in 744 tissue microarray core samples from primary and metastatic colorectal carcinomas, colorectal adenomas, and normal colorectal mucosa with both the PharmDx kit and the clone 31G7 monoclonal antibodies. The stains were compared for staining intensity by using an automated image-analysis system. The intensity of positive staining (brown color) was measured on a scale from 0 to 255. The staining intensity also was scored manually as 0, 1 +, 2 and 3 RESULTS. Statistically, the median staining intensities scored by the automated system between the 2 antibodies did not differ significantly, although, within each category of samples (normal, adenoma, carcinoma, and metastases), the PharmDx antibody staining was slightly more intense than the clone 31G7 antibody staining. There was a linear correlation between automated image-analysis and manual scoring categories. The median automated image-analysis intensity scores for the 4 manual scoring categories with the PharmDx kit were as follows: 0 staining, 67.5; 1 + staining, 75.5; 2 + staining, 89.6; and 3 + staining, 106.0. The median automated image-analysis intensity scores for the 4 manual scoring categories with the clone 31G7 antibody were as follows: 0 staining, 71.3; 1 + staining, 73.6; 2 + staining, 84.6; and 3 + staining, 99.1. The classification of tumors as EGFR-negative (0 staining) or positive (I +, 2 +, or 3 + staining) was concordant in 151 of 160 carcinomas (94.4%) with 2 antibodies using manual scoring. Five samples (3%) that scored I + with the PharmDx kit antibody scored 0 with the clone 31G7 antibody; whereas 4 samples (2.5%) that scored I + with the clone 31G7 antibody scored 0 with the PharmDx kit antibody. CONCLUSIONS. The EGFR expression results obtained by immunohistochemistry CO. using both the EGFR PharmaDx kit and the 31G7 clone were comparable. Either antibody may be used for immunohistochemical detection of EGFR in colorectal carcinomas. In addition, manual scoring had an excellent correlation with automated scoring. C1 Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. RP Shia, J (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. EM shiaj@mskcc.org OI HEDVAT, CYRUS/0000-0003-0045-3491; Shia, Jinru/0000-0002-4351-2511; Saltz, Leonard/0000-0001-8353-4670 FU NCI NIH HHS [2 P01 CA65930-05A2] NR 18 TC 27 Z9 29 U1 1 U2 2 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 2006 VL 106 IS 8 BP 1857 EP 1862 DI 10.1002/cncr.21782 PG 6 WC Oncology SC Oncology GA 032PT UT WOS:000236787500029 PM 16532444 ER PT J AU Glasker, S Li, J Xia, JB Okamoto, H Zeng, WF Lonser, RR Zhuang, ZP Oldfield, EH Vortmeyer, AO AF Glasker, S Li, J Xia, JB Okamoto, H Zeng, WF Lonser, RR Zhuang, ZP Oldfield, EH Vortmeyer, AO TI Hemangioblastomas share protein expression with embryonal hemangioblast progenitor cell SO CANCER RESEARCH LA English DT Article ID HIPPEL-LINDAU-DISEASE; CENTRAL-NERVOUS-SYSTEM; CEREBELLAR CAPILLARY HEMANGIOBLASTOMA; STROMAL CELLS; ENDOTHELIAL-CELLS; ERYTHROID-DIFFERENTIATION; DEVELOPING BRAIN; GROWTH-FACTOR; HISTOGENESIS; SCL AB Hemangioblastomas are central nervous system (CNS) tumors of unknown histogenesis, which can occur sporadically or in von Hippel-Lindau disease. Hemangioblastomas are composed of neoplastic "stromal" cells of unknown origin, accompanied by intensive reactive angiogenesis. Failure to specify the cytologic origin of the stromal cell has precluded the development of nonsurgical therapies and limits understanding of its basic biology. We report that the stromal cells express proteins (Scl, brachyury, Csf-1R, Gata-1, Fik-1, and Tie-2) that characterize embryonic progenitor cells with hemangioblastic differentiation potential and conclude that embryonic progenitors with hemangioblast potential represent a possible cytologic equivalent of the stromal cell. We also identified a new autocrine/ paracrine stimulatory loop between the receptor Tie-2 and the hypoxia-inducible factor target Ang-1, which, combined with previous observations, suggests that a variety of autocrine loops may be initiated in hemangioblastomas, depending on the differentiation status of the tumor cells and the extent of H1F downstream activation. Finally, the consistent identification of Scl in the stromal cells may help explain the unique and characteristic topographical distribution of hemangioblastomas within the CNS. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Freiburg, Neurochirurg Klin, Freiburg, Germany. RP Vortmeyer, AO (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Rm 5D37,10 Ctr Dr, Bethesda, MD 20892 USA. EM vortmeyera@mail.nih.gov NR 50 TC 48 Z9 53 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 2006 VL 66 IS 8 BP 4167 EP 4172 DI 10.1158/0008-5472.CAN-05-3505 PG 6 WC Oncology SC Oncology GA 033JM UT WOS:000236843200029 PM 16618738 ER PT J AU Spence, SL Shaffer, AL Staudt, LM Amde, S Manney, S Terry, C Weisz, K Nissley, P AF Spence, SL Shaffer, AL Staudt, LM Amde, S Manney, S Terry, C Weisz, K Nissley, P TI Transformation of late passage insulin-like growth factor-I receptor null mouse embryo fibroblasts by SV40 T antigen SO CANCER RESEARCH LA English DT Article ID LARGE TUMOR-ANTIGEN; SIGNAL-TRANSDUCTION; MULTIPLE-MYELOMA; CELL-LINES; GENE; INHIBITION; EXPRESSION; PROTEIN; VIVO; PAPILLOMAVIRUS AB There is evidence that the insulin-like growth factor-1 (IGF-I) receptor is required for transformation by a variety of viral and cellular oncogenes in a mouse embryo fibroblast model. To further investigate the IGF-I receptor signaling pathways that are required for the permissive effect of the receptor on transformation by SV40 T antigen, we established three independent fibroblast cell lines each from wild-type and IGF-I receptor null embryos (R-). We transfected the wildtype and R- cell lines with an SV40 T antigen plasmid and selected three clones from each cell line that expressed T antigen. As in previous reports, none of the cloned R- cell lines expressing T antigen were transformed as measured by the ability to form large colonies in soft agar. However, with further passage, all three T antigen-expressing clones from one of the R- cell lines (R(-)3) formed large colonies in soft agar and the transformation of these T antigen-expressing clones was confirmed by tumorigenesis experiments in immunodeficient mice. DNA microarray analysis comparing gene expression between early passage and late passage R(-)3/T antigen clones showed, among other changes, an increase in the expression of ErbB-3 mRNA in the late passage clones. Also, the expression of ErbB-3 protein was dramatically increased in the late passage R-3/T antigen clones. We conclude that late passage IGF-I receptor null mouse embryo fibroblasts can be transformed by SV40 T antigen, and that ErbB-3 may play a role in permitting transformation by T antigen. C1 Natl Canc Inst, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Nissley, P (reprint author), Natl Canc Inst, Metab Branch, NIH, Bldg 10,Room 4N115, Bethesda, MD 20892 USA. EM spniss@mail.nih.gov NR 50 TC 5 Z9 5 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 2006 VL 66 IS 8 BP 4233 EP 4239 DI 10.1158/0008-5472.CAN-05-2257 PG 7 WC Oncology SC Oncology GA 033JM UT WOS:000236843200037 PM 16618746 ER PT J AU Nakamura, K Martin, KC Jackson, JK Beppu, K Woo, CW Thiele, CJ AF Nakamura, K Martin, KC Jackson, JK Beppu, K Woo, CW Thiele, CJ TI Brain-derived neurotrophic factor activation of TrkB induces vascular endothelial growth factor expression via hypoxia-inducible factor-1 alpha in neuroblastoma cells SO CANCER RESEARCH LA English DT Article ID PROSTATE-CANCER; UP-REGULATION; BDNF; DIFFERENTIATION; GENE; IDENTIFICATION; RECEPTORS; PATHWAY; TRANSCRIPTION; ANGIOGENESIS AB The extent of angiogenesis and/or vascular endothelial growth factor (VEGF) expression in neuroblastoma tumors correlates with metastases, N-myc amplification, and poor clinical outcome. Recently, we have shown that insulin-like growth factor-I and serum-derived growth factors stimulate VEGF expression in neuroblastoma cells via induction of hypoxia-inducible factor-1 alpha (HIF-1 alpha). Because another marker of poor prognosis in neuroblastoma tumors is high expression of brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor, TrkB, we sought to evaluate the involvement of BDNF and TrkB in the regulation of VEGF expression. VEGF mRNA levels in neuroblastoma cells cultured in serum-free media increased after 8 to 16 hours in BDNF. BDNF induced increases in VEGF and HIF-1 alpha protein, whereas HIF-1 beta levels were unaffected. BDNF induced a 2- to 4-fold increase in VEGF promoter activity, which could be abrogated if the hypoxia response element in the VEGF promoter was mutated. Transfection of HIF-1 alpha small interfering RNA blocked BDNF-stimulated increases in VEGF promoter activity and VEGF protein expression. The BDNF-stimulated increases in HIF-1 alpha and VEGF expression required TrkB tyrosine kinase activity and were completely blocked by inhibitors of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) pathways. These data indicate that BDNF plays a role in regulating VEGF levels in neuroblastoma cells and that targeted therapies to BDNF/TrkB, PI3K, mTOR signal transduction pathways, and/or HIF-1 alpha have the potential to inhibit VEGF expression and limit neuroblastoma tumor growth. C1 NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Miyazaki Prefectural Miyazaki Hosp, Dept Surg, Miyazaki, Japan. Korea Univ, Coll Med, Dept Pediat, Seoul 136701, South Korea. RP Thiele, CJ (reprint author), NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, NIH, POB Bldg 10,CRC I-3954,10 Ctr Dr,MSC-1105, Bethesda, MD 20892 USA. EM ct47d@nih.gov FU Intramural NIH HHS NR 43 TC 112 Z9 120 U1 1 U2 10 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 2006 VL 66 IS 8 BP 4249 EP 4255 DI 10.1158/0008-5472.CAN-05-2789 PG 7 WC Oncology SC Oncology GA 033JM UT WOS:000236843200039 PM 16618748 ER PT J AU Miyazaki, H Patel, V Wang, HX Edmunds, RK Gutkind, JS Yeudall, WA AF Miyazaki, H Patel, V Wang, HX Edmunds, RK Gutkind, JS Yeudall, WA TI Down-regulation of CXCL5 inhibits squamous carcinogenesis SO CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; CHEMOKINE RECEPTORS; ENDOTHELIAL-CELLS; CARCINOMA-CELLS; PROLIFERATION; EXPRESSION; ANGIOGENESIS; KINASE; HEAD; INVOLVEMENT AB We report a novel role for the CXC-chemokine, CXCL5, in the proliferation and invasion of head and neck squamous cell carcinoma (HNSCC). Previously, we reported transcriptional up-regulation of CXCL5 in metastatic cells. In this study, we provide biological validation of these findings and show that CXCL5 is intimately involved in tumor cell proliferation, migration, and invasion. Cells derived from a lymph node metastasis, but not from a synchronous primary tumor, secreted CXCL5 as judged by Western blotting of conditioned media. We used RNA interference to generate cell lines (shL5) in which CXCL5 expression was greatly reduced, and tested whether this modulated the cell phenotype. shL5 cells showed decreased proliferation compared with cells harboring non-targeting control sequences. In addition, we found that the ability of shL5 cells to migrate and invade in vitro through a basement membrane substitute was greatly impaired compared with control cells. Finally, whereas control cells were highly tumorigenic in nude mice, the tumorigenic potential in vivo of shL5 cells was found to be ablated. Taken together, these data suggest that CXCL5 production contributes to both enhanced proliferation and invasion of squamous cell carcinomas and that targeting of chemokine pathways may represent a potential therapeutic modality for these lesions. C1 Virginia Commonwealth Univ, Philips Inst Oral & Craniofacial Mol Biol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Dept Biochem, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Massey Canc Ctr, Richmond, VA 23298 USA. Natl Inst Dental & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD USA. RP Yeudall, WA (reprint author), Virginia Commonwealth Univ, Philips Inst Oral & Craniofacial Mol Biol, POB 980566,521 N 11th St, Richmond, VA 23298 USA. EM wayeudall@vcu.edu RI Gutkind, J. Silvio/A-1053-2009 NR 36 TC 68 Z9 74 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 2006 VL 66 IS 8 BP 4279 EP 4284 DI 10.1158/0008-5472.CAN-05-4398 PG 6 WC Oncology SC Oncology GA 033JM UT WOS:000236843200043 PM 16618752 ER PT J AU Marin, HE Peraza, MA Billin, AN Willson, TM Ward, JM Kennett, MJ Gonzalez, FJ Peters, JM AF Marin, HE Peraza, MA Billin, AN Willson, TM Ward, JM Kennett, MJ Gonzalez, FJ Peters, JM TI Ligand activation of peroxisome proliferator-activated receptor beta inhibits colon carcinogenesis SO CANCER RESEARCH LA English DT Article ID PPAR-DELTA; ACROMEGALIC PATIENTS; CELL-PROLIFERATION; COLORECTAL-CANCER; GENE-EXPRESSION; DOME EPITHELIUM; LYMPHOID-TISSUE; ADENOMA GROWTH; CATHEPSIN-E; GAMMA GENE AB There is considerable debate whether peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) ligands potentiate or suppress colon carcinogenesis. Whereas administration of a PPAR beta ligand causes increased small intestinal tumorigenesis in Apc(min/+) mice, PPAR beta-null (Pparb(-/-)) mice exhibit increased colon polyp multiplicity in colon cancer bioassays, suggesting that ligand activation of this receptor will inhibit colon carcinogenesis. This hypothesis was examined by treating wild-type (Pparb(+/+)) and Pparb(-/-) with azoxymethane, coupled with a highly specific PPAR beta ligand, GW0742. Ligand activation of PPAR beta in Pparb(+/+) mice caused an increase in the expression of mRNA encoding adipocyte differentiation-related protein, fatty acid-binding protein, and cathepsin E. These findings are indicative of colonocyte differentiation, which was confirmed by immunohistochemical analysis. No PPAR beta-dependent differences in replicative DNA synthesis or expression of phosphatase and tensin homologue, phosphoinositide-dependent kinase, integrin-linked kinase, or phospho-Akt were detected in ligand-treated mouse colonic epithelial cells although increased apoptosis was found in GW0742-treated Pparb(+/+) mice. Consistent with increased colonocyte differentiation and apoptosis, inhibition of colon polyp multiplicity was also found in ligand-treated Pparb(+/+) mice, and all of these effects were not found in Pparb(-/-) mice. In contrast to previous reports suggesting that activation of PPAR beta potentiates intestinal tumorigenesis, here we show that ligand activation of PPAR beta attenuates chemically induced colon carcinogenesis and that PPAR beta-dependent induction of cathepsin E could explain the reported disparity in the literature about the effect of ligand activation of PPAR beta in the intestine. C1 Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. Penn State Univ, Grad Program Biochem Microbiol & Mol Biol, University Pk, PA 16802 USA. GlaxoSmithKline Inc, Nucl Receptor Discovery Res, Res Triangle Pk, NC USA. NIAID, Infect Dis Pathogenesis Sect, Comparat Med Branch, Bethesda, MD 20892 USA. NIAID, SoBran Inc, Bethesda, MD 20892 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, 312 Life Sci Bldg, University Pk, PA 16802 USA. EM jmp21@psu.edu RI Peters, Jeffrey/D-8847-2011; OI Billin, Andrew/0000-0001-7752-0934 FU NCI NIH HHS [CA89607, CA97999] NR 41 TC 92 Z9 94 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 2006 VL 66 IS 8 BP 4394 EP 4401 DI 10.1158/0008-5472.CAN-05-4277 PG 8 WC Oncology SC Oncology GA 033JM UT WOS:000236843200056 PM 16618765 ER PT J AU Kawakami, K Terabe, M Kawakami, M Berzofsky, JA Puri, RK AF Kawakami, K Terabe, M Kawakami, M Berzofsky, JA Puri, RK TI Characterization of a novel human tumor antigen interleukin-13 receptor alpha 2 chain SO CANCER RESEARCH LA English DT Article ID REED-STERNBERG CELLS; IL-13 RECEPTOR; PSEUDOMONAS EXOTOXIN; IN-VIVO; FUNCTIONAL-CHARACTERIZATION; SIGNAL-TRANSDUCTION; HODGKIN LYMPHOMA; CANCER VACCINES; DECOY RECEPTOR; BREAST-CANCER AB The interleukin (IL)-13 receptor alpha 2 (IL-13R alpha 2) chain is a primary binding and internalization subunit for a Th2-derived immune regulatory cytokine, IL-13. Although extremely high levels of IL-13R alpha 2 chain are expressed on a variety of human tumor cells and specimens, its precise role in tumor immunology has not been defined. To investigate the role of IL-13R alpha 2 in tumor immunity, we used D5 melanoma cells stably transfected with the human M-13R alpha 2 gene (D5 alpha 2) to assess the effect of an IL-13R alpha 2 DNA vaccine in immunocompetent animals. Prophylactic immunization of mice with the IL-13R alpha 2 DNA vaccine resulted in protection against D5 alpha 2 tumor development. In vivo depletion experiments in C57BL/6 and RAG-2 knockout mice indicated that both T and B cells, but not natural killer cells, were required for the tumor protection. In addition, antibody induced by the IL-13R alpha 2 DNA vaccine showed a modest but significant inhibitory effect on D5 alpha 2 cells in vitro, suggesting that the antibody is biologically functional. The IL-13R alpha 2 DNA vaccine also exhibited antitumor activity against established D5 alpha 2 tumors in mice. Histologic analysis of regressing tumors identified infiltration of CD4(+) and CD8(+) T cells and the expression of CXCL9 chemokine in tumors. Taken together, our results identify the human IL-13R alpha 2 chain as a novel tumor rejection antigen. C1 Univ Tokyo, Grad Sch Med, Dept Adv Clin Sci & Therapeut, Bunkyo Ku, Tokyo 1138655, Japan. US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NCI, Vaccine Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kawakami, K (reprint author), Univ Tokyo, Grad Sch Med, Dept Adv Clin Sci & Therapeut, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM kawakami-k@umin.ac.jp FU Intramural NIH HHS NR 43 TC 20 Z9 22 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 2006 VL 66 IS 8 BP 4434 EP 4442 DI 10.1158/0008-5472.CAN-05-1265 PG 9 WC Oncology SC Oncology GA 033JM UT WOS:000236843200061 PM 16618770 ER PT J AU Ouyang, N Williams, JL Tsioulias, GJ Gao, JJ Iatropoulos, MJ Kopelovich, L Kashfi, K Rigas, B AF Ouyang, N Williams, JL Tsioulias, GJ Gao, JJ Iatropoulos, MJ Kopelovich, L Kashfi, K Rigas, B TI Nitric oxide-donating aspirin prevents pancreatic cancer in a hamster tumor model SO CANCER RESEARCH LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NF-KAPPA-B; GROWTH-INHIBITION; CYCLOOXYGENASE-2 INHIBITOR; OXIDATIVE STRESS; CELL-LINES; EXPRESSION; APOPTOSIS; CARCINOGENESIS; INDUCTION AB To evaluate the chemopreventive effect of nitric oxide-donating aspirin (NO-ASA), an ASA bearing a NO-releasing moiety, against pancreatic cancer, we studied six groups of female Syrian golden hamsters: groups I to 3 (n = 12 each) were given saline and groups 4 to 6 (n = 17) the carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) s.c. in five weekly injections (the first, 70 mg/kg, and the remaining, 20 mg/kg each). Control and BOP-treated hamsters were fed a NO-ASA 3,000 ppm or conventional ASA 3,000 ppm or control diet for 19 weeks. Groups I to 3 had no tumors. Compared with the BOP/vehicle group, NO-ASA reduced the incidence (88.9%, P < 0.003) and multiplicity (94%, P < 0.05) of pancreatic cancer; ASA had no statistically significant effect. NO-ASA arrested the transition from PanIN2 to PanIN3 and carcinoma. The proliferation (proliferating cell nuclear antigen) / apoptosis (terminal deoxyribonucleotide transferase-mediated nick-end labeling) ratio of ductal cells increased with the histologic severity of the ductal lesion; NO-ASA suppressed it significantly during all stages except PanINIA. p21(WAF1/CIP1), undetectable in normal cells, was progressively induced in neoplastic cells and suppressed by NO-ASA up to PanIN3. Nuclear factor-kappa B activation, absent in normal tissue, increased progressively (17-fold in cancer); NO-ASA suppressed it throughout and significantly in PanIN1B and PanIN2. Cyclooxygenase-2 expression, absent during early stages, was induced 6-fold in carcinoma and suppressed by NO-ASA in PanIN3 and carcinoma. Conventional ASA had no effect on these molecular markers. Thus, NO-ASA profoundly prevented pancreatic cancer and modulated multiple molecular targets in this model system; conventional ASA had no such effects. NO-ASA merits further evaluation as a chemopreventive agent against pancreatic cancer. C1 SUNY Stony Brook, Div Canc Prevent, Stony Brook, NY 11794 USA. Mt Sinai Sch Med, Dept Surg, New York, NY USA. CUNY, Sch Med, Dept Physiol & Pharmacol, New York, NY 10021 USA. New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA. NCI, Chemoprevent Branch, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Rigas, B (reprint author), SUNY Stony Brook, Div Canc Prevent, Life Sci Bldg,Room 006, Stony Brook, NY 11794 USA. EM basil.rigas@sunysb.edu FU NCI NIH HHS [CA92423, CA34527, CA92423-S1] NR 41 TC 51 Z9 56 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2006 VL 66 IS 8 BP 4503 EP 4511 DI 10.1158/0008-5472.CAN-05-3118 PG 9 WC Oncology SC Oncology GA 033JM UT WOS:000236843200069 PM 16618778 ER PT J AU Michaud, DS Daugherty, SE Berndt, SI Platz, EA Yeager, M Crawford, ED Hsing, A Huang, WY Hayes, RB AF Michaud, DS Daugherty, SE Berndt, SI Platz, EA Yeager, M Crawford, ED Hsing, A Huang, WY Hayes, RB TI Genetic polymorphisms of interleukin-1B (IL-1B), IL-6, IL-8, and IL-10 and risk of prostate cancer SO CANCER RESEARCH LA English DT Article ID LINKAGE PHASE; ALPHA GENE; TUMORIGENICITY; ANGIOGENESIS; METAANALYSIS; ASSOCIATION; TESTS AB Chronic intraprostatic inflammation is suspected to play a role in the pathogenesis of prostate cancer. Polymorphisms in cytokine genes can influence inflammation and immune response and may be related to the risk of prostate cancer. Four common single nucleotide polymorphisms (SNPs) in the genes encoding interleukin-1B (IL-1B), IL-6, and IL-8 were assessed in 503 prostate cancer cases and 652 controls, and three SNPs in IL-10 were assessed in an additional 817 prostate cancer cases and 1,190 controls (for a total of 1,320 prostate cancer cases and 1,255 controls). Cases and controls were selected from the on-going Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial and were frequency matched on age, ethnicity, time-period since initial screening, and date of blood draw. Single-locus analyses were conducted using conditional logistic regression. In addition, we did a haplotype analysis for the three IL-10 SNPs tested. Overall, no associations were detected between the seven polymorphisms in the four cytokine genes examined in this study and prostate cancer risk. Further stratifying by use of nonsteroidal anti-inflammatory drugs did not modify the associations. Findings were similar for early or advanced prostate cancers. Similarly, we observed no association between the major IL-10 haplotypes and the risk of prostate cancer. At least seven common polymorphisms in genes of inflammatory cytokines IL-1B, IL-6, IL-8, and IL-10 do not seem to play a role in the risk of prostate cancer. C1 NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Med Inst, Brady Urol Inst, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. NCI, Intramural Res Support Program, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. Univ Colorado, Denver, CO 80202 USA. RP Hayes, RB (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, 6120 Execut Blvd,MSC 7240,EPS 8114, Bethesda, MD 20892 USA. EM hayesr@mail.nih.gov RI Michaud, Dominique/I-5231-2014 FU Intramural NIH HHS NR 30 TC 74 Z9 76 U1 2 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 15 PY 2006 VL 66 IS 8 BP 4525 EP 4530 DI 10.1158/008-5472.CAN-05-3987 PG 6 WC Oncology SC Oncology GA 033JM UT WOS:000236843200072 PM 16618781 ER PT J AU Reddy, BS Wang, CX Kong, AN Khor, TO Zheng, X Steele, VE Kopelovich, L Rao, CV AF Reddy, BS Wang, CX Kong, AN Khor, TO Zheng, X Steele, VE Kopelovich, L Rao, CV TI Prevention of azoxymethane-induced colon cancer by combination of low doses of atorvastatin, aspirin, and celecoxib in F 344 rats SO CANCER RESEARCH LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; COA REDUCTASE INHIBITOR; CYCLOOXYGENASE-2 INHIBITOR; COLORECTAL-CANCER; GASTROINTESTINAL-TRACT; INTESTINAL POLYPOSIS; INDUCED APOPTOSIS; MURINE MODEL; CHEMOPREVENTION; CARCINOGENESIS AB Preclinical and clinical studies have provided evidence that aspirin, celecoxib, (cyclooxygenase-2 inhibitor), and statins (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) inhibit colon carcinogenesis. Chronic use of high doses of these agents may induce side effects in ostensibly normal individuals. Combining low doses of agents may be an effective way I to increase their efficacy and minimize toxicity. We assessed the efficacy of atorvastatin (lipitor), celecoxib, and aspirin, given individually at high dose levels and in combination at lower doses against azoxymethane-induced colon carcinogenesis, in male F 344 rats. One day after the last azoxymethane treatment (15 mg/kg body weight, s.c., once weekly for 2 weeks) groups of male F 344 rats were fed the AIN-76A diet or AIN-76A diet containing 150 ppm atorvastatin, 600 ppm celecoxib, and 400 ppm aspirin, 100 ppm atorvastatin + 300 ppm celecoxib, and 100 ppm atorvastatin + 200 ppm aspirin. Rats were killed 42 weeks later, and colon tumors were processed histopathologically and analyzed for cell proliferation and apoptosis immunohistochemically. Administration of these agents individually and in combination significantly suppressed the incidence and multiplicity of colon adenocarcinomas. Low doses of these agents in combination inhibited colon carcinogenesis more effectively than when they were given individually at higher doses. Inhibition of colon carcinogenesis by these agents is associated with the inhibition of cell proliferation and increase in apoptosis in colon tumors. these observations are of clinical significance because this can pave the way for the use of combinations of these agents in small doses against colon cancer. C1 Rutgers State Univ, Dept Biol Chem, Ernest Mario Sch Pharm, Susan Lehman Cullman Lab Canc Res, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Pharmaceut, Piscataway, NJ 08854 USA. New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, OU Canc Inst, Oklahoma City, OK USA. RP Reddy, BS (reprint author), Rutgers State Univ, Dept Biol Chem, Ernest Mario Sch Pharm, Susan Lehman Cullman Lab Canc Res, 164 Frelinghuysen Rd, Piscataway, NJ 08854 USA. EM breddy@rci.rutgers.edu RI Chinthalapally, Rao/B-3633-2010 FU NCI NIH HHS [CA-17613, 1R01-CA-37663, 1R01-CA-94962, N01-CN-43308] NR 35 TC 65 Z9 69 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 2006 VL 66 IS 8 BP 4542 EP 4546 DI 10.1158/0008-5472.CAN-05-4428 PG 5 WC Oncology SC Oncology GA 033JM UT WOS:000236843200074 PM 16618783 ER PT J AU Steinbach, D Schramm, A Eggert, A Onda, M Dawczynski, K Rump, A Pastan, I Wittig, S Pfaffendorf, N Voigt, A Zintl, F Gruhn, B AF Steinbach, D Schramm, A Eggert, A Onda, M Dawczynski, K Rump, A Pastan, I Wittig, S Pfaffendorf, N Voigt, A Zintl, F Gruhn, B TI Identification of a set of seven genes for the monitoring of minimal residual disease in pediatric acute myeloid leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; POLYMERASE-CHAIN-REACTION; T-CELL RESPONSES; FLOW-CYTOMETRY; PROGNOSTIC-SIGNIFICANCE; MONOCLONAL-ANTIBODIES; PRAME GENE; EXPRESSION; CHILDHOOD; RELAPSE AB Background: Monitoring of minimal residual disease (MRD) has become a strong diagnostic tool in acute lymphoblastic leukemia. It is used for risk-adapted therapy and for the recognition of pending relapses. In acute myeloid leukemia (AML), there is still a need for more suitable MRD markers. Experimental Design: A stepwise approach which combined genome-wide expression profiling, TaqMan low density arrays, and a TaqMan real-time PCR-based screening was used to identify new markers for the monitoring of MRD in AML. Leukemic cells from 52 children with AML and 145 follow-up samples from 25 patients were analyzed. Results: Seven genes were identified which are vastly overexpressed in many patients with AML compared with healthy bone marrow: CCL23, GAGED2, MSLN, SPAG6, and ST18 as well as the previously described markers WT1 and PRAME. The expression of all genes decreased to normal levels in patients who achieved a continuous complete remission. Elevated levels of at least one gene were found prior to relapse in 7 out of 10 patients who relapsed. Conclusions: This set of genes should allow a sensitive and specific monitoring of MRD in AML. Notably, some of these markers could also serve as therapeutic targets or might be involved in leukemogenesis. MSLN is already used as a target for immunotherapy in clinical trials in other malignancies. C1 Univ Childrens Hosp Jena, D-07740 Jena, Germany. Univ Childrens Hosp Essen, Essen, Germany. Univ Dresden, Fac Med, Dresden, Germany. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Steinbach, D (reprint author), Univ Childrens Hosp Jena, Kochstr 2, D-07740 Jena, Germany. EM Daniel@Steinba.ch OI Rump, Andreas/0000-0001-7116-6364 FU Intramural NIH HHS NR 34 TC 60 Z9 65 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2006 VL 12 IS 8 BP 2434 EP 2441 DI 10.1158/1078-0432.CCR-05-2552 PG 8 WC Oncology SC Oncology GA 037UR UT WOS:000237173300008 PM 16638849 ER PT J AU Matsumoto, K Hyodo, F Matsumoto, A Koretsky, AP Sowers, AL Mitchell, JB Krishna, MC AF Matsumoto, K Hyodo, F Matsumoto, A Koretsky, AP Sowers, AL Mitchell, JB Krishna, MC TI High-resolution mapping of tumor redox status by magnetic resonance imaging using nitroxides as redox-sensitive contrast agents SO CLINICAL CANCER RESEARCH LA English DT Article ID ELECTRON-PARAMAGNETIC-RESONANCE; MURINE TUMOR; CELLULAR-METABOLISM; OXIDATIVE STRESS; TEMPOL; MRI; OXYGEN; HYDROXYLAMINES; ANTIOXIDANTS; REDUCTION AB Purpose: There is considerable research directed toward the identification and development of functional contrast agents for medical imaging that superimpose tissue biochemical/molecular information with anatomical structures. Nitroxide radicals were identified as in vivo radioprotectors. Being paramagnetic, they can provide image contrast in magnetic resonance imaging (MRI) and electron paramagnetic resonance imaging (EPRI). The present study sought to determine the efficacy of nitroxide radioprotectors as functional image contrast agents. Experimental Design: Nitroxide radioprotectors, which act as contrast agents, were tested by EPRI and MRI to provide tissue redox status information noninvasively. Results: Phantom studies showed that the nitroxide, 3-carbamoyl-PROXYL (3CP), undergoes time-dependent reduction to the corresponding diamagnetic hydroxylamine only in the presence of reducing agents. The reduction rates of 3CP obtained by EPRI and MRI were in agreement suggesting the feasibility of using MRI to monitor nitroxide levels in tissues. The levels of 3CP were examined by EPRI and MRI for differences in reduction between muscle and tumor (squamous cell carcinoma) implanted in the hind leg of C3H mice simultaneously. In vivo experiments showed a T1-dependent image intensity enhancement afforded by 3CP which decreased in a time-dependent manner. Reduction of 3CP was found to be the dominant mechanism of contrast loss. The tumor regions exhibited a faster decay rate of the nitroxide compared to muscle (0.097 min(-1) versus 0.067 min(-1), respectively). Conclusions: This study shows that MRI can be successfully used to co-register tissue redox status along with anatomic images, thus providing potentially valuable biochemical information from the region of interest. C1 NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Room B3-B69,Bldg 10, Bethesda, MD 20892 USA. EM murali@helix.nih.gov RI Koretsky, Alan/C-7940-2015; Yamada, Ken-ichi/E-6318-2012 OI Koretsky, Alan/0000-0002-8085-4756; FU Intramural NIH HHS [Z01 NS003047-01] NR 42 TC 78 Z9 83 U1 3 U2 27 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 2006 VL 12 IS 8 BP 2455 EP 2462 DI 10.1158/1078-0432.CCR-05-2747 PG 8 WC Oncology SC Oncology GA 037UR UT WOS:000237173300011 PM 16638852 ER PT J AU Romeo, MJ Wunderlich, J Ngo, L Rosenberg, SA Steinberg, SM Berman, DM AF Romeo, MJ Wunderlich, J Ngo, L Rosenberg, SA Steinberg, SM Berman, DM TI Measuring tissue-based biomarkers by immunochromatography coupled with reverse-phase lysate microarray SO CLINICAL CANCER RESEARCH LA English DT Article ID PROTEIN MICROARRAYS; DRUG DISCOVERY; RT-PCR; EXPRESSION; PATHWAYS; MARKERS; TIME AB Purpose: There is a need for new technologies to study tissue-based biomarkers. The current gold standard, immunohistochemistry, is compromised by variability in tissue processing and observer bias. Reverse transcription-PCR (RT-PCR), immunocytochemistry, and reverse-phase lysate microarrays (RPM) are promising alternative technologies but have not yet been validated, or correlated, on the same patient-derived tissues. Furthermore, RPM is currently limited by time-consuming microdissection and low amounts of evaluable protein lysates. Experimental Design: Metastatic melanoma was surgically excised from 30 patients and macroscopically dissected from surrounding stroma. Each specimen was processed by formalin-fixation (immunohistochemistry), cytospin (immunocytochemistry), or disaggreagation and enrichment (RT-PCR and RPM). The latter protocol uses immunochromatography to remove hematopoetic-derived cells, thus enriching for melanoma cells. Each sample was measured for the expression of gp100 or MART-1 normalized to actin. Results: Immunochromatography coupled with RPM (I-RPM) is reproducible (r >= 0.70) and, for gp100, correlates strongly with immunohistochemistry and immunocytochemistry (r=0.78 and 0.76, respectively) and moderately with transcript levels, measured by RT-PCR (r=0.61). In contrast, for MART-1, I-RPM correlates strongly with transcript level (r=0.78) but only moderately strong correlations are noted with immunohistochemistry and immunocytochemistry (r=0.64 and 0.59, respectively). In general, transcript levels show only moderately strong correlations with immunohistochemistry and immunocytochemistry (r=0.41-0.64). Conclusion: I-RPM is a promising technology for quantitative grading of tissue biomarkers; however, antigen-dependent correlations are noted. C1 NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Berman, DM (reprint author), Bristol Myers Squibb Co, POB 4000, Princeton, NJ 08543 USA. EM david.berman@bms.com FU Intramural NIH HHS [Z01 SC003811-32] NR 17 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2006 VL 12 IS 8 BP 2463 EP 2467 DI 10.1158/1078-0432.CCR-05-1479 PG 5 WC Oncology SC Oncology GA 037UR UT WOS:000237173300012 PM 16638853 ER PT J AU Lindsey, KR Gritz, L Sherry, R Abati, A Fetsch, PA Goldfeder, LC Gonzales, MI Zinnack, KA Rogers-Freezer, L Haworth, L Mavroukakis, SA White, DE Steinberg, SM Restifo, NP Panicali, DL Rosenberg, SA Topalian, SL AF Lindsey, KR Gritz, L Sherry, R Abati, A Fetsch, PA Goldfeder, LC Gonzales, MI Zinnack, KA Rogers-Freezer, L Haworth, L Mavroukakis, SA White, DE Steinberg, SM Restifo, NP Panicali, DL Rosenberg, SA Topalian, SL TI Evaluation of prime/boost regimens using recombinant poxvirus/tyrosinase vaccines for the treatment of patients with metastatic melanoma SO CLINICAL CANCER RESEARCH LA English DT Article ID CD4(+) T-CELLS; TUMOR-INFILTRATING LYMPHOCYTES; COLONY-STIMULATING FACTOR; IMMUNE-RESPONSES; IMMUNOLOGICAL ADJUVANTS; DOSE INTERLEUKIN-2; DIVERSIFIED PRIME; CANCER-PATIENTS; POX VIRUS; TYROSINASE AB Purpose: Two clinical trials were conducted to evaluate the clinical efficacy and immunologic impact of vaccination against the tyrosinase protein plus systemic interleukin 2 (IL-2) administration in patients with advanced metastatic melanoma. Experimental Design: Full-length tyrosinase was employed as an immunogen to induce diverse immunologic responses against a commonly expressed melanoma antigen. Heterologous prime/boost vaccination with recombinant vaccinia and fowlpox vectors encoding tyrosinase was first explored in a randomized three-arm phase II trial, in which vaccines were administered alone or concurrently with low-dose or high-dose IL-2. In a subsequent single cohort phase II trial, all patients received the same vaccines and high-dose IL-2 sequentially rather than concurrently. Results: Among a total of 64 patients treated on these trials, 8 objective partial responses (12.5%) were observed, all in patients receiving high-dose IL-2. Additional patients showed evidence of lesional regression (mixed tumor response) or overall regression that did not achieve partial response status (minor response). In vitro evidence of enhanced immunity against tyrosinase following protocol treatments was documented in 3 of 49 (6%) patients tested serologically, 3 of 23 (13%) patients tested for T-cell recognition of individual tyrosinase peptides, and 4 of 16 (25%) patients tested for T-cell recognition of full-length tyrosinase protein with real-time reverse transcription-PCR techniques. Conclusions: Whereas prime/boost immunization with recombinant vaccinia and fowlpox viruses enhanced antityrosinase immunity in some patients with metastatic melanoma, it was ineffective alone in mediating clinical benefit, and in combination with IL-2 did not mediate clinical benefit significantly different from that expected from treatment with IL-2 alone. C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Cambridge, MA USA. NCI, Biostat & Data Management Sect, Cambridge, MA USA. Ther Biol Corp, Cambridge, MA USA. RP Topalian, SL (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, 10 Ctr Dr,CRC 3-5752, Bethesda, MD 20892 USA. EM Suzanne_Topalian@nih.gov RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z01 SC003811-32, Z99 CA999999] NR 46 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2006 VL 12 IS 8 BP 2526 EP 2537 DI 10.1158/1078-0432.CCR-05-2061 PG 12 WC Oncology SC Oncology GA 037UR UT WOS:000237173300021 PM 16638862 ER PT J AU Namba, R Young, LJ Abbey, CK Kim, L Damonte, P Borowsky, AD Qi, JY Tepper, CG MacLeod, CL Cardiff, RD Gregg, JP AF Namba, R Young, LJ Abbey, CK Kim, L Damonte, P Borowsky, AD Qi, JY Tepper, CG MacLeod, CL Cardiff, RD Gregg, JP TI Rapamycin inhibits growth of premalignant and malignant mammary lesions in a mouse model of ductal carcinoma in situ SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN-BREAST-CANCER; ESTROGEN-RECEPTOR; MAMMALIAN TARGET; INTRAEPITHELIAL NEOPLASIA; MTOR INHIBITOR; CYCLIN D1; PATHWAY; EXPRESSION; CELLS; PROGRESSION AB Purpose: Rapamycin has been shown to have antitumor effects in various tumor models. To study the effect of rapamycin at different stages of breast cancer development, we used two unique mouse models of breast cancer with activated phosphatidylinositol 3-kinase (PI3K) pathway. Met-1 tumors are highly invasive and metastatic, and mammary intraepithelial neoplasia-outgrowths (MIN-O), a model for human ductal carcinoma in situ, are transplantable premalignant mammary lesions that develop invasive carcinoma with predictable latencies. Both of these models were derived from mammary lesions in Tg(MMTV-PyV-mT) mice. Experimental Design: Met-1 tumors were used to study the effect of rapamycin treatment on invasive disease. Transplanted MIN-O model was used to study the effect of rapamycin on premalignant mammary lesions, Animals were in vivo micro - positron emission tomography imaged to follow the lesion growth and transformation to tumor during the treatment. Cell proliferation, angiogenesis, and apoptosis was assayed by immunohistochemistry. Results: Rapamycin inhibited in vitro tumor cell proliferation and in vivo Met-1 tumor growth. The growth inhibition was correlated with dephosphorylation of mammalian target of rapamycin (mTOR) targets. Rapamycin treatment significantly reduced the growth of the premalignant MIN-O lesion, as well as tumor incidence and tumor burden. Growth inhibition was associated with reduced cell proliferation and angiogenesis and increased apoptosis. Conclusions: In PyV-mT mouse mammary models, rapamycin inhibits the growth of premalignant lesions and invasive tumors. Although the inhibitory effect of rapamycin was striking, rapamycin treatment did not completely obliterate the lesions. C1 Univ Calif Davis, Sch Med, Dept Pathol & Lab Med, Davis, CA 95616 USA. Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. Univ Calif Davis, Dept Biochem & Mol Biol, Davis, CA 95616 USA. NCI, Bethesda, MD 20892 USA. RP Gregg, JP (reprint author), Univ Calif Davis, Sch Med, Dept Pathol & Lab Med, Room 2460,MIND Wetlab Bldg,2805 5th St, Sacramento, CA 95817 USA. EM jpgregg@ucdavis.edu RI Qi, Jinyi/A-1768-2010 OI Qi, Jinyi/0000-0002-5428-0322 NR 37 TC 62 Z9 63 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2006 VL 12 IS 8 BP 2613 EP 2621 DI 10.1158/1078-0432.CCR-05-2170 PG 9 WC Oncology SC Oncology GA 037UR UT WOS:000237173300033 PM 16638874 ER PT J AU Hanbauer, I Moskovitz, J AF Hanbauer, I Moskovitz, J TI The yeast cytosolic thioredoxins are involved in the regulation of methionine sulfoxide reductase A SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE yeast; methionine sulfoxide reductase; thioredoxin; oxidative stress; transcription factors; methionine oxidation; free radicals ID OXIDATIVE STRESS-RESPONSE; ALZHEIMERS-DISEASE BRAIN; NF-KAPPA-B; SACCHAROMYCES-CEREVISIAE; SUBSTRATE STEREOSPECIFICITY; ANTIOXIDANT DEFENSE; ESCHERICHIA-COLI; FREE-RADICALS; DNA-SYNTHESIS; IDENTIFICATION AB Previously we have shown that the binding complex fort-nation of methionine sulfoxide reductase A (msrA) promoter and calcium phospholipid binding protein (CPBP) enhances msrA transcription and expression. The msrA promoter-CPBP-binding complex (PmsrA-CPBP) formation was similar in Delta trx1, Delta trx2, and Delta trx3 yeast strains and their control, with or without exposure to H2O2. In Delta trx1/Delta trx2 double mutant the PmsrA-CPBP was similar to its parent strain, following exposure to H2O2 for 30 min. However, a late-onset loss of Pmst-A-CPBP binding activity occurred following exposure to H2O2 for 24 hours. Hence, it was inferred that both Trx1 and Trx2 are involved in the PmsrA-CPBP formation during prolonged oxidative stress conditions. In addition, the survival rate of the Delta trx1 Delta/trx2 double mutant was similar to 10% of its parent strain when exposed to H2O2. The MsrA activity was obliterated in Delta trx1/Delta trx2 and Delta trx1 strains and remained intact in the Delta trx2 and Delta trx3 strains. The msrA mRNA level in Delta trx1 was significantly reduced in comparison to that of its control, slightly reduced in Delta trx2, and unchanged in Delta trx3, respectively. It is suggested that under normal growth conditions Trx1 is essential for msrA transcription and activity. Moreover, following long-term oxidative stress conditions, Trx1 and Trx2 appear to promote PmsrA-CPBP-binding activity and cell survival. Published by Elsevier Inc. C1 Univ Kansas, Dept Pharmacol & Toxicol, Sch Pharm, Lawrence, KS 66045 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Univ Kansas, Dept Pharmacol & Toxicol, Sch Pharm, Lawrence, KS 66045 USA. EM moskovij@ku.edu FU Intramural NIH HHS NR 30 TC 8 Z9 8 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD APR 15 PY 2006 VL 40 IS 8 BP 1391 EP 1396 DI 10.1016/j.freeradbiomed.2005.12.017 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 032IX UT WOS:000236769200012 PM 16631529 ER PT J AU Drel, VR Pacher, P Stevens, MJ Obrosova, IG AF Drel, VR Pacher, P Stevens, MJ Obrosova, IG TI Aldose reductase inhibition counteracts nitrosative stress and poly(ADP-ribose) polymerase activation in diabetic rat kidney and high-glucose-exposed human mesangial cells SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE aldose reductase; fidarestat; oxidative-nitrosative stress; poly(ADP-ribose) polymerase; streptozotocin-diabetic rats; superoxide; free radicals ID PROTEIN-KINASE-C; ALPHA-LIPOIC ACID; GROWTH-FACTOR OVEREXPRESSION; LIPID-PEROXIDATION PRODUCTS; OXIDATIVE STRESS; POLYOL PATHWAY; ANGIOTENSIN-II; ENDOTHELIAL DYSFUNCTION; SUPEROXIDE-DISMUTASE; GLOMERULAR INJURY AB Both increased aldose reductase (AR) activity and oxidative/nitrosative stress have been implicated in the pathogenesis of diabetic nephropathy, but the relation between the two factors remains a subject of debate. This study evaluated the effects of AR inhibition on nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation in diabetic rat kidney and high-glucose-exposed human mesangial cells. In animal experiments., control (C) and streptozotocin-diabetic (D) rats were treated with/without the AR inhibitor fidarestat (F, 16 mg kg(-1) day(-1)) for 6 weeks starting from induction of diabetes. Glucose, sorbitol, and fructose concentrations were significantly increased in the renal cortex of D vs C (p < 0.01 for all three comparisons), and sorbitol pathway intermediate, but not glucose, accumulation, was completely prevented in D + F. F at least partially prevented diabetes-induced increase in kidney weight as well as nitrotyrosine (NT, a marker of peroxynitrite-induced injury and nitrosative stress), and poly(ADP-ribose) (a marker of PARP activation) accumulation, assessed by both immunohistochemistry and Western blot analysis, in glomerular and tubular compartments of the renal cortex. In vitro studies revealed the presence of both AR and PARP-1 in human mesangial cells, and none of these two variables were affected by high glucose or F treatment. Nitrosylated and poly(ADP-ribosyl)ated proteins (Western blot analysis) accumulated in cells cultured in 30 mM D-glucose (vs 5.55 mM glucose, p < 0.01), but not in cells cultured in 30 mM L-glucose or 30 mM D-glucose plus 10 mu M F. AR inhibition counteracts nitrosative stress and PARP activation in the diabetic renal cortex and high-glucose-exposed human mesangial cells. These findings reveal new beneficial properties of the AR inhibitor F and provide the rationale for detailed studies of F on diabetic nephropathy. (c) 2006 Elsevier Inc. All rights reserved. C1 Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. RP Obrosova, IG (reprint author), Louisiana State Univ, Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. EM obrosoig@pbrc.edu RI Pacher, Pal/B-6378-2008; Drel, Viktor/G-8883-2016 OI Pacher, Pal/0000-0001-7036-8108; Drel, Viktor/0000-0003-4542-0132 FU Intramural NIH HHS [Z01 AA000375-02]; NIDDK NIH HHS [1R21DK070720-01, R21 DK070720] NR 78 TC 68 Z9 80 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 2006 VL 40 IS 8 BP 1454 EP 1465 DI 10.1016/j.freeradbiomed.2005.12.034 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 032IX UT WOS:000236769200018 PM 16631535 ER PT J AU Mclaughlin, P Zhou, Y Ma, T Liu, J Zhang, W Hong, JS Kovacs, M Zhang, J AF Mclaughlin, P Zhou, Y Ma, T Liu, J Zhang, W Hong, JS Kovacs, M Zhang, J TI Proteomic analysis of microglial contribution to mouse strain-dependent dopaminergic neurotoxicity SO GLIA LA English DT Article DE SWR/J; MPTP; inflammation; microglia; proteomics; SILAC ID CELL-CULTURE SILAC; PARKINSONS-DISEASE; GENE-EXPRESSION; AMINO-ACIDS; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; SACCHAROMYCES-CEREVISIAE; QUANTITATIVE PROTEOMICS; PROSTAGLANDIN E-2; MASS-SPECTROMETRY; MAP KINASE AB Although the pathogenesis of Parkinson's disease (PD) remains unknown, it appears that microglial activation is associated with enhanced neurodegeneration in animal models of PD as well as in PD patients. Experimentally, C57BL/6 and SWR/J mice demonstrate striking differences in the extent of dopaminergic (DAergic) neurodegeneration induced by a parkinsonian toxicant 1-methyl-4-phenyl.2,3,6-tetrahydropyridine (MPTP). The purpose of this study was to determine whether differences in microglial activation between these two strains of mice could provide insight into the variability seen in toxicant induced neuronal death, and subsequently to use a high-throughput proteomic method, combining stable isotope labeling with amino acids in cell culture (SILAC) with liquid chromatography and tandem mass spectrometry, to compare the microglial proteomes of C57BL/6 and SWR/J mice after stimulation with a classical microglial activator, lipopolysaccharide (LIPS). We found that DAergic neurotoxicity induced by LPS in a primary neuron-microglia coculture was two old greater with microglia isolated from the brains of C57BL/6 mice compared with that of SWR/J mice. Upon proteomic analysis we found that, out of over 1000 proteins dentified and quantified, 400 displayed a significant difference in their relative abundance between these two murine;trains. Several proteins, which had relatively higher levels n C57BL/6 mice, have previously been implicated in LPS-mediated microglial activation, including those involved in;he COX-2 pathway and in prostaglandin E-2 (PGE(2)) production. To validate our proteomic results we confirmed the increased expression level of iNOS in C57BL/6 vs. SWR/J microglia with semiquantitative Western blot. Further analysis of our proteomic discovery data will likely reveal numerous novel proteins involved in inflammation-mediated neurotoxicity in PD. (c) 2006 Wiley-Liss, Inc. C1 Univ Washington, Sch Med, Div Neuropathol, Harborview Med Ctr,Dept Pathol, Seattle, WA 98104 USA. NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Zhang, J (reprint author), Univ Washington, Sch Med, Div Neuropathol, Harborview Med Ctr,Dept Pathol, Box 359635, Seattle, WA 98104 USA. EM zhangj@u.washington.edu FU NIEHS NIH HHS [ES-05842] NR 57 TC 44 Z9 46 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD APR 15 PY 2006 VL 53 IS 6 BP 567 EP 582 DI 10.1002/glia.20294 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 020ZL UT WOS:000235951900001 PM 16419087 ER PT J AU Lipska, BK Peters, T Hyde, TM Halim, N Horowitz, C Mitkus, S Weickert, CS Matsumoto, M Sawa, A Straub, RE Vakkalanka, R Herman, MM Weinberger, DR Kleinman, JE AF Lipska, BK Peters, T Hyde, TM Halim, N Horowitz, C Mitkus, S Weickert, CS Matsumoto, M Sawa, A Straub, RE Vakkalanka, R Herman, MM Weinberger, DR Kleinman, JE TI Expression of DISC1 binding partners is reduced in schizophrenia and associated with DISC1 SNPs SO HUMAN MOLECULAR GENETICS LA English DT Article ID BRAIN-DEVELOPMENT; NEURITE OUTGROWTH; BIPOLAR DISORDER; MESSENGER-RNA; RAT-BRAIN; DISRUPTED-IN-SCHIZOPHRENIA-1; NUDEL; GENE; TRANSLOCATION; HIPPOCAMPUS AB DISC1 has been identified as a schizophrenia susceptibility gene based on linkage and SNP association studies and clinical data suggesting that risk SNPs impact on hippocampal structure and function. In cell and animal models, C-terminus-truncated DISC1 disrupts intracellular transport, neural architecture and migration, perhaps because it fails to interact with binding partners involved in neuronal differentiation such as fasciculation and elongation protein zeta-1 (FEZ1), platelet-activating factor acetylhydrolase, isoform Ib, PAFAH1B1 or lissencephaly 1 protein (LIS1) and nuclear distribution element-like (NUDEL). We hypothesized that altered expression of DISC1 and/or its molecular partners may underlie its pathogenic role in schizophrenia and explain its genetic association. We examined the expression of DISC1 and these selected binding partners as well as reelin, a protein in a related signaling pathway, in the hippocampus and dorsolateral prefrontal cortex of postmortem human brain patients with schizophrenia and controls. We found no difference in the expression of DISC1 or reelin mRNA in schizophrenia and no association with previously identified risk DISC1 SNPs. However, the expression of NUDEL, FEZ1 and LIS1 was each significantly reduced in the brain tissue from patients with schizophrenia and expression of each showed association with high-risk DISC1 polymorphisms. Although, many other DISC1 binding partners still need to be investigated, these data implicate genetically linked abnormalities in the DISC1 molecular pathway in the pathophysiology of schizophrenia. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. Astellas Pharma Inc, Drug Discovery Res, Mol Med Res Labs, Funct Genom, Tsukuba, Ibaraki 3058585, Japan. Johns Hopkins Univ, Sch Med, Dept Psychiat Neurobiol, Baltimore, MD 21205 USA. RP Lipska, BK (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, 10 Ctr Dr,Bldg 10,Room 4N306, Bethesda, MD 20892 USA. EM lipskab@intra.nimh.nih.gov RI Shannon Weickert, Cynthia/G-3171-2011; Matsumoto, Mitsuyuki/G-3207-2012; Lipska, Barbara/E-4569-2017 OI Matsumoto, Mitsuyuki/0000-0002-1172-2354; FU Intramural NIH HHS NR 51 TC 105 Z9 112 U1 1 U2 6 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 2006 VL 15 IS 8 BP 1245 EP 1258 DI 10.1093/hmg/ddl040 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 030DK UT WOS:000236613300001 PM 16510495 ER PT J AU Zhu, PP Soderblom, C Tao-Cheng, JH Stadler, J Blackstone, C AF Zhu, PP Soderblom, C Tao-Cheng, JH Stadler, J Blackstone, C TI SPG3A protein atlastin-1 is enriched in growth cones and promotes axon elongation during neuronal development SO HUMAN MOLECULAR GENETICS LA English DT Article ID HEREDITARY SPASTIC PARAPLEGIA; CHARCOT-MARIE-TOOTH; EARLY-ONSET; HIPPOCAMPAL AXONS; MUTATIONS; GENE; DYNAMIN; DOMAIN; ASSOCIATION; FAMILIES AB The hereditary spastic paraplegias (HSPs) (SPG1-29) comprise a group of inherited neurological disorders characterized principally by spastic lower extremity weakness due to a length-dependent, retrograde axonopathy of corticospinal motor neurons. Mutations in the gene encoding the dynamin superfamily member atlastin-1, an oligomeric GTPase highly localized to the Golgi apparatus in the adult brain, are responsible for SPG3A, a common autosomal dominant HSP. A distinguishing feature of SPG3A is its frequent early onset, raising the possibility that developmental abnormalities may be involved in its pathogenesis. Here, we demonstrate that several missense SPG3A mutant atlastin-1 proteins have impaired GTPase activity and thus may act in a dominant-negative, loss-of-function manner by forming mixed oligomers with wild-type atlastin-1. Using confocal and electron microscopies, we have also found that atlastin-1 is highly enriched in vesicular structures within axonal growth cones and varicosities as well as at axonal branch points in cultured cerebral cortical neurons, prefiguring a functional role for atlastin-1 in axonal development. Indeed, knock-down of atlastin-1 expression in these neurons using small hairpin RNAs reduces the number of neuronal processes and impairs axon formation and elongation during development. Thus, the 'long axonopathy' in early-onset SPG3A may result from abnormal development of axons because of loss of atlastin-1 function. C1 NINDS, Cellular Neurol Unit, NIH, Bethesda, MD 20892 USA. NINDS, Electron Microscopy Facil, NIH, Bethesda, MD 20892 USA. RP Blackstone, C (reprint author), NINDS, Cellular Neurol Unit, NIH, Bldg 35,Room 2C-913,35 Convent Dr, Bethesda, MD 20892 USA. EM blackstc@ninds.nih.gov FU Intramural NIH HHS NR 42 TC 63 Z9 66 U1 1 U2 4 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 2006 VL 15 IS 8 BP 1343 EP 1353 DI 10.1093/hmg/ddl054 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 030DK UT WOS:000236613300010 PM 16537571 ER PT J AU Dupuy, AJ Jenkins, NA Copeland, NG AF Dupuy, AJ Jenkins, NA Copeland, NG TI Sleeping beauty: a novel cancer gene discovery tool SO HUMAN MOLECULAR GENETICS LA English DT Review ID HUMAN TUMOR-CELLS; CHROMOSOMAL TRANSPOSITION; MOUSE; MUTAGENESIS; MECHANISMS; GENOMES; TECHNOLOGIES; EXPRESSION; RESISTANCE; MUTATIONS AB The National Cancer Institute and the National Human Genome Research Institute recently announced a 3-year 100-million-dollar pilot study to use large-scale resequencing of genes in human tumors to identify new cancer genes. The hope is that some of these genes can be used as drug targets for developing better therapeutics for treating cancer. Although this effort will identify new cancer genes, it could be made more efficient by preferentially resequencing genes identified as novel candidate cancer genes in animal models of cancer. Although retroviral insertional mutagenesis has proven to be an effective tool for identifying novel cancer genes in the mouse, these studies are limited by the fact that retroviral mutagenesis primarily induces hematopoietic and mammary cancer, but little else, while the majority of cancers affecting humans are solid tumors. Recently, two groups have shown that sleeping beauty (SB) transposon-based insertional mutagenesis can also identify novel candidate cancer genes in the mouse. Unlike retroviral infection, SB transposition can be controlled to mutagenize any target tissue and thus potentially induce many different kinds of cancer, including solid tumors. SB transposition in animal models of cancer could therefore greatly facilitate the identification of novel human cancer genes and the development of better cancer therapies. C1 Natl Canc Inst, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Copeland, NG (reprint author), Natl Canc Inst, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. EM copeland@ncifcrf.gov FU Intramural NIH HHS NR 37 TC 30 Z9 32 U1 0 U2 4 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 2006 VL 15 SI 1 BP R75 EP R79 DI 10.1093/hmg/ddl061 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 039QE UT WOS:000237320500009 PM 16651372 ER PT J AU Temple, G Lamesch, P Milstein, S Hill, DE Wagner, L Moore, T Vidal, M AF Temple, G Lamesch, P Milstein, S Hill, DE Wagner, L Moore, T Vidal, M TI From genome to proteome: developing expression clone resources for the human genome SO HUMAN MOLECULAR GENETICS LA English DT Review ID SITE-SPECIFIC RECOMBINATION; LENGTH CDNA LIBRARIES; OLIGO-CAPPING METHOD; MESSENGER-RNA; INTERACTION NETWORK; FUNCTIONAL PROTEOMICS; RAPID CONSTRUCTION; ISOFORM DIVERSITY; GENETIC SYSTEM; LARGE NUMBERS AB cDNA clones have long been valuable reagents for studying the structure and function of proteins. With recent access to the entire human genome sequence, it has become possible and highly productive to compare the sequences of mRNAs to their genes, in order to validate the sequences and protein-coding annotations of each (1,2). Thus, well-characterized collections of human cDNAs are now playing an essential role in defining the structure and function of human genes and proteins. In this review, we will summarize the major collections of human cDNA clones, discuss some limitations common to most of these collections and describe several noteworthy proteomics applications, focusing on the detection and analysis of protein-protein interactions (PPI). These human cDNA collections contain principally two types of cDNA clones. The largest collections comprise cDNAs with full-length protein coding sequences (FL-CDS). Some but not all of these cDNA clones may represent the entire mRNA sequence, but many are missing considerable non-coding UTR sequence, usually at the 5' end. A second type of cDNA clone, a 'full-ORF' (F-ORF) expression clone, is one where the annotated protein-coding sequence, excised of 5' UTR and 3' UTR sequence, has been transferred to a vector designed to facilitate transfer to other vectors for protein expression. C1 NHGRI, Mammalian Gene Collect, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CCSB, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Fac Univ Notre Dame Paix, Unite Rech & Biol Mol, B-5000 Namur, Belgium. Open Biosyst, Huntsville, AL 35806 USA. RP Temple, G (reprint author), NHGRI, Mammalian Gene Collect, NIH, Bethesda, MD 20892 USA. EM gtemple@mail.nih.gov RI Hill, David/B-6617-2011 NR 89 TC 22 Z9 24 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 15 PY 2006 VL 15 SI 1 BP R31 EP R43 DI 10.1093/hmg/ddl048 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 039QE UT WOS:000237320500004 PM 16651367 ER PT J AU Yang, XQ Lu, PR Fujii, C Nakamoto, Y Gao, JL Kaneko, S Murphy, PM Mukaida, N AF Yang, XQ Lu, PR Fujii, C Nakamoto, Y Gao, JL Kaneko, S Murphy, PM Mukaida, N TI Essential contribution of a chemokine, CCL3, and its receptor, CCR1, to hepatocellular carcinoma progression SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE angiogenesis; chemokine; carcinogenesis; Kupffer cell; matrix metalloproteinase ID HEPATITIS-B VIRUS; ENDOTHELIAL GROWTH-FACTOR; GENE-EXPRESSION; LIVER CARCINOGENESIS; PROGENITOR CELLS; MICE; ANGIOGENESIS; HEPATOCARCINOGENESIS; DIETHYLNITROSAMINE; INFLAMMATION AB We previously observed that a chemokine, macrophage inflammatory protein-1 alpha/CCL3, and its receptor, CCR1, were aberrantly expressed in human hepatocellular carcinoma (HCC) tissues. Here, we show that CCL3 and CCR1 are also expressed in 2 different models of this cancer; N-nitrosodiethylamine (DEN)-induced HCC and HCC induced by hepatitis B virus surface (HBs) antigen-primed splenocyte transfer to myelo-ablated syngeneic HBs antigen transgenic mice. At 10 months after DEN treatment, foci number and sizes were remarkably reduced in CCR1- and CCL3-deficient mice, compared with those or wild-type (WT) mice, although tumor incidence were marginally, but significantly, higher in CCR1- and CCL3-deficient mice than in WT mice. Of note is that tumor angiogenesis was also markedly diminished in CCL3- and CCR1-deficient mice, with a concomitant reduction in the number of intratumoral Kupffer cells, a rich source of growth factors and matrix metalloproteinases (MMPs). Among growth factors and MMPs that we examined, only MMP9 and MMP13 gene expression was augmented progressively in liver of WT mice after DEN treatment. Moreover, MMP9, but not MMP13, gene expression was attenuated in CCR1- and CCL3-deficient mice, compared with that of WT mice. Furthermore, MMP9 was expressed mainly by mononuclear cells but not hepatoma cells, and MMP9-expressing cell numbers were decreased in CCR1- or CCL3-deficient mice, compared with WT mice. These observations suggest the contribution of the CCR1-CCL3 axis to HCC progression. (c) 2005 Wiley-Liss, Inc. C1 Kanazawa Univ, Div Mol Bioregulat, Canc Res Inst, Kanazawa, Ishikawa 9200934, Japan. Kanazawa Univ, Canc Res Inst, Ctr Dev Mol Target Drugs, Kanazawa, Ishikawa 920, Japan. Kanazawa Univ, Grad Sch Med, Dept Gastroenterol, Kanazawa, Ishikawa 920, Japan. NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Mukaida, N (reprint author), Kanazawa Univ, Div Mol Bioregulat, Canc Res Inst, 13-1 Takara Machi, Kanazawa, Ishikawa 9200934, Japan. EM naofumim@kenroku.kanazawa-u.ac.jp RI Mukaida, Naofumi/D-7623-2011 OI Mukaida, Naofumi/0000-0002-4193-1851 NR 44 TC 55 Z9 63 U1 1 U2 7 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 2006 VL 118 IS 8 BP 1869 EP 1876 DI 10.1002/ijc.21596 PG 8 WC Oncology SC Oncology GA 027ES UT WOS:000236397200003 PM 16284949 ER PT J AU Villanueva, CM Cantor, KP King, WD Jaakkola, JJK Cordier, S Lynch, CF Porru, S Kogevinas, M AF Villanueva, CM Cantor, KP King, WD Jaakkola, JJK Cordier, S Lynch, CF Porru, S Kogevinas, M TI Total and specific fluid consumption as determinants of bladder cancer risk SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE bladder cancer; fluid consumption; tap water; pooled analysis; case-control study ID DISINFECTION BY-PRODUCTS; LOWER URINARY-TRACT; DRINKING-WATER SOURCE; ALCOHOL-DRINKING; POOLED ANALYSIS; LIFE-STYLE; COFFEE; EXPOSURE; MEN; TRIHALOMETHANES AB We pooled the data from 6 case-control studies of bladder cancer with detailed information on fluid intake and water pollutants, particularly trihalomethanes (THM), and evaluated the bladder cancer risk associated with total and specific fluid consumption. The analysis included 2,729 cases and 5,150 controls. Odds ratios (OR) and 95% confidence intervals (CI) for fluid consumption were adjusted for age, gender, study, smoking status, occupation and education. Total fluid intake was associated with an increased risk of bladder cancer in men. The adjusted OR for 1 1/day increase in intake was 1.08, (95% CI 1.03-1.14, p-value for linear trend < 0.001), while no trend was observed in women (OR = 1.04, 0.94-1.15; p-value = 0.7). OR was 1.33 (1.12-1.58) for men in the highest category of intake (> 3.5 1/day) as compared to those in the lowest (<= 2 1/day). An increased risk was associated with intake of tap water. OR for > 2 1/day vs. < 0.5 1/day was 1.46 (1.20-1.78), with a higher risk among men (OR = 1.50, 1.21-1.88). No increased risk was observed for the same intake groups of nontap water in men (OR = 0.97, 0.77-1.22) or in women (OR = 0.85, 0.50-1.42). Increased bladder cancer risks were observed for an intake of > 5 cups of coffee daily vs. < 5 and for THM exposure, but neither exposure confounded or modified the OR for tap water intake. The association of bladder cancer with tap water consumption, but not with nontap water fluids, suggests that carcinogenic chemicals in tap water may explain the increased risk. (c) 2005 Wiley-Liss, Inc. C1 IMIM, Resp & Environm Hlth Res Unit, Barcelona 08003, Spain. NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Bethesda, MD USA. Queens Univ, Dept Community Hlth, Kingston, ON K7L 3N6, Canada. Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. Univ Birmingham, Inst Occupat & Environm Med, Birmingham, W Midlands, England. Univ Rennes 1, INSERM, U625, Rennes, France. Univ Iowa, Dept Epidemiol, Iowa City, IA USA. Univ Brescia, Inst Occupat Hlth, Brescia, Italy. RP Villanueva, CM (reprint author), IMIM, Resp & Environm Hlth Res Unit, Doctor Aiguader 80, Barcelona 08003, Spain. EM cvillanueva@imim.es RI Jaakkola, Jouni/G-4314-2012; Villanueva, Cristina/N-1942-2014; Cordier, Sylvaine/F-7919-2013; Kogevinas, Manolis/C-3918-2017 OI Villanueva, Cristina/0000-0002-0783-1259; NR 43 TC 53 Z9 56 U1 1 U2 10 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 2006 VL 118 IS 8 BP 2040 EP 2047 DI 10.1002/ijc.21587 PG 8 WC Oncology SC Oncology GA 027ES UT WOS:000236397200028 PM 16284957 ER PT J AU Spacek, LA Shihab, HM Lutwama, F Summerton, J Mayanja, H Ronald, A Margolick, JB Nilles, TL Quinn, TC AF Spacek, LA Shihab, HM Lutwama, F Summerton, J Mayanja, H Ronald, A Margolick, JB Nilles, TL Quinn, TC TI Evaluation of a low-cost method, the guava EasyCD4 assay, to enumerate CD4-positive lymphocyte counts in HIV-Infected patients in the United States and Uganda SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE CD4-positive lymphocyte counts; monitoring and evaluation; antiretroviral therapy resource-limited setting; Uganda ID T-CELL QUANTITATION; FLOW-CYTOMETRY; MANUAL METHOD; CD4(+); IMPLEMENTATION AB Objective: To evaluate the EasyCD4 assay, a less expensive method to enumerate CD4(+) lymphocytes, in resource-limited settings. Design: Cross-sectional study conducted in the United States and Uganda. Methods: We compared CD4(+) cell counts obtained on replicate samples from HIV-infected patients by the EasyCD4 assay, a microcapillary flow-based system, and by standard flow cytometry or FACSCount with linear regression and the Bland-Altman method. Results: Two hundred eighteen samples were analyzed (77 in the United States and 141 in Uganda). In the United States, mean +/- SD CD4 was 697 +/- 438 cells/mu L by standard flow cytometry and 688 +/- 451 cells/mu L by EasyCD4. In Uganda, the mean +/- SD CD4 was 335 +/- 331 cells/mu L by FACSCOUnt and 340 +/- 327 cells/mu L by EasyCD4. The 2 methods were highly correlated (US cohort, r(2) = 0.97, slope = 1.0, intercept = - 18; Ugandan cohort, r(2) = 0.92; slope = 0.95; intercept = 23). The mean differences ill CD4 cell counts were 9.0 and -4.6 cells/mu L for the US and Ugandan cohorts, respectively, and they were not significant ill either cohort. In the Ugandan cohort, sensitivity and specificity of the EasyCD4 for CD4 below 200 cells/ mu L were 90% and 98%, respectively. Positive predictive value was 96% negative predictive value was 93%. Conclusions: Our results Suggest that EasyCD4 may be used with high positive and negative predictive value in resource-limited settings. C1 Johns Hopkins Med Inst, Baltimore, MD USA. Makerere Univ, Kampala, Uganda. Univ Manitoba, Winnipeg, MB R3T 2N2, Canada. Natl Inst Hlth, Natl Inst Allergy & Infect Dis, Bethesda, MD USA. RP Spacek, LA (reprint author), Johns Hopkins Sch Med, Room 456,1830 E Monument St, Baltimore, MD 21287 USA. EM lspacek@jhmi.edu OI Ronald, Allan/0000-0002-5746-3490 FU NIAID NIH HHS [K23 AI 060384-01] NR 15 TC 24 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 15 PY 2006 VL 41 IS 5 BP 607 EP 610 DI 10.1097/01.qai.0000214807.98465.a2 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 032AZ UT WOS:000236747600009 PM 16652034 ER PT J AU Rosenberg, SA Restifo, NP AF Rosenberg, SA Restifo, NP TI Response to comment on "Tumor' progression can occur despite the induction of very high levels of self/tumor antigen-specific CD8(+) T cells in patients with melanoma" SO JOURNAL OF IMMUNOLOGY LA English DT Letter ID AUTOIMMUNITY; REGRESSION C1 NCI, Clin Res Ctr, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Clin Res Ctr, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008 NR 8 TC 0 Z9 0 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 2006 VL 176 IS 8 BP 4511 EP 4512 PG 2 WC Immunology SC Immunology GA 059YV UT WOS:000238769000002 ER PT J AU Wald, O Weiss, ID Wald, H Shoham, H Bar-Shavit, Y Beider, K Galun, E Weiss, L Flaishon, L Shachar, I Nagler, A Lu, B Gerard, C Gao, JL Mishani, E Farber, J Peled, A AF Wald, O Weiss, ID Wald, H Shoham, H Bar-Shavit, Y Beider, K Galun, E Weiss, L Flaishon, L Shachar, I Nagler, A Lu, B Gerard, C Gao, JL Mishani, E Farber, J Peled, A TI IFN-gamma acts on T cells to induce NK cell mobilization and accumulation in target organs SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; INTERFERON-GAMMA; BONE-MARROW; IN-VIVO; INTERLEUKIN-12; CHEMOKINES; HEPATITIS; TUMOR; LIVER; MICE AB The mechanism(s) that regulates NK cell mobilization and the significance of this process to NK cell activity are unknown. After Con A-induced hepatitis, NK cells are mobilized from the spleen and bone marrow into the periphery in an IFN-gamma-dependent fashion. Intraperitoneal administration of IFN-gamma stimulates the mobilization of NK cells into the circulation, but not their cell death or proliferation. Increased number of circulating NK cells was coupled with their accumulation in the peritoneum, liver, and tumor-bearing lung tissue. Furthermore, increased number of NK cells in the lung reduced metastasis of Lewis lung carcinoma cells (3LL cell line) resulting in significantly extended NK-dependent survival. Mobilization of NK cells was specific and required the presence of T cells. Moreover, mobilization and migration of spleen NK cells in response to IFN-gamma treatment is dependent on the chemokine receptor CXCR3. Mechanistic insights regarding the role of IFN-gamma in the regulation of NK cell mobilization and their accumulation at sites of tumor metastasis may lead to the development of novel immunotherapy for cancer. C1 Hadassah Univ Hosp, Goldyne Savad Inst Gene Therapy, IL-91120 Jerusalem, Israel. Hadassah Univ Hosp, Dept Bone Marrow Transplant, IL-91120 Jerusalem, Israel. Weizmann Inst Sci, IL-76100 Rehovot, Israel. Chaim Sheba Med Ctr, Bone Marrow Transplantat Dept, IL-52621 Tel Hashomer, Israel. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, Dept Med Biophys & Nucl Med, Cyclotoron Radiovhem Unit, IL-91120 Jerusalem, Israel. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Peled, A (reprint author), Hadassah Univ Hosp, Goldyne Savad Inst Gene Therapy, POB 12000, IL-91120 Jerusalem, Israel. EM peled@hadassah.org.il NR 38 TC 63 Z9 63 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2006 VL 176 IS 8 BP 4716 EP 4729 PG 14 WC Immunology SC Immunology GA 059YV UT WOS:000238769000031 PM 16585565 ER PT J AU Schito, ML Demidov, ON Saito, S Ashwell, JD Appella, E AF Schito, ML Demidov, ON Saito, S Ashwell, JD Appella, E TI Wip1 phosphatase-deficient mice exhibit defective T cell maturation due to sustained p53 activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR-BETA-CHAIN; KINASE SIGNALING PATHWAYS; THYMOCYTE DEVELOPMENT; IMMATURE THYMOCYTES; GENE REARRANGEMENT; MOUSE THYMOCYTES; DOWN-REGULATION; PRE-TCR; IN-VIVO; CATENIN AB The PP2C phosphatase Wip1 dephosphorylates p38 and blocks UV-induced p53 activation in cultured human cells. Although the level of TCR-induced p38 MAPK activity is initially comparable between Wip1(-/-) and wild-type thymocytes, phosphatase-deficient cells failed to down-regulate p38 MAPK activity after 6 h. Analysis of young Wip1-deficient mice,showed that they had fewer splenic T cells. Their thymi were smaller, contained significantly fewer cells, and failed to undergo age-dependent involution compared with wild-type animals. Analysis of thymocyte subset numbers by flow cytometry suggested that cell numbers starting at the double-negative (DN)4 stage are significantly reduced in Wip1-deficient mice, and p53 activity is elevated in cell-sorted DN4 and double-positive subpopulations. Although apoptosis and proliferation was normal in Wip1(-/-) DN4 cells, they appeared to be in cell cycle arrest. In contrast, a significantly higher percentage of apoptotic cells were found in the double-positive population, and down-regulation of thymocyte p38 MAPK activation by anti-CD3 was delayed. To examine the role of p38 MAPK in early thymic subpopulations, fetal thymic organ cultures cultured in the presence/absence of a p38 MAPK inhibitor did not correct the thymic phenotype. In contrast, the abnormal thymic phenotype of Wip1-deficient mice was reversed in the absence of p53. These data suggest that Wip1 down-regulates p53 activation in the thymus and is required for normal alpha beta T cell development. C1 NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. NCI, NIH, Lab Immune Cell Biol, Bethesda, MD 20892 USA. RP Schito, ML (reprint author), NCI, NIH, Cell Biol Lab, Bldg 37,Room 2140, Bethesda, MD 20892 USA. EM schitom@mail.nih.gov OI Demidov, Oleg/0000-0003-4323-7174 FU Intramural NIH HHS NR 41 TC 26 Z9 27 U1 1 U2 3 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 2006 VL 176 IS 8 BP 4818 EP 4825 PG 8 WC Immunology SC Immunology GA 059YV UT WOS:000238769000042 PM 16585576 ER PT J AU Pedras-Vasconcelos, JA Goucher, D Puig, M Tonelli, LH Wang, V Ito, S Verthelyi, D AF Pedras-Vasconcelos, JA Goucher, D Puig, M Tonelli, LH Wang, V Ito, S Verthelyi, D TI CpG oligodeoxynucleotides protect newborn mice from a lethal challenge with the neurotropic Tacaribe arenavirus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; LISTERIA-MONOCYTOGENES; VIRUS-INFECTION; CELL RESPONSES; BACTERIAL-DNA; INNATE IMMUNITY; GENITAL HERPES; NEONATAL MICE; LASSA-VIRUS; IFN-GAMMA AB The innate immune system is key to limiting the early spread of most pathogens and directing the development of Ag-specific immunity. Recently, a number of synthetic molecules that activate the innate immune system by stimulating TLRs have been identified. Among them, synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs (CpG ODNs) were shown to activate TLR9-bearing B cells, macrophages, and dendritic cells to induce a strong proinfiammatory milieu and a type 1-biased immune response that protects mice from a variety of parasitic, bacterial, and viral infections. Although the protective effect of CpG ODN in adult mice was well established, its effectiveness in neonates, which have lower numbers of dendritic, 13, and T cells and tend to favor Th2 responses, was unclear. This study uses the New World arenavirus Tacaribe, a neurotropic pathogen that is lethal in newborn mice, to explore the effectiveness of TLR-mediated innate immune responses. Neonatal BALB/c mice treated with CpG ODN at the time of infection had reduced viral load (p < 0.01) and increased survival (52 %, p < 0.001 i.p.; 36 %, p < 0.05 intranasally). Protection was achieved in mice treated no later than 3 days postchallenge and appears to be mediated by an increase in Ag-specific Abs (IgG and IgM) and. to require inducible NO synthase expression and NO production. To our knowledge, this is the first study assessing the mechanisms by which CpG ODN can protect mice from a neurotropic viral infection. C1 US FDA, Ctr Biol Evaluat & Res, Off Biotechnol Prod, Div Therapeut Prot, Bethesda, MD 20892 USA. NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div viral Prod, Rockville, MD 20852 USA. RP Verthelyi, D (reprint author), Bldg 29A,Room 3B19,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Verthelyi@cber.fda.gov NR 59 TC 36 Z9 40 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2006 VL 176 IS 8 BP 4940 EP 4949 PG 10 WC Immunology SC Immunology GA 059YV UT WOS:000238769000056 PM 16585590 ER PT J AU Brown, EE Fallin, MD Goedert, JJ Hutchinson, A Vitale, F Lauria, C Giuliani, M Marshall, V Mbisa, G Serraino, D Messina, A Durum, S Whitby, D Chanock, SJ AF Brown, EE Fallin, MD Goedert, JJ Hutchinson, A Vitale, F Lauria, C Giuliani, M Marshall, V Mbisa, G Serraino, D Messina, A Durum, S Whitby, D Chanock, SJ CA Kaposi Sarcoma Genetics Working TI Host immunogenetics and control of human herpesvirus-8 infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; PROTEIN-COUPLED RECEPTOR; PRIMARY EFFUSION LYMPHOMA; NECROSIS-FACTOR-ALPHA; KAPOSIS-SARCOMA; PROMOTER POLYMORPHISM; B-CELLS; HAPLOTYPE RECONSTRUCTION; INFLAMMATORY CYTOKINES; PERIPHERAL-BLOOD AB Background. Kaposi sarcoma (KS) is primarily caused by human herpesvirus (HHV)-8 infection, and the risk is increased with high HHV-8 lytic or latent antibody titers or the detection of HHV-8 DNA in peripheral blood mononuclear cells (PBMCs). Host genes important for control of HHV-8 infection are not well characterized. Methods. In 172 HHV-8 latent nuclear antigen ( LANA)-seropositive adults in Italy without KS, we examined correlations of common variants in host immune genes with the detection of HHV-8 DNA in PBMCs and with high lytic and latent antibody titers. Twenty-eight single-nucleotide polymorphisms in 14 genes were analyzed. We detected HHV-8 DNA in PBMCs with real-time amplification of the K6 gene, anti-K8.1 ( lytic) titers with enzyme-linked immunosorbent assay, and anti-LANA ( latent) titers with immunofluorescence. Results. Detection of HHV-8 DNA in PBMCs was not significantly related to any variant examined. In contrast, a 3-locus haplotype of IL4, which contains the -1098G allele ( rs2243248), was overrepresented among subjects with high lytic titers ( odds ratio [ OR], 2.8 [ 95% confidence interval {CI}, 1.1-6.7]), compared with those with low titers, as was the functional promoter variant of IL6, C-236C ( rs1800795) ( OR, 3.7 [ 95% CI, 1.1-12.8]). Compared with subjects with low HHV-8 latent antibody titers, analysis of inferred haplotypes for IL12A revealed an overrepresentation of -798T/277A in subjects with high HHV-8 latent antibody titers ( OR, 2.4 [ 95% CI, 1.1-5.2]). Conclusions. Our observations are the first to provide preliminary evidence suggesting that common variants in key host immune genes could influence the control of HHV-8 infection. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. NCI, Pediat Oncol Branch, Canc Res Ctr, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. NCI, SAIC Frederick Inc, Core Genotyping Facil, Ctr Adv Technol, Gaithersburg, MD USA. NCI, Mol Immunoregulat Lab, Frederick, MD 21701 USA. NCI, SAIC Frederick, Viral Epidemiol Sect, AIDS Vaccine Program, Frederick, MD 21701 USA. Univ Palermo, Dipartimento Igiene & Microbiol Giuseppe Alessand, Palermo, Italy. Lega Italiana Lotta Contro & Tumori, Sez Ragusa, Ragusa, Italy. Ist Super Sanita, Reparto Epidemiol, Dipartimento Malattie Infett Parassitarie & Immun, I-00161 Rome, Italy. Natl Canc Inst, Epidemiol Unit, Aviano, Italy. Univ Catania, Dipartimento Sci Biomed, I-95124 Catania, Italy. RP Brown, EE (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8005 MSC 7248, Rockville, MD 20852 USA. EM brownbe@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N02-CP-91027, N01-CO-12400] NR 63 TC 17 Z9 18 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2006 VL 193 IS 8 BP 1054 EP 1062 DI 10.1086/501470 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 023CF UT WOS:000236102200002 PM 16544245 ER PT J AU Ramirez, BL Howard, OMZ Dong, HF Edamatsu, T Gao, P Hartlein, M Kron, M AF Ramirez, BL Howard, OMZ Dong, HF Edamatsu, T Gao, P Hartlein, M Kron, M TI Brugia malayi asparaginyl-transfer RNA synthetase induces chemotaxis of human leukocytes and activates G-protein-coupled receptors CXCR1 and CXCR2 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POTENTIALLY PROTECTIVE ANTIGEN; IMMATURE DENDRITIC CELLS; LYMPHATIC FILARIASIS; INTERFERON-GAMMA; T-LYMPHOCYTES; CUTTING EDGE; MAST-CELLS; MICE; INFECTIONS; EXPRESSION AB Background. Lymphatic filariasis is a chronic human parasitic disease in which the parasites repeatedly provoke acute and chronic inflammatory reactions in the host bloodstream and lymphatics. Excretory-secretory products derived from filariae are believed to play an important role in the development of associated immunologic conditions; however, the specific mechanisms involved in these changes are not well understood. Recently, human cytoplasmic aminoacyl-transfer (t) RNA synthetases, which are autoantigens in idiopathic inflammatory myopathies, were shown to activate chemokine receptors on T lymphocytes, monocytes, and immature dendritic cells by recruiting immune cells that could induce innate and adaptive immune responses. Filarial ( Brugia malayi) asparaginyl-tRNA synthetase ( AsnRS) is known to be an immunodominant antigen that induces strong human immunoglobulin G3 responses. Methods. Recombinant B. malayi AsnRS was used to perform cellular function assays-for example, chemotaxis and kinase activation assays. Results. Unlike human AsnRS, parasite AsnRS is chemotactic for neutrophils and eosinophils. Recombinant B. malayi AsnRS but not recombinant human AsnRS induced chemotaxis of CXCR1 and CXCR2 single-receptor transfected HEK-293 cell lines, blocked CXCL1-induced calcium flux, and induced mitogen-activated protein kinase. Conclusions. Our findings suggest that a filarial parasite chemoattractant protein may contribute to the development of chronic inflammatory disease and that chemokine receptors may be therapeutic targets to ameliorate parasite-induced pathology. C1 Univ Philippines, Coll Med, Dept Biochem & Mol Biol, Manila, Philippines. NCI, Canc Res Ctr, Mol Immunoregulat Lab, Frederick, MD 21701 USA. NCI, Sci Applicat Int Corp, Frederick Basic Res Program, Frederick, MD 21701 USA. Inst Max Von Laue Paul Langevin, Grenoble, France. Med Coll Wisconsin, Dept Med, Biotechnol & Bioengn Ctr, Milwaukee, WI 53226 USA. RP Howard, OMZ (reprint author), POB B,1050 Boyles St, Frederick, MD 21702 USA. EM howardz@ncifcrf.gov RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 FU FIC NIH HHS [TW-06625]; NCI NIH HHS [CO-12400]; NIAID NIH HHS [AI-53877] NR 35 TC 16 Z9 16 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2006 VL 193 IS 8 BP 1164 EP 1171 DI 10.1086/501369 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 023CF UT WOS:000236102200015 PM 16544258 ER PT J AU Lempicki, RA Polis, MA Yang, J McLaughlin, M Koratich, C Huang, DW Fullmer, B Wu, L Rehm, CA Masur, H Lane, HC Sherman, KE Fauci, AS Kottilil, S AF Lempicki, RA Polis, MA Yang, J McLaughlin, M Koratich, C Huang, DW Fullmer, B Wu, L Rehm, CA Masur, H Lane, HC Sherman, KE Fauci, AS Kottilil, S TI Gene expression profiles in hepatitis C virus (HCV) and HIV coinfection: Class prediction analyses before treatment predict the outcome of anti-HCV therapy among HIV-coinfected persons SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ALPHA-2A PLUS RIBAVIRIN; INFECTED PATIENTS; LYMPHOCYTE-ACTIVATION; IMMUNODEFICIENCY; DISEASES; DISTINCT AB Therapy for hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients results in modest cure rates. Gene expression patterns in peripheral blood mononuclear cells from 29 patients coinfected with HIV and HCV were used to predict virological response to therapy for HCV infection. Prediction analysis using pretherapy samples identified 79 genes that correctly classified all 10 patients who did not respond to therapy, 8 of 10 patients with a response at the end of treatment, and 7 of 9 patients with sustained virological response (86% overall). Analysis of 17 posttreatment samples identified 105 genes that correctly classified all 9 patients with response at the end of treatment and 7 of 8 patients with sustained virological response (94% overall). Failure of anti-HCV therapy was associated with elevated expression of interferon-stimulated genes. Gene expression patterns may provide a tool to predict anti-HCV therapeutic response. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Program, SAIC Frederick Inc, NIH, Frederick, MD 21701 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. Univ Cincinnati, Cincinnati, OH USA. RP Kottilil, S (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Rm 11N204,900 Rockville Pike, Bethesda, MD 20892 USA. EM skottilil@niaid.nih.gov RI Lempicki, Richard/E-1844-2012; OI Lempicki, Richard/0000-0002-7059-409X; Polis, Michael/0000-0002-9151-2268 FU NCI NIH HHS [CO-12400] NR 15 TC 53 Z9 54 U1 0 U2 1 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 2006 VL 193 IS 8 BP 1172 EP 1177 DI 10.1086/501365 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 023CF UT WOS:000236102200016 PM 16544259 ER PT J AU Faulhaber-Walter, R Mizel, D Briggs, JP Schnermann, JB AF Faulhaber-Walter, R Mizel, D Briggs, JP Schnermann, JB TI GFR measurements in conscious mice with single bolus FITC-inulin and minimized plasma volume sampling SO MEDIZINISCHE KLINIK LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0723-5003 J9 MED KLIN JI Med. Klin. PD APR 15 PY 2006 VL 101 IS 4 BP A102 EP A102 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 042WT UT WOS:000237562000328 ER PT J AU Berl, MM Vaidya, CJ Gaillard, WD AF Berl, MM Vaidya, CJ Gaillard, WD TI Functional imaging of developmental and adaptive changes in neurocognition SO NEUROIMAGE LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the International-Neuropsychological-Society CY FEB 04-07, 2004 CL St Louis, MO SP Int Neuropsychol Soc DE development; fMRI; pediatric; cognition; language ID TEMPORAL-LOBE EPILEPSY; DEFICIT HYPERACTIVITY DISORDER; CEREBRAL-BLOOD-FLOW; RIGHT-HEMISPHERIC ORGANIZATION; VISUOSPATIAL WORKING-MEMORY; MAGNETIC-RESONANCE IMAGES; COMMON STEREOTACTIC SPACE; LANGUAGE DOMINANCE; BRAIN ACTIVATION; SENTENCE COMPREHENSION AB Characterization of brain-behavior relationships through functional magnetic imaging (fMRI) within typically or atypically developing populations poses methodological and interpretational challenges. We consider theoretical, methodological, and artifactual factors that influence characterization of developmental and adaptive changes in childhood. Findings from anatomical and physiological brain development studies are highlighted as they may influence functional imaging results. Then, we consider several patterns of functional activation within the context of developmental processes as well as neurologic disease. Hypotheses regarding the development of cognitive networks are proposed to account for the individual differences seen in normal and atypical development. We also identify potential sources of unwanted variability related to experimental design and task performance and suggest possible solutions to help minimize these effects. Lastly, a challenge for current studies is a lack of group and individual analysis methods that can be reliably applied to capture and quantify factors that contribute to variability introduced by developmental and disease processes. We review current methods and propose potential solutions. (c) 2005 Elsevier Inc. All rights reserved. C1 George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Neurosci, Washington, DC 20037 USA. Georgetown Univ, Dept Psychol, Washington, DC 20057 USA. NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. RP Berl, MM (reprint author), George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Neurosci, Washington, DC 20037 USA. EM mberl@cnmc.org FU NICHD NIH HHS [P30HD40677]; NIMH NIH HHS [R01 MH65395]; NINDS NIH HHS [R01 NS44280] NR 122 TC 44 Z9 45 U1 5 U2 9 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 2006 VL 30 IS 3 BP 679 EP 691 DI 10.1016/j.neuroimage.2005.10.007 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 033ZY UT WOS:000236894800001 PM 16332444 ER PT J AU Liu, H Rainey, C Lauer, KK Piacentine, L Bloom, A Risinger, R Ward, BD Stein, E Li, SJ AF Liu, H Rainey, C Lauer, KK Piacentine, L Bloom, A Risinger, R Ward, BD Stein, E Li, SJ TI Peripheral blood pressure changes induced by dobutamine do not alter BOLD signals in the human brain SO NEUROIMAGE LA English DT Article DE fMRI; dobutamine; cocaine; brain; BOLD; blood pressure ID PREFRONTAL CORTICAL PROJECTIONS; MAGNETIC-RESONANCE; FUNCTIONAL MRI; RAT-BRAIN; BETA-2-ADRENERGIC RECEPTORS; PHARMACOLOGICAL MRI; CINGULATE CORTEX; MACAQUE MONKEYS; RHESUS-MONKEY; ACTIVATION AB In extending the use of functional MRI to neuropharmacology, a primary area of concern is that peripheral blood pressure changes induced by pharmacological agents could independently produce a change in the blood oxygenation level-dependent (BOLD) signal, resulting in difficulties distinguishing or interpreting drug-induced neural activations. In the present study, we utilized intravenous dobutamine, a beta-adrenergic receptor agonist, to increase the mean arterial blood pressure (MABP), while examining the effects of MABP changes on the BOLD signal in cocaine-dependent participants. Dobutamine infusion significantly increased the MABP from 93 8 mm Hg to 106 +/- 12 mm Hg (P < 0.0005), but did not produce a significant global BOLD signal. Yet, a few voxels in the anterior cingulate showed BOLD signal changes that paralleled the changes in blood pressure (BP). Our observations support the conclusion that following the infusion of psychoactive agents, brain BOLD signals accurately reflect neuronal activity, even in the face of relatively large peripheral cardiovascular effects that transiently increase systemic BP. (c) 2005 Elsevier Inc. All rights reserved. C1 Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Psychiat, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Anesthesiol, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Pharmacol, Milwaukee, WI 53226 USA. Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Li, SJ (reprint author), Med Coll Wisconsin, Dept Biophys, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM sjli@mcw.edu FU NCRR NIH HHS [RR00058, M01 RR000058]; NIDA NIH HHS [DA10214, R01 DA010214] NR 42 TC 7 Z9 7 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 15 PY 2006 VL 30 IS 3 BP 745 EP 752 DI 10.1016/j.neuroimage.2005.10.047 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 033ZY UT WOS:000236894800008 PM 16376576 ER PT J AU Pelled, G Dodd, SJ Koretsky, AP AF Pelled, G Dodd, SJ Koretsky, AP TI Catheter confocal fluorescence imaging and functional magnetic resonance imaging of local and systems level recovery in the regenerating rodent sciatic nerve SO NEUROIMAGE LA English DT Article ID PERIPHERAL-NERVE; CRUSH INJURY; IN-VIVO; RE-INNERVATION; BRAIN DISEASE; ANIMAL-MODELS; RAT; NEURONS; MRI; STIMULATION AB The goal of the present work was to develop minimally invasive imaging techniques to monitor local regeneration of peripheral nerves and to determine the extent of return to function of brain cortical regions associated with that nerve. The sciatic nerve crush model was applied to Sprague-Dawley rats and conventional histological staining for myelin, axons and cell architecture was carried out, as well as traditional behavioral testing, to verify that nerve regeneration was occurring. The rate of sciatic nerve regeneration was measured by determining the distance a lipophilic, fluorescence probe (DiO) would move along the nerve's membrane following a direct injection into the sciatic nerve. This movement was monitored using a catheter based, confocal fluorescence microscope. Two to five days after the crush, the dyc moved 1.4 + 0.6 mm/day, as compared to a distance of 5.3 + 0.5 mm/day in the normal nerve. Between 9 and 13 days following the crush, the distance the dye moved increases to 5.5 + 0.5 mm/day, similar to the control, and by 15 days following the crush, the distance increased to 6.5 + 0.9 mm/day. Functional Magnetic Resonance Imaging (fMRI) measurements were performed on cc-chloralose anesthetized rats to monitor the return of somatosensory cortical functions, which were activated by the stimulation of the lesioned peripheral nerve. fMRI results showed the return of cortical activation around 15 days following the crush procedure. However, the somatosensory cortical region activated by stimulating the crushed hindpaw was significantly smaller in extent than the intact hindpaw stimulation. These findings demonstrate that fluorescence imaging and fMRI can integrate local and system level correlates of nerve regeneration in a non-destructive manner, thus enabling serial imaging of individual animals. Published by Elsevier Inc. C1 NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Koretsky, AP (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, B1D 728 10 Ctr Dr, Bethesda, MD 20892 USA. EM KoretskyA@ninds.nih.gov RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU Intramural NIH HHS [Z01 NS002989-08] NR 51 TC 13 Z9 15 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 2006 VL 30 IS 3 BP 847 EP 856 DI 10.1016/j.neuroimage.2005.10.027 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 033ZY UT WOS:000236894800017 PM 16343952 ER PT J AU King, JA Blair, RJR Mitchell, DGV Dolan, RJ Burgess, N AF King, JA Blair, RJR Mitchell, DGV Dolan, RJ Burgess, N TI Doing the right thing: A common neural circuit for appropriate violent or compassionate behavior SO NEUROIMAGE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; CORTICAL PROJECTIONS; FRONTAL-CORTEX; MEMORY; AMYGDALA; NETWORK; FASCICULARIS; HIPPOCAMPUS; AGGRESSION; MODULATION AB Humans have a considerable facility, to adapt their behavior in a manner that is appropriate to social or societal context. A failure of this ability can lead to social exclusion and is a feature of disorders such as psychopathy and disruptive behavior disorder. We investigated the neural basis of this ability using a customized video game played by 12 healthy participants in an fMRI scanner. Two conditions involved extreme examples of context-appropriate action: shooting an aggressive humanoid assailant or healing a passive wounded person. Two control conditions involved carefully matched stimuli paired with inappropriate actions: shooting the person or healing the assailant. surprisingly, the same circuit, including the amygdala and ventromedial prefrontal cortex, was activated when participants acted in a context-appropriate manner, whether being compassionate towards an injured conspecific or aggressive towards a violent assailant. The findings indicate a common system that guides behavioral expression appropriate to social or societal context irrespective of its aggressive or compassionate nature. (c) 2005 Elsevier Inc. All rights reserved. C1 UCL, Inst Cognit Neurosci, London WC1N 2AR, England. UCL, Dept Anat, London WC1N 2AR, England. NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. UCL, Inst Neurol, Wellcome Dept Imaging Neurosci, London WC1N 3BG, England. RP King, JA (reprint author), UCL, Inst Cognit Neurosci, 17 Queen Sq, London WC1N 2AR, England. EM John.King@ucl.ac.uk; n.burgess@ucl.ac.uk RI Burgess, Neil/B-2420-2009; king, john/G-3570-2011; OI Burgess, Neil/0000-0003-0646-6584; Dolan, Ray/0000-0001-9356-761X FU Medical Research Council [G117/433]; Wellcome Trust NR 41 TC 38 Z9 39 U1 4 U2 7 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 2006 VL 30 IS 3 BP 1069 EP 1076 DI 10.1016/j.neujroimage.2005.10.011 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 033ZY UT WOS:000236894800040 PM 16307895 ER PT J AU Yamada, H Shimoyama, N Sora, I Uhl, GR Fukuda, Y Moriya, H Shimoyama, M AF Yamada, H Shimoyama, N Sora, I Uhl, GR Fukuda, Y Moriya, H Shimoyama, M TI Morphine can produce analgesia via spinal kappa opioid receptors in the absence of mu opioid receptors SO BRAIN RESEARCH LA English DT Article DE opioid receptor; morphine; analgesia; knockout mouse; tail flick test ID KNOCKOUT MICE; INTRATHECAL MORPHINE; DELTA-AGONISTS; ANTINOCICEPTION; RAT; LACKING; WITHDRAWAL; RESPONSES; SNC80; GENE AB Previous studies have demonstrated the virtual lack of analgesia in mu opioid receptor knockout mice after systemic administration of morphine. Thus, it has been suggested that analgesic actions of morphine are produced via the mu opioid receptor, despite its ability to bind to kappa and delta receptors in vitro. However, it is not clear whether the results of these studies reflect the effect of morphine in the spinal cord. In the present study, we report study of the analgesic actions of spinally-administered morphine and other opioid receptor agonists in mu opioid receptor knockout and wild type mice. Morphine produced a dose-dependent antinociceptive effect in the tail flick test in the knockout mice, although higher doses were needed to produce antinociception than in wild type mice. The antinociceptive effect of morphine was completely blocked by naloxone (a non-selective opioid antagonist) and nor-binaltorphimine (nor-BNI, a selective kappa-opioid receptor antagonist), but not by naltrindole (a selective delta-opioid receptor antagonist). U-50,488H (a selective kappa-opioid receptor agonist) also produced a dose-dependent antinociceptive effect in knockout mice but presented lower analgesic potency in knockout mice than in wild type mice. Analgesic effects of [D-Pen2,D-Pen5]enkephalin (DPDPE, a selective delta-opioid receptor agonist) were observed in wild type mice but abolished in knockout mice. SNC80 (a selective delta-opioid receptor agonist) was not antinociceptive even in wild type mice. The present study demonstrated that morphine can produce thermal antinociception via the kappa opioid receptor in the spinal cord in the absence of the mu opioid receptor. Lower potency of U50,488H in mu opioid receptor knockout mice suggests interaction between kappa and mu opioid receptors at the spinal level. (c) 2006 Elsevier B.V. All rights reserved. C1 Chiba Univ, Grad Sch Med, Dept Automat Physiol, Chuo Ku, Chiba 2608670, Japan. Chiba Univ, Grad Sch Med, Dept Orthoped Surg, Chiba, Japan. Tohoku Univ, Grad Sch Med, Div Psychobiol, Dept Neurosci, Sendai, Miyagi, Japan. NIDA, Mol Neurobio Branch, DHSS, NIH, Bethesda, MD 20892 USA. RP Chiba Univ, Grad Sch Med, Dept Automat Physiol, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan. EM shimoyama@faculty.chiba-u.jp FU Intramural NIH HHS NR 44 TC 27 Z9 30 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD APR 14 PY 2006 VL 1083 BP 61 EP 69 DI 10.1016/j.brainres.2006.01.095 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 040JG UT WOS:000237374200007 PM 16530171 ER PT J AU McVeigh, ER AF McVeigh, ER TI Emerging imaging techniques SO CIRCULATION RESEARCH LA English DT Review DE imaging; microPET; microSPECT; near infrared imaging; quantum dots; ultrasound imaging ID POSITRON-EMISSION-TOMOGRAPHY; REPORTER GENE-EXPRESSION; FLUORESCENT QUANTUM DOTS; CORONARY-ARTERY DISEASE; IN-VIVO; INTRAVASCULAR ULTRASOUND; MICROPET-II; PINHOLE SPECT; SMALL ANIMALS; SCANNER AB This article reviews recent developments in selected imaging technologies focused on the cardiovascular system. The techniques covered are: ultrasound biomicroscopy (UBM), microSPECT, microPET, near infrared imaging, and quantum dots. For each technique, the basic physical principles are explained and recent example applications demonstrated. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP McVeigh, ER (reprint author), NIH, DHHS, 10 Ctr Dr,Bldg 10,Room B1D416, Bethesda, MD 20892 USA. EM emcveigh@nih.gov FU Intramural NIH HHS [Z01 HL004608-08] NR 61 TC 32 Z9 32 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 14 PY 2006 VL 98 IS 7 BP 879 EP 886 DI 10.1161/01.RES.0000216870.73358.d9 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 032RC UT WOS:000236791100006 PM 16614313 ER PT J AU Wihlborg, AK Balogh, J Wang, LW Borna, C Dou, Y Joshi, BV Lazarowski, E Jacobson, KA Arner, A Erlinge, D AF Wihlborg, AK Balogh, J Wang, LW Borna, C Dou, Y Joshi, BV Lazarowski, E Jacobson, KA Arner, A Erlinge, D TI Positive inotropic effects by uridine triphosphate (UTP) and uridine diphosphate (UDP) via P2Y(2) and P2Y(6) receptors on cardiomyocytes and release of UTP in man during myocardial infarction SO CIRCULATION RESEARCH LA English DT Article DE P2-receptors; inotropy; heart; UTP; UDP ID PROTEIN-COUPLED RECEPTOR; VASCULAR SMOOTH-MUSCLE; EXTRACELLULAR NUCLEOTIDES; ADENOSINE-TRIPHOSPHATE; PHOSPHOLIPASE-C; P2 RECEPTORS; TISSUE DISTRIBUTION; RAT ATRIA; ATP; HEART AB The aim of this study was to examine a possible role for extracellular pyrimidines as inotropic factors for the heart. First, nucleotide plasma levels were measured to evaluate whether UTP is released in patients with coronary heart disease. Then, inotropic effects of pyrimidines were examined in isolated mouse cardiomyocytes. Finally, expression of pyrimidine-selective receptors ( a subgroup of the P2 receptors) was studied in human and mouse heart, using real time polymerase chain reaction, Western blot, and immunohistochemistry. Venous plasma levels of UTP were increased (57%) in patients with myocardial infarction. In electrically stimulated cardiomyocytes the stable P2Y(2/4) agonist UTP gamma S increased contraction by 52%, similar to beta(1)-adrenergic stimulation with isoproterenol (65%). The P2Y(6)-agonist UDP gamma S also increased cardiomyocyte contraction (35%), an effect abolished by the P2Y(6)-blocker MRS2578. The phospholipase C inhibitor U73122 inhibited both the UDP beta S and the UTP gamma S-induced inotropic effect, indicating an IP3-mediated effect via P2Y(6) receptors. The P2Y(14) agonist UDP-glucose was without effect. Quantification of mRNA with real time polymerase chain reaction revealed P2Y(2) as the most abundant pyrimidine receptor expressed in cardiomyocytes from man. Presence of P2Y(6) receptor mRNA was detected in both species and confirmed at protein level with Western blot and immunohistochemistry in man. In conclusion, UTP levels are increased in humans during myocardial infarction, giving the first evidence for UTP release in man. UTP is a cardiac inotropic factor most likely by activation of P2Y(2) receptors in man. For the first time we demonstrate inotropic effects of UDP, mediated by P2Y(6) receptors via an IP3-dependent pathway. Thus, the extracellular pyrimidines ( UTP and UDP) could be important inotropic factors involved in the development of cardiac disease. C1 Lund Univ, Dept Cardiol, S-22237 Lund, Sweden. Lund Univ, Dept Expt Med Sci, S-22237 Lund, Sweden. NIH, Mol Recognit Sect, Bethesda, MD USA. Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. RP Wihlborg, AK (reprint author), Lund Univ, Dept Cardiol, Tornavagen 10 BMC-C12, S-22237 Lund, Sweden. EM karin.wihlborg@kard.lu.se RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20] NR 43 TC 58 Z9 62 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 14 PY 2006 VL 98 IS 7 BP 970 EP 976 DI 10.1161/01.RES.0000217402.73402.cd PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 032RC UT WOS:000236791100017 PM 16543499 ER PT J AU Jaschke, H Neumann, S Moore, S Thomas, CJ Colson, AO Costanzi, S Kleinau, G Jiang, JK Paschke, R Raaka, BM Krause, G Gershengorn, MC AF Jaschke, H Neumann, S Moore, S Thomas, CJ Colson, AO Costanzi, S Kleinau, G Jiang, JK Paschke, R Raaka, BM Krause, G Gershengorn, MC TI A low molecular weight agonist signals by binding to the transmembrane domain of thyroid-stimulating hormone receptor (TSHR) and luteinizing hormone/chorionic gonadotropin receptor (LHCGR) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; VIRUS TYPE-1 ENTRY; MODELS; IDENTIFICATION; ACTIVATION; RHODOPSIN; DYNAMICS; LIGAND AB Many cognate low molecular weight (LMW) agonists bind to seven transmembrane-spanning receptors within their transmembrane helices (TMHs). The thienopyrimidine org41841 was identified previously as an agonist for the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) and suggested to bind within its TMHs because it did not compete for LH binding to the LHCGR ectodomain. Because of its high homology with LHCGR, we predicted that thyroid-stimulating hormone receptor (TSHR) might be activated by org41841 also. We show that org41841 is a partial agonist for TSHR but with lower potency than for LHCGR. Analysis of three-dimensional molecular models of TSHR and LHCGR predicted a binding pocket for org41841 in common clefts between TMHs 3, 4, 5, 6, and 7 and extracellular loop 2 in both receptors. Evidence for this binding pocket was obtained in signaling studies with chimeric receptors that exhibited improved responses to org41841. Furthermore, a key receptor-ligand interaction between the highly conserved negatively charged E3.37 and the amino group of org41841 predicted by docking of the ligand into the three-dimensional TSHR model was experimentally confirmed. These findings provide the first evidence that, in contrast to the ectodomain binding of cognate ligands, a LMW agonist can bind to and activate glycoprotein hormone receptors via interaction with their transmembrane domain. C1 Leibniz Inst Mol Pharmacol, D-13125 Berlin, Germany. NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Computat Chem Core Lab, NIH, Bethesda, MD 20892 USA. Univ Leipzig, Dept Med 3, D-04103 Leipzig, Germany. RP Jaschke, H (reprint author), Leibniz Inst Mol Pharmacol, Robert Roessle Str 10, D-13125 Berlin, Germany. EM marving@intra.niddk.nih.gov RI Costanzi, Stefano/G-8990-2013; OI Costanzi, Stefano/0000-0003-3183-7332 FU Intramural NIH HHS [Z01 DK070005-04] NR 26 TC 56 Z9 60 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 14 PY 2006 VL 281 IS 15 BP 9841 EP 9844 DI 10.1074/jbc.C600014200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 029WE UT WOS:000236594300004 PM 16488885 ER PT J AU Zhao, J Kong, HJ Li, HX Huang, B Yang, M Zhu, C Bogunovic, M Zheng, F Mayer, L Ozato, K Unkeless, J Xiong, HB AF Zhao, J Kong, HJ Li, HX Huang, B Yang, M Zhu, C Bogunovic, M Zheng, F Mayer, L Ozato, K Unkeless, J Xiong, HB TI IRF-8/interferon (IFN) consensus sequence-binding protein is involved in toll-like receptor (TLR) signaling and contributes to the cross-talk between TLR and IFN-gamma signaling pathways SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTERFERON REGULATORY FACTOR-7; IMMUNE-RESPONSES; HOST-DEFENSE; ALPHA GENES; KAPPA-B; ACTIVATION; INDUCTION; MURINE; VIRUS; CELLS AB Toll-like receptor (TLR) and interferon-gamma (IFN-gamma) signaling pathways are important for both innate and adaptive immune responses. However, the cross-talk between these two signaling pathways is incompletely understood. Here we show that IFN-gamma and LPS synergistically induce the expression of proinflammatory factors, including interleukin-1 (IL-1), IL-6, IL-12, NO, and tumor necrosis factor-alpha (TNF-alpha). Comparable synergism was observed between IFN-gamma and peptidoglycan (PGN; a TLR2 ligand) and poly(I:C) (a TLR3 ligand) in the induction of IL-12 promoter activity. IFN-gamma enhanced lipopolysaccharide (LPS)-induced ERK and JNK phosphorylation but had no effect on LPS-induced NF-kappa B activation. Interestingly, we found that IRF-8-/- macrophages were impaired in the activation of LPS-induced ERK and JNK and the production of proinflammatory cytokines induced by LPS or IFN-gamma plus LPS. Retroviral transduction of IRF-8 into IRF-8-/- macrophages rescued ERK and JNK activation. Furthermore, co-immunoprecipitation experiments show that IRF-8 physically interacts with TRAF6 at a binding site between amino acid residues 356 and 305 of IRF-8. Transfection of IRF-8 enhanced TRAF6 ubiquitination, which is consistent with a physical interaction of IRF-8 with TRAF6. Taken together, the results suggest that the interaction of IRF-8 with TRAF6 modulates TLR signaling and may contribute to the crosstalk between IFN-gamma and TLR signal pathways. C1 Mt Sinai Sch Med, Immunobiol Ctr, New York, NY 10029 USA. NICHHD, Lab Mol Growth & Regulat, NIH, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Gene & Cell Med, New York, NY 10029 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. Mt Sinai Sch Med, Dept Geriatr, New York, NY 10029 USA. RP Xiong, HB (reprint author), Mt Sinai Sch Med, Immunobiol Ctr, Box 1630,1 Gustave L Levy Pl, New York, NY 10029 USA. EM Huabao.Xiong@mssm.edu NR 37 TC 82 Z9 86 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 14 PY 2006 VL 281 IS 15 BP 10073 EP 10080 DI 10.1074/jbc.M507788200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 029WE UT WOS:000236594300032 PM 16484229 ER PT J AU Ueda, T Postnikov, YV Bustin, M AF Ueda, T Postnikov, YV Bustin, M TI Distinct domains in high mobility group n variants modulate specific chromatin modifications SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHROMOSOMAL-PROTEINS HMG-14; HISTONE H3; NUCLEOSOME CORES; GENE-REGULATION; PHOSPHORYLATION; ACETYLATION; H1; TRANSCRIPTION; MSK1 AB We have demonstrated that levels of specific modification in histone H3 are modulated by members of the nucleosome-binding high mobility group N (HMGN) protein family in a variant-specific manner. HMGN1(but not HMGN2) inhibits the phosphorylation of both H3S10 and H3S28, whereas HMGN2 enhances H3K14 acetylation more robustly than HMGN1. Two HMGN domains are necessary for modulating chromatin modifications, a non-modification-specific domain necessary for chromatin binding and a modification-specific domain localized in the C terminus of the HMGNs. Thus, chromatin-binding structural proteins such as HMGNs affect the levels of specific chromatin modifications and therefore may play a role in epigenetic regulation. C1 NCI, Prot Sect, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Bustin, M (reprint author), NCI, Prot Sect, Lab Metab, NIH, Bldg 37,Rm 3122, Bethesda, MD 20892 USA. EM bustin@helix.nih.gov RI Bustin, Michael/G-6155-2015 FU Intramural NIH HHS [Z01 BC004496-30] NR 23 TC 33 Z9 33 U1 1 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 14 PY 2006 VL 281 IS 15 BP 10182 EP 10187 DI 10.1074/jbc.M600821200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 029WE UT WOS:000236594300044 PM 16484217 ER PT J AU Nemoto, S Combs, CA French, S Ahn, BH Fergusson, MM Balaban, RS Finkel, T AF Nemoto, S Combs, CA French, S Ahn, BH Fergusson, MM Balaban, RS Finkel, T TI The mammalian longevity-associated gene product p66(shc) regulates mitochondrial metabolism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT FLUORESCENCE RECOVERY; SYSTEMATIC RNAI SCREEN; PHOTOBLEACHING ED-FRAP; LIFE-SPAN; OXIDATIVE STRESS; CAENORHABDITIS-ELEGANS; C-ELEGANS; SIGNALING PATHWAY; IN-VITRO; APOPTOSIS AB Previous studies have determined that mice with a homozygous deletion in the adapter protein p66(shc) have an extended life span and that cells derived from these mice exhibit lower levels of reactive oxygen species. Here we demonstrate that a fraction of p66(shc) localizes to the mitochondria and that p66(shc-/-) fibroblasts have altered mitochondrial energetics. In particular, despite similar cytochrome content, under basal conditions, the oxygen consumption of spontaneously immortalized p66(shc-/-) mouse embryonic fibroblasts were lower than similarly maintained wild type cells. Differences in oxygen consumption were particularly evident under chemically uncoupled conditions, demonstrating that p66(shc-/-) cells have a reduction in both their resting and maximal oxidative capacity. We further demonstrate that reconstitution of p66(shc) expression in p66(shc-/-) cells increases oxygen consumption. The observed defect in oxidative capacity seen in p66(shc-/-) cells is partially offset by augmented levels of aerobic glycolysis. This metabolic switch is manifested by p66(shc-/-) cells exhibiting an increase in lactate production and a stricter requirement for extracellular glucose in order to maintain intracellular ATP levels. In addition, using an in vivo NADH photobleaching technique, we demonstrate that mitochondrial NADH metabolism is reduced in p66(shc-/-) cells. These results demonstrate that p66(shc) regulates mitochondrial oxidative capacity and suggest that p66(shc) may extend life span by repartitioning metabolic energy conversion away from oxidative and toward glycolytic pathways. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Light Microscopy Facil, Bethesda, MD 20892 USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10-6N-240,10 Ctr Dr, Bethesda, MD 20892 USA. EM finkelt@nih.gov RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 FU Intramural NIH HHS NR 27 TC 98 Z9 109 U1 3 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 14 PY 2006 VL 281 IS 15 BP 10555 EP 10560 DI 10.1074/jbc.M511626200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 029WE UT WOS:000236594300086 PM 16481327 ER PT J AU Uruno, T Remmert, K Hammer, JA AF Uruno, T Remmert, K Hammer, JA TI CARMIL is a potent capping protein antagonist - Identification of a conserved CARMIL domain that inhibits the activity of capping protein and uncaps capped actin filaments SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BARBED-END; ARP2/3 COMPLEX; ACANTHAMOEBA-CASTELLANII; ENA/VASP PROTEINS; FAMILY PROTEINS; MYOSIN-I; POLYMERIZATION; MOTILITY; BINDING; DICTYOSTELIUM AB Acanthamoeba CARMIL was previously shown to co-purify with capping protein (CP) and to bind pure CP. Here we show that this interaction inhibits the barbed end-capping activity of CP. Even more strikingly, this interaction drives the uncapping of actin filaments previously capped with CP. These activities are CP-specific; CARMIL does not inhibit the capping activities of either gelsolin or CapG and does not uncap gelsolin-capped filaments. Although full-length (FL) CARMIL (residues 1-1121) possesses both anti-CP activities, C-terminal fragments like glutathione S-transferase (GST)-P (940-1121) that contain the CARMIL CP binding site are at least 10 times more active. We localized the full activities of GST-P to its C-terminal 51 residues (1071-1121). This sequence contains a stretch of 25 residues that is highly conserved in CARMIL proteins from protozoa, flies, worms, and vertebrates (CARMIL Homology domain 3; CAH3). Point mutations showed that the majority of the most highly conserved residues within CAH3 are critical for the anti-CP activity of GST-AP (862-1121). Finally, we found that GST-AP binds CP similar to 20-fold more tightly than does FL-CARMIL. This observation together with the elevated activities of C-terminal fragments relative to FL-CARMIL suggests that FL-CARMIL might exist primarily in an autoinhibited state. Consistent with this idea, proteolytic cleavage of FL-CARMIL with thrombin generated an similar to 14-kDa C-terminal fragment that expresses full anti-CP activities. We propose that, after some type of physiological activation event, FL-CARMIL could function in vivo as a potent CP antagonist. Given the pivotal role that CP plays in determining the global actin phenotype of cells, our results suggest that CARMIL may play an important role in the physiological regulation of actin assembly. C1 NHLBI, Cell Biol Lab, Sect Mol Cell Biol, NIH, Bethesda, MD 20892 USA. RP Hammer, JA (reprint author), NHLBI, Cell Biol Lab, Sect Mol Cell Biol, NIH, Bldg 50,Rm 2523,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hammerj@nhlbi.nih.gov NR 48 TC 36 Z9 36 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 14 PY 2006 VL 281 IS 15 BP 10635 EP 10650 DI 10.1074/jbc.M513186200 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 029WE UT WOS:000236594300096 PM 16434392 ER PT J AU Ramakrishnan, B Ramasamy, V Qasba, PK AF Ramakrishnan, B Ramasamy, V Qasba, PK TI Structural snapshots of beta-1,4-galactosyltransferase-1 along the kinetic pathway SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE beta-1,4-galactosyltransferase; conformational change; structural snapshots; catalytic intermediates; role of conserved water molecule ID N-ACETYLGLUCOSAMINYLTRANSFERASE I; ALPHA-LACTALBUMIN LA; CRYSTAL-STRUCTURE; BOVINE BETA-1,4-GALACTOSYLTRANSFERASE; CONFORMATIONAL-CHANGES; CATALYTIC MECHANISM; UDP-GAL; COMPLEX; DONOR; GALACTOSYLTRANSFERASE AB During the catalytic cycle of beta 1,4-galactosyltransferase-1 (Gal-T1), upon the binding of Mn2+ followed by UDP-Gal, two flexible loops, a long and a short loop, change their conformation from open to closed. We have determined the crystal structures of a human M340H-Gal-T1 mutant in the open conformation (apo-enzyme), its Mn2+ and Mn2+-UDP-Gal-bound complexes, and of a pentenary complex of bovine Gal-T1-Mn2+-UDP-GaINAc-Glc-alpha-lactalbumin. These studies show that during the conformational changes in Gal-T1, the coordination of Mn2+ undergoes significant changes. It loses a coordination bond with a water molecule bound in the open conformation of Gal-T1 while forming a new coordination bond with another water molecule in the closed conformation, creating an active ground-state structure that facilitates enzyme catalysis. In the crystal structure of the pentenary complex, the N-acetylglucosamine (GlcNAc) moiety is found cleaved from UDP-GalNAc and is placed 2.7 A away from the 04 oxygen atom of the acceptor Glc molecule, yet to form the product. The anomeric Cl atom of the cleaved GalNAc moiety has only two covalent bonds with its nonhydrogen atoms (05 and C2 atoms), similar to either an oxocarbenium ion or N-acetylgalactal form, which are crystallographically indistinguishable at the present resolution. The structure also shows that the newly formed, metal-coordinating water molecule forms a hydrogen bond with the beta-phosphate group of the cleaved UDP moiety. This hydrogen bond formation results in the rotation of the P-phosphate group of UDP away from the cleaved GalNAc moiety, thereby preventing the re-formation of the. UDP-sugar during catalysis. Therefore, this water molecule plays an important role during catalysis in ensuring that the catalytic reaction proceeds in a forward direction. Published by Elsevier Ltd. C1 NCI, Struct Glycobiol Sect, Nanobiol Program, Canc Res Ctr,SAIC Frederick Inc, Ft Detrick, MD 21702 USA. RP Qasba, PK (reprint author), NCI, Struct Glycobiol Sect, Nanobiol Program, Canc Res Ctr,SAIC Frederick Inc, Ft Detrick, MD 21702 USA. EM qasba@helix.nih.gov FU Intramural NIH HHS; PHS HHS [N01-C0-12400] NR 36 TC 33 Z9 34 U1 2 U2 7 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 14 PY 2006 VL 357 IS 5 BP 1619 EP 1633 DI 10.1016/j.jmb.2006.01.088 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 030IZ UT WOS:000236629400022 PM 16497331 ER PT J AU Sam, V Tai, CH Garnier, J Gibrat, JF Lee, B Munson, PJ AF Sam, Vichetra Tai, Chin-Hsien Garnier, Jean Gibrat, Jean-Francois Lee, Byungkook Munson, Peter J. TI ROC and confusion analysis of structure comparison methods identify the main causes of divergence from manual protein classification SO BMC BIOINFORMATICS LA English DT Article ID STRUCTURE ALIGNMENT; FOLD SPACE; SCOP; SIMILARITIES; CATH; DATABASE; SEQUENCES; GENOMICS; DISTANCE; CURVE AB Background: Current classification of protein folds are based, ultimately, on visual inspection of similarities. Previous attempts to use computerized structure comparison methods show only partial agreement with curated databases, but have failed to provide detailed statistical and structural analysis of the causes of these divergences. Results: We construct a map of similarities/dissimilarities among manually defined protein folds, using a score cutoff value determined by means of the Receiver Operating Characteristics curve. It identifies folds which appear to overlap or to be "confused" with each other by two distinct similarity measures. It also identifies folds which appear inhomogeneous in that they contain apparently dissimilar domains, as measured by both similarity measures. At a low (1%) false positive rate, 25 to 38% of domain pairs in the same SCOP folds do not appear similar. Our results suggest either that some of these folds are defined using criteria other than purely structural consideration or that the similarity measures used do not recognize some relevant aspects of structural similarity in certain cases. Specifically, variations of the "common core" of some folds are severe enough to defeat attempts to automatically detect structural similarity and/or to lead to false detection of similarity between domains in distinct folds. Structures in some folds vary greatly in size because they contain varying numbers of a repeating unit, while similarity scores are quite sensitive to size differences. Structures in different folds may contain similar substructures, which produce false positives. Finally, the common core within a structure may be too small relative to the entire structure, to be recognized as the basis of similarity to another. Conclusion: A detailed analysis of the entire available protein fold space by two automated similarity methods reveals the extent and the nature of the divergence between the automatically determined similarity/dissimilarity and the manual fold type classifications. Some of the observed divergences can probably be addressed with better structure comparison methods and better automatic, intelligent classification procedures. Others may be intrinsic to the problem, suggesting a continuous rather than discrete protein fold space. C1 US Dept HHS, NIH, CIT, DCB,Math & Stat Comp Lab, Bethesda, MD USA. NCI, Mol Biol Lab, CCR, US Dept DHHS,NIH, Bethesda, MD 20892 USA. INRA, Math Informat & Genome, Jouy En Josas, France. RP Munson, PJ (reprint author), US Dept HHS, NIH, CIT, DCB,Math & Stat Comp Lab, Bethesda, MD USA. EM vsam@mail.nih.gov; taic@mail.nih.gov; jean.garnier@jouy.inra.fr; jean-francois.gibrat@jouy.inra.fr; BKLee@mail.nih.gov; munson@helix.nih.gov FU Intramural NIH HHS NR 39 TC 19 Z9 19 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD APR 13 PY 2006 VL 7 AR 206 DI 10.1186/1471-2105-7-206 PG 20 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 067LA UT WOS:000239302600001 PM 16613604 ER PT J AU Pecina, S Schulkin, J Berridge, KC AF Pecina, Susana Schulkin, Jay Berridge, Kent C. TI Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress? SO BMC BIOLOGY LA English DT Article ID PAVLOVIAN-INSTRUMENTAL TRANSFER; MESSENGER-RIBONUCLEIC-ACID; MEDIAL PREFRONTAL CORTEX; INDUCED RELAPSE; PARAVENTRICULAR NUCLEUS; STRIA TERMINALIS; COCAINE SEEKING; HEDONIC IMPACT; BED NUCLEUS; RAT-BRAIN AB Background: Corticotropin-releasing factor (CRF) is typically considered to mediate aversive aspects of stress, fear and anxiety. However, CRF release in the brain is also elicited by natural rewards and incentive cues, raising the possibility that some CRF systems in the brain mediate an independent function of positive incentive motivation, such as amplifying incentive salience. Here we asked whether activation of a limbic CRF subsystem magnifies the increase in positive motivation for reward elicited by incentive cues previously associated with that reward, in a way that might exacerbate cue-triggered binge pursuit of food or other incentives? We assessed the impact of CRF microinjections into the medial shell of nucleus accumbens using a pure incentive version of Pavlovian-Instrumental transfer, a measure specifically sensitive to the incentive salience of reward cues ( which it separates from influences of aversive stress, stress reduction, frustration and other traditional explanations for stress-increased behavior). Rats were first trained to press one of two levers to obtain sucrose pellets, and then separately conditioned to associate a Pavlovian cue with free sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250 or 500 ng/0.2 mu l) or amphetamine (20 mu g/0.2 mu l). Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test. Results: Microinjections of the highest dose of CRF (500 ng) or amphetamine (20 mu g) selectively enhanced the ability of Pavlovian reward cues to trigger phasic peaks of increased instrumental performance for a sucrose reward, each peak lasting a minute or so before decaying after the cue. Lever pressing was not enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or during the presentation without a cue, showing that the CRF enhancement could not be explained as a result of generalized motor arousal, frustration or stress, or by persistent attempts to ameliorate aversive states. Conclusion: We conclude that CRF in nucleus accumbens shell amplifies positive motivation for cued rewards, in particular by magnifying incentive salience that is attributed to Pavlovian cues previously associated with those rewards. CRF-induced magnification of incentive salience provides a novel explanation as to why stress may produce cue-triggered bursts of binge eating, drug addiction relapse, or other excessive pursuits of rewards. C1 Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. Georgetown Univ, Dept Physiol & Biophys, CNE Branch, NIMH, Washington, DC 20057 USA. RP Pecina, S (reprint author), Univ Michigan, Dept Psychol, 580 Union Dr, Ann Arbor, MI 48109 USA. EM pesu@umich.edu; jschulkin@acog.org; berridge@umich.edu RI Berridge, Kent/C-1525-2009 OI Berridge, Kent/0000-0002-6031-2626 FU NIDA NIH HHS [DA015188, R01 DA015188]; NIMH NIH HHS [MH63649, R01 MH063649] NR 60 TC 82 Z9 83 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7007 J9 BMC BIOL JI BMC Biol. PD APR 13 PY 2006 VL 4 AR 8 DI 10.1186/1741-7007-4-8 PG 16 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 040ZZ UT WOS:000237423700001 PM 16613600 ER PT J AU Castellino, F Huang, AY Altan-Bonnet, G Stoll, S Scheinecker, C Germain, RN AF Castellino, F Huang, AY Altan-Bonnet, G Stoll, S Scheinecker, C Germain, RN TI Chemokines enhance immunity by guiding naive CD8(+) T cells to sites of CD4 T cell-dendritic cell interaction SO NATURE LA English DT Article ID LYMPH-NODES; IN-VIVO; CD8-T-CELL MEMORY; CD4-T-CELL HELP; LYMPHOCYTES; EXPRESSION; ANTIGEN; MIGRATION; GENERATION; MOTILITY AB CD8(+) T cells have a crucial role in resistance to pathogens and can kill malignant cells; however, some critical functions of these lymphocytes depend on helper activity provided by a distinct population of CD4(+) T cells. Cooperation between these lymphocyte subsets involves recognition of antigens co-presented by the same dendritic cell, but the frequencies of such antigen-bearing cells early in an infection and of the relevant naive T cells are both low. This suggests that an active mechanism facilitates the necessary cell-cell associations. Here we demonstrate that after immunization but before antigen recognition, naive CD8(+) T cells in immunogen-draining lymph nodes upregulate the chemokine receptor CCR5, permitting these cells to be attracted to sites of antigen-specific dendritic cell-CD4(+) T cell interaction where the cognate chemokines CCL3 and CCL4 (also known as MIP-1 alpha and MIP-1 beta) are produced. Interference with this actively guided recruitment markedly reduces the ability of CD4(+) T cells to promote memory CD8(+) T-cell generation, indicating that an orchestrated series of differentiation events drives nonrandom cell-cell interactions within lymph nodes, optimizing CD8(+) T-cell immune responses involving the few antigen-specific precursors present in the naive repertoire. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Mainz, Dept Dermatol, D-55131 Mainz, Germany. Med Univ Vienna, Dept Rheumatol, Gen Hosp Vienna, A-1090 Vienna, Austria. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rgermain@nih.gov OI Huang, Alex/0000-0002-5701-4521 FU Intramural NIH HHS NR 38 TC 394 Z9 406 U1 1 U2 15 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 13 PY 2006 VL 440 IS 7086 BP 890 EP 895 DI 10.1038/nature04651 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 031WU UT WOS:000236736700031 PM 16612374 ER PT J AU Brubaker, L Cundiff, GW Fine, P Nygaard, I Richter, HE Visco, AG Zyczynski, H Brown, MB Weber, AM AF Brubaker, L Cundiff, GW Fine, P Nygaard, I Richter, HE Visco, AG Zyczynski, H Brown, MB Weber, AM CA Pelvic Floor Disorders Network TI Abdominal sacrocolpopexy with Burch colposuspension to reduce urinary stress incontinence SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PELVIC ORGAN PROLAPSE; FREE VAGINAL TAPE; FOLLOW-UP; GENITOURINARY PROLAPSE; SURGICAL-PROCEDURES; RANDOMIZED-TRIAL; CONTINENT WOMEN; FLOOR DISORDERS; REPAIR; SURGERY AB BACKGROUND: We designed this trial to assess whether the addition of standardized Burch colposuspension to abdominal sacrocolpopexy for the treatment of pelvic-organ prolapse decreases postoperative stress urinary incontinence in women without preoperative symptoms of stress incontinence. METHODS: Women who did not report symptoms of stress incontinence and who chose to undergo sacrocolpopexy to treat prolapse were randomly assigned to concomitant Burch colposuspension or to no Burch colposuspension (control) and were evaluated in a blinded fashion three months after the surgery. The primary outcomes included measures of stress incontinence (symptoms, stress testing, or treatment) and measures of urge symptoms. Enrollment was stopped after the first interim analysis because of a significantly lower frequency of stress incontinence in the group that underwent the Burch colposuspension. RESULTS: Of 322 women who underwent randomization, 157 were assigned to Burch colposuspension and 165 to the control group. Three months after surgery, 23.8 percent of the women in the Burch group and 44.1 percent of the controls met one or more of the criteria for stress incontinence (P<0.001). There was no significant difference between the Burch group and the control group in the frequency of urge incontinence (32.7 percent vs. 38.4 percent, P=0.48). After surgery, women in the control group were more likely to report bothersome symptoms of stress incontinence than those in the Burch group who had stress incontinence (24.5 percent vs. 6.1 percent, P<0.001). CONCLUSIONS: In women without stress incontinence who are undergoing abdominal sacrocolpopexy for prolapse, Burch colposuspension significantly reduced postoperative symptoms of stress incontinence without increasing other lower urinary tract symptoms. C1 Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA. Johns Hopkins Univ, Dept Obstet & Gynecol, Baltimore, MD USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Univ Iowa, Dept Obstet & Gynecol, Iowa City, IA 52242 USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. NICHHD, Contracept & Reprod Hlth Branch, Populat Res Ctr, NIH, Bethesda, MD 20892 USA. RP Brubaker, L (reprint author), Loyola Univ, Med Ctr, Dept Obstet & Gynecol, 2160 S 1st Ave, Maywood, IL 60153 USA. FU NICHD NIH HHS [U01 HD41249, U10 HD041248, U10 HD041263, U10 HD41248, U10 HD41250, U10 HD41261, U10 HD41263, U10 HD41267, U10 HD41268, U10 HD41269] NR 28 TC 243 Z9 253 U1 0 U2 8 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 13 PY 2006 VL 354 IS 15 BP 1557 EP 1566 DI 10.1056/NEJMoa054208 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 031WW UT WOS:000236736900004 PM 16611949 ER PT J AU Nelson, KB Leviton, A AF Nelson, KB Leviton, A TI Hypothermia for neonates with hypoxic-ischemic encephalopathy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NINDS, Bethesda, MD 20892 USA. Childrens Hosp Boston, Boston, MA 02215 USA. RP Nelson, KB (reprint author), NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM alan.leviton@childrens.harvard.edu NR 2 TC 3 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 13 PY 2006 VL 354 IS 15 BP 1643 EP 1644 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 031WW UT WOS:000236736900027 PM 16615186 ER PT J AU Zhang, DW Jeang, KT Lee, CGL AF Zhang, DW Jeang, KT Lee, CGL TI p53 negatively regulates the expression of FAT10, a gene upregulated in various cancers SO ONCOGENE LA English DT Article DE FAT10; diubiquitin; promoter; 5 ' UTR; p53 ID UBIQUITIN-LIKE PROTEIN; WILD-TYPE P53; MHC CLASS-I; CELL-CYCLE; TRANSCRIPTIONAL REPRESSION; HEPATOCELLULAR-CARCINOMA; INTERFERON-GAMMA; TUMOR-SUPPRESSOR; MAMMALIAN-CELLS; CHECKPOINT AB FAT10 is a member of the ubiquitin-like modi. er family of proteins and has been implicated to play important roles in antigen presentation, cytokine response, apoptosis and mitosis. We have recently demonstrated the upregulation of FAT10 gene expression in 90% of hepatocellular carcinoma patients. Here, we identified and characterized the promoter of the FAT10 gene to elucidate the mechanism of FAT10 gene expression. Notably, we found that the 50 untranslated region (5'UTR), from the transcription start site to 15 bases before the translational start site, displays significant promoter activity. Regions upstream of the 5'UTR (from +26 to -1997) do not confer any promoter activity. Curiously, FAT10 promoter activity and expression is significantly repressed in KB3-1 and HepG2 cells, which have wild-type p53, than in p53-negative Hep3B cells. The role of p53 in regulating FAT10 expression was evident by the significant down-regulation (P < 0.05) of FAT10 mRNA expression and promoter activity when wild-type p53 was transfected into p53-null Hep3B cells. Conversely, inhibiting p53 expression through siRNA against p53 significantly enhanced FAT10 expression and promoter activity. p53 was found to bind in vivo to the 50 half consensus sequence of p53binding site located at the FAT10 promoter. Hence, we propose that FAT10 is a downstream target of p53 and dysregulation of FAT10 expression in p53-defective cells could contribute to carcinogenesis. C1 Natl Canc Ctr, Div Med Sci, Singapore 169610, Singapore. Natl Univ Singapore, Dept Biochem, Yong Loo Lin Sch Med, Singapore 117548, Singapore. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Lee, CGL (reprint author), Natl Canc Ctr, Div Med Sci, Level 6,Lab 5,11 Hosp Dr, Singapore 169610, Singapore. EM bchleec@nus.edu.sg RI Jeang, Kuan-Teh/A-2424-2008 NR 41 TC 45 Z9 54 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 13 PY 2006 VL 25 IS 16 BP 2318 EP 2327 DI 10.1038/sj.onc.1209220 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 032HC UT WOS:000236764300004 PM 16501612 ER PT J AU Talwar, S Munson, PJ Barb, J Fiuza, C Cintron, AP Logun, C Tropea, M Khan, S Reda, D Shelhamer, JH Danner, RL Suffredini, AF AF Talwar, S Munson, PJ Barb, J Fiuza, C Cintron, AP Logun, C Tropea, M Khan, S Reda, D Shelhamer, JH Danner, RL Suffredini, AF TI Gene expression profiles of peripheral blood leukocytes after endotoxin challenge in humans SO PHYSIOLOGICAL GENOMICS LA English DT Article DE innate immunity; inflammation; leukocyte transcriptome ID SYSTEMIC INFLAMMATION; CYTOKINE RELEASE; WHOLE-BLOOD; ANTIINFLAMMATORY AGENTS; INNATE IMMUNITY; SEPTIC PATIENTS; DOWN-REGULATION; T-LYMPHOCYTES; SEPSIS; ACTIVATION AB To define gene expression profiles that occur during the initial activation of human innate immunity, we administered intravenous endotoxin (n = 8) or saline (n = 4) to healthy subjects and hybridized RNA from blood mononuclear cells (0, 0.5, 6, 24, 168 h) or whole blood (0, 3, 6, 24, 168 h) to oligonucleotide probe arrays. The greatest change in mononuclear cell gene expression occurred at 6 h (439 induced and 428 repressed genes, 1% false discovery rate, and 50% fold change) including increased expression of genes associated with pathogen recognition molecules and signaling cascades linked to receptors associated with cell mobility and activation. Induced defense response genes included cytokines, chemokines, and their respective receptors, acute-phase transcription factors, proteases, arachidonate metabolites, and oxidases. Repressed defense response genes included those associated with co-stimulatory molecules, T and cytotoxic lymphocytes, natural killer (NK) cells, and protein synthesis. Gene expression profiles of whole blood had similar biological themes. Over 100 genes not typically associated with acute inflammation were differentially regulated after endotoxin. By 24 h, gene expression had returned to baseline values. Thus the inflammatory response of circulating leukocytes to endotoxin in humans is characterized by a rapid amplification and subsidence of gene expression. These results indicate that a single intravascular exposure to endotoxin produces a large but temporally short perturbation of the blood transcriptome. C1 NIH, CCMD, CC, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Suffredini, AF (reprint author), NIH, CCMD, CC, Bldg 10,Rm 7D-43,10 Ctr Dr, Bethesda, MD 20892 USA. EM asuffredini@mail.cc.nih.gov FU Intramural NIH HHS NR 51 TC 59 Z9 62 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD APR 13 PY 2006 VL 25 IS 2 BP 203 EP 215 DI 10.1152/physiolgenomics.00192.2005 PG 13 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 032RE UT WOS:000236791300003 PM 16403844 ER PT J AU Pisitkun, T Bieniek, J Tchapyjnikov, D Wang, GH Wu, WW Shen, RF Knepper, MA AF Pisitkun, T Bieniek, J Tchapyjnikov, D Wang, GH Wu, WW Shen, RF Knepper, MA TI High-throughput identification of IMCD proteins using LC-MS/MS SO PHYSIOLOGICAL GENOMICS LA English DT Article DE inner medullary collecting duct; systems biology; mass spectrometry; liquid chromatography; aquaporin-2; epithelial Na channel; vasopressin ID MEDULLARY COLLECTING DUCT; AQUAPORIN-2 TRAFFICKING; BRATTLEBORO RAT; SYNTAXIN 7; VASOPRESSIN; WATER; KIDNEY; CELLS; PERMEABILITY; CALMODULIN AB The inner medullary collecting duct (IMCD) is an important site of vasopressin-regulated water and urea transport. Here we have used protein mass spectrometry to investigate the proteome of the IMCD cell and how it is altered in response to long-term vasopressin administration in rats. IMCDs were isolated from inner medullas of rats, and IMCD proteins were identified by liquid chromatography/tandem mass spectrometry (LC-MS/MS). We present a WWW-based "IMCD Proteome Database" containing all IMCD proteins identified in this study (n = 704) and prior MS-based identification studies (n = 301). We used the isotope-coded affinity tag (ICAT) technique to identify IMCD proteins that change in abundance in response to vasopressin. Vasopressin analog (dDAVP) or vehicle was infused subcutaneously in Brattleboro rats for 3 days, and IMCDs were isolated for proteomic analysis. dDAVP and control samples were labeled with different cleavable ICAT reagents (mass difference 9 amu) and mixed. This was followed by one-dimensional SDS-PAGE separation, in-gel trypsin digestion, biotin-avidin affinity purification, and LC-MS/MS identification and quantification. Responses to vasopressin for a total of 165 proteins were quantified. Quantification, based on semiquantitative immunoblotting of 16 proteins for which antibodies were available, showed a high degree of correlation with ICAT results. In addition to aquaporin-2 and gamma-epithelial Na channel (gamma-ENaC), five of the immunoblotted proteins were substantially altered in abundance in response to dDAVP, viz., syntaxin-7, Rap1, GAPDH, heat shock protein (HSP) 70, and cathepsin D. A 28-protein vasopressin signaling network was constructed using literature-based network analysis software focusing on the newly identified proteins, providing several new hypotheses for future studies. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 6N260, Bethesda, MD 20892 USA. EM knep@helix.nih.gov OI Pisitkun, Trairak/0000-0001-6677-2271 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 35 TC 49 Z9 49 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD APR 13 PY 2006 VL 25 IS 2 BP 263 EP 276 DI 10.1152/physiolgenomics.00214.2005 PG 14 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 032RE UT WOS:000236791300009 PM 16449382 ER PT J AU Castrop, H Oppermann, M Weiss, Y Huang, Y Mizel, D Lu, H Germain, S Schweda, F Theilig, F Bachmann, S Briggs, J Kurtz, A Schnermann, J AF Castrop, H Oppermann, M Weiss, Y Huang, Y Mizel, D Lu, H Germain, S Schweda, F Theilig, F Bachmann, S Briggs, J Kurtz, A Schnermann, J TI Reporter gene recombination in juxtaglomerular granular and collecting duct cells by human renin promoter-Cre recombinase transgene SO PHYSIOLOGICAL GENOMICS LA English DT Article DE renin; kidney development ID DEPENDENT HYPERTENSIVE-RATS; ANGIOTENSIN-SYSTEM; MESSENGER-RNA; TUBULAR RENIN; EXPRESSION; MICE; MOUSE; TRANSCRIPTION; KIDNEY; ENHANCEMENT AB To assess the feasibility of using the renin promoter for expressing Cre recombinase in juxtaglomerular (JG) cells only, we generated five independent transgenic mouse lines (designated hRen-Cre) expressing Cre recombinase under control of a 12.2-kb human renin promoter. In the kidneys of adult mice Cre mRNA (RT-PCR) was found in the renal cortex, with Cre protein (immunohistochemistry) being localized in afferent arterioles and to a lower degree in interlobular arteries. Cre mRNA levels were regulated in a renin-typical fashion by changes in oral salt intake, water restriction, or isoproterenol infusion, indicating the presence of key regulatory elements within 12.2 kb of the 5'-flanking region of the human renin gene. hRen-Cre mice were interbred with both the ROSA26-EGFP and ROSA26-lacZ reporter strains to assess renin promoter activity from Cre-mediated excision of a floxed stop cassette and subsequent enhanced green fluorescent protein (EGFP) and beta-galactosidase (beta-gal) detection. In adult mice, beta-gal staining and EGFP were observed in afferent arterioles and interlobular arteries, overlapping with Cre protein expression. In addition, intense beta-gal staining was found in cortical and medullary collecting ducts where Cre expression was minimal. In embryonic kidneys, beta-gal staining was detected in the developing collecting duct system beginning at embryonic day 12, showing substantial activity of the human renin promoter in the branching ureteric bud. Our data indicate that besides its well-known activity in JG cells and renal vessels the human renin promoter is transiently active in the collecting duct system during kidney development, complicating the use of this approach for JG cell-specific excision of floxed targets. C1 Univ Regensburg, Inst Physiol, D-93040 Regensburg, Germany. NIDDKD, NIH, Bethesda, MD 20892 USA. Hop European, Serv Hematol Biol A, F-75015 Paris, France. INSERM, Unit 36, F-75005 Paris, France. Coll France, F-75005 Paris, France. Charite Univ Med Berlin, Inst Anat, Berlin, Germany. RP Castrop, H (reprint author), Univ Regensburg, Inst Physiol, Univ Str 31, D-93040 Regensburg, Germany. EM hayo@castrop.com RI Briggs, Josephine/B-9394-2009; Germain, Stephane/E-2301-2016 OI Briggs, Josephine/0000-0003-0798-1190; Germain, Stephane/0000-0001-5992-1275 FU Intramural NIH HHS NR 35 TC 10 Z9 11 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD APR 13 PY 2006 VL 25 IS 2 BP 277 EP 285 DI 10.1152/physiolgenomics.00302.2005 PG 9 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 032RE UT WOS:000236791300010 PM 16418317 ER PT J AU Hashimoto, T Cui, CY Schlessinger, D AF Hashimoto, T Cui, CY Schlessinger, D TI Repertoire of mouse ectodysplasin-A (EDA-A) isoforms SO GENE LA English DT Article DE alternative splicing; ectodermal dysplasia; EDAR; NF-kappa B; TROY; XEDAR ID HYPOHIDROTIC ECTODERMAL DYSPLASIA; FACTOR RECEPTOR SUPERFAMILY; FAMILY-MEMBER; KAPPA-B; HAIR-FOLLICLES; CELL-DEATH; MUTATIONS; PROTEIN; HOMOLOG; GENE AB Mutations in ectodysplasin-A (EDA) cause loss of hair, sweat glands, and teeth in man and mouse. Isoform EDA-A1 protein shows partial rescue of the affected Tabby mouse phenotypes, suggesting that other isoforms may be required for full function. We describe genomic structure for five EDA isoforms, EIDA-A V, A5, A5', A6, and A6, in addition to the previously known EDA-A1, A2, A3, and A4. The novel isoforms together account for similar to 12% of total EDA transcripts. The most different, EDA-A6 and A6', which lack the critical domain for interaction with NF-kappa B-activating receptors, were nevertheless confirmed to be present in mouse and human skin tissue. Other isoforms, EDA-A5 and A5', for example, activated NF-kappa B through receptors EDAR and XEDAR. These properties make new isoforms candidates for modulators of EDA function. Published by Elsevier B.V. C1 NIH, Genet Lab, NIA, Baltimore, MD 21224 USA. RP Schlessinger, D (reprint author), NIH, Genet Lab, NIA, Baltimore, MD 21224 USA. EM schlessingerd@grc.nia.nih.gov FU Intramural NIH HHS NR 37 TC 12 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 12 PY 2006 VL 371 IS 1 BP 42 EP 51 DI 10.1016/j.gene.2005.11.003 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 034RG UT WOS:000236947700006 PM 16423472 ER PT J AU Bertolino, A Blasi, G Latorre, V Rubino, V Rampino, A Sinibaldi, L Caforio, G Petruzzella, V Pizzuti, A Scarabino, T Nardini, M Weinberger, DR Dallapiccola, B AF Bertolino, A Blasi, G Latorre, V Rubino, V Rampino, A Sinibaldi, L Caforio, G Petruzzella, V Pizzuti, A Scarabino, T Nardini, M Weinberger, DR Dallapiccola, B TI Additive effects of genetic variation in dopamine regulating genes on working memory cortical activity in human brain SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dorsolateral prefrontal cortex; anterior cingulate; working memory; dopamine; catechol-O-methyltransferase; dopamine transporter ID CATECHOL-O-METHYLTRANSFERASE; VAL(108/158) MET GENOTYPE; RAT PREFRONTAL CORTEX; TRANSPORTER AVAILABILITY; MESSENGER-RNA; DEFAULT MODE; IN-VITRO; SCHIZOPHRENIA; RECEPTORS; STRIATUM AB Functional polymorphisms in the catechol-O-methyltransferase ( COMT) and the dopamine transporter ( DAT) genes modulate dopamine inactivation, which is crucial for determining neuronal signal-to-noise ratios in prefrontal cortex during working memory. We show that the COMT Met(158) allele and the DAT 3' variable number of tandem repeat 10-repeat allele are independently associated in healthy humans with more focused neuronal activity ( as measured with blood oxygen level-dependent functional magnetic resonance imaging) in the working memory cortical network, including the prefrontal cortex. Moreover, subjects homozygous for the COMT Met allele and the DAT10-repeat allele have the most focused response, whereas the COMTVal and the DAT9-repeat alleles have the least. These results demonstrate additive genetic effects of genes regulating dopamine signaling on specific neuronal networks subserving working memory. C1 Univ Bari, Dipartimento Sci Neurol & Psichiat, Sect Mental Disorders, Psychiat Neurosci Grp, I-70124 Bari, Italy. Univ Bari, Dept Med Biochem & Med Biol, I-70124 Bari, Italy. NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. Ist Ricovero & Cura & Carattere Sci Casa Solliev, Dept Neuroradiol, I-71013 San Giovanni Rotondo, Foggia, Italy. Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00100 Rome, Italy. IRCCS, CSS Mendel, I-00184 Rome, Italy. RP Bertolino, A (reprint author), Univ Bari, Dipartimento Sci Neurol & Psichiat, Sect Mental Disorders, Psychiat Neurosci Grp, Piazza Giulio Cesare 9, I-70124 Bari, Italy. EM bertolia@psichiat.uniba.it RI Picchioni, Marco/E-3300-2010; Bertolino, Alessandro/O-6352-2016; Rampino, Antonio/Q-4465-2016; Dallapiccola, Bruno/K-8692-2016 OI Picchioni, Marco/0000-0001-6681-147X; Bertolino, Alessandro/0000-0002-1251-1380; Rampino, Antonio/0000-0002-9654-3266; Petruzzella, Vittoria/0000-0001-8771-6033; Dallapiccola, Bruno/0000-0002-5031-1013 NR 35 TC 148 Z9 149 U1 3 U2 17 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 12 PY 2006 VL 26 IS 15 BP 3918 EP 3922 DI 10.1523/JNEUROSCI.4975-05.2006 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 034EY UT WOS:000236913000006 PM 16611807 ER PT J AU Szego, EM Barabas, K Balog, J Szilagyi, N Korach, KS Juhasz, G Abraham, IM AF Szego, EM Barabas, K Balog, J Szilagyi, N Korach, KS Juhasz, G Abraham, IM TI Estrogen induces estrogen receptor alpha-dependent cAMP response element-binding protein phosphorylation via mitogen activated protein kinase pathway in basal forebrain cholinergic neurons in vivo SO JOURNAL OF NEUROSCIENCE LA English DT Article DE steroid; ChAT; nongenomic; transgenic mice; signaling pathways; estrogen ID STIMULATED ACETYLCHOLINE-RELEASE; LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; CREB PHOSPHORYLATION; MEDIATES NEUROPROTECTION; BCL-2 EXPRESSION; HORMONE NEURONS; SENILE-DEMENTIA; MOUSE-BRAIN; CA2+ INFLUX AB In addition to classical genomic mechanisms, estrogen also exerts nonclassical effects via a signal transduction system on neurons. To study whether estrogen has a nonclassical effect on basal forebrain cholinergic system, we measured the intensity of cAMP response element-binding protein (CREB) phosphorylation (pCREB) in cholinergic neurons after administration of 17 beta-estradiol to ovariectomized (OVX) mice. A significant time-dependent increase in the number of pCREB-positive cholinergic cells was detected after estrogen administration in the medial septum-diagonal band (MS-DB) and the substantia innominata ( SI). The increase was first observed 15 min after estrogen administration. The role of classical estrogen receptors (ERs) was evaluated using ER knock-out mice in vivo. The estrogen-induced CREB phosphorylation in cholinergic neurons was present in ER beta knock-out mice but completely absent in ER beta knock-out mice in MS-DB and SI. A series of in vitro studies demonstrated that estrogen acted directly on cholinergic neurons. Selective blockade of the mitogen activated protein kinase (MAPK) pathway in vivo completely prevented estrogen-induced CREB phosphorylation in cholinergic neurons in MS-DB and SI. In contrast, blockade of protein kinase A (PKA) was effective only in SI. Finally, studies in intact female mice revealed levels of CREB phosphorylation within cholinergic neurons that were similar to those of estrogen-treated OVX mice. These observations demonstrate an ER alpha-mediated nonclassical effect of estrogen on the cholinergic neurons and that these actions are present under physiological conditions. They also reveal the role of MAPK and PKA-MAPK pathway activation in nonclassical estrogen signaling in the basal forebrain cholinergic neurons in vivo. C1 Eotvos Lorand Univ, Neurobiol Res Grp, Hungarian Acad Sci, H-1117 Budapest, Hungary. Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, Receptor Biol Sect, Res Triangle Pk, NC 27709 USA. RP Abraham, IM (reprint author), Eotvos Lorand Univ, Neurobiol Res Grp, Hungarian Acad Sci, Pazmany St 1-C, H-1117 Budapest, Hungary. EM abraham@dec001.geobio.elte.hu OI Korach, Kenneth/0000-0002-7765-418X NR 61 TC 84 Z9 87 U1 0 U2 5 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 12 PY 2006 VL 26 IS 15 BP 4104 EP 4110 DI 10.1523/JNEUROSCI.0222-06.2006 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 034EY UT WOS:000236913000026 PM 16611827 ER PT J AU Lee, CH Danilowicz, C Conroy, RS Coljee, VW Prentiss, M AF Lee, C. H. Danilowicz, C. Conroy, R. S. Coljee, V. W. Prentiss, M. TI Impacts of magnesium ions on the unzipping of gimel-phage DNA SO JOURNAL OF PHYSICS-CONDENSED MATTER LA English DT Article; Proceedings Paper CT Workshop on Biopolymers 2005 CY MAY 30-JUN 03, 2005 CL Trieste, ITALY ID RAMAN-SPECTROSCOPY; DUPLEX STABILITY; METAL COMPLEXES; FORCE; MG2+; CURVATURE; CATIONS AB We used magnetic tweezers to exert a constant force to separate double stranded lambda-phage DNA as a function of temperature and buffer content. The separation was performed at temperatures ranging from 20 to 50 degrees C in various Mg2+ buffers, including a T4 ligase buffer and a PCR buffer. At 30 degrees C and pH 7.4 (10 mM Tris), we measured the unzipping force as a function of concentration for Mg2+ concentrations between 0.2 and 50 mM, and determined that the unzipping force is proportional to the logarithm of concentration. For comparison, we performed the analogous experiment as a function of Na+ concentration and found that the unzipping force is also proportional to the log of concentration, but requires a much higher cation concentration to achieve the same unzipping force as in Mg2+ buffer. We also constructed the phase diagram in the force-temperature plane for the unzipping in 10 and 50 mM MgCl2 at pH 7.4 (10 mM Tris). The phase diagram for 10 mM Mg2+ is similar to the one measured previously for phosphate buffer saline (PBS) but the phase diagram for 50 mM Mg2+ deviates significantly from those for 10 MM Mg2+ and PBS at temperatures between 20 and 35 degrees C. C1 Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. Lab Funct Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Prentiss, M (reprint author), Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. EM prentiss@fas.harvard.edu RI Conroy, Richard/D-1979-2009 OI Conroy, Richard/0000-0002-8896-6090 NR 39 TC 2 Z9 2 U1 3 U2 8 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0953-8984 J9 J PHYS-CONDENS MAT JI J. Phys.-Condes. Matter PD APR 12 PY 2006 VL 18 IS 14 SI SI BP S205 EP S213 DI 10.1088/0953-8984/18/14/S05 PG 9 WC Physics, Condensed Matter SC Physics GA 047MZ UT WOS:000237884700006 ER PT J AU Zurla, C Franzini, A Galli, G Dunlap, DD Lewis, DEA Adhya, S Finzi, L AF Zurla, C Franzini, A Galli, G Dunlap, DD Lewis, DEA Adhya, S Finzi, L TI Novel tethered particle motion analysis of CI protein-mediated DNA looping in the regulation of bacteriophage lambda SO JOURNAL OF PHYSICS-CONDENSED MATTER LA English DT Article; Proceedings Paper CT Workshop on Biopolymers 2005 CY MAY 30-JUN 03, 2005 CL Trieste, ITALY ID REPRESSOR; OPERATORS AB The tethered particle motion (TPM) technique has attracted great interest because of its simplicity and the wealth of information that it can provide on protein-induced conformational changes in nucleic acids. Here we present an approach to TPM methodology and analysis that increases the efficiency of data acquisition and facilitates interpretation of TPM assays. In particular, the statistical analysis that we propose allows fast data processing, minimal data selection and visual display of the distribution of molecular behaviour. The methodology proved useful in verifying Cl protein-mediated DNA looping in bacteriophage; and in differentiating between two different types of loops, stable and dynamic, whose relative occurrence seems to be a function of the distance between the operators as well as their relative angular orientation. Furthermore, the statistical analysis indicates that Cl binding per se slightly shortens the DNA. C1 Univ Milan, Dept Biol, I-20133 Milan, Italy. San Raffaele Sci Inst, ALEMBIC, I-20132 Milan, Italy. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Finzi, L (reprint author), Univ Milan, Dept Biol, Via Celoria 26, I-20133 Milan, Italy. EM lfinzi@emory.edu NR 10 TC 24 Z9 24 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0953-8984 J9 J PHYS-CONDENS MAT JI J. Phys.-Condes. Matter PD APR 12 PY 2006 VL 18 IS 14 SI SI BP S225 EP S234 DI 10.1088/0953-8984/18/14/S07 PG 10 WC Physics, Condensed Matter SC Physics GA 047MZ UT WOS:000237884700008 ER PT J AU Kummer, W Wiegand, S Akinci, S Wessler, I Schinkel, AH Wess, J Koepsell, H Haberberger, RV Lips, KS AF Kummer, W Wiegand, S Akinci, S Wessler, I Schinkel, AH Wess, J Koepsell, H Haberberger, RV Lips, KS TI Role of acetylcholine and polyspecific cation transporters in serotonin-induced bronchoconstriction in the mouse SO RESPIRATORY RESEARCH LA English DT Article ID EXTRANEURONAL MONOAMINE TRANSPORTER; PERIPHERAL AIRWAYS; RAT; MICE; 5-HYDROXYTRYPTAMINE; RELEASE; CONTRACTION; ACTIVATION; FORMOTEROL; EXPRESSION AB Background: It has been proposed that serotonin (5-HT)-mediated constriction of the murine trachea is largely dependent on acetylcholine (ACh) released from the epithelium. We recently demonstrated that ACh can be released from non-neuronal cells by corticosteroid-sensitive polyspecific organic cation transporters (OCTs), which are also expressed by airway epithelial cells. Hence, the hypothesis emerged that 5-HT evokes bronchoconstriction by inducing release of ACh from epithelial cells via OCTs. Methods: We tested this hypothesis by analysing bronchoconstriction in precision-cut murine lung slices using OCT and muscarinic ACh receptor knockout mouse strains. Epithelial ACh content was measured by HPLC, and the tissue distribution of OCT isoforms was determined by immunohistochemistry. Results: Epithelial ACh content was significantly higher in OCT1/2 double-knockout mice (42 +/- 10 % of the content of the epithelium-denuded trachea, n = 9) than in wild-type mice (16.8 +/- 3.6 %, n = 11). In wild-type mice, 5-HT (1 mu M) caused a bronchoconstriction that slightly exceeded that evoked by muscarine (1 mu M) in intact bronchi but amounted to only 66% of the response to muscarine after epithelium removal. 5-HT-induced bronchoconstriction was undiminished in M-2/M-3 muscarinic ACh receptor double-knockout mice which were entirely unresponsive to muscarine. Corticosterone (1 mu M) significantly reduced 5-HT-induced bronchoconstriction in wildtype and OCT1/2 double-knockout mice, but not in OCT3 knockout mice. This effect persisted after removal of the bronchial epithelium. Immunohistochemistry localized OCT3 to the bronchial smooth muscle. Conclusion: The doubling of airway epithelial ACh content in OCT1/2(-/-) mice is consistent with the concept that OCT1 and/or 2 mediate ACh release from the respiratory epithelium. This effect, however, does not contribute to 5-HT-induced constriction of murine intrapulmonary bronchi. Instead, this activity involves 1) a non-cholinergic epithelium-dependent component, and 2) direct stimulation of bronchial smooth muscle cells, a response which is partly sensitive to acutely administered corticosterone acting on OCT3. These data provide new insights into the mechanisms involved in 5-HT-induced bronchoconstriction, including novel information about non-genomic, acute effects of corticosteroids on bronchoconstriction. C1 Univ Giessen, Inst Anat & Cell Biol, D-35385 Giessen, Germany. Univ Mainz, Dept Pathol, D-6500 Mainz, Germany. Netherlands Canc Inst, Div Expt Therapy, NL-1066 CX Amsterdam, Netherlands. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. Univ Wurzburg, Inst Anat & Cell Biol, D-97070 Wurzburg, Germany. Flinders Univ S Australia, Dept Anat & Histol, Adelaide, SA 50001, Australia. RP Kummer, W (reprint author), Univ Giessen, Inst Anat & Cell Biol, D-35385 Giessen, Germany. EM wolfgang.kummer@anatomie.med.uni-giessen.de; silke.wiegand@anatomie.med.uni-giessen.de; sibel.akinci@web.de; wessler@uni-mainz.de; a.schinkel@nki.nl; jwess@helix.nih.gov; Hermann@koepsell.de; Rainer.Haberberger@flinders.edu.au; katrin.s.lips@anatomie.med.uni-giessen.de OI Haberberger, Rainer Viktor/0000-0001-8043-3786 NR 24 TC 41 Z9 41 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-9921 J9 RESP RES JI Respir. Res. PD APR 12 PY 2006 VL 7 AR 65 DI 10.1186/1465-9921-7-65 PG 12 WC Respiratory System SC Respiratory System GA 049QT UT WOS:000238032200001 PM 16608531 ER PT J AU Liu, JY Wyatt, LS Amara, RR Moss, B Robinson, HL AF Liu, JY Wyatt, LS Amara, RR Moss, B Robinson, HL TI Studies on in vitro expression and in vivo immunogenicity of a recombinant MVA HIV vaccine SO VACCINE LA English DT Article DE recombinant MVA; potency; vaccine ID IMMUNODEFICIENCY VIRUS SIV; GAG-POL; PROTECTIVE IMMUNITY; RHESUS MACAQUES; ANKARA; IMMUNIZATION; DNA; REPLICATION; CHALLENGE; VECTORS AB Here we conduct dose-response studies for in vitro expression and in vivo immunogenicity for a recombinant modified vaccinia Ankara (MVA) vaccine that expresses HIV Gag, Pol, and Env proteins. The dose-response studies for in vitro expression used fluorescent-activated cell sorting to score Gag- and Env-expressing cells and showed good increases for antigen expression with increasing MVA dose. In these studies, a 1000-fold increase in the dose of MVA resulted in a 300-fold increase in the frequency of antigen-expressing cells. In contrast, dose-response studies for in vivo immunogenicity showed < 10-fold increases in elicited T cells and Ab for 100-1000-fold increases in the dose of inoculated MVA. These studies used intracellular cytokine assays to enumerate responding CD8 and CD4 T cells and an ELISA to score anti-Env Ab. The shallow dose-response curves for immunogenicity were observed post priming as well as post boosting of an MVA or a DNA prime. (c) 2006 Elsevier Ltd. All fights reserved. C1 Emory Univ, Emory Vaccine Ctr, Sch Med, Atlanta, GA 30322 USA. Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Robinson, HL (reprint author), Emory Univ, Emory Vaccine Ctr, Sch Med, 954 Gatewood Rd,Box 129, Atlanta, GA 30322 USA. EM hrobins@rmy.emory.edu FU NCRR NIH HHS [RR 00165]; NIAID NIH HHS [P01 AI 49364]; NIDA NIH HHS [P30 DA 12121] NR 28 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 12 PY 2006 VL 24 IS 16 BP 3332 EP 3339 DI 10.1016/j.vaccine.2006.01.017 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 034MA UT WOS:000236931900037 PM 16472543 ER PT J AU Stewart, I Webb, PM Schluter, PJ Fleming, LE Burns, JW Gantar, M Backer, LC Shaw, GR AF Stewart, Ian Webb, Penelope M. Schluter, Philip J. Fleming, Lora E. Burns, John W., Jr. Gantar, Miroslav Backer, Lorraine C. Shaw, Glen R. TI Epidemiology of recreational exposure to freshwater cyanobacteria - an international prospective cohort study SO BMC PUBLIC HEALTH LA English DT Article ID BLUE-GREEN-ALGAE; HEALTH AB Background: Case studies and anecdotal reports have documented a range of acute illnesses associated with exposure to cyanobacteria and their toxins in recreational waters. The epidemiological data to date are limited; we sought to improve on the design of some previously conducted studies in order to facilitate revision and refinement of guidelines for exposure to cyanobacteria in recreational waters. Methods: A prospective cohort study was conducted to investigate the incidence of acute symptoms in individuals exposed, through recreational activities, to low ( cell surface area < 2.4 mm(2)/mL), medium ( 2.4 - 12.0 mm(2)/mL) and high (> 12.0 mm(2)/mL) levels of cyanobacteria in lakes and rivers in southeast Queensland, the central coast area of New South Wales, and northeast and central Florida. Multivariable logistic regression analyses were employed; models adjusted for region, age, smoking, prior history of asthma, hay fever or skin disease ( eczema or dermatitis) and clustering by household. Results: Of individuals approached, 3,595 met the eligibility criteria, 3,193 (89%) agreed to participate and 1,331 (37%) completed both the questionnaire and follow-up interview. Respiratory symptoms were 2.1 (95% CI: 1.1 - 4.0) times more likely to be reported by subjects exposed to high levels of cyanobacteria than by those exposed to low levels. Similarly, when grouping all reported symptoms, individuals exposed to high levels of cyanobacteria were 1.7 ( 95% CI: 1.0 - 2.8) times more likely to report symptoms than their low-level cyanobacteria-exposed counterparts. Conclusion: A significant increase in reporting of minor self-limiting symptoms, particularly respiratory symptoms, was associated with exposure to higher levels of cyanobacteria of mixed genera. We suggest that exposure to cyanobacteria based on total cell surface area above 12 mm(2)/mL could result in increased incidence of symptoms. The potential for severe, life-threatening cyanobacteria-related illness is likely to be greater in recreational waters that have significant levels of cyanobacterial toxins, so future epidemiological investigations should be directed towards recreational exposure to cyanotoxins. C1 Univ Queensland, Natl Res Ctr Environm Toxicol, Coopers Plains, Qld 4108, Australia. Univ Queensland, Sch Populat Hlth, Herston, Qld 4006, Australia. Cooperat Res Ctr Water Qual & Treatment, Salisbury, SA 5108, Australia. Queensland Inst Med Res, Herston, Qld 4006, Australia. Auckland Univ Technol, Fac Hlth & Environm Sci, Auckland 1020, New Zealand. Univ Miami, NIEHS, Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. PBS&J, Jacksonville, FL 32207 USA. Florida Int Univ, Dept Biol, Miami, FL 33199 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. Griffith Univ, Sch Publ Hlth, Meadowbrook, Qld 4131, Australia. RP Stewart, I (reprint author), Univ Queensland, Natl Res Ctr Environm Toxicol, 39 Kessels Rd, Coopers Plains, Qld 4108, Australia. EM i.stewart@uq.edu.au; Penny.Webb@qimr.edu.au; philip.schluter@aut.ac.nz; LFleming@med.miami.edu; JWBurns@pbsj.com; gantarm@fiu.edu; lfb9@cdc.gov; g.shaw@griffith.edu.au RI Stewart, Ian/F-4336-2012; OI Stewart, Ian/0000-0002-7847-3188; Webb, Penelope/0000-0003-0733-5930; Schluter, Philip/0000-0001-6799-6779 FU NIEHS NIH HHS [S11 ES011181] NR 21 TC 22 Z9 25 U1 5 U2 24 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD APR 11 PY 2006 VL 6 AR 93 DI 10.1186/1471-2458-6-93 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 083QW UT WOS:000240474300001 PM 16606468 ER PT J AU Pahwa, R Factor, SA Lyons, KE Ondo, WG Gronseth, G Bronte-Stewart, H Hallett, M Miyasaki, J Stevens, J Weiner, WJ AF Pahwa, R Factor, SA Lyons, KE Ondo, WG Gronseth, G Bronte-Stewart, H Hallett, M Miyasaki, J Stevens, J Weiner, WJ TI Practice parameter: Treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology SO NEUROLOGY LA English DT Review ID DEEP-BRAIN-STIMULATION; SUBTHALAMIC NUCLEUS STIMULATION; PLACEBO-CONTROLLED TRIAL; CHRONIC ELECTRICAL-STIMULATION; MULTICENTER DOUBLE-BLIND; TERM-FOLLOW-UP; THALAMIC-STIMULATION; BILATERAL STIMULATION; MOVEMENT-DISORDERS; RANDOMIZED-TRIAL AB Objective: To make evidence-based treatment recommendations for the medical and surgical treatment of patients with Parkinson disease (PD) with levodopa-induced motor fluctuations and dyskinesia. To that end, five questions were addressed. 1. Which medications reduce off time? 2. What is the relative efficacy of medications in reducing off time? 3. Which medications reduce dyskinesia? 4. Does deep brain stimulation (DBS) of the subthalamic nucleus (STN), globus pallidus interna (GPi), or ventral intermediate (VIM) nucleus of the thalamus reduce off time, dyskinesia, and antiparkinsonian medication usage and improve motor function? 5. Which factors predict improvement after DBS? Methods: A 10-member committee including movement disorder specialists and general neurologists evaluated the available evidence based on a structured literature review including MEDLINE, EMBASE, and Ovid databases from 1965 through June 2004. Results, Conclusions, and Recommendations: 1. Entacapone and rasagiline should be offered to reduce off time (Level A). Pergolide, pramipexole, ropinirole, and tolcapone should be considered to reduce off time (Level B). Apomorphine, cabergoline, and selegiline may be considered to reduce off time (Level C). 2. The available evidence does not establish superiority of one medicine over another in reducing off time (Level B). Sustained release carbidopa/levodopa and bromocriptine may be disregarded to reduce off time (Level C). 3. Amantadine may be considered to reduce dyskinesia (Level C). 4. Deep brain stimulation of the STN may be considered to improve motor function and reduce off time, dyskinesia, and medication usage (Level C). There is insufficient evidence to support or refute the efficacy of DBS of the GPi or VIM nucleus of the thalamus in reducing off time, dyskinesia, or medication usage, or to improve motor function. 5. Preoperative response to levodopa predicts better outcome after DBS of the STN (Level B). C1 Univ Kansas, Med Ctr, Kansas City, KS USA. Emory Univ, Sch Med, Atlanta, GA USA. Baylor Coll Med, Houston, TX 77030 USA. Stanford Univ Hosp, San Francisco, CA USA. NIH, Bethesda, MD 20892 USA. Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. Ft Wayne Neurol Ctr, Ft Wayne, IN USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Pahwa, R (reprint author), Amer Acad Neurol, 1080 Montreal Ave, St Paul, MN 55116 USA. OI Miyasaki, Janis/0000-0002-6372-6007 NR 59 TC 267 Z9 285 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 11 PY 2006 VL 66 IS 7 BP 983 EP 995 DI 10.1212/01.wnl.0000215250.82576.87 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 030ZG UT WOS:000236673300007 PM 16606909 ER PT J AU Miyasaki, JM Shannon, K Voon, V Ravina, B Kleiner-Fisman, G Anderson, K Shulman, LM Gronseth, G Weiner, WJ AF Miyasaki, JM Shannon, K Voon, V Ravina, B Kleiner-Fisman, G Anderson, K Shulman, LM Gronseth, G Weiner, WJ TI Practice Parameter: Evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology SO NEUROLOGY LA English DT Review ID COGNITIVE IMPAIRMENT; NONMOTOR SYMPTOMS; CONTROLLED TRIAL; LEWY BODIES; RATING-SCALE; RIVASTIGMINE; INSTRUMENT; OLANZAPINE; CLOZAPINE; VALIDITY AB Objective: To make evidence-based treatment recommendations for patients with Parkinson disease (PD) with dementia, depression, and psychosis based on these questions: 1) What tools are effective to screen for depression, psychosis, and dementia in PD? 2) What are effective treatments for depression and psychosis in PD? 3) What are effective treatments for PD dementia or dementia with Lewy bodies (DLB)? Methods: A nine-member multispecialty committee evaluated available evidence from a structured literature review using MEDLINE, and the Cochrane Database of Health and Psychosocial Instruments from 1966 to 2004. Additional articles were identified by panel members. Results: The Beck Depression Inventory-I, Hamilton Depression Rating Scale, and Montgomery Asberg Depression Rating Scale should be considered to screen for depression in PD (Level B). The Mini-Mental State Examination and the Cambridge Cognitive Examination should be considered to screen for dementia in PD (Level B). Amitriptyline may be considered to treat depression in PD without dementia (Level C). For psychosis in PD, clozapine should be considered (Level B), quetiapine may be considered (Level C), but olanzapine should not be considered (Level B). Donepezil or rivastigmine should be considered for dementia in PD (Level B) and rivastigmine should be considered for DLB (Level B). Conclusions: Screening tools are available for depression and dementia in patients with PD, but more specific validated tools are needed. There are no widely used, validated tools for psychosis screening in Parkinson disease (PD). Clozapine successfully treats psychosis in PD. Cholinesterase inhibitors are effective treatments for dementia in PD, but improvement is modest and motor side effects may occur. C1 Univ Toronto, Toronto, ON, Canada. Rush Univ, Med Ctr, Chicago, IL 60612 USA. NIH, Bethesda, MD 20892 USA. Univ Rochester, Rochester, NY USA. Univ Pennsylvania, Philadelphia, PA USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Kansas, Kansas City, KS USA. RP Miyasaki, JM (reprint author), Amer Acad Neurol, 1080 Montreal Ave, St Paul, MN 55116 USA. OI Miyasaki, Janis/0000-0002-6372-6007 NR 35 TC 215 Z9 231 U1 0 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 11 PY 2006 VL 66 IS 7 BP 996 EP 1002 DI 10.1212/01.wnl.0000215428.46057.3d PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 030ZG UT WOS:000236673300008 PM 16606910 ER PT J AU Thijs, RD Kruit, MC van Buchem, MA Ferrari, MD Launer, LJ van Dijk, JG AF Thijs, RD Kruit, MC van Buchem, MA Ferrari, MD Launer, LJ van Dijk, JG TI Syncope in migraine - The population-based CAMERA study SO NEUROLOGY LA English DT Article ID NERVOUS-SYSTEM FUNCTION; AUTONOMIC DYSFUNCTION; CARDIOVASCULAR REFLEXES; TACHYCARDIA SYNDROME; HEADACHE; PREVALENCE; MANAGEMENT; DIAGNOSIS AB Objective: To examine the association between migraine and syncope-related autonomic nervous system (ANS) symptoms. Methods: A population-based study among migraineurs with and without aura (n = 323) and control subjects (n = 153) was conducted. A systematic questionnaire and cardiovascular measurements during rest, while standing, and after venipuncture addressed the prevalence of syncope, orthostatic intolerance, orthostatic hypotension (OH), and the postural tachycardia syndrome (POTS) in migraineurs and control subjects. Results: The lifetime prevalence of syncope in all participants was 41%, more often in women (45 vs 32%; p = 0.02). Compared with control subjects, migraineurs had a higher lifetime prevalence of syncope (46 vs 31%; p = 0.001), frequent syncope (five or more attacks) (13 vs 5%; p = 0.02), and orthostatic intolerance (32 vs 12%; p = 0.001). There was no association between ANS symptoms and the severity of migraine or migraine subtype. Cardiovascular measurements and the prevalence of POTS and OH did not differ significantly between migraineurs and control subjects. Conclusion: This population-based study demonstrated an elevated prevalence of syncope and orthostatic intolerance in migraineurs without clear interictal signs of autonomic nervous system dysfunction. C1 Leiden Univ, Med Ctr, Dept Neurol & Clin Neurophysiol, NL-2300 RC Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. Natl Inst Publ Hlth & Environm, Ctr Prevent & Hlth Serv Res, NL-3720 BA Bilthoven, Netherlands. NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. RP Thijs, RD (reprint author), Leiden Univ, Med Ctr, Dept Neurol & Clin Neurophysiol, Postal Zone J3-R,POB 9600, NL-2300 RC Leiden, Netherlands. EM r.d.thijs@lumc.nl RI Kruit, Mark/K-2431-2012 OI Kruit, Mark/0000-0002-4319-834X FU Intramural NIH HHS NR 25 TC 58 Z9 59 U1 1 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 11 PY 2006 VL 66 IS 7 BP 1034 EP 1037 DI 10.1212/01.wnl.0000204186.43597.66 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 030ZG UT WOS:000236673300014 PM 16606915 ER PT J AU Sumner, CJ Kolb, SJ Harmison, GG Jeffries, NO Schadt, K Finkel, RS Dreyfuss, G Fischbeck, KH AF Sumner, CJ Kolb, SJ Harmison, GG Jeffries, NO Schadt, K Finkel, RS Dreyfuss, G Fischbeck, KH TI SMN mRNA and protein levels in peripheral blood - Biomarkers for SMA clinical trials SO NEUROLOGY LA English DT Article ID SPINAL MUSCULAR-ATROPHY; MOTOR-NEURON PROTEIN; VALPROIC ACID INCREASES; GENE-EXPRESSION; SINGLE NUCLEOTIDE; SURVIVAL; SEVERITY; CELLS; PCR; IDENTIFICATION AB Background: Clinical trials of drugs that increase SMN protein levels in vitro are currently under way in patients with spinal muscular atrophy. Objective: To develop and validate measures of SMN mRNA and protein in peripheral blood and to establish baseline SMN levels in a cohort of controls, carriers, and patients of known genotype, which could be used to follow response to treatment. Methods: SMN1 and SMN2 gene copy numbers were determined in blood samples collected from 86 subjects. Quantitative reverse transcription PCR was used to measure blood levels of SMN mRNA with and without exon 7. A cell immunoassay was used to measure blood levels of SMN protein. Results: Blood levels of SMN mRNA and protein were measured with high reliability. There was little variation in SMN levels in individual subjects over a 5-week period. Levels of exon 7-containing SMN mRNA and SMN protein correlated with SMN1 and SMN2 gene copy number. With the exception of type I SMA, there was no correlation between SMN levels and disease severity. Conclusion: SMN mRNA and protein levels can be reliably measured in the peripheral blood and used during clinical trials in spinal muscular atrophy, but these levels do not necessarily predict disease severity. C1 NINDS, Neurogenet Branch, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Dept Neurol, Philadelphia, PA USA. Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Sumner, CJ (reprint author), NINDS, Neurogenet Branch, Bldg 35-Rm 2A1010,35 Convent Dr, Bethesda, MD 20892 USA. EM sumnerc@ninds.nih.gov RI Kolb, Stephen/E-3415-2011 FU Intramural NIH HHS; NINDS NIH HHS [K22-NS0048199-01] NR 34 TC 48 Z9 48 U1 1 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 11 PY 2006 VL 66 IS 7 BP 1067 EP 1073 DI 10.1212/01.wnl.0000201929.56928.13 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 030ZG UT WOS:000236673300020 PM 16481599 ER PT J AU Yang, Y Kovacs, M Sakamoto, T Zhang, F Kiehart, DP Sellers, JR AF Yang, Y Kovacs, M Sakamoto, T Zhang, F Kiehart, DP Sellers, JR TI Dimerized Drosophila myosin VIIa: A processive motor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE fluorescence imaging with one-nanometer accuracy; kinetics; processivity ID DUTY RATIO MOTOR; HAND-OVER-HAND; KINETIC MECHANISM; FLUORESCENT-PROBE; ATPASE ACTIVITY; LINKER PROTEIN; STEP-SIZE; ACTIN; SHAKER-1; DOMAIN AB The molecular mechanism of processive movement of single myosin molecules from classes V and VI along their actin tracks has recently attracted extraordinary attention. Another member of the myosin superfamily, myosin VII, plays vital roles in the sensory function of Drosophila and mammals. We studied the molecular mechanism of Drosophila myosin Vila, using transient kinetics and single-molecule motility assays. Myosin Vila moves along actin filaments as a processive, double-headed single molecule when dimerized by the inclusion of a leucine zipper at the C terminus of the coiled-coil domain. Its motility is approximate to 8-10 times slower than that of myosin V, and its step size is 30 nm, which is consistent with the presence of five IQ motifs in its neck region. The kinetic basis for the processive motility of myosin Vila is the relative magnitude of the release rate constants of phosphate (fast) and ADP (slow) as in myosins V and VI. The ATPase pathway is rate-limited by a reversible interconversion between two distinct ADP-bound actomyosin states, which results in high steady-state occupancy of a strongly actin-bound myosin species. The distinctive features of myosin Vila (long run lengths, slow motility) will be very useful in video-based single-molecule applications. in cells, this kinetic behavior would allow myosin Vila to exert and hold tension on actin filaments and, if dimerized, to function as a processive cargo transporter. C1 NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. Eotvos Lorand Univ, Dept Biochem, H-1117 Budapest, Hungary. Duke Univ, Dept Biol, Dev Cell & Mol Biol Grp, Durham, NC 27708 USA. RP Sellers, JR (reprint author), NHLBI, Lab Mol Physiol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM sellersj@nhlbl.nih.gov RI Kovacs, Mihaly/A-6841-2011 FU FIC NIH HHS [D43 TW006230, 1 R01 TW007241-01, R01 TW006230, R01 TW007241]; NIDCD NIH HHS [R01 DC007673] NR 40 TC 37 Z9 38 U1 2 U2 7 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 11 PY 2006 VL 103 IS 15 BP 5746 EP 5751 DI 10.1073/pnas.0509935103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 034AK UT WOS:000236896200022 PM 16585515 ER PT J AU Missirlis, F Holmberg, S Georgieva, T Dunkov, BC Rouault, TA Law, JH AF Missirlis, F Holmberg, S Georgieva, T Dunkov, BC Rouault, TA Law, JH TI Characterization of mitochondrial ferritin in Drosophila SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE iron; metabolism; mitochondria; paraquat; testis ID IRON-METABOLISM; INSECT FERRITIN; EXPRESSION; MELANOGASTER; CELLS; GENE; HOMEOSTASIS; CLONING AB Mitochondrial function depends on iron-containing enzymes and proteins, whose maturation requires available iron for biosynthesis of iron-sulfur clusters and heme. Little is known about how mitochondrial iron homeostasis is maintained, although the recent discovery of a mitochondrial ferritin in mammals and plants has uncovered a potential key player in the process. Here, we show that Drosophila melanogaster expresses mitochondrial ferritin from an intron-containing gene. It has high similarity to the mouse and human mitochondrial ferritin sequences and, as in mammals, is expressed mainly in testis. This ferritin contains a putative mitochondrial targeting sequence and an epitope-tagged version localizes to mitochondria in transfected cells. Overexpression of mitochondrial ferritin fails to alter both total-body iron levels and iron that is bound to secretory ferritins. However, the viability of iron-deficient flies is compromised by overexpression of mitochondrial ferritin, suggesting that it may sequester iron at the expense of other important cellular functions. The conservation of mitochondrial ferritin in an insect species underscores the importance of this iron-storage molecule. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Arizona, Dept Biochem & Mol Biophys, Tucson, AZ 85721 USA. Univ Arizona, Ctr Insect Sci, Tucson, AZ 85721 USA. RP Law, JH (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM jhlaw@u.arizona.edu RI Missirlis, Fanis/C-1137-2011 OI Missirlis, Fanis/0000-0003-0467-8444 FU Intramural NIH HHS; NIGMS NIH HHS [GM 58918, GM 60471, R01 GM058918] NR 32 TC 67 Z9 72 U1 1 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 11 PY 2006 VL 103 IS 15 BP 5893 EP 5898 DI 10.1073/pnas.0601471103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 034AK UT WOS:000236896200047 PM 16571656 ER PT J AU Egland, KA Liu, XF Squires, S Nagata, S Man, YG Bera, TK Onda, M Vincent, JJ Strausberg, RL Lee, B Pastan, I AF Egland, KA Liu, XF Squires, S Nagata, S Man, YG Bera, TK Onda, M Vincent, JJ Strausberg, RL Lee, B Pastan, I TI High expression of a cytokeratin-associated protein in many cancers SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE breast cancer; colon cancer; intermediate filaments; mitosis; prostate cancer ID CELLS; RECEPTOR AB We have described previously a cDNA library made from membrane-bound polysomal mRNA prepared from breast and prostate cancer cell lines. The library is highly enriched for cDNAs encoding membrane proteins, secreted proteins, and cytokeratins. To characterize this library, 25,277 cDNA clones were sequenced and aligned with various databases; 1,439 clones did not align with known genes. From this set of clones we identified a previously uncharacterized gene encoding a 334-aa protein. Although protein structural motif prediction programs indicate that the gene encodes a membrane protein comprising a signal sequence, a series of leucine-rich repeats, and a single transmembrane domain with a cytoplasmic tail, confocal microscopy of MCF7 breast cancer cells demonstrates that the protein is not directly associated with the plasma membrane or intracellular membranes but instead colocalizes with intermediate filaments and cytokeratins within the cell. Immunofluorescence studies also show that protein expression is increased greatly in mitotic MCF7 cells, and immunohistochemistry demonstrates its expression in human breast cancer cells. Analysis of mRNA levels in 25 different normal tissues by RT-PCR shows that this gene is expressed highly in normal prostate and salivary gland, very weakly in colon, pancreas, and intestine, and not at all in other tissues. RT-PCR studies on human cancer samples show that the RNA is expressed highly in many cancer cell lines and cancer specimens, including 26 of 33 human breast cancers, 3 of 3 prostate cancers, 3 of 3 colon cancers, and 3 of 3 pancreatic cancers. We name the protein CAPC, cytokeratin-associated protein in cancer. C1 Univ S Dakota, Sch Med, S Dakota Hlth Res Fdn, Signal Transduct Inst, Sioux Falls, SD 57105 USA. Sioux Valley Hosp & Hlth Syst, Sioux Falls, SD 57105 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Gynecol & Breast Canc Pathol, Washington, DC 20306 USA. Craig Venter Inst, Rockville, MD 20850 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov FU Intramural NIH HHS NR 14 TC 13 Z9 14 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 11 PY 2006 VL 103 IS 15 BP 5929 EP 5934 DI 10.1073/pnas.0601296103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 034AK UT WOS:000236896200053 PM 16585525 ER PT J AU Bielekova, B Catalfamo, M Reichert-Scrivner, S Packer, A Cerna, M Waldmann, TA McFarland, H Henkart, PA Martin, R AF Bielekova, B Catalfamo, M Reichert-Scrivner, S Packer, A Cerna, M Waldmann, TA McFarland, H Henkart, PA Martin, R TI Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2R alpha-targeted therapy (daclizumab) in multiple sclerosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CD25; IL-2; immunoregulatory natural killer cells ID HUMANIZED ANTI-TAC; T-CELLS; INTERLEUKIN-2 RECEPTOR; NK CELLS; IL-2 RECEPTOR; AUTOIMMUNE-DISEASE; INTERFERON-BETA; DA RAT; RESPONSES; EXPRESSION AB Administration of daclizumab, a humanized mAb directed against the IL-2R alpha chain, strongly reduces brain inflammation in multiple sclerosis patients. Here we show that daclizumab treatment leads to only a mild functional blockade of CD4(+) T cells, the major candidate in multiple sclerosis pathogenesis. Instead, daclizumab therapy was associated with a gradual decline in circulating CD4(+) and CD8(+) T cells and significant expansion of CD56(bright) natural killer (INK) cells in vivo, and this effect correlated highly with the treatment response. In vitro studies showed that NK cells inhibited T cell survival in activated peripheral blood mononuclear cell cultures by a contact-dependent mechanism. Positive correlations between expansion of CD56(bright) NK cells and contraction of CD4(+) and CD8(+) T cell numbers in individual patients in vivo provides supporting evidence for NK cell-mediated negative immunoregulation of activated T cells during daclizumab therapy. Our data support the existence of an immunoregulatory pathway wherein activated CD56(bright) NK cells inhibit T cell survival. This immunoregulation has potential importance for the treatment of autoimmune diseases and transplant rejection and toward modification of tumor immunity. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Dept Neurol, Cincinnati, OH 45230 USA. Univ Barcelona, Hosp Gen Valle Hebron, Catalan Inst Res & Adv Studies, Barcelona 08035, Spain. Univ Barcelona, Hosp Gen Valle Hebron, Unidad Neuroimmunol Clin, Barcelona 08035, Spain. RP Bielekova, B (reprint author), NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. EM bibi.bielekova@uc.edu FU Intramural NIH HHS NR 36 TC 312 Z9 322 U1 1 U2 7 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 11 PY 2006 VL 103 IS 15 BP 5941 EP 5946 DI 10.1073/pnas.0601335103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 034AK UT WOS:000236896200055 PM 16585503 ER PT J AU Thornley-Brown, D Wang, XL Wright, JT Randall, OS Miller, ER Lash, JP Gassman, J Contreras, G Appel, LJ Agodoa, LY Cheek, D AF Thornley-Brown, D Wang, XL Wright, JT Randall, OS Miller, ER Lash, JP Gassman, J Contreras, G Appel, LJ Agodoa, LY Cheek, D CA African American Study Kidney Dis TI Differing effects of antihypertensive drugs on the incidence of diabetes mellitus among patients with hypertensive kidney disease SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; LIPID-LOWERING TREATMENT; END-POINT REDUCTION; INSULIN-RESISTANCE; BLOOD-PRESSURE; CARDIOVASCULAR MORBIDITY; LOSARTAN INTERVENTION; GLUCOSE; OUTCOMES; RISK AB Background: The African American Study of Kidney Disease and Hypertension was a multicenter trial of African Americans with hypertensive kidney disease randomized to an angiotensin-converting enzyme inhibitor (ramipril), a beta-blocker (metoprolol succinate), or a calcium channel blocker (amlodipine besylate). We compared the incidence of type 2 diabetes mellitus (DM) and the composite outcome of impaired fasting glucose or DM (IFG/DM) for the African American Study of Kidney Disease and Hypertension interventions. Methods: Cox regression models were used to evaluate (post hoc) the association of the randomized interventions and the relative risk (RR) of DM and IFG/DM and to assess the RR of DM and IFG/DM by several prerandomization characteristics. Results: Among 1017 participants, 147 (14.5%) developed DM; 333 (42.9%) of 776 participants developed IFG/DM. Respective DM event rates were 2.8%, 4.4%, and 4.5% per patient-year in the ramipril-, amlodipine-, and meto-prolol-treated groups. The RRs of DM with ramipril treatment were 0.53 (P = .001) compared with metoprolol treatment and 0.49 (P = .003) compared with amlodipine treatment. Respective IFG/DM event rates were 11.3%, 13.3%, and 15.8% per patient-year in the ramipril-, amlodipine, and metoprolol-treated groups. The RRs of IFG/DM with ramipril treatment were 0.64 (P < .001) compared with metoprolol treatment and 0.76 (P = .09) compared with amlodipine treatment. The RRs of DM and IFG/ DM with amlodipine treatment compared with metoprolol treatment were 1.07 (P = .76) and 0.84 (P = .26), respectively. Conclusion: Ramipril treatment was associated with a significantly lower risk of DM in African Americans with hypertensive kidney disease than amlodipine or metoprolol treatment. C1 Univ Alabama, Div Nephrol, Birmingham, AL 35294 USA. Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Case Western Reserve Univ, Louis Stokes Cleveland Vet Adm Med Ctr, Cleveland, OH 44106 USA. Howard Univ Hosp, Washington, DC USA. Johns Hopkins Univ, Dept Med & Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Welch Ctr, Baltimore, MD USA. NIA, Baltimore, MD 21224 USA. Univ Illinois, Nephrol Sect, Chicago, IL USA. Univ Miami, Div Nephrol, Miami, FL 33152 USA. NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Div Pediat Nephrol, Charleston, SC 29425 USA. RP Thornley-Brown, D (reprint author), Univ Alabama, Div Nephrol, PB 234,1530 3rd Ave S, Birmingham, AL 35294 USA. EM dtb@uab.edu FU NCRR NIH HHS [M01 RR00032, M01 RR00080, M01 RR00827, P20 RR11145, 5M01 RR00071, 2P20 RR11104] NR 39 TC 19 Z9 21 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 10 PY 2006 VL 166 IS 7 BP 797 EP 805 DI 10.1001/archinte.166.7.797 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 031BT UT WOS:000236679800014 PM 16606818 ER PT J AU Einhorn, PT Cutler, JA AF Einhorn, PT Cutler, JA TI Action on racial disparity in hypertension control SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID LIPID-LOWERING TREATMENT; ATTACK TRIAL ALLHAT C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Einhorn, PT (reprint author), NHLBI, Div Epidemiol & Clin Applicat, 6701 Rockledge Dr,Room 8122, Bethesda, MD 20892 USA. EM einhornp@mail.nih.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 10 PY 2006 VL 166 IS 7 BP 812 EP 812 DI 10.1001/archinte.166.7.812 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 031BT UT WOS:000236679800016 PM 16606820 ER PT J AU Acharya, U Edwards, MB Jorquera, RA Silva, H Nagashima, K Labarca, P Acharya, JK AF Acharya, U Edwards, MB Jorquera, RA Silva, H Nagashima, K Labarca, P Acharya, JK TI Drosophila melanogaster Scramblases modulate synaptic transmission SO JOURNAL OF CELL BIOLOGY LA English DT Article ID MEMBRANE PHOSPHOLIPID SCRAMBLASE; VESICLE POOLS; NEUROMUSCULAR-JUNCTION; TRANSBILAYER MOVEMENT; SURFACE EXPOSURE; INTERFERON-ALPHA; IMMUNE-RESPONSE; RESERVE POOL; PROTEIN; GENE AB Scramblases are a family of single-pass plasma membrane proteins, identified by their purported ability to scramble phospholipids across the two layers of plasma membrane isolated from platelets and red blood cells. However, their true in vivo role has yet to be elucidated. We report the generation and isolation of null mutants of two Scramblases identified in Drosophila melanogaster. We demonstrate that flies lacking either or both of these Scramblases are not compromised in vivo in processes requiring scrambling of phospholipids. instead, we show that D. melanogaster lacking both Scramblases have more vesicles and display enhanced recruitment from a reserve pool of vesicles and increased neurotransmitter secretion at the larval neuromuscular synapses. These defects are corrected by the introduction of a genomic copy of the Scramb 1 gene. The lack of phenotypes related to failure of scrambling and the neurophysiological analysis lead us to propose that Scramblases play a modulatory role in the process of neurotransmission. C1 NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. Ctr Estudios Cient, Valdivia 5110246, Chile. Sci Applicat Int Corp, Image Anal Lab, EM Facil, Frederick, MD 21702 USA. Univ Austral Chile, Valdivia 5099200, Chile. RP Acharya, JK (reprint author), NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. EM acharyaj@mail.ncifcrf.gov RI Jorquera, Ramon/H-9985-2012 OI Jorquera, Ramon/0000-0002-5460-1755 FU Intramural NIH HHS NR 52 TC 19 Z9 21 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD APR 10 PY 2006 VL 173 IS 1 BP 69 EP 82 DI 10.1083/jcb.200506159 PG 14 WC Cell Biology SC Cell Biology GA 032IA UT WOS:000236766900010 PM 16606691 ER PT J AU Raychaudhuri, S Im, YJ Hurley, JH Prinz, WA AF Raychaudhuri, S Im, YJ Hurley, JH Prinz, WA TI Nonvesicular sterol movement from plasma membrane to ER requires oxysterol-binding protein-related proteins and phosphoinositides SO JOURNAL OF CELL BIOLOGY LA English DT Article ID YEAST SACCHAROMYCES-CEREVISIAE; PHOSPHATIDYLINOSITOL TRANSFER PROTEINS; PLECKSTRIN HOMOLOGY DOMAIN; ENDOPLASMIC-RETICULUM; BREFELDIN-A; SHUTTLE VECTORS; GOLGI PROTEINS; TRANSPORT; CHOLESTEROL; METABOLISM AB Sterols are moved between cellular membranes by nonvesicular pathways whose functions are poorly understood. In yeast, one such pathway transfers sterols from the plasma membrane (PM) to the endoplasmic reticulum (ER). We show that this transport requires oxysterol-binding protein (OSBP)-related proteins (ORPs), which are a large family of conserved lipid-binding proteins. We demonstrate that a representative member of this family, Osh4p/Kes1p, specifically facilitates the nonvesicular transfer of cholesterol and ergosterol between membranes in vitro. In addition, Osh4p transfers sterols more rapidly between membranes containing phosphoinositides (PIPs), suggesting that PIPs regulate sterol transport by ORPs. We confirmed this by showing that PM to ER sterol transport slows dramatically in mutants with conditional defects in PIP biosynthesis. Our Findings argue that ORPs move sterols among cellular compartments and that sterol transport and intracellular distribution are regulated by PIPs. C1 NIDDKD, Lab Cell Biochem & Biol, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIDDKD, Mol Biol Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP NIDDKD, Lab Cell Biochem & Biol, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM wprinz@helix.nih.gov OI Raychaudhuri, Sumana/0000-0002-3164-0057 FU Intramural NIH HHS NR 56 TC 153 Z9 153 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD APR 10 PY 2006 VL 173 IS 1 BP 107 EP 119 DI 10.1083/jcb.200510084 PG 13 WC Cell Biology SC Cell Biology GA 032IA UT WOS:000236766900013 PM 16585271 ER PT J AU Kobayashi, H Kawamoto, S Bernardo, M Brechbiel, MW Knopp, MV Choyke, PL AF Kobayashi, H Kawamoto, S Bernardo, M Brechbiel, MW Knopp, MV Choyke, PL TI Delivery of gadolinium-labeled nanoparticles to the sentinel lymph node: Comparison of the sentinel node visualization and estimations of intra-nodal gadolinium concentration by the magnetic resonance imaging SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE breast cancer; MRI; sentinel lymph node; nanoparticle; gadolinium neutron capture therapy ID NEUTRON-CAPTURE THERAPY; POLYAMIDOAMINE DENDRIMER CORE; DOUBLE-STRAND BREAKS; MRI CONTRAST AGENTS; GLOMERULAR-FILTRATION; CT LYMPHOGRAPHY; GENE DELIVERY; BRAIN-TUMORS; OLIGO-DNA; IN-VITRO AB Sentinel node imaging is commonly performed prior to surgery for breast cancer and melanoma. While current methods are based on radio-lymphoscintigraphy, MR lymphangiography (MRL) offers the benefits of better spatial resolution without ionizing radiation. However, the optimal nanoparticle for imaging the sentinel nodes remains unclear. Gadolinium-labeled (Gd) contrast agents ranging in diameter from < 1 to 12 nm were evaluated to determine which size provides the most rapid and most concentrated delivery of contrast agent to the lymph nodes in a mouse model of lymphatic metastases. Specifically, PAMAM-G2, -G4, -G6 and -G8, and DAB-G5 Gd-dendrimer agents, as well as Gadomer-17 and Gd-DTPA, were compared. Among these agents, the G6 Gd dendrimer depicted the lymphatics and lymph nodes with the highest peak concentrations and this occurred 24-36 min post-injection (p < 0.01; all except G8). Based on ex vivo concentration phantoms, high accumulations of Gd(III) ions occurred within lymph nodes (1.7-4.4 mM Gd/270-680 ppm Gd) with high target to background ratios (> 100). These concentrations are sufficient to contemplate the use of Gd-neutron capture therapy of regional lymph nodes. Thus, when injected interstitially, the PAMAM-G6 Gd dendrimer not only provides excellent opacification of sentinel lymph nodes, but also provides the potential for targeted therapy of sentinel lymph nodes. Published by Elsevier B.V. C1 NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. NCI, SAIC Frederick, Mol Imaging Program, Ctr Canc Res,NIH, Frederick, MD 21701 USA. NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Dept Radiol, Columbus, OH 43210 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room 1B40,MSC1088,10 Ctr Dr, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov FU Intramural NIH HHS NR 58 TC 85 Z9 93 U1 3 U2 32 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD APR 10 PY 2006 VL 111 IS 3 BP 343 EP 351 DI 10.1016/j.jconrel.2005.12.019 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 037NO UT WOS:000237153900012 PM 16490277 ER PT J AU Lee, PR Cohen, JE Fields, RD AF Lee, PR Cohen, JE Fields, RD TI Immune system evasion by peripheral nerve sheath tumor SO NEUROSCIENCE LETTERS LA English DT Article DE NF1; T265; Schwann; splicing; MHC2TA; TAP1; CD74; cancer; MHC ID CLASS-II GENES; INVARIANT CHAIN; SCHWANN-CELLS; NEUROFIBROMATOSIS; EXPRESSION AB Mechanisms by which tumor cells evade detection by the host's immune system are thought to play a role in progression to malignancy, but this has not been investigated in the context of neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant disorder, in which aggressive peripheral nerve tumors, known as malignant peripheral nerve sheath tumors (MPNSTs), develop in 5-10% of patients. Large scale gene expression profiling of a MPNST-derived cell line, T265, and normal human Schwann cells (hSCs) identified a large group of immune function genes down-regulated in T265 cells. Here we report that the aberrant expression of immune system related genes extends beyond MHC class I and II genes in T265 cells to include a transcription factor (MHC2TA) and other critical components of the antigen processing and presentation apparatus. TAP1, the transporter-activator protein that loads peptide antigens onto MHC class I molecules, is down-regulated, and CD74, a chaperone protein whose function is in processing and transport of MHC class II molecules, is down-regulated and alternatively spliced to produce an RNA transcript not evident in normal human Schwann cells. These findings reveal multiple molecular pathways and at least two cellular mechanisms acting to reduce the normal immune system molecules involved in antigen processing and presentation in cells derived from a peripheral nerve sheath tumor. Acquiring a "silent" immune signature may be a critical step in the progress towards malignancy in MPNSTs. Published by Elsevier Ireland Ltd. C1 NICHD, Nervous Syst Dev & Plast Sect, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHD, Nervous Syst Dev & Plast Sect, NIH, Bldg 35,room 2A211,MSC 3713,35 Lincoln Dr, Bethesda, MD 20892 USA. EM fieldsd@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 12 TC 6 Z9 8 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 10 PY 2006 VL 397 IS 1-2 BP 126 EP 129 DI 10.1016/j.neulet.2005.12.027 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 025CA UT WOS:000236241700026 PM 16406348 ER PT J AU Caston, JR Luque, D Trus, BL Rivas, G Alfonso, C Gonzalez, JM Carrascosa, JL Annamalai, P Ghabrial, SA AF Caston, JR Luque, D Trus, BL Rivas, G Alfonso, C Gonzalez, JM Carrascosa, JL Annamalai, P Ghabrial, SA TI Three-dimensional structure and stoichiometry of Helmintosporium victoriae190S totivirus SO VIROLOGY LA English DT Article DE Hv190SV; double-stranded RNA; virus capsid; cryo-electron microscopy; three-dimensional structure ID DOUBLE-STRANDED-RNA; PENICILLIUM-CHRYSOGENUM-VIRUS; MAJOR CAPSID PROTEIN; L-A VIRUS; HELMINTHOSPORIUM-VICTORIAE; MOLECULAR CHARACTERIZATION; ELECTRON-MICROGRAPHS; ANGSTROM RESOLUTION; SECONDARY STRUCTURE; ATOMIC-STRUCTURE AB Most double-stranded RNA viruses have a characteristic capsid consisting of 60 asymmetric coat protein dimers in a so-called T = 2 organization, a feature probably related to their unique life cycle. These capsids organize the replicative complex(es) that is actively involved in genome transcription and replication. Available structural data indicate that their RNA-dependent RNA polymerase (RDRP) is packaged as an integral capsid component, either as a replicative complex at the pentameric vertex (as in reovirus capsids) or as a fusion protein with the coat protein (as in some totivirus). In contrast with members of the family Reoviridae, there are two well-established capsid arrangements for dsRNA fungal viruses, exemplified by the totiviruses L-A and UmV and the chrysovirus PcV. Whereas L-A and UmV have a canonical T = 2 capsid, the PcV capsid is based on a T = 1 lattice composed of 60 capsid proteins. We used cryo-electron microscopy combined with three-dimensional reconstruction techniques and hydrodynamic analysis to determine the structure at 13.8 A resolution of Helminthosporium victoriae 190S virus (Hv190SV), a totivirus isolated from a filamentous fungus. The Hv190SV capsid has a smooth surface and is based on a T = 2 lattice with 60 equivalent dimers. Unlike the RDRP of some other totiviruses, which are expressed as a capsid protein-RDRP fusion protein, the Hv190SV RDRP is incorporated into the capsid as a separate, nonfused protein, free or non-covalently associated to the capsid interior. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Autonoma Madrid, CSIC, Ctr Nacl Biotecnol, Dept Estructura Macromol, E-28049 Madrid, Spain. NIAMS, Imaging Sci Lab, CIT, NIH,DHHS, Bethesda, MD 20892 USA. NIAMS, Struct Biol Res Lab, NIH, DHHS, Bethesda, MD 20892 USA. CSIC, Ctr Invest Biol, E-28006 Madrid, Spain. Univ Kentucky, Dept Plant Pathol, Lexington, KY 40546 USA. RP Caston, JR (reprint author), Univ Autonoma Madrid, CSIC, Ctr Nacl Biotecnol, Dept Estructura Macromol, Darwin 3,Cantoblanco, E-28049 Madrid, Spain. EM jrcaston@cnb.uam.es RI Alfonso, Carlos/K-1316-2014; Caston, Jose/L-5896-2014; Luque, Daniel/I-6467-2015; OI Alfonso, Carlos/0000-0001-7165-4800; Caston, Jose/0000-0003-2350-9048; Luque, Daniel/0000-0002-0151-6020; Gonzalez, Jose M/0000-0001-5569-0705; Rivas, German/0000-0003-3450-7478 FU Intramural NIH HHS NR 55 TC 17 Z9 18 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 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 2006 VL 347 IS 2 BP 323 EP 332 DI 10.1016/j.virol.2005.11.038 PG 10 WC Virology SC Virology GA 038CS UT WOS:000237196600007 PM 16413593 ER PT J AU Rulli, SJ Muriaux, D Nagashima, K Mirro, J Oshima, M Baumann, JG Rein, A AF Rulli, SJ Muriaux, D Nagashima, K Mirro, J Oshima, M Baumann, JG Rein, A TI Mutant murine leukemia virus Gag proteins lacking proline at the N-terminus of the capsid domain block infectivity in virions containing wild-type Gag SO VIROLOGY LA English DT Article DE retroviruses; capsid proteins; infectivity; reverse transcription; dominant negative; trans-dominant; phenotypic mixing; virus maturation ID REVERSE-TRANSCRIPTASE; VIRAL REPLICATION; GENE-TRANSFER; CORE; RNA; DNA; MORPHOGENESIS; INHIBITION; MATURATION; CELLS AB We have investigated the properties of murine leukemia virus Gag mutants in which the p12-CA cleavage site is altered. In one mutant, the cleavage is blocked; in the other, the conserved proline at the N-terminus of CA has been replaced with glycine. No infectivity was detected in either mutant. Mutant particles cannot synthesize full-length DNA upon infecting permissive cells. Particles composed of a mixture of wild-type and mutant proteins have severely impaired infectivity. These mixed particles are defective in their ability to synthesize DNA upon infection, but this defect is less severe than the loss of infectivity. Thus, proteins lacking the correct N-terminus of CA inhibit DNA synthesis and also interfere with formation or integration of a full-length, normal provirus. The results imply that CA proteins function as part of a large, highly organized structure in reverse transcription and apparently at a later step as well. Published by Elsevier Inc. C1 SAIC Frederick, Natl Canc Inst Frederick, HIV Drug Resistance Program, Frederick, MD 21702 USA. SAIC Frederick, Natl Canc Inst Frederick, Image Anal Lab, Frederick, MD 21702 USA. RP Rein, A (reprint author), SAIC Frederick, Natl Canc Inst Frederick, HIV Drug Resistance Program, POB B, Frederick, MD 21702 USA. EM rein@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 36 TC 24 Z9 24 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 2006 VL 347 IS 2 BP 364 EP 371 DI 10.1016/j.virol.2005.12.012 PG 8 WC Virology SC Virology GA 038CS UT WOS:000237196600011 PM 16427108 ER PT J AU Fetsch, PA Abati, A Litman, T Morisaki, K Honjo, Y Mittal, K Bates, SE AF Fetsch, PA Abati, A Litman, T Morisaki, K Honjo, Y Mittal, K Bates, SE TI Localization of the ABCG2 mitoxantrone resistance-associated protein in normal tissues SO CANCER LETTERS LA English DT Article DE ABCG2; ABC transporter; immunohistochemistry; multidrug resistance ID BINDING CASSETTE ABC; ACUTE MYELOID-LEUKEMIA; BLOOD-BRAIN-BARRIER; BREAST-CANCER CELLS; MULTIDRUG-RESISTANCE; HALF-TRANSPORTER; P-GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; PLASMA-MEMBRANE; STEM-CELLS AB Reduced drug accumulation due to overexpression of individual members of the ATP binding cassette (ABC) superfamily of membrane transporters has been investigated as a cause of multidrug resistance and treatment failure in oncology. This study was designed to develop an immunohistochemical assay to determine the expression and localization of the 72 kDa ABC halftransporter ABCG2 in normal tissues. Formalin-fixed, paraffin embedded archival tissue from 31 distinct normal tissues with an average of eight separate tissue samples of each were immunostained with rabbi t-anti -A BCG2 antibody 405 using a modified avidin-biotin procedure. As a negative control, each sample was also stained with antibody pre-adsorbed with peptide to assess background staining. As a means of verification, selected tissues were also stained with the commercially available monoclonal antibody 5D3. ABCG2 positivity was consistently found in alveolar pneumocytes, sebaccous glands, transitional epithelium of bladder, interstitial cells of testes, prostate epithelium, endocervical cells of uterus, squamous epithelium of cervix, small and large intestinal mucosa/epithelial cells, islet and acinar cells of pancreas, zona reticularis layer of adrenal gland, kidney cortical tubules and hepatocytes. Placental syncytiotrophoblasts showed both cytoplasmic and surface staining. Our results support a hypothesis concluding that ABCG2 plays a role in the protection of organs from cytotoxins. However, many of the cell types expressing ABCG2 have a significant secretory function. These data suggest a dual function for ABCG2 in some tissues: the excretion of toxins and xenobiotics including anti-cancer agents and a potential, as-yet undefined role in the secretion of endogenous substrates. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 NCI, Canc Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NYU, Sch Med, Pathol Lab, New York, NY 10016 USA. NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), NCI, Canc Therapeut Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM sebates@helix.nih.gov NR 39 TC 88 Z9 93 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD APR 8 PY 2006 VL 235 IS 1 BP 84 EP 92 DI 10.1016/j.canlet.2005.04.024 PG 9 WC Oncology SC Oncology GA 037EV UT WOS:000237130400012 PM 15990223 ER PT J AU Sander, M Van Houten, B AF Sander, M Van Houten, B TI Integrating multiple views of the cell: DNA repair jumps to higher level at Stowe workshop SO DNA REPAIR LA English DT Editorial Material C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Page One Editorial Serv, Boulder, CO USA. RP Van Houten, B (reprint author), NIEHS, NIH, 11 TW Alexander Dr,Box 12233, Res Triangle Pk, NC 27709 USA. EM vanhout1@niehs.nih.gov NR 0 TC 2 Z9 2 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 8 PY 2006 VL 5 IS 4 BP 523 EP 527 DI 10.1016/j.dnarep.2005.11.003 PG 5 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 034KI UT WOS:000236927500011 PM 16676404 ER PT J AU Laxminarayan, R Mills, AJ Breman, JG Measham, AR Alleyne, G Claeson, M Jha, P Musgrove, P Chow, J Shahid-Salles, S Jamison, DT AF Laxminarayan, R Mills, AJ Breman, JG Measham, AR Alleyne, G Claeson, M Jha, P Musgrove, P Chow, J Shahid-Salles, S Jamison, DT TI Advancement of global health: key messages from the Disease Control Priorities Project SO LANCET LA English DT Article ID ANTIMICROBIAL RESISTANCE; DEVELOPING-COUNTRIES AB The Disease Control Priorities Project (DCPP), a joint project of the Fogarty International Center of the US National Institutes of Health, the WHO, and The World Bank, was launched in 2001 to identify policy changes and intervention strategies for the health problems of low-income and middle-income countries. Nearly 500 experts worldwide compiled and reviewed the scientific research on a broad range of diseases and conditions, the results of which are published this week. A major product of DCPP, Disease Control Priorities in Developing Countries, 2nd edition (DCP2), focuses on the assessment of the cost-effectiveness of health-improving strategies (or interventions) for the conditions responsible for the greatest burden of disease. DCP2 also examines crosscutting issues crucial to the delivery of quality health services, including the organisation, financial support, and capacity of health systems. Here, we summarise the key messages of the project. C1 Resources Future Inc, Washington, DC 20036 USA. London Sch Hyg & Trop Med, London WC1, England. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Pan Amer Hlth Org, Washington, DC USA. World Bank, Washington, DC 20433 USA. Univ Toronto, Toronto, ON, Canada. St Michaels Hosp, McLaughlin Ctr Mol Med, Ctr Global Hlth Res, Toronto, ON M5B 1W8, Canada. Global Hlth, Hlth Affairs, Bethesda, MD USA. Populat Reference Bur, Washington, DC USA. RP Laxminarayan, R (reprint author), Resources Future Inc, 1616 P St NW Suite 600, Washington, DC 20036 USA. EM ramanan@rff.org OI Mills, Anne/0000-0001-9863-9950 NR 17 TC 155 Z9 157 U1 0 U2 24 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD APR 8 PY 2006 VL 367 IS 9517 BP 1193 EP 1208 DI 10.1016/S0140-6736(06)68440-7 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 030ZH UT WOS:000236673400028 PM 16616562 ER PT J AU Kostelansky, MS Sun, J Lee, SH Kim, J Ghirlando, R Hierro, A Emr, SD Hurley, JH AF Kostelansky, MS Sun, J Lee, SH Kim, J Ghirlando, R Hierro, A Emr, SD Hurley, JH TI Structural and functional organization of the ESCRT-I trafficking complex SO CELL LA English DT Article ID RECEPTOR DOWN-REGULATION; EPIDERMAL-GROWTH-FACTOR; MULTIVESICULAR-BODY; SORTING COMPLEX; ENDOSOMAL TRAFFICKING; POLYCISTRONIC EXPRESSION; UBIQUITINATED PROTEINS; MOLECULAR REPLACEMENT; CRYSTAL-STRUCTURE; TSG101 PROTEIN AB The endosomal sorting complex required for transport (ESCRT) complexes are central to receptor downregulation, lysosome biogenesis, and budding of HIV. The yeast ESCRT-I complex contains the Vps23, Vps28, and Vps37 proteins, and its assembly is directed by the C-terminal steadiness box of Vps23, the N-terminal half of Vps28, and the C-terminal half of Vps37. The crystal structures of a Vps23:Vps28 core sub-complex and the Vps23:Vps28:Vps37 core were solved at 2.1 and 2.8 angstrom resolution. Each subunit contains a structurally similar pair of helices that form the core. The N-terminal domain of Vps28 has a hydrophobic binding site on its surface that is conformationally dynamic. The C-terminal domain of Vps28 binds the ESCRT-II complex. The structure shows how ESCRT-I is assembled by a compact core from which the Vps23 UEV domain, the Vps28 C domain, and other domains project to bind their partners. C1 NIDDKD, Mol Biol Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Chem & Biochem, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM hurley@helix.nih.gov RI Ghirlando, Rodolfo/A-8880-2009; Hierro, Aitor/F-9998-2011 OI Hierro, Aitor/0000-0002-7721-1581 FU NIDDK NIH HHS [Z01 DK036118-12] NR 60 TC 52 Z9 56 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 7 PY 2006 VL 125 IS 1 BP 113 EP 126 DI 10.1016/j.cell.2006.01.049 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 039NY UT WOS:000237314200018 PM 16615894 ER PT J AU Wexler-Cohen, Y Johnson, BT Puri, A Blumenthal, R Shai, Y AF Wexler-Cohen, Y Johnson, BT Puri, A Blumenthal, R Shai, Y TI Structurally altered peptides reveal an important role for N-terminal heptad repeat binding and stability in the inhibitory action of HIV-1 peptide DP178 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; SURFACE-PLASMON RESONANCE; MEMBRANE-FUSION; ENVELOPE GLYCOPROTEIN; SYNTHETIC PEPTIDE; CELL-FUSION; GP41; AMINO; CONFORMATION; PARDAXIN AB Human immunodeficiency virus 1 gp41 folds into a six-helix bundle whereby three C-terminal heptad repeat regions pack in an anti-parallel manner against the coiled-coil formed by three N-terminal heptad repeats (NHR). Peptides that inhibit bundle formation contributed significantly to the understanding of the entry mechanism of the virus. DP178, which partially overlaps C-terminal heptad repeats, prevents bundle formation through an undefined mechanism; additionally it has been suggested to bind other ENV regions and arrest fusion in an unknown manner. We used two structurally altered DP178 peptides; in each, two sequential amino acids were substituted into their D configuration, D-SQ in the hydrophilic N-terminal region and D-LW in the hydrophobic C-terminal. Importantly, we generated an elongated NHR peptide, N54, obtaining the full N-helix docking site for DP178. Interestingly, D-LW retained wild type fusion inhibitory activity, whereas D-SQ exhibited significantly reduced activity. In correlation with the inhibitory data, CD spectroscopy and fluorescence studies revealed that all the DP178 peptides interact with N54, albeit with different stabilities of the bundles. We conclude that strong binding of DP178 N-terminal region to the endogenous NHR, without significant contribution of the C-terminal sequence of DP178 to core formation, is vital for DP178 inhibition. The finding that D-amino acid incorporation in the C terminus did not affect activity or membrane binding as revealed by surface plasmon resonance correlates with an additional membrane binding site, or membrane anchoring role, for the C terminus, which works synergistically with the N terminus to inhibit fusion. C1 Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. NCI, Sect Membrane Struct & Funct, Ctr Canc Res, Nanobiol Program,NIH, Frederick, MD 21702 USA. RP Shai, Y (reprint author), Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. EM Yechiel.Shai@weizmann.ac.il FU Intramural NIH HHS NR 33 TC 25 Z9 26 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 7 PY 2006 VL 281 IS 14 BP 9005 EP 9010 DI 10.1074/jbc.M512475200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027HB UT WOS:000236404700004 PM 16455666 ER PT J AU Peterson, JH Szabady, RL Bernstein, HD AF Peterson, JH Szabady, RL Bernstein, HD TI An unusual signal peptide extension inhibits the binding of bacterial presecretory proteins to the signal recognition particle, trigger factor, and the SecYEG complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INNER MEMBRANE-PROTEINS; ESCHERICHIA-COLI; DEPENDENT TRANSLOCATION; TARGETING PATHWAY; 2-PARTNER SECRETION; CRYSTAL-STRUCTURE; NASCENT CHAINS; RIBOSOME; EXPORT; AUTOTRANSPORTER AB Considerable evidence indicates that the Escherichia coli signal recognition particle (SRP) selectively targets proteins that contain highly hydrophobic signal peptides to the SecYEG complex cotranslationally. Presecretory proteins that contain only moderately hydrophobic signal peptides typically interact with trigger factor (TF) and are targeted post-translationally. Here we describe a striking exception to this rule that has emerged from the analysis of an unusual 55-amino acid signal peptide associated with the E. coli autotransporter EspP. The EspP signal peptide consists of a C-terminal domain that resembles a classical signal peptide plus an N-terminal extension that is conserved in other autotransporter signal peptides. Although a previous study showed that proteins containing the C-terminal domain of the EspP signal peptide are targeted cotranslationally by SRP, we found that proteins containing the full-length signal peptide were targeted post-translationally via a novel TF-independent mechanism. Mutation of an invariant asparagine residue in the N-terminal extension, however, restored cotranslational targeting. Remarkably, proteins containing extremely hydrophobic derivatives of the EspP signal peptide were also targeted post-translationally. These and other results suggest that the N-terminal extension alters the accessibility of the signal peptide to SRP and TF and promotes post-translational export by reducing the efficiency of the interaction between the signal peptide and the SecYEG complex. Based on data, we propose that the N-terminal extension mediates an interaction with an unidentified cytoplasmic factor or induces the formation of an unusual signal peptide conformation prior to the onset of protein translocation. C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Bernstein, HD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bldg 5,Rm 201, Bethesda, MD 20892 USA. EM harris_bernstein@nih.gov FU Intramural NIH HHS NR 45 TC 43 Z9 45 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 7 PY 2006 VL 281 IS 14 BP 9038 EP 9048 DI 10.1074/jbc.M508681200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027HB UT WOS:000236404700008 PM 16455668 ER PT J AU Kino, T Souvatzoglou, E Charmandari, E Ichijo, T Driggers, P Mayers, C Alatsatianos, A Manoli, I Westphal, H Chrousos, GP Segars, JH James, HS AF Kino, T Souvatzoglou, E Charmandari, E Ichijo, T Driggers, P Mayers, C Alatsatianos, A Manoli, I Westphal, H Chrousos, GP Segars, JH James, HS TI Rho family guanine nucleotide exchange factor Brx couples extracellular signals to the glucocorticoid signaling system SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP-BINDING PROTEINS; LYSOPHOSPHATIDIC ACID; TRANSCRIPTIONAL ACTIVITY; CALCINEURIN INHIBITION; RECEPTOR SUPERFAMILY; NUCLEAR-LOCALIZATION; NEURITE RETRACTION; POLYBASIC REGION; SMALL GTPASES; FKBP51 AB Glucocorticoids regulate many crucial biologic functions through their cytoplasmic/nuclear glucocorticoid receptors (GR). Excess, deficiency, or alteration in tissue sensitivity to glucocorticoids has been associated with major causes of human morbidity and mortality. Brx, a cytoplasmic Rho family guanine nucleotide exchange factor, binds to and influences the activity of several nuclear hormone receptors. We examined the functional and molecular interactions between GR and Brx. The glucocorticoid sensitivity of lymphocytes obtained from mice haplo-insufficient for Brx was significantly decreased. Conversely, GR-mediated transcriptional activity of a glucocorticoid response element (GRE)-mediated glucocorticoid-responsive promoter was enhanced by Brx in a guanine nucleotide exchange factor domain-dependent fashion. Brx interacted with GR, forming a ternary complex with RhoA. In a chromatin immunoprecipitation assay, Brx and RhoA were co-precipitated with GREs only in the presence of ligand-activated GR. Extracellularly administered lysophosphatidic acid, which activates its signaling cascade through a specific membrane GTP-binding protein (G-protein)-coupled receptor in a G-protein alpha(13)-, Brx-, and RhoA-dependent fashion, enhanced GR transcriptional activity, whereas depletion of endogenous Brx attenuated this effect. These findings suggest that glucocorticoid signaling and, hence, the tissue sensitivity to glucocorticoids, may be coupled to extracellular signals via Brx and small G-proteins. Nuclear Brx might act as a local GRE-GR-transcriptosome activator by mediating the effect of small G-proteins on glucocorticoid-regulated genes. C1 NICHD, Pediat Endocrinol Sect, Reprod Biol & Med Branch, Clin Res Ctr,NIH, Bethesda, MD 20892 USA. NICHD, Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD 20892 USA. NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece. RP Kino, T (reprint author), NICHD, Pediat Endocrinol Sect, Reprod Biol & Med Branch, Clin Res Ctr,NIH, Bldg 10,Rm 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM kinot@mail.nih.gov RI Charmandari, Evangelia/B-6701-2011; OI Manoli, Irini/0000-0003-1543-2941 FU Intramural NIH HHS [Z01 HD008732-06, Z99 HD999999] NR 50 TC 24 Z9 26 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 7 PY 2006 VL 281 IS 14 BP 9118 EP 9126 DI 10.1074/jbc.M509339200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027HB UT WOS:000236404700017 PM 16469733 ER PT J AU Phillips, TM Wellner, E AF Phillips, TM Wellner, E TI Measurement of neuropeptides in clinical samples using chip-based immunoaffinity capillary electrophoresis SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 28th International Symposium on Capillary Chromatography and Electrophoresis CY MAY 22-25, 2005 CL Las Vegas, NV DE chip-based CE; immunoassay; neuropeptides; inflammatory cytokines; muscle pain ID GENE-RELATED PEPTIDE; SUBSTANCE-P; MUSCLE; CYTOKINES; ONLINE; NEUROENDOCRINE; MICRODIALYSIS; INFLAMMATION; IMMUNOASSAY; EXTRACTION AB The current interest in micro-fabrication has extended to the clinical arena where there is a growing lobby for promoting these for point-of-care purposes. The advantages of such devices are their relative speed of analysis, lower reagent costs, and their application to clinical screening and diagnosis. Two chip-based capillary electrophoresis systems have been designed and their performance evaluated for rapidly measuring the concentrations of inflammatory neuropeptides in tissue fluids of patients with neuropeptide-associated muscle pain. Both chips were manufactured to fit a commercially available chip electrophoresis system. One chip was designed to perform electrokinetic flow immunoassays while the other utilized an immunoaffinity port, containing an array of immobilized antibodies, to capture the analytes of interest. Comparison of the results to commercially available high-sensitivity immunoassays demonstrated that both chip-based systems could provide a relatively fast, accurate procedure for studying inflammatory biomarkers in complex biological fluids. However, the immunoaffinity capture system proved the superior of the two chips. Using this system, twelve different inflammation-associated mediators could be determined in approximately 2 min as compared to 30 min when using the flow immunoassay chip. With the ever-expanding array of antibodies that are commercially available, this chip-based system can be applied to a wide variety of different analyses. (c) 2006 Elsevier B.V. All rights reserved. C1 NIH, Ultramicro Analyt Immunochem Resource, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. RP Phillips, TM (reprint author), NIH, Ultramicro Analyt Immunochem Resource, Div Bioengn & Phys Sci, Bldg 13,Room 3N15,9000 Rockville Pike, Bethesda, MD 20892 USA. EM phillipt@mail.nih.gov NR 31 TC 37 Z9 37 U1 0 U2 1 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 7 PY 2006 VL 1111 IS 1 BP 106 EP 111 DI 10.1016/j.chroma.2006.01.102 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 027TT UT WOS:000236439200012 PM 16472819 ER PT J AU Yang, W Lee, JY Nowotny, M AF Yang, W Lee, JY Nowotny, M TI Making and breaking nucleic acids: Two-Mg2+-ion catalysis and substrate specificity SO MOLECULAR CELL LA English DT Review ID DNA-POLYMERASE-I; ECORV RESTRICTION-ENDONUCLEASE; 3'-5' EXONUCLEASE ACTIVITY; 2-METAL ION CATALYSIS; COLI RNASE HI; ESCHERICHIA-COLI; ACTIVE-SITE; METAL-IONS; HOMING ENDONUCLEASE; CRYSTAL-STRUCTURES AB DNA and a large proportion of RNA are antiparallel duplexes composed of an unvarying phosphosugar backbone surrounding uniformly stacked and highly similar base pairs. How do the myriad of enzymes (including ribozymes) that perform catalysis on nucleic acids achieve exquisite structure or sequence specificity? In all DNA and RNA polymerases and many nucleases and transposases, two Mg2+ ions are jointly coordinated by the nucleic acid substrate and catalytic residues of the enzyme. Based on the exquisite sensitivity Of Mg2+ ions to the ligand geometry and electrostatic environment, we propose that two-metal-ion catalysis greatly enhances substrate recognition and catalytic specificity. C1 NIDDK, Mol Biol Lab, 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 Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 FU Intramural NIH HHS NR 70 TC 295 Z9 304 U1 5 U2 35 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD APR 7 PY 2006 VL 22 IS 1 BP 5 EP 13 DI 10.1016/j.molcel.2006.03.013 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 034AX UT WOS:000236897700002 PM 16600865 ER PT J AU Lal, A Abdelmohsen, K Pullmann, R Kawai, T Galban, S Yang, XL Brewer, G Gorospe, M AF Lal, A Abdelmohsen, K Pullmann, R Kawai, T Galban, S Yang, XL Brewer, G Gorospe, M TI Posttranscriptional derepression of GADD45 alpha by genotoxic stress SO MOLECULAR CELL LA English DT Article ID MESSENGER-RNA STABILITY; AU-RICH ELEMENT; ANTIGEN-RELATED PROTEIN; BINDING PROTEIN; GENE-EXPRESSION; TRANSLATIONAL CONTROL; HUR; PATHWAY; ALPHA; TIA-1 AB The growth arrest- and DNA damage-inducible gene GADD45 alpha is potently upregulated in response to stress stimuli. Here, two RNA binding proteins, the mRNA decay-promoting AUF1 and the translational suppressor TIAR, were found to interact specifically with the 3' untranslated region (UTR) of the GADD45 alpha mRNA in HeLa cells. These associations were prominent in unstimulated cells, decreasing dramatically after treatment with the genotoxin methyl methanesulfonate (MMS). Analysis of both endogenous and chimeric GADD45 alpha mRNA revealed that in untreated cells AUF1 strongly reduced GADD45 alpha mRNA stability, whereas TIAR potently inhibited GADD45 alpha translation. After genotoxic stress, AUF1 and TIAR dissociated from the GADD45 alpha mRNA, thereby allowing coordinated elevations in both GADD45 alpha mRNA half-life and translation rate, respectively. We propose that the posttranscriptional derepression of GADD45 alpha critically contributes to its potent upregulation after DNA damage. C1 NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Microbiol Mol Genet & Immunol, Piscataway, NJ 08854 USA. RP Lal, A (reprint author), NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM ashishl@grc.nia.nih.gov; myriam-gorospe@nih.gov FU NCI NIH HHS [CA052443] NR 50 TC 58 Z9 63 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD APR 7 PY 2006 VL 22 IS 1 BP 117 EP 128 DI 10.1016/j.molcel.2006.03.016 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 034AX UT WOS:000236897700012 PM 16600875 ER PT J AU Gruber, T Freeley, M Thuille, N Heit, I Shaw, S Long, A Baier, G AF Gruber, T Freeley, M Thuille, N Heit, I Shaw, S Long, A Baier, G TI Comment on "PDK1 nucleates T cell receptor-induced signaling complex for NF-kappa B activation" SO SCIENCE LA English DT Editorial Material ID PROTEIN-KINASE-C; PKC-THETA; PHOSPHORYLATION C1 Innsbruck Med Univ, Dept Med Genet Mol & Clin Pharmacol, Innsbruck, Austria. Royal Coll Surgeons Ireland, Dept Biochem, Dublin 2, Ireland. AltanaPharma, Constance, Germany. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Baier, G (reprint author), Innsbruck Med Univ, Dept Med Genet Mol & Clin Pharmacol, Innsbruck, Austria. EM gottfried.baier@i-med.ac.at RI Baier, Gottfried/E-8755-2012; OI Thuille, Nikolaus/0000-0002-2253-3946; Freeley, Michael/0000-0002-5763-6582 NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 7 PY 2006 VL 312 IS 5770 DI 10.1126/science.1122000 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 029SJ UT WOS:000236584400020 ER PT J AU Luo, WM Yu, QS Kulkarni, SS Parrish, DA Holloway, HW Tweedie, D Shafferman, A Lahiri, DK Brossi, A Greig, NH AF Luo, WM Yu, QS Kulkarni, SS Parrish, DA Holloway, HW Tweedie, D Shafferman, A Lahiri, DK Brossi, A Greig, NH TI Inhibition of human acetyl- and butyrylcholinesterase by novel carbamates of (-)- and (+)-tetrahydrofurobenzofuran and methanobenzodioxepine SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ALZHEIMERS-DISEASE; CRYSTAL-STRUCTURE; BINDING-SITE; ANTICHOLINESTERASE ACTIVITY; CHOLINESTERASE-INHIBITORS; SELECTIVE INHIBITORS; TORPEDO-CALIFORNICA; DONEPEZIL TREATMENT; ANALOGS; PHENSERINE AB A new enantiomeric synthesis utilizing classical resolution provided two novel series of optically active inhibitors of cholinesterase: (-)- and (+)-O-carbamoyl phenols of tetrahydrofurobenzofuran and methanobenzodioxepine. An additional two series of (-)- and (+)-O-carbamoyl phenols of pyrroloindole and furoindole were obtained by known procedures, and their anticholinesterase actions were similarly quantified against freshly prepared human acetyl- (AChE) and butyrylcholinesterase (BChE). Both enantiomeric forms of each series demonstrated potent cholinesterase inhibitory activity (with IC50 values as low as 10 nM for AChE and 3 nM for BChE), with the exception of the (+)-O-carbamoyl phenols of pyrroloindole, which lacked activity (IC50 values > I mu M). Based on the biological data of these four series, a structure-activity relationship (SAR) analysis was provided by molecular volume calculations. In addition, a probable transition-state model was established according to the known X-ray structure of a transition-state complex of Torpedo californica AChE-m-(N,N,N-trimethylammonio)-2,2,2-trifluoroacetophenone (TcAChE-TMTFA). This model proved valuable in explaining the enantioselectivity and enzyme subtype selectivity of each series. These carbamates are more potent than, or similarly potent to, anticholinesterases in current clinical use, providing not only inhibitors of potential clinical relevance but also pharmacological tools to define drug-enzyme binding interactions within an enzyme crucial in the maintenance of cognition and numerous systemic physiological functions in health, aging, and disease. C1 NIA, Drug Design & Dev Sect, Neurosci Lab, Ctr Gerontol Res,NIH, Baltimore, MD 21224 USA. NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. USN, Res Lab, Struct Matter Lab, Dept Navy, Washington, DC 20375 USA. Israel Inst Biol Res, Dept Biochem & Mol Genet, IL-74100 Ness Ziona, Israel. Indiana Univ, Sch Med, Inst Psychiat, Indianapolis, IN 46202 USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Ctr Gerontol Res,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Greign@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000311-07, Z99 AG999999]; NIA NIH HHS [AG18379, AG18884, R01 AG018379, R01 AG018884] NR 58 TC 40 Z9 41 U1 0 U2 17 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 6 PY 2006 VL 49 IS 7 BP 2174 EP 2185 DI 10.1021/JM050578P PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 029VU UT WOS:000236593300006 PM 16570913 ER PT J AU Hallur, G Jimeno, A Dalrymple, S Zhu, T Jung, MK Hidaleo, M Isaacs, JT Sukumar, S Hamel, E Khan, SR AF Hallur, G Jimeno, A Dalrymple, S Zhu, T Jung, MK Hidaleo, M Isaacs, JT Sukumar, S Hamel, E Khan, SR TI Benzoylphenylurea sulfur analogues with potent antitumor activity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MULTIDRUG-RESISTANCE; TUBULIN; GROWTH; CELLS; PRODRUGS; CANCER; AGENTS AB A novel series of BPU analogues were synthesized and evaluated for antitumor activity. In particular, BPU sulfur analogues 6n and 7d were shown to possess up to10-fold increased potency, when compared to I (NSC-639829), against cancer cell lines. 6n was more effective than I in causing apoptosis of MCF-7 cells. When compared to other drugs with a similar mechanism of action, 6n retained significant ability to inhibit tubulin assembly, with an IC50 of 2.1 mu M. C1 Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Chem Therapeut, Baltimore, MD 21231 USA. NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diagnosis,NIH, Frederick, MD 21702 USA. SAIC Frederick Inc, NCI, Frederick, MD 21702 USA. RP Khan, SR (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Chem Therapeut, Baltimore, MD 21231 USA. EM khansa@jhmi.edu RI HIDALGO, MANUEL/I-4995-2015 OI HIDALGO, MANUEL/0000-0002-3765-3318 FU NCI NIH HHS [N01-CO-12400] NR 20 TC 20 Z9 20 U1 0 U2 3 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 6 PY 2006 VL 49 IS 7 BP 2357 EP 2360 DI 10.1021/jm051261s PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 029VU UT WOS:000236593300025 PM 16570932 ER PT J AU Samuels, JF Riddle, MA Greenberg, BD Fyer, AJ McCracken, JT Rauch, SL Murphy, DL Grados, MA Pinto, A Knowles, JA Piacentini, J Cannistraro, PA Cullen, B Bienvenu, OJ Rasmussen, SA Pauls, DL Willour, VL Shugart, YY Liang, KY Hoehn-Saric, R Nestadt, G AF Samuels, JF Riddle, MA Greenberg, BD Fyer, AJ McCracken, JT Rauch, SL Murphy, DL Grados, MA Pinto, A Knowles, JA Piacentini, J Cannistraro, PA Cullen, B Bienvenu, OJ Rasmussen, SA Pauls, DL Willour, VL Shugart, YY Liang, KY Hoehn-Saric, R Nestadt, G TI The OCD Collaborative Genetics Study: Methods and sample description SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE obsessive compulsive disorder; genetics; genetic linkage ID OBSESSIVE-COMPULSIVE DISORDER; COMPLEX SEGREGATION ANALYSIS; PEDIATRIC PROBANDS; EPIDEMIOLOGY; FAMILY; SUSCEPTIBILITY; SCHIZOPHRENIA; ASSOCIATION; RATIONALE; LINKAGE AB Results from twin and family studies suggest that obsessive-compulsive disorder (OCD) may be transmitted in families but, to date, genes for the disorder have not been identified. The OCD Collaborative Genetics Study (OCGS) is a six-site collaborative genetic linkage study of OCD. Specimens and blinded clinical data will be made available through the National Institute of Mental Health (NIMH) cell repository. In this initial report, we describe the methods of the study and present clinical characteristics of affected individuals for researchers interested in this valuable resource for genetic studies of OCD. The project clinically evaluated and collected blood specimens from 238 families containing 299 OCD-affected sibling pairs and their parents, and additional affected relative pairs, for a genome-wide linkage study. Of the 999 individuals interviewed to date, 624 were diagnosed with "definite" OCD. The mean age of subjects was 36 years (range 7-95). The majority of affected individuals (66%) were female. The mean age at onset of obsessive-compulsive symptoms was 9.5 years. Specific mood disorders, anxiety disorders, eating disorders, and skin picking were more prevalent in female cases, whereas ties, Tourette disorder, and alcohol dependence were more prevalent in male cases. Compared to "definite" cases of OCD,'probable' cases (n = 82) had, on average, later age at onset of obsessive-compulsive symptoms, lower severity score, and fewer numbers of different categories of obsessions and compulsions, and they were less likely to have received treatment for their symptoms. (c) 2006 Wiley-Liss, Inc. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. RP Samuels, JF (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 4-181, Baltimore, MD 21287 USA. RI Piacentini, John/C-4645-2011; Liang, Kung-Yee/F-8299-2011; Pinto, Anthony/D-2718-2017; OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 FU NCRR NIH HHS [RR00052]; NIMH NIH HHS [R01 MH050214, R01 MH050214-09] NR 31 TC 50 Z9 50 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD APR 5 PY 2006 VL 141B IS 3 BP 201 EP 207 DI 10.1002/ajmg.b.30224 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 031BL UT WOS:000236679000001 PM 16511842 ER PT J AU Kim, EJ Perreira, M Thomas, CJ Hanover, JA AF Kim, EJ Perreira, M Thomas, CJ Hanover, JA TI An O-GlcNAcase-specific inhibitor and substrate engineered by the extension of the N-acetyl moiety SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID INSULIN-RESISTANCE; GLYCOSYLATION; NUCLEAR; PUGNAC C1 NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. NIDDK, Chem Biol Core Facil, NIH, Bethesda, MD 20892 USA. RP Hanover, JA (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. EM jah@helix.nih.gov FU Intramural NIH HHS [Z01 DK070005-04] NR 14 TC 30 Z9 31 U1 1 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 5 PY 2006 VL 128 IS 13 BP 4234 EP 4235 DI 10.1021/ja0582915 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 028WA UT WOS:000236518300035 PM 16568991 ER PT J AU Powers, AE Marden, SF McConnell, LCDRR Leidy, NK Campbell, CM Soeken, KL Barker, C Daveye, RT Dybul, MR AF Powers, AE Marden, SF McConnell, LCDRR Leidy, NK Campbell, CM Soeken, KL Barker, C Daveye, RT Dybul, MR TI Effect of long-cycle structured intermittent versus continuous HAART on quality of life in patients with chronic HIV infection SO AIDS LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; TREATMENT INTERRUPTIONS; MEDICAL OUTCOMES; RANDOMIZED-TRIAL; HEALTH-STATUS; HIV-1-INFECTED PATIENTS; PROTEASE INHIBITORS; VIRAL LOAD; ADHERENCE AB Objective: To examine the effect of repeated, long-cycle structured intermittent versus continuous HAART on health-related quality of life (HRQL) and symptom distress in patients with chronic HIV infection and plasma HIV RNA of less than 50 copies/ml. Design: Prospective survey of adult patients (n=46) enrolled in a randomized clinical trial evaluating intermittent versus continuous HAART on immunological and virologic parameters. Patients (n=23) randomized to structured intermittent therapy received serial cycles of 4 weeks on/8 weeks off HAART. Outcome measures: HRQL was measured by the physical and mental health summary scores of the Medical Outcomes Study HIV Health Survey (MOS-HIV). Symptom distress was measured by the Symptom Distress Scale. Patients completed initial questionnaires prior to randomization and at weeks 4, 12, and 40 of the trial via a touch screen computer in an outpatient clinic. Results: Baseline demographic and clinical characteristics were equivalent in both treatment groups. Although the mental health summary score declined significantly over time for the structured intermittent group, linear mixed modeling ANOVA indicated no significant difference across time for MOS-HIV summary and Symptom Distress Scale scores between the two treatment arms. Conclusion: In this small sample, repeated long-cycle structured intermittent therapy may not provide HRQL or symptom distress advantage compared to continuous HAART in patients with chronic HIV infection over 10 months of treatment. Further research in a heterogenous chronic HIV population and longer follow-up period is warranted. (C) 2006 Lippincott Williams & Wilkins. C1 NIAID, NIH, Bethesda, MD 20892 USA. NIH, Nursing Serv, Bethesda, MD 20892 USA. NIH, Patient Care Serv, Bethesda, MD 20892 USA. MEDTAP Int, Bethesda, MD USA. Univ Maryland, Baltimore, MD 21201 USA. Scios Inc, Fremont, CA USA. RP Powers, AE (reprint author), NIAID, NIH, 6700-B Rockledge Dr,Room 1213, Bethesda, MD 20892 USA. EM apowers@niaid.nih.gov NR 69 TC 9 Z9 11 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 4 PY 2006 VL 20 IS 6 BP 837 EP 845 DI 10.1097/01.aids.0000218547.39339.13 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 031OI UT WOS:000236713500006 PM 16549967 ER PT J AU Elmer, PJ Obarzanek, E Vollmer, WM Simons-Morton, D Stevens, VJ Young, DR Lin, PH Champagne, C Harsha, DW Svetkey, LP Ard, J Brantley, PJ Proschan, MA Erlinger, TP Appel, LJ AF Elmer, PJ Obarzanek, E Vollmer, WM Simons-Morton, D Stevens, VJ Young, DR Lin, PH Champagne, C Harsha, DW Svetkey, LP Ard, J Brantley, PJ Proschan, MA Erlinger, TP Appel, LJ CA PREMIER Collaborative Res Grp TI Effects of comprehensive lifestyle modification on diet, weight, physical fitness, and blood pressure control: 18-Month results of a randomized trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID JOINT-NATIONAL-COMMITTEE; UNITED-STATES; CLINICAL-TRIAL; HYPERTENSION PREVENTION; SODIUM REDUCTION; VEGETABLE INTAKE; HEALTH-PROGRAM; 7TH REPORT; PHASE-II; RISK AB Background: The main 6-month results from the PREMIER trial showed that comprehensive behavioral intervention programs improve lifestyle behaviors and lower blood pressure. Objective: To compare the 18-month effects of 2 multicomponent behavioral interventions versus advice only on hypertension status, lifestyle changes, and blood pressure. Design: Multicenter, 3-arm, randomized trial conducted from January 2000 through November 2002. Setting: 4 clinical centers and a coordinating center. Patients: 810 adult volunteers with prehypertension or stage 1 hypertension (systolic blood pressure, 120 to 159 mm Hg; diastolic blood pressure, 80 to 95 mm Hg). Interventions: A multicomponent behavioral intervention that implemented long-established recommendations ("established"); a multicomponent behavioral intervention that implemented the established recommendations plus the Dietary Approaches to Stop Hypertension (DASH) diet ("established plus DASH"); and advice only. Measurements: Lifestyle variables and blood pressure status. Follow-up for blood pressure measurement at 18 months was 94%. Results: Compared with advice only, both behavioral interventions statistically significantly reduced weight, fat intake, and sodium intake. The established plus DASH intervention also statistically significantly increased fruit, vegetable, dairy, fiber, and mineral intakes. Relative to the advice only group, the odds ratios for hypertension at 18 months were 0.83 (95% Cl, 0.67 to 1.04) for the established group and 0.77 (Cl, 0.62 to 0.97) for the established plus DASH group. Although reductions in absolute blood pressure at 18 months were greater for participants in the established and the established plus DASH groups than for the advice only group, the differences were not statistically significant. Limitations: The exclusion criteria and the volunteer nature of this cohort may limit generalizability. Although blood pressure is a well-accepted risk factor for cardiovascular disease, the authors were not able to assess intervention effects on clinical cardiovascular events in this limited time and with this sample size. Conclusions: Over 18 months, persons with prehypertension and stage 1 hypertension can sustain multiple lifestyle modifications that improve control of blood pressure and could reduce the risk for chronic disease. C1 Kaiser Permanente, Ctr Hlth Res, Portland, OR 97227 USA. NHLBI, Bethesda, MD 20892 USA. Univ Maryland, College Pk, MD 20742 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. Univ Alabama, Birmingham, AL 35233 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Vollmer, WM (reprint author), Kaiser Permanente, Ctr Hlth Res, 3800 N Interstate Ave, Portland, OR 97227 USA. EM William.Vollmer@kpchr.org FU NHLBI NIH HHS [UO1 HL60570, UO1 HL60571, UO1 HL60573, UO1 HL60574, UO1 HL62828] NR 50 TC 283 Z9 300 U1 5 U2 40 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 4 PY 2006 VL 144 IS 7 BP 485 EP 495 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 031DU UT WOS:000236685100003 PM 16585662 ER PT J AU Shkriabai, N Datta, SAK Zhao, ZJ Hess, S Rein, A Kvaratskhelia, M AF Shkriabai, N Datta, SAK Zhao, ZJ Hess, S Rein, A Kvaratskhelia, M TI Interactions of HIV-1 Gag with assembly cofactors SO BIOCHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CAPSID PROTEIN; MATRIX PROTEIN; NUCLEOCAPSID PROTEIN; DIMERIZATION DOMAIN; MASS-SPECTROMETRY; TERMINAL REGION; IN-VITRO; RNA; IDENTIFICATION AB HIV-1 Gag is the only protein required for retroviral particle assembly. There is evidence suggesting that phosphatidylinositol phosphate and nucleic acid are essential for viruslike particle assembly. To elucidate structural foundations of interactions of HIV-1 Gag with the assembly cofactors PI(4,5)P-2 and RNA, we employed mass spectrometric protein footprinting. In particular, the NHS-biotin modification approach was used to identify the lysine residues that are exposed to the solvent in free Gag and are protected from biotinylation by direct protein-ligand or protein-protein contacts in Gag complexes with PI(4,5)P-2 and/or RNA. Of 21 surface lysines readily modified in free Gag, only K30 and K32, located in the matrix domain, were strongly protected in the Gag-PI(4,5)P-2 complex. Nucleic acid also protected these lysines, but only at significantly higher concentrations. In contrast, nucleic acids and not PI(4,5)P2 exhibited strong protection of two nucleocapsid domain residues: K391 and K424. In addition, K314, located in the capsid domain, was specifically protected only in the presence of both PI(4,5)P-2 and nucleic acid. We suggest that concerted binding of PI(4,5)P-2 and nucleic acid to the matrix and nucleocapsid domains, respectively, promotes protein-protein interactions involving capsid domains. These protein-protein interactions must be involved in virus particle assembly. C1 Ohio State Univ, Hlth Sci Ctr, Ctr Retrovirus Res, Columbus, OH 43210 USA. Ohio State Univ, Hlth Sci Ctr, Coll Pharm, Ctr Comprehens Canc, Columbus, OH 43210 USA. NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Kvaratskhelia, M (reprint author), Ohio State Univ, Hlth Sci Ctr, Ctr Retrovirus Res, 500 W 12th Ave,238 LM Parks Hall, Columbus, OH 43210 USA. EM Kvaratskhelia.1@osu.edu RI Hess, Sonja/K-4842-2013; OI Hess, Sonja/0000-0002-5904-9816; Datta, Siddhartha/0000-0002-4098-7490 FU Intramural NIH HHS; NIAID NIH HHS [AI062520] NR 37 TC 91 Z9 95 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 4 PY 2006 VL 45 IS 13 BP 4077 EP 4083 DI 10.1021/bi052308e PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 028XE UT WOS:000236521300004 PM 16566581 ER PT J AU He, K Liu, K Daviglus, ML Morris, SJ Loria, CM Van Horn, L Jacobs, DR Savage, PJ AF He, K Liu, K Daviglus, ML Morris, SJ Loria, CM Van Horn, L Jacobs, DR Savage, PJ TI Magnesium intake and incidence of metabolic syndrome among young adults SO CIRCULATION LA English DT Article DE follow-up studies; magnesium; nutrition; risk factors; syndrome X ID MIDDLE-AGED WOMEN; DIETARY MAGNESIUM; INSULIN-RESISTANCE; FASTING INSULIN; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; SERUM; CARDIA; RISK AB Background-Studies suggest that magnesium intake may be inversely related to risk of hypertension and type 2 diabetes mellitus and that higher intake of magnesium may decrease blood triglycerides and increase high-density lipoprotein (HDL) cholesterol levels. However, the longitudinal association of magnesium intake and incidence of metabolic syndrome has not been investigated. Methods and Results-We prospectively examined the relations between magnesium intake and incident metabolic syndrome and its components among 4637 Americans, aged 18 to 30 years, who were free from metabolic syndrome and diabetes at baseline. Metabolic syndrome was diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III definition. Diet was assessed by an interviewer-administered quantitative food frequency questionnaire, and magnesium intake was derived from the nutrient database developed by the Minnesota Nutrition Coordinating Center. During the 15 years of follow-up, 608 incident cases of the metabolic syndrome were identified. Magnesium intake was inversely associated with incidence of metabolic syndrome after adjustment for major lifestyle and dietary variables and baseline status of each component of the metabolic syndrome. Compared with those in the lowest quartile of magnesium intake, multivariable-adjusted hazard ratio of metabolic syndrome for participants in the highest quartile was 0.69 (95% confidence interval [CI], 0.52 to 0.91; P for trend <0.01). The inverse associations were not materially modified by gender and race. Magnesium intake was also inversely related to individual component of the metabolic syndrome and fasting insulin levels. Conclusions-Our findings suggest that young adults with higher magnesium intake have lower risk of development of metabolic syndrome. C1 Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Univ Missouri, Columbia Res Reactor Ctr, Columbia, MO 65211 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. Univ Oslo, Dept Nutr, Oslo, Norway. RP He, K (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1102, Chicago, IL 60611 USA. EM kahe@northwestern.edu FU NHLBI NIH HHS [N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095] NR 44 TC 149 Z9 154 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 4 PY 2006 VL 113 IS 13 BP 1675 EP 1682 DI 10.1161/CIRCULATIONAHA.105.588327 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 029EC UT WOS:000236540700010 PM 16567569 ER PT J AU Ingkanisorn, WP Kwong, RY Bohme, NS Geller, NL Rhoads, KL Dyke, CK Paterson, DI Syed, MA Aletras, AH Arai, AE AF Ingkanisorn, WP Kwong, RY Bohme, NS Geller, NL Rhoads, KL Dyke, CK Paterson, DI Syed, MA Aletras, AH Arai, AE TI Prognosis of negative adenosine stress magnetic resonance in patients presenting to an emergency department with chest pain SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID QUANTITATIVE CORONARY-ANGIOGRAPHY; SPIRAL COMPUTED-TOMOGRAPHY; ACUTE CARDIAC ISCHEMIA; MYOCARDIAL-INFARCTION; PERFUSION; LIKELIHOOD; REGRESSION; ACCURACY; PANEL AB OBJECTIVES This study was designed to determine the diagnostic value of adenosine cardiac magnetic resonance (CMR) in troponin-negative patients with chest pain. BACKGROUND We hypothesized that adenosine CAIR could determine which troponin-negative patients with chest pain in an emergency department have coronary artery disease (CAD) or future adverse cardiac events. METHODS Adenosine stress CMR was performed on 135 patients who presented to the emergency department with chest pain and had acute myocardial infarction (MI) excluded by troponin-I. The main study outcome was detecting am, evidence of significant CAD. Patients were contacted at one year to determine the incidence of significant CAD defined as coronary artery stenosis > 50% on angiography, abnormal correlative stress test, new MI, or death. RESULTS Adenosine perfusion abnormalities had 100% sensitivity and 93% specificity as the single most accurate component of the CMR examination. Both cardiac risk factors and CMR were significant in Kaplan-Meier analysis (log-rank test, p = 0.0006 and p < 0.0001, respectively). However, an abnormal CMR added significant prognostic value in predicting future diagnosis of CAD, MI, or death over clinical risk factors. In receiver operator curve analysis, adenosine CMR was a more accurate predictor than cardiac risk factors (p < 0.002). CONCLUSIONS In patients with chest pain who had MI excluded by troponin-I and non-diagnostic electrocardiograms, an adenosine CMR examination predicted with high sensitivity and specificity which patients had significant CAD during one-year follow-up. Furthermore, no patients with a normal adenosine CMR study had a subsequent diagnosis of CAD or an adverse outcome. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. Suburban Hosp, Bethesda, MD USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Arai, AE (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Room BID416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA. EM araia@nih.gov OI Carnegie, Nicole/0000-0001-7664-6682; Aletras, Anthony/0000-0002-3786-3817 NR 27 TC 147 Z9 155 U1 1 U2 1 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 4 PY 2006 VL 47 IS 7 BP 1427 EP 1432 DI 10.1016/j.jacc.2005.11.059 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 030PQ UT WOS:000236647200017 PM 16580532 ER PT J AU Hees, PS Fleg, JL Mirza, ZA Ahmed, S Siu, CO Shapiro, EP AF Hees, PS Fleg, JL Mirza, ZA Ahmed, S Siu, CO Shapiro, EP TI Effects of normal aging on left ventricular lusitropic, inotropic, and chronotropic responses to dobutamine SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CARDIOVASCULAR-RESPONSES; HEART-DISEASE; HEALTHY-MEN; AGE; RESPONSIVENESS; ISOPROTERENOL; CONTRACTILITY; STIMULATION; DYSFUNCTION; RELAXATION AB OBJECTIVES The purpose of this study was to characterize how aging impacts the left ventricular (LV) functional reserve. BACKGROUND Early diastolic LV filling slows markedly with advancing age, but the effects of beta-adrenergic stimulation on filling, and its major determinant, relaxation, have not been investigated in an aging population. Although the responses of contractility and heart rate to catecholamines reportedly diminish with age, the effect of age on the responses to steady-state dobutamine infusions is unclear. METHODS Groups of younger (40 +/- 10 years, n = 26) and older (68 +/- 11 years, n = 24) normal adult patients were studied at baseline and at three progressive dobutamine infusion dosages (5, 10, and 20 mu g/kg/min). The LV function was evaluated by two-dimensional and Doppler echocardiography. Myocardial relaxation was evaluated from cardiovascular magnetic resonance (CMR)-based rho, a preload-independent surrogate for T. Effective LV pump-function index (PFi), defined as systolic blood pressure/end-systolic LV diameter, was measured. RESULTS Both groups showed expected dose-dependent increases in heart rate and LV systolic function, diastolic function, and relaxation. Early LV filling reserve was much greater in younger than older patients (E-wave increase from baseline to highest dose, 24.0 vs. 9.5 cm/s, p < 0.004), although the dose responses of p were indistinguishable (0.18% vs. 0.19%/ms, p = 0.22). Whereas dobutamine caused a significantly greater increase of PFi in younger than older patients (30.1 vs. 15.6 min Hg/cm, p < 0.0001), there was no diffierence in heart rate augmentation (37 vs. 38 beats/min, p = 0.94). CONCLUSIONS Aging is accompanied by a blunted inotropic but preserved chronotropic response to steady-state dobutamine infusion. Although LV filling reserve declines with age, relaxation reserve does not. C1 Johns Hopkins Med Inst, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Sch Med, Div Cardiol, Baltimore, MD 21205 USA. NIA, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. Wright State Univ, Sch Med, Dept Med, Dayton, OH 45435 USA. Wright State Univ, Sch Med, Div Cardiol, Dayton, OH 45435 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Div Cardiol, Birmingham, AL 35294 USA. Data Power Inc, Ringoes, NJ USA. RP Hees, PS (reprint author), Johns Hopkins Bayview Med Ctr, Div Cardiol, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM phees@welch.jhu.edu FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL46223]; NIA NIH HHS [R01 AG023624-02] NR 19 TC 13 Z9 15 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 4 PY 2006 VL 47 IS 7 BP 1440 EP 1447 DI 10.1016/j.jacc.2005.11.052 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 030PQ UT WOS:000236647200019 PM 16580534 ER PT J AU Sebbane, F Jarrett, CO Gardner, D Long, D Hinnebusch, BJ AF Sebbane, F Jarrett, CO Gardner, D Long, D Hinnebusch, BJ TI Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE vector-borne disease ID FEEDING MECHANISM; ESCHERICHIA-COLI; SURFACE PROTEASE; EVOLUTION; VECTOR; TRANSMISSION; PSEUDOTUBERCULOSIS; INFECTION; CHEOPIS; ORIGIN AB Yersinia pestis is transmitted by fleas and causes bubonic plague, characterized by severe local lymphadenitis that progresses rapidly to systemic infection and life-threatening septicemia. Here, we show that although flea-borne transmission usually leads to bubonic plague in mice, it can also lead to primary septicemic plague. However, intradermal injection of Y. pestis, commonly used to mimic transmission by fleabite, leads only to bubonic plague. A Y. pestis strain lacking the plasmid-encoded cell-surface plasminogen activator, which is avirulent by intradermal or s.c. injection, was able to cause fatal primary septicemic plague at low incidence, but not bubonic plague, when transmitted by fleas. The results clarify a long-standing uncertainty about the etiology of primary septicemic plague and support an evolutionary scenario in which plague first emerged as a flea-borne septicemic disease of limited transmissibility. Subsequent acquisition of the plasminogen activator gene by horizontal transfer enabled the bubonic form of disease and increased the potential for epidemic spread. C1 NIAID, Lab Zoonot Pathogens, NIH, Hamilton, MT 59840 USA. NIAID, Rocky Mt Labs, Vet Branch, NIH, Hamilton, MT 59840 USA. RP Hinnebusch, BJ (reprint author), NIAID, Lab Zoonot Pathogens, NIH, Hamilton, MT 59840 USA. EM jhinnebusch@niaid.nih.gov RI Sebbane, Florent/D-4213-2009 NR 39 TC 140 Z9 147 U1 0 U2 16 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 4 PY 2006 VL 103 IS 14 BP 5526 EP 5530 DI 10.1073/pnas.0509544103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 030LP UT WOS:000236636400052 PM 16567636 ER PT J AU Churbanov, A Rogozin, IB Deogun, JS Ali, H AF Churbanov, Alexander Rogozin, Igor B. Deogun, Jitender S. Ali, Hesham TI Method of predicting Splice Sites based on signal interactions SO BIOLOGY DIRECT LA English DT Article ID PRE-MESSENGER-RNA; HIDDEN MARKOV-MODELS; SR PROTEINS; SEQUENCE INFORMATION; GENE STRUCTURE; BINDING-SITES; HNRNP A1; RECOGNITION; MOTIFS; IDENTIFICATION AB Background: Predicting and proper ranking of canonical splice sites (SSs) is a challenging problem in bioinformatics and machine learning communities. Any progress in SSs recognition will lead to better understanding of splicing mechanism. We introduce several new approaches of combining a priori knowledge for improved SS detection. First, we design our new Bayesian SS sensor based on oligonucleotide counting. To further enhance prediction quality, we applied our new de novo motif detection tool MHMMotif to intronic ends and exons. We combine elements found with sensor information using Naive Bayesian Network, as implemented in our new tool SpliceScan. Results: According to our tests, the Bayesian sensor outperforms the contemporary Maximum Entropy sensor for 5' SS detection. We report a number of putative Exonic (ESE) and Intronic (ISE) Splicing Enhancers found by MHMMotif tool. T-test statistics on mouse/rat intronic alignments indicates, that detected elements are on average more conserved as compared to other oligos, which supports our assumption of their functional importance. The tool has been shown to outperform the SpliceView, GeneSplicer, NNSplice, Genio and NetUTR tools for the test set of human genes. SpliceScan outperforms all contemporary ab initio gene structural prediction tools on the set of 5' UTR gene fragments. Conclusion: Designed methods have many attractive properties, compared to existing approaches. Bayesian sensor, MHMMotif program and SpliceScan tools are freely available on our web site. C1 Univ Nebraska, Coll Informat Sci & Technol, Dept Comp Sci, Omaha, NE 68182 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Nebraska, Dept Comp Sci & Engn, Lincoln, NE 68588 USA. RP Churbanov, A (reprint author), Univ Nebraska, Coll Informat Sci & Technol, Dept Comp Sci, Omaha, NE 68182 USA. EM achurbanov@mail.unomaha.edu; rogozin@ncbi.nlm.nih.gov; deogun@cse.unl.edu; hesham@unomaha.edu FU NCRR NIH HHS [P20 RR016469] NR 80 TC 19 Z9 22 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD APR 3 PY 2006 VL 1 AR 10 DI 10.1186/1745-6150-1-10 PG 23 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 133SH UT WOS:000244033000001 PM 16584568 ER PT J AU Tan, ML Brooks, BR Ichiye, T AF Tan, ML Brooks, BR Ichiye, T TI Temperature dependence of diffusion properties of soft sticky dipole water SO CHEMICAL PHYSICS LETTERS LA English DT Article ID AQUEOUS-ELECTROLYTE SOLUTIONS; PERIODIC BOUNDARY-CONDITIONS; STATIC DIELECTRIC-CONSTANT; EFFECTIVE PAIR POTENTIALS; LIQUID WATER; SUPERCOOLED WATER; MOLECULAR-DYNAMICS; ELECTROSTATIC SYSTEMS; MAXIMUM DENSITY; SELF-DIFFUSION AB The isobaric diffusivities for the soft sticky dipole water model between 230 and 330 K were studied in molecular dynamics simulations using Ewald summations for the long-range interactions. This simple single-point, angularly dependent model with parameters optimized at room temperature reproduces the experimental diffusion rates over a wide range of temperatures better than multi-point models. Its ability to reproduce the unusual temperature dependence of the diffusivities of supercooled water indicates the tetrahedral nature of water is important. Moreover, comparisons with other models indicate more tetrahedral potentials correlate with increasing the so-called Angell critical temperature and decreasing power of the temperature dependence. Published by Elsevier B.V. C1 Georgetown Univ, Dept Chem, Washington, DC 20057 USA. NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Ichiye, T (reprint author), Georgetown Univ, Dept Chem, 37th & O St,NW, Washington, DC 20057 USA. EM ti9@georgetown.edu NR 35 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-2614 J9 CHEM PHYS LETT JI Chem. Phys. Lett. PD APR 3 PY 2006 VL 421 IS 1-3 BP 166 EP 170 DI 10.1016/j.cplett.2006.01.048 PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 030VG UT WOS:000236662600034 ER PT J AU Yang, WY Barnes, AJ Ripple, MG Fowler, DR Cone, EJ Moolchan, ET Chung, HS Huestis, MA AF Yang, WY Barnes, AJ Ripple, MG Fowler, DR Cone, EJ Moolchan, ET Chung, HS Huestis, MA TI Simultaneous quantification of methamphetamine, cocaine, codeine, and metabolites in skin by positive chemical ionization gas chromatography-mass spectrometry SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE skin; tissue; biopsy; methamphetamine; cocaine; codeine ID SOLID-PHASE EXTRACTION; STRATUM-CORNEUM; SWEAT PATCH; HUMAN HAIR; URINE; AMPHETAMINE; PLASMA; DRUGS; BLOOD; ABUSE AB A positive chemical ionization gas chromatography-mass spectrometric method was validated to simultaneously quantify drugs and metabolites in skin collected after controlled administration of methamphetamine, cocaine, and codeine. Calibration curves (2.5-100 ng/skin biopsy) for methamphetamine, amphetamine, cocaine, norcocaine, benzoylecgonine, cocaethylene, norcocaethylene, anhydroecgonine methyl ester, morphine, codeine, and 6-acetylmorphine (5-100 ng/skin biopsy for ecgonine methyl ester and ecgonine ethyl ester) exhibited correlation coefficients > 0.999 and concentrations +/- 20% of target. Intra- and inter-run precisions were < 10%. This procedure should be useful for postmortem analysis; data are included on drug concentrations in skin after controlled drug administration. (c) 2006 Elsevier B.V. All rights reserved. C1 NIDA, NIH, Baltimore, MD 21224 USA. Natl Inst Sci Invest, Seoul 158707, South Korea. Off Chief Med Examiner, Baltimore, MD 21201 USA. ConeChem Res LLC, Severna Pk, MD 21146 USA. RP Huestis, MA (reprint author), NIDA, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS NR 26 TC 21 Z9 21 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD APR 3 PY 2006 VL 833 IS 2 BP 210 EP 218 DI 10.1016/j.jchromb.2006.02.002 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 029LN UT WOS:000236564200014 PM 16500159 ER PT J AU Choyke, PL Kobayashi, H AF Choyke, PL Kobayashi, H TI Functional magnetic resonance imaging of the kidney using macromolecular contrast agents SO ABDOMINAL IMAGING LA English DT Article; Proceedings Paper CT 11th Annual Symposium of the European-Society-of-Urogenital-Radiology CY SEP, 2004 CL Santiago Compostela, SPAIN SP European Soc Urogenital Radiol DE magnetic resonance; macromolecular contrast agents; kidney function; proteinuria; cis-platinum nephrotoxicity; ischemia ID RENAL-ARTERY STENOSIS; MR-ANGIOGRAPHY; QUANTIFICATION; RENOGRAPHY; DTPA AB Background: Functional magnetic resonance (MR) imaging of the kidney relies on low-molecular-weight contrast agents. These agents are glomerular filtration markers and are neither secreted nor reabsorbed by the tubules but are filtered at the glomerulus. Low-molecular-weight contrast agents provide limited functional information. A new generation of macromolecular magnetic contrast agents is under development for MR angiography. These agents may provide additional renal functional information not provided by low-molecular-weight agents. Methods: We review the use of macromolecular contrast agents such as gadolinium-bound albumin (Gd-albumin), gadolinium-bound dendrimer (Gd-dendrimer), and ultrasmall particles of iron oxide (USPIO) in specific renal parenchymal diseases. These data are largely derived from animal studies because many of these agents have not been extensively deployed in human populations. Results: Different specific uses have been documented for macromolecular contrast agents. Gd-albumin appears to detect the source of proteinuria and localize the site of recurrent proteinuria after transplantation. Gd-dendrimer uptake reflects damage to the proximal straight tubule in the outer medulla. USPIO agents demonstrate sites of inflammatory changes within the kidney. Conclusion: Although not yet in widespread clinical use, macromolecular MR contrast agents may play a role in the evaluation of functional diseases of the kidneys. C1 NCI, Mol Imaging Program, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, Bldg 10,Room B3B69, Bethesda, MD 20892 USA. EM pchoyke@nih.gov NR 21 TC 29 Z9 30 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD APR PY 2006 VL 31 IS 2 BP 224 EP 231 DI 10.1007/s00261-005-0390-9 PG 8 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 028MI UT WOS:000236491200012 PM 16283582 ER PT J AU Frenkel, V Etherington, A Greene, M Quijano, J Xie, JW Hunter, F Dromi, S Li, KCP AF Frenkel, V Etherington, A Greene, M Quijano, J Xie, JW Hunter, F Dromi, S Li, KCP TI Delivery of liposomal doxorubicin (Doxil) in a breast cancer tumor model: Investigation of potential enhancement by pulsed-high intensity focused ultrasound exposure SO ACADEMIC RADIOLOGY LA English DT Article DE pulsed-high intensity focused ultrasound; liposomal doxorubicin; enhanced delivery; acoustic radiation forces ID LOCALIZED PROSTATE-CANCER; DRUG-DELIVERY; SOLID TUMORS; TRANSPORT; THERAPY; CARDIOTOXICITY; CHEMOTHERAPY; TISSUE; TRIAL AB Rationale and Objectives. To investigate the potential of using pulsed high-intensity focused ultrasound (HIFU) exposures to enhance the delivery, and hence therapeutic effect of liposomal doxorubicin (Doxil) in a murine breast cancer tumor model. Materials and Methods. Tumors were grown in the bilateral flanks of mice using a mammary adenocarcinoma cell line. Experiments consisted of exposing one of two tumors to pulsed-HIFU, followed by tail vein injections of Doxil. Tumor growth rates were monitored, and assays carried out for doxorubicin concentration in these tumors as well as in a second (squamous cell carcinoma) tumor model and in muscle. Laser scanning confocal microscopy was used with fluorescent probes to observe both the uptake of polystyrene nanoparticles and dilation of exposed blood vessels. Additional experiments involving histologic analysis and real-time temperature measurements were performed to determine the safety of the exposures. Results. Pulsed-HIFU exposures were shown to be safe, producing no apparent deleterious effects in the tumors. The exposures, however, were not found to enhance the delivery of Doxil, and consequently did not allow for lower doses for obtaining tumor regression. Imaging with a fluorescent dextran showed blood vessels to be dilated as a result of the exposures. Experiments with polystyrene nanoparticles of similar size to the liposomes showed a greater abundance to be present in the treated tumors. Conclusion. Although past studies have shown the advantages of pulsed-HIFU exposures for enhancing delivery, this was not observed with the liposomes, apparently because of their inherent ability to preferentially accumulate into tumors on their own. Potential mechanisms for enhanced uptake of non-liposomal nanoparticles are discussed. C1 NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Frenkel, V (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bldg 10,Room 1N306A,10 Ctr Dr, Bethesda, MD 20892 USA. EM vfrenkel@cc.nih.gov NR 38 TC 95 Z9 98 U1 0 U2 24 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD APR PY 2006 VL 13 IS 4 BP 469 EP 479 DI 10.1016/j.acra.2005.08.024 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 029AT UT WOS:000236530900010 PM 16554227 ER PT J AU Kageyama, Y Sugiyama, H Ayame, H Iwai, A Fujii, Y Huang, LE Kizaka-Kondoh, S Hiraoka, M Kihara, K AF Kageyama, Y Sugiyama, H Ayame, H Iwai, A Fujii, Y Huang, LE Kizaka-Kondoh, S Hiraoka, M Kihara, K TI Suppression of VEGF transcription in renal cell carcinoma cells by pyrrole-imidazole hairpin polyamides targeting the hypoxia responsive element SO ACTA ONCOLOGICA LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; MINOR-GROOVE; BASE-PAIRS; RECOGNITION; DNA; SEQUENCE; GENE; INHIBITION AB Hypoxia inducible factor (HIF), a master regulator of critical genes for cell survival under hypoxic conditions, is known to be related to tumorigenesis and progression of renal cell carcinoma. N-methylpyrrole (Py)-N-methylimidazole (Im) hairpin polyamides are synthetic organic compounds that recognize and bind to the minor grooves of specific DNA sequences. We synthesized three Py-Im hairpin polyamides targeting the flanking sequences of hypoxia responsive element (HRE; a binding site of HIF) in the promoter region of the vascular endothelial growth factor ( VEGF) gene. The effects of the polyamides on HIF-induced transcription were evaluated by a luciferase assay using a reporter plasmid containing a VEGF promoter. Real time reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay were performed to examine the effects of the polyamides on the transcription and secretion of VEGF in A498 renal cell carcinoma cells, which have a frame-shift mutation in the von Hippel-Lindau gene. A combination of three Py-Im hairpin polyamides suppressed HIF-induced transcription in reporter assays using 293 cells and successfully suppressed transcription and translation of the VEGF gene in A498 cells. Inhibition of the HIF-HRE interaction was confirmed by an electrophoresis mobility shift assay. An approach using Py-Im hairpin polyamides may be a new strategy for the treatment of renal cell carcinoma. C1 Tokyo Med & Dent Univ, Grad Sch, Dept Urol, Bunkyo Ku, Tokyo 1138519, Japan. Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Chiyoda Ku, Tokyo 1010062, Japan. Kyoto Univ, Grad Sch Sci, Dept Chem, Sakyo Ku, Kyoto 6068502, Japan. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Kyoto Univ, Grad Sch Med, Dept Therapeut Radiol & Oncol, Kyoto 6068507, Japan. RP Kageyama, Y (reprint author), Tokyo Med & Dent Univ, Grad Sch, Dept Urol, Bunkyo Ku, 1-5-45, Tokyo 1138519, Japan. EM kageyys.uro@tmd.ac.jp RI Sugiyama, Hiroshi/C-7687-2011; Kondoh, Shinae/C-6937-2015 OI Kondoh, Shinae/0000-0003-3085-5782 NR 21 TC 20 Z9 20 U1 3 U2 7 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PD APR PY 2006 VL 45 IS 3 BP 317 EP 324 DI 10.1080/02841860500486648 PG 8 WC Oncology SC Oncology GA 036VQ UT WOS:000237104700009 PM 16644575 ER PT J AU Maier, EM Osterrieder, S Whybra, C Ries, M Gal, A Beck, M Roscher, AA Muntau, AC AF Maier, EM Osterrieder, S Whybra, C Ries, M Gal, A Beck, M Roscher, AA Muntau, AC TI Disease manifestations and X inactivation in heterozygous females with Fabry disease SO ACTA PAEDIATRICA LA English DT Article; Proceedings Paper CT 5th International Symposium on Lysosomal Storage Diseases CY APR, 2005 CL Valencia, SPAIN DE Fabry disease; lysosomal storage disorder; heterozygotes; X inactivation; HUMARA assay ID ENZYME REPLACEMENT THERAPY; GALACTOSIDASE-A GENE; CHROMOSOME-INACTIVATION; CLINICAL-MANIFESTATIONS; MUTATION ANALYSIS; TWIN SISTERS; PHENOTYPE; CARRIERS; ADRENOLEUKODYSTROPHY; DISCORDANT AB Aim: Fabry disease is an X-linked lysosomal storage disorder characterized by an accumulation of neutral glycosphingolipids in multiple organ systems caused by alpha-galactosidase A deficiency due to mutations in the GLA gene. The majority of heterozygous females show the characteristic signs and symptoms of the disease, and some of them are severely affected. The current hypothesis for the occurrence of disease manifestations in females is skewed X inactivation favouring the mutant GLA allele. Method: We analyzed the patterns of X inactivation in the leukocytes of 28 biochemically and genetically characterized symptomatic Fabry disease heterozygotes and their correlation with clinical and biochemical disease expression. Results: X inactivation patterns in symptomatic females who are heterozygous for Fabry disease did not differ from those of female controls of the same age (p = 0.669). Thirteen (46%) of the 28 females with Fabry disease showed random X inactivation, ten (36%) moderate skewing, and five (18%) highly skewed X inactivation. Segregation analysis was performed in the families of six females who had highly or moderately skewed X inactivation. In four of these females, skewing favoured the wild-type GLA allele and in the other two skewing favoured the mutant allele. Patterns of X inactivation or the extent of skewing were not related to the severity of clinical manifestations or to residual enzyme activity. Conclusion: In this study we provide evidence that heterozygous females with Fabry disease show random X inactivation. Our data do not support the hypothesis that the occurrence and severity of disease manifestations in the majority of Fabry heterozygotes are related to skewed X inactivation. C1 Univ Munich, Dr Von Hauner Childrens Hosp, Res Ctr, Dept Biochem Genet & Mol Biol, D-80337 Munich, Germany. Univ Mainz, Dept Pediat, D-6500 Mainz, Germany. NIH, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. Univ Hamburg, Med Ctr Eppendorf, Hamburg, Germany. RP Muntau, AC (reprint author), Univ Munich, Dr Von Hauner Childrens Hosp, Res Ctr, Dept Biochem Genet & Mol Biol, D-80337 Munich, Germany. EM ania.muntau@med.uni-muenchen.de OI Ries, Markus/0000-0002-5054-5741 NR 46 TC 57 Z9 62 U1 0 U2 2 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD APR PY 2006 VL 95 SU 451 BP 30 EP 38 DI 10.1080/08035320600618809 PG 9 WC Pediatrics SC Pediatrics GA 041LC UT WOS:000237456700006 PM 16720462 ER PT J AU Bleyer, AJ Hart, TC AF Bleyer, AJ Hart, TC TI Genetic factors associated with gout and hyperuricemia SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE genetics; gout; hyperuricemia; medullary cystic kidney disease; uromodulin; familial juvenile hyperuricemic nephropathy ID TAMM-HORSFALL GLYCOPROTEIN; URIC-ACID; UMOD GENE; UROMODULIN; NEPHROPATHY; DISEASE; MUTATIONS; PROTEIN; EXCRETION; FJHN AB Hyperuricemia and gout are common conditions that have long been known to have a heritable component. Obesity, diabetes, and chronic kidney failure are conditions with multifactorial inheritance that are associated with gout. In addition, social factors such as protein and alcohol intake affect serum uric acid levels. The current review discusses basic uric acid metabolism and the multigenetic inheritance of hyperuricemia. Several monogenic disorders affecting Uric acid metabolism are reviewed. The genetics, pathophysiology, diagnosis, and treatment of familial juvenile hyperuricemic nephropathy/medullary cystic kidney disease, autosomal dominant disorders associated with hyperuricemia and progressive kidney failure, are described. (c) 2006 by the National Kidney Foundation, Inc. C1 Wake Forest Univ, Dept Internal Med, Sch Med, Nephrol Sect, Winston Salem, NC 27157 USA. Natl Inst Dent & Craniofacial Res, Human Craniofacial Genet Sect, NIH, Bethesda, MD USA. RP Bleyer, AJ (reprint author), Wake Forest Univ, Dept Internal Med, Sch Med, Nephrol Sect, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM ableyer@wfubmc.edu FU NIDDK NIH HHS [DK62252] NR 24 TC 15 Z9 17 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD APR PY 2006 VL 13 IS 2 BP 124 EP 130 DI 10.1053/j.ackd.2006.01.008 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 032JC UT WOS:000236769700007 PM 16580613 ER PT J AU Ingram, DK Zhu, M Mamczarz, J Zou, SG Lane, MA Roth, GS deCabo, R AF Ingram, DK Zhu, M Mamczarz, J Zou, SG Lane, MA Roth, GS deCabo, R TI Calorie restriction mimetics: an emerging research field SO AGING CELL LA English DT Review DE aging; cancer; glucose; insulin; metabolism; stress ID PROTECTS HIPPOCAMPAL-NEURONS; EXTEND LIFE EXPECTANCY; DIETARY RESTRICTION; CAENORHABDITIS-ELEGANS; SIGNALING PATHWAY; CARDIOVASCULAR-DISEASE; DOPAMINERGIC-NEURONS; LONGEVITY REGULATION; PARKINSONS-DISEASE; STRESS RESISTANCE AB When considering all possible aging interventions evaluated to date, it is clear that calorie restriction (CR) remains the most robust. Studies in numerous species have demonstrated that reduction of calories 30-50% below ad libitum levels of a nutritious diet can increase lifespan, reduce the incidence and delay the onset of age-related diseases, improve stress resistance, and decelerate functional decline. A current major focus of this research area is whether this nutritional intervention is relevant to human aging. Evidence emerging from studies in rhesus monkeys suggests that their response to CR parallels that observed in rodents. To assess CR effects in humans, clinical trials have been initiated. However, even if results from these studies could eventually substantiate CR as an effective pro-longevity strategy for humans, the utility of this intervention would be hampered because of the degree and length of restriction required. As an alternative strategy, new research has focused on the development of 'CR mimetics'. The objective of this strategy is to identify compounds that mimic CR effects by targeting metabolic and stress response pathways affected by CR, but without actually restricting caloric intake. For example, drugs that inhibit glycolysis (2-deoxyglucose), enhance insulin action (metformin), or affect stress signaling pathways (resveratrol), are being assessed as CR mimetics (CRM). Promising results have emerged from initial studies regarding physiological responses which resemble those observed in CR (e.g. reduced body temperature and plasma insulin) as well as protection against neurotoxicity (e.g. enhanced dopamine action and up-regulated neurotrophic factors). Ultimately, lifespan analyses in addition to expanded toxicity studies must be accomplished to fully assess the potential of any CRM. Nonetheless, this strategy clearly offers a very promising and expanding research endeavor. C1 NIA, Lab Expt Gerontol, Intramural Res Program, Baltimore, MD 21224 USA. GeroSci Inc, Pylesville, MD 21132 USA. RP Ingram, DK (reprint author), NIA, Lab Expt Gerontol, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ingramd@grc.nia.nih.gov RI de Cabo, Rafael/E-7996-2010; de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 NR 114 TC 227 Z9 240 U1 2 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD APR PY 2006 VL 5 IS 2 BP 97 EP 108 DI 10.1111/j.1474-9726.2006.00202.x PG 12 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 039OH UT WOS:000237315600001 PM 16626389 ER PT J AU Sayers, SP Guralnik, JM Newman, AB Brach, JS Fielding, RA AF Sayers, SP Guralnik, JM Newman, AB Brach, JS Fielding, RA TI Concordance and discordance between two measures of lower extremity function: 400 meter self-paced walk and SPPB SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE aging; contraction velocity; functional ability; mobility; muscle power ID SKELETAL-MUSCLE; ELDERLY PEOPLE; OLDER MEN; WOMEN; POWER; LIFE; DISABILITY; VELOCITY AB Background and aims: The purpose of the study was to assess the concurrent validity of the 400 meter self-paced walk test (400-m W) against the commonly used short physical performance battery (SPPB). A secondary purpose was to determine whether the 400-m W could better discriminate physical performance among high functioning older adults by examining the distribution of 400-m W scores. Methods: 101 men and women (80.8 +/- 0.4 years) were recruited to participate in the study. The 400-m W and SPPB assessed lower extremity function. Lower extremity muscle strength, power, and contraction velocity was assessed using bilateral leg press (LP). Health history was obtained with questionnaire. Results: 400-m W demonstrated moderate correlations with SPPB (Pearson r = 0.74; p < 0.001). In 36 ;high functioning individuals (SPPB score = 10, 11, 12), participants above the median 400-m W performance time (n = 20) had more medical conditions (2.8 +/- 0.4 vs 1.7 +/- 0.3; p = 0.038), more reported falls (0.80 +/- 0.2 vs 0.19 +/- 0.1; p = 0.016), more medications (3.7 +/- 0.4 vs 1.8 +/- 0.4; p = 0.001), had lower LP power at 70% of the one repetition maximum (1RM) (336 +/- 45 W vs 663 +/- 78 W; p = 0.001) and 40% 1RM (329 +/- 43 W vs 580 +/- 75 W; p = 0.005), and had slower LP contraction velocity at 40% 1RM (77 +/- 5.5 m/s vs 112 +/- 8.4 m/s; p=0.001) compared with those below the median (n = 16). Conclusions: A substantial number of apparently well functioning older adults demonstrated some limitations in the ability to walk 400 meters. Use of the 400-m W may be justified to obtain information to better discriminate among high functioning elderly. C1 Boston Univ, Human Physiol Lab, Dept Hlth Sci, Sargent Coll Rehabil Sci, Boston, MA USA. NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Div Geriatr Med, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Div Geriatr Med, Sch Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA USA. Tufts Univ, Sarcopenia Lab, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. RP Sayers, SP (reprint author), Univ Missouri, Sch Hlth Profess, Dept Phys Therapy, 114 Lewis Hall, Columbia, MO 65211 USA. EM sayerss@missouri.edu RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU NIA NIH HHS [R01-AG-18844]; PHS HHS [263-MA-202876, P50-A11669, H133P99004] NR 15 TC 26 Z9 27 U1 0 U2 3 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 2006 VL 18 IS 2 BP 100 EP 106 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 047SC UT WOS:000237898000003 PM 16702778 ER PT J AU Francesconi, P Cantin, E Bavazzano, E Lauretani, F Bandinelli, S Buiatti, E Ferrucci, L AF Francesconi, P Cantin, E Bavazzano, E Lauretani, F Bandinelli, S Buiatti, E Ferrucci, L TI Classification of residents in nursing homes in Tuscany (Italy) using resource utilization groups version III (RUG-III) SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE case-mix classification; long-term care; nursing home; RUG-III system ID LONG-TERM-CARE; HEALTH-CARE; SYSTEM; FACILITIES AB Background and aims: Samples of nursing homes in Tuscany (Italy) classify their residents and determine their case-mix according to the Resource Utilization Groups System, Version III (RUG-III). Methods: A large sample of nursing homes was selected, based on willingness to participate, representation of both public and private institutions, and wide geographic representation. Two registered nurses assessed all residents using the RUG questionnaire. The information collected was then used to group residents into 44 RUGs, and facility-specific case-mix indices were calculated using the RUG-specific weights previously validated in Italy. Results: A total of 3981 residents from 93 nursing homes were assessed. Most residents were over 75 years old (87.4%) and women (68.6%). A large percentage was classified into RUGs within the following primary categories: reduced physical function (33.6%), impaired cognition (17.6%) and clinically complex (17.6%). The resulting nursing home case-mix indices ranged from 0.627 to 1.108 (mean 0.807 +/- 0.110). No significant association was found between type of facility, level of fees, or extent of staff in the nursing homes and their case-mix indices. Conclusions: RUG-III can provide information on types of nursing home residents and their care needs. This is useful for monitoring and evaluating long-term care services for the elderly, and allows for more effective planning and allocation of staffing and financial resources. C1 NIA, Clin Res Branch, Longitudinal Studies Sect, ASTRA Unit,Harbor Hosp, Baltimore, MD 21225 USA. Tuscany Reg Agcy Hlth, Florence, Italy. Italian Natl Inst Res & Care Aging, Lab Clin Epidemiol, Florence, Italy. RP Ferrucci, L (reprint author), NIA, Clin Res Branch, Longitudinal Studies Sect, ASTRA Unit,Harbor Hosp, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov FU Intramural NIH HHS [Z99 AG999999] NR 12 TC 2 Z9 3 U1 3 U2 6 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 2006 VL 18 IS 2 BP 133 EP 140 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 047SC UT WOS:000237898000007 PM 16702782 ER PT J AU McCutchen, CW AF McCutchen, CW TI Comment on "Low-Aspect-Ratio Wing Aerodynamics at Low Reynolds Numbers" SO AIAA JOURNAL LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP McCutchen, CW (reprint author), 5213 Acacia Ave, Bethesda, MD 20814 USA. NR 5 TC 0 Z9 0 U1 0 U2 2 PU AMER INST AERONAUT ASTRONAUT PI RESTON PA 1801 ALEXANDER BELL DRIVE, STE 500, RESTON, VA 22091-4344 USA SN 0001-1452 J9 AIAA J JI AIAA J. PD APR PY 2006 VL 44 IS 4 BP 924 EP 924 DI 10.2514/1.12330 PG 1 WC Engineering, Aerospace SC Engineering GA 032CS UT WOS:000236752100027 ER PT J AU Hong, DS Goldstein, RB Rotheram-Borus, MJ Wong, FL Gore-Felton, C AF Hong, DS Goldstein, RB Rotheram-Borus, MJ Wong, FL Gore-Felton, C CA NIMH TI Perceived partner serostatus, attribution of responsibility for prevention of HIV transmission, and sexual risk behavior with "main" partner among adults living with HIV SO AIDS EDUCATION AND PREVENTION LA English DT Article ID INJECTION-DRUG USERS; YOUNG GAY MEN; NEGOTIATED SAFETY; UNPROTECTED INTERCOURSE; SITUATIONAL FACTORS; INFECTED PERSONS; SEROPOSITIVE MEN; AIDS; INTERVENTION; PREDICTORS AB Persons living with HIV (PLH) often attribute HIV status to sexual partners based on observable partner characteristics. The present study investigated the relationship of sexual behavior with most recent "main" partner to that partner's perceived serostatus among 1,232 PLH interviewed in clinics and community agencies in Los Angeles, California. PLH who believed their most recent main partner to be HIV-negative more often identified partner appearance as a basis for their perceptions than those who believed their most recent main partner to be HIV-positive. PLH who perceived their most recent main partner as HIV-negative were more likely to assume responsibility for partner protection and always to use condoms, and less likely to report recent unprotected vaginal or anal sex with that partner. Unprotected receptive anal intercourse with their most recent main partner was less common among African American, Latino, and White participants who believed that partner to be HIV-negative. Although PLH appear protective toward HIV-negative main partners, interventions to encourage valid methods of identifying partner serostatus are needed. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Ctr Community Hlth, Los Angeles, CA 90024 USA. Med Coll Wisconsin, Ctr AIDS Intervent Res, Milwaukee, WI 53226 USA. Claremont Grad Univ, Claremont, CA 91711 USA. RP Goldstein, RB (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Ln,Room 3068,MS 9304, Bethesda, MD 20892 USA. EM goldster@mail.nih.gov OI Goldstein, Rise/0000-0002-9603-9473 FU NIMH NIH HHS [P30-MH062246, P30-MH43520, P30-MH57226, U10-MH57615, U10-MH57616, U10-MH57631, U10-MH57636, P30-MH058107] NR 31 TC 10 Z9 10 U1 1 U2 2 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0899-9546 J9 AIDS EDUC PREV JI Aids Educ. Prev. PD APR PY 2006 VL 18 IS 2 BP 150 EP 162 DI 10.1521/aeap.2006.18.2.150 PG 13 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 037AN UT WOS:000237119200005 PM 16649960 ER PT J AU Zapata, A Shippenberg, TS AF Zapata, A Shippenberg, TS TI Endogenous kappa opioid receptor systems modulate the responsiveness of mesoaccumbal dopamine neurons to ethanol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol; opioid peptides; microdialysis; mesolimbic dopamine ID ALCOHOL-PREFERRING AA; SUBSEQUENT WITHDRAWAL SEIZURES; AVOIDING ANA RATS; MESSENGER-RNA; MESOLIMBIC DOPAMINE; NOR-BINALTORPHIMINE; NUCLEUS-ACCUMBENS; KNOCKOUT MICE; DYNORPHIN; RELEASE AB Background: Endogenous kappa-opioid receptor (KOPR) systems modulate the actions of several drugs of abuse. Their role in modulating the effects of ethanol is unknown. An increase in nucleus accumbens extracellular dopamine (DA) has been implicated in mediating the rewarding and locomotor-activating effects of ethanol and virtually all drugs of abuse. The present microdialysis studies were conducted to determine whether the lack of KOPR alters ethanol-evoked DA levels in the nucleus accumbens of naive mice and whether a similar effect is observed in mice repeatedly exposed to ethanol. Methods: Gene deletion techniques were used in conjunction with in vivo microdialysis to examine the influence of lack of KOPR on ethanol-evoked DA in the nucleus accumbens. To determine whether pharmacological inactivation of KOPR produces similar effects in naive mice and those repeatedly exposed to ethanol, the KOPR antagonist norbinaltorphimine (n-BNI) was administered in wild-type mice before repeated air or ethanol vapor inhalation. Microdialysis was conducted 24 hours later. Results: Acute ethanol administration increased DA levels in the nucleus accumbens of wild-type mice. In littermates lacking the KOPR gene, ethanol-evoked DA levels were enhanced. Prior ethanol exposure reduced ethanol-evoked DA levels in vehicle-treated and n-BNI-treated mice. Statistical analysis, however, revealed a significant main effect of n-BNI, indicating that KOPR blockade increased ethanol-evoked DA levels in naive mice and repeated ethanol exposure attenuated. but did not abolish, this effect. Conclusions: These findings demonstrate that inhibition of KOPR leads to increased sensitivity to the DA-releasing effects of ethanol in the nucleus accumbens. C1 NIDA IRP, Behav Neurosci Branch, Integrat Neurosci Sect, Baltimore, MD 21224 USA. RP Zapata, A (reprint author), NIDA IRP, Behav Neurosci Branch, Integrat Neurosci Sect, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Azapata@intra.nida.nih.gov FU NIAAA NIH HHS [AA U01 13486-INIA] NR 38 TC 29 Z9 30 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2006 VL 30 IS 4 BP 592 EP 597 DI 10.1111/j.1530-0277.2006.00069.x PG 6 WC Substance Abuse SC Substance Abuse GA 032EI UT WOS:000236756300002 PM 16573576 ER PT J AU Szabo, G Aloman, C Polyak, SJ Weinman, SA Wands, J Zakhari, S AF Szabo, G Aloman, C Polyak, SJ Weinman, SA Wands, J Zakhari, S TI Hepatitis C infection and alcohol use: A dangerous mix for the liver and antiviral immunity SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID VIRUS CORE PROTEIN; ACCESSORY CELL-FUNCTION; OXIDATIVE STRESS; DENDRITIC CELLS; B-VIRUS; TRANSCRIPTIONAL ACTIVATION; SERINE PHOSPHORYLATION; GENETIC IMMUNIZATIONS; MITOCHONDRIAL INJURY; INHIBITS INTERFERON AB This article presents the proceedings of a symposium presented at the meeting of the Research Society on Alcoholism, held in Santa Barbara, California, in June 2005. The organizers and chairs were Sam Zakhari and Gyongyi Szabo. The presentations included (1) Mitochondrial Abnormalities Induced by Hepatitis C-Alcohol Interaction by Steven Weinman; (2) Effects of Acute and Chronic Ethanol on Innate Antiviral Signaling, Pathways, Hepatitis C Replication, and Human Liver Cell Transcription by Stephen Polyak; (3) Ethanol Alters Dendritic Cell Function In Vivo and Impairs the Subsequent Cellular Immune Responses to Hepatitis C Proteins by Costica Aloman; and (4) Pathogenic Interactions Between Hepatitis C Virus and Alcohol Use in Humans: Dendritic Cells as Common Targets by Gyongyi Szabo. This symposium summarizes the state of knowledge of cellular and molecular pathways by which alcohol and HCV have pathogenic interactions resulting in depression of the immune response and liver damage in chronic HCV infection. C1 Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. Rhode Isl Hosp, Liver Res Ctr, Providence, RI USA. Brown Med Sch, Providence, RI USA. Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. Univ Texas, Med Branch, Dept Internal Med, Galveston, TX 77550 USA. Univ Texas, Med Branch, Dept Neurosci & Cell Biol, Galveston, TX 77550 USA. NIAAA, NIH, Bethesda, MD USA. RP Szabo, G (reprint author), Univ Massachusetts, Sch Med, Dept Med, LRB 215,364 Plantat St, Worcester, MA 01605 USA. EM gyongyi.szabo@umassmed.edu RI Polyak, Stephen/B-5743-2011; Weinman, Steven/E-7012-2011 FU NIAAA NIH HHS [AA13301, R21 AA013301, AA14372, R21 AA013301-02, AA12863] NR 73 TC 39 Z9 39 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2006 VL 30 IS 4 BP 709 EP 719 DI 10.1111/j.1530-0277.2006.00083.x PG 11 WC Substance Abuse SC Substance Abuse GA 032EI UT WOS:000236756300016 PM 16573590 ER PT J AU Houghton, LA Sherwood, KL Pawlosky, R Ito, S O'Connor, DL AF Houghton, LA Sherwood, KL Pawlosky, R Ito, S O'Connor, DL TI [6S]-5-Methyltetrahydrofolate is at least as effective as folic acid in preventing a decline in blood folate concentrations during lactation SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE folate; lactation; folate supplements; folic acid; 5-methyltetrahydrofolate ID TOTAL HOMOCYSTEINE CONCENTRATIONS; PLASMA TOTAL HOMOCYSTEINE; SPINA-BIFIDA PREGNANCY; METHYLENETETRAHYDROFOLATE REDUCTASE; COMMON MUTATION; NATIONAL-HEALTH; MATERNAL FOLATE; BREAST-MILK; WOMEN; SUPPLEMENTATION AB Background: Studies in nonpregnant, nonlactating women suggest that folate supplementation in the form of 5-methyltetrahydrofolate ([6S]-5-methylTHF) is at least as effective as folic acid in increasing blood folate indexes. No data, however, are available on the effect of supplemental [6S]-5-methylTHF on blood folate concentrations during lactation. Objective: We assessed the relative effectiveness of [6S]-5-methylTHF, a placebo, and folic acid in maintaining blood folate indexes during lactation in a sample of healthy Canadian women consuming folic acid-fortified foods. Design: This study was designed as a 16-wk, randomized, placebo-controlled intervention. Pregnant women (n = 72) advised to consume a folic acid-containing prenatal supplement (1000 mu g/d) during pregnancy were enrolled at 36 wk gestation. After delivery, the women were randomly assigned to receive [6S]-5-methylTHF (416 mu g/d, 906 nmol/d) or a placebo or were assigned to a folic acid (400 mu/d, 906 nmol/d) reference group. Results: At 16 wk of lactation, the mean red blood cell (RBC) folate concentration in women in the [6S]-5-methylTHF group (2178; 95% Cl: 1854, 2559 nmol/L) was greater than that in the folic acid (1967-7 1628, 2377 nmol/L; P < 0.05) and placebo (1390; 1198, 1613 nmol/L; P < 0.002) groups after adjustment for baseline concentrations (36 wk gestation). The distribution of folate forms in RBCs did not differ significantly between the [6S]-5-methylTHF and placebo groups. However, the folic acid group had greater amounts of 5-formylTHF (P < 0.03). Conclusion: [6S]-5-MethylTHF appeared to be as effective as, and perhaps more effective than, folic acid in preserving RBC folate concentrations during lactation. C1 Univ Toronto, Hosp Sick Children, Dept Nutr Sci, Toronto, ON M5G 1X8, Canada. Natl Inst Alcoholism & Alcohol Abuse, NIH, Rockville, MD USA. RP O'Connor, DL (reprint author), Univ Toronto, Hosp Sick Children, Dept Nutr Sci, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM deborah_l.o'connor@sickkids.ca RI Houghton, Lisa/F-5305-2011 OI Houghton, Lisa/0000-0002-2276-6205 NR 49 TC 34 Z9 36 U1 0 U2 5 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 2006 VL 83 IS 4 BP 842 EP 850 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 033AA UT WOS:000236817100018 PM 16600937 ER PT J AU Swinburn, BA Jolle, D Kremer, PJ Salbe, AD Ravussin, E AF Swinburn, BA Jolle, D Kremer, PJ Salbe, AD Ravussin, E TI Estimating the effects of energy imbalance on changes in body weight in children SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE energy intake; energy expenditure; energy balance; weight change; children ID PHYSICAL-ACTIVITY; LONGITUDINAL CHANGES; METABOLIC-RATE; OBESITY; EXPENDITURE; GIRLS; CHILDHOOD; REQUIREMENTS; BOYS AB Background: Estimating changes in weight from changes in energy balance is important for predicting the effect of obesity prevention interventions. Objective: The objective was to develop and validate an equation for predicting the mean weight of a population of children in response to a change in total energy intake (TEI) or total energy expenditure (TEE). Design: In 963 children with a mean (+/- SD) age of 8.1 +/- 2.8 y (range: 4-18 y) and weight of 31.5 +/- 17.6 kg, TEE was measured by using doubly labeled water. Log weight (dependent variable) and log TEE (independent variable) were analyzed in a linear regression model with height, age, and sex as covariates. It was assumed that points of dynamic balance, called "settling points," occur for populations wherein energy is in balance (TEE = TEI), weight is stable (ignoring growth), and energy flux (EnFlux) equals TEE. Results: TEE (or EnFlux) explained 74% of the variance in weight. The unstandardized regression coefficient was 0.45 (95% CI: 0.38, 0.51; R-2 = 0.86) after including covariates. Conversion into proportional chances (time, to time,) gave the equation (weight(2)/weight(1)) = (EnFlux(2)/EnFlux(1))(0-45). In 3 longitudinal studies (n = 212; mean follow-up of 3.4 y), the equation predicted the mean follow-up measured weight to within 0.5%. Conclusions: The relation of EnFlux with weight was positive, which implied that a high TEI (rather than low physical activity and low TEE) was the main determinant of high body weight. Two populations of children with a 10% difference in mean EnFlux Would have a 4.5% difference in mean weight. C1 Deakin Univ, Sch Exercise & Nutr Sci, Burwood, Vic 3125, Australia. Deakin Univ, Sch Hlth & Social Dev, Burwood, Vic 3125, Australia. NIDDK, NIH, Phoenix, AZ USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. RP Swinburn, BA (reprint author), Deakin Univ, Sch Exercise & Nutr Sci, 221 Burwood Highway, Burwood, Vic 3125, Australia. EM boyd.swinburn@deakin.edu.au NR 32 TC 65 Z9 67 U1 1 U2 4 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 2006 VL 83 IS 4 BP 859 EP 863 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 033AA UT WOS:000236817100020 PM 16600939 ER PT J AU Stolzenberg-Solomon, RZ Chang, SC Leitzmann, MF Johnson, KA Johnson, C Buys, SS Hoover, RN Ziegler, RG AF Stolzenberg-Solomon, RZ Chang, SC Leitzmann, MF Johnson, KA Johnson, C Buys, SS Hoover, RN Ziegler, RG TI Folate intake, alcohol use, and postmenopausal breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE folate; alcohol; breast cancer; prospective study; cohort; epidemiology; diet ID FOOD FREQUENCY QUESTIONNAIRES; DIETARY-FOLATE; PROSPECTIVE COHORT; MAMMARY-TUMORS; WOMEN; CONSUMPTION; MICRONUTRIENTS; FORTIFICATION; METHYLATION; DEFICIENCY AB Background: Several epidemiologic studies suggest that higher folate intakes are associated with lower breast cancer risk, particularly in women with moderate alcohol consumption. Objective: We investigated the association between dietary folate, alcohol consumption, and postmenopausal breast cancer in women from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort. Design: Dietary data were collected at study enrollment between 1993 and 2001. Folate content was assigned on the basis of prefortification (ie, pre- 1998) databases. Of the 25 400 women participants with a baseline age of 55-74 y and with complete dietary and multivitamin information, 691 developed breast cancer between September 1993 and May 2003. We used Cox proportional hazard models with age as the underlying time metric to generate hazard ratios (HRs) and 95% CIs. Results: The adjusted HRs were 1.19 (95% CI: 1.01, 1.41; P for trend = 0.04) for women reporting supplemental folic acid intake >= 400 mg/d compared with subjects reporting no Supplemental intake. Comparison of the highest with the lowest quintile gave adjusted HRs of 1.04 (95% Cl: 0.83, 1.31; P for trend = 0.56) and 1.32 (95% CI: 1.04. 1.68: P for trend = 0.03) for food and total folate intake, respectively. Alcohol consumption was positively associated with breast cancer risk (highest compared with lowest quintile: HR = 1.37; 95% CI: 1.08, 1.76; P for trend = 0.02); the risk was greatest in women with lower total folate intake. Conclusions: Our results do not Support the hypothesis that high folate intake reduces breast cancer risk; instead, they suggest that a high intake, generally attributable to supplemental folic acid, may increase the risk in postmenopausal women. However, our results confirm previous studies showing positive associations between moderate alcohol consumption and breast cancer. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. NIH, Div Canc Prevent, Breast & Gynecol Canc Res Grp, Rockville, MD USA. Henry Ford Hlth Sci Ctr, Detroit, MI USA. Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. RP Stolzenberg-Solomon, RZ (reprint author), 6120 Executive Blvd,Suite 320, Rockville, MD 20852 USA. EM rs221z@nih.gov OI Johnson, Christine Cole/0000-0002-6864-6604 FU Intramural NIH HHS NR 43 TC 167 Z9 169 U1 3 U2 12 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 2006 VL 83 IS 4 BP 895 EP 904 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 033AA UT WOS:000236817100025 PM 16600944 ER PT J AU Loucks, EB Sullivan, LM Hayes, LJ D'Agostino, RB Larson, MG Vasan, RS Benjamin, EJ Berkman, LF AF Loucks, EB Sullivan, LM Hayes, LJ D'Agostino, RB Larson, MG Vasan, RS Benjamin, EJ Berkman, LF TI Association of educational level with inflammatory markers in the Framingham Offspring Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; inflammation; risk factors; social class ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; MONOCYTE CHEMOATTRACTANT PROTEIN-1; INTERCELLULAR-ADHESION MOLECULE-1; CARDIOVASCULAR RISK-FACTORS; SOLUBLE P-SELECTIN; MYOCARDIAL-INFARCTION; SOCIOECONOMIC-STATUS; CYTOKINE CONCENTRATIONS; PLASMA-LEVELS AB Socioeconomic position consistently predicts coronary heart disease; however, the biologic mechanisms that may mediate this association are not well understood. The objective of this study was to determine whether socioeconomic position (measured as educational level) is associated with inflammatory risk factors for coronary heart disease, including C-reactive protein, interleukin-6, soluble intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and P-selectin. The study sample included 2,729 participants (53.4% women; mean age, 62 +/- 10 years) from the US Framingham Offspring Study cohort who attended examination cycles 3 (1984-1987) and 7 (1998-2001) and provided educational attainment data. Inflammatory markers were measured in fasting serum samples. Multivariable linear regression analyses were performed, adjusting for potential confounders including age, sex, and clinical risk factors. In age- and sex-adjusted analyses, educational attainment was significantly inversely associated with C-reactive protein (p < 0.0001), interleukin-6 (p < 0.0001), soluble intercellular adhesion molecule-1 (p < 0.0001), and monocyte chemoattractant protein-1 (p = 0.0004). After further adjustment for clinical risk factors, educational level remained significantly associated with C-reactive protein (p = 0.0002), soluble intercellular adhesion molecule-1 (p = 0.01), and monocyte chemoattractant protein-1 (p = 0.01). In conclusion, educational attainment is associated with inflammatory risk factors for coronary heart disease. The association provides evidence suggestive of a biologic pathway by which socioeconomic position may predispose to coronary heart disease. C1 Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Boston Univ, Dept Biostat, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Dept Med & Prevent Med, Boston, MA 02215 USA. RP Loucks, EB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM eloucks@hsph.harvard.edu RI Loucks, Eric/I-1272-2014; OI Loucks, Eric/0000-0002-9962-0386; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Sullivan, Lisa/0000-0003-0726-7149 FU NHLBI NIH HHS [1R01 HL076784, 1R01 HL64753, N01-HC-25195] NR 35 TC 58 Z9 58 U1 0 U2 2 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 2006 VL 163 IS 7 BP 622 EP 628 DI 10.1093/aje/kwj076 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 025FO UT WOS:000236250900005 PM 16421236 ER PT J AU Perkins, NJ Schisterman, EF AF Perkins, NJ Schisterman, EF TI The inconsistency of "optimal" cutpoints obtained using two criteria based on the receiver operating characteristic curve SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE area under curve; biological markers; cutpoints; data interpretation, statistical; epidemiologic methods; ROC curve; statistics; Youden index ID OPTIMAL CUT-POINT; YOUDEN INDEX; TESTS AB The use of biomarkers is of ever-increasing importance in clinical diagnosis of disease. In practice, a cutpoint is required for dichotomizing naturally continuous biomarker levels to distinguish persons at risk of disease from those who are not. Two methods commonly used for establishing the "optimal" cutpoint are the point on the receiver operating characteristic curve closest to (0,1) and the Youden index, J. Both have sound intuitive interpretations-the point closest to perfect differentiation and the point farthest from none, respectively-and are generalizable to weighted sensitivity and specificity. Under the same weighting of sensitivity and specificity, these two methods identify the same cutpoint as "optimal" in certain situations but different cutpoints in others. In this paper, the authors examine situations in which the two criteria agree or disagree and show that J is the only "optimal" cutpoint for given weighting with respect to overall misclassification rates. A data-driven example is used to clarify and demonstrate the magnitude of the differences. The authors also demonstrate a slight alteration in the (0,1) criterion that retains its intuitive meaning while resulting in consistent agreement with J. In conclusion, the authors urge that great care be taken when establishing a biomarker cutpoint for clinical use. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20852 USA. American Univ, Dept Math & Stat, Washington, DC 20016 USA. RP Schisterman, EF (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd, Bethesda, MD 20852 USA. EM schistee@mail.nih.gov OI Perkins, Neil/0000-0002-6802-4733; Schisterman, Enrique/0000-0003-3757-641X FU Intramural NIH HHS; NICHD NIH HHS [Z01 HD008761-03] NR 19 TC 473 Z9 483 U1 4 U2 17 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 2006 VL 163 IS 7 BP 670 EP 675 DI 10.1093/aje/kwj063 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 025FO UT WOS:000236250900011 PM 16410346 ER PT J AU Ni, HY Wu, C Prineas, R Shea, S Liu, K Kronmal, R Bild, D AF Ni, HY Wu, C Prineas, R Shea, S Liu, K Kronmal, R Bild, D TI Comparison of dinamap PRO-100 and mercury sphygmomanometer blood pressure measurements in a population-based study SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; sphygmomanometer; Dinamap monitor ID HYPERTENSION-SOCIETY PROTOCOL; CORONARY-ARTERY CALCIFICATION; RANDOM ZERO SPHYGMOMANOMETER; PORTABLE MONITOR; INSTRUMENT; STIFFNESS; ACCURACY; DEVICES AB Background: The accuracy of automated oscillometric devices has been questioned. In addition the acceptability of these devices for research under the field conditions is unclear. Methods: We compared blood pressure (BP) readings obtained using the Dinamap PRO-100 with readings obtained using a standard mercury sphygmomanometer in 305 participants aged 48 to 86 years who were enrolled in the ongoing Multi-Ethnic Study of Atherosclerosis. The BP was measured three times by each device in random order in each participant. Results: Approximately one half of the participants were male and 46.6% had hypertension. The Dinamap and mercury measurements were well correlated (r = 0.89 for systolic BP and r = 0.81 for diastolic BP). Overall the Dinamap underestimated BP: the mean difference (Dinamap - mercury sphygmomanometer) was -0.5 mm Hg (P = .36, SD = 9.8 mm Hg) for systolic BP and -2.9 mm Hg (P < .001, SD = 6.6 mm Hg) for diastolic BP. However, the Dinamap device tended to overestimate systolic BP in participants who were 75 to 86 years of age, who had a pulse pressure >= 60 mm Hg, or who had stages I to III hypertension. On the other hand, the Dinamap underestimated diastolic BP among these same subgroups but with a smaller underestimate than for the rest of the study sample. Conclusions: Although the BP measurements obtained by the Dinamap PRO-100 tend on average to be slightly lower than those obtained by the standard mercury sphygmomanometer in middle-aged and older persons, the discrepancies may vary with age, pulse pressure, and BP. Health care providers and researchers should know of this variation and should interpret Dinamap-measured BP with caution. (c) 2006 American Journal of Hypertension, Ltd. C1 NHLBI, Epidemiol Biometry Program, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Columbia Univ, Dept Med & Epidemiol, New York, NY 10027 USA. Northwestern Univ, Sch Publ Hlth, Chicago, IL 60208 USA. Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. RP Ni, HY (reprint author), NHLBI, Epidemiol Biometry Program, Div Epidemiol & Clin Applicat, NIH, 6701 Rockledge Dr,Rockledge 2 Ctr, Bethesda, MD 20892 USA. EM nihanyu@mail.nih.gov FU NHLBI NIH HHS [N01-HC-95165, N01-HC-95159, N01-HC-95166] NR 31 TC 19 Z9 20 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD APR PY 2006 VL 19 IS 4 BP 353 EP 360 DI 10.1016/j.amjhyper.2005.10.020 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 030GC UT WOS:000236621400005 PM 16580569 ER PT J AU Ng, YH Meyer, KB Kusek, JW Yan, GF Rocco, MV Kimmel, PL Benz, RL Beddhu, S Dwyer, JT Toto, RD Eknoyan, G Unruh, ML AF Ng, YH Meyer, KB Kusek, JW Yan, GF Rocco, MV Kimmel, PL Benz, RL Beddhu, S Dwyer, JT Toto, RD Eknoyan, G Unruh, ML TI Hemodialysis timing, survival, and cardiovascular outcomes in the hemodialysis (HEMO) study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE hemodialysis (HD); outcomes; circadian rhythms; cardiovascular disease ID ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-LIFE; CIRCADIAN VARIATION; BLOOD-PRESSURE; MAINTENANCE HEMODIALYSIS; KIDNEY-DISEASE; MEMBRANE FLUX; RISK-FACTOR; TIME; CHRONOTHERAPY AB Background. The timing of medical therapies has been shown to influence the outcomes and side effects of treatments for disease. This report examines the extent to which hemodialysis treatment time of day was associated with cardiovascular mortality and morbidity and all-cause mortality in a secondary analysis of the Hemodialysis Study. Methods Dialysis start time defined dialysis shift: morning beginning between 0400 and 0930 hours (n = 822); midday, between 0930 and 1530 hours (n = 851); and evening, between 1530 and 2200 hours (n = 172). Outcome measures included all-cause mortality, cardiac death, composite end point of all-cause mortality or first cardiac hospitalization, and composite end point of first cardiac hospitalization or cardiac death. Results: Morning hemodialysis was associated with a lower likelihood of cardiovascular events compared with the evening shift in all-cause mortality or first cardiac hospitalization (evening versus morning, relative risk [RR], 1.29; 95% confidence interval [CI], 1.01 to 1.65; P = 0.043), as well as first cardiac hospitalization or cardiac death (evening versus morning, RR, 1.44; 95% Cl, 1.11 to 1.89; P = 0.007). No differences were noted in the other 2 outcomes, and there was no statistically significant difference between the morning and midday shifts. Although crude mortality rates were greater in the midday compared with morning (RR, 1.21; 95% Cl, 1.05 to 1.39; P = 0.008), this association was attenuated after adjustment (RR, 1.04; 95% Cl, 0.89 to 1.22; P = 0.64). Conclusion: Making extensive adjustment for patient characteristics, this report does not support the association of lower all-cause mortality with morning hemodialysis or a particular benefit for older patients. C1 Pittsburgh Med Ctr, Pittsburgh, PA USA. Lankenau Hosp & Med Res Ctr, Wynnewood, PA USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. NIDDKD, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. George Washington Univ, Washington, DC USA. Univ Utah, Salt Lake City, UT USA. Vet Affairs Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. Univ Texas, SW Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Unruh, ML (reprint author), A909 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM unruh@pitt.edu OI Dwyer, Johanna/0000-0002-0783-1769; Meyer, Klemens/0000-0001-5253-4950 FU NIDDK NIH HHS [DK-66006, U01 DK49271] NR 38 TC 10 Z9 11 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2006 VL 47 IS 4 BP 614 EP 624 DI 10.1053/j.ajkd.2005.12.024 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 032EK UT WOS:000236756500006 PM 16564939 ER PT J AU Fu, SS Partin, MR Snyder, A An, LC Nelson, DB Clothier, B Nugent, S Willenbring, ML Joseph, AM AF Fu, SS Partin, MR Snyder, A An, LC Nelson, DB Clothier, B Nugent, S Willenbring, ML Joseph, AM TI Promoting repeat tobacco dependence treatment: Are relapsed smokers interested? SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article; Proceedings Paper CT National Meeting of the VA-Health-Services-Research-and-Development-Service CY MAR 10, 2004 CL Washington, DC SP VA Hlth Serv Res Dev Serv ID HEALTH MAINTENANCE ORGANIZATION; OF-VETERANS-AFFAIRS; CHRONIC CARE MODEL; SMOKING-CESSATION; COST-EFFECTIVENESS; AFRICAN-AMERICANS; CHRONIC ILLNESS; ABSTINENCE; INTERVENTIONS; INSURANCE AB Background: Promotion of repeat tobacco dependence treatment among relapsed smokers interested in "recycling" (repeat quit attempt) may be a promising approach to increase quit rates. Objective: To report relapsed smokers' interest in recycling and their treatment preferences. Study Design: Descriptive analysis of a population of relapsed smokers who were randomized to receive a recycling intervention strategy to increase tobacco dependence treatment rates, as part of a randomized controlled trial at 5 Veterans Affairs medical centers. Methods: individuals prescribed a tobacco dependence medication in 2002 were eligible and were identified from the Department of Veterans Affairs Pharmacy Benefits Management database. Intervention group participants (n = 951) were contacted for a standardized telephone interview approximately 6 months after the prescription fill date to assess smoking status, interest in recycling, and treatment preferences. Bivariate analyses and generalized linear mixed-model regressions were used to describe outcomes. Results: The response rate to the intervention telephone call was 621% (586/951), at which 61% (357/586) of respondents had relapsed. Almost two thirds of relapsed smokers were interested in recycling within 30 days. Of these, 91% wanted behavioral or pharmacologic smoking cessation treatment, and 64% wanted behavioral and pharmacologic treatment. In multivariate analyses, independent predictors of interest in recycling within 30 days included black race, lower smoking level, and greater number of smoking-related medical conditions. Conclusion: Most smokers who attempt to quit but relapse want to quit again right away, and most are interested in receiving behavioral and pharmacologic treatment. C1 Vet Affairs Med Ctr, Sect Gen Internal Med, Ctr Chron Dis Outcomes Res, VA Hlth Serv Res & Dev Ctr Excellence, Minneapolis, MN 55417 USA. Univ Minnesota, Dept Internal Med, Minneapolis, MN USA. NIAAA, Rockville, MD 20852 USA. RP Fu, SS (reprint author), Vet Affairs Med Ctr, Sect Gen Internal Med, Ctr Chron Dis Outcomes Res, VA Hlth Serv Res & Dev Ctr Excellence, 152-2E,1 Vet Dr, Minneapolis, MN 55417 USA. EM steven.fu@va.gov NR 44 TC 28 Z9 29 U1 3 U2 7 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD APR PY 2006 VL 12 IS 4 BP 235 EP 243 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 033UQ UT WOS:000236876100005 PM 16610925 ER PT J AU Pentz, RD Billot, L Wendler, D AF Pentz, RD Billot, L Wendler, D TI Research on stored biological samples: Views of African American and white American cancer patients SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE tissue banking; ethics; minorities; African Americans; informed consent; research participation; white Americans ID CONSENT; POPULATION; EXPERIENCE; BIOBANKS AB Proposals on consent for research with biological samples should be informed by empirical studies of individuals views. Studies to date queried mostly white research subjects. The aim of this study was to compare the views of two groups of patients: cancer patients at a university clinic (Winship Cancer Institute at Emory Healthcare) and cancer patients at an inner city county hospital (Grady) who were given the option of tissue banking. Overall, 315/452 (70%) patients completed the survey. The Grady cohort was 86% African American; the Winship cohort was 82% White. The vast majority (95%) of individuals in both cohorts agreed to provide biological sample for future research. Both cohorts were willing for their samples to be used to study cancer and other diseases, including Alzheimer disease. Few participants preferred to control the disease to be studied (10%) or wished to be contacted again for consent for each future research project (11%). In our sample, almost all clinical patients, regardless of site of care, ethnicity or socioeconomic status, were willing to provide a biological sample for research purpose and allow investigators to determine the research to be done without contacting patients again. These findings support the recommendation to offer individuals a simplified consent with a one-time binary choice whether to provide biological samples for future research. (c) 2006 Wiley-Liss, Inc. C1 Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Stat Collaborat Inc, Washington, DC USA. NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Pentz, RD (reprint author), Emory Univ, Winship Canc Inst, 1365 Clifton Rd NE,C3008, Atlanta, GA 30322 USA. EM Rebecca.Pentz@emoryhealthcare.org OI Billot, Laurent/0000-0002-4975-9793 NR 14 TC 44 Z9 44 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 1 PY 2006 VL 140A IS 7 BP 733 EP 739 DI 10.1002/ajma.a.31154 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 031BN UT WOS:000236679200011 PM 16523508 ER PT J AU Arnold, RM Han, PKJ Seltzer, D AF Arnold, RM Han, PKJ Seltzer, D TI Opioid contracts in chronic nonmalignant pain management: Objectives and uncertainties SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE opioid; contract; chronic pain; therapy ID SELF-REPORT; THERAPY; HISTORY; ABUSE; CARE AB In this article, we review the principal objectives and ideal elements of opioid contracts, as articulated by proponents of the practice. We examine the limited empirical evidence for the effectiveness of opioid contracts in achieving their intended objectives and identify areas of uncertainty and of ethical concern regarding their implementation. We argue that the challenge in deciding about implementing opioid contracts in clinical practice relates to the multiplicity of potential objectives they might serve, to a lack of empirical evidence regarding their effectiveness, and to ethical concerns over their implementation. Specialty and primary care clinicians contemplating the use of opioid contracts in treating patients with chronic nonmalignant pain need to be sensitive to these considerations, and further debate and research is necessary to establish the proper objectives, elements, effectiveness, and ethical justifications of opioid contracts in clinical practice. (C) 2006 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Div Gen Internal Med, Sect Palliat Care & Med Eth, Dept Med, Pittsburgh, PA 15213 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Arnold, RM (reprint author), Univ Pittsburgh, Div Gen Internal Med, Sect Palliat Care & Med Eth, Dept Med, 200 Lothrop Ave,Suite 932W, Pittsburgh, PA 15213 USA. EM rabob@pitt.edu OI Han, Paul/0000-0003-0165-1940 NR 28 TC 46 Z9 46 U1 2 U2 7 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD APR PY 2006 VL 119 IS 4 BP 292 EP 296 DI 10.1016/j.amjmed.2005.09.019 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 026BN UT WOS:000236311800002 PM 16564767 ER PT J AU van den Heuvel, DMJ ten Dam, VH de Craen, AJM Admiraal-Behloul, F van Es, ACGM Palm, WM Spilt, A Bollen, ELEM Blauw, GJ Launer, L Westendorp, RGJ van Buchem, MA AF van den Heuvel, DMJ ten Dam, VH de Craen, AJM Admiraal-Behloul, F van Es, ACGM Palm, WM Spilt, A Bollen, ELEM Blauw, GJ Launer, L Westendorp, RGJ van Buchem, MA CA PROSPER Study Grp TI Measuring longitudinal white matter changes: Comparison of a visual rating scale with a volumetric measurement SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID FOLLOW-UP; HYPERINTENSITIES; MRI; LESIONS; AGE; PROGRESSION AB BACKGROUND AND PURPOSE: Detection of longitudinal changes in white matter hyperintensities (WMH) by using visual rating scales is problematic. We compared a widely used visual rating scale with a volumetric method to study longitudinal white matter changes. METHODS: WMH were assessed with the visual Scheltens scale and a volumetric method in 100 elderly subjects aged 70-81 years for whom repetitive MR images were available with an interval of 33 (SD, 1.4) months. Reliability was determined by intraclass correlation coefficients. To examine the sensitivity of both the visual and volumetric method, we calculated Spearman rank correlations of WMH ratings and volume measurements with age. RESULTS: Reliability of the visual rating scale was good, whereas reliability of the volumetric measurement was excellent. For baseline measurements of WMH, we found weaker associations between WMH and age when assessed with the visual scale (r = 0.20, P = .045) than with the volumetric method (r = 031, P = .002). Longitudinal evaluation of WMH assessments showed regression in 26% of the subjects when analyzed with the visual rating scale against 12% of the subjects when using volumetric measurements. Compared with the visual rating, the correlation between progression in WMH and age was twice as high when using the volumetric measurement (r = 0.19, P = .062 and r = 0.39, P < .001, respectively). CONCLUSION: Volumetric measurements of WMH offer a more reliable, sensitive, and objective alternative to visual rating scales in studying longitudinal white matter changes. C1 Leiden Univ, Med Ctr, Dept Radiol, NL-2300 RC Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands. Leiden Univ, Med Ctr, Div Image Proc, NL-2300 RC Leiden, Netherlands. Leiden Univ, Med Ctr, Div Neurol, NL-2300 RC Leiden, Netherlands. NIA, Div Epidemiol Demog Biostat, NIH, Bethesda, MD 20892 USA. RP van den Heuvel, DMJ (reprint author), Leiden Univ, Med Ctr, Dept Radiol, C2-S,POB 9600, NL-2300 RC Leiden, Netherlands. NR 16 TC 44 Z9 44 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD APR PY 2006 VL 27 IS 4 BP 875 EP 878 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 033BY UT WOS:000236822500033 PM 16611781 ER PT J AU Levine, RJ Qian, C Maynard, SE Yu, KF Epstein, FH Karumanchi, SA AF Levine, RJ Qian, C Maynard, SE Yu, KF Epstein, FH Karumanchi, SA TI Serum sFlt1 concentration during preeclampsia and mid trimester blood pressure in healthy nulliparous women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med DE precclampsia; blood pressure; soluble fms-like tyrosine kinase 1; sFIt1; cardiovascular disease; placental growth factor ID RISK-FACTORS; ACUTE HYPERGLYCEMIA; GESTATIONAL-AGE; BIRTH-WEIGHT; PREGNANCY; GROWTH; IMPACT; TRIAL; PATHOPHYSIOLOGY; HYPERTENSION AB Objective: The purpose of this study was to determine whether serum fins-like tyrosine kinase I (sFIt1) concentration during preeclampsia were associated with mid trimester blood pressure, other maternal characteristics, or pregnancy outcomes. Study design: We performed a nested case-control study within the Calcium for Preeclampsia Prevention Study cohort. Each woman with preeclampsia (case) was matched to 1 normotensive control. A total of 120 pairs of women was chosen randomly. Serum concentrations of sFlt1 and placental growth factor were measured throughout pregnancy, but before labor and delivery. We focused on data from 40 women with blood specimens that were obtained after the onset of preeclampsia. After logarithmic transformation, we determined mean serum sFlt1 concentrations of all control specimens within gestational age windows during which case specimens had been obtained after the onset of preeclampsia. Within each of these gestational age windows, we computed all upper bound for the control specimens equal to 2 standard deviations above the mean. After the onset of preeclampsia, 16 women with log-transformed serum sFlt1 values greater than the upper bound of the control specimens were considered to have high preeclampsia serum sFlt1 levels. The 24 other women were considered to have low preeclampsia serum sFlt1 levels. Results: Women with high or low concentrations of serum sFlt1 during preeclampsia (arithmetic means, 5746 and 3007 pg/mL, respectively) had similar pregnancy outcomes and similar maternal characteristics, except for blood pressure at Calcium for Preeclampsia Prevention Study enrollment. Systolic and diastolic blood pressure at enrollment at 13 to 21 weeks of gestation were significantly higher in the 24 women with low serum sFlt1 concentrations during preeclampsia (systolic blood pressure, 114 nun Hg, diastolic blood pressure, 65 mm Hg) than in the 16 women who had preeclampsia at high serum sFlt1 concentrations (systolic blood pressure, 106 mm Hg,diastolic blood pressure, 59 nun Hg). Blood pressure at 13 to 21 weeks among the women with high preeclampsia serum sFlt1 concentrations was identical to the blood pressure among normotensive control subjects. In linear regression analyses of data from all 40 women, both systolic (P <.0001) and diastolic (P =.014) blood pressures at enrollment were correlated negatively with natural logarithm serum sFlt1 concentration after onset of preeclampsia. Conclusion: Women with higher mid trimester blood pressure had preeclampsia at lower serum sFlt1 concentrations. Because higher blood pressure may reflect Occult endothelial damage, these observations may explain increased susceptibility to preeclampsia among women with preexisting vascular disease. (C) 2006 Mosby, Inc. All rights reserved. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Allied Technol Grp, Rockville, MD USA. Univ Massachusetts, Med Ctr, Dept Med, Worcester, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Obstet, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Gynecol, Boston, MA USA. RP Levine, RJ (reprint author), NICHD, NIH, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. EM LevineRJ@mail.nih.gov FU Intramural NIH HHS; NHLBI NIH HHS [HL079594]; NICHD NIH HHS [N01-HD-1-3121, N01-HD-1-3122, N01-HD-1-3123, N01-HD-1-3124, N01-HD-1-3125, N01-HD-1-3126, N01-HD-5-3246]; NIDDK NIH HHS [DK02825, DK64255] NR 36 TC 69 Z9 73 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2006 VL 194 IS 4 BP 1034 EP 1041 DI 10.1016/j.ajog,2005.10.192 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 029XD UT WOS:000236596800020 PM 16580293 ER PT J AU Toso, L Endres, M Vink, J Abebe, DT Brenneman, DE Spong, CY AF Toso, L Endres, M Vink, J Abebe, DT Brenneman, DE Spong, CY TI Learning enhancement with neuropeptides SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Gynecological-and-Obstetrical-Society CY SEP 29-OCT 01, 2005 CL Victoria, CANADA SP Amer Gynecolog Obstetr Soc DE neuropeptide; learning enhancement; pregnancy ID DEPENDENT NEUROTROPHIC FACTOR; VASOACTIVE-INTESTINAL-PEPTIDE; FEMTOMOLAR-ACTING PEPTIDES; FETAL ALCOHOL SYNDROME; PROTECTIVE PEPTIDES; OXIDATIVE STRESS; MOUSE MODEL; NEURONS; GROWTH; MAZE AB Objective: Previous work has demonstrated that two synthetic peptides can prevent prenatal alcohol-induced damage as assessed by prevention of learning abnormalities in adult offspring as well as improve outcome from traumatic brain damage. The Current studies were undertaken to evaluate whether these peptides Could enhance performance in a learning and memory paradigm when administered either prenatally or to aged mice. Study design: For prenatal treatment, C57Bl6/J mice were treated on gestational day 8 with 1 oral administration of D-NAP or D-SAL alone or D-NAP+D-SAL ora double dose of D-SAL. Control groups were same-regimen treated with vehicle alone. Learning was assessed in adult male offspring (35-50 days) by using the Morris water maze. To evaluate aged animals, 12-month-old mice were treated with D-NAP and D-SAL or vehicle alone daily and tested on the Morris water maze. Results: Offspring exposed prenatally to D-NAP+D-SAL learned significantly faster than controls, with an earlier onset of learning and an overall decreased latency to find the hidden platform (P <.05). Animals exposed prenatally to either D-NAP or D-SAL alone learned similar to control, with a trend toward faster latencies. Aged animals who received D-NAP+D-SAL learned significantly faster than age-matched controls, with an earlier onset of learning (P <.05). Conclusion: Combined D-NAP+D-SAL enhanced learning in healthy young mice and aged mice. These findings suggest potential therapeutic interventions not only during a critical developmental period, but also in aged animals. (C) 2006 Mosby, Inc. All rights reserved. C1 NICHD, Unit Perinatal & Dev Neurobiol, NIH, Bethesda, MD 20892 USA. NIAAA, NIH, Bethesda, MD USA. RP Toso, L (reprint author), NICHD, Unit Perinatal & Dev Neurobiol, NIH, Bethesda, MD 20892 USA. NR 20 TC 14 Z9 15 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2006 VL 194 IS 4 BP 1153 EP 1158 DI 10.1016/j.ajog.2005.12.023 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 029XD UT WOS:000236596800046 PM 16580319 ER PT J AU Mercer, BM Macpherson, CA Goldenberg, RL Goepfert, AR Haugel-De Mouzon, S Varner, MW Iams, JD Meis, PJ Moawad, AH Miodovnik, M Caritis, SN Van Dorsten, JP Sorokin, Y Thurnau, GR Spong, CY AF Mercer, BM Macpherson, CA Goldenberg, RL Goepfert, AR Haugel-De Mouzon, S Varner, MW Iams, JD Meis, PJ Moawad, AH Miodovnik, M Caritis, SN Van Dorsten, JP Sorokin, Y Thurnau, GR Spong, CY CA NICHD Maternal-Fetal Med Unit TI Are women with recurrent spontaneous preterm births different from those without such history? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Gynecological-and-Obstetrical-Society CY SEP 29-OCT 01, 2005 CL Victoria, CANADA SP Amer Gynecolog Obstetr Soc DE preterm birth; recurrence; prediction; risk factors ID CORTICOTROPIN-RELEASING HORMONE; PERIODONTAL-DISEASE; GENE POLYMORPHISMS; PREDICTION; ASSOCIATION; DELIVERY; RISK; INTERLEUKIN-6; INFECTION; MEMBRANES AB Objective: This Study was undertaken to determine whether women with recurrent spontaneous preterm births (rSPBs) have different clinical characteristics or systemic markers than those with isolated preterm (iSPBs) or recurrent term births (rTBs), when assessed remote from delivery. Study design: We compared clinical characteristics and findings (including cervical ultrasound, bacterial vaginosis, fetal fibronectin), maternal plasma markers obtained at 22 to 24 weeks' gestation (inflammatory cytokines, cortisol, and corticotrophin-releasing hormone), between women with rSPBs (2 or 3 consecutive SPBs and no TBs), iSPBs (1 SPB and 1 or 2 TBs), and rTBs (2) or 3 consecutive TBs and no SPBs). Results: A total of 1257 women met our inclusion criteria, 47 rSPBs, 241 iSPBs (80 current and 161 prior iSPBs), and 969 rTBs. Before pregnancy, women with rSPBs had lower weights (P <.0001) and body mass indexes (BMIs) (P <.001), and were more likely to be less than 100 lbs (P =.008) or less than 19.8 kg/m(2) BMI (P =.001). At 22 to 24 weeks those with rSPBs remained lighter and leaner, and had more advanced Bishop scores than iSPBs and rTBs. Ultrasound demonstrated progressive decrease in cervical length for those with rTBs, prior iSPBs.. current iSPBs, and rSPBs, and also progressively more frequent short cervixes with worsening history (P <.001). Cervical length was shorter for women of lower pregravid weight and BMI, but not with shorter height. At 22 to 24 weeks, women with rSPBs had more common uterine contractions and tocolytic agents, but not more infections or antibiotic therapy. Those with an SPB in the current gestation had higher fetal fibronectin levels and more frequent vaginal bleeding, regardless of prior outcome. Maternal cortisol and corticotrophin-releasing hormone were higher in women with iSPBs and rSPBs than in rTB controls, (P =.001 and .0027), a finding more apparent with SPB in the current pregnancy. However, maternal cytokines were not increased with either iSPBs or rSPBs. Conclusion: Women with rSPBs are leaner, contract more, have shorter cervixes, and have more advanced Bishop scores than women with iSPBs or rTBs. (C) 2006 Mosby, Inc. All rights reserved. C1 Case Western Reserve Univ, Dept Reprod Biol, Cleveland, OH 44106 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Wake Forest Univ, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA. Univ Pittsburgh, Magee Womens Hosp, Dept Obstet & Gynecol, Pittsburgh, PA 15213 USA. Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Univ Oklahoma, Dept Obstet & Gynecol, Oklahoma City, OK USA. NICHHD, Dept Obstet & Gynecol, Bethesda, MD 20892 USA. RP Mercer, BM (reprint author), Case Western Reserve Univ, Dept Reprod Biol, Cleveland, OH 44106 USA. RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973 FU NICHD NIH HHS [HD27905, HD19897, HD21410, HD21414, HD27860, HD27861, HD27869, HD27883, HD27915, HD27917, HD34208, HD36801, HD40544] NR 30 TC 36 Z9 37 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2006 VL 194 IS 4 BP 1176 EP 1184 DI 10.1016/j.ajog.2006.01.069 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 029XD UT WOS:000236596800055 PM 16580328 ER PT J AU Haigney, MCP Wei, SK Schulze, DH Ruknudin, AM AF Haigney, MCP Wei, SK Schulze, DH Ruknudin, AM TI Response to "beta-adrenergic stimulation does not activate Na+/Ca2+ exchange current in guinea pig, mouse, and rat ventricular myocytes" SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Letter C1 Uniformed Serv Univ Hlth Sci, Div Cardiol, Dept Med, Bethesda, MD 20814 USA. Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Haigney, MCP (reprint author), Uniformed Serv Univ Hlth Sci, Div Cardiol, Dept Med, A3060,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM MCPH@aol.com; dschulze@umaryland.edu; aruknudi@umaryland.edu NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 2006 VL 290 IS 4 BP C1271 EP C1271 DI 10.1152/ajpcell.00541.2005. PG 1 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 029OP UT WOS:000236573300037 PM 16531570 ER PT J AU Jacobson, L Ansari, T McGuinness, OP AF Jacobson, L Ansari, T McGuinness, OP TI Counterregulatory deficits occur within 24 h of a single hypoglycemic episode in conscious, unrestrained, chronically cannulated mice SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE hypoglycemia-associated autonomic failure; hypoglycemia unawareness; catecholamines; norepinephrine; glucocorticoids ID CORTICOTROPIN-RELEASING HORMONE; NORMAL HUMANS; ANTECEDENT HYPOGLYCEMIA; RECURRENT HYPOGLYCEMIA; SUBSEQUENT HYPOGLYCEMIA; INSULIN-RESISTANCE; CENTRAL MECHANISMS; DIABETES-MELLITUS; GLUCOSE-UPTAKE; RESPONSES AB Hypoglycemia-induced counterregulatory failure is a dangerous complication of insulin use in diabetes mellitus. Controlled hypoglycemia studies in gene knockout models, which require the use of mice, would aid in identifying causes of defective counterregulation. Because stress can influence counterregulatory hormones and glucose homeostasis, we developed glucose clamps with remote blood sampling in conscious, unrestrained mice. Male C57BL/6 mice implanted with indwelling carotid artery and jugular vein catheters were subjected to 2 h of hyperinsulinemic glucose clamps 24 h apart, with a 6-h fast before each clamp. On day 1, blood glucose was maintained (euglycemia, 178 +/- 4 mg/dl) or decreased to 62 +/- 1 mg/dl ( hypoglycemia) by insulin (20 mU . kg(-1) . min(-1)) and variable glucose infusion. Donor blood was continuously infused to replace blood sample volume. Baseline plasma epinephrine (32 +/- 8 pg/ml), corticosterone (16.1 +/- 1.8 mu g/dl), and glucagon (35 +/- 3 pg/ml) were unchanged during euglycemia but increased significantly during hypoglycemia, with a glycemic threshold of similar to 80 mg/ dl. On day 2, all mice underwent a hypoglycemic clamp ( blood glucose, 64 +/- 1 mg/ dl). Compared with mice that were euglycemic on day 1, previously hypoglycemic mice had significantly higher glucose requirements and significantly lower plasma glucagon and corticosterone (n = 6/ group) on day 2. Epinephrine tended to decrease, although not significantly, in repeatedly hypoglycemic mice. Pre- and post-clamp insulin levels were similar between groups. We conclude that counterregulatory responses to acute and repeated hypoglycemia in unrestrained, chronically cannulated mice reproduce aspects of counterregulation in humans, and that repeated hypoglycemia in mice is a useful model of counterregulatory failure. C1 Albany Med Coll, Ctr Neuropharmacol & Nuerosci, Albany, NY 12208 USA. Vanderbilt Univ, Mouse Metab Phenotyping Ctr, Nashville, TN USA. Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. RP Jacobson, L (reprint author), Albany Med Coll, Ctr Neuropharmacol & Nuerosci, MC-136, Albany, NY 12208 USA. EM JACOBSL@mail.amc.edu FU NIDDK NIH HHS [R21 DK059757, R21 DK062442, U24 DK059637, DK-62442, DK-59637, DK-59757] NR 47 TC 23 Z9 24 U1 0 U2 1 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 2006 VL 290 IS 4 BP E678 EP E684 DI 10.1152/ajpendo.00383.2005 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 028WW UT WOS:000236520500010 PM 16533951 ER PT J AU Simon, FR Iwahashi, M Hu, LJ Qadri, I Arias, IM Ortiz, D Dahl, R Sutherland, E AF Simon, FR Iwahashi, M Hu, LJ Qadri, I Arias, IM Ortiz, D Dahl, R Sutherland, E TI Hormonal regulation of hepatic multidrug resistance-associated protein 2 (Abcc2) primarily involves the pattern of growth hormone secretion SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE estrogen; thyroid; glucocorticoids; bilirubin ID ORGANIC ANION TRANSPORTER; SEX-DEPENDENT EXPRESSION; DUBIN-JOHNSON-SYNDROME; EXPORT PUMP MRP2; RAT-LIVER; BILIARY-EXCRETION; BILE-SALT; SULFOBROMOPHTHALEIN SODIUM; THYROID-HORMONE; FEMALE RATS AB Biliary excretion is the rate-limiting step in transfer of bilirubin, other organic anions, and xenobiotics across the liver. Multidrug resistance-associated protein 2 (Mrp2, Abcc2) is the major transporter for conjugated endo- and xenobiotic-conjugated compounds into bile. Hormones regulate bilirubin and xenobiotic secretion into bile, which have dimorphic differences. Therefore, we examined the possible role of sex steroids and growth hormone in the regulation of Mrp2. In similar to 8-wk-old rats, mRNA, transcriptional activity, and hepatic content of Mrp2 were selectively increased fourfold (P < 0.001) in females compared with males. In males, estrogens increased and testosterone decreased Mrp2 mRNA and protein, whereas no significant effect was measured in females, suggesting either a direct effect on the liver or an alteration in growth hormone secretory pattern. After hypophysectomy, Mrp2 mRNA was markedly reduced and the effects of estrogens and testosterone on Mrp2 were prevented, supporting the role of pituitary hormones in controlling Mrp2 expression. Mrp2 increased following growth hormone infusion in males. Mrp2 mRNA was decreased in growth hormone-deficient "Little" mice. Growth hormone infusions in hypophysectomized rats partially restored Mrp2 levels, whereas thyroxine addition returned Mrp2 mRNA and protein to basal levels. Morphology as well as biochemical measurements demonstrated that Mrp2 was localized to the bile canaliculus in equal density in both genders, whereas hormone replacements increased Mrp2 in hypophysectomized animals. In cultured hepatocytes, thyroxine did not have an effect, but growth hormone alone and combined with thyroxine increased Mrp2 mRNA levels. In conclusion, Mrp2 levels are regulated by the combination of thyroxine and different growth hormone secretory patterns. C1 Univ Colorado, Hlth Sci Ctr, Dept Med B145, Div Gastroenterol & Hepatol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med B145, Div Gastroenterol & Hepatol, Denver, CO 80262 USA. Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. NICHHD, Unit Cellular Polar, NIH, Bethesda, MD 20892 USA. RP Simon, FR (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Med B145, Div Gastroenterol & Hepatol, 4200 E 9th Ave, Denver, CO 80262 USA. EM Franz.simon@uchsc.edu RI Qadri, Ishtiaq/I-6889-2013 FU NIDDK NIH HHS [DK-15851] NR 84 TC 14 Z9 16 U1 0 U2 1 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 2006 VL 290 IS 4 BP G595 EP G608 DI 10.1152/ajpgi.00240.2005 PG 14 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 021OJ UT WOS:000235992200004 PM 16537972 ER PT J AU Teng, BY Ansari, HR Oldenburg, PJ Schnermann, J Mustafa, SJ AF Teng, BY Ansari, HR Oldenburg, PJ Schnermann, J Mustafa, SJ TI Isolation and characterization of coronary endothelial and smooth muscle cells from A(1) adenosine receptor-knockout mice SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE coronary artery; endothelial cells; smoothelin ID A(2B) RECEPTORS; PROTEIN-KINASE; ARTERY; A(2A); DIFFERENTIATION; FIBROBLASTS; INVOLVEMENT; ACTIVATION; TISSUES; SYSTEM AB Mice have been used widely in vivo and in vitro cardiovascular research. The availability of knockout mice provides further clues to the physiological significance of specific receptor subtypes. Adenosine A(1) receptor (A(1)AR)- knockout (A(1)KO) mice and their wild-type (A(1)WT) controls were employed in this investigation. The heart and aortic arch were carefully removed and retroinfused with enzyme solution (1mg/ml collagenase type I, 0.5 mg/ml soybean trypsin inhibitor, 3% BSA, and 2% antibiotics) through the aortic arch. The efflux was collected at 30-, 60-, and 90-min intervals. The cells were centrifuged, and the pellets were mixed with medium [medium 199-F-12 medium with 10% FBS and 2% antibiotics (for endothelial cells) and advanced DMEM with 10% FBS, 10% mouse serum, 2% GlutaMax, and 2% antibiotics (for smooth muscle cells)] and plated. Endothelial cells were characterized by a cobblestone appearance and positive staining with acetylated LDL labeled with 1,1'-dioctadecyl-3,3,3', 3-tetramethylindocarbocyanine perchlorate. Smooth muscle cells were characterized by positive staining of smooth muscle alpha-actin and smooth muscle myosin heavy chain. Homogeneity of the smooth muscle cells was similar to 91%. Western blot analysis showed expression of smoothelin in the cells from passages 3, 7, and 11 in A(1)WT and A(1)KO mice. Furthermore, the A(1)AR was characterized by Western blot analysis using an A(1)AR-specific antibody. To our knowledge, this is the first isolation and successful characterization of smooth muscle cells from the mouse coronary system. C1 E Carolina Univ, Brody Sch Med, Dept Pharmacol & Toxicol, Greenville, NC USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Mustafa, SJ (reprint author), W Virginia Univ, Sch Med, Dept Physiol & Pharmacol, Hlth Sci Ctr, 2267 Hlth Sci S,POB 9104, Morgantown, WV 26506 USA. EM smustafa@hsc.wvu.edu FU NHLBI NIH HHS [HL-027339, R01 HL027339, R01 HL094447] NR 26 TC 26 Z9 27 U1 0 U2 1 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 2006 VL 290 IS 4 BP H1713 EP H1720 DI 10.1152/ajpheart.00826.2005 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 021GU UT WOS:000235972500050 PM 16299260 ER PT J AU Hashimoto, S Huang, Y Briggs, J Schnermann, J AF Hashimoto, S Huang, Y Briggs, J Schnermann, J TI Reduced autoregulatory effectiveness in adenosine 1 receptor-deficient mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE glomerular filtration rate; renal blood flow; aortic clamp; autoregulatory index ID GLOMERULAR-FILTRATION RATE; RENAL BLOOD-FLOW; JUXTAMEDULLARY AFFERENT ARTERIOLES; SNGFR AUTO-REGULATION; TUBULOGLOMERULAR FEEDBACK; HYPERTENSIVE RATS; CYCLIC-AMP; MEDIATION AB Adjustments of renal vascular resistance in response to changes in blood pressure are mediated by an interplay between the myocyte-inherent myogenic and the kidney-specific tubuloglomerular feedback ( TGF) mechanisms. Using mice with deletion of the A(1) adenosine receptor ( A1AR) gene, we tested the prediction that the absence of TGF, previously established to result from A1AR deficiency, is associated with a reduction in the efficiency of autoregulation. In anesthetized wild-type ( A1AR+/+) and A1AR-deficient mice ( A1AR-/-), glomerular filtration rate ( GFR) and renal blood flow ( RBF) were determined before and after reducing renal perfusion pressure through a suprarenal aortic clamp. In response to a blood pressure reduction by 15.9 +/- 1.34 mmHg in A1AR-/- ( n = 9) and by 14.2 +/- 0.9 mmHg in A1AR+/+ mice ( n = 8; P = 0.31), GFR fell by 187.9 +/- 37 mu l/min and by 72.3 +/- 10 mu l/min in A1AR-/- and A1AR+/+ mice, respectively ( P = 0.013). Similarly, with pressure reductions of 14.8 +/- 1.1 and 13.3 +/- 1.5 ;mmHg in A1AR-/- ( n = 9) and wild-type mice ( n = 8), respectively ( P = 0.43), RBF fell by 0.17 +/- 0.02 ml/min in A1AR-/- mice and by only 0.08 +/- 0.02 ml/min in wild-type animals ( P = 0.0039). Autoregulatory indexes for both GFR and RBF were significantly higher in A1AR-/- compared with A1AR+/+ mice, indicating reduced regulatory responsiveness in the knockout animals. We conclude that autoregulation of renal vascular resistance is less complete in A1AR-deficient mice, an effect that is presumably related to absence of TGF regulation in these animals. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Schnermann, J (reprint author), NIDDKD, NIH, Bldg 10 Rm 4 D51,10 Ctr Dr MSC 1370, Bethesda, MD 20892 USA. EM jurgens@intra.niddk.nih.gov RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 FU Intramural NIH HHS NR 21 TC 26 Z9 26 U1 0 U2 1 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 2006 VL 290 IS 4 BP F888 EP F891 DI 10.1152/ajprenal.00381.2005 PG 4 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 020DZ UT WOS:000235889900020 PM 16263804 ER PT J AU Pruitt, MEC Knepper, MA Graves, B Schmidt-Nielsen, B AF Pruitt, MEC Knepper, MA Graves, B Schmidt-Nielsen, B TI Effect of peristaltic contractions of the renal pelvic wall on solute concentrations of the renal inner medulla in the hamster SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE urinary concentrating mechanism; urea; osmolality ID COUNTERCURRENT MULTIPLICATION SYSTEM; TIME-COURSE; TISSUE COMPOSITION; COLLECTING DUCT; URINE; RAT; OSMOLALITY; MECHANISM; PAPILLA; FLOW AB The mechanism of solute accumulation in the renal inner medulla remains an unresolved issue. Experiments were carried out in hamsters to address the possibility that the peristaltic contractions of the renal pelvic wall surrounding the inner medulla play a role in the inner medullary concentrating process. The right renal pelvis was subjected to one of four manipulations ( surgical removal of the pelvic wall, paralysis of the pelvic wall with xylocaine, inhibition of pelvic contractions by direct application of heat, or sham treatment) followed by analysis of the inner medullary solute concentrations in the right kidney vs. the untouched left kidney. Removal of the pelvic wall resulted in a marked reduction in inner medullary osmolality, confirming prior observations. Paralysis of the pelvic wall with xylocaine produced a similar decrease in inner medullary osmolality, despite the fact that urine flow was maintained. In contrast, sham treatment ( surgical exposure of the right renal pelvic wall without any further manipulation) did not decrease inner medullary osmolality. To test whether the decrease in urinary osmolality following xylocaine treatment could have been due to a side effect of the drug, pelvic peristaltic contractions were eliminated in another way, by direct application of heat to denature the smooth muscle of the pelvic wall. This procedure also significantly decreased inner medullary osmolality. We conclude that elimination of the contractions of the renal pelvic wall in the hamster significantly impairs inner medullary concentrating ability. C1 Natl Heart Lung & Blood Inst, Lab Kidney & Electrolyte Metab, NIH, Bethesda, MD 20892 USA. Mt Desert Isl Biol Lab, Salsbury Cove, ME USA. RP Knepper, MA (reprint author), Natl Heart Lung & Blood Inst, Lab Kidney & Electrolyte Metab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr,MSC-1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01-HL-01285]; NIADDK NIH HHS [AM-15972] NR 21 TC 12 Z9 12 U1 0 U2 1 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 2006 VL 290 IS 4 BP F892 EP F896 DI 10.1152/ajprenal.00323.2005 PG 5 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 020DZ UT WOS:000235889900021 PM 16234309 ER PT J AU Klabunde, CN Schenck, AP Davis, AW AF Klabunde, CN Schenck, AP Davis, AW TI Barriers to colorectal cancer screening among medicare consumers SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT 132nd Annual Meeting of the American-Public-Health-Association CY NOV 06-10, 2004 CL Washington, DC SP Amer Public Hlth Assoc ID OLDER WOMEN; COVERAGE; RECOMMENDATION; BENEFICIARIES; SURVEILLANCE; GUIDELINES; RATIONALE; SERVICES; TESTS; RISK AB Background: Few studies have examined lack of physician recommendation and other reasons for under-utilization of colorectal cancer (CRC) screening in the Medicare Population. Methods: Data from a telephone survey conducted in 2001 in a random sample of Medicare consumers residing in North and South Carolina were used to examine barriers to CRC screening, focusing on consumers' reports of receiving a physician's recommendation to obtain CRC screening and reasons for not being screened. Analyses were restricted to respondents with no history of CRC (n =1901). Descriptive statistics were used to characterize respondents' CRC screening status, receipt of a physician's recommendation for screening, and reasons for not being screened. Logistic regression modeling was used to examine factors associated with receiving a physician recommendation for fecal Occult blood test, sigmoidoscopy, colonoscopy, any endoscopy, and an), CRC test. Results: Thirty-one percent of Medicare consumers had never been tested for CRC, and 18% had been tested but were not current with Medicare-covered intervals. Overall, 28% reported not receiving a physician recommendation for screening. Predictors of receiving a physician recommendation included sociodemographic (younger age, white race, more education), health status (increased CRC risk, comorbidity), and healthcare access (had a routine/preventive care visit in the past 12 months) factors. Lack of knowledge/awareness and the physician not ordering the test were commonly cited reasons for not having CRC tests. Conclusions: Colorectal cancer screening was under-utilized by Medicare consumers in two states, and lack of physician recommendation was an important contributing factor. Providing a benefit under the Medicare program does not ensure its widespread use by consumers or their physicians. C1 N Carolina Inc, Cary, NC 27511 USA. NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Stat Res & Applicat Branch, Surveillance Res Program, Div Canc Control & Populat Sci, Rockville, MD USA. RP Schenck, AP (reprint author), N Carolina Inc, 100 Regency Forest Dr,Suite 200, Cary, NC 27511 USA. EM aschenck@ncqio.sdps.org FU NCI NIH HHS [Y1-PC-1007] NR 24 TC 105 Z9 106 U1 1 U2 3 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 2006 VL 30 IS 4 BP 313 EP 319 DI 10.1016/j.amepre.2005.11.006 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 024HN UT WOS:000236186200006 PM 16530618 ER PT J AU Schenck, AP Klabunde, CN Davis, WW AF Schenck, AP Klabunde, CN Davis, WW TI Racial differences in colorectal cancer test use by medicare consumers SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT 132nd Annual Meeting of the American-Public-Health-Association CY NOV 06-10, 2004 CL Washington, DC SP Amer Public Hlth Assoc ID AFRICAN-AMERICANS; PREVENTIVE SERVICES; SCREENING BEHAVIOR; DISPARITIES; WOMEN; BENEFICIARIES; NATION; ADULTS; OLDER; CARE AB Background: Lower use of colorectal cancer (CRC) screening has been suggested as a factor in higher rates of CRC incidence and mortality among African Americans. Racial differences in colorectal cancer test use are not well understood. Methods: The study sample included respondents aged 50 to 80 to a 2001 telephone survey of Medicare consumers from two states. The analyses, initiated in 2004, were limited to respondents with no history of CRC (n = 1901). Three CRC tests were examined: fecal occult blood tests (FOBTs), sigmoidoscopy, and colonoscopy. Type of testing and testing according to Medicare coverage intervals by race were compared. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained from unadjusted and adjusted models to assess the independent associations between race and test use. Results: Adherence to the Medicare-covered intervals for CRC tests was low (56.8% for whites, 39.1% for African Americans), and did not significantly differ by race after adjustment. African Americans were, however, significantly less likely to have ever been tested (OR=0.48, 95% CI=0.33-0.70) and more likely to have had an endoscopic test than an FOBT (OR=3.06,95% CI=1.70-5.51). Conclusions: The type Of test used to screen for colorectal cancer has important implications for compliance with recommended screening intervals. Understanding reasons for racial differences in CRC test use may help identify approaches to increasing test use in the Medicare population. C1 Med Review N Carolina, Cary, NC 27511 USA. NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Stat Res & Applicat Branch, Surveillance Res Program, Div Canc Control & Populat Sci, Rockville, MD USA. RP Schenck, AP (reprint author), Med Review N Carolina, 100 Regency Forest,Suite 200, Cary, NC 27511 USA. EM aschenck@ncqio.sdps.org FU NCI NIH HHS [Y1-PC-1007] NR 32 TC 23 Z9 23 U1 1 U2 1 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 2006 VL 30 IS 4 BP 320 EP 326 DI 10.1016/j.amepre.2005.11.005 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 024HN UT WOS:000236186200007 PM 16530619 ER PT J AU Stanyon, R Dumas, F Stone, G Bigoni, F AF Stanyon, R Dumas, F Stone, G Bigoni, F TI Multidirectional chromosome painting reveals a remarkable syntenic homology between the greater galagos and the slow loris SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE lorisoids; strepsirrhines; genome evolution; phylogeny; primates; cytogenetics ID PRIMATE PHYLOGENY; DIVERGENCE; EVOLUTION; HISTORY; HUMANS; LEMURS AB We report on the first reciprocal chromosome painting of lorisoids and humans. The chromosome painting showed a remarkable syntenic homology between Otolemur and Nycticebus. Eight derived syntenic associations of human segments are common to both Otolemur and Nycticebus, indicative of a considerable period of common evolution between the greater galago and the slow loris. Five additional Robertsonian translocations form the slow loris karyotype, while the remaining chromosomes are syntenically equivalent, although some differ in terms of centromere position and heterochromatin additions. Strikingly, the breakpoints of the human chromosomes found fragmented in these two species are apparently identical. Only fissions of homologs to human chromosomes 1 and 15 provide significant evidence of a cytogenetic link between Lemuriformes and Lorisiformes. The association of human chromosomes 7/16 in both lorisoids strongly suggests that this chromosome was present in the ancestral primate genome. C1 NCI, Comparat Mol Cytogenet Core, MCGP, Frederick, MD 21701 USA. Univ Palermo, DBA, Palermo, Italy. RP Stanyon, R (reprint author), Univ Florence, Lab Anthropol, Dept Anim Biol, Via Proconsol 12, I-50122 Florence, Italy. EM stanyon@unifi.it OI Stanyon, Roscoe/0000-0002-7229-1092 NR 28 TC 11 Z9 11 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD APR PY 2006 VL 68 IS 4 BP 349 EP 359 DI 10.1002/ajp.20229 PG 11 WC Zoology SC Zoology GA 028RC UT WOS:000236504900003 PM 16534804 ER PT J AU Zuvekas, SH Vitiello, B Norquist, GS AF Zuvekas, SH Vitiello, B Norquist, GS TI Recent trends in stimulant medication use among US children SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PSYCHOTROPIC MEDICATIONS; PREVALENCE; HYPERACTIVITY; PERSPECTIVE; HEALTH; TRIAL AB Objective: Stimulant medications, such as methylphenidate and amphetamines, are commonly prescribed to treat attention deficit hyperactivity disorder. Stimulant use increased fourfold from 1987 ( 0.6%) to 1996 ( 2.4%) among subjects 18-year- old and younger in the U. S. The aim of this study was to determine whether pediatric use of stimulants continued to rise during the period 1997 - 2002. Method: The Medical Expenditure Panel Survey ( MEPS) database for the years 1997 - 2001 was analyzed. The MEPS is a yearly survey of a nationally representative sample of civilian, noninstitutionalized U. S. households, conducted by the U. S. Agency for Health Care Research and Quality. Previously reported estimates from the 1996 MEPS and the 1987 National Medical Expenditure Survey, the predecessor to MEPS, were also replicated to compare recent trends to changes between 1987 and 1996. Results: The prevalence use of stimulants among subjects under 19 years of age was 2.7% ( 95% C.I. 2.3 - 3.1) in 1997 and 2.9% ( 95% C.I. 2.5 - 3.3) in 2002, with no statistically significant change during these 6 years. Likewise, when pooling data across years and comparing the rate in 1997 - 1998 ( 2.8%) with the rate in 2001 - 2002 ( 3.0%), no statistically significant changes emerged. Use was highest among 6 - 12 year olds ( 4.8% in 2002), as compared with 3.2% among 13 - 19 year olds and 0.3% among children under 6. An estimated 2.2 million ( 95% C.I. 1.9 - 2.6) children received stimulant medication in 2002 as compared to 2.0 million ( 95% C.I. 1.7 - 2.3) in 1997. Conclusions: The steep increase in the utilization of stimulants among children 18 years and younger that occurred over the 1987 - 1996 period attenuated in the following years through 2002, and has remained stable among very young children. C1 NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Agcy Hlth Care Res & Qual, Div Social & Econ Res, Ctr Financing Access & Cost Trends, Rockville, MD USA. RP Vitiello, B (reprint author), NIMH, Div Serv & Intervent Res, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov NR 20 TC 105 Z9 106 U1 1 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2006 VL 163 IS 4 BP 579 EP 585 DI 10.1176/appi.ajp.163.4.579 PG 7 WC Psychiatry SC Psychiatry GA 029EF UT WOS:000236541200007 PM 16585430 ER PT J AU McEvoy, JP Lieberman, JA Stroup, TS Davis, SM Meltzer, HY Rosenheck, RA Swartz, MS Perkins, DO Keefe, RSE Davis, CE Severe, J Hsiao, JK AF McEvoy, JP Lieberman, JA Stroup, TS Davis, SM Meltzer, HY Rosenheck, RA Swartz, MS Perkins, DO Keefe, RSE Davis, CE Severe, J Hsiao, JK CA CATIE Investigators TI Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID TRIALS; CHLORPROMAZINE; HALOPERIDOL; RISKS AB Objective: When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness ( CATIE) investigation. Method: Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine ( N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial ( olanzapine [ N=19], quetiapine [ N=15], or risperidone [ N=16]). Results: Time until treatment discontinuation for any reason was significantly longer for clozapine ( median=10.5 months) than for quetiapine ( median=3.3), or risperidone ( median=2.8), but not for olanzapine ( median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation. Conclusions: For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects. C1 John Umstead Hosp, Clin Res Serv, Durham, NC 27705 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. Columbia Univ, New York State Psychiat Inst, Dept Psychiat, Coll Phys & Surg, New York, NY USA. Univ N Carolina, Dept Biostat, Sch Publ Hlth, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Quintiles Inc, Res Triangle Pk, NC USA. Vanderbilt Univ, Dept Psychiat, Sch Med, Nashville, TN USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP McEvoy, JP (reprint author), John Umstead Hosp, Clin Res Serv, 1003 12th St,Bldg 32, Durham, NC 27705 USA. EM jpmcevoy@duke.edu RI Meltzer, Herbert/E-8131-2013; Stroup, Thomas/F-9188-2014 OI Stroup, Thomas/0000-0002-3123-0672 NR 18 TC 484 Z9 495 U1 7 U2 29 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2006 VL 163 IS 4 BP 600 EP 610 DI 10.1176/appi.ajp.163.4.600 PG 11 WC Psychiatry SC Psychiatry GA 029EF UT WOS:000236541200011 PM 16585434 ER PT J AU Terleph, TA Klein, RG Roberson-Nay, R Mannuzza, S Moulton, JL Woldehawariat, G Guardino, M Pine, DS AF Terleph, TA Klein, RG Roberson-Nay, R Mannuzza, S Moulton, JL Woldehawariat, G Guardino, M Pine, DS TI Stress responsivity and HPA axis activity in juveniles: Results from a home-based CO2 inhalation study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CARBON-DIOXIDE; CHILDREN; DISORDERS AB Objective: A previous laboratory-based study found elevated cortisol levels in anxious children susceptible to CO2-induced panic, but the effects of parent diagnosis were not considered. The current home-based study tested the hypothesis that parental panic disorder and offspring response to CO2 are associated with elevated cortisol levels in juvenile offspring. Method: A total of 131 offspring ( ages 9-19) of parents with panic disorder, major depression, and no mental disorder underwent CO2 inhalation. Parent and child diagnoses were assessed. Salivary cortisol was assayed before and after CO2 inhalation. Results: Neither parents with panic disorder, parents with major depression, or offspring anxiety predicted offspring cortisol levels. Independent of parent and child diagnoses, anxiety response to CO2 predicted elevated cortisol levels in offspring. Conclusions: As in adults, anxiety response to CO2 in juveniles is associated with elevated cortisol levels, but elevated cortisol levels are not related to parent or child diagnoses. C1 NIMH, Sect Dev & Affect Neurosci, Intramural Res Program, NIH, Bethesda, MD 20817 USA. NYU, Ctr Child Study, New York, NY USA. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. Freedom From Fear, Staten Isl, NY USA. RP Pine, DS (reprint author), NIMH, Sect Dev & Affect Neurosci, Intramural Res Program, NIH, Bldg 15-K,Rm 110,MSC 2670, Bethesda, MD 20817 USA. EM daniel.pine@nih.gov FU NIMH NIH HHS [R01 MH-59171] NR 7 TC 13 Z9 13 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2006 VL 163 IS 4 BP 738 EP U2 DI 10.1176/appi.ajp.163.4.738 PG 3 WC Psychiatry SC Psychiatry GA 029EF UT WOS:000236541200030 PM 16585453 ER PT J AU Marenco, S Steele, SU Egan, MF Goldberg, TE Straub, RE Sharrief, AZ Weinberger, DR AF Marenco, S Steele, SU Egan, MF Goldberg, TE Straub, RE Sharrief, AZ Weinberger, DR TI Effect of metabotropic glutamate receptor 3 genotype on N-acetylaspartate measures in the dorsolateral prefrontal cortex SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 12-16, 2004 CL San Juan, PR SP Vanderbilt Univ, Sch Med, Dept Psychiaty, Amer Coll Neuropsychopharmacol ID SCHIZOPHRENIA; GRM3; GENE; POPULATION AB Objective: This study was carried out to confirm prior evidence of an effect of a single nucleotide polymorphism ( SNP) in the metabotropic glutamate receptor 3 ( GRM3) gene ( a putative risk factor for schizophrenia) on measures of N-acetylaspartate in healthy comparison subjects. Method: Fifty-four carefully screened healthy volunteers genotyped at SNP rs6465084 underwent magnetic resonance spectroscopic imaging ( MRSI) at 3 T and selected neuropsychological testing. Results: The A/A genotype group exhibited a significant reduction of N-acetylaspartate/ creatine levels in the right dorsolateral prefrontal cortex compared to the G carriers. A tendency in the same direction was seen in the left dorsolateral prefrontal cortex and in the white matter adjacent to the prefrontal cortex. Conclusions: These findings provide further evidence that GRM3 affects prefrontal function and that variation in GRM3, monitored by SNP rs6465084, affects GRM3 function. C1 NIMH, Marenco Genes & Cognit Program, Clin Brain Disorders Branch, Intramural Program,NIH, Bethesda, MD 20892 USA. RP Marenco, S (reprint author), NIMH, Marenco Genes & Cognit Program, Clin Brain Disorders Branch, Intramural Program,NIH, Bldg 10,Rm 4S235,10 Ctr Dr, Bethesda, MD 20892 USA. EM marencos@mail.nih.gov RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 FU Intramural NIH HHS; NIMH NIH HHS [Z01 MH002716-11] NR 8 TC 33 Z9 34 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2006 VL 163 IS 4 BP 740 EP 742 DI 10.1176/appi.ajp.163.4.740 PG 3 WC Psychiatry SC Psychiatry GA 029EF UT WOS:000236541200031 PM 16585454 ER PT J AU Parry, MS AF Parry, MS TI Sara Josephine Baker (1873-1945) SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Biographical-Item C1 NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20894 USA. RP Parry, MS (reprint author), NIH, Hist Med Div, Natl Lib Med, 8600 Rockville Pike,Bldg 38,Room 1E-21, Bethesda, MD 20894 USA. NR 1 TC 1 Z9 1 U1 0 U2 1 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 2006 VL 96 IS 4 BP 620 EP 621 DI 10.2105/AJPH.2005.079145 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 027QD UT WOS:000236429200017 ER PT J AU Parry, MS AF Parry, MS TI Dorothea Dix (1802-1887) SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Biographical-Item C1 NIH, Exhibit Program, Hist Med Div, Natl Lib Med, Bethesda, MD 20894 USA. RP Parry, MS (reprint author), NIH, Exhibit Program, Hist Med Div, Natl Lib Med, 8600 Rockville Pike,Bldg 38,Rm 1E-21, Bethesda, MD 20894 USA. EM parrym@mail.nlm.nih.gov NR 1 TC 0 Z9 0 U1 1 U2 6 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 2006 VL 96 IS 4 BP 624 EP 625 DI 10.2105/AJPH.2005.079152 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 027QD UT WOS:000236429200019 ER PT J AU Saluja, G Brenner, RA Trumble, AC Smith, GS Schroeder, T Cox, C AF Saluja, G Brenner, RA Trumble, AC Smith, GS Schroeder, T Cox, C TI Swimming pool drownings among US residents aged 5-24 years: Understanding racial/ethnic disparities SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CAUSE-SPECIFIC MORTALITY; UNITED-STATES; CHILDREN; PREVENTION; ADOLESCENTS; INFANTS; COUNTY AB Objective. We examined circumstances surrounding swimming pool drownings among US residents aged 5 to 24 years to understand why Black males and other racial/ethnic groups have high drowning rates. Methods. We obtained data about drowning deaths in the United States (1995-1998) from death certificates, medical examiner reports, and newspaper clippings collected by the US Consumer Product Safety Commission. Results. During the study period, 678 US residents aged 5 to 24 years drowned in pools. Seventy-five percent were male, 47% were Black, 33% were White, and 12% were Hispanic. Drowning rates were highest among Black males, and this increased risk persisted after we controlled for income. The majority of Black victims (51%) drowned in public pools, the majority of White victims (55%) drowned in residential pools, and the majority of Hispanic victims (35%) drowned in neighborhood pools (e.g., an apartment complex pool). Foreign-born males also had an increased risk for drowning compared with American-born males. Conclusions. Targeted interventions are needed to reduce the incidence of swimming pool drownings across racial/ethnic groups, particularly adult supervision at public pools. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Liberty Mutual Res Inst Safety, Hopkinton, MA USA. US Consumer Prod Safety Commiss, Bethesda, MD USA. RP Saluja, G (reprint author), NICHD, NIH, DHHS, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Rm 7B03 MSC 7510, Bethesda, MD 20892 USA. EM salujag@mail.nih.gov OI Smith, Gordon/0000-0002-2911-3071 NR 20 TC 23 Z9 23 U1 0 U2 6 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 2006 VL 96 IS 4 BP 728 EP 733 DI 10.2105/AJPH.2004.057067 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 027QD UT WOS:000236429200038 PM 16507730 ER PT J AU Segal, BH Walsh, TJ AF Segal, BH Walsh, TJ TI Current approaches to diagnosis and treatment of invasive aspergillosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE Aspergillus; immunocompromised; neutropenia; transplant ID COLONY-STIMULATING FACTOR; CHRONIC GRANULOMATOUS-DISEASE; POLYMERASE-CHAIN-REACTION; CELL TRANSPLANT RECIPIENTS; BONE-MARROW-TRANSPLANTATION; LIPOSOMAL AMPHOTERICIN-B; EXPERIMENTAL PULMONARY ASPERGILLOSIS; COMBINATION ANTIFUNGAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; ACUTE MYELOGENOUS LEUKEMIA AB Filamentous fungi (moulds) are ubiquitous soil inhabitants whose conidia are inhaled into the respiratory tract, where they may cause life-threatening infections. Among these infections is invasive aspergillosis, which is a major cause of morbidity and mortality in the severely immunocompromised. Risk factors for invasive aspergillosis include prolonged and severe neutropenia, hematopoietic stem cell and solid organ transplantation, advanced AIDS, and chronic granulomatous disease. Invasive aspergillosis most commonly involves the sinopulmonary tract reflecting inhalation as the principal portal of entry. Chest computed tomography scans and new non-culture-based assays such as antigen detection and polymerase chain reaction may facilitate the early diagnosis of invasive aspergillosis, but have limitations. Reflecting an important unmet need, there has been a significant expansion in the antifungal armamentarium. The second-generation triazole, voriconazole, was superior to conventional amphotericin B as primary therapy for invasive aspergillosis, and is the new standard of care for this infection. There is significant interest in combination antifungal therapy pairing an echinocandin with either an azole or amphotericin B formulation as therapy for invasive aspergillosis. In addition, there has been an increased understanding of the immunology of Aspergillus infection, paving the way to novel immune augmentation strategies in animal models that merit evaluation in phase I clinic trials. C1 SUNY Buffalo, Dept Med, Roswell Pk Canc Inst, Div Infect Dis, Buffalo, NY 14263 USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Segal, BH (reprint author), SUNY Buffalo, Dept Med, Roswell Pk Canc Inst, Div Infect Dis, Elm & Carlton St, Buffalo, NY 14263 USA. EM brahm.segal@roswellpark.org NR 118 TC 164 Z9 192 U1 2 U2 11 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 2006 VL 173 IS 7 BP 707 EP 717 DI 10.1164/rccm.200505-727SO PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 029AQ UT WOS:000236530600004 PM 16387806 ER PT J AU Avila, NA Dwyer, AJ Rabel, A DeCastro, RM Moss, J AF Avila, NA Dwyer, AJ Rabel, A DeCastro, RM Moss, J TI CT of pleural abnormalities in lymphangioleiomyomatosis and comparison of pleural findings after different types of pleurodesis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT 103rd Annual Meeting of the American-Roentgen-Ray-Society CY MAY, 2003 CL SAN DIEGO, CA SP Amer Roentgen Ray Soc DE CT; lung diseases; lymphangioleiomyomatosis; pleura; pleurodesis ID BORE-CATHETER THORACOSTOMY; TALC PLEURODESIS; EFFUSIONS; LYMPHANGIOMYOMATOSIS; SCLEROTHERAPY; TETRACYCLINE; TOMOGRAPHY; METASTASES AB OBJECTIVE. The objective of our article was to describe the spectrum and frequency of pleural abnormalities on CT in patients with lymphangioleiomyomatosis (LAM) and the pleural findings associated with different types of pleurodesis (talc, mechanical, and chemical) performed to treat the complications of pleural disease in these patients. MATERIALS AND METHODS. Two hundred fifty-eight patients with LAM underwent CT of the chest. Pleural abnormalities assessed included pleural thickening, presence of a pleural mass, areas of high attenuation, effusion, and pneumothorax. In patients who had had pleurodesis, the CT findings were correlated with the type of procedure performed. RESULTS. One hundred thirty-three (52%) of 258 patients had pleurodesis (unilateral, 68/133; bilateral, 65/133). Pleural abnormalities were more common in patients who had pleurodesis (101/133, 76%) than in those who had not (47/125, 38%) and were more prevalent on the operated side than on the unoperated side of those 68 patients who had unilateral pleurodesis. The frequencies of findings for the group without pleurodesis versus the group with pleurodesis were pleural thickening (26% vs 65%), effusion (10% vs 13%), loculated effusion (2.4% vs 11%), pneumothorax (1.6% vs 10%), areas of high attenuation (1.6% vs 23%), and mass (0.8% vs 14%), respectively. Areas of high attenuation in the pleura were present in all types of pleurodesis (mechanical, 8%; chemical. 13%; talc, 40%) and in two patients who had had repeated thoracentesis or pleurectomy. Pleural masses were present in patients who had had all types of pleurodesis (mechanical, 10%; chemical, 9%; talc, 24%) and in one patient who had had thoracentesis and thoracostomy; the masses commonly enhanced and did not change in size over time. CONCLUSION. Pleural abnormalities are common in patients with LAM as complications of the disease itself and as sequelae of pleurodesis and other pleura manipulations. Pneumothorax and pleural effusion result from the underlying pathophysiology of LAM, whereas areas of high attenuation and masses develop after all types of pleurodesis and other manipulations of the pleura (i.e.. thoracentesis, thoracostomy). C1 Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Avila, NA (reprint author), Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bldg 10,Rm 1C-660,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. NR 29 TC 8 Z9 9 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2006 VL 186 IS 4 BP 1007 EP 1012 DI 10.2214/AJR.04.1912 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 026DD UT WOS:000236316000017 PM 16554571 ER PT J AU Vega, F Chang, CC Schwartz, MR Preti, HA Younes, M Ewton, A Verm, R Jaffe, ES AF Vega, F Chang, CC Schwartz, MR Preti, HA Younes, M Ewton, A Verm, R Jaffe, ES TI Atypical NK-cell proliferation of the gastrointestinal tract in a patient with antigliadin antibodies but not celiac disease SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE atypical NK-cell proliferation; gastrointestinal tract; celiac disease ID T-CELL; AGGRESSIVE NEOPLASM; CLINICAL-FEATURES; LYMPHOMA; ENTEROPATHY; MALIGNANCIES; NASAL; CLASSIFICATION; LESIONS; CD56 AB We describe a unique case of atypical. natural killer (NK)-cell proliferation likely related to gluten sensitivity, mimicking NK-cell lymphoma. The patient, a 32-year-old man, has had persistent multiple crythematous bull-eye lesions in the stomach, small bowel, and large bowel for 3 years. Histologically, the lesions were well circumscribed and relatively superficial, composed of atypical medium-sized to large-sized lymphocytes with slightly irregular nuclear contours, a dispersed chromatin pattern, and clear cytoplasm. Immunohistochemistry and flow cytometry showed that the cells were NK cells expressing CD56 (aberrantly bright). T-cell intracellular antigen (TIA)-1, cytoplasmic CD3, and CD94, but not surface CD3, with bright aberrant expression of CD7 and a lack of other NK cell-associated markers. Polymerase chain reaction for rearrangement of the T-cell receptor-gamma chain gene showed no evidence of a clonal T-cell population, and in situ hybridization for Epstein-Barr Virus encoded RNA was negative. There was no evidence of the involvement of peripheral blood or bone marrow. Although a diagnosis or extranodal NK/T-cell lymphoma was considered because of the atypical morphology and immunophenotypic aberrancy, no chemotherapy was given because of the relatively Superficial nature of the infiltrates, lack of significant symptoms, and negativity for Epstein-Barr virus. Two years after initial presentation., the patient was found to have high titers of antigliadin antibodies with no other evidence of celiac disease. After instituting a gluten-free diet, many of the lesions regressed, suggesting that this atypical NK-cell proliferation may be driven by all anomalous immune response. Awareness of this case may prevent pathologists from mis-diagnosing similar lesions as NK/T-cell lymphomas. It is as yet unknown whether this process occurs more commonly in patients with gluten sensitivity, or in other settings. and the pathogenesis is as Yet undetermined. C1 Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. Methodist Hosp, Dept Oncol, Houston, TX 77030 USA. Methodist Hosp, Dept Gastroenterol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. RP Chang, CC (reprint author), Methodist Hosp, Dept Pathol, 6565 Fannin MS 205, Houston, TX 77030 USA. EM jeffchang@tmh.tmc.edu OI Younes, Mamoun/0000-0001-9618-3451; Vega, Francisco/0000-0001-5956-452X FU Intramural NIH HHS NR 29 TC 14 Z9 14 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2006 VL 30 IS 4 BP 539 EP 544 DI 10.1097/00000478-200604000-00017 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 033US UT WOS:000236876500017 PM 16625103 ER PT J AU Kirk, AD AF Kirk, AD TI Meteorology and tolerance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material C1 NIDDK, Transplantat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Kirk, AD (reprint author), NIDDK, Transplantat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM allank@intra.niddk.nih.gov RI Kirk, Allan/B-6905-2012 FU Intramural NIH HHS NR 6 TC 9 Z9 11 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 2006 VL 6 IS 4 BP 645 EP 646 DI 10.1111/j.1600-6143.2006.01244.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 019ME UT WOS:000235839900001 PM 16539618 ER PT J AU Kunapuli, P Lee, S Zheng, W Alberts, M Kornienko, O Rebecca, MA AF Kunapuli, P Lee, S Zheng, W Alberts, M Kornienko, O Rebecca, MA TI Identification of small molecule antagonists of the human mas-related gene-X1 receptor SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE GPCRs; MRG-X1; high-throughput screening; reporter gene assay; receptor trafficking; GFP; Azabicyclo-octanes ID PROTEIN-COUPLED RECEPTORS; BETA-LACTAMASE; FAMILY; GPCRS; MINIATURIZATION; TRANSCRIPTION; ARRESTINS; REPORTER; LIGANDS; ASSAYS AB The recently identified mas-related-gene (MRG) family of receptors, located primarily in sensory neurons of the dorsal root ganglion, has been implicated in the perception of pain. Thus, antagonists of this class of receptors have been postulated to be useful analgesics. Toward this end, we developed a cell-based beta-lactamase (BLA) reporter gene assay to identify small molecule antagonists of the human MRG-X1 receptor from a library of compounds. Single-cell clones expressing functional receptors were selected using the BLA reporter gene technology. The EC50 for the MRG agonist peptide, BAM 15, appeared to be comparable between the BLA assay and the intracellular Ca2+ transient assays in these cells. Ultra high-throughput screening of approximately 1 million compounds in a 1.8-mu l cell-based BLA reporter gene assay was conducted in a 3456-well plate format. Compounds exhibiting potential antagonist profile in the BLA assay were confirmed in the second messenger Ca2+ transient assay. A cell-based receptor trafficking assay was used to further validate the mechanism of action of these compounds. Several classes of compounds, particularly the 2,3-disubstituted azabicyclo-octanes, appear to be relatively potent antagonists at the human MRG-X1 receptors, as confirmed by the receptor trafficking assay and radioligand binding studies. Furthermore, the structure-activity relationship reveals that within this class of compounds, the diphenylmethyl moiety is constant at the 2-substituent, whereas the 3-substituent is directly correlated with the antagonist activity of the compound. (c) 2006 Elsevier Inc. All rights reserved. C1 Merck Res Labs, Dept Automated Biotechnol, N Wales, PA 19454 USA. NIH, Bethesda, MD 20892 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. RP Kunapuli, P (reprint author), Merck Res Labs, Dept Automated Biotechnol, N Wales, PA 19454 USA. EM priya-kunapuli@merck.com RI Zheng, Wei/J-8889-2014 OI Zheng, Wei/0000-0003-1034-0757 NR 20 TC 17 Z9 17 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD APR 1 PY 2006 VL 351 IS 1 BP 50 EP 61 DI 10.1016/j.ab.2006.01.014 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 027PR UT WOS:000236428000007 PM 16510108 ER PT J AU Limb, CJ Kemeny, S Ortigoza, EB Rouhani, S Braun, AR AF Limb, CJ Kemeny, S Ortigoza, EB Rouhani, S Braun, AR TI Left hemispheric lateralization of brain activity during passive rhythm perception in musicians SO ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY LA English DT Article DE rhythm; functional magnetic resonance imaging; perisylvian; auditory cortex ID TRANSCRANIAL DOPPLER SONOGRAPHY; ANTERIOR TEMPORAL LOBECTOMY; AUDITORY-CORTEX; CEREBRAL HEMODYNAMICS; LANGUAGE; COMPREHENSION; ASYMMETRY; SPEECH; SOUNDS; PITCH AB The nature of hemispheric specialization of brain activity during rhythm processing remains poorly understood. The locus for rhythmic processing has been difficult to identify and there have been several contradictory findings. We therefore used functional magnetic resonance imaging to study passive rhythm perception to investigate the hypotheses that rhythm processing results in left hemispheric lateralization of brain activity and is affected by musical training. Twelve musicians and 12 nonmusicians listened to regular and random rhythmic patterns. Conjunction analysis revealed a shared network of neural structures (bilateral superior temporal areas, left inferior parietal lobule, and right frontal operculum) responsible for rhythm perception independent of musical background. In contrast, random-effects analysis showed greater left lateralization of brain activity in musicians compared to nonmusicians during regular rhythm perception, particularly within the perisylvian cortices (left frontal operculum, superior temporal gyrus, inferior parietal lobule). These results suggest that musical training leads to the employment of left-sided perisylvian brain areas, typically active during language comprehension, during passive rhythm perception. C1 Natl Inst Deafness & Other Commun Disorders, Language Sect, Voice Speech & Language Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA. Johns Hopkins Univ, Peabody Conservatory Mus, Baltimore, MD USA. RP Limb, CJ (reprint author), Natl Inst Deafness & Other Commun Disorders, Language Sect, Voice Speech & Language Branch, 10 Ctr Dr, Bethesda, MD 20892 USA. EM limbc@nidcd.nih.gov FU Intramural NIH HHS NR 54 TC 22 Z9 23 U1 1 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4884 J9 ANAT REC PART A JI Anat. Rec. Part A PD APR PY 2006 VL 288A IS 4 BP 382 EP 389 DI 10.1002/ar.a.20298 PG 8 WC Anatomy & Morphology SC Anatomy & Morphology GA 032MY UT WOS:000236779900008 PM 16550585 ER PT J AU Lim, CJ AF Lim, CJ TI Structural and functional neural correlates of music perception SO ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY LA English DT Article DE music; functional MRI; auditory cortex; Heschl's gyrus; planum temporale ID PARABELT AUDITORY-CORTEX; ANTERIOR TEMPORAL LOBECTOMY; ABSOLUTE PITCH; MACAQUE MONKEYS; HESCHLS GYRUS; SENTENCE COMPREHENSION; BLOOD OXYGENATION; PLANUM TEMPORALE; CORPUS-CALLOSUM; BRAIN-REGIONS AB This review article highlights state-of-the-art functional neuroimaging studies and demonstrates the novel use of music as a tool for the study of human auditory brain structure and function. Music is a unique auditory stimulus with properties that make it a compelling tool with which to study both human behavior and, more specifically, the neural elements involved in the processing of sound. Functional neuroimaging techniques represent a modern and powerful method of investigation into neural structure and functional correlates in the living organism. These methods have demonstrated a close relationship between the neural processing of music and language, both syntactically and semantically. Greater neural activity and increased volume of gray matter in Heschl's gyrus has been associated with musical aptitude. Activation of Broca's area, a region traditionally considered to subserve language, is important in interpreting whether a note is on or off key. The planum temporale shows asymmetries that are associated with the phenomenon of perfect pitch. Functional imaging studies have also demonstrated activation of primitive emotional centers such as ventral striatum, midbrain, amygdala, orbitofrontal cortex, and ventral medial prefrontal cortex in listeners of moving musical passages. In addition, studies of melody and rhythm perception have elucidated mechanisms of hemispheric specialization. These studies show the power of music and functional neuroimaging to provide singularly useful tools for the study of brain structure and function. C1 Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Peabody Conservatory Mus, Baltimore, MD USA. Johns Hopkins Univ Hosp, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. RP Lim, CJ (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 10 Ctr Dr,3C-716, Bethesda, MD 20892 USA. EM limbc@nided.nih.gov NR 84 TC 0 Z9 0 U1 4 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4884 J9 ANAT REC PART A JI Anat. Rec. Part A PD APR PY 2006 VL 288A IS 4 BP 435 EP 446 DI 10.1002/ar.a.20316 PG 12 WC Anatomy & Morphology SC Anatomy & Morphology GA 032MY UT WOS:000236779900013 ER PT J AU Sampson, HA Munoz-Furlong, A Campbell, RL Adkinson, NF Bock, SA Branum, A Brown, SGA Camargo, CA Cydulka, R Galli, SJ Gidudu, J Gruchalla, RS Harlor, AD Hepner, DL Lewis, LM Lieberman, PL Metcalfe, DD O'Connor, R Muraro, A Rudman, A Schmitt, C Scherrer, D Simons, FE Thomas, S Wood, JP Decker, WW AF Sampson, HA Munoz-Furlong, A Campbell, RL Adkinson, NF Bock, SA Branum, A Brown, SGA Camargo, CA Cydulka, R Galli, SJ Gidudu, J Gruchalla, RS Harlor, AD Hepner, DL Lewis, LM Lieberman, PL Metcalfe, DD O'Connor, R Muraro, A Rudman, A Schmitt, C Scherrer, D Simons, FE Thomas, S Wood, JP Decker, WW TI Second Symposium on the Definition and Management of Anaphylaxis: Summary report - Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network Symposium SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID EMERGENCY-DEPARTMENT VISITS; EPINEPHRINE ABSORPTION; PEANUT; SHOCK; CHILDREN; MODEL; FOOD; EPIDEMIOLOGY; MULTICENTER; ADOLESCENTS C1 Mayo Clin, Rochester, MN 55905 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Food Allergy & Anaphylaxis Network, Fairfax, VA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. Food Allergy & Anaphylaxis Network, Boulder, CO USA. Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Fremantle Hosp, Fremantle, WA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Ctr Dis Control & Prevent, Lilbum, GA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Amer Acad Pediat, Eugene, OR USA. Amer Soc Anesthesiol, Boston, MA USA. Soc Acad Emergency Med, St Louis, MO USA. Amer Coll Allergy Asthma & Immunol, Cordova, TN USA. NIAID, Bethesda, MD 20892 USA. Natl Inst Hlth, Bethesda, MD 20892 USA. Natl Assoc EMS Physicians, Baltimore, MD USA. Univ Padua, I-35100 Padua, Italy. Amer Acad Allergy Asthma & Immunol, Winnipeg, MB, Canada. Amer Coll Emergency Physicians, Dallas, TX USA. Amer Acad Emergency Med, Scottsdale, AZ USA. RP Decker, WW (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM decker.wyatt@mayo.edu RI Osborne, Nicholas/N-4915-2015; OI Osborne, Nicholas/0000-0002-6700-2284; Brown, Simon/0000-0002-9961-0890 NR 47 TC 161 Z9 168 U1 0 U2 9 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD APR PY 2006 VL 47 IS 4 BP 373 EP 380 DI 10.1016/j.annemergmed.2006.01.018 PG 8 WC Emergency Medicine SC Emergency Medicine GA 029IH UT WOS:000236555300013 PM 16546624 ER PT J AU Colliver, JD Compton, WM Gfroerer, JC Condon, T AF Colliver, JD Compton, WM Gfroerer, JC Condon, T TI Projecting drug use among aging baby boomers in 2020 SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE drug use; drug abuse; forecasting; model; elderly ID BALTIMORE ECA SAMPLE; SURVIVAL ANALYSIS; USE DISORDERS; DEPENDENCE; DEATH AB PURPOSE: Greater rates of lifetime drug use among the baby-boom generation, combined with the size of that generation, Suggest that the number of elderly persons using drugs Will increase in the next two decades. Given the potential public health demands implied by increasing numbers of elderly drug users, the goal is to project the numbers of current drug users aged 50 years and older in 2020. METHODS: Using the modeling and projection methods of Gfroerer et al (2003) applied to data from the 1999 to 2001 National Household Surveys on Drug Abuse, projections were developed for the use of marijuana, nonmedical use of any prescription-type psychotherapeutic drug, and any illicit drug use. RESULTS: From 1999 to 2001 to 2020, past-year marijuana use in persons 50 years and older is forecast to increase from 1.0% to 2.9%. The number of users is expected to increase from 719,000 to almost 3.3 million, reflecting the combined effects of the increase in rate of use and a projected 51.9% increase in the civilian nininstutionalised population in this age group. Use of any illicit drug Will increase from 2.2% (1.6 million) to 3.1% (3.5 million), and nonmedical use of psychotherapeutic drugs Will increase from 1.2% (911,000) to 2.4% (almost 2.7 million). CONCLUSIONS: These projections call attention to changes to be considered in planning and to the need for improved knowledge of the biomedical and psychosocial effects of nonmedical drug use on aging and elderly individuals. C1 NIDA, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Subst Abuse & Mental Hlth Serv Adm, Off Appl Studies, Dept Hlth & Human Serv, Rockville, MD USA. RP Compton, WM (reprint author), NIDA, NIH, Dept Hlth & Human Serv, 6001 Execut Blvd,MSC 9589, Bethesda, MD 20892 USA. EM wcompton@nida.nih.gov NR 24 TC 88 Z9 89 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD APR PY 2006 VL 16 IS 4 BP 257 EP 265 DI 10.1016/j.annepidem.2005.08.003 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 027OH UT WOS:000236424400003 PM 16275134 ER PT J AU Bai, O Vorbach, S Hallett, M Floeter, MK AF Bai, O Vorbach, S Hallett, M Floeter, MK TI Movement-related cortical potentials in primary lateral sclerosis SO ANNALS OF NEUROLOGY LA English DT Article ID HEREDITARY SPASTIC PARAPLEGIA; MOTOR-NEURON DISEASE; PRECEDING VOLUNTARY MOVEMENT; INCLUSION-BODY DISEASE; SELF-PACED MOVEMENTS; FRONTOTEMPORAL DEMENTIA; CLINICAL-FEATURES; TIME-COURSE; ALSIN GENE; 2 FINGERS AB Objective: Some patients with primary lateral sclerosis (PLS) have a clinical course suggestive of a length-dependent dying-back of corticospinal axons. We measured movement-related cortical potentials (MRCPs) in these patients to determine whether cortical functions that are generated through short, intracortical connections were preserved when functions conducted by longer corticospinal projections were impaired. Methods. An electroencephalogram was recorded from scalp electrodes of 10 PLS patients and 7 age-matched healthy control subjects as they made individual finger-tap movements on a keypad. MRCPs were derived from back-averaging the electroencephalogram to the movement. Results: MRCPs produced by finger taps were markedly reduced in PLS patients, including components generated by premotor areas of the cortex as well as the primary motor cortex. In contrast, the P-band event-related desynchronization from the motor cortex was preserved. Interpretation. These findings suggest that impairment in PLS is not limited to the distal axons of corticospinal neurons, but also affects neurons within the primary motor cortex and premotor cortical areas. The loss of the MRCP may serve as a useful marker of upper motor neuron dysfunction. Preservation of event-related desynchronization suggests that the cells of origin differ from the large pyramidal cells that generate the MRCP. C1 Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bethesda, MD USA. Natl Inst Neurol Disorders & Stroke, Electromyog Sect, NIH, Bethesda, MD USA. RP Floeter, MK (reprint author), 10 Ctr Dr MSC-1404,Bldg 10 CRC 7-5680, Bethesda, MD 20892 USA. EM floeterm@ninds.nih.gov FU Intramural NIH HHS NR 56 TC 22 Z9 22 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2006 VL 59 IS 4 BP 682 EP 690 DI 10.1002/ana.20803 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 029ZZ UT WOS:000236604200018 PM 16566016 ER PT J AU Fukuda, T Ewan, L Bauer, M Mattaliano, RJ Zaal, K Ralston, E Plotz, PH Raben, N AF Fukuda, T Ewan, L Bauer, M Mattaliano, RJ Zaal, K Ralston, E Plotz, PH Raben, N TI Dysfunction of endocytic and autophagic pathways in a lysosomal storage disease SO ANNALS OF NEUROLOGY LA English DT Article ID ACID ALPHA-GLUCOSIDASE; ENZYME REPLACEMENT THERAPY; INFANTILE POMPES-DISEASE; SKELETAL-MUSCLE FIBERS; KNOCKOUT MICE; CLINICAL-TRIAL; NATURAL COURSE; GOLGI-COMPLEX; CELLS; RECOMBINANT AB Objective To understand the mechanisms of skeletal muscle destruction and resistance to enzyme replacement therapy in Pompe disease, a deficiency of lysosomal acid a-glucosidase (GAA), in which glycogen accumulates in lysosomes primarily in cardiac and skeletal muscles. Methods: We have analyzed compartments of the lysosomal degradative pathway in GAA-deficient myoblasts and single type I and type 11 muscle fibers isolated from wild-type, untreated, and enzyme replacement therapy-treated GAA knock-out mice. Results. Studies in myoblasts from GAA knock-out mice showed a dramatic expansion of vesicles of the endocytic/autophagic pathways, decreased vesicular movement in overcrowded cells, and an acidification defect in a subset of late endosomes/lysosomes. Analysis by confocal microscopy of isolated muscle fibers demonstrated that the consequences of the lysosomal glycogen accumulation are strikingly different in type I and II muscle fibers. Only type II fibers, which are the most resistant to therapy, contain large regions of autophagic buildup that span the entire length of the fibers. Interpretation The vastly increased autophagic buildup may be responsible for skeletal muscle damage and prevent efficient trafficking of replacement enzyme to lysosomes. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Genzyme Corp, Cell & Prot Therapeut R&D, Framingham, MA 01701 USA. NIAMSD, Light Imaging Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. RP Raben, N (reprint author), NIAMS, NIH, 9000 Rockville Pike,Clin Ctr Bldg 10-9N244, Bethesda, MD 20892 USA. EM rabenn@arb.niams.nih.gov FU Intramural NIH HHS NR 46 TC 135 Z9 140 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2006 VL 59 IS 4 BP 700 EP 708 DI 10.1002/ana.20807 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 029ZZ UT WOS:000236604200020 PM 16532490 ER PT J AU Morbach, H Singh, SK Faber, C Lipsky, PE Girschick, HJ AF Morbach, H Singh, SK Faber, C Lipsky, PE Girschick, HJ TI Analysis of RAG expression by peripheral blood CD5+ and CD5- B cells of patients with childhood systemic lupus erythematosus SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID RECOMBINATION ACTIVATING GENE; SURROGATE LIGHT-CHAINS; V(D)J RECOMBINATION; B-1 CELLS; CD154-CD40 INTERACTIONS; ANTIBODY REPERTOIRE; ESCAPE TOLERANCE; CUTTING EDGE; HUMAN TONSIL; LYMPHOCYTES AB Background: The assembly of immunoglobulin genes during B cell development in the bone marrow is dependent on the expression of recombination activating genes (RAG) 1 and 2. Recently, RAG expression in peripheral blood IgD+ B cells outside the bone marrow has been demonstrated and is associated with the development of autoimmune diseases. Objective: To investigate RAG expression in the CD5+ or CD5- IgD+ B cell compartment in childhood systemic lupus erythematosus (SLE). Methods: Using a combination of flow cytometric cell sorting and reverse transcriptase polymerase chain reaction analysis of cDNA libraries generated from individual cells, the expression of RAG, VpreB, and CD154 mRNA by individual peripheral blood B cells of three paediatric SLE patients was examined in detail. Results: While only one patient had a significantly increased frequency of RAG+ B cells in the CD5- B cell population, all patients showed higher frequencies of RAG+ B cells in the CD5+IgD+ B cell population. The frequency of RAG+ IgD+CD5+/- B cells was reduced during intravenous cyclophosphamide treatment. In healthy age matched children, RAG expressing IgD+ B cells were hardly detectable. Coexpression of RAG and VpreB or CD154 mRNA could only be found in SLE B cells. Conclusions: RAG expression in peripheral blood B cells of SLE patients is particularly increased in the IgD+CD5+ B cell population. CD5+ and CD5- B cells in SLE have the potential to undergo receptor revision leading to the generation of high affinity pathogenic autoantibodies. C1 Univ Wurzburg, Sect Paediat Rheumatol & Osteol, Childrens Hosp, D-97080 Wurzburg, Germany. NIAMS, NIH, Autoimmun Branch, Bethesda, MD USA. RP Girschick, HJ (reprint author), Univ Wurzburg, Sect Paediat Rheumatol & Osteol, Childrens Hosp, Josef Schneider Str 2, D-97080 Wurzburg, Germany. EM Hermann.Girschick@mail.uni-wuerzburg.de NR 46 TC 17 Z9 18 U1 0 U2 2 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 2006 VL 65 IS 4 BP 482 EP 487 DI 10.1136/ard.2005.040840 PG 6 WC Rheumatology SC Rheumatology GA 029AF UT WOS:000236529300010 PM 16126793 ER PT J AU Tsai, HF Krol, AA Sarti, KE Bennett, JE AF Tsai, HF Krol, AA Sarti, KE Bennett, JE TI Candida glabrata PDR1, a transcriptional regulator of a pleiotropic drug resistance network, mediates azole resistance in clinical isolates and petite mutants SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CANDIDA-ALBICANS STRAINS; SACCHAROMYCES-CEREVISIAE; FLUCONAZOLE RESISTANCE; MULTIDRUG-RESISTANCE; ANTIFUNGAL AGENTS; TRANSPORTER GENE; REDUCED AFFINITY; UP-REGULATION; GLABRATA; YEAST AB Candida glabrata, a yeast with intrinsically low susceptibility to azoles, frequently develops increased azole resistance during prolonged treatment. Transposon mutagenesis revealed that disruption of CgPDR1 resulted in an 8- to 16-fold increase in fluconazole susceptibility of C. glabrata. CgPDR1 is a homolog of Saccharomyces cerevisiae PDR1, which encodes a transcriptional regulator of multidrug transporters. Northern blot analyses indicated that CgPDR1 regulated both constitutive and drug-induced expression of CgCDRI, a multidrug transporter gene. In agreement with the Northern analysis, the Cgpdr1 mutant had increased rhodamine accumulation, in contrast to the decreased accumulation in the CgPDR1-overexpressing strain. Northern analyses also indicated the importance of CgPDR1 in fluconazole resistance arising during therapy. Two clinically resistant isolates had higher expression of CgPDR1 and CgCDR1 compared to their paired susceptible isolates. Integrative transformation of CgPDR1 from the two resistant isolates converted the Cgpdr1 mutant into azole-resistant strains with upregulated CgPDRI expression. Two different amino acid substitutions, W297S in one isolate and F575L in the other, accounted for the upregulated CgPDR1 expression and the resistance. Finally, CgPDR1 was shown to be required for the azole resistance due to mitochondrial deficiency. Thus, CgPDR1 encodes a transcriptional regulator of a pleiotropic drug resistance network and contributes to the azole resistance of clinical isolates and petite mutants. C1 NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Bennett, JE (reprint author), NIH, Ctr Clin, Room 11C304, Bethesda, MD 20892 USA. EM Jbennett@niaid.nih.gov FU Intramural NIH HHS NR 44 TC 96 Z9 105 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 2006 VL 50 IS 4 BP 1384 EP 1392 DI 10.1128/AAC.50.4.1384-1392.2006 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 031EA UT WOS:000236685700038 PM 16569856 ER PT J AU Petraitis, V Petraitiene, R Solomon, J Kelaher, AM Murray, HA Mya-San, C Bhandary, AK Sein, T Avila, NA Basevicius, A Bacher, J Walsh, TJ AF Petraitis, V Petraitiene, R Solomon, J Kelaher, AM Murray, HA Mya-San, C Bhandary, AK Sein, T Avila, NA Basevicius, A Bacher, J Walsh, TJ TI Multidimensional volumetric imaging of pulmonary infiltrates for measuring therapeutic response to antifungal therapy in experimental invasive pulmonary aspergillosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID LIPOSOMAL AMPHOTERICIN-B; GALACTOMANNAN ANTIGENEMIA; FILAMENTOUS FUNGI; EFFICACY; PHARMACOKINETICS; RABBITS; SAFETY; EPIDEMIOLOGY; VORICONAZOLE; CASPOFUNGIN AB Pulmonary infiltrates in neutropenic hosts with invasive pulmonary aspergillosis are caused by vascular invasion, hemorrhagic infarction, and tissue necrosis. Monitoring the dynamics of pulmonary infiltrates of invasive aspergillosis is an important tool for assessing response to antifungal therapy. We, therefore, introduced a multidimensional volumetric imaging (MDVI) method for analysis of the response of the volume of pulmonary infiltrates over time to antifungal therapy in experimental invasive pulmonary aspergillosis (IPA) in persistently neutropenic rabbits. We developed a semiautomatic method to measure the volume of lung lesions, which was implemented as an extension of the MEDx visualization and analysis software using ultrafast computerized tomography (UFCT). Volumetric infiltrate measures were compared with UFCT reading, histopathological resolution of lesions, microbiological clearance of Aspergillus fumigatus, and galactomarman index (GMI). We also studied the MDVI method for consistency and reproducibility in comparison to UFCT. Treatment groups consisted of deoxycholate amphotericin B (DAMB) at 0.5 or 1 mg/kg of body weight/day and untreated controls (UC). Therapeutic monitoring of pulmonary infiltrates using MDVI demonstrated a significant decrease in the infiltrate volume in DAMB-treated rabbits in comparison to UC (P <= 0.001). Volumetric data by MDVI correlated with conventional CT pulmonary scores (r 0.83, P < 0.001). These results correlated with validated biological endpoints: pulmonary infarct scores (r 0.85, P <= 0.001), lung weights (r = 0.76, P <= 0.01), residual fungal burden (r = 0.65, P <= 0.05), and GMI (r = 0.78, P < 0.01). MDVI correlated with key biological markers, improved the objectivity of radiological assessment of therapeutic response to antifungal therapy, and warrants evaluation for monitoring therapeutic response in immunocompromised patients with invasive aspergillosis. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. SAIC Frederick Inc, Frederick, MD USA. Med Numer Inc, Sterling, VA USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. Kaunas Univ Med, Dept Radiol, Kaunas, Lithuania. NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bldg 10,CRC,Rm 1W-5740,10 Ctr Dr,MSC 1100, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov FU Intramural NIH HHS NR 28 TC 13 Z9 14 U1 0 U2 2 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 2006 VL 50 IS 4 BP 1510 EP 1517 DI 10.1128/AAC.50.4.10-1517.2006 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 031EA UT WOS:000236685700053 PM 16569871 ER PT J AU Diaz, PI Chalmers, NI Rickard, AH Kong, C Milburn, CL Palmer, RJ Kolenbrander, PE AF Diaz, PI Chalmers, NI Rickard, AH Kong, C Milburn, CL Palmer, RJ Kolenbrander, PE TI Molecular characterization of subject-specific oral microflora during initial colonization of enamel SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID STREPTOCOCCUS-GORDONII; BACTERIAL DIVERSITY; MICROBIAL ECOLOGY; DENTAL PLAQUE; COAGGREGATION; IDENTIFICATION; BIOFILMS; CAVITY; COMMUNICATION; HYBRIDIZATION AB The initial microbial colonization of tooth surfaces is a repeatable and selective process, with certain bacterial species predominating in the nascent biofilm. Characterization of the initial microflora is the first step in understanding interactions among community members that shape ensuing biofilm development. Using molecular methods and a retrievable enamel chip model, we characterized the microbial diversity of early dental biofilms in three subjects. A total of 531 16S rRNA gene sequences were analyzed, and 97 distinct phylotypes were identified. Microbial community composition was shown to be statistically different among subjects. In all subjects, however, 4-h and 8-h communities were dominated by Streptococcus spp. belonging to the Streptococcus oralis/Streptococcus mitis group. Other frequently observed genera (comprising at least 5% of clone sequences in at least one of the six clone libraries) were Actinomyces, Gemella, Granulicatella, Neisseria, Prevotella, Rothia, and Veillonella. Fluorescence in situ hybridization (FISH) confirmed that the proportion of Streptococcus sp. sequences in the clone libraries coincided with the proportion of streptococcus probe-positive organisms on the chip. FISH also revealed that, in the undisturbed plaque, not only Streptococcus spp. but also the rarer Prevotella spp. were usually seen in small multigeneric clusters of cells. This study shows that the initial dental plaque community of each subject is unique in terms of diversity and composition. Repetitive and distinctive community composition within subjects suggests that the spatiotemporal interactions and ecological shifts that accompany biofilm maturation also occur in a subject-dependent manner. C1 NIDCR, NIH, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. Univ Maryland, Sch Dent, Dept Biomed Sci, Baltimore, MD 21201 USA. RP Kolenbrander, PE (reprint author), NIDCR, NIH, Oral Infect & Immun Branch, Bldg 30,Room 310,30 Convent Dr, Bethesda, MD 20892 USA. EM pkolenbrander@dir.nider.nih.gov RI Diaz, Patricia/E-9465-2012 FU Intramural NIH HHS NR 42 TC 169 Z9 178 U1 2 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD APR PY 2006 VL 72 IS 4 BP 2837 EP 2848 DI 10.1128/AEM.72.4.2837-2848.2006 PG 12 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 032BR UT WOS:000236749400069 PM 16597990 ER PT J AU Buckel, TBH Goldstein, AM Fraser, MC Rogers, B Tucker, MA AF Buckel, TBH Goldstein, AM Fraser, MC Rogers, B Tucker, MA TI Recent tanning bed use - A risk factor for melanoma SO ARCHIVES OF DERMATOLOGY LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; ULTRAVIOLET-RADIATION; PRONE FAMILIES; DYSPLASTIC NEVI; HISTORY AB Background: Individuals at increased risk of melanoma should use sun-protective measures to decrease their risk of developing melanoma. Observation: We report a case of a 39-year-old patient with a CDKN2A mutation who developed 3 primary melanomas within a few years of initiating tanning bed use. Conclusion: Intense UV exposure as an adult likely contributed to the development of additional primary melanomas in this individual. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tucker, MA (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Execut Plaza S,Mail Stop Code 7236,6120 Execut Bl, Bethesda, MD 20892 USA. EM tuckerp@exchange.nih.gov RI Tucker, Margaret/B-4297-2015 NR 14 TC 13 Z9 13 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD APR PY 2006 VL 142 IS 4 BP 485 EP 488 DI 10.1001/archderm.142.4.485 PG 4 WC Dermatology SC Dermatology GA 033NG UT WOS:000236854700011 PM 16618869 ER PT J AU Bloch, M Rubinow, DR Berlin, K Kevala, KR Kim, HY Schmidt, PJ AF Bloch, M Rubinow, DR Berlin, K Kevala, KR Kim, HY Schmidt, PJ TI Monoamines and neurosteroids in sexual function during induced hypogonadism in healthy men SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID ANABOLIC ANDROGENIC STEROIDS; PLACEBO-CONTROLLED TRIAL; CEREBROSPINAL-FLUID; BODY-COMPOSITION; DOUBLE-BLIND; AGING MALE; TESTOSTERONE; BEHAVIOR; MOOD; DEPRESSION AB Context: Although the behavioral effects of high-dose androgen administration may involve alterations in serotonergic activity, few studies have investigated the impact of androgen withdrawal on the central nervous system in humans. Objective: To examine the effects of pharmacologically induced hypogonadism on several cerebrospinal fluid (CSF) systems that could mediate the behavioral concomitants of hypogonadism. Design: Double-blind assessment of the effects of the short-term induction of hypogonadism and subsequent replacement with testosterone and placebo in a crossover design. Setting: National Institutes of Health, Bethesda, Md. Participants: Twelve healthy male volunteers. Interventions: We administered the gonadotropin-releasing hormone agonist leuprolide acetate (7.5 mg in-tramuscularly every 4 weeks) to the healthy male volunteers, creating a hypogonadal state, and then either replaced testosterone (200 mg intramuscularly) or administered a placebo every 2 weeks for 1 month. Main Outcome Measures: Mood and behavioral symptoms were monitored with daily self-ratings, and lumbar punctures were performed during both hypogonadal ( placebo) and testosterone-replaced conditions for CSF levels of steroids and monoamine metabolites. Results: The CSF testosterone, dihydrotestosterone, and androsterone levels were significantly lower during hypogonadism ( P = .002, .04, and .046, respectively), but no significant changes were observed in CSF measures of 5-hydroxyindoleacetic acid, homovanillic acid, dehydroepiandrosterone, or pregnenolone. Decreased sexual interest was observed during the hypogonadal state compared with both baseline and testosterone replacement (P = .009) and correlated significantly with CSF measures of androsterone during both hypogonadism and testosterone replacement (r = -0.76 and -0.81, respectively; P < .01). Moreover, the change in severity of decreased sexual interest correlated significantly with the change in CSF androsterone levels between testosterone replacement and hypogonadism (r = -0.68; P < .05). The CSF 5-hydroxyindoleacetic acid and homovanillic acid levels did not correlate significantly with any behavioral or CSF measure. Conclusion: These data suggest that the neurosteroid androsterone contributes to the regulation of sexual function in men. C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. NIAAA, NIH, Bethesda, MD USA. RP Schmidt, PJ (reprint author), NIMH, Behav Endocrinol Branch, Bldg 10-CRC,Room 65340 SE,10 Ctr Dr MSC 1276, Bethesda, MD 20892 USA. EM peterschmidt@mail.nih.gov NR 68 TC 7 Z9 7 U1 0 U2 2 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 2006 VL 63 IS 4 BP 450 EP 456 DI 10.1001/archpsyc.63.4.450 PG 7 WC Psychiatry SC Psychiatry GA 031TG UT WOS:000236726400013 PM 16585475 ER PT J AU Cantor, FK AF Cantor, FK TI Interferon beta-1a treatment and African Americans SO ARCHIVES OF NEUROLOGY LA English DT Letter ID MULTIPLE-SCLEROSIS C1 Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Cantor, FK (reprint author), Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Room 5B16,10 Ctr Dr, Bethesda, MD 20892 USA. EM cantorf@ninds.nih.gov NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 2006 VL 63 IS 4 BP 627 EP 628 DI 10.1001/archneur.63.4.627-c PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 032YO UT WOS:000236813000033 PM 16606785 ER PT J AU Chew, E Gillies, M Bird, A AF Chew, E Gillies, M Bird, A TI Macular telangiectasia - A simplified classification SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material C1 CRC, NIH, Bethesda, MD 20892 USA. RP Chew, E (reprint author), CRC, NIH, Bldg 10,Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA. EM echew@nei.nih.gov RI gillies, mark/B-3242-2012 FU Intramural NIH HHS [Z99 EY999999] NR 2 TC 12 Z9 12 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 2006 VL 124 IS 4 BP 573 EP 574 DI 10.1001/archopht.124.4.573 PG 2 WC Ophthalmology SC Ophthalmology GA 031CB UT WOS:000236680600019 PM 16606887 ER PT J AU Lee, SW Kim, WJ Park, JA Choi, YK Kwon, YW Kim, KW AF Lee, SW Kim, WJ Park, JA Choi, YK Kwon, YW Kim, KW TI Blood-brain barrier interfaces and brain tumors SO ARCHIVES OF PHARMACAL RESEARCH LA English DT Review DE blood-brain barrier; brain angiogenesis; barriergenesis; tight junctions; oxygen tension; glioblastoma ID ENDOTHELIAL GROWTH-FACTOR; HUMAN GLIOBLASTOMA-MULTIFORME; JUNCTIONAL ADHESION MOLECULE; TIGHT JUNCTION; GLUCOSE-TRANSPORTER; IN-VIVO; DEVELOPMENTAL EXPRESSION; DIABETIC-RETINOPATHY; VESSEL DEVELOPMENT; OXYGEN-TENSION AB In the developing brain, capillaries are differentiated and matured into the blood-brain barrier (BBB), which is composed of cerebral endothelial cells, astrocyte end-feet, and pericytes. Since the BBB regulates the homeostasis of central nervous system (CNS), the maintenance of the BBB is important for CNS function. The disruption of the BBB may result in many brain disorders including brain tumors. However, the molecular mechanism of BBB formation and maintenane is poorly understood. Here, we summarize recent advances in the role of oxygen tension and growth factors on BBB development and maintenance, and in BBB dysfunction related with brain tumors. C1 Seoul Natl Univ, Neurovasc Coordinat Res Ctr, Coll Pharm, Seoul 151742, South Korea. Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul 151742, South Korea. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab, Boston, MA 02129 USA. NIAID, Immunopathol Lab, Rockville, MD 20852 USA. RP Kim, KW (reprint author), Seoul Natl Univ, Neurovasc Coordinat Res Ctr, Coll Pharm, Seoul 151742, South Korea. EM qwonkim@plaza.snu.ac.kr NR 100 TC 30 Z9 32 U1 1 U2 5 PU PHARMACEUTICAL SOCIETY KOREA PI SEOUL PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA SN 0253-6269 J9 ARCH PHARM RES JI Arch. Pharm. Res. PD APR PY 2006 VL 29 IS 4 BP 265 EP 275 DI 10.1007/BF02968569 PG 11 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 038DK UT WOS:000237198500001 PM 16681030 ER PT J AU Brodsky, B Trivedi, S Peddada, S Flagler, N Wormser, U Nyska, A AF Brodsky, B Trivedi, S Peddada, S Flagler, N Wormser, U Nyska, A TI Early effects of iodine on DNA synthesis in sulfur mustard-induced skin lesions SO ARCHIVES OF TOXICOLOGY LA English DT Article DE sulfur mustard; skin lesions; iodine; DNA synthesis ID HISTOPATHOLOGIC FEATURES; TOXICITY; TOXICOLOGY; EXPOSURE; INJURY; AGENTS; PIGS; GAS AB Sulfur mustard (SM) is powerful alkylator and highly cytotoxic blisterogen in both humans and animals. This study in male guinea pigs shows that, at an early stage (5 h) after SM exposure, a marked increase occurred in epithelial nuclear vacuolation, epidermal thickening, and dermal acute inflammation. Topical iodine treatment reduced the severity of these parameters. The rate of DNA synthesis expressed by incorporation of bromodeoxyuridine was reduced upon topical treatment with iodine only or SM only by 46 and 72%, respectively. Iodine treatment following SM exposure exerted an effect similar to that of SM only, indicating that DNA synthesis is not directly involved in the mechanism of action of iodine-induced protection. C1 Hebrew Univ Jerusalem, Inst Life Sci, Sch Pharm, Dept Pharmacol, IL-91904 Jerusalem, Israel. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Wormser, U (reprint author), Hebrew Univ Jerusalem, Inst Life Sci, Sch Pharm, Dept Pharmacol, IL-91904 Jerusalem, Israel. EM wormser@cc.huji.ac.il RI Peddada, Shyamal/D-1278-2012 NR 19 TC 10 Z9 11 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD APR PY 2006 VL 80 IS 4 BP 212 EP 216 DI 10.1007/s00204-005-0032-6 PG 5 WC Toxicology SC Toxicology GA 027OR UT WOS:000236425400006 PM 16252085 ER PT J AU Kim-Shapiro, DB Schechter, AN Gladwin, MT AF Kim-Shapiro, DB Schechter, AN Gladwin, MT TI Unraveling the reactions of nitric oxide, nitrite, and hemoglobin in physiology and therapeutics SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review DE nitric oxide; nitrite; hemoglobin; vasodilation; red blood cell ID RED-BLOOD-CELLS; S-NITROSOHEMOGLOBIN; RELAXING FACTOR; IN-VIVO; ERYTHROCYTE CONSUMPTION; CIRCULATING NITRITE; XANTHINE-OXIDASE; LIGAND-BINDING; HUMAN PLASMA; HYPOXIC VASODILATION AB The ability of oxyhemoglobin to inhibit nitric oxide (NO)-dependent activation of soluble guanylate cyclase and vasodilation provided some of the earliest experimental evidence that NO was the endothelium-derived relaxing factor ( EDRF). The chemical behavior of this dioxygenation reaction, producing nearly diffusion limited and irreversible NO scavenging, presents a major paradox in vascular biology: The proximity of large amounts of oxyhemoglobin (10 mmol/L) to the endothelium should severely limit paracrine NO diffusion from endothelium to smooth muscle. However, several physical factors are now known to mitigate NO scavenging by red blood cell encapsulated hemoglobin. These include diffusional boundaries around the erythrocyte and a red blood cell free zone along the endothelium in laminar flowing blood, which reduce reaction rates between NO and red cell hemoglobin by 100- to 600-fold. Beyond these mechanisms that reduce NO scavenging by hemoglobin within the red cell, 2 additional mechanisms have been proposed suggesting that NO can be stored in the red blood cell either as nitrite or as an S-nitrosothiol (S-nitroso-hemoglobin). The latter controversial hypothesis contends that NO is stabilized, transported, and delivered by intra-molecular NO group transfers between the heme iron and beta-93 cysteine to form S-nitrosohemoglobin (SNO-Hb), followed by hypoxia-dependent delivery of the S-nitrosothiol in a process that links regional oxygen deficits with S-nitrosothiol-mediated vasodilation. Although this model has generated a field of research examining the potential endocrine properties of intravascular NO molecules, including S-nitrosothiols, nitrite, and nitrated lipids, a number of mechanistic elements of the theory have been challenged. Recent data from several groups suggest that the nitrite anion (NO2-) may represent the major intravascular NO storage molecule whose transduction to NO is made possible through an allosterically controlled nitrite reductase reaction with the heme moiety of hemoglobin. As subsequently understood, the hypoxic generation of NO from nitrite is likely to prove important in many aspects of physiology, pathophysiology, and therapeutics. C1 Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA. NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Crit Care Med Dept, Bethesda, MD 20892 USA. RP Kim-Shapiro, DB (reprint author), Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA. EM shapiro@wfu.edu OI Schechter, Alan N/0000-0002-5235-9408 FU NHLBI NIH HHS [HL58091, R01 HL058091] NR 133 TC 159 Z9 168 U1 1 U2 12 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 2006 VL 26 IS 4 BP 697 EP 705 DI 10.1161/01.ATV.0000204350.44226.9a PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 024VA UT WOS:000236223200006 PM 16424350 ER PT J AU Holvoet, P Harris, TB Tracy, RP Kritchevsky, SB AF Holvoet, P Harris, TB Tracy, RP Kritchevsky, SB TI Oxidized LDL and the metabolic syndrome SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Letter ID LOW-DENSITY-LIPOPROTEIN; BODY-COMPOSITION; RISK; DISEASE; HEALTH; MEN C1 Katholieke Univ Leuven, Dept Cardiovasc Dis, Atherosclerosis & Metab Unit, B-3000 Louvain, Belgium. Natl Inst Aging, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD USA. Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. Univ Vermont, Dept Biochem, Burlington, VT 05405 USA. Wake Forest Univ Hlth Sci, J Paul Sticht Ctr Aging, Winston Salem, NC 27109 USA. RP Holvoet, P (reprint author), Katholieke Univ Leuven, Dept Cardiovasc Dis, Atherosclerosis & Metab Unit, B-3000 Louvain, Belgium. NR 5 TC 1 Z9 1 U1 0 U2 0 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 2006 VL 26 IS 4 BP E31 EP E31 DI 10.1161/01.ATV.0000210271.36395.43 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 024VA UT WOS:000236223200044 PM 16556859 ER PT J AU Nesterova, M Johnson, N Cheadle, C Cho-Chung, YS AF Nesterova, M Johnson, N Cheadle, C Cho-Chung, YS TI Autoantibody biomarker opens a new gateway for cancer diagnosis SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE extracellular protein kinase A; autoantibody; cancer biomarker; cancer diagnosis; enzyme immunoassay ID DEPENDENT PROTEIN-KINASE; BREAST-CANCER; COLORECTAL-CANCER; CATALYTIC SUBUNIT; PROSTATE-CANCER; TUMOR-MARKERS; ANTIBODIES; P53; CELLS; SERA AB The list of cancer markers of current interest has grown considerably, but none of the markers used in clinical work is a true tumor marker. These cancer biomarkers are based on the determination of tumor antigens. Here, we report a single method of autoantibody enzyme immunoassay (EIA) screens for a spectrum of serum tumor markers. A comparison of the autoantibody-based EIA to conventional antigen EIA kits, using receiver operating characteristic (ROC) plots, showed that the autoantibody EIA can significantly enhance the sensitivity and specificity of tumor markers. The detection of serum autoantibodies for a spectrum of serum tumor markers, as demonstrated here, suggests that most, if not all, serum cancer biomarkers produce autoantibodies. A unique autoantibody biomarker screening method, as presented here, might therefore facilitate achieving the accurate and early diagnosis of cancer. C1 NCI, Cellular Biochem Sect, Basic Res Lab, CCR, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Basic Res Lab, CCR, Bldg 10,Room 5B05,9000 Rockville Pike, Bethesda, MD 20892 USA. EM yc12b@nih.gov FU Intramural NIH HHS NR 26 TC 44 Z9 51 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD APR PY 2006 VL 1762 IS 4 BP 398 EP 403 DI 10.1016/j.bbadis.2005.12.010 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 026CM UT WOS:000236314300002 PM 16483750 ER PT J AU Pace, A Tapia, JA Garcia-Marin, LJ Jensen, RT AF Pace, A Tapia, JA Garcia-Marin, LJ Jensen, RT TI The Src family kinase, Lyn, is activated in pancreatic acinar cells by gastrointestinal hormones/neurotransmitters and growth factors which stimulate its association with numerous other signaling molecules SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE pancreas; src; src kinase; lyn; cholecystokinin; pancreatic secretion; pancreatic growth; pancreatic growth factor ID FOCAL ADHESION KINASE; PROTEIN-TYROSINE KINASES; APICAL PLASMA-MEMBRANE; C-DEPENDENT MECHANISM; PKC-DELTA; FACTOR RECEPTOR; CHOLECYSTOKININ; PHOSPHORYLATION; PATHWAY; INVOLVEMENT AB Src family kinases (SFK) play a central signaling role for growth factors, cytokines, G-protein-coupled receptors and other stimuli. SFKs play important roles in pancreatic acinar cell secretion, endocytosis, growth, cytoskeletal integrity and apoptosis, although little is known of the specific SFKs involved. In this study we demonstrate the SFK, Lyn, is present in rat pancreatic acini and investigate its activation/signaling. Ca2+-mobilizing agents, cAMP-mobilizing agents and pancreatic growth factors activated Lyn. CCK, a physiological regulator of pancreatic function, rapidly activated Lyn. The specific SFK inhibitor, PP2, decreased Lyn activation; however, the inactive analogue, PP3, bad no effect. Inhibition of CCKstimulated changes in [Ca2+](i) decreased Lyn activation by 55%; GFX, a PKC inhibitor by 36%; and the combination by 95%. CCK activation of Lyn required stimulation of high and low affinity CCKA receptor states. CCK stimulated an association of Lyn with PKC-delta, She, p 125(FAK) and PYK2 as well as with their autophosphorylated forms, but not with Cb1, p85, p 130(CAS) or ERK 1/2. These results show Lyn is activated by diverse pancreatic stimulants. CCK's activation of Lyn is likely an important mediator of its ability to cause tyrosine phosphorylation of numerous important cellular mediators such as p125(FAK), PYK2, PKC-delta and She, which play central roles in CCK's effects on acinar cell function. Published by Elsevier B.V. C1 NIDDK, NIH, DDB, Bethesda, MD 20892 USA. Univ Klinikum Hamburg Eppendorf, D-20246 Hamburg, Germany. Univ Extremadura, Dept Fisiol, Caceres 10074, Spain. RP Jensen, RT (reprint author), NIDDK, NIH, DDB, Bldg 10,Rm 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov RI Garcia-Marin, Luis /L-4680-2014; Tapia, Jose/C-5181-2008 OI Garcia-Marin, Luis /0000-0002-1795-7381; Tapia, Jose/0000-0002-3614-6867 NR 51 TC 21 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD APR PY 2006 VL 1763 IS 4 BP 356 EP 365 DI 10.1016/j.bbamcr.2006.03.004 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 054AH UT WOS:000238347200003 PM 16713446 ER PT J AU Jothi, R Zotenko, E Tasneem, A Przytycka, TM AF Jothi, R Zotenko, E Tasneem, A Przytycka, TM TI COCO-CL: hierarchical clustering of homology relations based on evolutionary correlations SO BIOINFORMATICS LA English DT Article ID HORIZONTAL GENE-TRANSFER; TRANSFER-RNA SYNTHETASES; PHYLOGENETIC TREES; PROTEIN-INTERACTION; EUKARYOTIC GENOMES; SEQUENCE DATABASES; COG DATABASE; ORTHOLOGY; FAMILY; PHYLOGENOMICS AB Motivation: Determining orthology relations among genes across multiple genomes is an important problem in the post-genomic era. Identifying orthologous genes can not only help predict functional annotations for newly sequenced or poorly characterized genomes, but can also help predict new protein-protein interactions. Unfortunately, determining orthology relation through computational methods is not straightforward due to the presence of paralogs. Traditional approaches have relied on pairwise sequence comparisons to construct graphs, which were then partitioned into putative clusters of orthologous groups. These methods do not attempt to preserve the non-transitivity and hierarchic nature of the orthology relation. Results: We propose a new method, COCO-CL, for hierarchical clustering of homology relations and identification of orthologous groups of genes. Unlike previous approaches, which are based on pairwise sequence comparisons, our method explores the correlation of evolutionary histories of individual genes in a more global context. COCO-CL can be used as a semi-independent method to delineate the orthology/paralogy relation for a refined set of homologous proteins obtained using a less-conservative clustering approach, or as a refiner that removes putative out-paralogs from clusters computed using a more inclusive approach. We analyze our clustering results manually, with support from literature and functional annotations. Since our orthology determination procedure does not employ a species tree to infer duplication events, it can be used in situations when the species tree is unknown or uncertain. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. Univ Illinois, Beckman Inst, Urbana, IL 61801 USA. RP Jothi, R (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM jothi@mail.nih.gov; przytyck@mail.nih.gov RI Jothi, Raja/G-3780-2015; OI Zotenko, Elena/0000-0002-0256-3195 FU Intramural NIH HHS NR 41 TC 37 Z9 39 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD APR 1 PY 2006 VL 22 IS 7 BP 779 EP 788 DI 10.1093/bioinformatics/btl009 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 025FU UT WOS:000236251500002 PM 16434444 ER PT J AU Whetzel, PL Parkinson, H Causton, HC Fan, LJ Fostel, J Fragoso, G Game, L Heiskanen, M Morrison, N Rocca-Serra, P Sansone, SA Taylor, C White, J Stoeckert, CJ AF Whetzel, PL Parkinson, H Causton, HC Fan, LJ Fostel, J Fragoso, G Game, L Heiskanen, M Morrison, N Rocca-Serra, P Sansone, SA Taylor, C White, J Stoeckert, CJ TI The MGED Ontology: a resource for semantics-based description of microarray experiments SO BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION; DATABASE; INFORMATION; EXCHANGE AB Motivation: The generation of large amounts of microarray data and the need to share these data bring challenges for both data management and annotation and highlights the need for standards. MIAME specifies the minimum information needed to describe a microarray experiment and the Microarray Gene Expression Object Model (MAGE-OM) and resulting MAGE-ML provide a mechanism to standardize data representation for data exchange, however a common terminology for data annotation is needed to support these standards. Results: Here we describe the MGED Ontology (MO) developed by the Ontology Working Group of the Microarray Gene Expression Data (MGED) Society. The MO provides terms for annotating all aspects of a microarray experiment from the design of the experiment and array layout, through to the preparation of the biological sample and the protocols used to hybridize the RNA and analyze the data. The MO was developed to provide terms for annotating experiments in line with the MIAME guidelines, i.e. to provide the semantics to describe a microarray experiment according to the concepts specified in MIAME. The MO does not attempt to incorporate terms from existing ontologies, e.g. those that deal with anatomical parts or developmental stages terms, but provides a framework to reference terms in other ontologies and therefore facilitates the use of ontologies in microarray data annotation. C1 Univ Penn, Sch Med, Ctr Bioinformat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. European Bioinformat Inst, Cambridge CB10 1SD, England. Univ London Imperial Coll Sci Technol & Med, Fac Med, MRC, Ctr Clin Sci, London W12 0NN, England. Ontol Workshop LLC, Columbia, MD 21045 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NCICB, NCI, Ctr Bioinformat, Rockville, MD 20852 USA. Univ Manchester, Dept Comp Sci, Manchester M13 9PL, Lancs, England. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Stoeckert, CJ (reprint author), Univ Penn, Sch Med, Ctr Bioinformat, Philadelphia, PA 19104 USA. EM Stoeckrt@pcbi.upenn.edu OI Parkinson, Helen/0000-0003-3035-4195; Sansone, Susanna-Assunta/0000-0001-5306-5690 FU NHGRI NIH HHS [1P41HG003619-01, P41HG003619] NR 21 TC 119 Z9 127 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD APR 1 PY 2006 VL 22 IS 7 BP 866 EP 873 DI 10.1093/bioinformatics/btl005 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 025FU UT WOS:000236251500014 PM 16428806 ER PT J AU Xirasagar, S Gustafson, SF Huang, CC Pan, QY Fostel, J Boyer, P Merrick, BA Tomer, KB Chan, DD Yost, KJ Choi, D Xiao, NQ Stasiewicz, S Bushel, P Waters, MD AF Xirasagar, S Gustafson, SF Huang, CC Pan, QY Fostel, J Boyer, P Merrick, BA Tomer, KB Chan, DD Yost, KJ Choi, D Xiao, NQ Stasiewicz, S Bushel, P Waters, MD TI Chemical effects in biological systems (CEBS) object model for toxicology data, SysTox-OM: design and application SO BIOINFORMATICS LA English DT Article ID TOXICOGENOMICS; INFORMATION AB Motivation: The CEBS data repository is being developed to promote a systems biology approach to understand the biological effects of environmental stressors. CEBS will house data from multiple gene expression platforms (transcriptomics), protein expression and protein-protein interaction (proteomics), and changes in low molecular weight metabolite levels (metabolomics) aligned by their detailed toxicological context. The system will accommodate extensive complex querying in a user-friendly manner. CEBS will store toxicological contexts including the study design details, treatment protocols, animal characteristics and conventional toxicological endpoints such as histopathology findings and clinical chemistry measures. All of these data types can be integrated in a seamless fashion to enable data query and analysis in a biologically meaningful manner. Results: An object model, the SysBio-OM (Xirasagar et al., 2004) has been designed to facilitate the integration of microarray gene expression, proteomics and metabolomics data in the CEBS database system. We now report SysTox-OM as an open source systems toxicology model designed to integrate toxicological context into gene expression experiments. The SysTox-OM model is comprehensive and leverages other open source efforts, namely, the Standard for Exchange of Nonclinical Data (http://www.cdisc.org/models/send/v2/index.html) which is a data standard for capturing toxicological information for animal studies and Clinical Data Interchange Standards Consortium (http://www.cdisc.org/models/sdtm/index.html) that serves as a standard for the exchange of clinical data. Such standardization increases the accuracy of data mining, interpretation and exchange. The open source SysTox-OM model, which can be implemented on various software platforms, is presented here. C1 Sci Applicat Int Corp, Germantown, MD 20874 USA. NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. Lockheed Martin Informat Technol, Res Triangle Pk, NC 27709 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. RP Xirasagar, S (reprint author), Sci Applicat Int Corp, 20201 Century Blvd,3rd Floor, Germantown, MD 20874 USA. EM xirasagars@saic.com RI Tomer, Kenneth/E-8018-2013 FU Intramural NIH HHS; NIEHS NIH HHS [N01-ES-25495] NR 13 TC 16 Z9 16 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD APR 1 PY 2006 VL 22 IS 7 BP 874 EP 882 DI 10.1093/bioinformatics/btk045 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 025FU UT WOS:000236251500015 PM 16410321 ER PT J AU Baas, JMP Milstein, J Donlevy, M Grillon, C AF Baas, JMP Milstein, J Donlevy, M Grillon, C TI Brainstem correlates of defensive states in humans SO BIOLOGICAL PSYCHIATRY LA English DT Article DE brainstem auditory evoked potentials; fear; anxiety; inferior colliculus ID AUDITORY-EVOKED-POTENTIALS; INFERIOR COLLICULUS; PANIC DISORDER; STARTLE; FEAR; ATTENTION; RESPONSES; AMYGDALA; ANXIETY; VOLUNTEERS AB Background: Brainstem auditory evoked potentials (BAEP) reflect the activation of brainstem nuclei in the first milliseconds after presentation of an auditory stimulus. These electrophysiological correlates of neural processing are highly automatic and not influenced by cognitive factor or task demands; however, data from patients with anxiety disorders suggest deviations in the BAEP. It has been hypothesized that these differences reflect heightened activation of structures involved in defensive states, such as the amygdala and locus coeruleus, projecting to the inferior colliculus, one of the brainstem generators of wave V of the BAEP. The present study investigated ibis possibility by testing BAEP during experimentally induced anxiety in healthy volunteers. Methods: In this study, BAEP were recorded from healthy normal volunteers under threat of shock, compared with safe conditions. Results: The first experiment (n = 12) showed that shock anticipation increased the amplitude of wave V A replication experiment (n = 13) confirmed this finding. Conclusions: Although BAEP are highly robust with respect to attentional manipulations, they are affected by transient activation of the fear system due to threat of shock. This finding indicates that some of the electrophysiological brainstem abnormalities observed in anxiety disorders can be replicated in healthy control subjects by inducing a transient state of anxiety. C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Baas, JMP (reprint author), Univ Utrecht, Dept Psychon, Van Unnik Rm 17-12,Heidelberglaan 2, NL-3584 CS Utrecht, Netherlands. EM j.m.p.baas@fss.uu.nl OI Baas, Johanna/0000-0001-6267-8712 FU Intramural NIH HHS NR 33 TC 36 Z9 36 U1 1 U2 7 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 2006 VL 59 IS 7 BP 588 EP 593 DI 10.1016/j.biopsych.2005.09.009 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 026DA UT WOS:000236315700003 PM 16388780 ER PT J AU Cornwell, BR Johnson, L Berardi, L Grillon, C AF Cornwell, BR Johnson, L Berardi, L Grillon, C TI Anticipation of public speaking in virtual reality reveals a relationship between trait social anxiety and startle reactivity SO BIOLOGICAL PSYCHIATRY LA English DT Article DE fear of negative evaluation; psychophysiology; public speaking; social anxiety; startle reflex; virtual reality ID EXPRESSION; DISORDER; PHOBIA AB Background: Startle reflex modification has become valuable to the study of fear and anxiety, but few studies have explored startle reactivity in socially threatening situation. Methods: Healthy participants ranging in trait social anxiety entered virtual reality (VR) that simulates standing center-stage in front of an audience to anticipate giving a speech and count backward. We measured startle and autonomic reactivity during anticipation of both tasks inside VR after single baseline recording outside VR. Results: Trait social anxiety, but not general trait anxiety, was positively correlated with startle before entering VR and most clearly during speech anticipation inside VR. Speech anticipation inside VR also elicited stronger physiologic responses relative to anticipation of counting. Conclusions: Under social-evaluative threat, startle reactivity showed robust relationships with fear of negative evaluation, a central aspect of social anxiety and clinical social phobia. Context-specific startle modification may be an endophenotype for subtypes of pathological anxiety. C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20895 USA. RP Cornwell, BR (reprint author), NIMH, Mood & Anxiety Disorders Program, 15k N Dr,Bldg 15k,MSC 2670, Bethesda, MD 20895 USA. EM cornwellb@mail.nih.gov FU Intramural NIH HHS NR 22 TC 50 Z9 50 U1 2 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 2006 VL 59 IS 7 BP 664 EP 666 DI 10.1016/j.biopsych.2005.09.015 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 026DA UT WOS:000236315700013 PM 16325155 ER PT J AU Schaefer, M Tewes, U Munte, TF Johannes, S AF Schaefer, M Tewes, U Munte, TF Johannes, S TI Lateralized irrelevant speech alters visuospatial selective attention mechanisms SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE selective attention; spatial attention; visual attention; event-related brain potentials; irrelevant speech effect; multisensory ID EVENT-RELATED POTENTIALS; ENDOGENOUS SPATIAL ATTENTION; BILATERAL STIMULUS ARRAYS; INDEX FOCUSED ATTENTION; CROSS-MODAL LINKS; AUDITORY-STIMULI; INTERMODAL ATTENTION; AUDIOVISUAL LINKS; BRAIN POTENTIALS; VISUAL-ATTENTION AB Recent studies indicate that the coordination of spatial attention across modalities may in part be mediated by a supramodal attentional system. We try to extend the concept of a supramodal system and hypothesized that involuntary modulations of auditory attentional processes by irrelevant speech signals influence visuospatial attention, suggesting crossmodal links between vision and speech. In order to test this we recorded event-related brain potentials (ERPs) of 12 healthy subjects in a visuospatial selective attention task. The task to identify target stimuli appearing at lateral visual field locations caused the expected enhancements of the early P1 and N1 ERP components to attended visual stimuli. Understandable and ununderstandable task irrelevant speech was presented either at the visually attended position or in the opposite visual field location. Speech contralateral to unattended visual stimuli led to a decreased NI amplitude. This effect was stronger for understandable speech. Thus, speech influences the allocation of visual spatial attention if it is presented in the unattended location. The results suggest crossmodal links of speech and visuospatial attention mechanisms at a very early stage of human perception. (c) 2005 Elsevier B.V. All rights reserved. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. Hannover Med Sch, Dept Psychol Med, Hannover, Germany. Otto Von Guericke Univ, Dept Neuropsychol, Magdeburg, Germany. Klin Bellikon, Bellikon, Switzerland. RP Schaefer, M (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bldg 10,Room 5N-234, Bethesda, MD 20892 USA. EM schaefem@ninds.nih.gov RI Munte, Thomas/C-2077-2014 NR 47 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD APR PY 2006 VL 72 IS 1 BP 51 EP 58 DI 10.1016/j.biopsycho.2005.07.007 PG 8 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 027JH UT WOS:000236411100005 PM 16188366 ER PT J AU Couriel, D Carpenter, PA Cutler, C Bolanos-Meade, J Treister, NS Gea-Banacloche, J Shaughnessy, P Hymes, S Kim, S Wayne, AS Chien, JW Neumann, J Mitchell, S Syrjala, K Moravec, CK Abramovitz, L Liebermann, J Berger, A Gerber, L Schubert, M Filipovich, AH Weisdorf, D Schubert, MM Shulman, H Schultz, K Mittelman, B Pavletic, S Vogelsang, GB Martin, PJ Lee, SJ Flowers, MED AF Couriel, D Carpenter, PA Cutler, C Bolanos-Meade, J Treister, NS Gea-Banacloche, J Shaughnessy, P Hymes, S Kim, S Wayne, AS Chien, JW Neumann, J Mitchell, S Syrjala, K Moravec, CK Abramovitz, L Liebermann, J Berger, A Gerber, L Schubert, M Filipovich, AH Weisdorf, D Schubert, MM Shulman, H Schultz, K Mittelman, B Pavletic, S Vogelsang, GB Martin, PJ Lee, SJ Flowers, MED TI Ancillary therapy and supportive care of chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: V. Ancillary Therapy and Supportive Care Working Group report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE chronic graft-versus-host disease; allogeneic cell transplantation; supportive care; consensus ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; PNEUMOCOCCAL CONJUGATE VACCINE; SEVERE DRY EYE; PNEUMOCYSTIS-CARINII-PNEUMONIA; INTRAVENOUS IMMUNE GLOBULIN; ORAL LICHEN-PLANUS; TERM-FOLLOW-UP; DOUBLE-BLIND; TOPICAL TACROLIMUS AB The Ancillary Therapy and Supportive Care Working Group had 3 goals: (1) to establish guidelines for ancillary therapy and supportive care in chronic graft-versus-host disease (GVHD), including treatment for symptoms and recommendations for patient education, preventive measures, and appropriate follow-up; (2) to provide guidelines for the prevention and management of infections and other common complications of treatment for chronic GVHD; and (3) to highlight the areas with the greatest need for clinical research. The definition of "ancillary therapy and supportive care" embraces the most frequent immunosuppressive or anti-inflammatory interventions used with topical intent and any other interventions directed at organ-specific control of symptoms or complications resulting from GVHD and its therapy. Also included in the definition are educational, preventive, and psychosocial interventions with this same objective. Recommendations are organized according to the strength and quality of evidence supporting them and cover the most commonly involved organs, including the skin, mouth, female genital tract, eyes, gastrointestinal tract, and lungs. Recommendations are provided for prevention of infections, osteoporosis, and steroid myopathy and management of neurocognitive and psychosocial adverse effects related to chronic GVHD. Optimal care of patients with chronic GVHD often requires a multidisciplinary approach. (C) 2006 American Society, for Blood and Marrow Transplantation. C1 Univ Texas, MD Anderson Canc Ctr, Dept Blood & Marrow Transplantat, Houston, TX 77030 USA. Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Texas Transplant Inst, San Antonio, TX USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. Univ Minnesota, Minneapolis, MN USA. Univ British Columbia, British Columbia Childrens Hosp, Vancouver, BC V5Z 1M9, Canada. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Couriel, D (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Blood & Marrow Transplantat, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM dcouriel@mdanderson.org NR 146 TC 181 Z9 192 U1 2 U2 7 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD APR PY 2006 VL 12 IS 4 BP 375 EP 396 DI 10.1016/j.bbmt.2006.02.003 PG 22 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 028NL UT WOS:000236494600001 PM 16545722 ER PT J AU Morrell, A Antony, S Kohlhagen, G Pommier, Y Cushman, M AF Morrell, A Antony, S Kohlhagen, G Pommier, Y Cushman, M TI Synthesis of benz[d]indeno[1,2-b]pyran-5,11-diones: Versatile intermediates for the design and synthesis of topoisomerase I inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE indenoisoquinoline; topoisomerase I inhibitor; synthesis; anticancer ID MJ-III-65 NSC-706744; MECHANISM; CAMPTOTHECIN; TOPOTECAN; CELLS; CYTOTOXICITY; POLYAMINES; TRANSPORT; COMPLEX; POISON AB A method has been developed that relies on a two-step, one-pot condensation between phthalide and 2-carboxybenzaldehydes to provide benz[a]indeno[ 1,2-h]pyran-5,11-diones in a multi-gram fashion. Treatment of these compounds with a primary amine allows rapid access to various N-substituted indenoisoquinolines, whose in vitro anticancer activity and topoisomerase I inhibition have been evaluated. (C) 2006 Elsevier Ltd. All rights reserved. C1 Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. EM cushman@pharmacy.purdue.edu FU NCI NIH HHS [ST32 CA09634-12, UO1 CA89566]; PHS HHS [C06-14400] NR 32 TC 48 Z9 48 U1 0 U2 5 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 2006 VL 16 IS 7 BP 1846 EP 1849 DI 10.1016/j.bmcl.2006.01.008 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 027GK UT WOS:000236402500016 PM 16442283 ER PT J AU Ghosh, AK Schiltz, G Perali, RS Leshchenko, S Kay, S Walters, DE Koh, Y Maeda, K Mitsuya, H AF Ghosh, AK Schiltz, G Perali, RS Leshchenko, S Kay, S Walters, DE Koh, Y Maeda, K Mitsuya, H TI Design and synthesis of novel HIV-1 protease inhibitors incorporating oxyindoles as the P-2 '-ligands SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE HIV proptease; inhibitors; oxyindole; TMC-1 14; design; synthesis ID HIGH-AFFINITY P-2-LIGANDS; BIOLOGICAL EVALUATION; OLEFIN METATHESIS; RECEPTOR; RESOLUTION; TEMPLATES; TMC114; AMIDES AB A series of novel oxyindole-derived HIV-1 protease inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 2 (TMC-114) bound to HIV-1 protease. The effects of substituents, spirocyclic rings, and ring sizes have been investigated. A number of inhibitors exhibited low nanomolar inhibitory potencies against HIV protease. (C) 2006 Elsevier Ltd. All rights reserved. C1 Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. Univ Illinois, Dept Chem, Chicago, IL 60607 USA. Rosalind Franklin Univ Med & Sci, Dept Biol Chem, N Chicago, IL 60064 USA. Kumamoto Univ, Sch Med, Dept Hematol & Infect Dis, Kumamoto 8608556, Japan. NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. EM akghosh@purdue.edu FU NIGMS NIH HHS [GM 53386] NR 33 TC 44 Z9 44 U1 0 U2 5 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 2006 VL 16 IS 7 BP 1869 EP 1873 DI 10.1016/j.bmcl.2006.01.011 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 027GK UT WOS:000236402500021 PM 16480871 ER PT J AU Klauda, JB Kucerka, N Brooks, BR Pastor, RW Nagle, JF AF Klauda, JB Kucerka, N Brooks, BR Pastor, RW Nagle, JF TI Simulation-based methods for interpreting X-ray data from lipid bilayers SO BIOPHYSICAL JOURNAL LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; COMPUTER-SIMULATION; SURFACE-TENSION; LIQUID/LIQUID INTERFACES; COMPONENT VOLUMES; PHASE DMPC; GEL PHASE; WATER; AREA; UNDULATIONS AB The fully hydrated liquid crystalline phase of the dimyristoylphosphatidycholine lipid bilayer at 30 degrees C was simulated using molecular dynamics with the CHARMM potential for five surface areas per lipid ( A) in the range 55-65 angstrom(2) that brackets the previously determined experimental area 60.6 angstrom(2). The results of these simulations are used to develop a new hybrid zero-baseline structural model, denoted H2, for the electron density profile, p(z), for the purpose of interpreting x-ray diffraction data. H2 and also the older hybrid baseline model were tested by fitting to partial information from the simulation and various constraints, both of which correspond to those available experimentally. The A, p(z), and F(q) obtained from the models agree with those calculated directly from simulation at each of the five areas, thereby validating this use of the models. The new H2 was then applied to experimental dimyristoylphosphatidycholine data; it yields A 60.6 +/- 0.5 angstrom(2), in agreement with the earlier estimate obtained using the hybrid baseline model. The electron density profiles also compare well, despite considerable differences in the functional forms of the two models. Overall, the simulated p( z) at A 60.7 angstrom(2) agrees well with experiment, demonstrating the accuracy of the CHARMM lipid force field; small discrepancies indicate targets for improvements. Lastly, a simulation-based model-free approach for obtaining A is proposed. It is based on interpolating the area that minimizes the difference between the experimental F( q) and simulated F( q) evaluated for a range of surface areas. This approach is independent of structural models and could be used to determine structural properties of bilayers with different lipids, cholesterol, and peptides. C1 NIH, Lab Computat Biol, Bethesda, MD 20892 USA. Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA. Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Rockville, MD 20852 USA. RP Klauda, JB (reprint author), NIH, Lab Computat Biol, Bldg 10, Bethesda, MD 20892 USA. EM klauda@helix.nih.gov RI Klauda, Jeffery/A-4345-2008; Nagle, John/B-1917-2015 OI Nagle, John/0000-0002-9844-5934 FU Intramural NIH HHS; NIGMS NIH HHS [GM44976, R01 GM044976, R01 GM044976-15A1] NR 42 TC 139 Z9 140 U1 1 U2 25 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 2006 VL 90 IS 8 BP 2796 EP 2807 DI 10.1529/biophysj.105.075697 PG 12 WC Biophysics SC Biophysics GA 024WK UT WOS:000236226900015 PM 16443652 ER PT J AU Root, DD Yadavalli, VK Forbes, JG Wang, K AF Root, DD Yadavalli, VK Forbes, JG Wang, K TI Coiled-coil nanomechanics and uncoiling and unfolding of the superhelix and alpha-helices of myosin SO BIOPHYSICAL JOURNAL LA English DT Article ID TITIN IMMUNOGLOBULIN DOMAINS; SINGLE-PEPTIDE MOLECULE; HYPERTROPHIC CARDIOMYOPATHY; FORCE MICROSCOPY; SCALLOP MYOSIN; ROD; MUSCLE; MUTATIONS; MECHANICS; PROTEINS AB The nanomechanical properties of the coiled-coils of myosin are fundamentally important in understanding muscle assembly and contraction. Force spectra of single molecules of double-headed myosin, single-headed myosin, and coiled-coil tail fragments were acquired with an atomic force microscope and displayed characteristic triphasic force-distance responses to stretch: a rise phase (R) and a plateau phase (P) and an exponential phase (E). The R and P phases arise mainly from the stretching of the coiled-coils, with the hinge region being the main contributor to the rise phase at low force. Only the E phase was analyzable by the worm-like chain model of polymer elasticity. Restrained molecular mechanics simulations on an existing x-ray structure of scallop S2 yielded force spectra with either two or three phases, depending on the mode of stretch. It revealed that coiled-coil chains separate completely near the end of the P phase and the stretching of the unfolded chains gives rise to the E phase. Extensive conformational searching yielded a P phase force near 40 pN that agreed well with the experimental value. We suggest that the flexible and elastic S2 region, particularly the hinge region, may undergo force-induced unfolding and extend reversibly during actomyosin powerstroke. C1 Univ N Texas, Dept Biol Sci, Denton, TX 76203 USA. NIAMSD, Muscle Prote & Nanotechnol Sect, Lab Muscle Biol, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Wang, K (reprint author), NIAMS, NIH, LMB, B50-Rm 1140, Bethesda, MD 20892 USA. EM wangk@exchange.nih.gov FU Intramural NIH HHS; NIAMS NIH HHS [R29 AR044737, R01 AR044737, AR44737] NR 57 TC 37 Z9 37 U1 0 U2 6 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 2006 VL 90 IS 8 BP 2852 EP 2866 DI 10.1529/biophysj.105.071597 PG 15 WC Biophysics SC Biophysics GA 024WK UT WOS:000236226900020 PM 16439474 ER PT J AU Nishizuka, S Washburn, NR Munson, PJ AF Nishizuka, S Washburn, NR Munson, PJ TI Evaluation method of ordinary flatbed scanners for quantitative density analysis SO BIOTECHNIQUES LA English DT Article C1 NCI, Mol Therapeut Program, NIH, Bethesda, MD 20892 USA. NCI, SAIC Frederick, Frederick, MD 21701 USA. Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Nishizuka, S (reprint author), NCI, Mol Therapeut Program, NIH, Bldg 37,Room 1126-B,9000 Rockville Pike, Bethesda, MD 20892 USA. EM nishizus@mail.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 5 TC 11 Z9 11 U1 0 U2 0 PU EATON PUBLISHING CO PI WESTBOROUGH PA ONE RESEARCH DRIVE, SUITE 400A, PO BOX 1070, WESTBOROUGH, MA 01581-6070 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD APR PY 2006 VL 40 IS 4 BP 442 EP + DI 10.2144/000112144 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 035JN UT WOS:000236997200004 PM 16629390 ER PT J AU Luderer, U Collins, TFX Daston, GP Fischer, LJ Gray, RH Mirer, FE Olshan, AF Setzer, RW Treinen, KA Vermeulen, R AF Luderer, U Collins, TFX Daston, GP Fischer, LJ Gray, RH Mirer, FE Olshan, AF Setzer, RW Treinen, KA Vermeulen, R TI NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Styrene SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review ID REINFORCED-PLASTICS INDUSTRY; DRUG-METABOLIZING-ENZYMES; SPERM CHROMATIN-STRUCTURE; CRL-CD RATS; ORGANIC-SOLVENTS; SPONTANEOUS-ABORTIONS; EXPOSED WORKERS; INHALED STYRENE; CHRONIC TOXICITY/ONCOGENICITY; CONGENITAL-MALFORMATIONS C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ Calif Irvine, Irvine, CA USA. US FDA, Laurel, MD USA. Procter & Gamble Co, Cincinnati, OH USA. Michigan State Univ, E Lansing, MI USA. Johns Hopkins Univ, Baltimore, MD USA. United Auto Workers Union, Int Union, Detroit, MI USA. Univ N Carolina, Chapel Hill, NC USA. US Environm Protect Agcy, Res Triangle Pk, NC USA. Schering Plough Res Inst, Lafayette, NJ USA. NCI, Bethesda, MD USA. RP Luderer, U (reprint author), NIEHS, EC-32,POB 12233, Res Triangle Pk, NC 27709 USA. RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 NR 132 TC 2 Z9 2 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD APR PY 2006 VL 77 IS 2 BP 110 EP 193 DI 10.1002/bdrb.20061 PG 84 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 036CN UT WOS:000237048600004 PM 16345075 ER PT J AU Gladwin, MT AF Gladwin, MT TI Does eNOS stand for erythrocytic NO synthase? SO BLOOD LA English DT Editorial Material ID NITRIC-OXIDE; HEMOGLOBIN AB Hepcidin overexpression may correct the molecular defect in a murine model of hemochromatosis, not only blocking intestinal Iron hyperabsorption and inappropriately high macrophage release, but also inducing redistribution of the hepatocyte-stored iron. C1 NHLBI, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NHLBI, Bethesda, MD 20892 USA. NR 7 TC 3 Z9 4 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 2006 VL 107 IS 7 BP 2595 EP 2596 DI 10.1182/blood-2006-01-0210 PG 2 WC Hematology SC Hematology GA 030TG UT WOS:000236656900010 ER PT J AU Piqueras, B Connolly, J Freitas, H Palucka, AK Banchereau, J AF Piqueras, B Connolly, J Freitas, H Palucka, AK Banchereau, J TI Upon viral exposure, myeloid and plasmacytoid dendritic cells produce 3 waves of distinct chemokines to recruit immune effectors SO BLOOD LA English DT Article ID MACROPHAGE INFLAMMATORY PROTEIN-3-BETA; T-CELLS; CXC CHEMOKINE; CUTTING EDGE; EBI1-LIGAND CHEMOKINE; B-CELLS; EXPRESSION; PLATELET-FACTOR-4; LIGAND; CC AB Host response to viral infection involves distinct effectors of innate and adaptive immunity, whose mobilization needs to be coordinated to ensure protection. Here we show that influenza virus triggers, in human blood dendritic-cell (DC) subsets (ie, plasmacytold and myeloid DCs), a coordinated chemokine (CK) secretion program with 3 successive waves. The first one, occurring at early time points (2 to 4 hours), includes CKs potentially attracting effector cells such as neutrophils, cytotoxic T cells, and natural killer (NK) cells (CXCL16, CXCL1, CXCL2, and CXCL3). The second one occurs within 8 to 12 hours and includes CKs attracting effector memory T cells (CXCL8, CCL3, CCL4, CCL5, CXCL9, CXCL10, and CXCL11). The third wave, which occurs after 24 to 48 hours, when DCs have reached the lymphoid organs, includes CCL19, CCL22, and CXCL13, which attract naive T and B lymphocytes. Thus, human blood DC subsets carry a common program of CK production, which allows for a coordinated attraction of the different immune effectors in response to viral infection. C1 NIAID, Cooperat Ctr Translat Res Human Immunol & Biodef, Dallas, TX USA. Baylor Inst Immunol Res, Dallas, TX USA. RP Banchereau, J (reprint author), 3434 Live Oak, Dallas, TX 75204 USA. EM piqueras@infobiogen.fr; karolinp@baylorhealth.edu; jacquesb@baylorhealth.edu RI Connolly, John/B-8099-2014 FU NCI NIH HHS [CA78 846]; PHS HHS [U19 AIO57 234] NR 38 TC 121 Z9 126 U1 3 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 2006 VL 107 IS 7 BP 2613 EP 2618 DI 10.1182/blood-2005-07-2965 PG 6 WC Hematology SC Hematology GA 030TG UT WOS:000236656900015 PM 16317096 ER PT J AU Calvani, M Rapisarda, A Uranchimeg, B Shoemaker, RH Melillo, G AF Calvani, M Rapisarda, A Uranchimeg, B Shoemaker, RH Melillo, G TI Hypoxic induction of an HIF-1 alpha-dependent bFGF autocrine loop drives angiogenesis in human endothelial cells SO BLOOD LA English DT Article ID PAS DOMAIN PROTEIN-1; INDUCIBLE FACTOR-1; TRANSCRIPTION FACTOR; TUMOR ANGIOGENESIS; GENE-EXPRESSION; THERAPEUTIC IMPLICATIONS; GROWTH; HIF-1; CANCER; INHIBITION AB Hypoxia is a major pathophysiological condition for the induction of angiogenesis, which is a crucial aspect of growth in solid tumors. In mammalian cells, the transcriptional response to oxygen deprivation is largely mediated by hypoxia-inducible factor 1 (HIF-1), a heterodimer composed of HIF-1 alpha and HIF-1 beta subunits. However, the response of endothelial cells to hypoxia and the specific involvement of HIF-alpha subunits in this process are still poorly understood. We show that human umbilical vein endothelial cells (HUVECs) cultured in the absence of growth factors survive and form tubelike structures when cultured under hypoxic, but not normoxic, conditions. HUVECs expressed both HIF-1 alpha and HIF-2 alpha when cultured under hypoxic conditions. Transfection of HIF-1 alpha, but not HIF-2 alpha, siRNA to HUVECs completely abrogated hypoxic induction of cords. Neutralizing antibodies to bFGF, but not IGF-1, VEGF, or PDGF-BB, blocked survival and sprouting of HUVECs under hypoxic conditions, suggesting the existence of an autocrine loop induced by low oxygen levels. Notably, bFGF-dependent induction of cord formation under normoxic conditions required HIF-1 alpha activity, which was also essential for hypoxic induction of bFGF mRNA and protein expression. These results uncover the existence of an HIF-1 alpha-bFGF amplification pathway that mediates survival and sprouting of endothelial cells under hypoxic conditions. C1 Natl Canc Inst, DTP Tumor Hypoxia Lab, Sci Applicat Int Corp Frederick, Ft Detrick, MD 21702 USA. RP Melillo, G (reprint author), Natl Canc Inst, DTP Tumor Hypoxia Lab, Sci Applicat Int Corp Frederick, Bldg 432,Rm 218, Ft Detrick, MD 21702 USA. EM melillog@ncifcrf.gov NR 42 TC 131 Z9 137 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 1 PY 2006 VL 107 IS 7 BP 2705 EP 2712 DI 10.1182/blood-2005-09-3541 PG 8 WC Hematology SC Hematology GA 030TG UT WOS:000236656900028 PM 16304044 ER PT J AU Athanasopoulos, AN Ecnomopoulou, M Orlova, VV Sobke, A Schneider, D Weber, H Augustin, HG Eming, SA Schubert, U Linn, T Nawroth, PP Hussain, MA Hammes, HP Herrmann, M Preissner, KT Chavakis, T AF Athanasopoulos, AN Ecnomopoulou, M Orlova, VV Sobke, A Schneider, D Weber, H Augustin, HG Eming, SA Schubert, U Linn, T Nawroth, PP Hussain, MA Hammes, HP Herrmann, M Preissner, KT Chavakis, T TI The extracellular adherence protein (Eap) of Staphylococcus aureus inhibits wound heating by interfering with host defense and repair mechanisms SO BLOOD LA English DT Article ID ANTIINFLAMMATORY FACTOR; TISSUE FACTOR; KAPPA-B; ANGIOGENESIS; RECEPTOR; BINDING; RECRUITMENT; INTEGRINS; MICE; INFECTIONS AB Staphylococcus aureus is a major human pathogen interfering with host-cell functions. Impaired wound healing is often observed in S aureus-infected wounds, yet, the underlying mechanisms are poorly defined. Here, we identify the extracellular adherence protein (Eap) of S aureus to be responsible for impaired wound healing. In a mouse wound-healing model wound closure was inhibited in the presence of wild-type S aureus and this effect was reversible when the wounds were incubated with an isogenic Eap-deficient strain. Isolated Eap also delayed wound closure. In the presence of Eap, recruitment of inflammatory cells to the wound site as well as neovascularization of the wound were prevented. In vitro, Eap significantly reduced intercellular adhesion molecule 1 (ICAM-1)-dependent leukocyte-endothelial interactions and diminished the consequent activation of the proinflammatory transcription factor nuclear factor kappa B (NF kappa B) in leukocytes associated with a decrease in expression of tissue factor. Moreover, Eap blocked alpha(v)-integrin-mediated endothelial-cell migration and capillary tube formation, and neovascularization in matrigels in vivo. Collectively, the potent anti-inflammatory and antiangiogenic properties of Eap provide an underlying mechanism that may explain the impaired wound healing in S aureus-infected wounds. Eap may also serve as a lead compound for new antiinflammatory and antiangiogenic therapies in several pathologies. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Heidelberg, Dept Internal Med, D-6900 Heidelberg, Germany. Univ Hosp Mannheim, Med Dept 5, Mannheim, Germany. Univ Saarland, Inst Med Microbiol, D-6600 Saarbrucken, Germany. Univ Giessen, Dept Internal Med, D-35390 Giessen, Germany. Univ Giessen, Inst Biochem, D-35390 Giessen, Germany. Res Tumor Biol Ctr, Dept Vasc Biol & Angiogenesis, Freiburg, Germany. Univ Cologne, Dept Dermatol, D-5000 Cologne 41, Germany. Univ Hosp Munster, Inst Med Microbiol, Munster, Germany. RP Chavakis, T (reprint author), NCI, Expt Immunol Branch, NIH, Ctr Dr,Rm 4B17, Bethesda, MD 20892 USA. EM chavakist@mail.nih.gov RI Herrmann, Mathias/B-6475-2013; Orlova, Valeria/C-6065-2014 OI Orlova, Valeria/0000-0002-1169-2802 FU Intramural NIH HHS NR 41 TC 60 Z9 60 U1 1 U2 8 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 2006 VL 107 IS 7 BP 2720 EP 2727 DI 10.1182/blood-2005-08-3140 PG 8 WC Hematology SC Hematology GA 030TG UT WOS:000236656900030 PM 16317095 ER PT J AU Dunleavy, K Wilson, WH AF Dunleavy, K Wilson, WH TI The case for rituximab in AIDS-related lymphoma SO BLOOD LA English DT Letter ID B-CELL LYMPHOMA; DOSE-ADJUSTED EPOCH; CHOP; THERAPY; CHEMOTHERAPY C1 NCI, Bethesda, MD 20892 USA. RP Wilson, WH (reprint author), NCI, Bldg 10,Room 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov NR 9 TC 11 Z9 11 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 1 PY 2006 VL 107 IS 7 BP 3014 EP 3015 DI 10.1182/blood-2005-09-3885 PG 2 WC Hematology SC Hematology GA 030TG UT WOS:000236656900074 PM 16554492 ER PT J AU Engel, ME Hickstein, DD Bauer, TR Calder, C Manes, B Frangoul, H AF Engel, ME Hickstein, DD Bauer, TR Calder, C Manes, B Frangoul, H TI Matched unrelated bone marrow transplantation with reduced-intensity conditioning for leukocyte adhesion deficiency SO BONE MARROW TRANSPLANTATION LA English DT Letter ID DISEASE PHENOTYPE C1 Vanderbilt Univ, Pediat Stem Cell Transplant Program, Nashville, TN 37240 USA. NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Engel, ME (reprint author), Vanderbilt Univ, Pediat Stem Cell Transplant Program, Nashville, TN 37240 USA. EM Haydar.Frangoul@Vanderbilt.edu NR 9 TC 8 Z9 8 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2006 VL 37 IS 7 BP 717 EP 718 DI 10.1038/sj.bmt.1705301 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 024NO UT WOS:000236202400014 PM 16489359 ER PT J AU Hardy, J Momeni, P Traynor, BJ AF Hardy, J Momeni, P Traynor, BJ TI Frontal temporal dementia: dissecting the aetiology and pathogenesis SO BRAIN LA English DT Editorial Material ID AMYOTROPHIC-LATERAL-SCLEROSIS; VALOSIN-CONTAINING PROTEIN; FRONTOTEMPORAL DEMENTIA; DISEASE; PARKINSONISM; MUTATION; CHROMOSOME-17 C1 NIMH, Sect Dev & Genet Epidemiol, Bethesda, MD 20892 USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov RI Hardy, John/C-2451-2009; Traynor, Bryan/G-5690-2010 FU Medical Research Council [G0701075] NR 19 TC 6 Z9 6 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD APR PY 2006 VL 129 BP 830 EP 831 DI 10.1093/brain/awl035 PN 4 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 025GB UT WOS:000236252200003 PM 16543401 ER PT J AU Bakay, M Wang, ZY Melcon, G Schiltz, L Xuan, JH Zhao, P Sartorelli, V Seo, J Pegoraro, E Angelini, C Shneiderman, B Escolar, D Chen, YW Winokur, ST Pachman, LM Fan, CG Mandler, R Nevo, Y Gordon, E Zhu, YT Dong, YB Wang, Y Hoffman, EP AF Bakay, M Wang, ZY Melcon, G Schiltz, L Xuan, JH Zhao, P Sartorelli, V Seo, J Pegoraro, E Angelini, C Shneiderman, B Escolar, D Chen, YW Winokur, ST Pachman, LM Fan, CG Mandler, R Nevo, Y Gordon, E Zhu, YT Dong, YB Wang, Y Hoffman, EP TI Nuclear envelope dystrophies show a transcriptional fingerprint suggesting disruption of Rb-MyoD pathways in muscle regeneration SO BRAIN LA English DT Article DE skeletal muscle; lamin A/C; emerin; Emery-Dreifuss muscular dystrophy ID DREIFUSS MUSCULAR-DYSTROPHY; A-TYPE LAMINS; FAMILIAL PARTIAL LIPODYSTROPHY; HUTCHINSON-GILFORD PROGERIA; RETINOBLASTOMA GENE-PRODUCT; CAUSE AUTOSOMAL-DOMINANT; IN-VIVO; MANDIBULOACRAL DYSPLASIA; DILATED CARDIOMYOPATHY; MYOGENIC DIFFERENTIATION AB Mutations of lamin A/C (LMNA) cause a wide range of human disorders, including progeria, lipodystrophy, neuropathies and autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD). EDMD is also caused by X-linked recessive loss-of-function mutations of emerin, another component of the inner nuclear lamina that directly interacts with LMNA. One model for disease pathogenesis of LMNA and emerin mutations is cell-specific perturbations of the mRNA transcriptome in terminally differentiated cells. To test this model, we studied 125 human muscle biopsies from 13 diagnostic groups (125 U133A, 125 U133B microarrays), including EDMD patients with LMNA and emerin mutations. A Visual and Statistical Data Analyzer (VISDA) algorithm was used to statistically model cluster hierarchy, resulting in a tree of phenotypic classifications. Validations of the diagnostic tree included permutations of U133A and U133B arrays, and use of two probe set algorithms (MAS5.0 and MBEI). This showed that the two nuclear envelope defects (EDMD LMNA, EDMD emerin) were highly related disorders and were also related to fascioscapulohumeral muscular dystrophy (FSHD). FSHD has recently been hypothesized to involve abnormal interactions of chromatin with the nuclear envelope. To identify disease-specific transcripts for EDMD, we applied a leave-one-out (LOO) cross-validation approach using LMNA patient muscle as a test data set, with reverse transcription-polymerase chain reaction (RT-PCR) validations in both LMNA and emerin patient muscle. A high proportion of top-ranked and validated transcripts were components of the same transcriptional regulatory pathway involving Rb1 and MyoD during muscle regeneration (CRI-1, CREBBP, Nap1L1, ECREBBP/p300), where each was specifically upregulated in EDMD. Using a muscle regeneration time series (27 time points) we develop a transcriptional model for downstream consequences of LMNA and emerin mutations. We propose that key interactions between the nuclear envelope and Rb and MyoD fail in EDMD at the point of myoblast exit from the cell cycle, leading to poorly coordinated phosphorylation and acetylation steps. Our data is consistent with mutations of nuclear lamina components leading to destabilization of the transcriptome in differentiated cells. C1 Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. Catholic Univ Amer, Dept Elect Engn & Comp Sci, Washington, DC 20064 USA. George Washington Univ, Sch Med, Dept Neurol, Washington, DC USA. NIAMSD, Muscle Dev Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92717 USA. Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, Chicago, IL 60611 USA. Virginia Polytech Inst & State Univ, Dept Elect Comp & Biomed Engn, Arlington, VA USA. Univ Padua, Dept Neurosci, Padua, Italy. Hadassah Med Ctr, IL-91120 Jerusalem, Israel. RP Hoffman, EP (reprint author), Childrens Natl Med Ctr, Med Genet Res Ctr, 111 Michigan Ave NW, Washington, DC 20010 USA. EM ehoffman@cnmcresearch.org OI Angelini, Corrado/0000-0002-9554-8794 FU NHGRI NIH HHS [R21/R33 HG002946-01]; NIAMS NIH HHS [R01 AR48289]; NICHD NIH HHS [R21 HD044891-01, 1P30HD40677-01]; NINDS NIH HHS [3R01 NS29525-09] NR 92 TC 166 Z9 167 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD APR PY 2006 VL 129 BP 996 EP 1013 DI 10.1093/brain/awl023 PN 4 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 025GB UT WOS:000236252200019 PM 16478798 ER PT J AU Mangels, KJ Johnson, MD Weil, RJ AF Mangels, KJ Johnson, MD Weil, RJ TI November 2005. 35-year-old woman with progressive bilateral leg weakness - Diagnosis - Intermediate grade melanocytoma SO BRAIN PATHOLOGY LA English DT Article ID MENINGEAL MELANOCYTOMA AB November 2005. A 35-year-old woman presented with one month's history of progressive bilateral leg weakness and altered sensation. There had been no pain. She had noted urinary frequency and constipation in the previous two weeks. On examination, the patient had diffuse lower extremity weakness (2-3/5), with a T6 sensory level to pain and temperature sensation. MRI demonstrated a T4-5 intradural mass ventral to the spinal cord, with an enhancing dural tail, consistent with meningioma. At surgery an intradural, extramedullary, firm, black neoplasm was encountered, which invaded the ventral dura and elevated and distorted the spinal cord. The mass was removed, leaving only microscopic invasion of the ventral dura. There was no bone invasion. Serial sections revealed a homogeneous black tumor without necrosis. H&E stained sections showed an occasionally fascicular tumor of melanocytes and small round blue tumor spindle cells with melanin pigmentation and 1 2 mitotic figures per 10 high-powered fields. The nuclei are generally ovalshaped and elongated, with prominent nucleoli. Necrosis, hemorrhage, and nuclear and cellular pleomorphism are not present and mitotic figures are rare. Immunohistochemical staining was positive for S-100 and HMB-45. MIB-1 labeling averaged 1-2%. A diagnosis of primary meningeal melanocytic tumor was made. Primary meningeal melanocytic tumors (PMMTs) are rare; fewer than 100 cases have been described. PMMTs of the CNS consist of a spectrum of tumors ranging from well-differentiated melanocytoma to its overtly malignant counterpart, melanoma. Intermediate grade melanocytomas (IMGs) are the least common variant, comprising about 10% of PMMTs reported. IGMS occur in the spinal leptomeninges and intracranially in approximately equal proportions. IGMs are more cellular than the well-differentiated variant, with 1-3 mitotic figures per 10 HPFs and MIB-1 labeling of < 6%.(1) By contrast, melanomas contain more mitotic figures (3-15 per 10 HPF) and MIB-1 labeling rates up to 15%.(1) Once metastasis, including drop metastasis from pigmented medulloblastomas, have been excluded, the differential includes pigmented meningiomas and schwannomas ( solitary or as part of Carney complex), as well as other pigmented CNS tumors such as ependymoma and pineoblastoma and systemic diseases such as lymphoma... For primary CNS melanocytic neoplasms, complete tumor resection is preferred, as it leads to cure of well-differentiated and intermediate-grade melanocytomas and most melanomas. Radiotherapy is recommended for incomplete resection of IMGs and melanomas; the recurrence potential of low-grade melanocytomas is less clear and watchful waiting may be employed, since recurrent tumors may be treated surgically prior to radiation. Two months after surgery, the patient had normal sensation and strength. She was given focused radiotherapy to the region of the ventral thecal sac to 40 cGy. At one year following surgery, the patient's neurological examination is normal and she remains free of residual disease by MR examination. C1 Vanderbilt Univ, Med Ctr, Dept Neurosurg, Nashville, TN 37240 USA. Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Mangels, KJ (reprint author), Vanderbilt Univ, Med Ctr, Dept Neurosurg, 221 Kirkland Hall, Nashville, TN 37240 USA. NR 8 TC 5 Z9 6 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD APR PY 2006 VL 16 IS 2 BP 183 EP + DI 10.1111/j.1750-3639.2006.00003_2.x PG 3 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 051ET UT WOS:000238144600011 PM 16768759 ER PT J AU Lee, MY Joung, YH Lim, EJ Park, JH Ye, SK Park, T Zhang, Z Park, DK Lee, KJ Yang, YM AF Lee, Moon Young Joung, Youn Hee Lim, Eun Joung Park, Jong-Hwan Ye, Sang-Kyu Park, Taekyu Zhang, Zheng Park, Dong Ki Lee, Kwang Jeon Yang, Young Mok TI Phosphorylation and activation of STAT proteins by hypoxia in breast cancer cells SO BREAST LA English DT Article DE STAT; hypoxia; breast cancer cell; tyrosine phosphorylation; serine phosphorylation ID TRANSCRIPTION FACTORS; HEPG2 CELLS; BINDING-ACTIVITY; GENE-EXPRESSION; GROWTH; DESFERRIOXAMINE; ERYTHROPOIETIN; INVOLVEMENT; RESPONSES; RECEPTOR AB Several constitutively activated signal transducers and activators of transcription (STAT) proteins have been observed in a wide number of human cancer cell lines and primary tumors. Normal cells maintain normoxic conditions but tumor cells are characteristically hypoxic. We studied the altered activation and tyrosine phosphorylation of STATs under hypoxic conditions (2% O(2)) or desferrioxamine (DFO) treatment in mouse mammary epithelial cells (HC11) and a human breast cancer cell-7). STAT1, -3 and -5 proteins are especially important and are observed at elevated levels in tumorigenesis. We also investigated the serine phosphorylation of STAT1, -3, and -5 under hypoxic conditions or DFO treatment in HC11 and MCF-7 cells. Here we show that DFO or hypoxia stimulates the tyrosine and/or serine phosphorylation and the expression of STAT proteins in breast cancer cells. Our data suggest that DFO or hypoxic condition is a critical stimulator for the activation of STAT proteins in breast cancer cells. These results may provide the basis for identifying another mechanism of breast tumorigenesis via the JAK/STAT pathway in hypoxia. Also, activation of STAT proteins by hypoxia may play an important role in the physiological phenomenon of embryonic stem cells and old cells with hypoxic conditions. (c) 2005 Elsevier Ltd. All rights reserved. C1 Konkuk Univ, Coll Med, Dept Pathol, Lab Human Genet, Chungju 380701, South Korea. Konkuk Univ, Biofood & Drug Res Ctr, Chungju 380701, South Korea. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Med, Dept Pharmacol, Seoul 110799, South Korea. Konkuk Univ, Coll Nat Sci, Dept Biotechnol, Biofood & Drug Res Ctr, Chungju 380701, South Korea. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Konkuk Univ, Coll Anim Husb, Dept Anim Biotechnol, Seoul 143701, South Korea. RP Yang, YM (reprint author), Konkuk Univ, Coll Med, Dept Pathol, Lab Human Genet, Chungju 380701, South Korea. EM ymyang@kku.ac.kr RI Ye, Sang Kyu/J-2768-2012 NR 32 TC 28 Z9 29 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD APR PY 2006 VL 15 IS 2 BP 187 EP 195 DI 10.1016/j.breast.2005.05.005 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 057JH UT WOS:000238591600007 PM 16084091 ER PT J AU Wayne, SJ Baumgartner, K Baumgartner, RN Bernstein, L Bowen, DJ Ballard-Barbash, R AF Wayne, SJ Baumgartner, K Baumgartner, RN Bernstein, L Bowen, DJ Ballard-Barbash, R TI Diet quality is directly associated with quality of life in breast cancer survivors SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; cancer survival; diet quality; quality of life ID PHYSICAL-ACTIVITY; OLDER EUROPEANS; UNITED-STATES; HEALTH-STATUS; HIGH-FIBER; LOW-FAT; WOMEN; MORTALITY; PATTERNS; MEN AB Purpose. To determine whether there is a direct relationship between diet quality and quality of life in breast cancer survivors. Methods. Subjects (n = 714) were members of the Health, Eating, Activity, and Lifestyle study, a study of breast cancer prognosis conducted in three areas of the western United States. Approximately 2 years after entry to this study, diet data were collecting using food frequency questionnaires. These data were used to classify diet quality using the Diet Quality Index. Approximately 10 months later, data on quality of life were gathered using the Medical Outcomes Study 36-Item short form health survey. Results. After controlling for age, education, race/ethnicity, body mass index, stage of disease, and time from diagnosis to quality of life measurement, women with excellent diet quality had significantly better scores than women with poor diet quality for overall mental health functioning and for 3 of 4 mental health subscale scores and 2 of 4 physical health subscale scores. Conclusion. Post-diagnosis diet quality is directly associated with subsequent mental and physical functioning in breast cancer survivors. This association is stronger for mental functioning than for physical functioning. The association remains strong after control for potential confounding variables. C1 Univ New Mexico, Div Epidemiol & Prevent Med, Dept Internal Med, Sch Med, Albuquerque, NM 87131 USA. Univ New Mexico, Canc Res & Treatment Ctr, Dept Internal Med, Sch Med, Albuquerque, NM 87131 USA. Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Los Angeles, CA 90033 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NCI, Appl Res Program, Bethesda, MD 20892 USA. RP Wayne, SJ (reprint author), Univ New Mexico, Div Epidemiol & Prevent Med, Dept Internal Med, Sch Med, Albuquerque, NM 87131 USA. EM swayne@salud.unm.edu FU NCI NIH HHS [N01-CN-75036-20] NR 36 TC 33 Z9 35 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD APR PY 2006 VL 96 IS 3 BP 227 EP 232 DI 10.1007/s10549-005-9018-6 PG 6 WC Oncology SC Oncology GA 043UG UT WOS:000237627100004 PM 16538543 ER PT J AU Robertson, SM Formentini, E Alfaro, RM Natarajan, V Falloon, J Penzak, SR AF Robertson, SM Formentini, E Alfaro, RM Natarajan, V Falloon, J Penzak, SR TI Lack of sex-related differences in saquinavir pharmacokinetics in an HIV-seronegative cohort SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE cytochrome P450; HIV; P-glycoprotein; pharmacokinetics; saquinavir; sex ID P-GLYCOPROTEIN EXPRESSION; RESISTANCE-ASSOCIATED PROTEIN; PLUS MINIDOSE RITONAVIR; HUMAN LIVER; HEALTHY-VOLUNTEERS; SMALL-INTESTINE; MDR1 GENE; GENDER; PHARMACODYNAMICS; METABOLISM AB Aims To examine the influence of sex on steady-state saquinavir pharmacokinetics in HIV-seronegative volunteers administered saquinavir without a concomitant protease inhibitor. Methods Thirty-eight healthy volunteers (14 female) received saquinavir soft-gel capsules 1200 mg three times daily for 3 days to achieve steady-state conditions. Following administration of the 10th dose, blood was collected serially over 8 h for measurement of saquinavir plasma concentrations. Saquinavir pharmacokinetic parameter values were determined using noncompartmental methods and compared between males and females. CYP3A phenotype (using oral midazolam) and MDR-1 genotypes at positions 3435 and 2677 were determined for all subjects in order to characterize possible mechanisms for any observed sex-related differences. Results There was no significant difference in saquinavir AUC(0-8) or any other pharmacokinetic parameter value between the sexes. These findings persisted after mathematically correcting for total body weight. The mean weight-normalized AUC(0-8) was 29.9 (95% confidence interval 15.5, 44.3) and 29.8 (18.6, 40.9) ng h(-1) ml(-1) kg(-1) for males and females, respectively. No significant difference in CYP3A phenotype was observed between the groups; likewise, the distribution of MDR-1 genotypes was similar for males and females. Conclusion In contrast to previous study findings, results from this investigation showed no difference in saquinavir pharmacokinetics between males and females. The discrepancy between our findings and those previously reported may be explained by the fact that we evaluated HIV-seronegative volunteers and administered saquinavir in the absence of concomitant protease inhibitors such as ritonavir. Caution must be exercised when extrapolating pharmacokinetic data from healthy volunteer studies (including sex-based pharmacokinetic differences) to HIV-infected populations or to patients receiving additional concurrent medications. C1 NIH, Clin Res Ctr, Dept Pharm, Bethesda, MD 20892 USA. NIH, Clin Res Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Frederick Inc, Frederick, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Robertson, SM (reprint author), NIH, Clin Res Ctr, Dept Pharm, Bldg 10,Room 1 N 257, Bethesda, MD 20892 USA. EM robertsonsa@cc.nih.gov NR 54 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD APR PY 2006 VL 61 IS 4 BP 379 EP 388 DI 10.1111/j.1365-2125.2006.02593.x PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 021YR UT WOS:000236022300004 PM 16542198 ER PT J AU Ng, D Marti, GE Fontaine, L Toro, JR Caporaso, N Goldin, LR AF Ng, D Marti, GE Fontaine, L Toro, JR Caporaso, N Goldin, LR TI High-density mapping and follow-up studies on chromosomal regions 1, 3, 6, 12, 13 and 17 in 28 families with chronic lymphocytic leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; family studies; linkage analysis ID LINKAGE ANALYSIS; GENOME; SCAN AB A subset of chronic lymphocytic leukaemia (CLL) shows familial aggregation. Studies show an increased risk for CLL and other lymphoproliferative disease among first-degree relatives of affected individuals. A genome-wide scan of 18 CLL families in 2003 detected LOD or non-parametric linkage scores >= 1.0 on chromosomes 1, 3, 6, 12, 13 and 17. Follow-up study with 28 families showed no evidence of linkage at 1p22.1-p21.2, 3q22.1, 3q26.2, 6q22.31-q23.2, 12q24.23, 14q32.13, 17p13.3. Chromosome 13q21.33 remains a region of interest with a P-value of 0.013 (marker D13S1291) and warrants additional molecular investigation as a susceptibility region for CLL. C1 NCI, Genet Epidemiol Branch, DCEG, DHHS, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Flow & Image Cytometry Sect, Lab Stem Cell Biol,Off Cellular Tissues & Gene Th, Bethesda, MD 20014 USA. Westat Res Inc, Rockville, MD USA. RP Ng, D (reprint author), NCI, Genet Epidemiol Branch, DCEG, DHHS, 6120 Execut Blvd,Room 7005,MSC 7236, Bethesda, MD 20892 USA. EM davidng@mail.nih.gov FU Intramural NIH HHS NR 12 TC 13 Z9 14 U1 0 U2 0 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 2006 VL 133 IS 1 BP 59 EP 61 DI 10.1111/j.1365-2141.2006.05972.x PG 3 WC Hematology SC Hematology GA 017YY UT WOS:000235730600006 PM 16512829 ER PT J AU Hill, A Sapsford, RJ Wang, X McGawley, GM Oxborough, DL Richards, SJ Rother, RP Gladwin, MT Hillmen, P AF Hill, A Sapsford, RJ Wang, X McGawley, GM Oxborough, DL Richards, SJ Rother, RP Gladwin, MT Hillmen, P TI Nitric oxide consumption and pulmonary hypertension in patients with paroxysmal nocturnal haemoglobinuria SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 46th Annual Scientific Meetign of the British-Society-for-Haematology CY APR 03-05, 2006 CL Edinburgh, ENGLAND SP British Soc Haematol C1 Leeds Gen Infirm, Dept Haematol, Leeds, W Yorkshire, England. Leeds Gen Infirm, Dept Echocardiog, Leeds, W Yorkshire, England. NHLBI, Vasc Therapeut Sect, NIH, Bethesda, MD USA. Alexion Pharmaceut Inc, Dept Discovery Res, Cheshire, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2006 VL 133 SU 1 BP 119 EP 119 PG 1 WC Hematology SC Hematology GA 026GD UT WOS:000236326500335 ER PT J AU Cantwell, MM Flynn, MAT Gibney, MJ AF Cantwell, MM Flynn, MAT Gibney, MJ TI Acute postprandial effect of hydrogenated fish oil, palm oil and lard on plasma cholesterol, triacylglycerol and non-esterified fatty acid metabolism in normocholesterolaemic males SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE hydrogenated fish oil; trans unsaturated fatty acids; palm oil; lard; postprandial response ID CORONARY-ARTERY-DISEASE; MYOCARDIAL-INFARCTION; ADIPOSE-TISSUE; HEART-DISEASE; LIPOPROTEINS; HUMANS; LIPIDS; ABSORPTION; WOMEN; RISK AB The majority of research has focused on the association between trans unsaturated fatty acids (TUFA) from hydrogenated vegetable oils and heart disease even though TUFA are also produced from hydrogenated fish oil. We compared the acute effect of three solid fats on postprandial cholesterol, triacylglycerol (TAG) and NEFA concentrations in normocholesterolaemic males. Eight healthy male volunteers consumed each of the three 40 g fat meals (partially hydrogenated fish oil (PHFO), palm oil and lard) in random order and blood samples were drawn at 2, 4, 6 and 8 h thereafter for lipid analysis. The postprandial response in plasma TAG, TAG-rich lipoprotein-TAG (TRL-TAG), total cholesterol and plasma NEFA, measured as the area under the postprandial curve, was not significantly different between the three meals (P > 0.05), which varied in MUFA, PUFA and TUFA content. There was no marked elevation of longer-chain fatty acids (C20-22, cis or trans isomers) into the TRL-TAG fraction following the PHFO meal even though they provided 40 % of the total fatty acids in the PHFO meal. The postprandial TRL-TAG response to PHFO was expected to be higher, as it is higher in TUFA, lower in PUFA and similar in saturated fatty acid composition compared with the lard and palm oil test meals. The absence of a higher postprandial response following ingestion of PHFO could be as a result of reduced absorption and increased oxidation of long-chain fatty acids (both cis and trans isomers). C1 Univ Dublin Trinity Coll, Dept Clin Med, Trinity Ctr Hlth Sci, Dublin 8, Ireland. Dublin Inst Technol, Dept Biol Sci, Dublin 8, Ireland. NCI, Canc Prevent Fellowship Program, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. Univ Calgary, Dept Community Hlth Sci, Calgary, AB, Canada. RP Gibney, MJ (reprint author), Univ Dublin Trinity Coll, Dept Clin Med, Trinity Ctr Hlth Sci, Dublin 8, Ireland. EM mgibney@tcd.ie NR 36 TC 4 Z9 4 U1 0 U2 4 PU CABI PUBLISHING PI WALLINGFORD PA C/O PUBLISHING DIVISION, NOSWORTHY WAY, WALLINGFORD OX10 8DE, OXON, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD APR PY 2006 VL 95 IS 4 BP 787 EP 794 DI 10.1079/BJN20051723 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 027AY UT WOS:000236386600015 PM 16571159 ER PT J AU Buggage, RR Bauer, RM Holland, SM Santos, CI Chan, CC AF Buggage, RR Bauer, RM Holland, SM Santos, CI Chan, CC TI Uveitis and a subretinal mass in a patient with chronic granulomatous disease SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CHORIORETINAL LESIONS; NADPH OXIDASE; CHILDHOOD C1 NEI, NIH, Immunol Lab, NIAID, Bethesda, MD 20892 USA. Winn Army Hosp, Ft Stewart, GA USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ Puerto Rico, Dept Ophthalmol, San Juan, PR 00936 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, NIH, Immunol Lab, NIAID, 10 Ctr Dr,Bldg 10,Room 10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov FU Intramural NIH HHS NR 10 TC 3 Z9 3 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 2006 VL 90 IS 4 BP 514 EP 515 DI 10.1136/bjo.2005.081505 PG 4 WC Ophthalmology SC Ophthalmology GA 023CH UT WOS:000236102400034 PM 16547340 ER PT J AU Maslov, LN Lishmanov, YB Barzakh, EI Lasukova, TV Rice, KK Oeltgen, PR AF Maslov, L. N. Lishmanov, Yu. B. Barzakh, E. I. Lasukova, T. V. Rice, K. K. Oeltgen, P. R. TI Negative inotropic and chronotropic effects of delta-opioid receptor antagonists are mediated via non-opioid receptors SO BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE delta-opioid receptor antagonists; cardiac rhythm; isolated perfused heart ID ACTIVATION; AFFINITY AB Ten-minute perfusion of intact isolated rat heart with Krebs-Henseleit solution containing delta-opioid receptor agonists (DPDPE, (-)-TAN-67) or delta-opioid receptor antagonists (naltrindole, TIPP[psi], ICI 174,864) at a final concentration of 0.1 mg/liter decreased HR, blood pressure in the left ventricle, and the rates of myocardial contraction and relaxation. Intravenous injection of delta-agonists (DPDPE, (-)-TAN-67, deltorphin II) or delta-antagonists (naltrindole, TIPP[psi], ICI 174,864) decreased HR in narcotized rats. Naloxone and naltrexone produced no effect on contractility and HR both in vivo and in vitro. Preliminary injection of naloxone and naltrexone did not prevent the negative chronotropic effect of ICI 174,864 in vitro. The negative inotropic and chronotropic effects of delta-opioid receptor antagonists are mediated by unknown non-opioid receptors in the heart. C1 Russian Acad Med Sci, Siberian Div, Tomsk Res Ctr, State Res Inst Cardiol, Tomsk, Russia. Tomsk State Pedag Univ, Tomsk, Russia. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Kentucky, Coll Med, Dept Pathol, Lexington, KY USA. RP Maslov, LN (reprint author), Russian Acad Med Sci, Siberian Div, Tomsk Res Ctr, State Res Inst Cardiol, Tomsk, Russia. EM maslov@cardio.tsu.ru RI Lishmanov, Yuri/F-5940-2014 OI Lishmanov, Yuri/0000-0002-3928-7462 NR 15 TC 5 Z9 6 U1 0 U2 1 PU CONSULTANTS BUREAU/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0007-4888 J9 B EXP BIOL MED+ JI Bull. Exp. Biol. Med. PD APR PY 2006 VL 141 IS 4 BP 420 EP 423 DI 10.1007/s10517-006-0188-y PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 082LG UT WOS:000240387700012 PM 17152360 ER PT J AU Brooks, JP Albert, PS O'Connell, J McLeod, DG Poggi, MM AF Brooks, JP Albert, PS O'Connell, J McLeod, DG Poggi, MM TI Lymphovascular invasion in prostate cancer - Prognostic significance in patients treated with radiotherapy after radical prostatectomy SO CANCER LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 17-21, 2005 CL Orlando, FL SP Amer Soc Clin Oncol DE extracapsular extension; Gleason score; lymph node involvement; perineural invasion; radical prostatectomy; seminal vesicle invasion; surgical margin status ID MICROVASCULAR INVASION; SALVAGE RADIOTHERAPY; SPECIMENS; PROGRESSION; PREDICTORS; CARCINOMA; DISEASE AB BACKGROUND. Lymphovascular invasion (LVI) is found ill approximately 5% to 53% of specimens after radical prostatectomy (RP). Although LVI is associated with higher rates of recurrence after RP, its prognostic significance after postprostatectomy radiotherapy (P-XRT) is unclear. METHODS. The medical records of men who received P-XRT from 1991 to 2001 at 2 institutions were reviewed for the presence of LVI in RP specimens. Multiple patient variables were evaluated for their association with LVI using Fisher exact tests and Wilcoxon rank-sum tests. The time to biochemical recurrence (BCR) and the time to distant metastases (DM) after RP were analyzed using Kaplan-Meier estimations, log-rank tests, and Cox regression analyses. RESULTS. Eighteen of 160 patients (11%) who received P-XRT had LVI in their RP specimen. High Gleason score and seminal vesicle invasion were associated significantly with LVI. After a median follow-up of 8.3 years after RP, 16 patients with LVI had BCR after P-XRT, 9 of whom developed DM. The median time to BCR in patients with LVI was 2.6 years (95% confidence interval [95% CI], 1.8-5.4) compared with 7.8 years (95% CI, 6.8-10.3) in patients without LVI (P <.001). Multi- revealed all adjusted relative risk for LVI of 5.5 (P <.001). Other variate analysis significant factors were Gleason score, undetectable post-RP serum prostate-specific antigen (PSA) levels, preradiotherapy serum PSA levels, and the interval from RP to P-XRT. LVI was the only significant factor associated with all increased risk of DM ill univariate analysis (hazard ratio, 7.4; P <.001). CONCLUSIONS. LVI was Useful as a pathologic marker for reduced efficacy of P-XRT after RP in terms of increased risk of BCR and DM. Future studies will be needed to validate these findings. C1 Natl Naval Med Res Inst, Div Radiat Oncol, Bethesda, MD 20889 USA. Walter Reed Army Med Ctr, Div Radiat Oncol, Washington, DC 20307 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Dept Urol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD 20814 USA. RP Poggi, MM (reprint author), Natl Naval Med Res Inst, Div Radiat Oncol, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM mpoggi@bethesda.med.navy.mil NR 14 TC 11 Z9 11 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 1 PY 2006 VL 106 IS 7 BP 1521 EP 1526 DI 10.1002/cncr.21774 PG 6 WC Oncology SC Oncology GA 024KI UT WOS:000236193500013 PM 16518811 ER PT J AU Chinn, PC Morena, RA Santoro, DA Kazules, T Kashmiri, SVS Schlom, J Hanna, N Braslawsky, G AF Chinn, PC Morena, RA Santoro, DA Kazules, T Kashmiri, SVS Schlom, J Hanna, N Braslawsky, G TI Pharmacokinetics and ibmor localization of In-111-labeled HuCC49 Delta C(H)2 in BALB/c mice and athymic murine colon carcinoma xenograft SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Article DE radioimmunotherapy; radioisotopes; In-111; monoclonal antibody; carcinoma; TAG-72; CC49; domain-deleted; chelate; Mx-DTPA; C(H)2; murine ID MONOCLONAL-ANTIBODY CC49; NON-HODGKINS-LYMPHOMA; SINGLE-CHAIN FV; B-CELL LYMPHOMA; IBRITUMOMAB TIUXETAN RADIOIMMUNOTHERAPY; PHASE-I; CH2 DOMAIN; NUDE-MICE; TRIAL; THERAPY AB The primary limitation of IgG antibodies for radioimmunotherapy of solid tumors is their prolonged serum half-life, leading to dose-limiting bone marrow toxicity at doses providing inadequate radiation to the tumor. A humanized C(H)2 domain-deleted variant of the anti-TAG-72 antibody CC49 (HuCC49 Delta C(H)2) has faster blood clearance, compared to the IgG, while retaining tumor targeting. We compared the pharmacokinetics and tumor uptake of In-111-HuCC49 Delta C(H)2 in BALE/c mice and a colon carcinoma (LS-174T) mouse xenograft with that of In-111-labeled chimeric CC49 (cCC49), an antibody with pharmacokinetics similar to the humanized CC49 parent., Immunoconjugates of HuCC49 Delta C(H)2 and cCC49 prepared with the In-111 chelator Mx-DTPA (1-isothiocyantobenzyl-3-methyldiethylenetriaminepentaacetic acid) retained low nM affinity and radiolabeling protocols provided greater than 95% radioincorporation with In-111 while retaining greater than 80% immunoreactivity. Blood clearance of In-111-HuCC49 Delta C(H)2 in BALB/c mice was monoexponential (t(1/2) 5.4 hours) and faster than In-111-cCC49 (biexponential clearance; t(1/2 alpha) 1.5 hours; t(1/2 beta) 162 hours). The In-111-HuCC49 Delta C(H)2 also cleared more rapidly from the blood in the murine xenograft. At 1 hour postinjection, blood concentrations for In-111-HuCC49 Delta C(H)2 and In-111-cCC49 were comparable (25.5 injected dose per g [%ID/g] and 21.3 %ID/g, respectively); tumor uptake for (111)InHuCC49 Delta C(H)2 was 7.9 %ID/g, compared to 7.5 %ID/g for In-111-cCC49. However, at 24 hours, blood concentration for In-111-HuCC49 Delta C(H)2 was less than In-111-cCC49 (0.9 %ID/g versus 5.2 %ID/g, respectively) with comparable tumor retention (14.4 %ID/g versus 19.0 %ID/g, respectively). Faster blood clearance of In-111-HuCC49 Delta C(H)2 and tumor localization comparable to that of In-111-cCC49 provided a fourfold improved tumor-to-blood ratio for In-111-HuCC49 Delta C(H)2 at 24 hours postinjection. C1 Biogen Idec, San Diego, CA 92122 USA. NCI, Bethesda, MD 20892 USA. RP Chinn, PC (reprint author), Biogen Idec, 5200 Res Pl, San Diego, CA 92122 USA. EM Paul.Chinn@biogenidic.com NR 51 TC 11 Z9 11 U1 2 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD APR PY 2006 VL 21 IS 2 BP 106 EP 116 DI 10.1089/cbr.2006.21.106 PG 11 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA 047JA UT WOS:000237874400005 PM 16706631 ER PT J AU Sellers, TA Caporaso, N Lapidus, S Petersen, GM Trent, J AF Sellers, TA Caporaso, N Lapidus, S Petersen, GM Trent, J TI Opportunities and barriers in the age of team science: strategies for success SO CANCER CAUSES & CONTROL LA English DT Review DE biotechnology; neoplasms; interdisciplinary communication; epidemiologic studies AB Objective To provide the voice of experience to investigators contemplating engagement in the realm of "team science". Methods Leaders were brought together from academia, government, and industry to share perspectives and insights based on real-life experiences. A panel discussion was held at the 2005 annual meeting of the American Association of Cancer Research. This article summarizes that forum. Results The panel focused on eight specific topics that were determined in advance to be the most important: the main justification for team science, funding team science, pre-arranged versus assigned partnerships, the role of novel technology with industrial partners, recognition for efforts and contribution in team science, budgets, keys to success when bridging disciplines and cultures, and balancing goals between academia and business. Although there were some differences of opinion, there were also a number of areas of agreement. Many practical suggestions were provided on how to succeed in the age of team science. Principal conclusion The nature of scientific discovery in cancer research is increasingly requiring team science. Understanding the perspectives of academia, government, and business in this new world order is essential to successful navigation and, ultimately, major accomplishment in the effort to defeat the disease. C1 Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Div Canc Prevent & Control, Tampa, FL 33612 USA. NCI, Bethesda, MD 20892 USA. Helicos Biosci, Cambridge, MA USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. Translat Genom Res Inst, Phoenix, AZ USA. RP Sellers, TA (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Div Canc Prevent & Control, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM sellerta@moffitt.usf.edu NR 2 TC 12 Z9 12 U1 0 U2 7 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 2006 VL 17 IS 3 BP 229 EP 237 DI 10.1007/s10552-005-0546-5 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 014ET UT WOS:000235462600001 PM 16489530 ER PT J AU Sansbury, LB Millikan, RC Schroeder, JC North, KE Moorman, PG Keku, TO de Cotret, AR Player, J Sandler, RS AF Sansbury, LB Millikan, RC Schroeder, JC North, KE Moorman, PG Keku, TO de Cotret, AR Player, J Sandler, RS TI COX-2 polymorphism, use of nonsteroidal anti-inflammatory drugs, and risk of colon cancer in African Americans (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE COX-2; colorectal cancer; race; NSAIDs; polymorphisms ID HUMAN GASTRIC-CARCINOMA; COLORECTAL-CANCER; ASPIRIN USE; LARGE-BOWEL; CYCLOOXYGENASE-2; EXPRESSION; CHEMOPREVENTION; PREVENTION; SYNTHASE-2; MECHANISM AB Introduction The inducible Cyclooxygenase (COX)-2 enzyme plays an important role in inflammation and carcinogenesis. Recent reports suggest that single nucleotide polymorphisms (SNPs) in the COX-2 gene may alter enzyme function and in turn modify an individual's risk of colon cancer. We explored the association between the COX-2 Val511Ala SNP and risk of colon cancer among 240 African American cases and 326 African American controls in a population-based, case-control study in North Carolina. Methods We used unconditional logistic regression models to determine the odds ratios (ORs) for genotype and risk of colon cancer. Results We observed a non-statistically significant inverse association between any Ala COX-2 genotype and risk of colon cancer (OR = 0.62, 95% CI: 0.33, 1.16) among African Americans. The inverse association was present among non-regular NSAID users, use >= 3 times/week, (OR = 0.66; 95% CI: 0.32, 1.37) and regular NSAID users, use >= 3 times/week for >= 3 months, (OR = 0.41; 95% CI: 0.11, 1.54). Conclusions Our results suggest that the COX-2 Val511Ala SNP does not antagonize the effect of NSAIDs on colon cancer risk and provides support that NSAID use and the COX-2 Val511Ala SNP may contribute to a reduced risk of colon cancer among African Americans. C1 NCI, Canc Prevent Fellowship Program, Div Canc Prevent, NIH,DHHS, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. Univ N Carolina, Sch Med, Div Gastroenterol & Hepatol, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC USA. RP Sansbury, LB (reprint author), NCI, Canc Prevent Fellowship Program, Div Canc Prevent, NIH,DHHS, 6116 Execut Blvd,MSC 8325,Suite 702,Room 7207, Bethesda, MD 20892 USA. EM sansburl@mail.nih.gov FU NCI NIH HHS [T32-CA09330, P30-CA16086, R01-CA66635]; NIEHS NIH HHS [ES10126] NR 48 TC 28 Z9 32 U1 0 U2 3 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 2006 VL 17 IS 3 BP 257 EP 266 DI 10.1007/s10552-005-0417-0 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 014ET UT WOS:000235462600004 PM 16489533 ER PT J AU Gumpertz, ML Pickle, LW Miller, BA Bell, BS AF Gumpertz, ML Pickle, LW Miller, BA Bell, BS TI Geographic patterns of advanced breast cancer in Los Angeles: Associations with biological and sociodemographic factors (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE breast neoplasms; sociodemographic factors; mammography; logistic models; spatial patterns ID HORMONE-RECEPTOR STATUS; NEW-YORK-CITY; ETHNIC-DIFFERENCES; PROGNOSTIC FACTORS; COLORECTAL-CANCER; CERVICAL-CANCER; AMERICAN WOMEN; WHITE WOMEN; MAMMOGRAPHY UTILIZATION; PROSTATE-CANCER AB Objective Examination of patterns of advanced breast cancer may provide evidence needed to direct health care resources to those communities or population groups in greatest need. We assessed to what degree biologic, ethnic, and sociodemographic factors could explain such patterns within Los Angeles County. Methods The proportion of cases of advanced disease among all breast cancer cases identified during 1992-1996 were analyzed using generalized linear mixed models with random census tract effects. Models included characteristics of the individual and her tumor, census tract of residence, and aggregated health districts. Results Approximately 6% of cases, ranging from 4% for Asian to 10% for Black women, were diagnosed as advanced, exhibiting striking geographic patterns. Tumor histology and hormone receptor status were most predictive of advanced disease. Sociodemographic variables such as marital status, median income, and distance to nearest mammography unit showed additional association with risk. Conclusions These models explain most of the geographical patterns and eliminate differences between White and Hispanic but not Asian or Black women, identify subpopulations at high risk of advanced disease, and suggest cancer control opportunities. C1 N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. NCI, Bethesda, MD 20892 USA. RP Gumpertz, ML (reprint author), N Carolina State Univ, Dept Stat, 2501 Founders Dr,Rm 202B Patterson Hall, Raleigh, NC 27695 USA. EM gumpertz@ncsu.edu NR 85 TC 36 Z9 36 U1 2 U2 4 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 2006 VL 17 IS 3 BP 325 EP 339 DI 10.1007/s10552-005-0513-1 PG 15 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 014ET UT WOS:000235462600011 PM 16489540 ER PT J AU Liu, YZ Cheney, MD Gaudet, JJ Chruszcz, M Lukasik, SM Sugiyama, D Lary, J Cole, J Dauter, Z Minor, W Speck, NA Bushweller, JH AF Liu, YZ Cheney, MD Gaudet, JJ Chruszcz, M Lukasik, SM Sugiyama, D Lary, J Cole, J Dauter, Z Minor, W Speck, NA Bushweller, JH TI The tetramer structure of the Nervy homology two domain, NHR2, is critical for AM1/ETO's activity SO CANCER CELL LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; TRANSCRIPTION FACTOR PU.1; HEMATOPOIETIC STEM-CELLS; AML1-ETO FUSION PROTEIN; GCN4 LEUCINE-ZIPPER; OLIGOMERIZATION DOMAIN; ADULT HEMATOPOIESIS; MONOMERIC PROTEINS; CRYSTAL-STRUCTURE AB AML1/ETO is the chimeric protein resulting from the t(8;21) in acute myeloid leukemia. The Nervy homology 2 (NHR2) domain in ETO mediates oligornerization and AML1/ETO's interactions with ETO, MTGR1, and MTG16, and with the corepressor molecules mSin3A and HDAC1 and HDAC3. We solved the NHR2 domain structure and found it to be an alpha-helical tetramer. We show that oligomerization contributes to AML1/ETO's inhibition of granulocyte differentiation, is essential for its ability to enhance the clonogenic potential of primary mouse bone marrow cells, and affects AML1/ETO's activity on several endogenous genes. Oligomerization is also required for AML1/ETO's interactions with ETO, MTGR1, and MTG16, but not with other corepressor molecules. C1 Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH 03755 USA. Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. Univ Virginia, Dept Chem, Charlottesville, VA 22906 USA. Univ Connecticut, Natl Analyt Ultracentifrugat Facil, Storrs, CT 06269 USA. Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT 06269 USA. Brookhaven Natl Lab, Natl Canc Inst, Macromol Crystallog Lab, Upton, NY 11973 USA. RP Speck, NA (reprint author), Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH 03755 USA. EM nancy.speck@dartmouth.edu; jhb4v@virginia.edu RI Cole, James/G-2586-2011; Chruszcz, Maksymilian/E-6407-2011; Minor, Wladek/F-3096-2014 FU NCI NIH HHS [CA 23108, R01 CA108056]; NIAMS NIH HHS [T32 AR07576]; NIGMS NIH HHS [T32 GM08704] NR 66 TC 65 Z9 72 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD APR PY 2006 VL 9 IS 4 BP 249 EP 260 DI 10.1016/j.ccr.2006.03.012 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 035WZ UT WOS:000237033700004 PM 16616331 ER PT J AU Sun, LX Hui, AM Su, Q Vortmeyer, A Kotliarov, Y Pastorino, S Passaniti, A Menon, J Walling, J Bailey, R Rosenblum, M Mikkelsen, T Fine, HA AF Sun, LX Hui, AM Su, Q Vortmeyer, A Kotliarov, Y Pastorino, S Passaniti, A Menon, J Walling, J Bailey, R Rosenblum, M Mikkelsen, T Fine, HA TI Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain SO CANCER CELL LA English DT Article ID C-KIT RECEPTOR; ENDOTHELIAL GROWTH-FACTOR; CHRONIC MYELOGENOUS LEUKEMIA; IN-VIVO; CYTOGENETIC RESPONSES; TUMOR ANGIOGENESIS; IMATINIB MESYLATE; MALIGNANT GLIOMAS; EXPRESSION; ASTROCYTOMAS AB Stem cell factor (SCF) is overexpressed by neurons following brain injury as well as by glioma cells; however, its role in gliomagenesis remains unclear. Here, we demonstrate that SCF directly activates brain microvascular endothelial cells (ECs) in vitro and induces a potent angiogenic response in vivo. Primary human gliomas express SCF in a grade-dependent manner and induce normal neurons to express SCF in brain regions infiltrated by glioma cells, areas that colocalize with prominent angiogenesis. Downregulation of SCF inhibits tumor-mediated angiogenesis and glioma growth in vivo, whereas overexpression of SCF is associated with shorter survival in patients with malignant gliomas. Thus, the SCF/c-Kit pathway plays an important role in tumor- and normal host cell-induced angiogenesis within the brain. C1 NCI, Neurooncol Branch, NINDS, NIH, Bethesda, MD 20892 USA. NINDS, Dept Neurosurg, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA. Henry Ford Hosp, Hermelin Brain Tumor Ctr, Dept Neurol, Detroit, MI 48202 USA. Henry Ford Hosp, Hermelin Brain Tumor Ctr, Dept Neurosurg, Detroit, MI 48202 USA. RP Fine, HA (reprint author), NCI, Neurooncol Branch, NINDS, NIH, Bethesda, MD 20892 USA. EM hfine@mail.nih.gov RI Kotliarov, Yuri/B-6938-2017 NR 53 TC 354 Z9 364 U1 0 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD APR PY 2006 VL 9 IS 4 BP 287 EP 300 DI 10.1016/j.ccr.2006.03.003 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 035WZ UT WOS:000237033700007 PM 16616334 ER PT J AU Ramanathan, RK Fakih, M Mani, S Deutsch, M Perez, RP Ritter, MA Eiseman, JL Ivy, SP Trump, DL Belani, CP Parise, RA Potter, DM Egorin, MJ AF Ramanathan, RK Fakih, M Mani, S Deutsch, M Perez, RP Ritter, MA Eiseman, JL Ivy, SP Trump, DL Belani, CP Parise, RA Potter, DM Egorin, MJ TI Phase I and pharmacokinetic study of the novel redox-active agent, motexafin gadolinium, with concurrent radiation therapy in patients with locally advanced pancreatic or biliary cancers SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE phase I study; motexafin gadolinium; radiation therapy; pancreatic cancer ID WHOLE-BRAIN RADIATION; RANDOMIZED-TRIAL; DOSE-ESCALATION; METASTASES; GEMCITABINE; TEXAPHYRIN; PACLITAXEL; SENSITIZER; CARCINOMA; ENHANCER AB Purpose: To determine the maximum tolerated dose and dose-limiting toxicity (DLT) of the novel anticancer agent, motexafin gadolinium (MGd), administered concurrently with radiation therapy (RT) in patients with locally advanced pancreatic or biliary tumors. The pharmacokinetics of MGd were also evaluated. Methods: Cohorts of three to six patients were treated with escalating doses of MGd, administered three times per week for a total of 16 doses concurrent with RT. The dose of RT was fixed at 5,040 cGy, and given in 28 fractions, from Monday to Friday of every week. Plasma MGd concentrations were measured by high performance liquid chromatography. Results: Eight patients were treated at dose level 1 (2.9 mg/kg), with one DLT (grade 3 fever). Three patients were treated at dose level 2 (3.6 mg/kg), and two DLTs were noted. One DLT was grade 3 nausea and vomiting (N/V), and the other was grade 3 skin toxicity. The most common toxicity was N/V. There were no objective responses. The median survival was 6 months. The MGd plasma concentration versus time profile in each patient was best fit by a two-compartment, open, linear model. There was minimal accumulation of MGd in plasma with the three-times/week dosing schedule. Simulation of the time course of MGd in the peripheral compartment indicated that maximal MGd concentrations of 1-2 mu mol/kg occurred between 4 and 6 h after MGd infusion. Conclusion: Dose level 1 (2.9 mg/kg of MGd) is the recommended dose for combination with (RT) in phase II studies for locally advanced pancreatic and biliary cancers. Patient tolerance might be improved by modification of the RT schedule and antiemetic prophylaxis. C1 Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. Univ Chicago, Sch Med, Dept Med, Div Hematol Oncol, Chicago, IL 60637 USA. Univ Pittsburgh, Med Ctr, Dept Radiat Oncol, Pittsburgh, PA 15213 USA. Dartmouth Coll, Hitchcock Med Ctr, Norris Cotton Canc Ctr, Mol Therapeut Res Programme, Lebanon, NH 03756 USA. Univ Wisconsin, Sch Med, Dept Human Oncol, Madison, WI 53792 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15213 USA. NCI, Investigat Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Ctr, Bethesda, MD 20892 USA. Univ Pittsburgh, Inst Canc, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Inst Canc, Biostat Facil, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15213 USA. Montefiore Med Ctr, Bronx, NY 10461 USA. RP Ramanathan, RK (reprint author), UPMC Canc Pavil 562,5150 Ctr Ave, Pittsburgh, PA 15232 USA. EM ramanathanrk@upmc.edu RI Perez, Raymond/R-6159-2016; OI Perez, Raymond/0000-0002-7432-2411; Belani, Chandra/0000-0001-5049-5329 FU NCI NIH HHS [U01-CA69855, P30CA47904, U01-CA069852-11, U01-CA62491, U01 CA062491, P30CA23108]; NCRR NIH HHS [5M01 RR 00056] NR 28 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 2006 VL 57 IS 4 BP 465 EP 474 DI 10.1007/s00280-005-0071-y PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 001VW UT WOS:000234571800007 PM 16133531 ER PT J AU Vadaparampil, ST Wideroff, L Breen, N Trapido, E AF Vadaparampil, ST Wideroff, L Breen, N Trapido, E TI The impact of acculturation on awareness of genetic testing for increased cancer risk among Hispanics in the year 2000 National Health Interview Survey SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENERAL-POPULATION; MOLECULAR ANALYSIS; FAMILY-HISTORY; SPANISH BREAST; BRCA1 GENE; MUTATIONS; COMMUNICATION; KNOWLEDGE; LATINOS; CARE AB Previous studies suggest disparities in use of preventive cancer services among U.S. Hispanics are partly explained by knowledge and access factors. One area of emerging interest is uptake of genetic counseling and testing services by underserved populations. This study aims to estimate the percentage of Hispanics in five ethnic subgroups who are aware of genetic testing for inherited cancer risk, and to assess the influence of acculturation factors primarily related to language on test awareness. Weighted data from 4,313 Hispanic respondents (age > 25 years) in the year 2000 National Health Interview Survey were analyzed. Overall, 20.6% of Hispanics had heard of genetic testing for cancer risk, with percentages highest among Puerto Ricans (27.3%) and lowest among Mexicans (14.3%). Completing the interview in Spanish and English [odds ratio (OR), 0.52; 95% confidence interval (95% CI), 0.35-0.781, or only Spanish (OR, 0.60; 95% CI, 0.42-0.86), was inversely associated with test awareness (reference group, only English). Having an intermediate (OR, 0.66; 95% CI, 0.48-0.90) or low (OR, 0.63; 95% CI, 0.39-1.01) level of English language preference was also inversely associated (reference, high level) whereas being born outside the United States was weakly associated (OR, 0.80; 95% CI, 0.57-1.11). Estimates were adjusted for age, education, ethnicity, parents' cancer history, health care access, and selected health behaviors and beliefs. Results of this national survey indicate that acculturation factors related to language may affect cancer genetic test awareness in Hispanics. These factors must be taken into account when informing individuals about the role of genetics in cancer risk and providing cancer genetic health services. C1 MRC, CANCONT, Tampa, FL 33612 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Hlth Outcomes & Behav Program, Tampa, FL USA. Univ S Florida, Coll Med, Dept Interdisciplinary Oncol, Tampa, FL USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Epidemiol & Genet Res Program, Bethesda, MD 20892 USA. RP Vadaparampil, ST (reprint author), MRC, CANCONT, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM vadapast@moffitt.usf.edu RI Hernandez, Jessica/G-6527-2011 NR 46 TC 32 Z9 32 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 2006 VL 15 IS 4 BP 618 EP 623 DI 10.1158/1055-9965.EPI-05-0378 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 036BF UT WOS:000237045100005 PM 16614100 ER PT J AU Clarke, CA Undurraga, DM Harasty, PJ Glaser, SL Morton, LM Holly, EA AF Clarke, CA Undurraga, DM Harasty, PJ Glaser, SL Morton, LM Holly, EA TI Changes in cancer registry coding for lymphoma subtypes: Reliability over time and relevance for surveillance and study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NON-HODGKINS-LYMPHOMA; FRANCISCO BAY AREA; SAN-FRANCISCO; HOMOSEXUAL MEN; UNITED-STATES; CLASSIFICATION; RISK; CALIFORNIA; ALLERGIES; HISTORY AB Because lymphoma comprises numerous histologic subtypes, understanding the reasons for ongoing increases in its incidence requires surveillance and etiologic study of these subtypes. However, this research has been hindered by many coexisting classification schemes. The Revised European American classification of Lymphoid Neoplasms (REAL)/WHO system developed in 1994 and now used in clinical settings was not incorporated into the International Classification of Diseases-Oncology (ICD-O), used by cancer registries, until the release of the third edition (ICD-O-3) in 2001. Studies including patients diagnosed before 2001 may have codes from earlier ICD-O versions that must be converted to ICD-O-3 and have higher proportions of unclassified (e.g., lymphoma and not otherwise specified) cases. To better understand (a) the agreement of computer-converted ICD-O-3 codes to ICD-O-3 codes generated directly from diagnostic pathology reports and W the reproducibility of unclassified status, we reviewed a population-based series of diagnostic pathology reports for lymphoma patients diagnosed before (1988-1994; n = 1,493) and after (1998-2000; n = 1,527) the REAL/ WHO scheme was introduced. Overall, computer- and coder-assigned ICD-O-3 codes agreed for 77% of patients in both groups and improved slightly (82%) when codes were grouped. The most common lymphoma subtypes, diffuse large B cell and follicular, had relatively good reliability (84-89%) throughout the study period. T-cell and natural killer cell lymphomas had worse agreement than B-cell lymphomas, even when grouped. Many (42-43%) lymphomas reported as unclassifiable could be assigned a subtype upon pathology report review. These findings suggest that the study of lymphoma subtypes could be improved by (a) use of more standardized terminology in pathology reports, (b) grouping individual ICD-O-3 codes to reduce misclassification bias, and (c) routine secondary editing of unclassified lymphomas by central cancer registries. C1 No Calif Canc Ctr, Fremont, CA 94538 USA. NCI, NIH, Dept Hlth & Human Serv, Rockville, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Clarke, CA (reprint author), No Calif Canc Ctr, 2201 Walnut Ave 300, Fremont, CA 94538 USA. EM tina@nccc.org RI Morton, Lindsay/B-5234-2015 OI Morton, Lindsay/0000-0001-9767-2310 FU NCI NIH HHS [CA45614, CA66529, CA89745, N01-CN-65107] NR 29 TC 59 Z9 59 U1 0 U2 0 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 2006 VL 15 IS 4 BP 630 EP 638 DI 10.1158/1055-9965.EP1-05-0549 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 036BF UT WOS:000237045100007 PM 16614102 ER PT J AU Petersen, GM de Andrade, M Goggins, M Hruban, RH Bondy, M Korczak, JF Gallinger, S Lynch, HT Syngal, S Rabe, KG Seminara, D Kiein, AP AF Petersen, GM de Andrade, M Goggins, M Hruban, RH Bondy, M Korczak, JF Gallinger, S Lynch, HT Syngal, S Rabe, KG Seminara, D Kiein, AP TI Pancreatic cancer genetic epidemiology consortium SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RISK-FACTORS; HEREDITARY PANCREATITIS; SUSCEPTIBILITY LOCUS; COLORECTAL-CANCER; BRCA2 MUTATIONS; FAMILY-HISTORY; CARCINOMA; ADENOCARCINOMA; KINDREDS; ONSET AB We have organized the Pancreatic Cancer Genetic Epidemiology (PACGENE) Consortium to identify susceptibility genes in familial pancreatic cancer (FPC). The Consortium comprises seven data collection centers, a statistical genetics core, and a pathology/archival genotyping core. We recruit kindreds containing two or more affected blood relatives ascertained through incident pancreatic adenocarcinoma cases, physician referrals, and/or through Internet recruitment. Accrual to a database containing core clinical, demographic, lifestyle, and family history information from questionnaires is ongoing, along with biospecimen collection. To date, 13,147 patients have been screened for family history, of whom 476 (50% male) probands and 1,912 of their adult (99% unaffected) relatives have been enrolled. Of these, 379 kindreds meet criteria for FPC, having at least two first-degree relatives with pancreatic cancer. Cumulative incidence curves using available age of diagnosis (onset) among and affected relatives were compared with those for incident pancreatic cancer cases reported to 13 U.S. Surveillance Epidemiology and End Results (SEER) sites from 1973 to 2000 (N = 72,700). The mean age +/- SD at diagnosis among 466 PACGENE probands and 670 affected relatives was 64.1 +/- 11.8 and was 65.4 +/- 11.6 for the subset of 369 FPC probands and 429 relatives. Both samples were significantly younger than the mean age at diagnosis in the SEER population (70.0 +/- 12.1 years; differences in curves versus SEER, P < 0.001). Age at diagnosis (excluding probands) in FPC kindreds does not decrease with increasing number of affected individuals. In our sample, younger age at diagnosis was observed whether we grouped probands by recruitment sites that predominantly recruited through high-risk referrals, or through screening all pancreatic cancer patients for family history. Linkage studies are ongoing. The PACGENE Consortium will be a valuable family-based resource that will greatly enhance genetic epidemiology research in pancreatic cancer. C1 Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. Johns Hopkins Univ, Sol Goldman Pancreat Res Ctr, Baltimore, MD USA. MD Anderson Canc Ctr, Houston, TX 77030 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Creighton Univ, Omaha, NE 68178 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. RP Petersen, GM (reprint author), Mayo Clin, Coll Med, Dept Hlth Sci Res, 200 1st St SW, Rochester, MN 55905 USA. EM peterg@mayo.edu RI Gallinger, Steven/E-4575-2013 FU NCI NIH HHS [P50 CA102701, R01 CA097075, R01 CA97075] NR 47 TC 72 Z9 75 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 2006 VL 15 IS 4 BP 704 EP 710 DI 10.1158/1055-9965.EPl-05-0734 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 036BF UT WOS:000237045100017 PM 16614112 ER PT J AU McQueen, A Vernon, SW Meissner, HI Klabunde, CN Rakowski, W AF McQueen, A Vernon, SW Meissner, HI Klabunde, CN Rakowski, W TI Are there gender differences in colorectal cancer test use prevalence and correlates? SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HEALTH INTERVIEW SURVEY; PSYCHOLOGICAL DISTRESS; SCREENING SCALES; UNITED-STATES; POPULATION; OLDER; PREDICTORS; BEHAVIOR; ADULTS; WOMEN AB Despite evidence that screening tests reduce colorectal cancer incidence and mortality, screening prevalence is low. Gender differences in test uptake have been reported, but few studies examine correlates of test use by gender. Differences, if present, may inform strategies to increase test use. We examined gender differences in the prevalence and correlates of colorectal cancer test use [fecal occult blood test (FOBT) and endoscopy] using data from the 2002 to 2003 Health Information National Trends Survey. Male (n = 999) and female (n = 1687) respondents ages >= 50 years, without a personal history of colorectal cancer, were interviewed by telephone. Age-adjusted prevalence rates were reported for lifetime, recent, and repeat use by gender and test type. Multivariable logistic regression analyses were used to identify correlates of test use stratified by gender and colorectal cancer test type. More females reported only using FOBT in lifetime and in the past year, whereas more males reported repeat endoscopy use. The use of other tests or combinations of tests did not differ by gender. Consistent positive correlates of colorectal cancer test use for both genders included age, recent physician visits, recent breast or prostate cancer screening, and knowledge of test-specific screening intervals. Correlates that differed by gender included comparative perceived risk, belief that colorectal cancer testing was too expensive, fear of finding colorectal cancer if tested, and attention to and trust in media sources of health information. Such differences, if confirmed in future studies, may inform the use of gender-specific intervention strategies or messages to increase colorectal cancer test use. C1 Univ Texas, Sch Publ Hlth, Ctr Hlth Promot & Prevent Res, Houston, TX 77030 USA. NCI, Behav Res Program, Rockville, MD USA. NCI, Appl Res Program, Bethesda, MD 20892 USA. Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. RP McQueen, A (reprint author), Univ Texas, Sch Publ Hlth, Ctr Hlth Promot & Prevent Res, 7000 Fannin,Suite 2568, Houston, TX 77030 USA. EM Amy.McQueen@uth.tmc.edu FU NCI NIH HHS [R01CA097263, K05CA090485, R21CA089475, R01CA076330, 2R25CA57712-11] NR 43 TC 51 Z9 51 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 2006 VL 15 IS 4 BP 782 EP 791 DI 10.1158/1055-9965.EPI-05-0629 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 036BF UT WOS:000237045100029 PM 16614124 ER PT J AU Irby, K Anderson, WF Henson, DE Devesa, SS AF Irby, K Anderson, WF Henson, DE Devesa, SS TI Emerging and widening colorectal carcinoma disparities between blacks and whites in the United States (1975-2002) SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID IOWA WOMENS HEALTH; DIABETES-MELLITUS; COLON-CANCER; HORMONE-THERAPY; RISK; SUBSITE; RATES; STAGE; EXPRESSION; SURVIVAL AB Background: Colorectal carcinoma (CRC) is the fourth most common cancer diagnosed and the second most common cause of cancer death in the U.S. Incidence and mortality rates have decreased since the mid-1980s, although more among Whites than Blacks. Methods: To determine if these racial differences were changing over time, we examined CRC rates in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program (1975-2002). Rates were stratified by gender, race, anatomic subsite, historic stage, and grade. Results: CRC rates were higher among men than women and higher among Blacks than Whites, with Black men having the highest rates during the latter years. Prior to the mid-1980s, male CRC rates were actually higher among Whites than Blacks; after which there was ethnic crossover with Black rates higher than White rates, and the gaps are widening. Proximal and transverse CRCs were more common and rectal cancers were less common among Blacks than Whites. Over time, rates for localized and regional stages increased among Blacks and decreased among Whites. Rates for distant stages declined for both racial groups, although less among Blacks. Black-to-White rate ratio for distant stage was similar to 1.30. Notably, Blacks compared with Whites had lower grade tumors, despite higher stages and mortality rates. Conclusions: CRC racial disparities have emerged and widened for three decades. These temporal trends probably reflect complicated racial differences between screening practice patterns and etiologic factors. C1 NCI, Descript Studies Sect, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet,NIH, Rockville, MD 20852 USA. George Washington Univ, Sch Publ Hlth & Hlth Sci, Washington, DC USA. George Washington Univ, Inst Canc, Off Canc Prevent & Control, Washington, DC 20052 USA. RP Anderson, WF (reprint author), NCI, Descript Studies Sect, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet,NIH, BB EPS,Room 8036,6120 Execut Blvd, Rockville, MD 20852 USA. EM wanderso@mail.nih.gov FU Intramural NIH HHS NR 54 TC 70 Z9 71 U1 2 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 2006 VL 15 IS 4 BP 792 EP 797 DI 10.1158/1055-9965.EPI-05-0879 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 036BF UT WOS:000237045100030 PM 16614125 ER PT J AU Chuang, EY Chen, X Tsai, MH Yan, HL Li, CY Mitchell, JB Nagasawa, H Wilson, PF Peng, YL Fitzek, MM Bedford, JS Little, JB AF Chuang, EY Chen, X Tsai, MH Yan, HL Li, CY Mitchell, JB Nagasawa, H Wilson, PF Peng, YL Fitzek, MM Bedford, JS Little, JB TI Abnormal gene expression profiles in unaffected parents of patients with hereditary-type retinoblastoma SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; BREAST-CANCER; PREDICT SURVIVAL; MUTATIONS; RADIATION; SENSITIVITY; CHILDREN; CHEMOTHERAPY; FIBROBLASTS; MORTALITY AB The hereditary form of retinoblastoma (Rb) is associated with a germ line mutation in one RB allele and is characterized by the occurrence of multiple, bilateral Rh tumors and a predisposition to the development of second cancers. In an earlier study, we observed an unexpected hypersensitivity to ionizing radiation in skin fibroblasts derived from unaffected parents of children with hereditary Rb. In at least four of these five families, there was no family history of Rb, indicating a new germ line mutation. We hypothesize that the increased parental cell sensitivity to radiation may reflect the presence of an as yet unrecognized genetic abnormality occurring in one or both parents of children with Rb. In the present study, we use DNA microarray technology to determine whether differences in gene expression profiles occurred in the unaffected parents of patients with hereditary Rb relative to normal individuals. Microarray analyses were validated by quantitative reverse transcription-PCR measurements. A distinct difference was observed in the patterns of gene expression between unaffected Rh parents and normal controls. By use of the prediction analysis for microarrays and principal component analysis methodologies, significant differences between the two groups were identified when as few as nine genes were analyzed. Further study of this phenomenon may offer a new insight into the genetic mechanisms of Rb and perhaps more broadly in cancer biology. C1 Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. NCI, Canc Res Ctr, Radiat Biol Branch, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Oncol Branch, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Frederick, MD USA. Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. Tufts Univ, New England Med Ctr, Dept Radiat Oncol, Boston, MA 02111 USA. Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. Natl Taiwan Univ, Dept Elect Engn, Taipei 10764, Taiwan. RP Bedford, JS (reprint author), Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. EM joel.bedford@colostate.edu RI Li, Chuan-Yuan/H-4148-2013 FU NCI NIH HHS [CA 81512] NR 36 TC 9 Z9 9 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 1 PY 2006 VL 66 IS 7 BP 3428 EP 3433 DI 10.1158/0008-5472.CAN-05-2847 PG 6 WC Oncology SC Oncology GA 030TO UT WOS:000236657800017 PM 16585164 ER PT J AU Smolen, GA Muir, B Mohapatra, G Barmettler, A Kim, WJ Rivera, MN Haserlat, SM Okimoto, RA Kwak, E Dahiya, S Garber, JE Bell, DW Sgroi, DC Chin, L Deng, CX Haber, DA AF Smolen, GA Muir, B Mohapatra, G Barmettler, A Kim, WJ Rivera, MN Haserlat, SM Okimoto, RA Kwak, E Dahiya, S Garber, JE Bell, DW Sgroi, DC Chin, L Deng, CX Haber, DA TI Frequent met oncogene amplification in a Brca1/Trp53 mouse model of mammary tumorigenesis SO CANCER RESEARCH LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; TRANSGENIC MICE; BREAST-CANCER; PROTOONCOGENE; METASTASIS; BRCA1; GENE; CARCINOMAS; MICROARRAY; EXPRESSION AB in a screen for gene copy number alterations in mouse mammary tumors initiated by loss of the Brea1 and Trp53 genes, we observed that the majority (11 of 15; 73%) had high-level amplification of wild-type Met, encoding a growth factor receptor implicated in tumor progression. Met amplification was localized to unstable double minute chromosomes and was uniquely found in mouse breast tumors driven by loss of Brca1 and Trp53. Whereas analogous MET amplification was not found in human breast cancers, the identification of a dominant somatic genetic lesion in the Brca1/Trp53 mouse model suggests that recurrent secondary hits may also exist in BRCA1-initiated human breast cancer. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Mol Pathol Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Haber, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu RI deng, chuxia/N-6713-2016 FU NCI NIH HHS [F32 CA 117737]; PHS HHS [P01 95281] NR 20 TC 25 Z9 25 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 2006 VL 66 IS 7 BP 3452 EP 3455 DI 10.1158/0008-5472.CAN-05-4181 PG 4 WC Oncology SC Oncology GA 030TO UT WOS:000236657800020 PM 16585167 ER PT J AU Huh, JI Calvo, A Charles, R Green, JE AF Huh, JI Calvo, A Charles, R Green, JE TI Distinct tumor stage-specific inhibitory effects of 2-methoxyestradiol in a breast cancer mouse model associated with Id-1 expression SO CANCER RESEARCH LA English DT Article ID ENDOGENOUS ESTROGEN METABOLITE; GROWTH IN-VITRO; PROSTATE-CANCER; RECEPTOR-ALPHA; CELLS; ANGIOGENESIS; APOPTOSIS; MICE; VIVO; CARCINOGENESIS AB 2-Methoxyestradiol (2ME(2)), a metabolite of 17-beta-estradiol, inhibits angiogenesis and has additional antitumor activities. We have analyzed the tumor stage-specific effects of 2ME(2) ill the C3(1)/Tag transgenic mouse model for breast cancer, which spontaneously develops estrogen receptor-negative mammary tumors following a predictable progression of lesion formation. When given either as a therapeutic agent in established tumors (late intervention study) or in mice with pre-invasive mammary lesions (early intervention study), tumor growth was reduced by 60% compared with untreated controls and was associated with an induction of apoptosis. In prevention study, a significant reduction in mammary. a intraepithelial neoplasia (MIN) lesions was observed in animals beginning treatment at 6 weeks of age, before the appearance of histopathologic abnormalities. However, although 2ME2 reduced the number of MIN lesions in the prevention study, a paradoxical increase in tumor multiplicity and growth rate was observed. This was associated with unusual cystic tumor formation, in which significant central necrosis was observed, surrounded by ail outer region of proliferative tumor cell growth. The characteristics of the cystic tumor formation in mice treated with 2ME(2) at early ages are consistent with ail impaired angiogenic response as observed in mice deficient for inhibitor of differentiation (Id-1). We further show that Id-1 expression is negatively regulated by 2ME(2), which may be an additional mechanism for the antiangiogenic effect of 2ME(2). Although 2ME(2) significantly reduced tumor growth at late stages, these results also suggest that altered tumor morphology and accelerated tumor growth may occur if 2ME2 is administered in a prevention setting for prolonged periods. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Green, JE (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Room C629,Bldg 41,41 Medlars Dr, Bethesda, MD 20892 USA. EM jegreen@nih.gov NR 36 TC 12 Z9 12 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 2006 VL 66 IS 7 BP 3495 EP 3503 DI 10.1158/0008-5472.CAN-04-2372 PG 9 WC Oncology SC Oncology GA 030TO UT WOS:000236657800026 PM 16585173 ER PT J AU Terabe, M Khanna, C Bose, S Melchionda, F Mendoza, A Mackall, CL Helman, LJ Berzofsky, JA AF Terabe, M Khanna, C Bose, S Melchionda, F Mendoza, A Mackall, CL Helman, LJ Berzofsky, JA TI CD1d-restricted natural killer T cells can down-regulate tumor immunosurveillance independent of interleukin-4 receptor-signal transducer and activator of transcription 6 or transforming growth factor-beta SO CANCER RESEARCH LA English DT Article ID NKT CELLS; MONOCLONAL-ANTIBODIES; OSTEOSARCOMA; ESCAPE; EXPRESSION; IMMUNITY; VARIANTS; MODEL; IL-13; MICE AB It has been shown previously that the suppression of tumor immunosurveillance may be a mechanism by which tumors resist immune detection and elimination. In this study, we evaluated the role of the immunoregulatory natural killer T (NKT) cells in the biology of immunosurveillance of osteosarcoma. The K7M2 mouse osteosarcoma cell line was implanted orthotopically into wild-type and NKT cell-deficient CD1d knockout (KO) BALB/c mice, anti mice were monitored for growth of primary tumors. Further, we examined the role of CD4(+) and/or CD8(+) cells by depleting the cells in vivo and measuring CTL activity in. vitro. We also asked the role of interleukin (IL)-4 receptor alpha (IL-4R alpha)-signal transducer and activator of transcription 6 (STAT6) signaling, including IL-13, and transforming growth factor beta (TGF-beta) by using gene-V disrupted mice or treating mice with cytokine antagonists. We were surprised to find a high rate of rejection of osteosarcoma primary tumors in 88% (14 of 16) of CD1d KO mice compared with syngeneic wild-type BALB/c mice that showed rejection of tumor in < 24% of mice. Further studies suggested that. the rejection of tumor in CD1d KO mice was dependent on CD8(+) lymphocytes. Distinct from other murine tumor models, the negative regulation induced by CD1d-restricted NKT cells was not dependent on IL-4R alpha-STAT6 signaling, including 11,43, or on TGF-beta. These data suggest that a novel Mid-restricted NKT cell-mediated mechanism for tumor immunosupppression is active in the K7M2 osteosarcoma model kind that NKT cells can regulate immunosurveillance through more than one pathway. C1 NCI, Vaccine Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Terabe, M (reprint author), NCI, Vaccine Branch, Canc Res Ctr, NIH, Bldg 10,Room 6B12,9000 Rockville Pike, Bethesda, MD 20892 USA. EM terabe@mail.nih.gov; khannac@mail.nih.gov FU Intramural NIH HHS NR 40 TC 38 Z9 39 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 2006 VL 66 IS 7 BP 3869 EP 3875 DI 10.1158/0008-5472.CAN-05-3421 PG 7 WC Oncology SC Oncology GA 030TO UT WOS:000236657800068 PM 16585215 ER PT J AU Simmons, DP Peach, ML Friedman, JR Green, MMB Nicklaus, MC De Luca, LM AF Simmons, DP Peach, ML Friedman, JR Green, MMB Nicklaus, MC De Luca, LM TI Evidence that sequence homologous region in LRAT-like proteins possesses anti-proliferative activity and DNA binding properties: translational implications and mechanism of action SO CARCINOGENESIS LA English DT Article ID LECITHIN-RETINOL ACYLTRANSFERASE; TUMOR-SUPPRESSOR; BIOLOGICAL-ACTIVITY; GROWTH-INHIBITION; CANCER-CELLS; ACID; RECEPTOR; GENE; PEPTIDES; ESTERIFICATION AB LRAT (lecithin:retinol acyltransferase), an enzyme whose levels are modulated during malignant conversion, has been reported as the founder member of a new LRAT-like family that includes tumor suppressors TIG-3(1-164) and Ha-Rev107(1-162). The mechanisms that link these three proteins to carcinogenesis as well as the significance of a reported shared sequence homologous region remain unclear. This begs the question if the tumor suppressors possess enzyme properties and/or if the LRAT enzyme possesses tumor suppressor properties. We use the reported homologous region as a first approach to address the question from the perspective that all three proteins can possess tumor suppressor properties. We postulated that the homologous sequence harbors an anti-proliferation domain within the full-length proteins and that dodecapeptides of this sequence possess anti-proliferative activity. We report that H-TIG-3(111-123), H-Ha-Rev107-1(111-123) and H-LRAT(160-171:C168L) exhibited in vitro growth inhibitory activity in a human cutaneous melanoma (HCM) model and affected tumor growth in a nude mouse model. Further, in peptide-sensitive HCM cells, these peptides crossed the plasma membrane and localized to the nucleus, where they could bind and activate promoters of transcription factors involved in G1 -> S transition. Moreover, peptide-induced abrogation of cyclin dependent kinase-2 expression was concomitant with sub-cellular re-distribution of cyclins E and A. Indeed, the sequence homologous region within each full-length wild-type protein as well as the growth inhibitory peptides can form alpha helices, a likely configuration for binding to DNA. This is the first report that this sequence homologous region (AA(111-123)) within these LRAT-like proteins harbors an anti-proliferative domain with DNA binding properties. Sequences from this sequence homologous region can be used as templates for anti-tumor drug design and as probes to investigate disease-related mechanisms and structure-activity relationships of the full-length proteins, TIG-3(1-164), Ha-Rev107(1-162) and LRAT(160-171). C1 NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP De Luca, LM (reprint author), NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. EM delucal@mail.nih.gov RI Nicklaus, Marc/N-4183-2014; OI Nicklaus, Marc/0000-0002-4775-7030 FU PHS HHS [N01-C0-12400] NR 47 TC 12 Z9 13 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2006 VL 27 IS 4 BP 693 EP 707 DI 10.1093/carcin/bgi235 PG 15 WC Oncology SC Oncology GA 025GF UT WOS:000236252600003 PM 16234259 ER PT J AU Kim, S Vermeulen, R Waidyanatha, S Johnson, BA Lan, Q Rothman, N Smith, MT Zhang, LP Li, GL Shen, M Yin, SN Rappaport, SM AF Kim, S Vermeulen, R Waidyanatha, S Johnson, BA Lan, Q Rothman, N Smith, MT Zhang, LP Li, GL Shen, M Yin, SN Rappaport, SM TI Using urinary biomarkers to elucidate dose-related patterns of human benzene metabolism SO CARCINOGENESIS LA English DT Article ID S-PHENYLMERCAPTURIC ACID; VOLATILE ORGANIC-COMPOUNDS; TRANS,TRANS-MUCONIC ACID; PERSONAL EXPOSURE; BONE-MARROW; OCCUPATIONAL EXPOSURE; UNEXPOSED SUBJECTS; ALBUMIN ADDUCTS; MUCONIC ACID; F344 RATS AB Although the toxicity of benzene has been linked to its metabolism, the dose-related production of metabolites is not well understood in humans, particularly at low levels of exposure. We investigated unmetabolized benzene in urine (UBz) and all major urinary metabolites [phenol (PH), E,E-muconic acid (MA), hydroquinone (HQ) and catechol (CA)] as well as the minor metabolite, S-phenylmercapturic acid (SPMA), in 250 benzene-exposed workers and 139 control workers in Tianjin, China. Median levels of benzene exposure were similar to 1.2 p.p.m. for exposed workers (interquartile range: 0.53-3.34 p.p.m.) and 0.004 p.p.m. for control workers (interquartile range: 0.002-0.007 p.p.m.). (Exposures of control workers to benzene were predicted from levels of benzene in their urine.) Metabolite production was investigated among groups of 30 workers aggregated by their benzene exposures. We found that the urine concentration of each metabolite was consistently elevated when the group's median benzene exposure was at or above the following air concentrations: 0.2 p.p.m. for MA and SPMA, 0.5 p.p.m. for PH and HQ, and 2 p.p.m. for CA. Dose-related production of the four major metabolites and total metabolites (mu mol/l/p.p.m. benzene) declined between 2.5 and 26-fold as group median benzene exposures increased between 0.027 and 15.4 p.p.m. Reductions in metabolite production were most pronounced for CA and PH < 1 p.p.m., indicating that metabolism favored production of the toxic metabolites, HQ and MA, at low exposures. C1 Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA. NCI, NIH, DHHS, Bethesda, MD 20892 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. RP Rappaport, SM (reprint author), Univ N Carolina, Sch Publ Hlth, CB 7431, Chapel Hill, NC 27599 USA. EM stephen_rappaport@unc.edu RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU Intramural NIH HHS; NIEHS NIH HHS [P30ES01896, P30ES10126, P42ES04705, P42ES05948, R01ES06721] NR 56 TC 60 Z9 62 U1 1 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 2006 VL 27 IS 4 BP 772 EP 781 DI 10.1093/carcin/bgi297 PG 10 WC Oncology SC Oncology GA 025GF UT WOS:000236252600011 PM 16339183 ER PT J AU Raval, AN Karmarkar, PV Guttman, MA Ozturk, C DeSilva, R Aviles, RJ Wright, VJ Schenke, WH Atalar, E McVeigh, ER Lederman, RJ AF Raval, AN Karmarkar, PV Guttman, MA Ozturk, C DeSilva, R Aviles, RJ Wright, VJ Schenke, WH Atalar, E McVeigh, ER Lederman, RJ TI Real-time MRI guided atrial septal puncture and balloon septostomy in swine SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE atrial septal puncture; congenital heart disease; real-time magnetic resonance imaging; interventional MRI; magnetic resonance ID LEFT-HEART CATHETERIZATION; MAGNETIC-RESONANCE FLUOROSCOPY; VENA-CAVA FILTER; CARDIAC-CATHETERIZATION; ANIMAL-MODEL; STENT PLACEMENT; INTERVENTIONAL CATHETERIZATION; TRANSSEPTAL CATHETERIZATION; TRANSCATHETER IMPLANTATION; ECHOCARDIOGRAPHIC GUIDANCE AB Cardiac perforation during atrial septal puncture (ASP) might be avoided by improved image guidance. X-ray fluoroscopy (XRF), which guides ASP, visualizes tissue poorly and does not convey depth information. Ultrasound is limited by device shadows and constrained imaging windows. Alternatively, real-time MRI (rtMRI) provides excellent tissue contrast in any orientation and may enable ASP and balloon atrial septostomy (BAS) in swine. Custom MRI catheters incorporated "active" (receiver antenna) and "passive" (iron or gadolinium) elements. Wholly rtMRI-guided transfemoral ASP and BAS were performed in 10 swine in a 1.5T interventional suite. Hemodynamic results were measured with catheters and velocity encoded MRI. Successful ASP was performed in all 10 animals. Necropsy confirmed septostomy confined within the fossa ovalis in all. BAS was successful in 9/10 animals. Antenna failure in a re-used needle led to inadvertent vena cava tear prior to BAS in 1 animal. ASP in the same animal was easily performed using a new needle. rtMRI illustrated clear device-tissue-lumen relationships in multiple orientations, and facilitated simple ASP and BAS. The mean procedure time was 19 +/- 10 minutes. Septostomy achieved a mean left to right shunt ratio of 1.3:1 in these healthy animals. Interactive rtMRI permits rapid transcatheter ASP and BAS in swine. Further technical development may enable novel applications. Published 2006 Wiley-Liss, inc. C1 NHLBI, Cardiovasc Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. NHLBI, Cardiac Energet Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Lederman, RJ (reprint author), NHLBI, Cardiovasc Branch, Div Intramural Res, NIH, Bldg 10,Room 2C713,MSC 1538, Bethesda, MD 20892 USA. EM lederman@nih.gov RI Atalar, Ergin/D-3184-2012; Ozturk, Cengizhan/A-6177-2016; OI Atalar, Ergin/0000-0002-6874-6103; Ozturk, Cengizhan/0000-0002-6966-0774; lederman, robert/0000-0003-1202-6673 FU Intramural NIH HHS [Z01 HL004608-08] NR 61 TC 18 Z9 18 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD APR PY 2006 VL 67 IS 4 BP 637 EP 643 DI 10.1002/ccd.20579 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 031SL UT WOS:000236724200023 PM 16532499 ER PT J AU Sanchez, JF Crooks, DR Lee, CT Schoen, CJ Amable, R Zeng, XM Florival-Victor, T Morales, N Truckenmiller, ME Smith, DR Freed, WJ AF Sanchez, JF Crooks, DR Lee, CT Schoen, CJ Amable, R Zeng, XM Florival-Victor, T Morales, N Truckenmiller, ME Smith, DR Freed, WJ TI GABAergic lineage differentiation of AF5 neural progenitor cells in vitro SO CELL AND TISSUE RESEARCH LA English DT Article DE neuronal development; glutamic acid decarboxylase; gamma-aminobutyric acid; differentiation; immortal cell line; rat ID GLUTAMIC-ACID DECARBOXYLASE; SV40 LARGE T; REGION-SPECIFIC DIFFERENTIATION; NEURONS; GABA; ANTIGEN; EXPRESSION; SYSTEM; PITX2; GAD AB We have previously described an immortal rat central-nervous-system progenitor cell line, AF5, which is able to exit the cell cycle and assume a differentiated state with neuronal properties. The phenotypic specification of differentiated AF5 cells, however, is not known. In the present study, when induced to differentiate by serum starvation in Neurobasal medium, AF5 cells down-regulate glial fibrillary acidic protein and up-regulate expression of beta-III-tubulin, medium-molecular-weight neurofilament protein, and neuronal growth-associated protein 43. Expression of the gamma-aminobutyric acid (GABA) lineage marker, glutamic acid decarboxylase 67 (GAD67), increases during differentiation, suggesting that AF5 cells adopt a GABAergic lineage. Time-course analysis of the GABAergic neuron specification transcription factor, Pitx2, by reverse transcription/polymerase chain reaction, has shown an increase in the Pitx2 transcript 48 h after initiation of differentiation. In differentiated AF5 cells, expression of the Pitx2 target gene products GAD65 and GABA transporter-1 increases. Cellular GABA levels in differentiated AF5 cells increase by about 26-fold, and GABA release into the medium is 150-fold higher compared with that of undifferentiated cells. Therefore, AF5 cells can be induced to differentiate to a neuronal phenotype with a GABAergic lineage. C1 NIDA, Cellular Neurobiol Res Branch, IRP, Baltimore, MD 21224 USA. NIDA, Dev & Plast Sect, Cellular Neurobiol Res Branch,DHHS, IRP,NIH, Baltimore, MD USA. Univ Calif Santa Cruz, Dept Environm Toxicol, Santa Cruz, CA 95064 USA. RP Sanchez, JF (reprint author), NIDA, Cellular Neurobiol Res Branch, IRP, 333 Cassell Dr,Triad Bldg,Room 3505, Baltimore, MD 21224 USA. EM jsanchez@mail.nih.gov FU Intramural NIH HHS [Z01 DA000410-10] NR 35 TC 16 Z9 18 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD APR PY 2006 VL 324 IS 1 BP 1 EP 8 DI 10.1007/s00441-005-0094-z PG 8 WC Cell Biology SC Cell Biology GA 017TK UT WOS:000235716000001 PM 16408195 ER PT J AU Hasebe, T Hartman, R Matsuda, H Shi, YB AF Hasebe, T Hartman, R Matsuda, H Shi, YB TI Spatial and temporal expression profiles suggest the involvement of gelatinase A and membrane type 1 matrix metalloproteinase in amphibian metamorphosis SO CELL AND TISSUE RESEARCH LA English DT Article DE matrix metalloproteinases (MMPs); MMP-2 (gelatinase A, GelA); MMP-14 (membrane type 1-MMP, MT1-MMP); tissue remodeling; thyroid hormone; Xenopus laevis (Anura) ID HORMONE RESPONSE GENES; XENOPUS-LAEVIS; FROG METAMORPHOSIS; TAIL RESORPTION; CELL-MIGRATION; TADPOLE TAIL; STROMELYSIN-3; APOPTOSIS; ACTIVATION; PATTERN AB The matrix metalloproteinases (MMPs) are a family of proteases capable of degrading various components of the extracellular matrix (ECM). Among them, the membrane type MMP-1 (MT1-MMP) has been shown to participate in the activation of MMP gelatinase A (GelA), suggesting that they may function together in development and pathogenesis. Here, we have investigated the spatiotemporal expression profiles of Xenopus laevis MT1-MMP and GelA genes during thyroid-hormone-dependent metamorphosis. We have focused our studies on two organs: (1) the intestine, which undergoes first the degeneration of the tadpole epithelium through apoptosis and then the development of adult epithelium and other tissues, and (2) the tail, which completely resorbs through programmed cell death. We show that both MT1-MMP and GelA are upregulated in the intestine and tail when both organs undergo metamorphosis. Within the organs, MT1-MMP and GelA are coexpressed in the connective tissues during both natural and thyroid-hormone-induced metamorphosis. In addition, MT1-MMP (but not GelA) is also expressed in the longitudinal muscle cells of the metamorphosing intestine. These results suggest that MT1-MMP and GelA function together in the ECM degradation or remodeling associated with metamorphosis and that MT1-MMP has additional GelA-independent roles in the development of adult longitudinal muscle in the intestine. C1 NICHHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), NICHHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. EM Shi@helix.nih.gov NR 51 TC 31 Z9 32 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD APR PY 2006 VL 324 IS 1 BP 105 EP 116 DI 10.1007/s00441-005-0099-7 PG 12 WC Cell Biology SC Cell Biology GA 017TK UT WOS:000235716000011 PM 16418836 ER PT J AU Nahirney, PC Fischman, DA Wang, K AF Nahirney, PC Fischman, DA Wang, K TI Myosin flares and actin leptomeres as myofibril assembly/disassembly intermediates in sonic muscle fibers SO CELL AND TISSUE RESEARCH LA English DT Article DE sonic muscle fiber; myosin; actin; myofibrillar intermediates; midshipman fish; Porichthys notatus (Teleostei) ID FISH PORICHTHYS-NOTATUS; BINDING-PROTEIN-C; TELEOST FISH; NONMUSCLE CELLS; PURKINJE-FIBERS; THICK FILAMENTS; HEAVY-CHAIN; SECONDARY MYOTUBES; SARCOMERIC MYOSIN; MIDSHIPMAN FISH AB The sonic muscle of type 1 male midshipman fish produces loud and enduring mating calls. Each sonic muscle fiber contains a tubular contractile apparatus with radially arranged myofibrillar plates encased in a desmin-rich cytoskeleton that is anchored to broad Z bands (similar to 1.2 mu m wide). Immunomicroscopy has revealed patches of myosin-rich "flares" emanating from the contractile tubes into the peripheral sarcoplasm along the length of the fibers. These flares contain swirls of thick filaments devoid of associated thin filaments. In other regions of the sarcoplasm at the inner surface of the sarcolemma and near Z bands, abundant ladder-like leptomeres occur with rungs every 160 nm. Leptomeres consist of dense arrays of filaments (similar to 4 nm) with a structure that resembles myofibrillar Z band structure. We propose that flares and leptomeres are distinct filamentous arrays representing site-specific processing of myofibrillar components during the assembly and disassembly of the sarcomere. Recent reports that myosin assembles into filamentous aggregates before incorporating into the A band in the skeletal muscles of vertebrates and Caenorhabditis elegans suggest that sonic fibers utilize a similar pathway. Thus, sonic muscle fibers, with their tubular design and abundant sarcoplasmic space, may provide an attractive muscle model to identify myofibrillar intermediates by structural and molecular techniques. C1 NIAMSD, Muscle Proteom & Nanotechnol Sect, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Dept Cell & Dev Biol, New York, NY 10021 USA. RP Wang, K (reprint author), NIAMSD, Muscle Proteom & Nanotechnol Sect, Muscle Biol Lab, NIH, Bldg 50,Room 1140, Bethesda, MD 20892 USA. EM wangk@exchange.nih.gov FU Intramural NIH HHS NR 46 TC 2 Z9 3 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD APR PY 2006 VL 324 IS 1 BP 127 EP 138 DI 10.1007/s00441-005-0110-3 PG 12 WC Cell Biology SC Cell Biology GA 017TK UT WOS:000235716000013 PM 16425023 ER PT J AU Mendrysa, SM Perry, ME AF Mendrysa, SM Perry, ME TI Tumor suppression by p53 without accelerated aging - Just enough of a good thing? SO CELL CYCLE LA English DT Article DE tumor suppression; aging; p53; cancer therapy; chemoprevention; Mdm2 ID SMALL-MOLECULE ANTAGONISTS; IN-VIVO; EMBRYONIC LETHALITY; ACTIVATE P53; LIFE-SPAN; MICE; MDM2; SENESCENCE; CELLS; PATHWAY AB The prevalence of mutations that inactivate the p53 tumor suppressor gene in human cancers reveals the importance of p53 in preventing cancer. Recent progress has generated increased enthusiasm for re-activating p53 in tumors with mutant p53 proteins as well as for increasing p53 function in tumors expressing wild-type p53 that is inhibited in trans. However, excessive p53 activity can be detrimental to the host, potentially limiting the utility of p53 activation as a therapeutic strategy. For example, uncontrolled p53 activity is lethal to the murine embryo, and p53 has been associated with increased aging in people and mice. Here we review the literature linking p53 to aging and discuss reports demonstrating that p53 can suppress tumor formation without accelerating aging. We raise the possibility that activation of p53 remains a promising strategy for cancer chemoprevention and therapy even if, under some circumstances, p53 might accelerate aging. C1 NCI, Lab Prot Dynam & Signaling, Rockville, MD 20852 USA. Purdue Univ, Dept Basic Med Sci, W Lafayette, IN 47907 USA. RP Perry, ME (reprint author), NCI, Lab Prot Dynam & Signaling, EPN Room 5034,6130 Execut Blvd, Rockville, MD 20852 USA. EM perryma@mail.nih.gov NR 33 TC 12 Z9 12 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR 1 PY 2006 VL 5 IS 7 BP 714 EP 717 DI 10.4161/cc.5.7.2632 PG 4 WC Cell Biology SC Cell Biology GA 053CY UT WOS:000238282900011 PM 16582632 ER PT J AU Iyer, LM Babu, MM Aravind, L AF Iyer, LM Babu, MM Aravind, L TI The HIRAN domain and recruitment of chromatin remodeling and repair activities to damaged DNA SO CELL CYCLE LA English DT Article DE DNA repair; chromatin; DNA-binding domain; HIP116; RAD5; KIAA1018; SMARCA-3; TDP1; VRR-Nuc ID SECONDARY STRUCTURE PREDICTION; MULTIPLE SEQUENCE ALIGNMENT; STRAND BREAK REPAIR; BINDING PROTEINS; MOLECULAR-CLONING; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION FACTOR; DATABASE SEARCHES; CONSERVED DOMAINS; CRYSTAL-STRUCTURE AB Aided by sensitive sequence profile searches we identify a novel conserved domain in the N-terminal regions of the SWI2/SNF2 proteins typified by HIP116 and Rad5p ( hence HIP116, Rad5p N-terminal domain: HIRAN domain). We show that the HIRAN domain is found as a standalone protein in several bacteria and prophages, or fused to other catalytic domains, such as a nuclease of the restriction endonuclease fold and TDP1-like DNA phosphoesterases, in the eukaryotes. Based on a network of contextual connections in the form of domain architectures, conserved gene neighborhoods and functional interactions we predict that the HIRAN domain is likely to function as a DNA-binding domain that probably recognizes features associated with damaged DNA or stalled replication forks. It might thus act as a sensor to initiate a damaged DNA checkpoint and engage different DNA repair and chromatin remodeling or modifying activities to these sites. In evolutionary terms, the fusion of the HIRAN domain, and the functionally analogous RAD18 Zn-finger and the PARP-type Zn-finger to SWI2/SNF2 ATPases appears to have been a notable factor for recruiting these ATPases for chromatin modification and remodeling in the context of DNA repair. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A, Bethesda, MD 20894 USA. EM aravind@ncbi.nlm.nih.gov FU Intramural NIH HHS; Medical Research Council [MC_U105185859] NR 75 TC 45 Z9 45 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR 1 PY 2006 VL 5 IS 7 BP 775 EP 782 DI 10.4161/cc.5.7.2629 PG 8 WC Cell Biology SC Cell Biology GA 053CY UT WOS:000238282900020 PM 16627993 ER PT J AU Tesauro, M Thompson, WC Moss, J AF Tesauro, M Thompson, WC Moss, J TI Effect of staurosporine-induced apoptosis on endothelial nitric oxide synthase in transfected COS-7 cells and primary endothelial cells SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE eNOS; endothelial nitric oxide synthase; nitric oxide; caspases; apoptosis ID MOLECULAR-MECHANISMS; S-NITROSYLATION; CASPASES; DEATH; INHIBITION; ACTIVATION; PROTEASES; GENE AB Nitric oxide (NO) may block apoptosis by inhibiting caspases via S-nitrosylation of cysteines. Here, we investigated whether effector caspases might cleave and thereby inhibit endothelial nitric oxide synthase (eNOS). Exposure of eNOS-transfected COS-7 cells and bovine aortic endothelial cells to stauro-sporine resulted in significant loss of 135-kDa eNOS protein and activity, and appearance of a 60-kDa eNOS fragment; effects were inhibited by the general caspase inhibitor, benzyloxy-carbonyl-Val- Ala-Asp[OMe]-fluoromethyl ketone (zVAD-fmk). In eNOS-transfected COS-7 cells, staurosporine-induced activation of caspase-3 and poly(ADP-ribose) polymerase (PARP) cleavage coincided with increased eNOS degradation and decreased activity. Loss of eNOS activity was greater than the degree of proteolysis. Incubation of immunoprecipitated eNOS with caspase-3, caspase-6 or caspase-7 resulted in eNOS cleavage. Staurosporine, a general protein kinase inhibitor, also reduced phosphorylation and decreased calmodulin binding, an effect that may explain the reduction in activity. eNOS, therefore, is both an inhibitor of apoptosis and a target of apoptosis-associated proteolysis. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, 9000 Rockville Pike,Bldg 10-Room 6D03, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov NR 29 TC 17 Z9 18 U1 0 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 2006 VL 13 IS 4 BP 597 EP 606 DI 10.1038/sj.cdd.4401770 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 022FP UT WOS:000236040800006 PM 16195740 ER PT J AU Deleu, S Choi, K Pesesse, X Cho, J Sulis, ML Parsons, R Shears, SB AF Deleu, S Choi, K Pesesse, X Cho, J Sulis, ML Parsons, R Shears, SB TI Physiological levels of PTEN control the size of the cellular Ins(1,3,4,5,6)P-5 Pool SO CELLULAR SIGNALLING LA English DT Article DE inositol phosphate; PTEN; glioblastoma; MIPP; phosphatase ID INOSITOL POLYPHOSPHATE PHOSPHATASE; TUMOR-SUPPRESSOR; 1,3,4,6-TETRAKISPHOSPHATE 5-KINASE; MYOINOSITOL HEXAKISPHOSPHATE; 3-PHOSPHATASE ACTIVITY; MASS CHANGES; IN-VITRO; CELLS; EXPRESSION; PENTAKISPHOSPHATE AB To understand how a signaling molecule's activities are regulated, we need insight into the processes controlling the dynamic balance between its synthesis and degradation. For the Ins(1,3,4,5,6)P-5 signal, this information is woefully inadequate. For example, the only known cytosolic enzyme with the capacity to degrade Ins(1,3,4,5,6)P5 is the tumour-suppressor PTEN [J.J. Caffrey, T. Darden, M.R. Wenk, S.B. Shears, FEBS Lett. 499 (2001) 6 [24]], but the biological relevance has been questioned by others [E.A. Orchiston, D. Bennett, N.R. Leslie, R.G. Clarke, L. Winward, C.P. Downes, ST. Safrany, J. Biol. Chem. 279 (2004) 1116 [1]]. The current study emphasizes the role of physiological levels of PTEN in Ins(1,3,4,5,6)P5 homeostasis. We employed two cell models. First, we used a human U87MG glioblastoma PTEN-null cell line that hosts an ecdysone-inducible PTEN expression system. Second, the human H 1299 bronchial cell line, in which PTEN is hypomorphic due to promoter methylation, has been stably transfected with physiologically relevant levels of PTEN. In both models, a novel consequence of PTEN expression was to increase Ins(1,3,4,5,6)P-5 pool size by 30-40% (p < 0.01); this response was wortmannin-insensitive and, therefore, independent of the PtdIns 3-kinase pathway. In U87MG cells, induction of the G129R catalytically inactive PTEN mutant did not affect Ins(1,3,4,5,6)P-5 levels. PTEN induction did not alter the expression of enzymes participating in Ins(1,3,4,5,6)P-5 synthesis. Another effect of PTEN expression in U87MG cells was to decrease InsP(6) levels by 13% (p < 0.02). The InsP(6)-phosphatase, M]PP, may be responsible for the latter effect; we show that recombinant human MIPP dephosphorylates InsP6 to D/L-Ins(1,2,4,5,6)P-5, levels of which increased 60% (p < 0.05) following PTEN expression in U87MG cells. Overall, our data add higher inositol phosphates to the list of important cellular regulators [Y. Huang, R.P. Wemyj, D.D. Norton, P. Precht, M.C. Seminario, R.L. Wange, Oncogene, 24 (2005) 3819 [57]] the levels of which are modulated by expression of the highly pleiotropic PTEN protein. Published by Elsevier Inc. C1 NIEHS, Inositol Signaling Sect, Lab Signal Transduct, DHSS, Res Triangle Pk, NC 27709 USA. Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. RP Shears, SB (reprint author), NIEHS, Inositol Signaling Sect, Lab Signal Transduct, DHSS, POB 12233, Res Triangle Pk, NC 27709 USA. EM shears@niehs.nih.gov FU NCI NIH HHS [R01 CA082783, R01 CA082783-06] NR 58 TC 8 Z9 8 U1 2 U2 4 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 2006 VL 18 IS 4 BP 488 EP 498 DI 10.1016/j.cellsig.2005.05.017 PG 11 WC Cell Biology SC Cell Biology GA 001PU UT WOS:000234549600010 PM 15979280 ER PT J AU Dreher, JC Kohn, P Berman, KF AF Dreher, JC Kohn, P Berman, KF TI Neural coding of distinct statistical properties of reward information in humans SO CEREBRAL CORTEX LA English DT Article DE dopamine; error prediction; fMRI; gambling; information theory; uncertainty ID HUMAN PREFRONTAL CORTEX; PREDICTION ERROR; DOPAMINE NEURONS; DECISION-MAKING; DORSAL STRIATUM; LEARNING-THEORY; HUMAN BRAIN; RESPONSES; MODEL; MODULATION AB Brain processing of reward information is essential for complex functions such as learning and motivation. Recent primate electrophysiological studies using concepts from information, economic and learning theories indicate that the midbrain may code two statistical parameters of reward information: a transient reward error prediction signal that varies linearly with reward probability and a sustained signal that varies highly non-linearly with reward probability and that is highest with maximal reward uncertainty (reward probability = 0.5). Here, using event-related functional magnetic resonance imaging, we disentangled these two signals in humans using a novel paradigm that systematically varied monetary reward probability, magnitude and expected reward value. The midbrain was activated both transiently with the error prediction signal and in a sustained fashion with reward uncertainty. Moreover, distinct activity dynamics were observed in post-synaptic midbrain projection sites: the prefrontal cortex responded to the transient error prediction signal while the ventral striatum covaried with the sustained reward uncertainty signal. These data suggest that the prefrontal cortex may generate the reward prediction while the ventral striatum may be involved in motivational processes that are useful when an organism needs to obtain more information about its environment. Our results indicate that distinct functional brain networks code different aspects of the statistical properties of reward information in humans. C1 NIMH, Unit Integrat Neuroimaging, Clin Brain Disorders Branch, NIH, Bethesda, MD USA. RP Dreher, JC (reprint author), Univ Lyon 1, CNRS, Inst Cognit Sci, 67 Bd Pinel, F-69675 Bron, France. EM dreher@isc.cnrs.fr NR 54 TC 114 Z9 115 U1 1 U2 10 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 2006 VL 16 IS 4 BP 561 EP 573 DI 10.1093/cercor/bhj004 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 020PO UT WOS:000235922200013 PM 16033924 ER PT J AU Kemeny, S Xu, J Park, GH Hosey, LA Wettig, CM Braun, AR AF Kemeny, S Xu, J Park, GH Hosey, LA Wettig, CM Braun, AR TI Temporal dissociation of early lexical access and articulation using a delayed naming task - An fMRI study SO CEREBRAL CORTEX LA English DT Article DE brain function; human brain mapping; magnetic resonance imaging; production; speech ID HUMAN EXTRASTRIATE CORTEX; EVENT-RELATED FMRI; SPEECH ARTICULATION; PARIETAL CORTEX; WORD PRODUCTION; LANGUAGE; OBJECT; REGIONS; AREA; CONJUNCTION AB Neuroimaging studies of overt speech hold an important practical advantage allowing monitoring of subject performance, particularly valuable in disorders like aphasia. However, speech production is not a monotonic process but a complex sequence of stages. Levelt and colleagues have described these as roughly corresponding to two originally independent systems - conceptual and sensorimotor - that are linked in the formulation and expression of spoken language. In the initial stages a word is chosen to match a concept (lexical selection); in the later stages the sound and motor patterns are encoded and the word is uttered (articulation). It has been difficult to discriminate these stages using conventional neuroimaging techniques. We designed a functional magnetic resonance imaging study in an attempt to do this, by introducing a latency into a conventional naming paradigm, delaying the articulated response. Our results showed that left hemisphere perisylvian areas were active throughout, interacting with visual and heteromodal areas during early lexical access and with motor and auditory areas during overt articulation. These results are consistent with the broadest version of the Levelt model and with that derived from Chomsky's minimalist program in which a core language system interacts with conceptual-intentional systems and articulatory-perceptual systems during the early and late stages of lexical access respectively. C1 NIDCD, Language Sect, Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA. RP Kemeny, S (reprint author), NIH, Ctr Clin, 9000 Rockville Pike Bld,10 Rm 3C-716, Bethesda, MD 20892 USA. EM kemenys@nidcd.nih.gov NR 46 TC 35 Z9 35 U1 0 U2 6 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 2006 VL 16 IS 4 BP 587 EP 595 DI 10.1093/cercor/bhj006 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 020PO UT WOS:000235922200015 PM 16049190 ER PT J AU Ye, WJ Sangaiah, R Degen, DE Gold, A Jayaraj, K Koshlap, KM Boysen, G Williams, J Tomer, KB Ball, LM AF Ye, WJ Sangaiah, R Degen, DE Gold, A Jayaraj, K Koshlap, KM Boysen, G Williams, J Tomer, KB Ball, LM TI A 2-iminohydantoin from the oxidation of guanine SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; C-13 NMR; COUPLING-CONSTANTS; LIPID-PEROXIDATION; MAJOR PRODUCT; DNA; SPIROIMINODIHYDANTOIN; SPECTRA; 8-OXO-7,8-DIHYDROGUANOSINE; DIMETHYLDIOXIRANE AB The nucleobase guanine was oxidized with dimethyldioxirane (DMDO) to explore the role of epoxidizing agents in oxidative DNA damage. Treatment of guanine with 10% molar excess DMDO in aqueous solution at 0 degrees C and pH 7.5 followed by workup under mild conditions gave 5-carboxamido-5-formamido2-iminohydantoin (1) as the sole isolable product in 71% yield. The structure of 1 was established on the basis of mass spectrometry and NMR studies on 1 and its isotopomers generated by the oxidation of [4-C-13] and [7-N-15]guanine, which yield [5-C-13]1 and [7-N-15]1. The distribution of C-13 and N-15 labels in the isotopomeric products supports initial epoxidation of the C4-C5 bond of guanine followed by a 1,2-acyl migration of guanine C6. Compound 1 is suggested as a possible primary DNA lesion from putative epoxidizing agents, including hydroperoxides present during biological processes such as lipid peroxidation. C1 Univ N Carolina, Dept Environm Sci & Engn CB7431, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Pharm CB7360, Chapel Hill, NC 27599 USA. NIEHS, Lab Struct Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Gold, A (reprint author), Univ N Carolina, Dept Environm Sci & Engn CB7431, Chapel Hill, NC 27599 USA. EM golda@email.unc.edu RI Tomer, Kenneth/E-8018-2013; OI Boysen, Gunnar/0000-0001-8364-9881 FU Intramural NIH HHS; NIEHS NIH HHS [P30ES10126, P42-ES005948] NR 41 TC 16 Z9 16 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD APR PY 2006 VL 19 IS 4 BP 506 EP 510 DI 10.1021/tx0600144 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 035LA UT WOS:000237001300002 PM 16608161 ER PT J AU Hardy, NM Fowler, DH Bishop, MR AF Hardy, Nancy M. Fowler, Daniel H. Bishop, Michael R. TI Immunotherapy of metastatic breast cancer: Phase I trial of reduced-intensity allogeneic hematopoietic stem cell transplantation with Th2/Tc2 T-cell exchange SO CLINICAL BREAST CANCER LA English DT Article DE adoptive cellular therapy; engraftment; graft engineering; graft-versus-host disease; graft-versus-turnor effect; type 2 cytokines ID BONE-MARROW-TRANSPLANTATION; TC2 PHENOTYPE; DEPLETION; RISK; REJECTION; LEUKEMIA; TH2; GVL C1 NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hardy, NM (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, 10 Ctr Dr CRC,Room 3E-3330, Bethesda, MD 20892 USA. EM hardyn@mail.nih.gov FU Intramural NIH HHS NR 12 TC 2 Z9 2 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD APR PY 2006 VL 7 IS 1 BP 87 EP 89 DI 10.3816/CBC.2006.n.019 PG 3 WC Oncology SC Oncology GA 114XQ UT WOS:000242699300011 PM 16764750 ER PT J AU Sparreboom, A Figg, WD AF Sparreboom, A Figg, WD TI Identifying sources of interindividual pharmacokinetic variability with population modeling SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID P-GLYCOPROTEIN; PACLITAXEL PHARMACOKINETICS; CANCER-PATIENTS; HUMAN LIVER; RESISTANCE; POLYMORPHISMS; EXPRESSION; TOXICITY; THERAPY; CYP2C8 C1 NCI, Clin Pharmacol Res Core, Med Oncol Branch, Bethesda, MD 20892 USA. RP Sparreboom, A (reprint author), NCI, Clin Pharmacol Res Core, Med Oncol Branch, 9000 Rockville Pike,Bldg 10,Room 5A01,MSC 1910, Bethesda, MD 20892 USA. EM SparrebA@mail.nih.gov RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 FU Intramural NIH HHS NR 22 TC 4 Z9 4 U1 1 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 1 PY 2006 VL 12 IS 7 BP 1951 EP 1953 DI 10.1158/1078-0432.CCR-06-0342 PN 1 PG 3 WC Oncology SC Oncology GA 034BI UT WOS:000236899000002 PM 16609000 ER EF