FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Howlett, GJ Minton, AP Rivas, G AF Howlett, Geoffrey J. Minton, Allen P. Rivas, German TI Analytical ultracentrifugation for association and assembly the study of protein SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Review ID VELOCITY ANALYTICAL ULTRACENTRIFUGATION; TRACER SEDIMENTATION EQUILIBRIUM; SIZE-DISTRIBUTION ANALYSIS; STATIC LIGHT-SCATTERING; SELF-ASSOCIATION; QUANTITATIVE CHARACTERIZATION; MACROMOLECULAR ASSOCIATIONS; DETERGENT SOLUTIONS; WEIGHT AVERAGE; POWERFUL TOOL AB Analytical ultracentrifugation remains pre-eminent among the methods used to study the interactions of macromolecules under physiological conditions. Recent developments in analytical procedures allow the high resolving power of sedimentation velocity methods to be coupled to sedimentation equilibrium approaches and applied to both static and dynamic associations. Improvements in global modeling based on numerical solutions of the Lamm equation have generated new sedimentation velocity applications with an emphasis on data interpretation using sedimentation coefficient or molar mass distributions. Procedures based on the use of multiple optical signals from absorption and interference optics for the analysis of the sedimentation velocity and equilibrium behavior of more complex interactions have now been developed. New applications of tracer sedimentation equilibrium experiments and the development of a fluorescence optical system for the analytical ultracentrifuge extend the accessible concentration range over several orders of magnitude and, coupled with the new analytical procedures, provide powerful new tools for studies of both weak and strong macromolecular interactions in solution. C1 Univ Melbourne, Dept Biochem & Mol Biol, Melbourne, Vic 3010, Australia. Univ Melbourne, Mol Sci & Biotechnol Inst, Melbourne, Vic 3010, Australia. NIDDK, Sect Phys Biochem, Biochem & Genet Lab, NIH, Bethesda, MD 20892 USA. CSIC, Ctr Invest Biol, E-28040 Madrid, Spain. RP Rivas, G (reprint author), Univ Melbourne, Dept Biochem & Mol Biol, Melbourne, Vic 3010, Australia. EM grivas@cib.csic.es OI Rivas, German/0000-0003-3450-7478 NR 46 TC 110 Z9 112 U1 4 U2 41 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1367-5931 J9 CURR OPIN CHEM BIOL JI Curr. Opin. Chem. Biol. PD OCT PY 2006 VL 10 IS 5 BP 430 EP 436 DI 10.1016/j.cbpa.2006.08.017 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 100FA UT WOS:000241652200008 PM 16935549 ER PT J AU Ma, BY Nussinov, R AF Ma, Buyong Nussinov, Ruth TI Simulations as analytical tools to understand protein aggregation and predict amyloid conformation SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Review ID MOLECULAR-DYNAMICS SIMULATIONS; BETA-SHEET; FIBRIL FORMATION; EXPERIMENTAL CONSTRAINTS; PEPTIDE OLIGOMERIZATION; PROTOFIBRIL FORMATION; STRUCTURAL MODEL; PRION PROTEIN; IN-SILICO; TRANSTHYRETIN AB Computational tools are increasingly being applied to solve the protein aggregation problem, providing insight into amyloid structures and aggregation mechanisms. The paradigm of A beta amyloid structure elucidation provides an example of an innovative experimental design and endeavor, echoing the computational testing of possible molecular associations, all reflected in the current Ma-Nussinov-Tycko model of the A beta amyloid. Simulations have shown that dimer formation can lock some misfolded conformations, and catalyze the shift of the equilibrium away from the native state. In most cases, a stable amyloid seed requires at least two-layered beta-sheets with properly registered side-chains. Under kinetic control, the final protein aggregations are the outcome of maximizing the van der Waals interactions between side chains and backbone hydrogen bonds. C1 NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 60 TC 169 Z9 172 U1 2 U2 36 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1367-5931 J9 CURR OPIN CHEM BIOL JI Curr. Opin. Chem. Biol. PD OCT PY 2006 VL 10 IS 5 BP 445 EP 452 DI 10.1016/j.cbpa.2006.08.018 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 100FA UT WOS:000241652200010 PM 16935548 ER PT J AU Muller, J Kassis, JA AF Mueller, Juerg Kassis, Judith A. TI Polycomb response elements and targeting of Polycomb group proteins in Drosophila SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID HISTONE METHYLTRANSFERASE ACTIVITY; DNA-BINDING PROTEINS; CELLULAR MEMORY MODULE; EMBRYONIC STEM-CELLS; GAGA FACTOR; HOMEOTIC GENE; TRANSCRIPTION FACTOR; BITHORAX COMPLEX; ENGRAILED GENE; DEVELOPMENTAL REGULATORS AB Polycomb group (PcG) proteins are conserved regulatory proteins that repress transcription of particular target genes in animals and plants. Studies over the past decade have established that most PcG proteins are not classic DNA binding factors but that they exist in multisubunit protein complexes that bind to and modify chromatin. Nevertheless, PcG repression of target genes in Drosophila requires specific cisregulatory sequences, called Polycomb response elements (PREs), and chromatin immunoprecipitation studies have shown that, in vivo, most PcG proteins are specifically bound at the PREs of target genes. However, the mechanisms by which these PcG protein complexes are recruited to PREs and how they repress transcription are still poorly understood. Recent studies challenge earlier models that invoke covalent histone modifications and chromatin binding as the key steps in the recruitment of PcG proteins to PREs. The available evidence suggests that PREs are largely devoid of nucleosomes and that PRE DNA serves as an assembly platform for many different PcG protein complexes through DNA-protein and protein-protein interactions. The emerging picture suggests that the binding and modification of chromatin by PcG proteins is needed for interaction of PRE-tethered PcG protein complexes with nucleosomes in the flanking chromatin in order to maintain a Polycomb-repressed chromatin state at promoters and coding regions of target genes. C1 European Mol Biol Lab, Gene Express Programme, D-69117 Heidelberg, Germany. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Muller, J (reprint author), European Mol Biol Lab, Gene Express Programme, Meyerhofstr 1, D-69117 Heidelberg, Germany. EM juerg.mueller@embl.de OI Kassis, Judith/0000-0001-9268-3213 FU Intramural NIH HHS NR 90 TC 168 Z9 171 U1 1 U2 11 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD OCT PY 2006 VL 16 IS 5 BP 476 EP 484 DI 10.1016/j.gde.2006.08.005 PG 9 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 095PP UT WOS:000241320300006 PM 16914306 ER PT J AU Barrett, J AF Barrett, John TI Improving outcome of allogeneic stem cell transplantation by immunomodulation of the early post-transplant environment SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; ANTIGEN-PRESENTING CELLS; CD4(+) T-CELLS; IMMUNE RECONSTITUTION; SELECTIVE DEPLETION; DONOR; RESPONSES; LYMPHOCYTES AB There has been great progress in understanding the alloresponse and the process of immune recovery after stem cell transplantation. Here, we highlight ways in which transplant outcome is determined by unique immunological features of the early post-transplant period that modulate the growth and function of the grafted donor T cells and stem cells. Better understanding of these early events and more detailed knowledge of the phenotype and function of transplanted donor cells facilitate strategies to optimize immune recovery, prevent graft-versus-host disease (GVHD) and boost immunity to viruses and leukemia. Approaches that optimize CD34 cell dose, techniques to remove GVHD-reacting T cells by T cell subset selection, suicide gene insertion or selective allodepletion, and the adoptive transfer of antigen-specific T cells have reached the stage of clinical trials. Furthermore, murine transplant experiments indicate ways to prevent GVHD while preserving immune function by depletion of naive cells, T cytotoxic 1 and T helper 1 cells, or by enrichment of regulatory T cells. Many of these approaches appear feasible in clinical transplantation and have yielded promising initial results, but proof that the goal of controlled selective immune reconstitution can be achieved is still awaited. C1 NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, J (reprint author), NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov NR 50 TC 18 Z9 18 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 2006 VL 18 IS 5 BP 592 EP 598 DI 10.1016/j.coi.2006.06.002 PG 7 WC Immunology SC Immunology GA 088MR UT WOS:000240816300014 PM 16872820 ER PT J AU Chang, L Blain, D Bertuzzi, S Brooks, BP AF Chang, Lan Blain, Delphine Bertuzzi, Stefano Brooks, Brian P. TI Uveal coloboma: clinical and basic science update SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Review DE coloboma; congenital cause of blindness; eye development; optic fissure closure ID WOLF-HIRSCHHORN-SYNDROME; OPTIC-NERVE COLOBOMAS; AUTOSOMAL RECESSIVE INHERITANCE; CONGENITAL EYE MALFORMATIONS; EPIDERMAL NEVUS SYNDROME; ABSENT CORPUS-CALLOSUM; FETAL ALCOHOL SYNDROME; 13Q DELETION SYNDROME; X-LINKED SYNDROME; OCULAR COLOBOMA AB Purpose of review To integrate knowledge on the embryologic and molecular basis of optic fissure closure with clinical observations in patients with uveal coloboma. Recent findings Closure of the optic fissure has been well characterized and many genetic alterations have been associated with coloboma; however, molecular mechanisms leading to coloboma remain largely unknown. In the past decade, we have gained better understanding of genes critical to eye development; however, mutations in these genes have been found in few individuals with coloboma. CHD7 mutations have been identified in patients with CHARGE syndrome (coloboma, heart defects, choanal atresia, retarded growth, genital anomalies, and ear anomalies or deafness). Animal models are bringing us closer to a molecular understanding of optic fissure closure. Summary Optic fissure closure requires precise orchestration in timing and apposition of two poles of the optic cup. The relative roles of genetics and environment on this process remain elusive. While most cases of coloboma are sporadic, autosomal dominant, autosomal recessive, and X-linked inheritance patterns have been described. Genetically, colobomata demonstrate pleiotropy, heterogeneity, variable expressivity, and reduced penetrance. Coloboma is a complex disorder with a variable prognosis and requires regular examination to optimize visual acuity and to monitor for potential complications. C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Ann Arbor, MI USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Brooks, BP (reprint author), 10 Ctr Dr,Bldg 10,Room 10N226,MSC 1860, Bethesda, MD 20892 USA. EM brooksb@mail.nih.gov NR 210 TC 50 Z9 51 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8738 EI 1531-7021 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD OCT PY 2006 VL 17 IS 5 BP 447 EP 470 DI 10.1097/01.icu.0000243020.82380.f6 PG 24 WC Ophthalmology SC Ophthalmology GA 082DL UT WOS:000240366800006 PM 16932062 ER PT J AU Mittendorf, EA Shifrin, AL Inabnet, WB Libutti, SK McHenry, CR Demeure, MJ AF Mittendorf, Elizabeth A. Shifrin, Alexander L. Inabnet, William B. Libutti, Steven K. McHenry, Christopher R. Demeure, Michael J. TI Islet cell tumors SO CURRENT PROBLEMS IN SURGERY LA English DT Review ID ZOLLINGER-ELLISON-SYNDROME; MULTIPLE ENDOCRINE NEOPLASIA; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; PANCREATIC NEUROENDOCRINE TUMORS; HEPATIC ARTERIAL CHEMOEMBOLIZATION; INTRAARTERIAL CALCIUM STIMULATION; LAPAROSCOPIC RADIOFREQUENCY ABLATION; CURATIVE GASTRINOMA RESECTION; CURRENT SURGICAL-MANAGEMENT; VONHIPPEL-LINDAU-DISEASE C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Columbia Univ Coll Phys & Surg, Thyroid Ctr, New York, NY 10032 USA. NCI, Tumor Angiogenesis Sect, Bethesda, MD 20892 USA. NCI, Endocrine Surg Serv, Surg Branch, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Metrohlth Med Ctr, Div Gen Surg, Cleveland, OH USA. Univ Arizona, Translat Genom Res Inst, Tucson, AZ USA. RP Mittendorf, EA (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. NR 288 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0011-3840 J9 CURR PROB SURG JI Curr. Probl. Surg. PD OCT PY 2006 VL 43 IS 10 BP 679 EP 765 DI 10.1067/j.cpsurg.2006.07.002 PG 87 WC Surgery SC Surgery GA 107BU UT WOS:000242146500002 ER PT J AU Kim, HP Imbert, J Leonard, WJ AF Kim, Hyoung Pyo Imbert, Jean Leonard, Warren J. TI Both integrated and differential regulation of components of the IL-2/IL-2 receptor system SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE IL-2; IL-2 receptor; transcription; gamma c; XSCID ID T-CELL-ACTIVATION; HUMAN INTERLEUKIN-2 RECEPTOR; NF-KAPPA-B; ALPHA-CHAIN GENE; SEVERE COMBINED IMMUNODEFICIENCY; NH2-TERMINAL KINASE (JNK)1; MESSENGER-RNA STABILITY; HUMAN IL-2 RECEPTOR; GAMMA-CHAIN; BETA-CHAIN AB Interleukin-2 was discovered in 1976 as a T-cell growth factor. It was the first type I cytokine cloned and the first for which a receptor component was cloned. Its importance includes its multiple actions, therapeutic potential, and lessons for receptor biology, with three components differentially combining to form high, intermediate, and low-affinity receptors. IL-21ka and IL-2R beta, respectively, are markers for double-negative thymocytes and regulatory T-cells versus memory cells. gamma(c) which is shared by six cytokines, is mutated in patients with X-linked severe-combined immunodeficiency. We now cover an under-reviewed area-the regulation of genes encoding IL-2 and lL-2R components, with an effort to integrate/explain this knowledge. Published by Elsevier Ltd. C1 NHLBI, Lab Mol Immunol, Ctr Immunol, NIH, Bethesda, MD 20892 USA. Univ Mediterranee, Inst J Paoli I Calmettes, INSERM, UMR599,Ctr Rech Cancerol Marseille, F-13009 Marseille, France. RP Kim, HP (reprint author), NHLBI, Lab Mol Immunol, Ctr Immunol, NIH, Bethesda, MD 20892 USA. EM kimhp@mail.nih.gov RI Imbert, Jean/G-3248-2013 OI Imbert, Jean/0000-0002-0478-9593 FU Intramural NIH HHS NR 160 TC 149 Z9 154 U1 2 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6101 J9 CYTOKINE GROWTH F R JI Cytokine Growth Factor Rev. PD OCT PY 2006 VL 17 IS 5 BP 349 EP 366 DI 10.1016/j.cytogfr.2006.07.003 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 104QU UT WOS:000241974500003 PM 16911870 ER PT J AU Miura, S Davis, S Klingensmith, J Mishina, Y AF Miura, Shigeto Davis, Shannon Klingensmith, John Mishina, Yuji TI BMP signaling in the epiblast is required for proper recruitment of the prospective paraxial mesoderm and development of the somites SO DEVELOPMENT LA English DT Article DE epiblast; primitive streak; paraxial mesoderm; somites; BMP; FGF; mouse ID MOUSE GASTRULATION; MORPHOGENETIC MOVEMENT; CELL FATE; PRIMITIVE STREAK; EMBRYO; GENE; EXPRESSION; DIFFERENTIATION; EMBRYOGENESIS; RECEPTOR AB Bmpr1a encodes the BMP type IA receptor for bone morphogenetic proteins (BMPs), including 2 and 4. Here, we use mosaic inactivation of Bmpr1a in the epiblast of the mouse embryo (Bmpr-MORE embryos) to assess functions of this gene in mesoderm development. Unlike Bmpr1a-null embryos, which fail to gastrulate, Bmpr-MORE embryos initiate gastrulation, but the recruitment of prospective paraxial mesoderm cells to the primitive streak is delayed. This delay causes a more proximal distribution of cells with paraxial mesoderm character within the primitive streak, resulting in a lateral expansion of somitic mesoderm to form multiple columns. Inhibition of FGF signaling restores the normal timing of recruitment of prospective paraxial mesoderm and partially rescues the development of somites. This suggests that BMP and FGF signaling function antagonistically during paraxial mesoderm development. C1 NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. Duke Univ, Ctr Med, Dept Cell Biol, Durham, NC 27710 USA. RP Mishina, Y (reprint author), NIEHS, Reprod & Dev Toxicol Lab, 111 TW Alexander Dr,POB 12233,MD C4-10,C458, Res Triangle Pk, NC 27709 USA. EM mishina@niehs.nih.gov FU Intramural NIH HHS; NICHD NIH HHS [P01HD39948]; NIDCR NIH HHS [R01DE013674] NR 41 TC 25 Z9 28 U1 1 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD OCT 1 PY 2006 VL 133 IS 19 BP 3767 EP 3775 DI 10.1242/dev.02552 PG 9 WC Developmental Biology SC Developmental Biology GA 083LR UT WOS:000240457900004 PM 16943278 ER PT J AU Cerrato, A Parisi, M Anna, SS Missirlis, F Guru, S Agarwal, S Sturgill, D Talbot, T Spiegel, A Collins, F Chandrasekharappa, S Marx, S Oliver, B AF Cerrato, Aniello Parisi, Michael Anna, Sonia Santa Missirlis, Fanis Guru, Siradanahalli Agarwal, Sunita Sturgill, David Talbot, Thomas Spiegel, Allen Collins, Francis Chandrasekharappa, Settara Marx, Stephen Oliver, Brian TI Genetic interactions between Drosophila melanogaster menin and Jun/Fos SO DEVELOPMENTAL BIOLOGY LA English DT Article DE API; oxidative stress; paraquat; life span; cleft thorax; tumor suppressor; multiple endocrine neoplasia type 1 ID HISTONE METHYLTRANSFERASE COMPLEX; MULTIPLE ENDOCRINE NEOPLASIA; JUND-ACTIVATED TRANSCRIPTION; EXPRESSION; PROTEIN; JNK; SUPPRESSOR; BINDING; TYPE-1; GROWTH AB Menin is a tumor suppressor required to prevent multiple endocrine neoplasia in humans. Mammalian menin protein is associated with chromatin modifying complexes and has been shown to bind a number of nuclear proteins, including the transcription factor JunD. Menin shows bidirectional effects acting positively on c-Jun and negatively on JunD. We have produced protein null alleles of Drosophila menin (mnn1) and have over expressed the Mnn1 protein. Flies homozygous for protein-null mnn1 alleles are viable and fertile. Localized over-expression of Man l causes defects in thoracic closure, a phenotype that sometimes results from insufficient Jun activity. We observed complex genetic interactions between mnn1 and jun in different developmental settings. Our data support the idea that one function of menin is to modulate Jun activity in a manner dependent on the cellular context. (c) 2006 Elsevier Inc. All rights reserved. C1 NIDDK, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NHGRI, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NICHHD, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Cerrato, A (reprint author), Univ Naples Federico II, Ist Endocrinol & Oncol Sperimentale, CNR, Dipartimento Biol & Patol Cellulare & Mol, Via S Pansini 5, I-80131 Naples, Italy. EM a.cerrato@sun.ceos.na.cnr.it RI Missirlis, Fanis/C-1137-2011; Agarwal, Sunita/D-1428-2016 OI Missirlis, Fanis/0000-0003-0467-8444; Agarwal, Sunita/0000-0002-7557-3191 FU Intramural NIH HHS [Z01 DK015600-12]; NIAID NIH HHS [R01 AI042819] NR 36 TC 8 Z9 8 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD OCT 1 PY 2006 VL 298 IS 1 BP 59 EP 70 DI 10.1016/j.ydbio.2006.06.013 PG 12 WC Developmental Biology SC Developmental Biology GA 092BD UT WOS:000241071100006 PM 16930585 ER PT J AU Podbilewicz, B Leikina, E Sapir, A Valansi, C Suissa, M Shemer, G Chernomordik, LV AF Podbilewicz, Benjamin Leikina, Evgenia Sapir, Amir Valansi, Clari Suissa, Meital Shemer, Gidi Chernomordik, Leonid V. TI The C-elegans developmental fusogen EFF-1 mediates homotypic fusion in heterologous cells and in vivo SO DEVELOPMENTAL CELL LA English DT Article ID INFLUENZA-VIRUS HEMAGGLUTININ; MEMBRANE-FUSION; CAENORHABDITIS-ELEGANS; BIOLOGICAL-MEMBRANES; MOSAIC ANALYSIS; PROTEIN; HEMIFUSION; HYPODERMIS; PORE; MECHANISMS AB During cell-cell fusion, two cells' plasma membranes merge, allowing the cytoplasms to mix and form a syncytium. Little is known about the mechanisms of cell fusion. Here, we asked whether eff-1, shown previously to be essential for fusion in Caenorhabditis elegans, acts directly in the fusion machinery. We show that expression of EFF-1 transmembrane protein drives fusion of heterologous cells into multinucleate syncytia. We obtained evidence that EFF-1-mediated fusion involves a hemifusion intermediate characterized by membrane mixing without cytoplasm mixing. Furthermore, syncytiogenesis requires EFF-1 in both fusing cells. To test whether this mechanism also applies in vivo, we conducted genetic mosaic analysis of C. elegans and found that homotypic epidermal fusion requires EFF-1 in both cells. Thus, although EFF-1-mediated fusion shares characteristics with viral and intracellular fusion, including an apparent hemifusion step, it differs from these reactions in the homotypic organization of the fusion machinery. C1 Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel. NICHHD, NIH, Sect Membrane Biol, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. RP Podbilewicz, B (reprint author), Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel. EM podbilew@tx.technion.ac.il; chernoml@mail.nih.gov RI Podbilewicz, Benjamin/N-4825-2014; Sapir, Amir/C-5758-2015; OI Sapir, Amir/0000-0001-9888-1800; Podbilewicz, Benjamin/0000-0002-0411-4182; Oren-Suissa, Meital/0000-0001-9937-8326 FU Intramural NIH HHS NR 52 TC 66 Z9 72 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD OCT PY 2006 VL 11 IS 4 BP 471 EP 481 DI 10.1016/j.devcel.2006.09.004 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 092UR UT WOS:000241123300009 PM 17011487 ER PT J AU Caretti, G Schiltz, RL Dilworth, FJ Di Padova, M Zhao, P Ogryzko, V Fuller-Pace, FV Hoffman, EP Tapscott, SJ Sartorelli, V AF Caretti, Giuseppina Schiltz, R. Louis Dilworth, F. Jeffrey Di Padova, Monica Zhao, Po Ogryzko, Vasily Fuller-Pace, Frances V. Hoffman, Eric P. Tapscott, Stephen J. Sartorelli, Vittorio TI The RNA helicases p68/p72 and the noncoding RNA SRA are coregulators of MyoD and skeletal muscle differentiation SO DEVELOPMENTAL CELL LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; GENE-EXPRESSION; TRANSCRIPTIONAL COACTIVATOR; MYOGENIC DIFFERENTIATION; HISTONE DEACETYLASES; BINDING-PROTEIN; DISTINCT ROLES; CHROMATIN; ACTIVATION; COMPLEXES AB MyoD regulates skeletal myogenesis. Since proteins associated with MyoD exert regulatory functions, their identification is expected to contribute important insights into the mechanisms governing gene expression in skeletal muscle. We have found that the RNA helicases p68/p72 are MyoD-associated proteins and that the noncoding RNA SRA also immunoprecipitates with MyoD. In vitro and in vivo experiments indicated that both p68/p72 and SRA are coactivators of MyoD. RNA interference toward either p68/p72 or SRA prevented proper activation of muscle gene expression and cell differentiation. Unexpectedly, reducing the levels of p68/p72 proteins impaired recruitment of the TATA binding protein TBP; RNA polymerase II; and the catalytic subunit of the ATPase SWI/SNF complex, Brg-1, and hindered chromatin remodeling. These findings reveal that p68/p72 play a critical role in promoting the assembly of proteins required for the formation of the transcription initiation complex and chromatin remodeling. C1 NIAMSD, Muscle Gene Express Grp, Lab Muscle Biol, NIH, Bethesda, MD 20829 USA. Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. Ottawa Hlth Res Inst, Mol Med Program, Ottawa, ON K1H 8L6, Canada. Res Ctr Genet Med, Washington, DC 20010 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Inst Gustave Roussy, CNRS, UMR 8126, F-94100 Villejuif, France. Univ Dundee, Ninewells Hosp & Med Sch, Canc Biol Grp, Div Pathol & Neurosci, Dundee DD1 9SY, Scotland. RP Sartorelli, V (reprint author), NIAMSD, Muscle Gene Express Grp, Lab Muscle Biol, NIH, Bethesda, MD 20829 USA. EM sartorev@mail.nih.gov RI Ogryzko, Vasily/M-6665-2015; OI Ogryzko, Vasily/0000-0002-8548-1389; DI PADOVA, Monica/0000-0003-3808-7159 FU Intramural NIH HHS NR 48 TC 133 Z9 146 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD OCT PY 2006 VL 11 IS 4 BP 547 EP 560 DI 10.1016/j.devcel.2006.08.003 PG 14 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 092UR UT WOS:000241123300015 PM 17011493 ER PT J AU Clauss, SB Walker, DL Kirby, ML Schimel, D Lo, CW AF Clauss, Sarah B. Walker, Diana L. Kirby, Margaret L. Schimel, Dan Lo, Cecilia W. TI Patterning of coronary arteries in wildtype and Connexin43 knockout mice SO DEVELOPMENTAL DYNAMICS LA English DT Article DE MicroCT; congenital heart disease; coronary arteries; mouse; connexin ID INTACT VENTRICULAR SEPTUM; PULMONARY ATRESIA; GREAT-ARTERIES; SMOOTH-MUSCLE; ORIGIN; TRANSPOSITION; COMMUNICATION; EMBRYOGENESIS; TETRALOGY; ANOMALIES AB Abnormal patterning of coronary arteries (CAs) is a clinically significant problem, and as yet, few animal models have been systematically investigated for coronary patterning defects. Here we characterized coronary artery (CA) insertion and branching patterns of the proximal coronary stems in the hearts of wildtype and heterozygous connexin43 knockout (Cx43 alpha 1 KO) mice. This study entailed the use of high-resolution micro CT imaging for three-dimensional coronary reconstructions. MicroCT of 17 wildtype mice showed a remarkably consistent pattern of CA deployment in the normal mouse heart. Two main CA stems are inserted from the left and right into the aorta. The right coronary artery then branches immediately into the right main and the septal-conal branch, while the left coronary artery branches further distally into the circumflex and the anterior descending CA. This patterning of CA anatomy was confirmed by histology, and by using a vascular smooth muscle or endothelial cell specific lacZ reporter gene to delineate the CAs. A parallel analysis of 25 heterozygous Cx43 alpha 1 KO mouse hearts showed 22 had defects in patterning of the CAs. They exhibited a wide variation in CA anatomy, including abnormal origin and course of the main CA stems, multiple accessories, and dual septal-conal branches. Overall, these studies show loss of one Cx43 alpha 1 allele (haploinsufficiency) leads to a high incidence of coronary patterning defects. These findings suggest CA patterning is sensitive to Cx43 alpha 1 gene dosage. C1 NHLBI, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Duke Univ, Raleigh, NC USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Lo, CW (reprint author), Bldg 50,Room 4537,MSC8019, Bethesda, MD 20814 USA. EM loc@nhlbi.nih.gov NR 28 TC 26 Z9 26 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD OCT PY 2006 VL 235 IS 10 BP 2786 EP 2794 DI 10.1002/dvdy.20887 PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 089UI UT WOS:000240906200014 PM 16802337 ER PT J AU Huth, C Heid, IM Vollmert, C Gieger, C Grallert, H Wolford, JK Langer, B Thorand, B Klopp, N Hamid, YH Pedersen, O Hansen, T Lyssenko, V Groop, L Meisinger, C Doring, A Lowel, H Lieb, W Hengstenberg, C Rathmann, W Martin, S Stephens, JW Ireland, H Mather, H Miller, GJ Stringham, HM Boehnke, M Tuomilehto, J Boeing, H Mohlig, M Spranger, J Pfeiffer, A Wernstedt, I Niklason, A Lopez-Bermejo, A Fernandez-Real, JM Hanson, RL Gallart, L Vendrell, J Tsiavou, A Hatziagelaki, E Humphries, SE Wichmann, HE Herder, C Illig, T AF Huth, Cornelia Heid, Iris M. Vollmert, Caren Gieger, Christian Grallert, Harald Wolford, Johanna K. Langer, Birgit Thorand, Barbara Klopp, Norman Hamid, Yasmin H. Pedersen, Oluf Hansen, Torben Lyssenko, Valeriya Groop, Leif Meisinger, Christa Doring, Angela Lowel, Hannelore Lieb, Wolfgang Hengstenberg, Christian Rathmann, Wolfgang Martin, Stephan Stephens, Jeffrey W. Ireland, Helen Mather, Hugh Miller, George J. Stringham, Heather M. Boehnke, Michael Tuomilehto, Jaakko Boeing, Heiner Mohlig, Matthias Spranger, Joachim Pfeiffer, Andreas Wernstedt, Ingrid Niklason, Anders Lopez-Bermejo, Abel Fernandez-Real, Jose-Manuel Hanson, Robert L. Gallart, Luis Vendrell, Joan Tsiavou, Anastasia Hatziagelaki, Erifili Humphries, Steve E. Wichmann, H. -Erich Herder, Christian Illig, Thomas TI IL6 gene promoter polymorphisms and type 2 diabetes - Joint analysis of individual participants' data from 21 studies SO DIABETES LA English DT Article ID BODY-MASS INDEX; INTERLEUKIN-6 GENE; TNF-ALPHA; -174 G/C; METAANALYSIS; MELLITUS; IL-6; ASSOCIATION; C-174G; PLASMA AB Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, -174G > C (rs1800795) and -573G > C (rs1800796), have been investigated for association with type 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on > 20,000 participants from 21 published and unpublished studies. Collected data represent eight different countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 -174G > C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found between IL6 -573G > C and type 2 diabetes. The observed association of the IL6 -174 C-allele with a reduced risk of type 2 diabetes provides further evidence for the hypothesis that immune mediators are causally related to type 2 diabetes; however, because the association is borderline significant, additional data are still needed to confirm this finding. C1 GSF, Inst Epidemiol, Neuherberg, Germany. Univ Munich, Inst Biometry & Epidemiol, Munich, Germany. Translat Gen Res Inst, Phoenix, AZ USA. Steno Diabet Ctr, Copenhagen, Denmark. Malmo Univ Hosp, Dept Clin Sci, Malmo, Sweden. Univ Lubeck, Inst Human Genet, Lubeck, Germany. Univ Regensburg, Clin & Policlin Internal Med 2, D-8400 Regensburg, Germany. Univ Dusseldorf, Leibniz Inst, German Diabet Ctr, D-4000 Dusseldorf, Germany. Univ Coll Swansea, Sch Med, Swansea, W Glam, Wales. UCL, Sch Med, Ctr Cardiovasc Genet, London, England. Ealing Gen Hosp, London, England. MRC, Wolfson Inst Prevent Med, Cardiovasc Res Grp, London, England. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Natl Publ Hlth Inst, Dibet & Genet Epidemiol Unit, Helsinki, Finland. Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. S Ostrobothnia Cent Hosp, Seinajoki, Finland. German Inst Human Nutr, Dept Epidemiol, Potsdam, Germany. German Inst Human Nutr, Dept Clin Nutr, Potsdam, Germany. Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden. Sahlgrens Univ Hosp, Dept Clin Pharmacol, S-41345 Gothenburg, Sweden. Univ Hosp Josep Trueta, Diabet Endocrinol & Nutr Unit, Girona, Spain. NIDDK, Phoenix, AZ USA. Univ Hosp Joan 23, Res Unit, Tarragona, Spain. Onassis Cardiac Surg Ctr, Mol Immunopathol & Histocompatibil Lab, Athens, Greece. Univ Athens, Hospt Attikon, Dept Internal Med 2, Athens, Greece. RP Illig, T (reprint author), GSF, Natl Res Ctr Environm & Hlth, Inst Epidemiol, Ingolstaedter Landstr 1, D-85764 Neuherberg, Germany. EM illig@gsf.de RI Genetic Epidemiology, Innsbruck Med.Univ./C-2095-2008; Humphries, Stephen/C-5075-2008; Lieb, Wolfgang/C-1990-2012; Huth, Cornelia/B-5350-2014; Meisinger, Christine/B-5358-2014; Thorand, Barbara/B-5349-2014; Grallert, Harald/B-3424-2013; Hanson, Robert/O-3238-2015; OI Huth, Cornelia/0000-0003-2421-433X; Thorand, Barbara/0000-0002-8416-6440; Hanson, Robert/0000-0002-4252-7068; Gieger, Christian/0000-0001-6986-9554; Meisinger, Christa/0000-0002-9026-6544; Fernandez-Real, Jose Manuel/0000-0002-7442-9323 FU Intramural NIH HHS NR 27 TC 62 Z9 67 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2006 VL 55 IS 10 BP 2915 EP 2921 DI 10.2337/db06-0600 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089VU UT WOS:000240910400033 PM 17003362 ER PT J AU Iannotti, RJ Nansel, TR Schneider, S Haynie, DL Simons-Morton, B Sobel, DO Zeitzoff, L Plotnick, LP Clark, L AF Iannotti, Ronald J. Nansel, Tonja R. Schneider, Stefan Haynie, Denise L. Simons-Morton, Bruce Sobel, Douglas O. Zeitzoff, Linda Plotnick, Leslie P. Clark, Loretta TI Assessing regimen adherence of adolescents with type 1 diabetes SO DIABETES CARE LA English DT Article ID SELF-MANAGEMENT; LONGITUDINAL ANALYSIS; METABOLIC-CONTROL; MELLITUS; CHILDREN; PREDICTORS; YOUTH AB OBJECTIVE - The purpose of this study is to evaluate two updated measures of diabetes regimen adherence. The Diabetes Self-Management Profile (DSMP) is a widely used, structured interview. Limitations include a substantial interviewer and respondent time burden and the need for well-trained inter-viewers to use appropriate prompts and score the open-ended responses. The Diabetes Behavior Rating Scale (DBRS) is a self-administered, fixed-choice survey. RESEARCH DESIGN AND METHODS - Both measures were administered to 146 youth with type I diabetes (aged 11-18 years) and their parents. Items were added to the DBRS to allow for both flexible and conventional regimens, and the DSMP was modified to use standardized wording across items, accommodate flexible regimens, and permit administration by nonmedical interviewers. RESULTS - Both measures had good evidence of internal consistency (for the DSMP: parent 0.75 and youth 0.70; for the DBRS: parent 0.84 and youth 0.84). Scores on the DSMP and the DBRS were significantly related (r = 0.72 for parents and 0.74 for youth). There was moderate agreement between parent and youth (DSMP, r = 0.51; DBRS, r = 0.48). The measures were correlated with HbA(1c) for both parent (DSMP, r = = -0.35; DBRS, r = -0.35) and youth (DSMP, r = -0.36; DBRS, r = -0.34) reports. CONCLUSIONS - Both measures exhibit good psychometric properties and good criterion validity but varied in terms of respondent and interviewer burden, issues that should be considered in selecting assessment procedures. C1 NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Dept Pediat, Washington, DC USA. Mt Washington Pediat Hosp, Pediat Endocrinol Clin, Baltimore, MD USA. John Hopkins Med Ctr, Pediat Endocrinol Dept, Baltimore, MD USA. RP Iannotti, RJ (reprint author), NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv,NIH, 6100 Execut Blvd,7B05, Bethesda, MD 20892 USA. EM iannottr@mail.nih.gov RI Schneider, Stefan/K-2815-2012; OI Nansel, Tonja/0000-0002-8298-7595; Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079 NR 21 TC 37 Z9 37 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2006 VL 29 IS 10 BP 2263 EP 2267 DI 10.2337/dc06-0685 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 091FZ UT WOS:000241013600014 PM 17003304 ER PT J AU Korf, ESC White, LR Scheltens, P Launer, LJ AF Korf, Esther S. C. White, Lon R. Scheltens, Ph Launer, Lenore J. TI Brain aging in very old men with type 2 diabetes - The Honolulu-Asia Aging Study SO DIABETES CARE LA English DT Article ID INSULIN-DEGRADING ENZYME; ATTENUATED INVERSION-RECOVERY; JAPANESE-AMERICAN MEN; ALZHEIMERS-DISEASE; CARDIOVASCULAR-DISEASE; COGNITIVE IMPAIRMENT; HIPPOCAMPAL ATROPHY; GLUCOSE-TOLERANCE; ELDERLY-PEOPLE; HEART-PROGRAM AB OBJECTIVE - Type 2 diabetes leads to cognitive impairment and dementia, which may reflect microvascular and macrovascular complications as well as neurodegenerative processes. There are few studies on the anatomical basis for loss of cognitive function in type 2 diabetes. The objective of this study was to investigate the association between type 2 diabetes and markers of brain aging on magnetic resonance images, including infarcts, lacunes, and white matter hyperintensities as markers of vascular damage and general and hippocampal atrophy as markers of neurodegeneration in Japanese-American men born between 1900 and 1919 and followed since 1965 in the Honolulu-Asia Aging Study. RESEARCH DESIGN AND METHODS - Prevalent and incident dementia was assessed. Associations between magnetic resonance imaging markers and diabetic status were estimated with logistic regression, controlling for sociodemographic and other vascular factors. RESULTS - The prevalence of type 2 diabetes in the cohort is 38%. Subjects with type 2 diabetes had a moderately elevated risk for lacunes (odds ratio [OR] 1.6 [95% CI 1.0-2.6]) and hippocampal atrophy (1.7 [0.9-2.9]). The risk for both hippocampal atrophy and lacunes/ infarcts was twice as high in subjects with compared with those without type 2 diabetes. Among the group with type 2 diabetes, those with the longest duration of diabetes, those taking insulin, and those with complications had relatively more pathologic brain changes. CONCLUSIONS - There is evidence that older individuals with type 2 diabetes have an elevated risk for vascular brain damage and neurodegenerative changes. These pathological changes may be the anatomical basis for an increased risk of cognitive impairment or dementia in type 2 diabetes. C1 NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. Vrije Univ Amsterdam, Med Ctr, Neurol & Alzheimer Ctr, Amsterdam, Netherlands. Pacific Res Inst Hlth, Honolulu, HI USA. RP Launer, LJ (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, 7201 Wisconsin Ave,Room 3C-309, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov FU Intramural NIH HHS; NHLBI NIH HHS [N01-HC-05102]; NIA NIH HHS [N01-AG-4-2149] NR 47 TC 99 Z9 114 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2006 VL 29 IS 10 BP 2268 EP 2274 DI 10.2337/dc06-0243 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 091FZ UT WOS:000241013600015 PM 17003305 ER PT J AU Obrosova, IG Drel, VR Kumagai, AK Szabo, C Pacher, P Stevens, MJ AF Obrosova, I. G. Drel, V. R. Kumagai, A. K. Szabo, C. Pacher, P. Stevens, M. J. TI Early diabetes-induced biochemical changes in the retina: comparison of rat and mouse models SO DIABETOLOGIA LA English DT Article DE mouse; NAD(+)/NADH ratio; oxidative stress; poly(ADP-ribosyl)ation; rat; retina; sorbitol pathway of glucose metabolism; streptozotocin diabetes; vascular endothelial growth factor ID ALDOSE REDUCTASE INHIBITOR; ENDOTHELIAL GROWTH-FACTOR; CAPILLARY CELL-DEATH; GALACTOSE-FED DOGS; ALPHA-LIPOIC ACID; POLY(ADP-RIBOSE) POLYMERASE; SORBITOL DEHYDROGENASE; POLYOL PATHWAY; FACTOR OVEREXPRESSION; LIPID-PEROXIDATION AB Recently, various transgenic and knock-out mouse models have become available for studying the pathogenesis of diabetic retinopathy. At the same time, diabetes-induced retinal changes in the wild-type mice remain poorly characterised. The present study compared retinal biochemical changes in rats and mice with similar (6-week) durations of streptozotocin-induced diabetes. Materials and methods The experiments were performed on Wistar rats and C57Bl6/J mice. Retinal glucose, sorbitol, fructose, lactate, pyruvate, glutamate, alpha-ketoglutarate and ammonia were measured spectrofluorometrically by enzymatic methods. Vascular endothelial growth factor (VEGF) protein was assessed by ELISA, and poly(ADP-ribosyl)ation by immunohistochemistry and western blot analysis. Free mitochondrial and cytosolic NAD(+)/NADH ratios were calculated from the glutamate and lactate dehydrogenase systems. Results Retinal glucose concentrations were similarly increased in diabetic rats and mice, vs controls. Diabetic rats manifested similar to 26- and 5-fold accumulation of retinal sorbitol and fructose, respectively, whereas elevation of both metabolites in diabetic mice was quite modest. Correspondingly, diabetic rats had (1) increased retinal malondialdehyde plus 4-hydroxyalkenal concentrations, (2) reduced superoxide dismutase (SOD), glutathione peroxidase, glutathione reductase and glutathione transferase activities, (3) slightly increased poly(ADP-ribose) immunoreactivity and poly(ADP-ribosyl)ated protein abundance, and (4) VEGF protein overexpression. Diabetic mice lacked these changes. SOD activity was 21-fold higher in murine than in rat retinas (the difference increased to 54-fold under diabetic conditions), whereas other antioxidative enzyme activities were 3- to 10-fold lower. With the exception of catalase, the key antioxidant defence enzyme activities were increased, rather than reduced, in diabetic mice. Diabetic rats had decreased free mitochondrial and cytosolic NAD(+)/NADH ratios, consistent with retinal hypoxia, whereas both ratios remained in the normal range in diabetic mice. Conclusions/interpretation Mice with short-term streptozotocin-induced diabetes lack many biochemical changes that are clearly manifest in the retina of streptozotocin-diabetic rats. This should be considered when selecting animal models for studying early retinal pathology associated with diabetes. C1 Louisiana State Univ Syst, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Inotek Pharmaceut Corp, Beverly, MA USA. NIAAA, NIH, Lab Physiol Studies, Bethesda, MD USA. RP Obrosova, IG (reprint author), Louisiana State Univ Syst, 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] NR 42 TC 54 Z9 54 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 2006 VL 49 IS 10 BP 2525 EP 2533 DI 10.1007/s00125-006-0356-7 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 082BR UT WOS:000240362000035 PM 16896942 ER PT J AU Jazii, FR Najafi, Z Malekzadeh, R Yazdanbod, M Conrads, TP Abnet, C Nouraen, O Karkhane, AA AF Rastgar Jazii, F. Najafi, Z. Malekzadeh, R. Yazdanbod, M. Conrads, T. P. Abnet, C. Nouraen, O. Karkhane, A. A. TI Proteomics and proteome analysis of Squamous Cell Carcinoma of Esophagus SO DIFFERENTIATION LA English DT Meeting Abstract C1 NIGEB, Tehran, Iran. Univ Tehran Med Sci, Digest Dis Res Ctr, Tehran, Iran. Univ Tehran Med Sci, Dept Surg Shariati Hosp, Tehran, Iran. Natl Canc Inst, Mass Spectrometry Ctr, Frederick, MD USA. DCEG Natl Canc Inst, Nutr Epidemiol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD OCT PY 2006 VL 74 IS 8 MA O29 BP 456 EP 457 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 085KN UT WOS:000240603100032 ER PT J AU Lee, WM Brown, KE Young, NS Dawson, GJ Schlauder, GG Gutierrez, RA Fontana, R Rossaro, L Davern, T Lalani, E AF Lee, W. M. Brown, K. E. Young, N. S. Dawson, G. J. Schlauder, G. G. Gutierrez, R. A. Fontana, R. Rossaro, L. Davern, T. Lalani, E. CA ALF Study Grp TI Brief report: No evidence for parvovirus B19 or hepatitis E virus as a cause of acute liver failure SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE parvovirus B19; hepatitis E virus; acute liver failure; encephalopathy; polymerase chain reaction ID INFECTION AB Viral hepatitis A and B are known to cause acute liver failure. While nearly 20% of acute liver failure cases are of indeterminate etiology, screening for other viruses has not been uniformly performed. We looked for evidence for parvovirus B 19 and hepatitis E virus in sera from U.S. acute liver failure patients. For B 19, 78 patients' sera, including 34 with indeterminate etiology, were evaluated by DNA dot-blot hybridization, reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay for immunoglobin G and M antibodies; none showed evidence for infection. In like manner, 126 patients' sera were analyzed for hepatitis E virus RNA by reverse transcription polymerase chain reaction and for hepatitis E virus immunoglobin G and M antibodies by enzyme-linked immunosorbent assay; no acute hepatitis E virus cases were identified. If a unique acute liver failure virus exists, it is neither of these candidate agents. C1 Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX 75390 USA. NHLBI, Bethesda, MD 20892 USA. Abbott Labs, Abbott Pk, IL 60064 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Lee, WM (reprint author), Univ Texas, SW Med Ctr, Div Digest & Liver Dis, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM William.Lee@utsouthwestern.edu FU FDA HHS [FD-R-001661]; NIDDK NIH HHS [R03 DK52827] NR 8 TC 20 Z9 20 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2006 VL 51 IS 10 BP 1712 EP 1715 DI 10.1007/s10620-005-9061-5 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099XY UT WOS:000241632300005 PM 16964546 ER PT J AU Johnson, BA Roache, JD Ait-Daoud, N Javors, MA Harrison, JM Elkashef, A Mojsiak, J Li, SH Bloch, DA AF Johnson, Bankole A. Roache, John D. Ait-Daoud, Nassima Javors, Martin A. Harrison, Joseph M. Elkashef, Ahmed Mojsiak, Jurij Li, Shou-Hua Bloch, Daniel A. TI A preliminary randomized, double-blind, placebo-controlled study of the safety and efficacy of ondansetron in the treatment of cocaine dependence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE ondansetron; cocaine dependence; humans; 5-HT3 receptors; benzoylecgonine; cognitive behavioral therapy ID 5-HT3 RECEPTOR ANTAGONIST; COGNITIVE-BEHAVIORAL THERAPY; EXTRACELLULAR DOPAMINE; NUCLEUS-ACCUMBENS; INDUCED LOCOMOTION; MESOLIMBIC SYSTEM; ALCOHOL-ABUSE; WITHDRAWAL; DRUGS; RATS AB Prior studies have demonstrated inefficacy among dopamine receptor antagonists for treating cocaine dependence. An alternative approach would be to investigate the ability of indirect inhibitors of cortico-mesolimbic dopamine release, such as the 5-HT3 receptor antagonist ondansetron, to reduce cocaine's reinforcing effects. We hypothesized that ondansetron might be more efficacious than placebo at reducing cocaine intake and promoting abstinence in cocaine-dependent individuals. In a pilot randomized, double-blind, 10-week controlled trial, 63 treatment-seeking, cocaine-dependent men and women received ondansetron (0.25mg, 1.0mg, or 4.0mg twice daily) or placebo. Up to three times per week, participants were assessed on several measures of cocaine use, including urine benzoylecgonine. Cognitive behavioral therapy was administered weekly. Ondansetron was well tolerated, causing no serious adverse events. The ondansetron 4.0 mg group had the lowest dropout rate among all treatment groups and a greater rate of improvement in percentage of participants with a cocaine-free week compared with the placebo group (p = 0.02), whereas the ondansetron 1.0 mg group had a lower rate of improvement in percentage of weekly mean non-use days than did placebo recipients (p = 0.04). These results suggest the possibility of a non-linear dose-response function, with evidence supporting efficacy for the 4.0 mg group. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Virginia, Dept Psychiat Med, Charlottesville, VA 22908 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Ophthalmol, San Antonio, TX 78229 USA. NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Biostat, Stanford, CA 94305 USA. RP Johnson, BA (reprint author), Univ Virginia, Dept Psychiat Med, POB 800623, Charlottesville, VA 22908 USA. EM bankolejohnson@virginia.edu FU NIDA NIH HHS [N01-DA-9-8101] NR 43 TC 32 Z9 33 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD OCT 1 PY 2006 VL 84 IS 3 BP 256 EP 263 DI 10.1016/j.drugalcdep.2006.02.011 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 095EB UT WOS:000241289900006 PM 16631323 ER PT J AU Parker, CN Shamu, CE Kraybill, B Austin, CP Bajorath, J AF Parker, Christian N. Shamu, Caroline E. Kraybill, Brian Austin, Christopher P. Bajorath, Juergen TI Measure, mine, model, and manipulate: the future for HTS and chemoinformatics? SO DRUG DISCOVERY TODAY LA English DT Editorial Material ID DOCKING COMPETITION C1 Novartis Pharm AG, CH-4002 Basel, Switzerland. Harvard Univ, Sch Med, ICCB Longwood, Boston, MA USA. NHGRI, Chem Gen Ctr, NIH, Bethesda, MD 20892 USA. Univ Bonn, Dept Life Sci Informat, D-53113 Bonn, Germany. RP Parker, CN (reprint author), Novartis Pharm AG, WSJ-088-2-06, CH-4002 Basel, Switzerland. EM bajorath@bit.uni-bonn.de NR 9 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD OCT PY 2006 VL 11 IS 19-20 BP 863 EP 865 DI 10.1016/j.drudis.2006.08.006 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 100EC UT WOS:000241649400001 PM 16997135 ER PT J AU Trebak, M AF Trebak, Mohamed TI Canonica transient receptor potential channels in disease: targets for novel drug therapy? SO DRUG DISCOVERY TODAY LA English DT Review ID NONSELECTIVE CATION CHANNELS; CAPACITATIVE CA2+ ENTRY; AIRWAY SMOOTH-MUSCLE; CALCIUM-ENTRY; TRP CHANNELS; ENDOTHELIAL PERMEABILITY; ION CHANNELS; IN-VIVO; TRPC3/6/7 SUBFAMILY; T-LYMPHOCYTES AB The canonical transient receptor potential (TRPC) channels constitute one of the three major families within the large transient receptor potential (TRP) superfamily. TRPC channels are the closest mammalian homologues of Drosophila TRP, the light-activated channel in Drosophila photoreceptor cells. All TRPC channels (TRPC1-7) are activated via phospholipase-C-coupled receptors and were, therefore, proposed to encode elusive native receptor-activated cation channels in many cell types. A physiological role has been established for all of the known TRPC channels, including the control of vascular tone (TRPC1, TRPC4 and TRPC6) or lymphocyte activation, which is essential for immune competence (TRPC1 and TRPC3). The emergence of TRPC channels in controlling a variety of biological functions offers new and promising targets for drug development. C1 NIEHS, Dept Hlth & Humam Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Trebak, M (reprint author), NIEHS, Dept Hlth & Humam Serv, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM trebak@niehs.nih.gov RI Trebak, Mohamed/E-7405-2014 FU Intramural NIH HHS NR 69 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD OCT PY 2006 VL 11 IS 19-20 BP 924 EP 930 DI 10.1016/j.drudis.2006.08.002 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 100EC UT WOS:000241649400009 PM 16997143 ER PT J AU Wrenn, CC Holmes, A AF Wrenn, Craige C. Holmes, Andrew TI The role of galanin in modulating stress-related neural pathways SO DRUG NEWS & PERSPECTIVES LA English DT Review ID OVEREXPRESSING TRANSGENIC MICE; LOCUS-COERULEUS NEURONS; RAT VENTRAL HIPPOCAMPUS; CENTRAL-NERVOUS-SYSTEM; CATECHOLAMINERGIC-CHOLINERGIC INTERACTIONS; PREPROGALANIN MESSENGER-RNA; CHRONIC RESTRAINT STRESS; DORSAL RAPHE NUCLEUS; RELEASE IN-VIVO; BASAL FOREBRAIN AB Galanin is a 29 or 30 amino acid peptide with a close anatomical and neurophysiological relationship with neural systems mediating stress. In rodent behavioral studies, the consequences of galanin activity on stress-related behaviors such as anxiety-like and depression-like behavior varies according to site of administration and behavioral assay used. However, galaninergic systems remain a promising novel target for new antianxiety and antidepressant drugs. Current work attempting to delineate which galanin receptor subtypes mediate which effects of galanin will undoubtedly inform the development of these drugs. Further, the well-established deleterious effects of galanin on cognitive function provide support for galanin as a novel link between stress, anxiety and memory. This link suggests that galaninergic drugs could provide a novel therapeutic option for psychopathologies, such as post-traumatic stress syndrome, in which abnormal memory and emotion are intertwined. (c) 2006 Prous Science. All rights reserved. C1 Drake Univ, Coll Pharm & Hlth Sci, Des Moines, IA 50311 USA. NIAAA, NIH, Sect Behav Sci & Genet, Lab Integrat Neurosci, Rockville, MD 20852 USA. RP Wrenn, CC (reprint author), Drake Univ, Coll Pharm & Hlth Sci, Des Moines, IA 50311 USA. EM wrenn@drake.edu FU Intramural NIH HHS NR 106 TC 11 Z9 11 U1 0 U2 1 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0214-0934 J9 DRUG NEWS PERSPECT JI Drug News Perspect. PD OCT PY 2006 VL 19 IS 8 BP 461 EP 467 DI 10.1358/dnp.2006.19.8.1043963 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 116SC UT WOS:000242821600003 PM 17160146 ER PT J AU Jamieson, PM Li, C Kukura, C Vaughan, J Vale, W AF Jamieson, Pauline M. Li, Chien Kukura, Christina Vaughan, Joan Vale, Wylie TI Urocortin 3 modulates the neuroendocrine stress response and is regulated in rat amygdala and hypothalamus by stress and glucocorticoids SO ENDOCRINOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; MESSENGER-RIBONUCLEIC-ACID; EDINGER-WESTPHAL NUCLEUS; ANXIETY-LIKE BEHAVIOR; PARAVENTRICULAR NUCLEUS; FACTOR-RECEPTOR; HORMONE-RECEPTOR; CRF2 RECEPTOR; CARDIOVASCULAR FUNCTION AB The endogenous corticotropin-releasing factor (CRF) type 2 receptor (CRFR2)-selective ligand urocortin 3 is expressed in discrete subcortical brain regions with fibers distributed mainly to hypothalamic and limbic structures. Close anatomical association between major urocortin 3 terminal fields and CRFR2 in hypothalamus, lateral septum, and medial amygdala ( MEA) suggest it is well placed to modulate behavioral and hormonal responses to stress. Urocortin 3 was administered intracerebroventricularly to male rats under basal conditions or before a restraint stress, and circulating ACTH, corticosterone, glucose, and insulin were measured. Urocortin 3 activated the hypothalamic-pituitary-adrenal axis under basal conditions and augmented ACTH responses to restraint stress. Elevated blood glucose with lowered insulin to glucose ratios in both groups suggested increased sympathetic activity. Circulating catecholamines were also increased by urocortin 3, providing additional evidence for sympathoadrenomedullary stimulation. Intracerebroventricular urocortin 3 increased vasopressin mRNA expression in the parvocellular division of the hypothalamic paraventricular nucleus, whereas CRF expression was unchanged, providing a possible mechanism by which urocortin 3 mediates its actions. Urocortin 3 mRNA expression was examined after exposure to stress-related paradigms. Restraint increased levels in MEA with a trend to increased expression in the rostral perifornical hypothalamic area, whereas hemorrhage and food deprivation decreased expression in MEA. Adrenalectomy markedly increased expression in the rostral perifornical hypothalamic area, and high-level corticosterone replacement restored this to control levels. The evidence that urocortin 3 has the potential to influence hormonal components of the stress response and the changes in its expression levels after stressors is consistent with a potential function for the endogenous peptide in modulating stress responses. C1 Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Vale, W (reprint author), Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM vale@salk.edu FU NIDDK NIH HHS [DK26741] NR 72 TC 42 Z9 42 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 2006 VL 147 IS 10 BP 4578 EP 4588 DI 10.1210/en.2006-0545 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 087IW UT WOS:000240737100008 PM 16809443 ER PT J AU Pedraza, N Rosell, M Villarroya, J Iglesias, R Gonzalez, FJ Solanes, G Villarroya, F AF Pedraza, Neus Rosell, Meritxell Villarroya, Joan Iglesias, Roser Gonzalez, Frank J. Solanes, Gemma Villarroya, Francesc TI Developmental and tissue-specific involvement of peroxisome proliferator-activated receptor-alpha in the control of mouse uncoupling protein-3 gene expression SO ENDOCRINOLOGY LA English DT Article ID FATTY-ACID OXIDATION; SKELETAL-MUSCLE; UP-REGULATION; MICE; DELTA; UCP3; THERMOGENESIS; TRANSCRIPTION; METABOLISM; MYOTUBES AB Uncoupling protein-3 (UCP3) is a member of the mitochondrial carrier family expressed preferentially in skeletal muscle and heart. It appears to be involved in metabolic handling of fatty acids in a way that minimizes excessive production of reactive oxygen species. Fatty acids are powerful regulators of UCP3 gene transcription. We have found that the role of peroxisome proliferator-activated receptor-alpha (PPAR alpha) on the control of UCP3 gene expression depends on the tissue and developmental stage. In adults, UCP3 mRNA expression is unaltered in skeletal muscle from PPAR alpha-null mice both in basal conditions and under the stimulus of starvation. In contrast, UCP3 mRNA is down- regulated in adult heart both in fed and fasted PPAR alpha-null mice. This occurs despite the increased levels of free fatty acids caused by fasting in PPAR alpha-null mice. In neonates, PPAR alpha-null mice show impaired UCP3 mRNA expression in skeletal muscle in response to milk intake, and this is not a result of reduced free fatty acid levels. The murine UCP3 promoter is activated by fatty acids through either PPAR alpha or PPAR delta but not by PPAR alpha or retinoid X receptor alone. PPAR delta-dependent activation could be a potential compensatory mechanism to ensure appropriate expression of UCP3 gene in adult skeletal muscle in the absence of PPAR alpha. However, among transcripts from other PPAR alpha and PPAR delta target genes, only those acutely induced by milk intake in wild-type neonates were altered in muscle or heart from PPAR alpha-null neonates. Thus, PPAR alpha-dependent regulation is required for appropriate gene regulation of UCP3 as part of the subset of fatty-acid-responsive genes in neonatal muscle and heart. C1 Univ Barcelona, Dept Bioquim & Biol Mol, E-08028 Barcelona, Spain. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Solanes, G (reprint author), Univ Barcelona, Dept Bioquim & Biol Mol, Avda Diagonal 645, E-08028 Barcelona, Spain. EM gsolanes@ub.edu RI Villarroya, Francesc/K-4357-2014; Pedraza Gonzalez, Neus/C-6390-2011; OI Pedraza Gonzalez, Neus/0000-0003-4749-5111; Villarroya, Francesc/0000-0003-1266-9142 NR 35 TC 14 Z9 14 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 2006 VL 147 IS 10 BP 4695 EP 4704 DI 10.1210/en.2006-0226 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 087IW UT WOS:000240737100022 PM 16857752 ER PT J AU Yang, Q Kurotani, R Yamada, A Kimura, S Gonzalez, FJ AF Yang, Qian Kurotani, Reiko Yamada, Atsushi Kimura, Shioko Gonzalez, Frank J. TI Peroxisome proliferator-activated receptor alpha activation during pregnancy severely impairs mammary lobuloalveolar development in mice SO ENDOCRINOLOGY LA English DT Article ID NUCLEAR HORMONE-RECEPTORS; DMBA-INDUCED MAMMARY; PPAR-ALPHA; GENE-EXPRESSION; CYCLIN D1; GLAND DEVELOPMENT; EPIDERMAL DIFFERENTIATION; OSTEOPROTEGERIN-LIGAND; DUCTAL MORPHOGENESIS; EPITHELIAL-CELLS AB To identify the potential functions of peroxisome proliferator-activated receptor alpha(PPAR alpha) in skin development, transgenic mice were generated to target constitutively activated PPAR alpha (VP16PPAR alpha) to the stratified epithelia by use of the keratin K5 promoter. In addition to marked alterations in epidermal development, the transgenic mice had a severe defect in lactation during pregnancy resulting in 100% pup mortality. In this study, the alteration of mammary gland development in these transgenic mice was investigated. The results showed that expression of the VP16PPAR alpha transgene during pregnancy resulted in impaired development of lobuloalveoli, which is associated with reduced proliferation and increased apoptosis of mammary epithelia. Mammary epithelia from transgenic mice also showed a significant reduction in the expression of beta-catenin and a down-regulation of one of its target genes, cyclin D1, which is thought to be required for lobuloalveolar development. Furthermore, upon PPAR alpha ligand treatment, similar effects on lobuloalveolar development were observed in wild-type mice, but not in PPAR alpha-null mice. These findings suggest that PPAR alpha activation has a marked influence in mammary lobuloalveolar development. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3106B, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 BC005708-14] NR 53 TC 20 Z9 20 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 2006 VL 147 IS 10 BP 4772 EP 4780 DI 10.1210/en.2006-0437 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 087IW UT WOS:000240737100030 PM 16857745 ER PT J AU Padilla-Banks, E Jefferson, WN Newbold, RR AF Padilla-Banks, Elizabeth Jefferson, Wendy N. Newbold, Retha R. TI Neonatal exposure to the phytoestrogen genistein alters mammary gland growth and developmental programming of hormone receptor levels SO ENDOCRINOLOGY LA English DT Article ID DIETHYLSTILBESTROL IN-UTERO; BREAST-CANCER; PREMENOPAUSAL WOMEN; DIETARY GENISTEIN; ORGANOCHLORINE EXPOSURE; PROGESTERONE RECEPTORS; ESTROGENIC CHEMICALS; POSTMENOPAUSAL WOMEN; ISOFLAVONE CONTENT; MATERNAL EXPOSURE AB Developmental effects of genistein (Gen) on the mammary gland were investigated using outbred female CD-1 mice treated neonatally on d 1-5 by sc injections at doses of 0.5, 5, or 50 mg/kg center dot d. Examination of mammary gland whole mounts (no. 4) before puberty (4 wk) revealed no morphological differences in development after Gen treatment. However, mice treated with Gen- 50 had stunted development characterized by less branching at 5 wk and decreased numbers of terminal end buds at 5 and 6 wk. Conversely, at 6 wk, Gen-0.5-treated mice exhibited advanced development with increased ductal elongation compared with controls. Measurements of hormone receptor levels showed increased levels of progesterone receptor protein and estrogen receptor-beta mRNA in Gen-0.5-treated mice compared with controls; ER alpha expression was decreased after all doses of Gen treatment. Lactation ability, measured by pup weight gain and survival, was not affected after neonatal Gen-0.5 and Gen-5. Mice treated with Gen-50 did not deliver live pups; therefore, lactation ability could not be determined. Evaluation of mammary glands in aged mice ( 9 months) showed no differences between Gen-0.5-treated mice and controls but mice treated with Gen-5 and Gen-50 exhibited altered morphology including reduced lobular alveolar development, dilated ducts, and focal areas of "beaded" ducts lined with hyperplastic ductal epithelium. In summary, neonatal Gen exposure altered mammary gland growth and development as well as hormone receptor levels at all doses examined; higher doses of Gen led to permanent long-lasting morphological changes. C1 NIEHS, Dev Endocrinol & Endocrine Disrupter Sect, Mol Toxicol Lab, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Newbold, RR (reprint author), NIEHS, Dev Endocrinol & Endocrine Disrupter Sect, Mol Toxicol Lab, NIH,Dept Hlth & Human Serv, POB 12233,Mail Drop E4-02, Res Triangle Pk, NC 27709 USA. EM newbold1@niehs.nih.gov FU Intramural NIH HHS NR 85 TC 42 Z9 43 U1 2 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 2006 VL 147 IS 10 BP 4871 EP 4882 DI 10.1210/en.2006-0389 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 087IW UT WOS:000240737100041 PM 16857750 ER PT J AU Bojanowski, CM Shen, DF Chew, EY Ning, BT Csaky, KG Green, WR Chan, CC Tuo, JS AF Bojanowski, Christine M. Shen, Defen Chew, Emily Y. Ning, Baitang Csaky, Karl G. Green, W. Richard Chan, Chi-Chao Tuo, Jingsheng TI An Apolipoprotein E variant may protect against age-related macular degeneration through cytokine regulation SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE age-related macular degeneration; apolipoprotein E; single nucleotide polymorphism; genetic susceptibility; cytokines ID COMPLEMENT FACTOR-H; C-REACTIVE PROTEIN; PIGMENT EPITHELIAL-CELLS; ENDOTHELIAL GROWTH-FACTOR; ALZHEIMERS-DISEASE; E GENE; CHOROIDAL NEOVASCULARIZATION; APOE GENOTYPE; AMYLOID-BETA; ANIMAL-MODEL AB Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness among the elderly in Western countries. Genetic factors, age, cigarette smoking, nutrition, and exposure to light have been identified as AMD risk factors. In this study, we investigated the association between ApoE C112R/R158C single nucleotide polymorphisms (which determine the E2, E3, and E4 isoforms) and age-related macular degeneration (AMD), and the mechanism underlying the association. Genomic DNA was extracted from 133 clinically screened controls, 94 volunteers with a younger mean age, 120 patients with advanced AMD, and 40 archived ocular AMD slides for single nucleotide polymorphism typing. The effects of recombinant ApoE isoforms on CCL2 (a chemokine), CX3CR1 (a chemokine receptor), and VEGF (a cytokine) expression in cultured human retinal pigment epithelium (RIPE) cells were tested and serum cholesterol profiles of the clinically screened subjects were analyzed. ApoE112R (EA) distribution differed significantly between AMD patients and controls. ApoE112R allele frequency was 10.9% in the AMD group when compared with 16.5% in the younger controls and 18.8% in the clinically screened controls. The pathologically diagnosed archived AMD cases had the lowest allele frequency of 5%. No significant differences in ApoE158C (E2) distribution were observed among the groups. A meta-analysis of 8 cohorts including 4,289 subjects showed a strong association between AMD and 112R, but not 158C. In vitro studies found that recombinant ApoE suppresses CCL2 and VEGF expression in RIPE cells. However, the E4 isoform showed more suppression than E3 in both cases. These results further confirm the association between ApoE112R and a decreased risk of AMD development. The underlying mechanisms may involve differential regulation of both CCL2 and VEGF by the ApoE isoforms. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. Natl Ctr Toxicol Res, Div Pharmacogen & Mol Epidemiol, Jefferson, AR 72079 USA. NEI, Sect Retinal Dis & Therapeut, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Sch, Wilmer Eye Inst, Baltimore, MD USA. RP Tuo, JS (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 10N103, Bethesda, MD 20892 USA. EM tuoj@nei.nih.gov OI Tuo, Jingsheng/0000-0002-1372-7810 FU Intramural NIH HHS [Z99 EY999999, Z01 EY000418-04] NR 59 TC 35 Z9 38 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2006 VL 47 IS 8 BP 594 EP 602 DI 10.1002/em.20233 PG 9 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 099TJ UT WOS:000241618600004 PM 16823865 ER PT J AU Samanic, C Rusiecki, J Dosemeci, M Hou, L Hoppin, JA Sandler, DP Lubin, J Blair, A Alavanja, MCR AF Samanic, Claudine Rusiecki, Jennifer Dosemeci, Mustafa Hou, Lifang Hoppin, Jane A. Sandler, Dale P. Lubin, Jay Blair, Aaron Alavanja, Michael C. R. TI Cancer incidence among pesticide applicators exposed to dicamba in the Agricultural Health Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cancer incidence; farming; neoplasms; pesticides; United States ID NON-HODGKINS-LYMPHOMA; RISK-FACTORS; IOWA; MEN; EXPOSURES; MINNESOTA AB BACKGROUND: Dicamba is an herbicide commonly applied to crops in the United States and abroad. We evaluated cancer incidence among pesticide applicators exposed to dicamba in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in North Carolina and Iowa. METHODS: Detailed pesticide exposure information was obtained through a self-administered questionnaire completed from 1993 to 1997. Cancer incidence was followed through 31 December 2002 by linkage to state cancer registries. We used Poisson regression to estimate rate ratios and 95% confidence intervals for cancer subtypes by tertiles of dicamba exposure. Two dicamba exposure metrics were used: lifetime exposure days and intensity-weighted lifetime exposure days (lifetime days x intensity score). RESULTS: A total of 41,969 applicators were included in the analysis, and 22,036 (52.5%) reported ever using dicamba. Exposure was not associated with overall cancer incidence nor were there strong associations with any specific type of cancer. When the reference group comprised low-exposed applicators, we observed a positive trend in risk between lifetime exposure days and lung cancer (p = 0.02), but none of the individual point estimates was significantly elevated. We so observed significant trends of increasing risk for colon cancer for both lifetime exposure days and intensity-weighted lifetime days, although these results are largely due to elevated risk at the highest exposure level. There was no apparent risk for non-Hodgkin lymphoma. CONCLUSIONS: Although associations between exposure and lung and colon cancer were observed, we did not find dear evidence for an association between dicamba exposure and cancer risk. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Alavanja, MCR (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,Room 8000, Rockville, MD 20852 USA. EM alavanjm@mail.nih.gov OI Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS NR 29 TC 20 Z9 25 U1 3 U2 11 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 2006 VL 114 IS 10 BP 1521 EP 1526 DI 10.1289/ehp.9204 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 090RW UT WOS:000240969700027 PM 17035136 ER PT J AU Schober, SE Mirel, LB Graubard, BI Brody, DJ Flegal, KM AF Schober, Susan E. Mirel, Lisa B. Graubard, Barry I. Brody, Debra J. Flegal, Katherine M. TI Blood lead levels and death from all causes, cardiovascular disease, and cancer: Results from the NHANES III Mortality Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cancer; cardiovascular disease; lead; mortality; National Health and Nutrition Examination Survey (NHANES); United States ID NUTRITION EXAMINATION SURVEYS; RENAL-FUNCTION; UNITED-STATES; BONE LEAD; NATIONAL-HEALTH; HYPERTENSION; PRESSURE; EXPOSURE; ASSOCIATION; POPULATION AB BACKGROUND, Analyses of mortality data for participants examined in 1976-1980 in the second National Health and Nutrition Examination Survey (NHANES II) suggested an increased risk of mortality at blood lead levels > 20 mu g/dL. Blood lead levels have decreased markedly since the late 1970s. In NHANES III, conducted during 1988-1994, few adults had levels > 20 mu g/dL. OBJECTIVE: Our objective in this study was to determine the risk of mortality in relation to lower blood lead levels observed for adult participants of NHANES III. METHODS: We analyzed mortality information for 9,757 participants who had a blood lead measurement and who were > 40 years of age at the baseline examination. Using blood lead levels categorized as < 5, 5 to < 10, and >= 10 mu g/dL, we determined the relative risk of mortality from all causes, cancer, and cardiovascular disease through Cox proportional hazard regression analysis. RESULTS: Using blood lead levels < 5 mu g/dL as the referent, we determined that the relative risk of mortality from all causes was 1.24 [95% confidence interval (CI), 1.05-1.48] for those with blood levels of 5-9 mu g/dL and 1.59 (95% CI, 1.28-1.98) for those with blood levels >= 10 mu g/dL (p for trend < 0.001). The magnitude of risk was similar for deaths due to cardiovascular disease and cancer, and tests for trend were statistically significant (p < 0.01) for both causes of death. CONCLUSION: In a nationally representative sample of the U.S. population, blood lead levels as low as 5-9 mu g/dL were associated with an increased risk of death from all causes, cardiovascular disease, and cancer. C1 Ctr Dis Control & Prevent, NCHS, Div Hlth & Nutr Examinat Stat, NHANES Program,CDC, Hyattsville, MD 20782 USA. Harris Corp, Falls Church, VA USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Schober, SE (reprint author), Ctr Dis Control & Prevent, NCHS, Div Hlth & Nutr Examinat Stat, NHANES Program,CDC, 3311 Toledo Rd,Room 4210, Hyattsville, MD 20782 USA. EM SSchober@cdc.gov RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X FU Intramural NIH HHS NR 33 TC 101 Z9 103 U1 1 U2 13 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 2006 VL 114 IS 10 BP 1538 EP 1541 DI 10.1289/ehp.9123 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 090RW UT WOS:000240969700030 PM 17035139 ER PT J AU Schwartz, DA Martin, WJ AF Schwartz, David A. Martin, Wharn J., II TI HEALing in New Orleans SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Schwartz, DA (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM david.schwartz@niehs.nih.gov; wjmartin@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 2006 VL 114 IS 10 BP A570 EP A570 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 090RW UT WOS:000240969700001 ER PT J AU Galperin, MY AF Galperin, Michael Y. TI A square archaeon, the smallest eukaryote and the largest bacteria SO ENVIRONMENTAL MICROBIOLOGY LA English DT Editorial Material ID SP STRAIN RHA1; OSTREOCOCCUS-TAURI; ALCANIVORAX-BORKUMENSIS; HALOQUADRATUM-WALSBYI; MICROBIAL DIVERSITY; MYXOCOCCUS-XANTHUS; GLIDING MOTILITY; GENOME SEQUENCE; CULTIVATION; PROTEINS C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS NR 35 TC 0 Z9 0 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD OCT PY 2006 VL 8 IS 10 BP 1683 EP 1687 DI 10.1111/J.1462-2920.2006.01131.x PG 5 WC Microbiology SC Microbiology GA 079VE UT WOS:000240205200001 PM 16958749 ER PT J AU Payne-Sturges, D Zenick, H Wells, C Sanders, W AF Payne-Sturges, Devon Zenick, Harold Wells, Charles Sanders, William TI We cannot do it alone: Building a multi-systems approach for assessing and eliminating environmental health disparities SO ENVIRONMENTAL RESEARCH LA English DT Editorial Material ID RESIDENTIAL SEGREGATION; INFANT-MORTALITY; AFRICAN-AMERICANS; UNITED-STATES; JUSTICE; SURVEILLANCE; MINORITY C1 [Payne-Sturges, Devon; Sanders, William] US EPA, Off Childrens Hlth Protect, Washington, DC 20460 USA. [Zenick, Harold] US EPA, Off Res & Dev, Natl Hlth & Environm Effects Res Lab, Washington, DC 20460 USA. [Wells, Charles] Natl Inst Environm Hlth Sci, Washington, DC 20460 USA. RP Payne-Sturges, D (reprint author), US EPA, Off Childrens Hlth Protect, 1200 Penn Ave,NW,MC 1007A, Washington, DC 20460 USA. EM payne-sturges.devon@epa.gov NR 30 TC 1 Z9 1 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 EI 1096-0953 J9 ENVIRON RES JI Environ. Res. PD OCT PY 2006 VL 102 IS 2 BP 141 EP 145 DI 10.1016/j.envres.2006.01.011 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 093MJ UT WOS:000241172100001 PM 16545364 ER PT J AU Payne-Sturges, D Gee, GC Crowder, K Hurley, BJ Lee, C Morello-Frosch, R Rosenbaum, A Schulz, A Wells, C Woodruff, T Zenick, H AF Payne-Sturges, Devon Gee, Gilbert C. Crowder, Kirstin Hurley, Bradford J. Lee, Charles Morello-Frosch, Rachel Rosenbaum, Arlene Schulz, Amy Wells, Charles Woodruff, Tracey Zenick, Hal TI Workshop Summary: Connecting social and environmental factors to measure and track environmental health disparities SO ENVIRONMENTAL RESEARCH LA English DT Editorial Material DE environmental justice; indicators; social disparities; race/ethnicity; community-based participatory research; health disparities; socioeconomic factors ID PUBLIC-HEALTH AB On May 24-25, 2005 in Ann Arbor, Michigan, the US Environmental Protection Agency, the National Institute of Environmental Health Sciences, and the University of Michigan sponsored a technical workshop on the topic of connecting social and environmental factors to measure and track environmental health disparities. The workshop was designed to develop a transdisciplinary scientific foundation for exploring the conceptual issues, data needs, and policy applications associated with social and environmental factors used to measure and track racial, ethnic, and class disparities in environmental health. Papers, presentations, and discussions focused on the use of multilevel analysis to study environmental health disparities, the development of an organizing framework for evaluating health disparities, the development of indicators, and the generation of community-based participatory approaches for indicator development and use. Group exercises were conducted to identify preliminary lists of priority health outcomes and potential indicators and to discuss policy implications and next steps. Three critical issues that stem from the workshop were: (a) stronger funding support is needed for community-based participatory research in environmental health disparities, (b) race/ethnicity and socioeconomic position need to be included in environmental health surveillance and research, and (c) models to elucidate the interrelations between social, physical, and built environments should continue to be developed and empirically tested. Published by Elsevier Inc. C1 US EPA, Off Childrens Hlth Protect, Washington, DC 20460 USA. Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. US EPA, Off Res & Dev, Natl Hlth & Environm Effects Res Lab B10501, Res Triangle Pk, NC 27709 USA. ICF Consulting, Montreal, PQ H1Z 2M3, Canada. US EPA, Off Environm Justice, Washington, DC 20460 USA. Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. Brown Univ, Ctr Environm Studies, Providence, RI 02912 USA. ICF Consulting, Rohnert Pk, CA 94928 USA. Univ Michigan, Dept Hlth Behav & Hlth Educ, Ctr Res Ethn Culture & Hlth, Sch Publ Hlth, Ann Arbor, MI 48109 USA. Natl Inst Environm Hlth Sci, Bethesda, MD 20892 USA. US EPA, Publ Hlth & Environm Policy Team, Natl Ctr Environm Econ, San Francisco, CA 94105 USA. RP Payne-Sturges, D (reprint author), US EPA, Off Childrens Hlth Protect, Ariel Rios Bldg,MC1107A,1200 Penn Ave,NW, Washington, DC 20460 USA. EM payne-sturges.devon@epa.gov OI Morello-Frosch, Rachel/0000-0003-1153-7287 NR 18 TC 21 Z9 21 U1 2 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD OCT PY 2006 VL 102 IS 2 BP 146 EP 153 DI 10.1016/j.envres.2005.11.001 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 093MJ UT WOS:000241172100002 PM 16438950 ER PT J AU Woodson, K O'Reilly, KJ Ward, DE Walter, J Hanson, J Walk, EL Tangrea, JA AF Woodson, Karen O'Reilly, Keith J. Ward, David E. Walter, Jack Hanson, Jeffrey Walk, Elyse L. Tangrea, Joseph A. TI CD44 and PTGS2 Methylation are Independent Prognostic Markers for Biochemical Recurrence Among Prostate Cancer Patients with Clinically Localized Disease SO EPIGENETICS LA English DT Article DE gene methylation; biochemical recurrence; prostate cancer AB Up to 30% of men with clinically localized disease who receive radical prostatectomy develop a biochemical recurrence. Gene methylation in tumor tissue may distinguish men with aggressive cancer. This study evaluated methylation of GSTP1, RAR beta 2, CD44 and PTGS2 with biochemical recurrence among 60 patients who underwent radical prosta tectomy using logistic regression and Kaplan Meier time to event analysis. Methylation of GSTP1 and RAR beta 2 was not associated with recurrence, however, CD44 and PTGS2 methylation were significant predictors. In multivariate models adjusting for Gleason grade, the methylation profile of CD44 and PTGS2 combined was an independent predictor of biochemical recurrence (associated with 9-fold increased risk). In addition, Kaplan Meier analysis showed CD44 and PTGS2 methylation was associated with shorter time to recurrence. CD44 and PTGS2 methylation may predict biochemical recurrence in prostate cancer patients undergoing radical prostatectomy and if validated in larger studies, may identify patients with aggressive cancer. C1 [Woodson, Karen] NCI, Genet Branch, Ctr Canc Res, NIH,Adv Technol Ctr, Bethesda, MD 20892 USA. [O'Reilly, Keith J.; Ward, David E.; Walter, Jack] Madigan Army Med Ctr, Urol Serv, Tacoma, WA 98431 USA. [O'Reilly, Keith J.; Ward, David E.; Walter, Jack] Madigan Army Med Ctr, Dept Anat Pathol, Tacoma, WA 98431 USA. [Tangrea, Joseph A.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Woodson, K (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH,Adv Technol Ctr, 8717 Grovemt Circle, Bethesda, MD 20892 USA. EM kw114v@nih.gov NR 18 TC 35 Z9 37 U1 1 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 J9 EPIGENETICS-US JI Epigenetics PD OCT-DEC PY 2006 VL 1 IS 4 BP 183 EP 186 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V04NB UT WOS:000207064000004 PM 17998819 ER PT J AU Theodore, WH Spencer, SS Wiebe, S Langfitt, JT Ali, A Shafer, PO Berg, AT Vickrey, BG AF Theodore, William H. Spencer, Susan S. Wiebe, Samuel Langfitt, John T. Ali, Amza Shafer, Patricia O. Berg, Anne T. Vickrey, Barbara G. TI Epilepsy in North America: A report prepared under the auspices of the Global Campaign against Epilepsy, the International Bureau for Epilepsy, the International League Against Epilepsy, and the World Health Organization SO EPILEPSIA LA English DT Review DE seizures; incidence; prevalence; treatment resources; stigma; cost; research ID QUALITY-OF-LIFE; SUDDEN UNEXPLAINED DEATH; NEWLY-DIAGNOSED EPILEPSY; TEMPORAL-LOBE EPILEPSY; UNITED-STATES; RISK-FACTORS; UNPROVOKED SEIZURES; CLINICAL-TRIALS; ANTIEPILEPTIC DRUGS; RACIAL DISPARITIES AB In North America, overall epilepsy incidence is approximately 50/100,000 per year, highest for children below five years of age, and the elderly. The best data suggest prevalence of 5-10/1000. Potential effects of gender, ethnicity, access to care and socioeconomic variables need further study. Studies of epilepsy etiology and classification mainly were performed without modern imaging tools. The best study found an overall standardized mortality ratio (SMR) for epilepsy relative to the general population of 2.3. There is evidence to suggest a greater increase in patients with symptomatic epilepsy, particularly children. People with epilepsy are more likely to report reduced Health-related Quality of Life than controls. They have reduced income, and are less likely to have full-time employment. They suffer from persistent stigma throughout the region, in developed as well as developing countries. Poor treatment access and health care disparities for people with epilepsy may be related to insufficient economic resources, rural isolation, gender, ethnicity, and lack of public and physician knowledge of modern approaches to epilepsy care. Despite high costs and severe disability, epilepsy may attract somewhat less research funding from public and private sources than other less common chronic neurological disorders. A Plan for Epilepsy in North America should address: basic and clinical research; primary prevention research; translation to care; stigma, quality of life, and self-management; industry relations; government and regional relations; and regional integration and resource sharing. C1 NIH, Bethesda, MD 20892 USA. Yale Univ, New Haven, CT USA. Univ Calgary, Calgary, AB, Canada. Univ Rochester, Rochester, NY USA. Univ W Indies, Kingston 7, Jamaica. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. No Illinois Univ, De Kalb, IL 60115 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Theodore, WH (reprint author), NIH, Bldg 10 Room 5N-250, Bethesda, MD 20892 USA. EM theodorw@ninds.nih.gov NR 127 TC 96 Z9 101 U1 2 U2 13 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2006 VL 47 IS 10 BP 1700 EP 1722 DI 10.1111/j.1528-1167.2006.00633.x PG 23 WC Clinical Neurology SC Neurosciences & Neurology GA 093TB UT WOS:000241191100015 PM 17054693 ER PT J AU Resnik, DB AF Resnik, David B. TI OPENNESS VERSUS SECRECY IN SCIENTIFIC RESEARCH SO EPISTEME-A JOURNAL OF INDIVIDUAL AND SOCIAL EPISTEMOLOGY LA English DT Article AB Openness is one of the most important principles in scientific inquiry, but there are many good reasons for maintaining secrecy in research, ranging from the desire to protect priority, credit, and intellectual property, to the need to safeguard the privacy of research participants or minimize threats to national or international security. This article examines the clash between openness and secrecy in science in light of some recent developments in information technology, business, and politics, and makes some practical suggestions for resolving conflicts between openness and secrecy. C1 Natl Inst Environm Sci, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), Natl Inst Environm Sci, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS [Z99 ES999999] NR 37 TC 12 Z9 12 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1742-3600 EI 1750-0117 J9 EPISTEME-J INDIV SOC JI Episteme PD OCT PY 2006 VL 2 IS 3 BP 135 EP 147 DI 10.3366/epi.2005.2.3.135 PG 13 WC Philosophy SC Philosophy GA V32UI UT WOS:000208975700001 PM 21113394 ER PT J AU Angst, J Gamma, A Endrass, J Rossler, W Ajdacic-Gross, V Eich, D Herrell, R Merikangas, KR AF Angst, Jules Gamma, Alex Endrass, Jerome Roessler, Wulf Ajdacic-Gross, Valdeta Eich, Dominique Herrell, Richard Merikangas, Kathleen Ries TI Is the association of alcohol use disorders with major depressive disorder a consequence of undiagnosed bipolar-II disorder? SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE alcohol use disorders; alcohol abuse; alcohol dependence; bipolar II disorder; major depression; comorbidity ID ANXIETY DISORDERS; COMMUNITY SAMPLE; SUICIDE ATTEMPTS; SUBSTANCE-ABUSE; DRUG-ABUSE; COMORBIDITY; PREVALENCE; COOCCURRENCE; DEPENDENCE; SPECTRUM AB Background There is emerging evidence that there is a spectrum of expression of bipolar disorder. This paper uses the well-established patterns of comorbidity of mood and alcohol use disorder to test the hypothesis that application of an expanded concept of bipolar-II (BP-II) disorder might largely explain the association of alcohol use disorders (AUD) with major depressive disorder (MDD). Method Data from the Zurich study, a community cohort assessed over 6 waves from ages 20/21 to 40/41, were used to investigate the comorbidity between mood disorders and AUD. Systematic diagnostic criteria were used for alcohol abuse, alcohol dependence, MDD, and BP-II. In addition to DSM criteria, two increasingly broad definitions of BP-II were employed. Results There was substantially greater comorbidity for the BP-II compared to major depression and for alcohol dependence compared to alcohol abuse. The broadest concept of BP-II explained two thirds of all cases of comorbidity of AUD with major depressive episodes (MDE). In fact, the broader the definition of BP-II applied, the smaller was the association of AUD with MDD, up to non-significance. In the majority of cases, the onset of bipolar manifestations preceded that of drinking problems by at least 5 years. Conclusions The findings that the comorbidity of mood disorders with AUD was primarily attributable to BP-II rather than MDD and that bipolar symptoms usually preceded alcohol problems may encourage new approaches to prevention and treatment of AUD. C1 Univ Zurich, Hosp Psychiat, Social Psychiat Res Grp, CH-8032 Zurich, Switzerland. NIMH, Sect Dev Genet Epidemiol, Intramural Res Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Psychiat Psychol Dienst Justizvollzug Kanton, Zurich, Switzerland. RP Angst, J (reprint author), Univ Zurich, Hosp Psychiat, Social Psychiat Res Grp, Lenggstr 31,Mail Box 1931, CH-8032 Zurich, Switzerland. EM jangst@bli.unizh.ch OI Ajdacic-Gross, Vladeta/0000-0002-7032-9237 NR 30 TC 29 Z9 29 U1 3 U2 3 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0940-1334 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD OCT PY 2006 VL 256 IS 7 BP 452 EP 457 DI 10.1007/s00406-006-0673-3 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 096LO UT WOS:000241378800009 PM 16917682 ER PT J AU Rendtorff, ND Zhu, M Fagerheim, T Antal, TL Jones, M Teslovich, TM Gillanders, EM Barmada, M Teig, E Trent, JM Friderici, KH Stephan, DA Tranebjaerg, L AF Rendtorff, Nanna D. Zhu, Mei Fagerheim, Toril Antal, Torben L. Jones, MaryPat Teslovich, Tanya M. Gillanders, Elizabeth M. Barmada, Michael Teig, Erik Trent, Jeffrey M. Friderici, Karen H. Stephan, Dietrich A. Tranebjaerg, Lisbeth TI A novel missense mutation in ACTG1 causes dominant deafness in a Norwegian DFNA20/26 family, but ACTG1 mutations are not frequent among families with hereditary hearing impairment SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE ACTG1; DFNA20/26; deafness; hereditary; late-onset; progressive ID STRUCTURAL BASIS; DUTCH FAMILY; BETA-ACTIN; LATE-ONSET; BINDING; GENE; LOCUS; INHIBITION; PROTEINS; COMPLEX AB The gamma-actin gene (ACTG1) encodes a major cytoskeletal protein of the sensory hair cells of the cochlea. Recently, mutations in ACTG1 were found to cause autosomal dominant, progressive, sensorineural hearing impairment linked to the DFNA20/26 locus on chromosome 17q25.3 in four American families and in one Dutch family. We report here the linkage of autosomal dominant, progressive, sensorineural hearing impairment in a large Norwegian family to the DFNA20/26 locus. Sequencing of ACTG1 identified a novel missense mutation (c. 1109T > C; p. V370A) segregating with the hearing loss. Functional analysis in yeast showed that the p. V370A mutation restricts cell growth at elevated temperature or under hyperosmolar stress. Molecular modelling suggested that the p. V370A mutation modestly alters a site for protein-protein interaction in gamma-actin and thereby modestly alters gamma-actin-based cytoskeletal structures. Nineteen Norwegian and Danish families with autosomal, dominant hearing impairment were analyzed for mutations in ACTG1 by sequencing, but no disease-associated mutations were identified. Finally, a long-term follow-up of the hearing loss progression associated with the p. V370A mutation in ACTG1 is provided. The present study expands our understanding of the genotype-phenotype relationship of this deafness gene and provides a sensitive and simple functional assay for missense mutations in this gene, which may assist future molecular diagnosis of autosomal-dominant hearing impairment. Finally, the present results do not indicate that mutations in ACTG1 are a frequent cause of autosomal-dominant postlingual sensorineural hearing impairment in Norway nor Denmark. C1 Univ Copenhagen, Wilhelm Johannsen Ctr Funct Genom, Dept Med Biochem & Genet, Copenhagen, Denmark. Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA. Univ Tromso Hosp, Dept Med Genet, N-9012 Tromso, Norway. Biotech Res & Innovat Ctr, Kinase Signalling Lab, Copenhagen, Denmark. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Inst Med Genet, Baltimore, MD USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. Univ Hosp Oslo, Dept Otorhinolaryngol, Oslo, Norway. Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ USA. Bispebjerg Hosp, Dept Audiol, DK-2400 Copenhagen, Denmark. RP Tranebjaerg, L (reprint author), Bispebjerg Hosp, Dept Audiol, H-S,Bispebjerg Bakke 23, DK-2400 Copenhagen, Denmark. EM tranebjaerg@imbg.ku.dk OI Barmada, M Michael/0000-0002-3604-6460 FU Intramural NIH HHS NR 29 TC 29 Z9 32 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD OCT PY 2006 VL 14 IS 10 BP 1097 EP 1105 DI 10.1038/sj.ejhg.5201670 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 093HD UT WOS:000241158000008 PM 16773128 ER PT J AU Alexopoulou, L Kranidioti, K Xanthoulea, S Denis, M Kotanidou, A Douni, E Blackshear, PJ Kontoyiannis, DL Kollias, G AF Alexopoulou, Lena Kranidioti, Ksanthi Xanthoulea, Sofia Denis, Maria Kotanidou, Anastasia Douni, Eleni Blackshear, Perry J. Kontoyiannis, Dimitris L. Kollias, George TI Transmembrane TNF protects mutant mice against intracellular bacterial infections, chronic inflammation and autoimmunity SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE animal models; cell surface molecules; cytokines; lymphoid organs; neuroimmunology ID TUMOR-NECROSIS-FACTOR; CENTRAL-NERVOUS-SYSTEM; FACTOR-ALPHA; RHEUMATOID-ARTHRITIS; LISTERIA-MONOCYTOGENES; TRANSGENIC MICE; FACTOR RECEPTOR; DEFICIENT MICE; MYCOBACTERIUM-TUBERCULOSIS; MULTIPLE-SCLEROSIS AB Using targeted mutagenesis in mice, we have blocked shedding of endogenous murine TNF by deleting its cleavage site. Mutant mice produce physiologically regulated levels of transmembrane TNF (tmTNF), which suffice to support thymocyte proliferation but cannot substitute for the hepatotoxic activities of wild-type TNF following LPS/D-galactosamine challenge in vivo and are not sufficient to support secondary lymphoid organ structure and function. Notably, however, tmTNF is capable of exerting anti-Listerial host defenses while remaining inadequate to mediate arthritogenic functions, as tested in the tristetraprolin-deficient model of TNF-dependent arthritis. Most interestingly, in the EAE model of autoimmune demyelination, tmTNF suppresses disease onset and progression and retains the autoimmune suppressive properties of wild-type TNF. Together, these results indicate that tmTNF preserves a subset of the beneficial activities of TNF while lacking detrimental effects. These data support the hypothesis that selective targeting of soluble TNF may offer several advantages over complete blockade of TNF in the treatment of chronic inflammation and autoimmunity. C1 Biomed Sci Res Ctr Alexander Fleming, Inst Immunol, Vari 16672, Greece. Univ Athens, Dept Crit Care & Pulm Serv, Evaggelismos Hosp, Athens, Greece. Natl Inst Environm Hlth Sci, Off Clin Res, Res Triangle Pk, NC USA. Natl Inst Environm Hlth Sci, Neurobiol Lab, Res Triangle Pk, NC USA. RP Kollias, G (reprint author), Biomed Sci Res Ctr Alexander Fleming, Inst Immunol, Vari 16672, Greece. EM g.kollias@fleming.gr RI Kollias, George/A-7079-2012; Alexopoulou, Lena/A-5041-2017 OI Kollias, George/0000-0003-1867-3150; Alexopoulou, Lena/0000-0003-4619-697X NR 70 TC 66 Z9 68 U1 0 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 2006 VL 36 IS 10 BP 2768 EP 2780 DI 10.1002/eji.200635921 PG 13 WC Immunology SC Immunology GA 097RJ UT WOS:000241465700021 PM 16983719 ER PT J AU Rossi, C Angelucci, A Costantin, L Braschi, C Mazzantini, M Babbini, F Fabbri, ME Tessarollo, L Maffei, L Berardi, N Caleo, M AF Rossi, Chiara Angelucci, Andrea Costantin, Laura Braschi, Chiara Mazzantini, Mario Babbini, Francesco Fabbri, Maria Elena Tessarollo, Lino Maffei, Lamberto Berardi, Nicoletta Caleo, Matteo TI Brain-derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE adult neurogenesis; dentate gyrus; enriched environment; mouse; neurotrophins ID LONG-TERM POTENTIATION; ADULT DENTATE GYRUS; FACTOR-DEFICIENT; SENSORY NEURONS; KNOCKOUT MICE; RAT-BRAIN; CELLS; MEMORY; PROLIFERATION; INFUSION AB Neurogenesis continues to occur in the adult mammalian hippocampus and is regulated by both genetic and environmental factors. It is known that exposure to an enriched environment enhances the number of newly generated neurons in the dentate gyrus. However, the mechanisms by which enriched housing produces these effects are poorly understood. To test a role for neurotrophins, we used heterozygous knockout mice for brain-derived neurotrophic factor (BDNF+/-) and mice lacking neurotrophin-4 (NT-4(-/-)) together with their wild-type littermates. Mice were either reared in standard laboratory conditions or placed in an enriched environment for 8 weeks. Animals received injections of the mitotic marker bromodeoxyuridine (BrdU) to label newborn cells. Enriched wild-type and enriched NT-4(-/-) mice showed a two-fold increase in hippocampal neurogenesis as assessed by stereological counting of BrdU-positive cells in the dentate gyrus and double labelling for BrdU and the neuronal marker NeuN. Remarkably, this enhancement of hippocampal neurogenesis was not seen in enriched BDNF+/- mice. Failure to up-regulate BDNF accompanied the lack of a neurogenic response in enriched BDNF heterozygous mice. We conclude that BDNF but not NT-4 is required for the environmental induction of neurogenesis. C1 CNR, Ist Neurosci, I-56100 Pisa, Italy. Scuola Normale Super Pisa, I-56100 Pisa, Italy. NCI, Neural Dev Grp, Mouse Canc Genet Program, Frederick, MD 21701 USA. Univ Florence, Dipartimento Psicol, Florence, Italy. RP Caleo, M (reprint author), CNR, Ist Neurosci, Via G Moruzzi 1, I-56100 Pisa, Italy. EM caleo@in.cnr.it OI CALEO, MATTEO/0000-0002-4333-6378 FU Intramural NIH HHS; Telethon [GGP030428] NR 44 TC 251 Z9 264 U1 3 U2 28 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD OCT PY 2006 VL 24 IS 7 BP 1850 EP 1856 DI 10.1111/j.1460-9568.2006.05059.x PG 7 WC Neurosciences SC Neurosciences & Neurology GA 095YL UT WOS:000241344100002 PM 17040481 ER PT J AU Ferrari, D Sanchez-Pernaute, R Lee, H Studer, L Isacson, O AF Ferrari, Daniela Sanchez-Pernaute, Rosario Lee, Hyojin Studer, Lorenz Isacson, Ole TI Transplanted dopamine neurons derived from primate ES cells preferentially innervate DARPP-32 striatal progenitors within the graft SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE dopamine; embryonic stem cells; Parkinson's disease; striatum; transplantation ID EMBRYONIC STEM-CELLS; FETAL VENTRAL MESENCEPHALON; LATERAL GANGLIONIC EMINENCE; CENTRAL-NERVOUS-SYSTEM; PARKINSONS-DISEASE; RAT MODEL; IN-VITRO; FUNCTIONAL RECOVERY; NEURAL PROGENITORS; INVITRO MATURATION AB The correct identity and functional capacity of transplanted dopamine (DA) neurons derived in vitro from embryonic stem (ES) cells is a critical factor for the development of an ES cell-based replacement therapy for Parkinson's disease. We transplanted primate Cyno-1 ES cells differentiated in vitro for 4 (progenitor ES cells) or 6 (differentiated ES cells) weeks, or control fetal primate cells into the striatum of hemi-parkinsonian rats. Partial behavioral recovery in amphetamine-induced rotation was correlated with the number of ES-derived tyrosine hydroxylase-positive (TH +) neurons in the grafts (r = 0.5, P < 0.05). Post mortem analysis of ES-derived grafts revealed TH + neurons with mature morphology, similar to fetal DA neurons, and expression of midbrain transcription factors, such as Engrailed (En) and Nurr-1. While the total number of TH + neurons was not different between the two groups, TH/En co-expression was significantly higher (> 90%) in grafts from differentiated ES cells than in grafts derived from progenitor cells (< 50%), reflecting a more heterogeneous cellular composition. Within the grafts there was an overlap between ES-derived TH + axonal arbors and clusters of primate ES-derived striatal neurons expressing brain factor 1 (Bf-1, Foxg1) and DA and cAMP-regulated phosphoprotein (DARPP-32). Such overlap was never observed for other regional transcription factors that define neighboring forebrain domains in the developing brain, such as Nkx2.1 (medial ganglionic eminence), Nkx2.2 (pallidal and diencephalic progenitors) or Pax6 (dorsal telencephalic progenitors). Despite the heterogeneity of ES-derived graft cell composition, these results demonstrate normal phenotypic specification, conserved natural axonal target selectivity and functionality of DA neurons derived from primate ES cells. C1 Harvard Univ, McLean Hosp, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02478 USA. McLean Hosp, Neuroregenerat Labs, Belmont, MA 02478 USA. Mem Sloan Kettering Canc Ctr, Div Neurosurg & Dev Biol, Lab Stem Cell & Tumor Biol, New York, NY 10021 USA. RP Sanchez-Pernaute, R (reprint author), Harvard Univ, McLean Hosp, Udall Parkinsons Dis Res Ctr Excellence, 115 Mill St, Belmont, MA 02478 USA. EM rosario_pernaute@hms.harvard.edu; isacson@hms.harvard.edu FU NCRR NIH HHS [P51 RR000168-440194, P51 RR000168, P51RR00168]; NINDS NIH HHS [P50 NS039793-07, P50 NS-39793, P50 NS039793] NR 56 TC 37 Z9 39 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD OCT PY 2006 VL 24 IS 7 BP 1885 EP 1896 DI 10.1111/j.1460-9568.2006.05093.x PG 12 WC Neurosciences SC Neurosciences & Neurology GA 095YL UT WOS:000241344100006 PM 17067292 ER PT J AU Liu, J Cheng, ML Shi, JZ Yang, Q Wu, J Li, CX Waalkes, MP AF Liu, Jie Cheng, Min-Liang Shi, Jin-Zheng Yang, Qin Wu, Jun Li, Cheng-Xiu Waalkes, Michael P. TI Differential effects between Maotai and ethanol on hepatic gene expression in mice: Possible role of metallothionein and heme oxygenase-1 induction by Maotai SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT 5th International Conference on Metallothionein CY OCT 08-12, 2005 CL Beijing, PEOPLES R CHINA SP Int Soc Neurochem, Nickel Producers Environm Res Assoc, Soc Toxicol, Res Western, Univ Western Ontario, Natl Nat Sci Fdn China, Minist Educ China DE ethanol; Maotai; gene expression; metallothionein; heme oxygenase-1; liver ID OXIDATIVE STRESS; LIVER; ALCOHOL; RATS; INJURY; LIGHT; HEPATOTOXICITY; CONSUMPTION; INFUSION; DISEASES AB Alcohol is a risk factor for liver fibrosis and hepatocellular carcinoma. On the other hand, light alcoholic beverage consumption is believed to be beneficial because of the effects of both alcohol and nonalcoholic components of the beverage. Maotai is a commonly consumed beverage in China containing 53% alcohol. Epidemiological and experimental studies show that Maotai is less toxic to the liver than ethanol alone. To examine the differential effects of Maotai and ethanol, a low dose of Maotai or an equal amount of ethanol (53%, v/v in water, 5 ml/kg) were given to male mice daily for 1 week, and hepatic RNA was extracted for microarray analysis. Approximately 10% of genes on the liver-selective custom array (588 genes) were altered following Maotai or ethanol administration, but Maotai treated livers had fewer alterations compared with ethanol alone. Real-time reverse transcription-polymerase chain reaction confirmed and extended microarray results on selected genes. An induction of metallothionein and heme oxygenase-1 occurred with Maotai, which could not be explained by alcohol consumption alone, whereas the attenuation of ethanol responsive genes such as quinone dehydrogenase, DNA-ligase 1, IGFBP1, and IL-1 beta suggests less liver injury occurred with Maotai. The expression of genes related to liver fibrosis, such as cytokeratin-18, was slightly increased by the high dose of ethanol, but was unchanged in the Maotai group. In summary, gene expression analysis indicates that Maotai induces a different response than ethanol alone. The dramatic induction of metallothionein and heme oxygenase-1 with Maotai could be important adaptive responses to reduce alcoholic liver injury. C1 Guiyang Med Coll Hosp, Guiyang 550004, Guizhou, Peoples R China. NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. Guiyang Tradit Med Coll, Guizhou, Peoples R China. RP Cheng, ML (reprint author), Guiyang Med Coll Hosp, Guiyang 550004, Guizhou, Peoples R China. EM Liu6@niehs.nih.gov; Chengml@21cn.com NR 26 TC 3 Z9 9 U1 1 U2 4 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD OCT PY 2006 VL 231 IS 9 BP 1535 EP 1541 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 092XV UT WOS:000241131900013 PM 17018877 ER PT J AU Watanabe, K Ikeda, H Hikosaka, O AF Watanabe, Katsumi Ikeda, Hanako Hikosaka, Okihide TI Effects of explicit knowledge of workspace rotation in visuomotor sequence learning SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE sequential learning; accuracy; speed; explicit knowledge; human ID MOTOR-SEQUENCE; FUNCTIONAL MRI; TIME-COURSE; PERFORMANCE; IMPLICIT; SKILL; PET; ACQUISITION; ATTENTION; ANATOMY AB Previous experimental and theoretical studies have suggested that two separate neural networks contribute to visuomotor learning of spatial sequences, one to the accuracy of performance and the other to the speed of performance (Nakahara et al. in J Cogn Neurosci 13:626-647, 2001). This study examined the influence of explicit knowledge of stimulus configuration (workspace) in visuomotor sequence learning. Twenty-eight right-handed subjects learned the sequences of button presses by trial and error (Hikosaka et al. in J Neurophysiol 76:617-621, 1996) in the course of two sessions. In the first session, both the number of completion failures (accuracy measure) and the performance time to complete a sequence (speed measure) decreased. In the second session, the workspace was rotated without notifying the subjects. About half the subjects remained unaware of the workspace rotation, and no transfer of learning occurred (i.e., neither accuracy nor speed of performance was preserved in the second session). The remaining subjects spontaneously noticed the rotation and they were able to use this knowledge to perform the task with less completion failures in the second session. However, the knowledge of workspace rotation did not decrease the performance time in the second session. The lack of influence of explicit knowledge on the speed of performance is consistent with the two-loop model of visuomotor sequence learning. C1 Univ Tokyo, Adv Sci & Technol Res Ctr, Meguro Ku, Tokyo 1538904, Japan. Natl Inst Adv Ind Sci & Technol, Tsukuba, Ibaraki, Japan. JST, ERATO, Shimojo Implicit Brain Funct Project, Kawaguchi, Saitama, Japan. Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 305, Japan. Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 305, Japan. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Watanabe, K (reprint author), Univ Tokyo, Adv Sci & Technol Res Ctr, Meguro Ku, 4-6-1 Komaba, Tokyo 1538904, Japan. EM kw@fennel.rcast.u-tokyo.ac.jp NR 38 TC 10 Z9 10 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD OCT PY 2006 VL 174 IS 4 BP 673 EP 678 DI 10.1007/s00221-006-0512-9 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 090VN UT WOS:000240980800010 PM 16724178 ER PT J AU Manson, SC Palace, J Frank, JA Matthews, PM AF Manson, Stephanie C. Palace, Jacqueline Frank, Joseph A. Matthews, Paul M. TI Loss of interhemispheric inhibition in patients with multiple sclerosis is related to corpus callosum atrophy SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE fMRI; multiple sclerosis; cognition; ipsilateral; deactivation ID TRANSCRANIAL MAGNETIC STIMULATION; FMRI SIGNAL DECREASES; PRIMARY MOTOR CORTEX; DIFFUSION TENSOR; AXONAL INJURY; MOVEMENT; MRI; LESIONS; ACTIVATION; FIBERS AB Axonal injury and loss in the corpus callosum (CC) is characteristic of the pathology of multiple sclerosis (MS). Functional magnetic resonance imaging (fMRI) potentially allows neurophysiological consequences of this interhemispheric axonal loss to be defined quantitatively. Here we have used 3T fMRI to study the activation in the contralateral primary sensorimotor cortex and deactivation (mediated by transcallosal tracts) in the homologous ipsilateral region in 14 patients with MS and in 14 matched healthy controls during a simple hand-tapping task. Both healthy controls and MS patients showed similar activation in the motor cortex contralateral to the hand moved, but the patients showed a significantly smaller relative deactivation in the ipsilateral motor cortex (P = 0.002). The difference was accounted for by the sub-group of MS patients who previously had impairment of motor function of the hand tested (MS-phd). The CC of the whole patient group was significantly thinner than for the controls (P = 0.001). Atrophy of the CC was correlated with loss of deactivation for the whole patient group (r = -0.50, P = 0.035), but particularly for MS-phd (r = -0.914, P = 0.004). Interhemispheric physiological inhibition thus is impaired in patients with MS, potentially contributing to impairment of motor control. This work suggests one way in which FMRI monitoring of the transcallosal interactions in motor cortex could become a tool for evaluation of therapies that may enhance function in reversibly impaired pathways. C1 Univ Oxford, John Radcliffe Hosp, Ctr Funct Magnet Resonance Imaging, Oxford OX3 9DU, England. NIH, Bethesda, MD 20892 USA. Radcliffe Infirm, Dept Clin Neurol, Oxford OX2 6HE, England. RP Matthews, PM (reprint author), Univ Oxford, John Radcliffe Hosp, Ctr Funct Magnet Resonance Imaging, Oxford OX3 9DU, England. EM paul@fmrib.ox.ac.uk OI Matthews, Paul M/0000-0002-1619-8328 NR 35 TC 40 Z9 40 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD OCT PY 2006 VL 174 IS 4 BP 728 EP 733 DI 10.1007/s00221-006-0517-4 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 090VN UT WOS:000240980800015 PM 16944115 ER PT J AU Jazbec, S Hardin, MG Schroth, E McClure, E Pine, DS Ernst, M AF Jazbec, Sandra Hardin, Michael G. Schroth, Elizabeth McClure, Erin Pine, Daniel S. Ernst, Monique TI Age-related influence of contingencies on a saccade task SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE eyemovement; cognitive control; sensation seeking ID DEFICIT HYPERACTIVITY DISORDER; EYE-MOVEMENTS; COGNITIVE-DEVELOPMENT; BRAIN-DEVELOPMENT; VOLUNTARY CONTROL; ANTISACCADE TASK; TEMPORAL-LOBE; ADOLESCENCE; CHILDREN; MRI AB Adolescence is characterized by increased risk-taking and sensation-seeking, presumably brought about by developmental changes within reward-mediating brain circuits. A better understanding of the neural mechanisms underlying reward-seeking during adolescence can have critical implications for the development of strategies to enhance adolescent performance in potentially dangerous situations. Yet little research has investigated the influence of age on the modulation of behavior by incentives with neuroscience-based methods. A monetary reward antisaccade task (the RST) was used with 23 healthy adolescents and 30 healthy adults. Performance accuracy, latency and peak velocity of saccade responses (prosaccades and antisaccades) were analyzed. Performance accuracy across all groups was improved by incentives (obtain reward, avoid punishment) for both, prosaccades and antisaccades. However, modulation of antisaccade errors (direction errors) by incentives differed between groups: adolescents modulated saccade latency and peak velocity depending on contingencies, with incentives aligning their performance to that of adults; adults did not show a modulation by incentives. These findings suggest that incentives modulate a global measure of performance (percent direction errors) in adults and adolescents, and exert a more powerful influence on the control of incorrect motor responses in adolescents than in adults. These findings suggest that this task can be used in neuroimaging studies as a probe of the influence of incentives on cognitive control from a developmental perspective as well as in health and disease. C1 NIMH, Emot Dev & Affect Neurosci Branch, Mood & Anxiety Disorders Program, NIH,HHS, Bethesda, MD 20892 USA. RP Ernst, M (reprint author), NIMH, Emot Dev & Affect Neurosci Branch, Mood & Anxiety Disorders Program, NIH,HHS, 15K N Dr, Bethesda, MD 20892 USA. EM ernstm@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 48 TC 47 Z9 48 U1 4 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD OCT PY 2006 VL 174 IS 4 BP 754 EP 762 DI 10.1007/s00221-006-0520-9 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 090VN UT WOS:000240980800018 PM 16733706 ER PT J AU Toris, CB Lane, JT Akagi, Y Blessing, KA Kador, PF AF Toris, Carol B. Lane, James T. Akagi, Yoshio Blessing, Karen A. Kador, Peter F. TI Aqueous flow in galactose-fed dogs SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE galactose; diabetes; dog; aqueous flow; intraocular pressure; ciliary body ID ALDOSE REDUCTASE INHIBITOR; RETINAL VESSEL CHANGES; DIABETES-MELLITUS; HUMOR DYNAMICS; RISK-FACTOR; INSULIN; COMPLICATIONS; PROGRESSION; CATARACTS; SORBINIL AB Dogs fed galactose develop diabetes-like ocular complications that include keratopathy, cataracts, and retinopathy. The purpose of this study was to investigate whether galactosemic dogs display reduced aqueous flow similar to that observed in patients with insulin-dependent diabetes mellitus. Twelve male beagles at 9 months of age were divided into three groups of four. The Galactose group was fed diet containing 30% galactose for 97 months and the Reversal group was fed the galactose diet for an initial 38 months then standard dog diet for the remaining period. The Control group was fed standard dog diet for 97 months. Aqueous flow was determined by fluorophotometry in one eye per dog at 96 and 97 months after the initiation of galactose feeding. Intraocular pressure (IOP) was measured once in the morning by pneumatonometry. Anterior chamber depth was measured by A-scan. At the end of the experiment, eyes were enucleated and processed for histological examination. Dogs fed galactose diet for 97 months had significantly (p < 0.05) increased body weights but similar IOP and anterior chamber depth compared to the other groups, and significantly (p = 0.05) reduced aqueous flow compared to the control group (4.4 +/- 2.2 vs. 6.8 +/- 2.4 mu l/min, mean standard deviation, respectively). Additionally, aqueous flow decreased in the Reversal group to 3.1 +/- 1.3 mu l/min (p = 0.002). This decrease correlated with morphological changes of the ciliary processes. Like patients with insulin-dependent diabetes mellitus, galactose-fed dogs demonstrate reduced aqueous flow. This reduction was irreversible and independent of the retinopathy present. This animal model may be useful for the study of aqueous humor dynamics in diabetes. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Nebraska, Dept Ophthalmol, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Pharmaceut Sci, Omaha, NE 68198 USA. Fukui Med Sch, Dept Ophthalmol, Fukui 91011, Japan. NEI, Lab Ocular Therapeut, NIH, Bethesda, MD USA. RP Toris, CB (reprint author), Univ Nebraska, Dept Ophthalmol, 985840 Nebraska Med Ctr, Omaha, NE 68198 USA. EM ctoris@unmc.edu NR 31 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD OCT PY 2006 VL 83 IS 4 BP 865 EP 870 DI 10.1016/j.exer.2006.04.005 PG 6 WC Ophthalmology SC Ophthalmology GA 087CR UT WOS:000240720600020 PM 16797006 ER PT J AU Ham, DI Fujimoto, C Gentleman, S Chan, CC Yu, CR Yu, S Egwuagu, CE Redmond, TM Gery, I AF Ham, Don-Il Fujimoto, Chiaki Gentleman, Susan Chan, Chi-Chao Yu, Cheng-Rong Yu, Shirley Egwuagu, Charles E. Redmond, T. Michael Gery, Igal TI The level of thymic expression of RPE65 inversely correlates with its capacity to induce experimental autoimmune uveitis (EAU) in different rodent strains SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE RPE65; autoimmunity; experimental autoimmune uveitis; immunopathology; immunotolerance; thymus; mouse strains ID RETINAL-PIGMENT EPITHELIUM; T-CELL TOLERANCE; GENE-THERAPY; SELF-ANTIGEN; PROTEIN; MICE; IMMUNIZATION; REPERTOIRE; MECHANISMS; RESISTANCE AB We have previously shown that immunization with RPE65 produces in rats of four strains a severe inflammatory eye disease, designated experimental autoimmune uveitis (EAU). Here, we examined the uveitogenicity of RPE65 in six strains of mice. Only one strain, C57B1/6, was found to develop consistently moderate levels of EAU, whereas other strains (BALB/c, B10.A, B10.BR, B10.RIII, C57BL/10J) were found to be essentially resistant to disease induced by RPE65. Analysis of the expression of RPE65 mRNA in thymi of the six mouse strains revealed detectable levels of the transcript in all strains, but with remarkable quantitative differences, with the lowest levels seen in thymi of C57B1/6 mice, the only strain susceptible to RPE65-induced EAU. Moreover, unlike the finding with the mice, no RPE65 mRNA was detected in thymi of any of the four rat strains (Lewis, BN, F344, SHR) all of which are susceptible to the disease. These data thus indicate that the susceptibility to RPE65-induced EAU is inversely related to the thymic expression of the molecule. The data also suggest that this disease can be induced only in mice in which thymic expression of RPE65 is sufficiently low to allow the escape from deletion of T-cells with the adequate capacity to initiate the pathogenic immune response. Published by Elsevier Ltd. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Ophthalmol, Seoul, South Korea. RP Gery, I (reprint author), NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM geryi@nei.nih.gov FU Intramural NIH HHS NR 37 TC 1 Z9 2 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD OCT PY 2006 VL 83 IS 4 BP 897 EP 902 DI 10.1016/j.exer.2006.04.013 PG 6 WC Ophthalmology SC Ophthalmology GA 087CR UT WOS:000240720600024 PM 16777093 ER PT J AU Wolkow, CA AF Wolkow, Catherine A. TI Identifying factors that promote functional aging in Caenorhabditis elegans SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE aging; Caenorhabditis elegans; muscle; functional decline; sarcopenia; insulin; integrin; dietary restriction ID LIFE-SPAN; C-ELEGANS; RNAI SCREEN; WILD-TYPE; LONGEVITY; BEHAVIOR; PHARYNX; MUTANT; GENES; LONG AB A major feature of aging is a reduction in muscle strength from sarcopenia, the loss of muscle mass. Sarcopenia impairs physical ability, reduces quality of life and increases the risk of fall and injury. Since aging is a process of stochastic decline, there may be many factors that impinge on the progression of sarcopenia. Possible factors that may promote muscle decline are contraction-related injury and oxidative stress. However, relatively little is understood about the cellular pathways affecting muscle aging, in part because lifespan studies are difficult to conduct in species with large muscles, such as rodents and primates. For this reason, shorter-lived invertebrate models of aging may be more useful for unraveling causes of sarcopenia and functional declines during aging. Recent studies have examined both physiological and genetic factors that affect aging-related declines in Caenorhabditis elegans nematodes. In C elegans, aging leads to significant functional declines that correlate with muscle deterioration, similar to those documented for longer-lived vertebrates. This article will examine the current research into aging-related functional declines in this species, focusing on recent studies of locomotory and feeding decline during aging in the nematode, C elegans. (c) 2006 Elsevier Inc. All rights reserved. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Wolkow, CA (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM wolkowca@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000320-06, NIH0011061953] NR 39 TC 21 Z9 22 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD OCT PY 2006 VL 41 IS 10 BP 1001 EP 1006 DI 10.1016/j.exger.2006.06.033 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 123JQ UT WOS:000243292600015 PM 16908112 ER PT J AU Cassiani-Ingoni, R Coksaygan, T Xue, HP Reichert-Scrivner, SA Wiendl, H Rao, MS Magnus, T AF Cassiani-Ingoni, Riccardo Coksaygan, Turhan Xue, Haipeng Reichert-Scrivner, Susan A. Wiendl, Heinz Rao, Mahendra S. Magnus, Tim TI Cytoplasmic translocation of Olig2 in adult glial progenitors marks the generation of reactive astrocytes following autoimmune inflammation SO EXPERIMENTAL NEUROLOGY LA English DT Article DE EAE; multiple sclerosis; demyelination; gliosis; Olig2; NG2; Nkx2.2 ID CENTRAL-NERVOUS-SYSTEM; TRANSCRIPTION FACTOR OLIG2; FIBRILLARY ACIDIC PROTEIN; NEURAL STEM-CELLS; MULTIPLE-SCLEROSIS; SPINAL-CORD; OLIGODENDROCYTE DIFFERENTIATION; PROINFLAMMATORY CYTOKINES; IMMATURE OLIGODENDROGLIA; DEMYELINATED LESIONS AB The injury response in the brain involves complex interplay between neural and immune components. Following inflammatory insults to the adult CNS. formation of an astroglial scar often impedes functional repair. Glial progenitor cells expressing the nuclear transcription factor Olig2 possibly generate astrocytes in response to various types of injuries; however, the mechanisms underlying this differentiation are unclear. In a model of immune-mediated injury (MOG(35-55)-experimental autoimmune encephalomyelitis), we show that the conversion from progenitor to reactive astrocyte is marked by the translocation of Olig2 into the cytoplasm. Evidence of this process is found for months after disease initiation in the absence of new inflammatory infiltrates. A proportion of cells with cytoplasmic Olig2 was found to express NG2 or Nkx2.2, but only Nkx2.2 was occasionally retained by GFAP(+) cells. We further show that differentiation to astrocytes is induced in glial progenitors in vitro through exposure to the pro-inflammatory cytokine IFN-gamma, but not to TNF-alpha. Together, these data ascribe a pivotal role to Olig2(+) glial precursor cells in the adult GINS. linking autoimmune inflammation and glial scar formation. (c) 2006 Elsevier Inc. All rights reserved. C1 NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, Ctr Excellence Biol & Mol Med, Rome, Italy. NIA, Stem Cell Biol Unit, Neurosci Lab, NIH, Baltimore, MD 21224 USA. Univ Wurzburg, Dept Neurol, Clin Res Grp Multiple Sclerosis & Neuroimmunol, D-8700 Wurzburg, Germany. Invitrogen Corp, Corp Res Labs, Carlsbad, CA 92008 USA. RP Cassiani-Ingoni, R (reprint author), NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, 10-5B16,10 Ctr Dr, Bethesda, MD 20892 USA. EM cassianr@ninds.nih.gov; magnust@mail.gov FU Intramural NIH HHS NR 62 TC 40 Z9 41 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2006 VL 201 IS 2 BP 349 EP 358 DI 10.1016/j.expneurol.2006.04.030 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 096RG UT WOS:000241393900009 PM 16814281 ER PT J AU Biagini, G Baldelli, E Longo, D Pradelli, L Zini, I Rogawski, MA Avoli, M AF Biagini, Giuseppe Baldelli, Enrica Longo, Daniela Pradelli, Luca Zini, Isabella Rogawski, Michael A. Avoli, Massimo TI Endogenous neurosteroids modulate epileptogenesis in a model of temporal lobe epilepsy SO EXPERIMENTAL NEUROLOGY LA English DT Article DE epileptogenesis; status epilepticus; Glia; hippocampus; neurosteroid; pilocarpine ID ANTICONVULSANT ACTIVITY; PILOCARPINE SEIZURES; HIPPOCAMPUS; BRAIN; RAT; PROGESTERONE; INHIBITOR; NEURONS; ACID; MICE AB Neurosteroids modulate seizure susceptibility, but their role in the regulation of epileptogenesis is unknown. Status epilepticus (SE) induces temporal lobe epileptogenesis following a latent period in which glial cells are activated. Here, we found that P450scc, the rate-limiting enzyme in steroid synthesis.. is upregulated in hippocampal glia during the latent period after pilocarpine-induced SE in rats. More prolonged SE was associated with greater P450scc expression and longer latencies to the development of seizures, suggesting that enhanced steroid synthesis retards epileptogenesis. The 5 alpha-reductase inhibitor finasteride, which blocks neurosteroid synthesis, reduced the latent period, indicating that glia-derived neurosteroids may be antiepileptogenic. (c) 2006 Elsevier Inc. All rights reserved. C1 NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. Univ Roma La Sapienza, Dipartimento Fisiol Umana & Farmacol V Erspamer, I-00185 Rome, Italy. McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada. McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada. Univ Modena, Dipartimento Sci Biomed, Sez Fisiol, I-41100 Modena, Italy. RP Biagini, G (reprint author), Univ Modena, Dipartimento Sci Biomed, Sez Fisiol, Via Campi 287, I-41100 Modena, Italy. EM gbiagini@unimore.it RI Rogawski, Michael/B-6353-2009; Biagini, Giuseppe/F-7668-2013; Biagini, Giuseppe/I-3227-2013 OI Rogawski, Michael/0000-0002-3296-8193; Biagini, Giuseppe/0000-0002-7130-2511; Biagini, Giuseppe/0000-0002-7130-2511 NR 25 TC 45 Z9 45 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2006 VL 201 IS 2 BP 519 EP 524 DI 10.1016/j.expneurol.2006.04.029 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 096RG UT WOS:000241393900026 PM 16780839 ER PT J AU McKee, AE Thiele, CJ AF McKee, Amy E. Thiele, Carol J. TI Targeting caspase 8 to reduce the formation of metastases in neuroblastoma SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE anoikis; apoptosis; caspase 8; metastasis; neuroblastoma ID FOCAL ADHESION KINASE; CELL-SURVIVAL; CYTOCHROME-C; DEATH-DOMAIN; CHILDHOOD NEUROBLASTOMAS; INDUCED APOPTOSIS; EXPRESSION; TUMOR; ACTIVATION; RESISTANCE AB The clinical challenge in neuroblastoma is the presence of metastasis at diagnosis in the majority of patients. Caspase 8 is an integral protein in death receptor-associated apoptosis, and loss of caspase 8 via the epigenetic phenomenon of methylation in neuroblastoma has led to increased resistance to chemotherapy. Recent evidence suggests that caspase 8 loss may also contribute to a metastatic phenotype; thus, caspase 8 may prove to be an attractive target for therapy both in treating primary tumours as well as preventing and treating metastatic lesions. Numerous methods have been described to manipulate caspase 8 levels both in vitro and in vivo, and investigation into caspase 8 isoforms may also bring forth additional therapeutic targets. C1 NCI, Cell & Mol Biol Sect, Paediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Thiele, CJ (reprint author), NCI, Cell & Mol Biol Sect, Paediat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10-CRC, Bethesda, MD 20892 USA. EM mckeea@mail.nih.gov; ct47a@nih.gov FU Intramural NIH HHS NR 44 TC 11 Z9 12 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD OCT PY 2006 VL 10 IS 5 BP 703 EP 708 DI 10.1517/14728222.10.5.703 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 087QF UT WOS:000240756400008 PM 16981827 ER PT J AU Blonder, J Xiao, Z Veenstra, TD AF Blonder, Josip Xiao, Zhen Veenstra, Timothy D. TI Proteomic profiling of differentiating osteoblasts SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE extracellular matrix; mineralization; osteoblast differentiation; proteomic technologies; regulation of protein function; transcription factors ID STEM-CELL DIFFERENTIATION; CODED AFFINITY TAGS; MASS-SPECTROMETRY; MEMBRANE-PROTEINS; INORGANIC-PHOSPHATE; QUANTITATIVE PROTEOMICS; EXPRESSION; BONE; ELECTROPHORESIS; MINERALIZATION AB The major event that triggers osteogenesis is the transition of mesenchymal stem cells into bone-forming, differentiating osteoblast cells. Osteoblast differentiation is the primary event of bone formation, exemplified by the synthesis, deposition and mineralization of extracellular matrix. Osteoblast differentiation is controlled tightly by sequential activation of diverse transcription factors that regulate the expression of specific genes. The spatial and temporal regulation of the differentiation process is not completely understood at the cellular or molecular level. Recent advances in mass spectrometry-based proteomics have allowed for the systematic qualitative and quantitative profiling of differentiating osteoblasts, enabling a better understanding of the multiple factors and signaling events that control the differentiation process at a molecular level. This review focuses on recent developments in the proteomic analysis of differentiating osteoblasts, including advances, challenges and future prospects of using mass spectrometry to investigate the local and systemic factors regulating bone formation and its homeostasis. C1 SAIC Frederick Inc, Natl Canc Inst Frederick, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. RP Blonder, J (reprint author), SAIC Frederick Inc, Natl Canc Inst Frederick, Lab Proteom & Analyt Technol, POB B, Frederick, MD 21702 USA. EM blonder@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 57 TC 16 Z9 17 U1 2 U2 4 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD OCT PY 2006 VL 3 IS 5 BP 483 EP 496 DI 10.1586/14789450.3.5.483 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 136PC UT WOS:000244235600015 PM 17078763 ER PT J AU Buchholz, UJ Nagashima, K Murphy, BR Collins, PL AF Buchholz, Ursala J. Nagashima, Kunio Murphy, Brian R. Collins, Peter L. TI Live vaccines for human metapneumovirus designed by reverse genetics SO EXPERT REVIEW OF VACCINES LA English DT Review DE live-attenuated vaccine; human metapneumovirus; immunity paramyxovirus; pneumovirus protective antigens; vaccine ID RESPIRATORY SYNCYTIAL VIRUS; REPLICATION IN-VITRO; L-POLYMERASE PROTEIN; G-GLYCOPROTEIN; FUSION PROTEIN; F-PROTEIN; MONOCLONAL-ANTIBODIES; PROTECTIVE IMMUNITY; NONHUMAN-PRIMATES; TRACT DISEASE AB Human metapneumovirus (HMPV) was first described in 2001 and has quickly become recognized as an important cause of respiratory tract disease worldwide, especially in the pediatric population. A vaccine against HMPV is required to prevent severe disease associated with infection in infancy. The primary strategy is to develop a live-attenuated virus for intranasal immunization, which is particularly well suited against a respiratory virus. Reverse genetics provides a means of developing highly characterized 'designer' attenuated vaccine candidates. To date, several promising vaccine candidates have been developed, each using a different mode of attenuation. One candidate involves deletion of the G glycoprotein, providing attenuation that is probably based on reduced efficiency of attachment. A second candidate involves deletion of the M2-2 protein, which participates in regulating RNA synthesis and whose deletion has the advantageous property of upregulating transcription and increasing antigen synthesis. A third candidate involves replacing the P protein gene of HMPV with its counterpart from the related avian metapneumovirus, thereby introducing attenuation owing to its chimeric nature and host range restriction. Another live vaccine strategy involves using an attenuated parainfluenza virus as a vector to express HMPV protective antigens, providing a bivalent pediatric vaccine. Additional modifications to provide improved vaccines will also be discussed. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NCI, SAIC, NIH, Frederick, MD 21701 USA. RP Buchholz, UJ (reprint author), NIAID, Infect Dis Lab, NIH, 50 Room 6505,50 S Dr MSC 8007, Bethesda, MD 20892 USA. EM ubuchholz@niaid.nth.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 80 TC 21 Z9 21 U1 0 U2 6 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD OCT PY 2006 VL 5 IS 5 BP 695 EP 706 DI 10.1586/14760584.5.5.695 PG 12 WC Immunology SC Immunology GA 116NV UT WOS:000242810500018 PM 17181442 ER PT J AU Nahirney, PC Forbes, JG Morris, HD Chock, SC Wang, K AF Nahirney, Patrick C. Forbes, Jeffrey G. Morris, H. Douglas Chock, Susanne C. Wang, Kuan TI What the buzz was all about: superfast song muscles rattle the tymbals of male periodical cicadas SO FASEB JOURNAL LA English DT Article DE multimodal imaging; Z-band lattice; myofilament length regulation; sarcomere proportion; supercontraction ID FISH PORICHTHYS-NOTATUS; INDIRECT FLIGHT-MUSCLE/; SKELETAL-MUSCLE; SOUND-PRODUCTION; MOTOR SYSTEM; Z-BAND; Z-LINE; FILAMENTS; PROTEIN; ARCHITECTURE AB Male cicadas produce mating calls by oscillating a pair of superfast tymbal muscles in their anterior abdominal cavity that pull on and buckle stiff-ribbed cuticular tymbal membranes located beneath the folded wings. The functional anatomy and rattling of the tymbal organ in 17 yr periodical cicada, Magicicada cassini (Brood X), were revealed by high-resolution microcomputed tomography, magnetic resonance imaging, electron microscopy, and laser vibrometry to understand the mechanism of sound production in these insects. Each 50 Hz muscle contraction yielded five to six stages of rib buckling in the tymbal, and a small release of muscle tension resulted in a rapid recovery due to the spring-loaded nature of the stiff ribs in the resilin-rich tymbal. The tymbal muscle sarcomeres have thick and thin filaments that are 30% shorter than those in flight muscles, with Z-bands that were thicker and configured into novel perforated hexagonal lattices. Caffeine-treated fibers supercontracted by allowing thick filaments to traverse the Z-band through its open lattice. This superfast sonic muscle illustrates design features, especially the matching hexagonal symmetry of the myofilaments and the perforated Z-band that contribute to high-speed contractions, long endurance, and potentially supercontraction needed for producing enduring mating songs and choruses. C1 NIAMSD, Muscle Proteom & Nanotechnol Sect, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Magnet Resonance Imaging Res Facil, NIH, Bethesda, MD 20892 USA. Dept Hlth & Human Serv, Bethesda, MD USA. RP Wang, K (reprint author), NIAMSD, Muscle Proteom & Nanotechnol Sect, Muscle Biol Lab, NIH, Bldg 50,Rm 1140, Bethesda, MD 20892 USA. EM wangk@exchange.nih.gov FU Intramural NIH HHS NR 41 TC 8 Z9 10 U1 4 U2 11 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 2006 VL 20 IS 12 BP 2017 EP 2026 DI 10.1096/fj.06-5991com PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 093GS UT WOS:000241156900010 PM 17012254 ER PT J AU DeCherney, AH AF DeCherney, Alan H. TI Fact sheet to act sheet SO FERTILITY AND STERILITY LA English DT Editorial Material AB Recent changes and future changes to Fertility and Sterility are discussed. These changes are based on the requirements of the baby boomers and generation X and have been made to satisfy the desires of various reader groups. Change is important and allows us to maintain our leadership position. C1 NICHHD, RBMB, NIH, Bethesda, MD 20892 USA. RP DeCherney, AH (reprint author), NICHHD, RBMB, NIH, Bldg 10,CRC,1 East,Rm 1-3140,10 Ctr Dr,MSC 1109, 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2006 VL 86 IS 4 BP 798 EP 799 DI 10.1016/j.fertnstert.2006.07.1451 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 093JU UT WOS:000241165400004 ER PT J AU Dixon, D Parrott, EC Segars, JH Olden, K Pinn, VW AF Dixon, Darlene Parrott, Estella C. Segars, James H. Olden, Kenneth Pinn, Vivian W. TI The second National Institutes of Health International Congress on advances in uterine leiomyoma research: conference summary and future recommendations SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 2nd NIH International Congress CY FEB 24-25, 2005 CL Bethesda, MD DE NIH conference summary; uterine leiomyoma; fibroid; clinical treatment; clinical/basic studies; research recommendations ID RISK-FACTORS; FIBROIDS; WOMEN; HYSTERECTOMY; HISTORY; DISEASE AB Objective: To summarize the proceedings of the Advances in Uterine Leiomyoma Research: 2nd NIH International Congress, which was convened on February 24-25, 2005 by the Department of Health and Human Services (DHHS), National Institutes of Health (NIH) in Bethesda, Maryland. Design: Scientific information was presented at a 2-day conference, which was a collaborative effort of agencies across the DHHS and members of the academic, clinical, and medical communities involved in uterine leiomyoma research. Conclusion(s): The conference brought together scientists in biomedicine, epidemiology, basic research, therapeutics, and translational medicine and fostered an exchange of scientific information among members of the uterine leiomyoma research and health care communities. This document summarizes this exchange and outlines research needs and recommendations for future research directions. C1 NIH, Off Res Womens Hlth, DHHS, Bethesda, MD 20892 USA. NIEHS, NIH, DHHS, Bethesda, MD 20892 USA. NICHD, NIH, DHHS, Bethesda, MD 20892 USA. RP Pinn, VW (reprint author), NIH, Off Res Womens Hlth, DHHS, 9000 Rockville Pike,Bldg 1,Room 201, Bethesda, MD 20892 USA. EM ODORWH-research@mail.nih.gov FU Intramural NIH HHS NR 32 TC 11 Z9 12 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2006 VL 86 IS 4 BP 800 EP 806 DI 10.1016/j.fertnstert.2006.02.116 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 093JU UT WOS:000241165400005 PM 17027353 ER PT J AU Legro, RS Myers, ER Barnhart, HX Carson, SA Diamond, MP Carr, BR Schlaff, WD Coutifaris, C McGovern, PG Cataldo, NA Steinkampf, MP Nestler, JE Gosman, G Guidice, LC Leppert, PC AF Legro, Richard S. Myers, Evan R. Barnhart, Huiman X. Carson, Sandra A. Diamond, Michael P. Carr, Bruce R. Schlaff, William D. Coutifaris, Christos McGovern, Peter G. Cataldo, Nicholas A. Steinkampf, Michael P. Nestler, John E. Gosman, Gabriella Guidice, Linda C. Leppert, Phyllis C. CA Reproductive Med Network TI The Pregnancy in Polycystic Ovary Syndrome Study: baseline characteristics of the randomized cohort including racial effects SO FERTILITY AND STERILITY LA English DT Article DE randomized controlled trial; insulin resistance; ethnicitye; ethnicity; ultrasound; obesity; metabolic syndrome; infertility; metformin; clomiphene; ovulation induction ID IMPAIRED GLUCOSE-TOLERANCE; NUTRITION EXAMINATION SURVEY; PLACEBO-CONTROLLED TRIAL; TOTAL SERUM TESTOSTERONE; QUALITY-OF-LIFE; INSULIN-RESISTANCE; METABOLIC SYNDROME; FASTING GLUCOSE; DOUBLE-BLIND; OVULATION INDUCTION AB Objective: To report the baseline characteristics and racial differences in the polycystic ovary syndrome (PCOS) phenotype from a large multicenter clinical trial (PPCOS). Design: Double-blind, randomized trial of three treatment regimens (with extended release metformin or clomiphene citrate). Setting: Academic medical centers. Patient(s): Six hundred twenty-six infertile women with PCOS, aged 18-39, with elevated T levels and oligomenorrhea (exclusion of secondary causes), seeking pregnancy, with >= 1 patient fallopian tube, normal uterine cavity, and a partner with sperm concentration >= 20 x 10(6)/mL in >= 1 ejaculate. Intervention(s): Baseline characterization. Main Outcome Measure(s): Historical, biometric, and biochemical measures of PCOS. Result(s): There were no significant differences in baseline variables between treatment groups. The overall mean (+/- SD) age of the subjects was 28.1 +/- 4.0 years, and the mean body mass index was 35.2 kg/m(2) (+/- 8.7). Polycystic ovaries (PCOs) were present in 90.3% of the subjects, and the man volume of each ovary was 10 cm(3) or more. Of the subjects, 7% had ovaries that were discordant for PCO morphology. At baseline, 18.3% of the subjects had an abnormal fasting glucose level (> 100 mg/dL). Asians tended to have a milder phenotype, and whites and African Americans were similar in these measures. Conclusion(s): The treatment groups were well matched for baseline parameters and we have added further information to the PCOS phenotype. C1 Penn State Univ, Milton S Hershey Med Ctr, Dept Obstet & Gynecol, Hershey, PA 17033 USA. Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Wayne State Univ, Detroit, MI USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Colorado, Denver, CO 80202 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Stanford Univ, Palo Alto, CA 94304 USA. Univ Alabama, Birmingham, AL 35487 USA. Virginia Commonwealth Univ, Sch Med, Dept Med, Richmond, VA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NICHHD, Reprod Sci Branch, Bethesda, MD 20892 USA. RP Legro, RS (reprint author), Penn State Coll Med, MS Hershey Med Ctr, Dept Obstet & Gynecol, 500 Univ Dr,H103, Hershey, PA 17033 USA. EM RSL1@PSU.EDU OI Diamond, Michael/0000-0001-6353-4489 FU NCRR NIH HHS [C06 RR016499, M01RR00056, M01RR10732]; NICHD NIH HHS [U01 HD38997, U10 HD27011, U10 HD27049, U10 HD33172, U10 HD38988, U10 HD38992, U10 HD38998, U10 HD38999, U10 HD39005, U54 HD29834] NR 61 TC 67 Z9 68 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2006 VL 86 IS 4 BP 914 EP 933 DI 10.1016/j.fertnstert.2006.03.037 PG 20 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 093JU UT WOS:000241165400020 PM 16963034 ER PT J AU Dezfulian, C Raat, NJH Gladwin, MT AF Dezfulian, Cameron Raat, Nicolaas J. H. Gladwin, Mark T. TI A pharmacogenomic study of atorvastatin effects on eNOS activity: Do "statins" modulate blood nitrite levels and intravascular oxidant stress in susceptible individuals? SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Editorial Material ID DEPENDENT HYPOXIC VASODILATION; CIRCULATING NO POOL; ISCHEMIA-REPERFUSION; SYNTHASE GENE; ENDOTHELIAL DYSFUNCTION; 5'-FLANKING REGION; INJURY; ERYTHROCYTES; TISSUES; HEMOGLOBIN C1 NHLBI, Vasc Med Branch, NIH, CRC, Bethesda, MD 20892 USA. NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA. Johns Hopkins Univ Hosp, Dept Anesthesia, Pediat Anesthesia & Crit Care Med Div, Baltimore, MD 21287 USA. RP Gladwin, MT (reprint author), NHLBI, Vasc Med Branch, NIH, CRC, Bldg 10,Room 5-52222,10 Ctr Dr,MSC 1454, Bethesda, MD 20892 USA. EM mgladwin@nih.gov OI Dezfulian, Cameron/0000-0002-4486-0446 NR 37 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD OCT 1 PY 2006 VL 41 IS 7 BP 1041 EP 1043 DI 10.1016/j.freeadbiomed.2006.05.034 PG 3 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 093BL UT WOS:000241142100003 PM 16962928 ER PT J AU Faulkner, KA Redfern, MS Rosano, C Landsittel, DP Studenski, SA Cauley, JA Zmuda, JM Simonsick, EM Kritchevsky, SB Newman, AB AF Faulkner, Kimberly A. Redfern, Mark S. Rosano, Caterina Landsittel, Douglas P. Studenski, Stephanie A. Cauley, Jane A. Zmuda, Joseph M. Simonsick, Eleanor M. Kritchevsky, Stephen B. Newman, Anne B. CA Hlth ABC Study TI Reciprocal influence of concurrent walking and cognitive testing on performance in older adults SO GAIT & POSTURE LA English DT Article DE dual-task; attention; walking; gait; cognition ID DUAL-TASK; ATTENTIONAL DEMANDS; ALZHEIMERS-DISEASE; POSTURAL CONTROL; ELDERLY-PEOPLE; TALKING; GAIT; FALLS; AGE; INTERFERENCE AB This study investigated how cognitive and walking performance are influenced when performed concurrently in older adults and what factors are associated with poorer dual-task responses. Using a dual-task study design, 217 subjects aged 74-85 years completed three information processing test conditions-(1) no test; (2) push-button simple reaction-time; and (3) visual-spatial decision reaction-time; and three walking test conditions-(1) seated; (2) walking over a 20 m straight course; and (3) walking over 20 m with a turn. Push-button and visual-spatial reaction-times increased approximately 21% and 6%, respectively, while walking compared to sitting (p < 0.008). Reaction-time tests had a relatively weak impact on walking-time. Poorer dual-task walking-time responses correlated with slower walking velocity and weaker muscle strength (p <.062). Findings suggest that walking requires significant cognitive resources among older adults and slower-walking adults and weaker adults may require higher cognitive loading while walking. (C) 2005 Elsevier B.V. All rights reserved. C1 Univ Pittsburgh, Pittsburgh, PA 15261 USA. Duquesne Univ, Pittsburgh, PA 15282 USA. NIA, Baltimore, MD 21225 USA. Wake Forest Univ, Winston Salem, NC 27157 USA. RP Faulkner, KA (reprint author), Univ Pittsburgh, 130 DeSoto St,Parran 509, Pittsburgh, PA 15261 USA. EM kaf24@pitt.edu RI Newman, Anne/C-6408-2013; Cauley, Jane/N-4836-2015; OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010; Kritchevsky, Stephen/0000-0003-3336-6781 FU NIA NIH HHS [T32-AG000181, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 30 TC 16 Z9 16 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD OCT PY 2006 VL 24 IS 2 BP 182 EP 189 DI 10.1016/j.gaitpost.2005.08.004 PG 8 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 093BB UT WOS:000241141100007 PM 16168655 ER PT J AU Habermann, JK Roblick, UJ Luke, BT Prieto, DA Finlay, WJJ Podust, VN Roman, JM Oevermann, E Schiedeck, T Homann, N Duchrow, M Conrads, TP Veenstra, TD Burt, SK Bruch, HP Auer, G Ried, T AF Habermann, Jens K. Roblick, Uwe J. Luke, Brian T. Prieto, Darue A. Finlay, William J. J. Podust, Vladimir N. Roman, John M. Oevermann, Elisabeth Schiedeck, Thomas Homann, Nils Duchrow, Michael Conrads, Thomas P. Veenstra, Timothy D. Burt, Stanley K. Bruch, Hans-Peter Auer, Gert Ried, Thomas TI Increased serum levels of complement C3a anaphylatoxin indicate the presence of colorectal tumors SO GASTROENTEROLOGY LA English DT Article ID OVARIAN-CANCER; PROTEOMIC PATTERNS; PROSTATE-CANCER; COLON-CANCER; BREAST-CANCER; BIOMARKERS; METHYLATION; VALIDATION; VARIANTS; PROMISE AB Background & Aims: Late diagnosis of colorectal carcinoma results in a significant reduction of average Survival times. Yet despite screening programs, about 70% of tumors are detected at advanced stages (International Union Against Cancer stages III/IV). We explored whether detection of malignant disease would be possible through identification of tumor-specific protein biomarkers in serum samples. Methods: A discovery set of sera from patients with colorectal malignancy (n = 58) and healthy control individuals (n = 32) were screened for potential differences using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Candidate proteins were identified and their expression levels were validated in independent sample sets using a specific immunoassay (enzyme-linked immunosorbent assay). Results: By using class comparison and custom-developed algorithms we identified several m/z values that were expressed differentially between the malignant samples and the healthy controls of the discovery set. Characterization of the most prominent m/z values revealed a member of the complement system, the stable form of C3a anaphylatoxin (ie, C3a-desArg). Based on a specific enzyme-linked immunosorbent assay, serum levels of complement C3a-desArg predicted the presence of colorectal malignancy in a blinded validation set (n = 59) with a sensitivity of 96.8% and a specificity of 96.2%. Increased serum levels were also detected in 86.1% of independently collected sera from patients with colorectal adenomas (n = 36), whereas only 5.6% were classified as normal. Conclusions: Complement C3a-desArg is present at significantly higher levels in serum from patients with colorectal adenomas (P < .0001) and carcinomas (P < .0001) than in healthy individuals. This suggests that quantification of C3a-desArg levels could ameliorate existing screening tests for colorectal cancer. C1 NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Schleswig Holstein, Dept Internal Med, Lubeck, Germany. NCI, Adv Biomed Comp Ctr, Sci Applicat Int Corp, Frederick, MD 21701 USA. NCI, Lab Proteom & Analyt Technol, Sci Applicat Int Corp, Frederick, MD 21701 USA. Dublin City Univ, Biomed Diagnost Grp, Dublin 9, Ireland. Ciphergen Biosyst Inc, Fremont, CA USA. Karolinska Inst, Ctr Canc, Dept Pathol & Oncol, Stockholm, Sweden. RP Ried, T (reprint author), NCI, Genet Branch, NIH, 50 South Dr,Bldg 50,Room 1408, Bethesda, MD 20892 USA. EM riedt@mail.nih.gov RI Bruch, Hans-Peter/E-7731-2010; Habermann, Jens/E-2968-2010 FU Intramural NIH HHS [Z01 BC010836-01]; NCI NIH HHS [N01CO12400, N01 CO 12400] NR 34 TC 54 Z9 57 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2006 VL 131 IS 4 BP 1020 EP 1029 DI 10.1053/j.gastro.2006.07.011 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 094NS UT WOS:000241246800012 PM 17030172 ER PT J AU Thorgeirsson, SS AF Thorgeirsson, Snorri S. TI Genomic decoding of hepatocellular carcinoma SO GASTROENTEROLOGY LA English DT Editorial Material ID HYBRIDIZATION DATA; TREE MODELS; CONSTRUCTION; TECHNOLOGIES; ONCOGENESIS; PROGRESSION; CANCER; SITES C1 NCI, Expt Carcinogenesis Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Canc Res Ctr, NIH, 37 Convent Dr,MSC 4262,Bldg 37,Room 4146A, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov NR 24 TC 4 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2006 VL 131 IS 4 BP 1344 EP 1346 DI 10.1053/j.gastro.2006.08.060 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 094NS UT WOS:000241246800043 PM 17030203 ER PT J AU Webster, MJ Herman, MM Kleinman, JE Weickert, CS AF Webster, M. J. Herman, M. M. Kleinman, J. E. Weickert, C. Shannon TI BDNF and trkB mRNA expression in the hippocampus and temporal cortex during the human lifespan SO GENE EXPRESSION PATTERNS LA English DT Article DE neurotrophin; development; neonate; aging; in situ hybridization ID LONG-TERM POTENTIATION; NERVE GROWTH-FACTOR; RAT VISUAL-CORTEX; B-IMMUNOREACTIVE STRUCTURES; POSTMORTEM HUMAN BRAINS; HUMAN PREFRONTAL CORTEX; AGE-RELATED-CHANGES; NEUROTROPHIC FACTOR; SYNAPTIC-TRANSMISSION; ALZHEIMERS-DISEASE AB Brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (trkB) influence neuronal survival, differentiation, synaptogenesis, and maintenance. Using in situ hybridization we examined the spatial and temporal expression of mRNAs encoding these proteins during diverse stages of life in the human hippocampus and inferior temporal cortex. We examined six postnatal time points: neonatal (1-3 months), infant (4-12 months), adolescent (14-18 years), young adult (20-24 years), adult (34-43 years), and aged (68-86 years). Within the hippocampus, levels of BDNF mRNA did not change significantly with age. However, levels of both the full-length form of trkB (trkB(TK+)) mRNA and the truncated form of trkB (trkB(TK-)) decreased over the life span (p < 0.05). In the temporal cortex, BDNF and trkB(TK+) mRNA levels were highest in neonates and decreased with age (r = -0.4 and r = -0.7, respectively, both p < 0.05). In contrast, TrkB(TK-) mRNA levels remained constant across the life span in the temporal cortex. The peak in both BDNF and trkB(TK+) mRNA expression in the neonate temporal cortex differs from that previously described for the frontal cortex where both mRNAs peak in expression during young adulthood. The increase in BDNF and trkB(TK+) mRNA in the temporal cortex of the neonate suggests that neurotrophin signaling is important in the early development of the temporal cortex. In addition, since BDNF and both forms of its high affinity receptor are expressed throughout the development, maturation, and aging of the human hippocampus and surrounding neocortex they are likely to play roles not only in early growth but also in maintenance of neurons throughout life. (c) 2006 Elsevier B.V. All rights reserved. C1 USUHS, Stanley Lab Brain Res, Bethesda, MD 20814 USA. NIMH, IRP, MINDS Unit, Bethesda, MD 20894 USA. NIMH, IRP, CBDB, Bethesda, MD 20894 USA. RP Webster, MJ (reprint author), USUHS, Stanley Lab Brain Res, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM websterm@stanleyresearch.org RI Shannon Weickert, Cynthia/G-3171-2011 NR 91 TC 97 Z9 99 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD OCT PY 2006 VL 6 IS 8 BP 941 EP 951 DI 10.1016/j.modgep.2006.03.009 PG 11 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 088HA UT WOS:000240801600024 PM 16713371 ER PT J AU Choleris, E Ogawa, S Kavaliers, M Gustafsson, JA Korach, KS Muglia, LJ Pfaff, DW AF Choleris, E. Ogawa, S. Kavaliers, M. Gustafsson, J. -A. Korach, K. S. Muglia, L. J. Pfaff, D. W. TI Involvement of estrogen receptor alpha, beta and oxytocin in social discrimination: a detailed behavioral analysis with knockout female mice SO GENES BRAIN AND BEHAVIOR LA English DT Article DE activity; anxiety; ethological analysis; social interactions; social recognition ID ELEVATED PLUS-MAZE; VOLES MICROTUS-OCHROGASTER; PULSED MAGNETIC-FIELD; AGGRESSIVE-BEHAVIOR; MATERNAL-BEHAVIOR; RISK-ASSESSMENT; SEX-DIFFERENCES; ANIMAL-MODELS; RECOGNITION; ANXIETY AB Social recognition, processing, and retaining information about conspecific individuals is crucial for the development of normal social relationships. The neuropeptide oxytocin (OT) is necessary for social recognition in male and female mice, with its effects being modulated by estrogens in females. In previous studies, mice whose genes for the estrogen receptor-alpha (alpha-ERKO) and estrogen receptor-beta (beta-ERKO) as well as OTKO were knocked out failed to habituate to a repeatedly presented conspecific and to dishabituate when the familiar mouse is replaced by a novel animal (Choleris et al. 2003, Proc Natl Acad Sci USA 100, 6192-6197). However, a binary social discrimination assay, where animals are given a simultaneous choice between a familiar and a previously unknown individual, offers a more direct test of social recognition. Here, we used alpha-ERKO, beta-ERKO, and OTKO female mice in the binary social discrimination paradigm. Differently from their wild-type controls, when given a choice, the KO mice showed either reduced (beta-ERKO) or completely impaired (OTKO and alpha-ERKO) social discrimination. Detailed behavioral analyses indicate that all of the KO mice have reduced anxiety-related stretched approaches to the social stimulus with no overall impairment in horizontal and vertical activity, non-social investigation, and various other behaviors such as, self-grooming, digging, and inactivity. Therefore, the OT, ER-alpha, and ER-beta genes are necessary, to different degrees, for social discrimination and, thus, for the modulation of social behavior (e.g. aggression, affiliation). C1 Univ Guelph, Dept Psychol, Guelph, ON N1G 2W1, Canada. Rockefeller Univ, Neurobiol & Behav Lab, New York, NY 10021 USA. Univ Western Ontario, Dept Psychol, London, ON, Canada. Karolinska Inst, Dept Med Nutr, Huddinge, Sweden. Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC USA. Washington Univ, Pain Ctr, Dept Pediat, St Louis, MO USA. RP Choleris, E (reprint author), Univ Guelph, Dept Psychol, Mackinnon Bldg,Room 3004, Guelph, ON N1G 2W1, Canada. EM echoleri@uoguelph.ca OI Korach, Kenneth/0000-0002-7765-418X NR 60 TC 91 Z9 92 U1 1 U2 14 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD OCT PY 2006 VL 5 IS 7 BP 528 EP 539 DI 10.1111/j.1601-183X.2006.00203.x PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 085VA UT WOS:000240631300004 PM 17010099 ER PT J AU Ozturk, SB Vishnu, MR Olarewaju, O Starita, LM Masison, DC Kinzy, TG AF Ozturk, Sedide B. Vishnu, Melanie R. Olarewaju, Olubunmi Starita, Lea M. Masison, Daniel C. Kinzy, Terri Goss TI Unique classes of mutations in the Saccharomyces cerevisiae G-protein translation elongation factor 1A suppress the requirement for guanine nucleotide exchange SO GENETICS LA English DT Article ID INSULIN STIMULATION; FACTOR 1-BETA; FACTOR TU; YEAST; PHOSPHORYLATION; FIDELITY; COMPLEX; KINASE; ACID; EEF1A-EEF1B-ALPHA AB C-proteins play critical roles in many cellular processes and are regulated by accessory proteins that modulate the nucleotide-bound state. Such proteins, including eukaryotic translation elongation factor 1A (eEF1A), are frequently reactivated by guanine nucleotide exchange factors (GEFs). In the yeast Saccharomyces cerevisiae, only the catalytic subunit of the GEF complex, eEF1B alpha, is essential for viability. The requirement for the TEF5 gene encoding eEF1B alpha can be suppressed by the presence of excess substrate, eEF1A. These cells, however, have defects in growth and translation. Two independent unbiased screens performed to dissect the cause of these phenotypes yielded dominant suppressors that bypass the requirement for extra eEF1A. Surprisingly all mutations are in the G-protein eEF1A and cluster in its GTP-binding domain. Five mutants were used to construct novel strains expressing only the eEF1A mutant at normal levels. These strains show no growth defects and little to no decreases in total translation, which raises questions as to the evolutional expression of GEF complexity and other potential functions of this complex. The location of the mutations on the eEF1A-eEF1B alpha structure suggests that their mechanism of suppression may depend on effects on the conserved G-protein elements: the P-loop and NKXD nucleotide-binding element. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet Microbiol & Immunol, Piscataway, NJ 08854 USA. NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Kinzy, TG (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet Microbiol & Immunol, 675 Hoes Lane, Piscataway, NJ 08854 USA. EM kinzytg@umdnj.edu FU NIGMS NIH HHS [R01 GM057483, R01 GM57483, R25 GM055145, T25 GM55145] NR 44 TC 9 Z9 9 U1 0 U2 3 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD OCT PY 2006 VL 174 IS 2 BP 651 EP 663 DI 10.1534/genetics.106.059899 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 102GJ UT WOS:000241798700009 PM 16951075 ER PT J AU Zou, F Xu, ZL Vision, T AF Zou, Fei Xu, Zongli Vision, Todd TI Assessing the significance of quantitative trait loci in replicable mapping populations SO GENETICS LA English DT Article ID RECOMBINANT-INBRED STRAINS; ARABIDOPSIS-THALIANA; GENETIC-ANALYSIS; LINES AB Replicable populations, such as panels of recombinant inbred or doubled haploid lines, are convenient resources for the mapping of QTL. To increase mapping power, replications are often collected within each RI line and a common way to analyze such data is to include in the QTL model only a single measurement from each line that represents the average among the replicates (a line means model). An obvious, but seldom explored, alternative, is to include every replicate in the model (a full data model). Here. we use simulations to compare these two approaches. Further, we propose an extension of the standard permutation procedure that is required to correctly control the type I error in mapping populations with nested structure. C1 Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Zou, F (reprint author), Univ N Carolina, Dept Biostat, 3107D McGavran Greenberg Hall,CB 7420, Chapel Hill, NC 27599 USA. EM fzou@bios.unc.edu RI Vision, Todd/B-4867-2010; OI Vision, Todd/0000-0002-6133-2581; xu, zongli/0000-0002-9034-8902 FU NIGMS NIH HHS [GM074175, R01 GM074175]; NIMH NIH HHS [MH070504, R03 MH070504] NR 17 TC 6 Z9 6 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 2006 VL 174 IS 2 BP 1063 EP 1068 DI 10.1534/genetics.106.059469 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 102GJ UT WOS:000241798700042 PM 16888335 ER PT J AU Scaglia, F Hsu, CH Kwon, H Bai, RK Perng, CL Chang, HM Dai, P Smith, EO Whiteman, DAH Feigenbaum, A Gropman, A Wong, LJC AF Scaglia, Fernando Hsu, Chang-Hung Kwon, Haeyoung Bai, Ren-Kui Perng, Cherng-Lih Chang, Hua-Mei Dai, Pu O'Brian Smith, E. Whiteman, David A. H. Feigenbaum, Annette Gropman, Andrea Wong, Lee-Jun C. TI Molecular bases of hearing loss in multi-systemic mitochondrial cytopathy SO GENETICS IN MEDICINE LA English DT Article DE mtDNA mutation; deafness; maternal inheritance; maternally inherited hearing loss; mitochondrial syndrome ID 12S RIBOSOMAL-RNA; AMINOGLYCOSIDE-INDUCED DEAFNESS; HEREDITARY OPTIC NEUROPATHY; NUCLEAR MODIFIER GENE; SENSORINEURAL DEAFNESS; CONNEXIN-26 MUTATIONS; AUDITORY NEUROPATHY; PEDIATRIC-PATIENTS; CLINICAL SPECTRUM; A1555G MUTATION AB Purpose: Hearing loss is a common clinical feature in classic mitochondrial syndromes. The purpose of this study was to evaluate the diverse molecular etiologies and natural history of hearing loss in multi-systemic mitochondrial cytopathies and the possible correlation between degree of hearing loss and neurological phenotype. Methods: In this retrospective study we evaluated the clinical features and molecular bases of hearing loss associated with multi-systemic mitochondrial cytopathy. Forty-five patients with sensorineural hearing loss and definite diagnosis of mitochondrial cytopathy according to the published diagnostic criteria were studied. Results: The sensorineural hearing loss was progressive and for the most part symmetrical with involvement of the higher frequencies. Both cochlear and retrocochlear involvement were found in this cohort. No correlation was found between the degree of hearing loss and the number and severity of neurological manifestations. Deleterious mtDNA point mutations of undisputed pathogenicity were identified in 18 patients. The A3243G mutation was the most frequently encountered among this group. MtDNA depletion, over-replication, and multiple deletions were found in further 11 cases. Conclusion: This study reveals an expanding spectrum of mtDNA abnormalities associated with hearing loss. No correlation was found between the degrees of hearing loss and the severity of neurological manifestations. C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Texas Childrens Hosp, Dept Genet, Houston, TX 77030 USA. Tri Serv Gen Hosp, Dept Neurol, Natl Def Med Ctr, Taipei, Taiwan. Tri Serv Gen Hosp, Div Clin Pathol, Natl Def Med Ctr, Taipei, Taiwan. Dong Duk Womens Univ, Dept Appl Chem, Seoul, South Korea. Vita Genom Inc, Taipei, Taiwan. 301 Gen Hosp, Dept Otolaryngol, Beijing, Peoples R China. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Shire Human Genet Therapies Inc, Cambridge, MA USA. Hosp Sick Children, Div Clin & Metab Dis, Toronto, ON M5G 1X8, Canada. Univ Toronto, Toronto, ON, Canada. Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD USA. RP Wong, LJC (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. NR 56 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD OCT PY 2006 VL 8 IS 10 BP 641 EP 652 DI 10.1097/01.gim.0000237781.10594.d1 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 102NJ UT WOS:000241818600006 PM 17079881 ER PT J AU Lee, HC Goodman, JL AF Lee, Hin C. Goodman, Jesse L. TI Anaplasma phagocytophilum causes global induction of antiapoptosis in human neutrophils SO GENOMICS LA English DT Article DE Anaplasma phagocytophilum; human granulocytic anaplasmosis; ehrlichiosis; antiapoptosis; microarray analysis; neutrophils ID HUMAN GRANULOCYTIC EHRLICHIOSIS; NF-KAPPA-B; INDUCED APOPTOSIS; CASPASE-3 ACTIVATION; DEATH RECEPTORS; HL-60 CELLS; AGENT; INFECTION; EXPRESSION; SURVIVAL AB Anoplasma phagocytophilum (Ap), the agent of the tick-borne disease human granulocytic anaplasmosis, is an obligate intracellular pathogen unique in its ability to target and replicate within neutrophils. It profoundly inhibits neutrophil apoptosis, prolonging neutrophil survival from hours to days. To determine the basis of antiapoptosis, we compared gene expression in Ap-infected vs mock-infected human neutrophils. Antiapoptosis genes were consistently and significantly up-regulated (2- to 15-fold) within 1-3 h. These genes synergistically inhibit apoptosis through. several interconnected pathways including p38MAPK (MAP2K3), ERK (IER3), PI3K (PRKCD), and NF-kappa B (BCL2A1, NFKB1, NFKBIA, GADD45B). Both extrinsic death receptor (TNFAIP3, CFLAR, SOD2) and intrinsic mitochondrial:(BCL2A1, PIM2, BIRC3) pathways were affected as confirmed by reductions in both caspase 3 and caspase 8 activities. Several important antiapoptotic genes noted to be up-regulated in Ap-infected neutrophils were not up-regulated during Ap infection of HL-60 cells (which is not antiapoptotic). In conclusion, just as apoptosis may be triggered through multiple molecular pathways, effective antiapoptosis of neutrophils is achieved rapidly and redundantly by this intracellular pathogen dependent on cell survival. Published by Elsevier Inc. C1 US FDA, Ctr Biol Evaluat & Res, Off Ctr Director, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Goodman, JL (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Ctr Director, NIH Campus,8800 Rockville Pike,Bldg 29B,Suite 5NN, Bethesda, MD 20892 USA. EM jesse.goodman@fda.hhs.gov NR 31 TC 27 Z9 29 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD OCT PY 2006 VL 88 IS 4 BP 496 EP 503 DI 10.1016/j.ygeno.2006.06.002 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 093WX UT WOS:000241202100012 PM 16876385 ER PT J AU Meijer, CJ Snijders, PJ Castle, PE AF Meijer, Chris J. Snijders, Peter J. Castle, Philip E. TI Clinical utility of HPV genotyping SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 6th International EUROGIN Congress CY APR 23-26, 2006 CL Paris, FRANCE ID HUMAN-PAPILLOMAVIRUS TYPE-16; ATYPICAL SQUAMOUS-CELLS; CERVICAL-CANCER; FOLLOW-UP; UNDETERMINED SIGNIFICANCE; CYTOLOGIC ABNORMALITIES; MANAGEMENT STRATEGIES; PARTICLE VACCINE; WOMEN; RISK C1 NCI, DHHS, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA. Vrije Univ Amsterdam, Med Ctr, Unit Mol Pathol, Dept Pathol, NL-1007 MB Amsterdam, Netherlands. RP Castle, PE (reprint author), NCI, DHHS, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA. EM castlep@mail.nib.gov NR 39 TC 84 Z9 89 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2006 VL 103 IS 1 BP 12 EP 17 DI 10.1016/j.ygyno.2006.07.031 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 089NJ UT WOS:000240887100004 PM 16934860 ER PT J AU Kirkpatrick, B Fleming, LE Backer, LC Bean, JA Tamer, R Kirkpatrick, G Kane, T Wanner, A Dalpra, D Reich, A Baden, DG AF Kirkpatrick, Barbara Fleming, Lora E. Backer, Lorraine C. Bean, Judy A. Tamer, Robert Kirkpatrick, Gary Kane, Terrance Wanner, Adam Dalpra, Dana Reich, Andrew Baden, Daniel G. TI Environmental exposures to Florida red tides: Effects on emergency room respiratory diagnoses admissions SO HARMFUL ALGAE LA English DT Article DE asthma; pneumonia; bronchitis; brevetoxins; sensitive populations; COPD; harmful algal blooms (HABs); red tides; Karenia brevis ID AEROSOLIZED BREVETOXINS; EVENTS; TOXINS AB Human exposure to Florida red tides formed by Karenia brevis, occurs from eating contaminated shellfish and inhaling aerosolized brevetoxins. Recent studies have documented acute symptom changes and pulmonary function responses after inhalation of the toxic aerosols, particularly among asthmatics. These findings suggest that there are increases in medical care facility visits for respiratory complaints and for exacerbations of underlying respiratory diseases associated with the occurrence of Florida red tides. This study examined whether the presence of a Florida red tide affected the rates of admission with a respiratory diagnosis to a hospital emergency room in Sarasota, FL. The rate of respiratory diagnoses admissions were compared for a 3-month time period when there was an onshore red tide in 2001 (red tide period) and during the same 3-month period in 2002 when no red tide bloom occurred (non-red tide period). There was no significant increase in the total number of respiratory admissions between the two time periods. However, there was a 19% increase in the rate of pneumonia cases diagnosed during the red tide period compared with the non-red tide period. We categorized home residence zip codes as coastal (within 1.6 km from the shore) or inland (> 1.6 km from shore). Compared with the non-red tide period, the coastal residents had a significantly higher (54%) rate of respiratory diagnoses admissions than during the red tide period. We then divided the diagnoses into subcategories (i.e. pneumonia, bronchitis, asthma, and upper airway disease). When compared with the non-red tide period, the coastal zip codes had increases in the rates of admission of each of the subcategories during the red tide period (i.e. 31, 56, 44, and 64%, respectively). This increase was not observed seen in the inland zip codes. C1 Mote Marine Lab, Environm Hlth Program, Sarasota, FL 33236 USA. NSF, Miami, FL 33149 USA. NIEHS, Oceans & Human Hlth Ctr, Miami, FL 33149 USA. Univ Miami, Marine & Freshwater Biomed Sci Ctr, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Miami, FL 33149 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. Univ Cincinnati, Cincinnati, OH USA. Childrens Hosp, Ctr Med, Cincinnati, OH USA. Lung Associates Sarasota, Sarasota, FL 34239 USA. Univ Miami, Sch Med, Miami, FL 33136 USA. Florida Dept Hlth, Tallahassee, FL 32399 USA. Univ N Carolina, Marine Sci Res Ctr, Wilmington, NC 28409 USA. RP Kirkpatrick, B (reprint author), Mote Marine Lab, Environm Hlth Program, 1600 Ken Thompson Pkwy, Sarasota, FL 33236 USA. EM bkirkpat@mote.org FU NIEHS NIH HHS [P01 ES010594, P01 ES010594-06A1] NR 25 TC 54 Z9 56 U1 3 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9883 J9 HARMFUL ALGAE JI Harmful Algae PD OCT PY 2006 VL 5 IS 5 BP 526 EP 533 DI 10.1016/j.hal.2005.09.004 PG 8 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA 088GT UT WOS:000240800900003 PM 20357898 ER PT J AU Arnlov, J Evans, JC Benjamin, EJ Larson, MG Levy, D Sutherland, P Siwik, DA Wang, TJ Colucci, WS Vasan, RS AF Arnlov, J. Evans, J. C. Benjamin, E. J. Larson, M. G. Levy, D. Sutherland, P. Siwik, D. A. Wang, T. J. Colucci, W. S. Vasan, R. S. TI Clinical and echocardiographic correlates of plasma osteopontin in the community: the Framingham Heart Study SO HEART LA English DT Editorial Material C1 NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Dept Med, Myocardiol Biol Unit, Boston, MA 02118 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM vasan@bu.edu RI Arnlov, Johan/N-9886-2013; OI Siwik, Deborah/0000-0002-7166-327X; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [K23 HL074077, 1K23 HL074077-01, 1R01HL67288, 2K24HL04334, K24 HL004334, N01-HC-25195, R01 HL067288] NR 5 TC 15 Z9 15 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD OCT PY 2006 VL 92 IS 10 BP 1514 EP 1515 DI 10.1136/hrt.2005.081406 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 084CC UT WOS:000240508300032 PM 16973806 ER PT J AU Tseng, FC Brown, EE Maiese, EM Yeager, M Welch, R Gold, BD Owens, M Cranston, B Hanchard, B El-Omar, E Hisada, M AF Tseng, Fan-Chen Brown, Elizabeth E. Maiese, Eric M. Yeager, Meredith Welch, Robert Gold, Benjamin D. Owens, Marilyn Cranston, Beverly Hanchard, Barrie El-Omar, Emad Hisada, Michie TI Polymorphisms in cytokine genes and risk of Helicobacter pylori infection among jamaican children SO HELICOBACTER LA English DT Article DE Helicobacter pylori seropositivity; cytokines; gene; single nucleotide polymorphism (SNP) ID INTERLEUKIN-1 POLYMORPHISMS; GASTRIC-CANCER; ATROPHIC GASTRITIS; TRANSCRIPTION; COLONIZATION; EXPRESSION; MUCOSA AB Background: Infection by Helicobacter pylori is often acquired during childhood. Recent studies suggest that inflammatory cytokines may play a role in susceptibility to, and disease phenotype caused by, H. pylori infection, but the association of host genetic variability with risk of H. pylori infection has not been studied in children. Methods: We investigated the relationship between the risk of H. pylori antibody positivity and cytokine gene polymorphisms among 199 two-year-old Jamaicans. H. pylori seropositivity was determined by a validated research enzyme-linked immunosorbent assay. Real-time Taqman (R) polymerase chain reaction was used to determine variants at 17 loci in 11 cytokine genes (IL1A, IL1B, IL2, TNF, TLR4, IL4, IL6, IL10, IL10RA, IL12A and IL13). We estimated the odds ratio and the 95% confidence interval for the association of genetic polymorphisms with H. pylori seropositivity, using logistic regression. Results: Forty (20.1%) of 199 children were seropositive. Children's H. pylori seropositivity correlated highly with maternal H. pylori seropositivity (OR = 7.98, 95% CI = 1.05-60.60, p = .02). Children carrying IL1A -889T had a lower risk of H. pylori positivity, compared to those carrying -889C, with each T allele associated with 43% risk reduction (OR = 0.57, 95% CI = 0.33-0.99, p-trend = .05). No other loci we examined were associated with the risk of H. pylori seropositivity. Conclusions: The IL1A -889 T allele, known to express a higher level of cytokine IL-1 alpha, is associated with a lower risk of H. pylori infection among Jamaican children. Our finding supports the hypothesis that an upregulation of pro-inflammatory cytokines may protect against persistent H. pylori colonization. C1 NCI, Viral Epidemiol Brach, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. NCI, Core Genotyping Facil, NIH, DHHS, Rockville, MD 20852 USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21218 USA. Emory Univ, Dept Pediat Gastroenterol, Atlanta, GA 30322 USA. Univ W Indies, Dept Pathol, Kingston 7, Jamaica. Univ Aberdeen, Dept Med & Therapeut, Aberdeen AB9 1FX, Scotland. RP Hisada, M (reprint author), NCI, Viral Epidemiol Brach, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 8008, Rockville, MD 20852 USA. EM hisadam@exchange.nih.gov RI Tseng, Fan-Chen/D-2097-2010 FU Intramural NIH HHS; NCI NIH HHS [N01-CP-21121, N01-CP-40548, N01-CP33043-21, N01-CP31006]; NIDDK NIH HHS [DK 53706-06] NR 25 TC 23 Z9 24 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD OCT PY 2006 VL 11 IS 5 BP 425 EP 430 DI 10.1111/j.1523-5378.2006.00433.x PG 6 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 081WX UT WOS:000240349400003 PM 16961803 ER PT J AU Kreitman, RJ Pastan, I AF Kreitman, Robert J. Pastan, Ira TI Immunotoxins in the treatment of refractory hairy cell leukemia SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID PSEUDOMONAS EXOTOXIN-A; SINGLE-CHAIN IMMUNOTOXIN; TERM-FOLLOW-UP; RECOMBINANT IMMUNOTOXIN; DIPHTHERIA-TOXIN; ANTI-CD22 IMMUNOTOXIN; ANTITUMOR-ACTIVITY; ANTI-TAC; PHASE-I; INTERLEUKIN-2 RECEPTORS AB An increasing number of patients who have hairy cell leukemia (HCL) have persistent disease that requires treatment, despite purine analogs, splenectomy, interferon, and rituximab. Many of these patients have been treated successfully with immunotoxins. An immunotoxin contains a protein toxin connected to a cell-binding ligand, such as an antibody. An immunotoxin recognizes the target cell, internalizes, and the toxin translocates to the cytosol where it inhibits protein synthesis enzymatically. Immunotoxins that show activity in HCL contain truncated Pseudommas exotoxin fused to the Fv fragments of anti-GD25 or anti-CD22 monoclonal antibodies. Both agents, termed LMB-2 and BL22, respectively, have been tested in patients who have HCL after failure of purine analogs and other therapies; major responses have been achieved in most patients. C1 NCI, Clin Immunotherapy Sect, Mol Biol Lab, Clin Immunotherapy Sect,Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Clin Immunotherapy Sect, Mol Biol Lab, Clin Immunotherapy Sect,Ctr Canc Res,NIH, 9000 Rockville Pike,Bldg 37,Room 5124B, Bethesda, MD 20892 USA. EM kreitmar@mail.nih.gov FU Intramural NIH HHS NR 61 TC 15 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2006 VL 20 IS 5 BP 1137 EP + DI 10.1016/j.hoc.2006.06.009 PG 16 WC Oncology; Hematology SC Oncology; Hematology GA 095DM UT WOS:000241288400011 PM 16990113 ER PT J AU Pruett, TL Freeman, JR Appelbaum, PS Gillespie, BW Armstrong, DR Emond, JC Weinrieb, RM Nixon, DC AF Pruett, Timothy L. Freeman, Jason R. Appelbaum, Paul S. Gillespie, Brenda W. Armstrong, Doug R. Emond, Jean C. Weinrieb, Robert M. Nixon, Devon C. CA Study Grp and the A2ALL TI Use of a computerized assessment to measure patient competency to provide informed consent for living liver donation: Findings from the adult to adult living donor liver transplantation cohort study (A2ALL) SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Virginia, Dept Surg, Charlottesville, VA USA. Univ Virginia, Dept Psychiat Med, Charlottesville, VA USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Columbia Univ, Coll Phys & Surg, Dept Surg, New York, NY USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Virginia, Charlottesville, VA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 11 BP 192A EP 192A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300012 ER PT J AU Kato, T Heller, T Matsumura, T Saito, S Sapp, RK Murthy, K Wakita, T Liang, JT AF Kato, Takanobu Heller, Theo Matsumura, Takuya Saito, Satoru Sapp, Ronda K. Murthy, Krishna Wakita, Takaji Liang, Jake T. TI Production of infectious hepatitis C virus of various genotypes in cell culture SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. Natl Inst Infect Dis, Dept Virol 2, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 28 BP 198A EP 199A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300029 ER PT J AU Shin, EC Mihalik, K Feinstone, SM Rice, CM Rehermann, B AF Shin, Eui-Cheol Mihalik, Kathleen Feinstone, Stephen M. Rice, Charles M. Rehermann, Barbara TI CD8 T cells are recruited to the liver in acute hepatitis C by HCV RNA-induced CXCR3-and CCR5-ligands SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIDDK, Immunol Sect, LDB, NIH, Bethesda, MD USA. US FDA, Lab Hepatitis Viruses, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 27 BP 198A EP 198A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300028 ER PT J AU Chalasani, N Kleiner, D Unalp-Arida, A Cummings, O AF Chalasani, Naga Kleiner, David Unalp-Arida, Aynur Cummings, Oscar TI Relationship between severity of steatosis and other histological features of steatohepatitis in patients with NAFLD: Preliminary findings from the nash clinical research network SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Indiana Univ, Sch Med, Indianapolis, IN USA. NCI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 32 BP 200A EP 200A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300033 ER PT J AU Takami, T Uchida, K Kaposi-Novak, P Gomez-Quiroz, LE Conner, EA Factor, VM Thorgeirsson, SS AF Takami, Taro Uchida, Koichi Kaposi-Novak, Pal Gomez-Quiroz, Luis E. Conner, Elizabeth A. Factor, Valentina M. Thorgeirsson, Snorri S. TI Loss of HGF/c-Met signaling pathway accelerates early stages of den-induced hepatocarcinogenesis SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RI Gomez-Quiroz, Luis/L-8415-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 46 BP 205A EP 205A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300047 ER PT J AU Conjeevaram, H Everhart, JE Afdhal, N Brown, RS Fried, MW Howell, CD Jeffers, LJ Terrault, NA Wiley, TE Hoofnagle, JH Wahed, A AF Conjeevaram, Hari Everhart, Jay E. Afdhal, Nezam Brown, Robert S. Fried, Michael W. Howell, Charles D. Jeffers, Lennox J. Terrault, Norah A. Wiley, Thelma E. Hoofnagle, Jay H. Wahed, Abdus TI Changes in body weight and insulin sensitivity during and after peginterferon and ribavirin therapy of chronic hepatitis C SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Michigan, Ann Arbor, MI 48109 USA. NIDDK, NIH, Bethesda, MD USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. New York Presbyterian Med Ctr, New York, NY USA. Univ N Carolina, Chapel Hill, NC USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif Davis, Chicago, IL USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Miami, Miami, FL 33152 USA. RI Wahed, Abdus/A-6441-2008 NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 86 BP 220A EP 220A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300087 ER PT J AU Kaplan, DE Nakamoto, N Ganesan, S Coleclough, J Kaminski, M Xin, D Abraham, S Chang, KM AF Kaplan, David E. Nakamoto, Nobuhiro Ganesan, Sutharsan Coleclough, Jennifer Kaminski, Mary Xin, Dong Abraham, Shaked Chang, Kyong-Mi TI Regulatory and effector T-cell responses in HCV-infected liver transplant recipients SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Penn, Div Gastroenterol, Philadelphia, PA USA. Vet Adm Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Div Transplant Surg, Philadelphia, PA USA. Immune Tolerance Network, San Francisco, CA USA. NIAID, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 137 BP 240A EP 240A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300138 ER PT J AU Borg, BB Kleiner, DE Liang, J Hoofnagle, JH AF Borg, Brian B. Kleiner, David E. Liang, Jake Hoofnagle, Jay H. TI Longitudinal analysis of fibrosis progression in chronic hepatitis C using analysis of multiple biopsies and generalized estimating equations (GEE) SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIH, NIDDK, Liver Dis Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 165 BP 250A EP 251A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300166 ER PT J AU Kaposi-Novak, P Libbrecht, L Factor, VM Lee, JS Coulouarn, C Sears, NC Roskams, T Thorgeirsson, SS AF Kaposi-Novak, Pal Libbrecht, Louis Factor, Valentina M. Lee, Ju-Seog Coulouarn, Cedric Sears, Nathaniel C. Roskams, Tania Thorgeirsson, Snorri S. TI Transcriptomics of human dysplastic liver lesions reveal the central role of MYC in malignant conversion SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. Univ Leuven, Dept Morphol, Louvain, Belgium. Univ Leuven, Dept Mol Pathol, Louvain, Belgium. RI Coulouarn, Cedric/E-5472-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 183 BP 257A EP 257A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300184 ER PT J AU Kang, XQ Liu, J Feng, WK Song, ZY McClain, CJ Kang, YJ Zhou, ZX AF Kang, Xinqin Liu, Jie Feng, Wenke Song, Zhenyuan McClain, Craig J. Kang, Y. James Zhou, Zhanxiang TI Zinc supplementation prevents alcohol-induced liver injury through modulation of gene expression SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Louisville, Dept Med, GI, Louisville, KY 40292 USA. NIEHS, NCI, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 185 BP 258A EP 258A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300186 ER PT J AU Kleiner, DE Behling, C Brunt, EM Lavine, JE McCullough, AJ Sanyal, AJ Schwimmer, JB Tonascia, J AF Kleiner, David E. Behling, Cynthia Brunt, Elizabeth M. Lavine, Joel E. McCullough, Arthur J. Sanyal, Arun J. Schwimmer, Jeffrey B. Tonascia, James CA NSCRNR Grp TI Comparison of adult and pediatric NAFLD - Confirmation of a second pattern of progressive fatty liver disease in children SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. Univ Calif San Diego, San Diego, CA 92103 USA. St Louis Univ, St Louis, MO 63103 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Virginia Commonwealth Univ, Med Ctr, Richmond, VA USA. Johns Hopkins Ctr Clin Trials, Baltimore, MD USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 189 BP 259A EP 260A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300190 ER PT J AU Loomba, R Lutchman, G Kleiner, D Borg, B Feld, J Modi, A Ghany, M Heller, T Doo, E Park, Y Ricks, M Denkinger, B Premkumar, A Sumner, A Liang, J Hoofnagle, JH AF Loomba, Rohit Lutchman, Glen Kleiner, David Borg, Brian Feld, Jordan Modi, Apurva Ghany, Marc Heller, Theo Doo, Edward Park, Yoon Ricks, Madia Denkinger, Blakeley Premkumar, Ahalya Sumner, Anne Liang, Jake Hoofnagle, Jay H. TI Pilot study of metformin in patients with nonalcoholic steatohepatitis SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIH, CC, Dept Radiol, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 190 BP 260A EP 260A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300191 ER PT J AU Elmowalid, GA Qiao, M Jeong, S Borg, B Baumert, T Sapp, R Murthy, K Hu, ZY Liang, J AF Elmowalid, Gamal A. Qiao, Ming Jeong, Suzan Borg, Brian Baumert, Thomas Sapp, Ronda Murthy, Krishna Hu, Zongyi Liang, Jake TI Immunization with hepatitis C virus-like particles induces partial protection against hepatitis C virus infection in chimpanzees SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIH, Liver Dis Branch, Bethesda, MD 20892 USA. Univ Freiburg, Dept Med, D-7800 Freiburg, Germany. SW Fdn Biomed Res, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 271 BP 291A EP 291A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300272 ER PT J AU Everson, GT Kulig, CC Shiffman, ML Sterling, RK Morgan, TR Hoefs, JC Curto, TM Everhart, JE Wagner, D AF Everson, Gregory T. Kulig, Clark C. Shiffman, Mitchell L. Sterling, Richard K. Morgan, Timothy R. Hoefs, John C. Curto, Teresa M. Everhart, James E. Wagner, David TI Altered hepatic metabolic function in patients with chronic hepatitis C is associated with obesity, insulin resistance, or hepatic steatosis, independent of cirrhosis: Results from the HALT-C Trial SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Colorado, Sch Med, Div Gastroenterol & Hepatol, Denver, CO USA. NIDDKD, Bethesda, MD 20892 USA. Univ Calif Irvine, Irvine, CA USA. Virginia Commonwealth Univ Hlth Syst, Richmond, VA USA. New England Res Inst, Watertown, MA 02172 USA. Metab Solut Inc, Nashua, NH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 292 BP 299A EP 299A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300293 ER PT J AU Nakamoto, N Ebinuma, H Li, Y Kwok, WW Price, D Levine, B Chang, KM AF Nakamoto, Nobuhiro Ebinuma, Hirotoshi Li, Yun Kwok, William W. Price, David Levine, Bruce Chang, Kyong-Mi TI In-vitro expansion of HCV-specific FoxP3+CD4+CD25+Treg cells SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Benaroya Res Inst, Seattle, WA USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RI Levine, Bruce/D-1688-2009; Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 299 BP 301A EP 301A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300300 ER PT J AU Feld, JJ Nanda, S Susan, P Schweigler, L Theodore, D Dougherty, K Zacks, S Shrestha, R Liang, TJ Fried, M AF Feld, Jordan J. Nanda, Santosh Susan, Pusek Schweigler, Lisa Theodore, Dickens Dougherty, Karen Zacks, Steven Shrestha, Roshan Liang, T. Jake Fried, Michael TI Hepatic gene expression profiles during treatment with peginterferon and ribavirin: Identifying important molecular pathways for treatment response SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIDDK, NIH, Liver Dis Branch, Bethesda, MD USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 336 BP 315A EP 315A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300337 ER PT J AU Modi, AA Feld, J Loomba, R Borg, B Heller, T Ghany, M Doo, E Liang, J Hoofnagle, J AF Modi, Apurva A. Feld, Jordan Loomba, Rohit Borg, Brian Heller, Theo Ghany, Marc Doo, Edward Liang, Jake Hoofnagle, Jay TI Improvement in immunological abnormalities in patients with chronic hepatitis C who have a sustained virological response to therapy SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 403 BP 341A EP 341A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300404 ER PT J AU Meunier, JC Takikawa, S Russell, RS Bukh, J Goossens, V Maertens, G Depla, E Emerson, SU Purcell, RH AF Meunier, Jean-Christophe Takikawa, Shingo Russell, Rodney S. Bukh, Jens Goossens, Vera Maertens, Geert Depla, Erik Emerson, Suzanne U. Purcell, Robert H. TI Identification of human monoclonal antibodies against HCV E1 that broadly neutralize retroviral pseudoparticles and JFH-1 based viruses SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIH, Bethesda, MD 20892 USA. Innogenet, Therapeut, Zwijnaarde, Belgium. Hvidovre Univ Hosp, Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 412 BP 344A EP 345A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300413 ER PT J AU Kuiken, C Combet, C Bukh, J Deleage, G Mizokami, M Richardson, R Sablon, E Yusim, K Pawlotsky, JM Simmonds, P AF Kuiken, Carla Combet, Christophe Bukh, Jens Deleage, Gilbert Mizokami, Masashi Richardson, Russel Sablon, Erwin Yusim, Karina Pawlotsky, Jean-Michel Simmonds, Peter TI A comprehensive system for consistent numbering of HCV sequences, proteins and epitopes SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Los Alamos Natl Lab, Los Alamos, NM USA. Inst Biol & Chim Prot, Lyon, France. Univ Paris, Creteil, France. NIH, Bethesda, MD 20892 USA. Nagoya City Univ, Grad Sch Med Sci, Nagoya, Aichi, Japan. Innogenet NV, Ghent, Belgium. Univ Edinburgh, Edinburgh, Midlothian, Scotland. RI DELEAGE, Gilbert/F-7163-2010 NR 2 TC 5 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 423 BP 348A EP 348A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300424 ER PT J AU Trotter, JF Blei, AT Everhart, JE Lok, AS Wisniewski, KA Freise, CE Saab, S Campsen, PJ AF Trotter, James F. Blei, Andres T. Everhart, James E. Lok, Anna S. Wisniewski, Karen A. Freise, Chris E. Saab, Sammy Campsen, P. Jeffrey CA Study Group A2ALL TI Outcomes of donors and recipients following living donor liver transplantation for acute liver failure SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Colorado, Div Transplant Surg, Denver, CO 80202 USA. Northwestern Univ, Dept Med, Chicago, IL 60611 USA. NIH, NIDDKD, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. NIH, Bethesda, MD 20892 USA. RI Lok, Anna /B-8292-2009 NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 463 BP 362A EP 362A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362301004 ER PT J AU Kagawa, T Mochizuki, K Numari, A Watanabe, N Mine, T Arias, IM AF Kagawa, Tatehiro Mochizuki, Kaori Numari, Asano Watanabe, Norihito Mine, Tetsuya Arias, Irwin M. TI Shortened biochemical half-life is responsible for the impaired bile acid transport function of D482G-PFIC2 mutation of bile salt export pump SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Tokai Univ, Isehara, Kanagawa, Japan. NIH, NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 518 BP 382A EP 382A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362301059 ER PT J AU Freise, CE Gillespie, BW Koffron, AJ Lok, AS Pruett, TL Emond, JC Fair, JH Fisher, RA Olthoff, KM Trotter, JF Ghobrial, RM AF Freise, Chris E. Gillespie, Brenda W. Koffron, Alan J. Lok, Anna S. Pruett, Timothy L. Emond, Jean C. Fair, Jeffrey H. Fisher, Robert A. Olthoff, Kim M. Trotter, James F. Ghobrial, R. Mark CA Study Grp and the A2ALL TI Comparison of complication rates in recipients of living donor and deceased donor liver transplants: Findings from the adult to adult living donor liver transplantation cohort study (A2ALL) SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Northwestern Univ, Dept Surg, Chicago, IL USA. Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Virginia, Dept Surg, Charlottesville, VA USA. Columbia Univ Coll Phys & Surg, Dept Surg, New York, NY 10032 USA. Univ N Carolina, Dept Surg, Chapel Hill, NC USA. Virginia Commonwealth Univ, Med Coll Virginia Hosp, Dept Surg, Richmond, VA USA. Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. Univ Colorado, Dept Surg, Denver, CO USA. Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. NIH, Bethesda, MD 20892 USA. RI Lok, Anna /B-8292-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 648 BP 429A EP 430A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362301189 ER PT J AU Adams, PC Reboussin, DM McLaren, CE Barton, JC Acton, RT Lovato, L McLaren, GD Moses, GC Press, R Chang, H Leiendecker-Foster, C Harriss, EL Gordeuk, VR Dawkins, FW Eckfeldt, JH AF Adams, Paul C. Reboussin, David M. McLaren, Christine E. Barton, James C. Acton, Ronald T. Lovato, Laura McLaren, Gordon D. Moses, Godfrey C. Press, Richard Chang, Henry Leiendecker-Foster, Catherine Harriss, Emily L. Gordeuk, Victor R. Dawkins, Fitzroy W. Eckfeldt, John H. TI Do the biological variability of transferrin saturation and unsaturated iron binding capacity limit their utility as screening tests for HFE C282Y-linked hemochromatosis SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Hosp, London, ON 27109, Canada. Wake Forest Univ, Winston Salem, NC USA. Southern Iron Disorders Ctr, Birmingham, AL 92717 USA. Univ Calif Irvine, Sch Med, Irvine, CA USA. Univ Alabama, Birmingham, AL 20059 USA. Howard Univ, Washington, DC USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. NHLBI, Bethesda, MD USA. Univ Minnesota, Minneapolis, MN USA. MDS Lab, Toronto, ON 97201, Canada. Oregon Hlth Sci Univ, Portland, OR USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 656 BP 432A EP 433A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362301197 ER PT J AU Feld, JJ Hussain, N David, K Hoofnagle, JH Ahlawat, S Anderson, V Dianne, H Gallin, JI Malech, HL Liang, TJ Holland, SM Heller, T AF Feld, Jordan J. Hussain, Nadeem David, Kleiner Hoofnagle, Jay H. Ahlawat, Sushil Anderson, Victoria Dianne, Hilligoss Gallin, John I. Malech, Harry L. Liang, T. Jake Holland, Steven M. Heller, Theo TI Portal hypertensive thrombocytopenia predicts mortality in chronic granulomatous disease (CGD) SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIH, NIDDK, Liver Dis Branch, Bethesda, MD 20892 USA. NIH, NIAID, Bethesda, MD 20892 USA. NIH, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 698 BP 448A EP 449A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362301239 ER PT J AU Hoefs, JC Everson, GT Shiffman, ML Morgan, TR Naishadham, D Wright, EC AF Hoefs, John C. Everson, Gregory T. Shiffman, Mitchell L. Morgan, Timothy R. Naishadham, Deepa Wright, Elizabeth C. TI Enhanced quantitative liver spleen scan (QLSS) prediction of liver disease severity in baseline halt-C patients with moderate fibrosis or cirrhosis SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Calif Irvine, Orange, CA 92668 USA. Univ Colorado, Sch Med, Denver, CO USA. Virginia Commonwealth Hlth Syst, Richmond, VA USA. Long Beach VA Hosp, Long Beach, CA USA. New England Res Inst, Watertown, MA 02172 USA. NIH, NIDDKD, Div Digest Dis & Nutr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 720 BP 456A EP 457A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362301261 ER PT J AU Russo, MW Fannin, R Parker, J Shah, R Heinloth, A Paules, R Tennant, R Watkins, P AF Russo, Mark W. Fannin, Rick Parker, Joel Shah, Ruchir Heinloth, Alexandra Paules, Richard Tennant, Ray Watkins, Paul TI Gene expression analysis of peripheral blood yields signs of acetaminophen exposure in the absence of detectable levels SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ N Carolina, Chapel Hill, NC USA. NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC USA. Constella Grp, Durham, NC USA. Univ N Carolina, GCRC, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 896 BP 521A EP 521A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362301437 ER PT J AU Jeong, WI Gao, B AF Jeong, Won-Il Gao, Bin TI STAT1 attenuates liver fibrosis via inhibiting of HSC proliferation and stimulating of NK cell killing of activated HSCS: Suppression of the anti-fibrotic effects of NK/IFN-G/STAT1 by chronic ethanol consumption SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIAAA, Rockville, MD 20852 USA. NIH, Rockville, MD USA. RI JEONG, WON IL/B-6615-2011 NR 0 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 1039 BP 575A EP 576A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302133 ER PT J AU Tang, Y Katuri, V Wang, RH Jogunoori, W Saha, T Deng, CX Brandhagen, DJ Sidawy, A Mishra, B Mishra, L AF Tang, Yi Katuri, Varalakshmi Wang, Rui-Hong Jogunoori, Wilma Saha, Tapas Deng, Chu-Xia Brandhagen, David J. Sidawy, Anton Mishra, Bibhuti Mishra, Lopa TI Crosstalk between ELF and HFE is important in suppression of hepatocellular carcinoma SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Georgetown Univ, Dept Surg, Washington, DC USA. DVAMC, Washington, DC USA. Mayo Clin, Rochester, MN USA. NIH, NIDDK, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 1103 BP 598A EP 598A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302197 ER PT J AU Coulouarn, C Factor, VM Thorgeirsson, SS AF Coulouarn, Cedric Factor, Valentina M. Thorgeirsson, Snorri S. TI Transcriptomic characterization of the multiple-step tumor progression in a c-Myc/Tgf alpha transgenic mouse model of HCC SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NCI, NIH, Bethesda, MD USA. RI Coulouarn, Cedric/E-5472-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 1155 BP 620A EP 620A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302249 ER PT J AU Jackson, ML Kleiner, D Liang, TJ Hoofnagle, JH Ghany, M AF Jackson, Melanie L. Kleiner, David Liang, T. Jake Hoofnagle, Jay H. Ghany, Marc TI Prevalence and management of autoimmune hepatitis in the setting of chronic hepatitis C SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Washington Hosp Ctr, Washington, DC 20010 USA. NIH, NIDDK Liver Dis Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 1207 BP 639A EP 639A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302301 ER PT J AU Brunt, EM Kleiner, DE Behling, C Wilson, L Lavine, JE Neuschwander-Tetri, BA AF Brunt, Elizabeth M. Kleiner, David E. Behling, Cynthia Wilson, Laura Lavine, Joel E. Neuschwander-Tetri, Brent A. CA Network Res Grp Nonalcoholic S TI Portal inflammation in NAFLD: Correlations from the NASH CRN database SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 St Louis Univ, St Louis, MO 63103 USA. NCI, Bethesda, MD 20892 USA. USC, San Diego, CA USA. JHU, Data Coordinating Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 1220 BP 644A EP 644A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302314 ER PT J AU Kowdley, KV Kleiner, DE Unlap, A Wilson, L AF Kowdley, Kris V. Kleiner, David E. Unlap, Aynur Wilson, Laura TI Prevalence and pattern of hepatic iron deposition and relationship to type 2 diabetes and fibrosis among patients with NAFLD: Preliminary findings from the NASH CRN SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Washington, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. Johns Hopkins, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 1224 BP 645A EP 646A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302318 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, Constance E. Everhart, James E. TI Relationship of liver injury with gallstone disease (GSD) in the United States population SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 1234 BP 649A EP 649A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302328 ER PT J AU Jazwinski, A Feld, JJ Kleiner, DE Ghany, MG Jake Liang, T Hoofnagle, JH Heller, T AF Jazwinski, Alison Feld, Jordan J. Kleiner, David E. Ghany, Marc G. Jake Liang, T. Hoofnagle, Jay H. Heller, Theo TI Elevated iron parameters and disease severity in hepatitis B: A more complex relationship than might be assumed SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIH, NIDDK, Bethesda, MD USA. NIH, NCI, Dept Pathol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 1320 BP 681A EP 682A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302414 ER PT J AU Matsumura, T Kato, T Hu, Z Juteau, LM Vaillant, A Liang, JT AF Matsumura, Takuya Kato, Takanobu Hu, Zongyi Juteau, Lean-Marc Vaillant, Andrew Liang, Jake T. TI A novel class of amphipathic DNA polymers inhibits hepatitis C virus infection by blocking viral entry SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 NIH, NIDDK, Liver Dis Branch, Bethesda, MD USA. REPLICor Inc, Laval, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA LB4 BP 693A EP 693A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302444 ER PT J AU Fontana, RJ Kleiner, DE Bilonick, R Terrault, N Afdhal, N Belle, SH Jeffers, LJ Ramcharran, D Ghany, MG Hoofnagle, JH AF Fontana, Robert J. Kleiner, David E. Bilonick, Richard Terrault, Norah Afdhal, Nezam Belle, Steven H. Jeffers, Lennox J. Ramcharran, Darmendra Ghany, Marc G. Hoofnagle, Jay H. CA Virahep-C Study Grp TI Modeling hepatic fibrosis in African American and Caucasian American patients with chronic hepatitis C virus infection SO HEPATOLOGY LA English DT Article ID ALANINE AMINOTRANSFERASE LEVELS; CHRONIC VIRAL-HEPATITIS; LIVER FIBROSIS; PEGINTERFERON ALPHA-2B; SERUM ASPARTATE; NATURAL-HISTORY; CIRRHOSIS; PROGRESSION; RIBAVIRIN; DISEASE AB Assessment of histological stage is an integral part of disease management in patients infected with the hepatitis C virus (HCV). The aim of this study was to develop a model incorporating objective clinical and laboratory parameters to estimate the probability of severe fibrosis (i.e., Ishak fibrosis >= 3) in previously untreated African American (AA) and Caucasian American (CA) patients with HCV genotype 1. The Ishak fibrosis scores of 205 CA and 194 AA patients enrolled in the Viral Resistance to Antiviral Therapy of Chronic Hepatitis C study (Virahep-C) were modeled using simple and multiple logistic regression. The model was then validated in an independent cohort of 461 previously untreated patients with HCV. The distribution of fibrosis scores was similar in the AA and CA patients as was the proportion of patients with severe fibrosis (35% vs. 39%, P = .47). After accounting for the number of portal areas in the biopsy, patient age, serum aspartate aminotransferase, alkaline phosphatase, and platelet count were independently associated with severe fibrosis in the overall cohort, and the relationship with fibrosis was similar in both the AA and CA subgroups. The area under the receiver operating characteristic curve (AUROC) of the Virahep-C model (0.837) was significantly better than in other published models (P = .0003). The AUROC of the Virahep-C model was 0.851 in the validation population. In conclusion, a model consisting of widely available clinical and laboratory features predicted severe hepatic fibrosis equally well in AA and CA patients with HCV genotype I and was superior to other published models. The excellent performance of the Virahep-C model in an external validation cohort suggests the findings are replicable and potentially generalizable. C1 Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. NCI, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Miami, Miami, FL 33152 USA. NIDDK, Bethesda, MD USA. RP Fontana, RJ (reprint author), 3912 Taubman Ctr, Ann Arbor, MI 48109 USA. EM rfontana@umich.edu OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS; NCRR NIH HHS [M01 RR00645, M02 RR00046]; NIDDK NIH HHS [U01 DK60349, U01 DK60309, U01 DK60324, U01 DK60327, U01 DK60329, U01 DK60335, U01 DK60340, U01 DK60341, U01 DK60342, U01 DK60344, U01 DK60345, U01 DK60346, U01 DK60352] NR 47 TC 31 Z9 34 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 BP 925 EP 935 DI 10.1002/hep.21335 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 095WE UT WOS:000241338200019 PM 17006909 ER PT J AU Sun, R Park, O Horiguchi, N Kulkarni, S Jeong, WI Sun, HY Radaeva, S Gao, B AF Sun, Rui Park, Ogyi Horiguchi, Norio Kulkarni, Shailin Jeong, Won-Il Sun, Hao-Yu Radaeva, Svetlana Gao, Bin TI STAT1 contributes to dsRNA inhibition of liver regeneration after partial hepatectomy in mice SO HEPATOLOGY LA English DT Article ID CHRONIC HEPATITIS-C; CYCLIN-DEPENDENT KINASE; CELL-MEDIATED HEPATITIS; VIRUS-INFECTION; HEPATOCYTE PROLIFERATION; INTERFERON-GAMMA; PROGENITOR CELLS; VIRAL-HEPATITIS; MESSENGER-RNA; UP-REGULATION AB Increasing evidence suggests that liver regeneration is suppressed in patients with chronic HCV infection; however, the underlying mechanisms remain unclear. Previously, we demonstrated that injection of the synthetic double-stranded RNA (dsRNA) poly I:C to mimic viral infection suppresses liver regeneration in the partial hepatectomy (PHx) model, whereby IFN-gamma contributes to the inhibition. In this study, we examined the role of the IFN-gamma-activated downstream signal (STAT1) and genes (IRF-1, p21(cip1), and SOCS1) in liver regeneration and hepatocyte proliferation. Results show that disruption of the STAT1 gene abolished poly I:C suppression of liver regeneration and the inhibitory effect of poly I:C on liver regeneration was diminished in IRF-1(-/-) and p21(cip1-/-) mice. Treatment with IFN-gamma in vitro inhibited cell proliferation of wild-type mouse hepatocytes, but not STAT1(-/-) hepatocytes. The inhibitory effect of IFN-gamma on cell proliferation was also diminished in IRF-1(-/-) and p21(cip1-/-) hepatocytes, but enhanced in SOCS1(-/-) hepatocytes. Hepatocyte proliferation was unaffected by treatment with poly I:C alone, but when hepatocytes were co-cultured with liver lymphocytes, proliferation was inhibited by IFN-gamma/STAT1-dependent mechanisms. Moreover, in HCV-infected livers with cirrhosis, activation of STAT1 was detected and correlated positively with liver injury (elevated serum levels of AST) but negatively with hepatocyte proliferation (hepatocyte PCNA and Ki-67 positive immunostaining). In conclusion, STAT1 is involved in dsRNA suppression of liver regeneration; not only does STAT1 activation contribute to liver injury, it may also block liver repair through inhibition of hepatocyte proliferation in HCV-infected patients, playing an important role in the pathogenesis of disease. C1 NIAAA, Sect Liver Biol, NIH, Lab Physiol Studies, Bethesda, MD 20892 USA. Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Peoples R China. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, NIH, Lab Physiol Studies, 5625 Fishers Lane,Rm 2S-33, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov RI JEONG, WON IL/B-6615-2011 NR 46 TC 38 Z9 42 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 BP 955 EP 966 DI 10.1002/hep.21344 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 095WE UT WOS:000241338200022 PM 17006930 ER PT J AU Coulouarn, C Gomez-Quiroz, LE Lee, JS Kaposi-Novak, P Conner, EA Goldina, TA Onishchenko, GE Factor, VM Thorgeirsson, SS AF Coulouarn, Cedric Gomez-Quiroz, Luis E. Lee, Ju-Seog Kaposi-Novak, Pal Conner, Elizabeth A. Goldina, Tatyana A. Onishchenko, Galina E. Factor, Valentina M. Thorgeirsson, Snorri S. TI Oncogene-specific gene expression signatures at preneoplastic stage in mice define distinct mechanisms of hepatocarcinogenesis SO HEPATOLOGY LA English DT Article ID TRANSGENIC MOUSE MODEL; C-MYC; HEPATOCELLULAR-CARCINOMA; TRANSCRIPTION FACTOR; TARGET GENES; CELL-CYCLE; ADIPOCYTE DIFFERENTIATION; MICROARRAY ANALYSIS; GENOMIC TARGETS; APOPTOSIS AB We applied a genome-wide microarray analysis to three transgenic mouse models of liver cancer in which targeted overexpression of c-Myc, E2f1, and a combination of the two was driven by the albumin promoter. Although gene expression profiles in HCC derived in all three transgenic lines were highly similar, oncogene-specific gene expression signatures were identified at an early dysplastic stage of hepatocarcinogenesis. Overexpression of E2f1 was associated with a strong alteration in lipid metabolism, and Srebp1 was identified as a candidate transcription factor responsible for lipogenic enzyme induction. The molecular signature of c-Myc overexpression included the induction of more than 60 genes involved in the translational machinery that correlated with an increase in liver mass. In contrast, the combined activity of c-Myc and E2f1 specifically enhanced the expression of genes involved in mitochondrial metabolism-particularly the components of the respiratory chain-and correlated with an increased ATP synthesis. Thus, the results suggest that E2f1, c-Myc, and their combination may promote liver tumor development by distinct mechanisms. In conclusion, determination of tissue-specific oncogene expression signatures might be useful to identify conserved expression modules in human cancers. C1 NCI, LEC, CCR, Bethesda, MD 20892 USA. Moscow MV Lomonosov State Univ, Dept Cell Biol & Histol, Moscow, Russia. RP Thorgeirsson, SS (reprint author), NCI, LEC, CCR, Bldg 37,Room 4146A,37 Convent Dr MSC 4262, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov RI Gomez-Quiroz, Luis/L-8415-2013; Coulouarn, Cedric/E-5472-2011; OI Gomez-Quiroz, Luis Enrique/0000-0002-5704-5985 FU Intramural NIH HHS NR 50 TC 36 Z9 38 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 BP 1003 EP 1011 DI 10.1002/hep.21293 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 095WE UT WOS:000241338200027 PM 17006931 ER PT J AU Bielinski, SJ Tang, WH Pankow, JS Miller, MB Mosley, TH Boerwinkle, E Olshen, RA Curb, JD Jaquish, CE Rao, DC Weder, A Arnett, DK AF Bielinski, Suzette J. Tang, Weihong Pankow, James S. Miller, Michael B. Mosley, Thomas H. Boerwinkle, Eric Olshen, Richard A. Curb, J. David Jaquish, Cashell E. Rao, D. C. Weder, Alan Arnett, Donna K. TI Genome-wide linkage scans for loci affecting total cholesterol, HDL-C, and triglycerides: the Family Blood Pressure Program SO HUMAN GENETICS LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; LEPTIN RECEPTOR GENE; DEPENDENT DIABETES-MELLITUS; LIPID-LEVELS; HYPERTENSION; HERITABILITY; INSULIN; OBESITY; TWINS; DEFICIENCY AB Atherosclerosis accounts for 75% of all deaths from cardiovascular disease and includes coronary heart disease (CHD), stroke, and other diseases of the arteries. More than half of all CHD is attributable to abnormalities in levels and metabolism of lipids. To locate genes that affect total cholesterol, high density lipoprotein cholesterol (HDL-C), and triglycerides, genome-wide linkage scans for quantitative trait loci were performed using variance components methods as implemented in SOLAR on a large diverse sample recruited as part of the Family Blood Pressure Program. Phenotype and genetic marker data were available for 9,299 subjects in 2,953 families for total cholesterol, 8,668 subjects in 2,736 families for HDL, and 7,760 subjects in 2,499 families for triglycerides. Mean lipid levels were adjusted for the effects of sex, age, age(2), age-by-sex interaction, body mass index, smoking status, and field center. HDL-C and triglycerides were further adjusted for average total alcoholic drinks per week and estrogen use. Significant linkage was found for total cholesterol on chromosome 2 (LOD = 3.1 at 43 cM) in Hispanics and for HDL-C on chromosome 3 (LOD = 3.0 at 182 cM) and 12 (LOD = 3.5 at 124 cM) in Asians. In addition, there were 13 regions that showed suggestive linkage (LOD >= 2.0); 7 for total cholesterol, 4 for HDL, and 2 for triglycerides. The identification of these loci affecting lipid phenotypes and the apparent congruence with previous linkage results provides increased support that these regions contain genes influencing lipid levels. C1 Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. Univ Mississippi, Med Ctr, Dept Geriatr Med, Jackson, MS 39216 USA. Univ Texas, Ctr Human Genet, Houston Hlth Sci Ctr, Houston, TX USA. Stanford Univ, Sch Med, Div Biostat, Stanford, CA 94305 USA. Pacific Hlth Res Inst, Honolulu, HI USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. Univ Michigan Hosp, Ann Arbor, MI 48109 USA. Univ Alabama, Dept Epidemiol, Birmingham, AL USA. RP Bielinski, SJ (reprint author), Univ Minnesota, Div Epidemiol & Community Hlth, W Bank Off Bldg Suite 300,1300 S 2nd St, Minneapolis, MN 55454 USA. EM Bielinski@epi.umn.edu RI Bielinski, Suzette/A-2238-2009 OI Bielinski, Suzette/0000-0002-2905-5430 FU NHLBI NIH HHS [U01 HL54497, 5 T32 HL007972, U01 HL54471, U01 HL54457, U01 HL54463, U01 HL54464, U01 HL54466, U01 HL54472, U01 HL54473, U01 HL54481, U01 HL54485, U01 HL54495, U01 HL54496, U01 HL54498, U01 HL54504, U01 HL54508, U01 HL54509, U01 HL54512, U01 HL54526, U01 HL54527, U01 HL64777] NR 34 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD OCT PY 2006 VL 120 IS 3 BP 371 EP 380 DI 10.1007/s00439-006-0223-0 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 085OR UT WOS:000240613900005 PM 16868761 ER PT J AU Chen, Q Zou, H Xu, XH Luo, M Zuo, YQ Chen, XH Song, L Chen, XL Yao, ZQ Zhao, TM AF Chen, Qiang Zou, Hai Xu, Xiaohong Luo, Mei Zuo, Yaqin Chen, Xianhui Song, Ling Chen, Xueli Yao, Zhiqiang Zhao, Tongmao TI Identification of a novel HLA-DRB1 allele (DRB1*1457) with a DRB1*04 sequence motif SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 16-20, 2006 CL San Diego, CA SP Amer Soc Histocompatibil & Immunogenet C1 Chinese Acad Med Sci, Sichuan Cord Blood Bank, HLA Lab, Inst Blood Transfus, Chengdu, Sichuan, Peoples R China. NIH, Mol & Cellular Immunogenet Sect, 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 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD OCT PY 2006 VL 67 IS 10 SU 1 BP S121 EP S121 DI 10.1016/j.humimm.2006.08.186 PG 1 WC Immunology SC Immunology GA 101OZ UT WOS:000241751400169 ER PT J AU Li, X Chouchane, L Adams, S Chen, D Wang, E Monaco, A Bouaouina, N Stroncek, D Marincola, FM AF Li, Xin Chouchane, Lotfi Adams, Sharon Chen, Deborah Wang, Ena Monaco, Alessandro Bouaouina, Noureddine Stroncek, David Marincola, Francesco M. TI Associations between HLA and the prevalence of nasopharyngeal carcinoma (NPC) among Tunisians SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 16-20, 2006 CL San Diego, CA SP Amer Soc Histocompatibil & Immunogenet C1 NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Fac Med Monastir, Lab Mol Immunol & Oncol, Monastir Tunisia, Tunisia. RI Monaco, Alessandro/O-5338-2015 OI Monaco, Alessandro/0000-0002-9941-7003 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 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD OCT PY 2006 VL 67 IS 10 SU 1 BP S157 EP S157 DI 10.1016/j.humimm.2006.08.247 PG 1 WC Immunology SC Immunology GA 101OZ UT WOS:000241751400228 ER PT J AU Uribe, MR Adams, S Schechterly, C Stroncek, D Alter, H Marincola, F AF Uribe, Marcela R. Adams, Sharon Schechterly, Cathy Stroncek, David Alter, Harvey Marincola, Francesco TI KIR genes and response to HCV infection in Caucasoid patients SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 16-20, 2006 CL San Diego, CA SP Amer Soc Histocompatibil & Immunogenet C1 NIH, DTM, HLA 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 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD OCT PY 2006 VL 67 IS 10 SU 1 BP S155 EP S155 DI 10.1016/j.humimm.2006.08.243 PG 1 WC Immunology SC Immunology GA 101OZ UT WOS:000241751400224 ER PT J AU Mavrakis, M Lippincott-Schwartz, J Stratakis, CA Bossis, I AF Mavrakis, Manos Lippincott-Schwartz, Jennifer Stratakis, Constantine A. Bossis, Ioannis TI Depletion of type IA regulatory subunit (RI alpha) of protein kinase A (PKA) in mammalian cells and tissues activates mTOR and causes autophagic deficiency SO HUMAN MOLECULAR GENETICS LA English DT Article ID NODULAR ADRENOCORTICAL DISEASE; CARNEY COMPLEX; CATALYTIC SUBUNITS; MOLECULAR ANALYSIS; LATE ENDOSOMES; YEAST; RAB7; MECHANISMS; MUTATIONS; PATHWAY AB The human PRKAR1A gene encodes the regulatory subunit 1-alpha (RI alpha) of the cAMP-dependent protein kinase A (PKA) holoenzyme. Regulation of the catalytic activity of PKA is the only well-studied function of RI alpha. Inactivating PRKAR1A mutations cause primary pigmented nodular adrenocortical disease (PPNAD) or Carney complex (CNC), an inherited syndrome associated with abnormal skin pigmentation and multiple neoplasias, including PPNAD. Histochemistry of tissues from CNC patients is indicative of autophagic deficiency and this led us to investigate the relationship between RI alpha and mammalian autophagy. We found that fluorescently tagged RI alpha associates with late endosomes and autophagosomes in cultured cells. The number of autophagosomes in prkar1a(-/-) mouse embryonic fibroblasts (MEFs) was reduced compared with wild-type MEFs. RI alpha co-immunoprecipitated with mTOR kinase, a major regulator of autophagy. Phosphorylated-mTOR levels and mTOR activity were dramatically increased in prkar1a(-/-) mouse cells, and in HEK 293 cells with RI alpha levels reduced by siRNA. Finally, phosphorylated-mTOR levels and mTOR activity were increased in CNC cells and in PPNAD tissues. These data suggest that RI alpha deficiency decreases autophagy by the activation of mTOR, providing a molecular basis to autophagic deficiency in PPNAD. C1 NICHHD, NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Mavrakis, M (reprint author), NICHHD, NIH, Cell Biol & Metab Branch, Room 101,Bldg 18T,18 Lib Dr, Bethesda, MD 20892 USA. EM mavrakim@mail.nih.gov NR 41 TC 57 Z9 57 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 1 PY 2006 VL 15 IS 19 BP 2962 EP 2971 DI 10.1093/hmg/ddl239 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 086TO UT WOS:000240696100013 PM 16963469 ER PT J AU Hallett, M AF Hallett, Mark TI Pathophysiology of writer's cramp SO HUMAN MOVEMENT SCIENCE LA English DT Article DE hand; motor control; neuroimaging; plasticity; sensorimotor ID FOCAL HAND DYSTONIA; HUMAN MOTOR CORTEX; CONTINGENT NEGATIVE-VARIATION; TRANSCRANIAL MAGNETIC STIMULATION; INTRACORTICAL INHIBITION; RECIPROCAL INHIBITION; SURROUND INHIBITION; CERVICAL DYSTONIA; BLEPHAROSPASM; EXCITABILITY AB Writer's cramp is a task-specific focal hand dystonia. The abnormality of task specificity is curious one and indicates that we need to learn more about the coupling of motor programs and their effectors. Writer's cramp appears to be triggered by spending much time writing by an individual with a fertile physiological substrate for producing the disorder. The fertile background, which is likely genetic, may be a decrease of inhibition, an increase of plasticity or an impairment in sensory function. Recent pathophysiological findings have implications for new therapies. Published by Elsevier B.V. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov NR 49 TC 68 Z9 69 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9457 J9 HUM MOVEMENT SCI JI Hum. Mov. Sci. PD OCT PY 2006 VL 25 IS 4-5 BP 454 EP 463 DI 10.1016/j.humov.2006.05.004 PG 10 WC Neurosciences; Psychology; Psychology, Experimental; Sport Sciences SC Neurosciences & Neurology; Psychology; Sport Sciences GA 105RH UT WOS:000242049500002 PM 16859794 ER PT J AU Awumey, EM Diz, DI Howlett, AC Putney, JW AF Awumey, Emmanuel M. Diz, Debra I. Howlett, Allyn C. Putney, James W., Jr. TI Downregulation of protein kinase C inhibits perivascular sensory nerve Ca2+-sensing receptor signaling SO HYPERTENSION LA English DT Meeting Abstract CT 11th Annual Meeting of the European-Council-for Cardiovascular Reseach CY SEP 29-OCT 01, 2006 CL Nice, FRANCE SP European Council Cardiovasc Res C1 N Carolina Cent Univ, Durham, NC USA. Wake Forest Univ, Winston Salem, NC 27109 USA. N Carolina Cent Univ, Durham, NC USA. Natl Inst Hlth, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD OCT PY 2006 VL 48 IS 4 BP E85 EP E86 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 127FR UT WOS:000243571200492 ER PT J AU Nishikawa, T Saito, J Suematsu, S Ito, Y Matsuzawa, Y Ito, H Kino, T Chrousos, G AF Nishikawa, Tetsuo Saito, Jun Suematsu, Sachiko Ito, Yuzuru Matsuzawa, Yoko Ito, Hiroko Kino, Tomoshige Chrousos, George TI Human renal mesangial cells can produce aldosterone in response to low-density lipoprotein(LDL) SO HYPERTENSION LA English DT Meeting Abstract CT 11th Annual Meeting of the European-Council- for Cardiovascular Reseach CY SEP 29-OCT 01, 2006 CL Nice, FRANCE SP European Council Cardiovasc Res C1 Yokohama Rosai Hosp, Yokohama, Kanagawa, Japan. NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2006 VL 48 IS 4 BP E49 EP E49 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 127FR UT WOS:000243571200305 ER PT J AU Figg, WD Ockers, S AF Figg, William D. Ockers, Sandra TI Prostate Cancer - 6th International Congress - 21-23 July 2006, Boca Raton, FL, USA SO IDRUGS LA English DT Editorial Material C1 NCI, Mol Pharmacol Sect, Canc Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Canc Therapeut Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1369-7056 J9 IDRUGS JI IDrugs PD OCT PY 2006 VL 9 IS 10 BP 675 EP 678 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 088MX UT WOS:000240816900003 PM 17016769 ER PT J AU Yewdell, JW AF Yewdell, Jonathan W. TI Confronting complexity: Real-world immunodominance in antiviral CD8(+) T cell responses SO IMMUNITY LA English DT Review ID INFLUENZA-A VIRUS; EPSTEIN-BARR-VIRUS; ACUTE HIV-1 INFECTION; HEPATITIS-C-VIRUS; IN-VIVO; HUMAN CYTOMEGALOVIRUS; CROSS-REACTIVITY; VACCINIA VIRUS; MURINE CYTOMEGALOVIRUS; ANTIGEN PRESENTATION AB Antiviral CD8(+) T cells respond to only a minute fraction of the potential peptide determinants encoded by viral genomes. Immunogenic determinants can be ordered into highly reproducible hierarchies based on the magnitude of cognate CD8(+) T cell responses. Until recently, this phenomenon, termed immunodominance, was largely defined and characterized in model systems utilizing a few strains of inbred mice infected with a handful of viruses with limited coding capacity. Here, I review work that has extended immunodominance studies to viruses of greater complexity and to the real world of human antiviral immunity. C1 NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 FU Intramural NIH HHS NR 101 TC 201 Z9 203 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 2006 VL 25 IS 4 BP 533 EP 543 DI 10.1016/j.immuni.2006.09.005 PG 11 WC Immunology SC Immunology GA 097WZ UT WOS:000241481500006 PM 17046682 ER PT J AU Huang, F Kitaura, Y Jang, IK Naramura, M Kole, HH Liu, LP Qin, HY Schlissel, MS Gu, H AF Huang, Fang Kitaura, Yasuyuki Jang, IhnKyung Naramura, Mayumi Kole, Hemanta H. Liu, Liping Qin, Haiyan Schlissel, Mark S. Gu, Hua TI Establishment of the major compatibility complex-dependent development of CD4(+) and CD8(+) T cells by the Cbl family proteins SO IMMUNITY LA English DT Article ID NF-KAPPA-B; CLASS-II MOLECULES; C-CBL; ANTIGEN RECEPTOR; THYMOCYTE DEVELOPMENT; SIGNAL-TRANSDUCTION; NEGATIVE REGULATION; POSITIVE SELECTION; UBIQUITIN LIGASES; TRANSGENIC MICE AB Casitas B cell lymphoma (Cbl) proteins are negative regulators for T cell antigen receptor (TCR) signaling. Their role in thymocyte development remains unclear. Here we show that simultaneous inactivation of c-Cbl and Cbl-b in thymocytes enhanced thymic negative selection and altered the ratio of CD4(+) and CD8(+) T cells. Strikingly, the mutant thymocytes developed into CD4(+)- and CD8(+)-Iineage T cells independent of the major histocompatibility complex (MHC), indicating that the CD4(+)- and CD8+-Iineage development programs are constitutively active in the absence of c-Cbl and Cbl-b. The mutant double-positive (DP) thymocytes exhibited spontaneous hyperactivation of nuclear factor-kappa B (NF-kappa B). Additionally, they failed to downregulate the pre-TCR and pre-TCR signaling. Thus, our data indicate that Cbl proteins play a critical role in establishing the MHC-dependent CD4(+) and CD8(+) T cell development programs. They likely do so by suppressing MHC-independent NF-kappa B activation, possibly through downmodulating pre-TCR signaling in DP thymocytes. C1 Columbia Univ Coll Phys & Surg, Dept Microbiol, New York, NY 10032 USA. NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Gu, H (reprint author), Columbia Univ Coll Phys & Surg, Dept Microbiol, 701 W 168th St, New York, NY 10032 USA. EM hg2065@columbia.edu OI Naramura, Mayumi/0000-0003-3658-0767 FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL48702] NR 53 TC 20 Z9 20 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 2006 VL 25 IS 4 BP 571 EP 581 DI 10.1016/j.immuni.2006.08.021 PG 11 WC Immunology SC Immunology GA 097WZ UT WOS:000241481500009 PM 17045823 ER PT J AU Yarovinsky, F Kanzler, H Hieny, S Coffman, RL Sher, A AF Yarovinsky, Felix Kanzler, Holger Hieny, Sara Coffman, Robert L. Sher, Alan TI Toll-like receptor recognition regulates immunodominance in an antimicrobial CD4(+) T cell response SO IMMUNITY LA English DT Article ID DENDRITIC CELLS; TOXOPLASMA-GONDII; IN-VIVO; BACTERIAL FLAGELLIN; IMMUNE-RESPONSE; LYMPHOCYTES-T; ANTIGEN; MICE; ADAPTER; IDENTIFICATION AB Although Toll-like Receptors (TLRs) play a major function in innate recognition of pathogens, their role in antigen processing and presentation in vivo is poorly understood. Here we establish that Toxoplasma gondii profilin, a TLR11 ligand present in the parasite, is an immunodominant antigen in the CD4(+) T cell response to the pathogen. The immunogenicity of profilin was entirely dependent on both TLR11 recognition and signaling through the adaptor myelold differentiation factor 88 (MyD88). Selective responsiveness to this parasite protein was regulated at the level of antigen presentation by dendritic cells (DC) and required both TLR signaling and major histocompatibility complex (MHC) class II recognition acting in cis. These findings support a major influence of TLR recognition in antigen presentation by DC in vivo and establish a mechanism by which TLR ligand association regulates the immunogenicity of microbial antigens. C1 NIAID, Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Dynavax Technol Corp Berkeley, Berkeley, CA 94710 USA. RP Yarovinsky, F (reprint author), NIAID, Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM fyarovinsky@niaid.nih.gov NR 36 TC 102 Z9 109 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 2006 VL 25 IS 4 BP 655 EP 664 DI 10.1016/j.immuni.2006.07.015 PG 10 WC Immunology SC Immunology GA 097WZ UT WOS:000241481500016 PM 17000122 ER PT J AU Whitehead, GS Burch, LH Berman, KG Piantadosi, CA Schwartz, DA AF Whitehead, Gregory S. Burch, Lauranell H. Berman, Katherine G. Piantadosi, Claude A. Schwartz, David A. TI Genetic basis of murine responses to hyperoxia-induced lung injury SO IMMUNOGENETICS LA English DT Article DE hyperoxia; oxygen toxicity; inflammation; superoxide dismutase; extracellular matrix ID PULMONARY OXYGEN-TOXICITY; SPRAGUE-DAWLEY RATS; SUPEROXIDE-DISMUTASE; BRONCHOPULMONARY DYSPLASIA; TRANSGENIC MICE; MESSENGER-RNA; EPITHELIAL-CELLS; FIBRONECTIN; EXPRESSION; ADULT AB To evaluate the effect of genetic background on oxygen (O-2) toxicity, nine genetically diverse mouse strains (129/SvIm, A/J, BALB/cJ, BTBR+(T)/tf/tf, CAST/Ei, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/NJ) were exposed to more than 99% O-2 for 72 h. Immediately following the hyperoxic challenge, the mouse strains demonstrated distinct pathophysiologic responses. The BALB/cJ and CAST/Ei strains, which were the only strains to demonstrate mortality from the hyperoxic challenges, were also the only strains to display significant neutrophil infiltration into their lower respiratory tract. In addition, the O-2-challenged BALB/cJ and CAST/Ei mice were among six strains (A/J, BALB/cJ, CAST/Ei, BTBR+(T)/tf/tf, DBA/2J, and C3H/HeJ) that had significantly increased interleukin 6 concentrations in the whole lung lavage fluid and were among all but one strain that had large increases in lung permeability compared with air-exposed controls. In contrast, the DBA/2J strain was the only strain not to have any significant alterations in lung permeability following hyperoxic challenge. The expression of the extracellular matrix proteins, including collagens I, III, and IV, fibronectin I, and tenascin C, also varied markedly among the mouse strains, as did the activities of total superoxide dismutase (SOD) and manganese-SOD (Mn-SOD or SOD2). These data suggest that the response to O-2 depends, in part, on the genetic background and that some of the strains analyzed can be used to identify specific loci and genes underlying the response to O-2. C1 Vet Adm Med Ctr, Durham, NC 27710 USA. Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Schwartz, DA (reprint author), Vet Adm Med Ctr, Durham, NC 27710 USA. EM schwartzd@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999, 001-2222-857]; NHLBI NIH HHS [U01 HL066611, HL66604, R01 HL062641, HL66611]; NIEHS NIH HHS [P01 ES012496, ES07498, ES012496, ES11961, R01 ES007498, U19 ES011375, ES11375, U19 ES012496, ES09607, P30 ES011961] NR 42 TC 19 Z9 20 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0093-7711 EI 1432-1211 J9 IMMUNOGENETICS JI Immunogenetics PD OCT PY 2006 VL 58 IS 10 BP 793 EP 804 DI 10.1007/s00251-006-0147-9 PG 12 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 094EQ UT WOS:000241222700002 PM 17001473 ER PT J AU Borrego, F Masilamani, M Marusina, AI Tang, X Coligan, JE AF Borrego, Francisco Masilamani, Madhan Marusina, Alina I. Tang, Xiaobin Coligan, John E. TI The CD94/NKG2 family of receptors - From molecules and cells to clinical relevance SO IMMUNOLOGIC RESEARCH LA English DT Review DE CD94/NKG2; DAP12 HLA-E; NK cells; CD8+T cells ID NATURAL-KILLER-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; CD8(+) T-CELLS; HUMAN CYTOMEGALOVIRUS-INFECTION; IMMUNOGLOBULIN-LIKE RECEPTORS; PEPTIDE-BINDING-SPECIFICITY; HLA-E EXPRESSION; E-DEPENDENT PROTECTION; IG-LIKE RECEPTORS; HUMAN NKG2A GENE AB Immune responses must be tightly regulated to avoid hyporesponsiveness on one hand or excessive inflammation and the development of autoimmunity (hyperresponsiveness) on the other hand. This balance is attained through the throttling of activating signals by inhibitory signals that ideally leads to an adequate immune response against an invader without excessive and extended inflammatory signals that promote the development of autoimmunity. The CD94/NKG2 family of receptors is composed of members with activating or inhibitory potential. These receptors are expressed predominantly on NK cells and a subset of CD8+ T cells, and they have been shown to play an important role in regulating responses against infected and tumorigenic cells. In this review, we discuss the current knowledge about this family of receptors, including ligand and receptor interaction, signaling, membrane dynamics, regulation of gene expression and their roles in disease regulation, infections, and cancer, and bone marrow transplantation. C1 NIH, NIAID, RCBS, Lab Allerg Dis, Rockville, MD 20852 USA. RP Borrego, F (reprint author), NIH, NIAID, RCBS, Lab Allerg Dis, Twinbrook 2,Room 205,12441 Parklawn Dr, Rockville, MD 20852 USA. EM jcoligan@niaid.nih.gov OI Masilamani, Madhan/0000-0001-8181-8848 FU Intramural NIH HHS NR 138 TC 54 Z9 59 U1 0 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD OCT PY 2006 VL 35 IS 3 BP 263 EP 277 DI 10.1385/IR:35:3:263 PG 15 WC Immunology SC Immunology GA 227ZY UT WOS:000250697800007 PM 17172651 ER PT J AU Caspi, RR AF Caspi, Rachel R. TI Ocular autoimmunity: the price of privilege? SO IMMUNOLOGICAL REVIEWS LA English DT Review DE experimental autoimmune uveitis; uveitis; immune privilege; immunological tolerance; autoimmune disease ID T-CELL-ACTIVATION; PROMISCUOUS GENE-EXPRESSION; CORNEAL ENDOTHELIAL-CELLS; IMMUNE PRIVILEGE; PIGMENT-EPITHELIUM; SUBRETINAL SPACE; RETINAL ANTIGEN; CILIARY BODY; THYMIC EXPRESSION; CENTRAL TOLERANCE AB The eye is the prototypic immune-privileged organ. Its antigens were once believed to be expressed exclusively in the eye, which resides behind an efficient blood-organ barrier, and were believed to be unknown to the immune system. Self-tolerance to ocular components was therefore believed to be based not on immune tolerance but on immune ignorance. It is now known that the relationship between the immune system and the eye is much more complex. On the one hand, immune privilege is now known to involve not only sequestration but also active mechanisms that (i) inhibit innate and adaptive immune processes within the eye and (ii) shape the response that develops systemically to antigens released from the eye. On the other hand, retinal antigens are found in the thymus and have been shown to shape the eye-specific T-cell repertoire. However, thymic elimination of self-reactive T cells is incomplete, and such 'escapee' T cells are tolerized in the periphery as they recirculate through the body by encounter with self-antigen in healthy tissues. Due to the relative inaccessibility of the healthy eye to the immune system, peripheral tolerance mechanisms may not operate efficiently for ocular antigens, leaving a weak link in the homeostasis of tolerance. The case shall be made that although immune privilege protects vision by keeping the immune system at bay, a potential for developing destructive anti-retinal autoimmunity may be the price for the day-to-day protection afforded by immune privilege against inflammatory insults. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20893 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,10-10N222, Bethesda, MD 20893 USA. EM rcaspi@helix.nih.gov NR 82 TC 77 Z9 80 U1 2 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 2006 VL 213 BP 23 EP 35 DI 10.1111/j.1600-065X.2006.00439.x PG 13 WC Immunology SC Immunology GA 084VJ UT WOS:000240562200003 PM 16972894 ER PT J AU Peters, N Sacks, D AF Peters, Nathan Sacks, David TI Immune privilege in sites of chronic infection: Leishmania and regulatory T cells SO IMMUNOLOGICAL REVIEWS LA English DT Review DE immune privilege; Leishmania; regulatory T cells; skin; interleukin-10; macrophage ID PROTEIN-KINASE-C; EXPERIMENTAL VISCERAL LEISHMANIASIS; NITRIC-OXIDE SYNTHASE; CHEMOKINE RECEPTOR EXPRESSION; DEPENDENT KILLING MECHANISM; TRANSCRIPTION FACTOR FOXP3; PHAGOCYTE NADPH OXIDASE; NECROSIS-FACTOR-ALPHA; HUMAN DENDRITIC CELLS; NATURAL-KILLER-CELLS AB Leishmania are digenetic protozoan parasites that are inoculated into the skin by vector sand flies, are taken up by macrophages, and produce a spectrum of chronic diseases in their natural reservoir and susceptible human hosts. During the early establishment of infection in the skin and lymphoid organs, Leishmania produce multiple effects on macrophage and dendritic cell functions that inhibit their innate anti-microbial defenses and impair their capacity to initiate T-helper 1 cell immunity. In addition, the skin is a site preconditioned for early parasite survival by virtue of a high frequency of steady-state, natural CD25(+)Foxp3(+) regulatory T cells (Tregs) that function to suppress the generation of unneeded immune responses to infectious and non-infectious antigens to which the skin is regularly exposed. In murine models of infection, antigen-induced CD25(+/-)Foxp3(-)interleukin (IL)-10(+) Treg cells act during the effector phase of the immune response to control immunopathology and may also delay or prevent healing. Finally, following resolution of infection in healed mice, CD25(+)Foxp3(+) Tregs function in an IL-10-dependent manner to prevent sterile cure and establish a long-term state of functional immune privilege in the skin. C1 NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, Bldg 4,Rm 126,4 Ctr Dr MSC 0425, Bethesda, MD 20892 USA. EM dsacks@nih.gov NR 218 TC 88 Z9 89 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 2006 VL 213 BP 159 EP 179 DI 10.1111/j.1600-065X.2006.00432.x PG 21 WC Immunology SC Immunology GA 084VJ UT WOS:000240562200012 PM 16972903 ER PT J AU Wahl, SM Wen, J Moutsopoulos, N AF Wahl, Sharon M. Wen, Jie Moutsopoulos, Niki TI TGF-beta: a mobile purveyor of immune privilege SO IMMUNOLOGICAL REVIEWS LA English DT Review DE immune privilege; TGF-beta; macrophages; tolerance; tumor; immune surveillance ID REGULATORY T-CELLS; GROWTH-FACTOR-BETA; IMMUNOLOGICAL SELF-TOLERANCE; NATURAL-KILLER-CELLS; IN-VIVO EXPANSION; DENDRITIC CELLS; CUTTING EDGE; TRANSFORMING GROWTH-FACTOR-BETA-1; SUPPRESSOR FUNCTION; MACROPHAGE INFILTRATION AB Functionally barricaded immune responses or sites of immune privilege are no longer considered dependent on specific anatomical considerations, but rather, they can develop in any location where immunoregulatory cells congregate and express or release products capable of deviating the host response to foreign antigens. Among the pivotal molecules involved in orchestrating these ectopic sites of immune suppression is transforming growth factor-beta (TGF-beta), a secreted and cell-associated polypeptide with a multiplicity of actions in innate and adaptive immunity. While beneficial in initiating and controlling immune responses and maintaining immune homeostasis, immunosuppressive pathways mediated by TGF-beta may obscure immune surveillance mechanisms, resulting in failure to recognize or respond adequately to self, foreign, or tumor-associated antigens. CD4(+)CD25(+)Foxp3(+) regulatory T cells represent a dominant purveyor of TGF-beta-mediated suppression and are found in infiltrating tumors and other sites of immune privilege, where they influence CD8(+) T cells; CD4(+) T-helper (Th)1, Th2, and Th17 cells; natural killer cells; and cells of myeloid lineage to choreograph and/or muck up host defense. Defining the cellular sources, mechanisms of action, and networking that distinguish the dynamic establishment of localized immune privilege is vital for developing strategic approaches to diminish or to embellish these tolerogenic events for therapeutic benefit. C1 NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), NIDCR, Oral Infect & Immun Branch, NIH, Bldg 30,Room 320,320 Convent Dr MSC 4352, Bethesda, MD 20892 USA. EM smwahl@dir.nidcr.nih.gov FU Intramural NIH HHS NR 201 TC 127 Z9 155 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 2006 VL 213 BP 213 EP 227 DI 10.1111/j.1600-065X.2006.00437.x PG 15 WC Immunology SC Immunology GA 084VJ UT WOS:000240562200015 PM 16972906 ER PT J AU Narum, DL Ogun, SA Batchelor, AH Holder, AA AF Narum, David L. Ogun, Solabomi A. Batchelor, Adrian H. Holder, Anthony A. TI Passive immunization with a multicomponent vaccine against conserved domains of apical membrane antigen 1 and 235-kilodalton rhoptry proteins protects mice against Plasmodium yoelii blood-stage challenge infection SO INFECTION AND IMMUNITY LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; MONOCLONAL-ANTIBODIES; FALCIPARUM-MALARIA; MULTIGENE FAMILY; ERYTHROCYTE INVASION; SEQUENCE DIVERSITY; ADHESIVE PROTEINS; BINDING; VIVAX; GENES AB During malaria parasite invasion of red blood cells, merozoite proteins bind receptors on the surface of the erythrocyte. Two candidate Plasmodium yoelii adhesion proteins are apical membrane antigen 1 (AMA1) and the 235-kDa rhoptry proteins (P235). Previously, we have demonstrated that passive immunization with monoclonal antibodies (MAbs) 45B1 and 25.77 against AMA1 and P235, respectively, protects against a lethal challenge infection with P. yoelii YM. We show that MAb 45B1 recognizes an epitope located on a conserved surface of PyAMA1, as determined by phage display and analysis of the three-dimensional structure of AMA1, in a region similar to that bound by the P. falciparum AMA1-specific inhibitory antibody 4G2. The epitope recognized by 25.77 could not be assigned. We report here that MAbs 45B1 and 25.77 also protect against challenge with the nonlethal parasite line 17X, in which PyAMA1 has a significantly different amino acid sequence from that in YM. When administered together, the two MAbs acted at least additively in providing protection against challenge with the virulent YM parasite. These results support the concept of developing a multicomponent blood-stage vaccine and the inclusion of polymorphic targets such as AMA1, which these results suggest contain conserved domains recognized by inhibitory antibodies. C1 EntreMed Inc, Rockville, MD 20850 USA. Natl Inst Med Res, Div Parasitol, London NW7 1AA, England. Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. RP Narum, DL (reprint author), NIH, Malaria Vaccine Dev Branch, 5640 Fishers Lane,Twinbrook 1, Rockville, MD 20852 USA. EM dnarum@niaid.nih.gov RI Holder, Anthony/A-7554-2013 OI Holder, Anthony/0000-0002-8490-6058 FU Medical Research Council [MC_U117532067] NR 58 TC 19 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2006 VL 74 IS 10 BP 5529 EP 5536 DI 10.1128/IAI.00573-06 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 090RF UT WOS:000240967900012 PM 16988228 ER PT J AU Long, EO Bryceson, YT March, ME AF Long, Eric O. Bryceson, Yenan T. March, Michael E. TI Control of NK cell effector functions SO INFLAMMATION RESEARCH LA English DT Meeting Abstract C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Karolinska Inst, Dept Med, Ctr Infect Med, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PD OCT PY 2006 VL 55 SU 2 BP S96 EP S96 PG 1 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 100KT UT WOS:000241668700011 ER PT J AU Murphy, P Barlic, J Zhang, C AF Murphy, Philip Barlic, Jana Zhang, Chelsea TI Chemokine coordination of inflammation in atherosclerotic plaque SO INFLAMMATION RESEARCH LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PD OCT PY 2006 VL 55 SU 2 BP S95 EP S96 PG 2 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 100KT UT WOS:000241668700010 ER PT J AU Wynn, TA AF Wynn, Thomas A. TI Regulation of fibrosis by type-2 cytokines and their receptors SO INFLAMMATION RESEARCH LA English DT Meeting Abstract C1 NIAID, Immunopathogenesis Sect, NIH, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PD OCT PY 2006 VL 55 SU 2 BP S94 EP S94 PG 1 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 100KT UT WOS:000241668700007 ER PT J AU Strober, W Kitani, A Watanabe, T AF Strober, Warren Kitani, Atsushi Watanabe, Tomohiro TI The ever-expanding immunological universe: Impact on mucosal immunity and inflammation SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract CT Inflammatory Bowel Disease Summit CY OCT 04-07, 2006 CL Cleveland, OH C1 NIH, Mucosal Immun Sect, Clin Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD OCT PY 2006 VL 12 SU 3 BP S4 EP S5 DI 10.1097/00054725-200610003-00010 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 109YN UT WOS:000242345600011 ER PT J AU Li, HM Man, C Jin, Y Deng, W Yip, YL Feng, HC Cheung, YC Lo, KW Meltzer, PS Wu, ZG Kwong, YL Yuen, APW Tsao, SW AF Li, H. M. Man, C. Jin, Y. Deng, W. Yip, Y. L. Feng, H. C. Cheung, Y. C. Lo, K. W. Meltzer, P. S. Wu, Z. G. Kwong, Y. L. Yuen, A. P. W. Tsao, S. W. TI Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE immortalization; telomerase; nasopharyngeal carcinoma; p16; RASSF1A ID EPSTEIN-BARR-VIRUS; COMPARATIVE GENOMIC HYBRIDIZATION; NF-KAPPA-B; ENCODED LATENT MEMBRANE-PROTEIN-1; SIGNALING PATHWAYS; CARCINOMA-CELLS; LIFE-SPAN; EXPRESSION; RASSF1A; LMP1 AB Nasopharyngeal carcinoma (NPC) is a common disease in Hong Kong and southern provinces of China. EBV infection is believed to play a critical role in the development of NPC. Previous studies on the transformation mechanism of EBV genes were mostly performed in either NPC or normasopharyngeal epithelial cells which may not be representative of premalignant nasopharyngeal epithelial cells. Establishment of a representative cell system would greatly facilitate the elucidation of the role of EBV infection in the development of NPC. Using telomerase alone, we were able to establish an immortalized nasopharyngeal epithelial cell line from primary nonmalignant nasopharyngeal biopsies. The telomerase-immortalized nasopharyngeal epithelial cells are largely diploid in karyotype. Interestingly, this newly immortalized nasopharyngeal epithelial cell line, referred as NP460hTert, harbors genetic alterations previously identified in premalignant and malignant nasopharyngeal epithelial cells. These include inactivation of p16 by homozygous deletion of the p16(INK4A) locus and downregulation of RASSF1A expression. The deletion of the p16(INK4A) locus appears to be the most crucial event for the immortalization of nasopharyngeal epithelial cells by telomerase and precedes RASSF1A downregulation. In addition, detailed analysis of the cytogenetic changes by conventional cytogenetics, spectral karyotyping (SKY) and array-based CGH revealed a gain of a 17q21-q25 fragment on 11p15 chromosome in all NP460hTert cells which occurred before deletion of the p16(INK4A) locus. Gain of 17q has been previously reported in NPC. In addition, activation of NF-kappa B was observed in immortalized NP460hTert cells at the later population doublings, and may play a role in the survival of immortalized NP epithelial cells. Id1 which is commonly expressed in various human cancers, including NPC, was also upregulated in the immortalized NP460hTert cells. Thus, the establishment of an immortalized nasopharyngeal epithelial cell line harboring common genetic alterations present in premalignant and cancerous nasopharyngeal epithelial cells may provide a valuable cell system to examine for early events involved in NPC carcinogenesis, particularly in elucidating the role of EBV infection in NPC development. (c) 2006 Wiley-Liss, Inc. C1 Univ Hong Kong, Dept Anat, Fac Med, Hong Kong, Hong Kong, Peoples R China. Univ Hong Kong, Dept Med, Fac Med, Hong Kong, Hong Kong, Peoples R China. Chinese Univ Hong Kong, Dept Cellular & Anat Pathol, Shatin, Hong Kong, Peoples R China. Natl Genome Res Inst, NIH, Bethesda, MD USA. Hong Kong Univ Sci & Technol, Dept Biochem, Saigon, Hong Kong, Peoples R China. Univ Hong Kong, Dept Surg, Fac Med, Hong Kong, Hong Kong, Peoples R China. RP Tsao, SW (reprint author), Univ Hong Kong, Dept Anat, Fac Med, Room L01-53,Lab Block,Fac Med Bldg,21 Sassoon Rd, Hong Kong, Hong Kong, Peoples R China. EM gswtsao@hkucc.hku.hk RI Li, Hoi Ming/B-5828-2008; Tsao, George/C-4422-2009; Cheung, Yuk Chun/C-4708-2009; Kwong, Yok Lam/C-4296-2009; Deng, Wen/C-4154-2009; Feng, Huichen/F-5502-2011 OI Feng, Huichen/0000-0003-3069-8174 NR 35 TC 71 Z9 74 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 1 PY 2006 VL 119 IS 7 BP 1567 EP 1576 DI 10.1002/ijc.22032 PG 10 WC Oncology SC Oncology GA 077QX UT WOS:000240046000008 PM 16688717 ER PT J AU Michl, J Scharf, B Schmidt, A Huynh, C Hannan, R von Gizycki, H Friedman, FK Brandt-Rauf, P Fine, RL Pincus, MR AF Michl, Josef Scharf, Bruce Schmidt, Anna Huynh, Chan Hannan, Raquibul von Gizycki, Hans Friedman, Fred K. Brandt-Rauf, Paul Fine, Robert L. Pincus, Matthew R. TI PNC-28, a p53-derived peptide that is cytotoxic to cancer cells, blocks pancreatic cancer cell growth in vivo SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE PNC-28 peptide; p53; pancreatic cancer; nude mice ID P53; MDM2; IDENTIFICATION; APOPTOSIS; INHIBITOR; NECROSIS; THERAPY; TARGET; DEATH; MICE AB PNC-28 is a p53 peptide from its mdm-2-binding domain (residues 17-26), which contains the penetratin sequence enabling cell penetration on its carboxyl terminal end. We have found that this peptide induces necrosis, but not apoptosis, of a variety of human tumor cell lines, including several with homozygous deletion of p53, and a ras-transformed rat acinar pancreatic carcinoma cell line, BMRPA1. Tuc3. On the other hand, PNC-28 has no effect on untransformed cells, such as rat pancreatic acinar cells, BMRPA1, and human breast epithelial cells and no effect on the differentiation of human stem cells. In this study, we now test PNC-28 in vivo for its ability to block the growth of BMRPA1. Tuc3 cells. When administered over a 2-week period in the peritoneal cavities of nude mice containing simultaneously transplanted tumors, PNC-28 causes complete destruction of these tumors. When delivered concurrently with tumor explantation at a remote site, PNC-28 causes a complete blockade of any tumor growth during its 2-week period of administration and 2 weeks posttreatment, followed by weak tumor growth that plateaus at low tumor sizes compared with tumor growth in the presence of a control peptide. When administered after tumor growth has occurred at a site remote from the tumor, PNC-28 causes a decrease in tumor size followed by a slow increase in tumor growth that is significantly slower than growth in the presence of control peptide. These results suggest that PNC-28 may be effective in treating cancers especially if delivered directly to the tumor. (c) 2006 Wiley-Liss, Inc. C1 Suny Downstate Med Ctr, Dept Pathol, Brooklyn, NY 11203 USA. Suny Downstate Med Ctr, Dept Anat & Cell Biol, Brooklyn, NY 11203 USA. Suny Downstate Med Ctr, Dept Microbiol & Immunol, Brooklyn, NY 11203 USA. Suny Downstate Med Ctr, Dept Vet Med, Brooklyn, NY 11203 USA. Suny Downstate Med Ctr, Sci Acad Comp Ctr, Dept Informat Serv, Brooklyn, NY 11203 USA. Natl Canc Inst, Lab Metab, Bethesda, MD USA. Columbia Coll Phys & Surg, Dept Environm Hlth Sci, New York, NY USA. Columbia Univ, Coll Phys & Surg, Div Med Oncol, Expt Therapeut Program, New York, NY USA. New York Harbor VA Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY USA. RP Michl, J (reprint author), Suny Downstate Med Ctr, Dept Pathol, 450 Clarkson Ave, Brooklyn, NY 11203 USA. EM josef.michl@downstate.edu; matthew.pincus2@med.va.gov RI Friedman, Fred/D-4208-2016 FU NCI NIH HHS [CA42500] NR 25 TC 21 Z9 21 U1 1 U2 6 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 OCT 1 PY 2006 VL 119 IS 7 BP 1577 EP 1585 DI 10.1002/ijc.22029 PG 9 WC Oncology SC Oncology GA 077QX UT WOS:000240046000009 PM 16688716 ER PT J AU Koshiol, JE Schroeder, JC Jamieson, DJ Marshall, SW Duerr, A Heilig, CM Shah, KV Klein, RS Cu-Uvin, S Schuman, P Celentano, D Smith, JS AF Koshiol, Jill E. Schroeder, Jane C. Jamieson, Denise J. Marshall, Stephen W. Duerr, Ann Heilig, Charles M. Shah, Keerti V. Klein, Robert S. Cu-Uvin, Susan Schuman, Paula Celentano, David Smith, Jennifer S. TI Time to clearance of human papillomavirus infection by type and human immunodeficiency virus serostatus SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE HIV; HPV type; papillomavirus; human; time to clearance ID CERVICAL-CANCER; NATURAL-HISTORY; YOUNG-WOMEN; SERONEGATIVE WOMEN; HPV TYPES; PERSISTENCE; LESIONS; DNA; TRANSFORMATION; EPIDEMIOLOGY AB Persistent infection with high-risk human papillomavirus (HPV) is central to cervical carcinogenesis. Certain high-risk types, such as HPV16, may be more persistent than other HPV types, and type-specific HPV persistence may differ by HIV serostatus. This study evaluated the association between HPV type and clearance of HPV infections in 522 HIV-seropositive and 279 HIV-seronegative participants in the HIV Epidemiology Research Study (HERS, United States, 1993-2000). Type-specific HPV infections were detected using MY09/MY11/HMB01-based PCR and 26 HPV type-specific probes. The estimated duration of type-specific infections was measured from the first HPV-positive visit to the first of two consecutive negative visits. Hazard ratios (HRs) and 95% confidence intervals (CIs) for HPV clearance were calculated using Cox models adjusted for study site and risk behavior (sexual or injection drugs). A total of 1,800 HPV infections were detected in 801 women with 4.4 years median follow-up. HRs for clearance of HPV16 and related types versus low-risk HPV types were 0.79 (95% CI: 0.64-0.97) in HIV-positive women and 0.86 (95% CI: 0.59-1.27) in HIV-negative women. HRs for HPV18 versus low-risk types were 0.80 (95% CI: 0.56-1.16) and 0.57 (95% CI: 0.22-1.45) for HIV-positive and -negative women, respectively. HPV types within the high-risk category had low estimated clearance rates relative to low-risk types, but HRs were not substantially modified by HIV serostatus. (c) 2006 Wiley-Liss, Inc. C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Brown Univ, Providence, RI 02912 USA. Virginia Commonwealth Univ, Richmond, VA USA. Wayne State Univ, Sch Med, Detroit, MI USA. RP Koshiol, JE (reprint author), NCI, 6120 Exeuct Blvd,MSC 7236, Bethesda, MD 20892 USA. EM koshiolj@mail.nih.gov RI Heilig, Charles/C-2753-2008; OI Heilig, Charles/0000-0003-1075-1310; Marshall, Stephen/0000-0002-2664-9233 FU NCI NIH HHS [CA09330-22]; NIAID NIH HHS [5 P30 AI050410-07]; PHS HHS [U64/CCU106795, U64/CCU206798, U64/CCU306802, U64/CCU506831] NR 35 TC 53 Z9 56 U1 0 U2 1 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 OCT 1 PY 2006 VL 119 IS 7 BP 1623 EP 1629 DI 10.1002/ijc.22015 PG 7 WC Oncology SC Oncology GA 077QX UT WOS:000240046000014 PM 16646070 ER PT J AU Ozaki, K Hishiya, A Hatanaka, K Nakajima, H Wang, G Hwu, P Kitamura, T Ozawa, K Leonard, WJ Nosaka, T AF Ozaki, Katsutoshi Hishiya, Ai Hatanaka, Keiko Nakajima, Hideaki Wang, Gang Hwu, Patrick Kitamura, Toshio Ozawa, Keiya Leonard, Warren J. Nosaka, Tetsuya TI Overexpression of interleukin 21 induces expansion of hematopoietic progenitor cells SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE interleukin 21; hematopoietic progenitor cells; overexpression; expansion; CFU-GM ID COMMON GAMMA-CHAIN; STEM-CELLS; GENE-EXPRESSION; IL-21 RECEPTOR; PLASMID DNA; IMMUNITY; IL-15 AB The interleukin 21 (IL-21) receptor is expressed on T-cells, B-cells, and natural killer cells, and IL-21 is critical for regulating immunoglobulin production in vivo in cooperation with IL-4. So far, however, little is known about a role for IL-21 outside the immune system. We investigated the effect of IL-21 on hematopoiesis in vivo by using the hydrodynamics gene-delivery method. Overexpression of IL-21 increases Sca-1(+) cells in the periphery and spleen. It also increases the numbers of c-Kit(+), Sca-1(+), and lineage(-/low) (KSL) cells and colony-forming units-granulocyte-macrophage (CFU-GM) in the spleen, indicating the expansion of hematopoietic progenitor cells. We found that even in RAG2(-/-) mice, which lack mature T-cells and B-cells, IL-21 induced an increase in KSL cells and CFU-GM in the spleen. These results demonstrate that IL-21 can induce the expansion of hematopoietic progenitor cells in vivo, even in the absence of mature T-cells and B-cells. C1 Jichi Med Univ, Div Hematol, Tochigi 3290498, Japan. NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. Univ Tokyo, Inst Med Sci, Div Hematopoiet Factors, Tokyo, Japan. Univ Tokyo, Inst Med Sci, Dept Cellular Therapy, Tokyo, Japan. RP Ozaki, K (reprint author), Jichi Med Univ, Div Hematol, 3311-1 Yakushiji, Tochigi 3290498, Japan. EM ozakikat@jichi.ac.jp FU Intramural NIH HHS NR 17 TC 15 Z9 15 U1 0 U2 4 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD OCT PY 2006 VL 84 IS 3 BP 224 EP 230 DI 10.1532/IJH97.06036 PG 7 WC Hematology SC Hematology GA 123TA UT WOS:000243317400007 PM 17050196 ER PT J AU Pak, AC Ashby, CR Heidbreder, CA Pilla, M Gilbert, J Xi, ZX Gardner, EL AF Pak, Arlene C. Ashby, Charles R., Jr. Heidbreder, Christian A. Pilla, Maria Gilbert, Jeremy Xi, Zheng-Xiong Gardner, Eliot L. TI The selective dopamine D-3 receptor antagonist SB-277011A reduces nicotine-enhanced brain reward and nicotine-paired environmental cue functions SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the Society-for-Neuroscience CY OCT 23-27, 2004 CL San Diego, CA SP Soc Neurosci DE brain-stimulation reward; conditioned locomotor activity; conditioned place preference; dopamine D-3 receptors; nicotine ID CONDITIONED PLACE PREFERENCE; VENTRAL TEGMENTAL AREA; COCAINE-SEEKING BEHAVIOR; SELF-STIMULATION THRESHOLDS; NUCLEUS-ACCUMBENS DOPAMINE; DRUG-ASSOCIATED STIMULI; D3 RECEPTOR; INDUCED REINSTATEMENT; THERAPEUTIC AGENTS; PARTIAL AGONIST AB Increasing evidence suggests that enhanced dopamine (DA) neurotransmission in the nucleus accumbens (NAc) may play a role in mediating the reward and reinforcement produced by addictive drugs and in the attentional processing of drug-associated environmental cues. The meso-accumbens DA system is selectively enriched with DA D-3 receptors, a DA receptor subtype increasingly implicated in reward-related brain and behavioural processes. From a variety of evidence, it has been suggested that selective DA D-3 receptor antagonism may be a useful pharmacotherapeutic approach for treating addiction. The present experiments tested the efficacy of SB-277011A, a selective DA D-3 receptor antagonist, in rat models of nicotine-enhanced electrical brain-stimulation reward (BSR), nicotine-induced conditioned locomotor activity (LMA), and nicotine-induced conditioned place preference (UP). Nicotine was given subcutaneously within the dose range of 0.25-0.6 mg/kg (nicotine-free base). SB-277011A, given intraperitoneally within the dose range of 1-12 mg/kg, dose-dependently reduced nicotine-enhanced BSR, nicotine-induced conditioned LMA, and nicotine-induced CPP. The results suggest that selective D3 receptor antagonism constitutes a new and promising pharmacotherapeutic approach to the treatment of nicotine dependence. C1 NIDA, Neuropsychopharmacol Sect, Intramural Res Program, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, Jamaica, NY 11439 USA. GlaxoSmithKline, Ctr Excellence Drug Discovery Psychiat, Dept Neuropsychopharmacol, Verona, Italy. RP Gardner, EL (reprint author), NIDA, Neuropsychopharmacol Sect, Intramural Res Program, Dept Hlth & Human Serv,NIH, Bldg C-393,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM egardner@intra.nida.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 113 TC 56 Z9 56 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD OCT PY 2006 VL 9 IS 5 BP 585 EP 602 DI 10.1017/S1461145706006560 PG 18 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 105WI UT WOS:000242062600010 PM 16942635 ER PT J AU Carpenter, DO El-Qaderi, S Fayzieva, D Gilani, AH Hambartsumyan, A Herz, K Isobaev, M Kasymov, O Kudyakov, R Majitova, Z Mamadov, E Nemer, L Revich, B Stege, P Suk, W Upshur, R Yilmaz, B Zaineh, K AF Carpenter, David O. El-Qaderi, Saleh Fayzieva, Dilorom Gilani, Anwar H. Hambartsumyan, Amelia Herz, Katherine Isobaev, Muzafar Kasymov, Omor Kudyakov, Rustam Majitova, Zayra Mamadov, Elshad Nemer, Leda Revich, Boris Stege, Piper Suk, William Upshur, Ross Yilmaz, Bayram Zaineh, Kamal TI Children's environmental health in Central Asia and the Middle East SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article DE lead; persistent organic pollutants; smoking; drinking water; Aral Sea; children; Asia; Middle East ID ARAL SEA REGION; EXPOSURE; POLLUTANTS AB Children in Central Asia and the Middle East bear disproportionate environmental threats to health, of which the most widespread and serious result from poverty, malnutrition, lack of access to safe drinking water and food, and exposures to toxic chemicals. Their psychological health is threatened in several parts of this region by internal wars and strife. Many, or even most, children are regularly exposed to environmental tobacco smoke. In many of these countries, children constitute very high percentages of the population. Because children constitute the future, it is critical that these threats to their health be addressed and reduced to the greatest extent possible through both provision of safe and adequate drinking water and nutrition and reduction of exposures to environmental contaminants. C1 SUNY Albany, Inst Hlth & Environm, Rensselaer, NY 12144 USA. Jordan Univ Sci & Technol, Dept Publ Hlth & Family Med, Irbid, Jordan. Acad Sci, Inst Water Problems, Tashkent, Uzbekistan. Aga Khan Univ, Coll Med, Dept Biol & Biomed Sci, Sindh, Pakistan. Khazer Ecol & Cultural NGO, Yerevan, Armenia. NIAID, NIH, Bethesda, MD 20892 USA. Acad Sci Republ Tajikistan, Dushanbe, Tajikistan. Minist Hlth Kyrgyz Republ, Sci & Prod Ctr Prevent Med, Bishkek, Kyrgyzstan. Univ Albany, Sch Publ Hlth, Albany, NY USA. Kazakhstan State Med Univ, Alma Ata, Kazakhstan. Azerbaijian Polytech Univ, Ecol Fund, Gyandja, Azerbaijan. WHO, Reg Off Europe, Childrens Hlth & Environm Programme, Rome, Italy. Russian Acad Sci, Ctr Demog & Human Ecol, Moscow, Russia. US EPA, Washington, DC 20460 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Toronto, Toronto, ON, Canada. Firat Univ, Fac Med, Dept Physiol, Elazig, Turkey. Hlth Work Comm, Ramallah, Palestine, Israel. RP Carpenter, DO (reprint author), SUNY Albany, Inst Hlth & Environm, 5 Univ Pl,Room A217, Rensselaer, NY 12144 USA. EM carpent@uamail.albany.edu RI Gilani, Anwar/E-9163-2015; OI Upshur, Ross/0000-0003-1128-0557 FU FIC NIH HHS [TW00636] NR 60 TC 2 Z9 2 U1 1 U2 3 PU ABEL PUBLICATION SERVICES PI BURLINGTON PA 1611 AQUINAS COURT, BURLINGTON, NC 27215 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD OCT-DEC PY 2006 VL 12 IS 4 BP 362 EP 368 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 113ZD UT WOS:000242635600010 PM 17168224 ER PT J AU Jia, G Takahashi, R Zhang, ZP Tsuji, Y Sone, H AF Jia, Guang Takahashi, Ryoya Zhang, Zhiping Tsuji, Yoshiaki Sone, Hideko TI Aldo-keto reductase 1 family B7 is the gene induced in response to oxidative stress in the livers of Long-Evans Cinnamon rats SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE AKR1B7; oxidative stress; oligonucleotide array; realtime PCR; Long Evans Cinnamon rat ID NF-KAPPA-B; MOUSE VAS-DEFERENS; LEC RATS; HEPATOCELLULAR-CARCINOMA; TRANSCRIPTIONAL REGULATION; ADRENOCORTICAL-CELLS; PLASMA ANTIOXIDANTS; LIPID-PEROXIDATION; HYDROXYL RADICALS; HEME OXYGENASE AB The Long-Evans Cinnamon (LEC) rat strain (Atp7b m/m), which accumulates copper in the liver due to mutations in the Atp7b gene, is a useful model for investigating the relationship between oxidative stress and hepatocarcinogenesis. To determine the effect of this mutation on oxidative stress marker genes, we performed oligonucleotide array analysis (Affymetrix), and compared the results in Atp7b m/m rats with those of a sibling line with the Atp7b w/w genotype. We focused our studies on the expression of the aldo-keto reductase I family B7 (AKR1B7)-like protein gene, since this gene codes for reductase enzymes involved in the detoxification of oxidizing compounds (e.g., aldehydes) and was differentially expressed in Atp7b m/m and Atp7b w/w rat liver. Akr1B7 mRNA expression was significantly increased in comparison with the expression of 4 other known oxidative stress responsive genes, haem-oxygenase-1 (HO-1), thioredoxin (Trx), aldehyde reductase (AKR1A1), and glucose-6-phosphate dehydrogenase (G6PDH). By searching binding motifs, five nuclear factor kappa B (NF-KB) binding sites were located in the 5'-upstream region of the Akr1b7 gene. Transient co-transfection with both I-kBa and the Akr1b7 6 kb promoter (p6.0-AKR-Luc) inhibited luciferase activity of p6.0-AKR-Luc in HepG2 cells. Cuprous ion however did not affect the transcription activity induced by p6.0-AKR-Luc. Gel-shift assay showed that the DNA binding activity of NF-KB increased in the livers of LEC rats, suggesting that the oxidative stress is mediated through NF-KB. The results indicate conclusively that in LEC rat liver, Akr1b7 might be up-regulated by oxidative stress mediated through NF-KB, but not that mediated directly by copper. C1 Natl Inst Environm Studies, Hlth Effects Res Team, Tsukuba, Ibaraki 3058506, Japan. Peking Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth Sci, Beijing 100083, Peoples R China. Toho Univ, Fac Pharmaceut Sci, Biochem Lab, Chiba 2748510, Japan. Natl Inst Environm Hlth Sci, Lab Reprod & Dev, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. RP Sone, H (reprint author), Natl Inst Environm Studies, Hlth Effects Res Team, 16-2 Onogawa, Tsukuba, Ibaraki 3058506, Japan. EM hsone@nies.go.jp FU NIDDK NIH HHS [R01 DK060007, R01 DK060007-03, DK60007] NR 51 TC 13 Z9 13 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 2006 VL 29 IS 4 BP 829 EP 838 PG 10 WC Oncology SC Oncology GA 088HX UT WOS:000240803900007 PM 16964378 ER PT J AU Tatum, JL Kelloff, GJ Gillies, RJ Arbeit, JM Brown, JM Chao, KSC Chapman, JD Eckelman, WC Fyles, AW Giaccia, AJ Hill, RP Koch, CJ Krishna, MC Krohn, KA Lewis, JS Mason, RP Melillo, G Padhani, AR Powis, G Rajendran, JG Reba, R Robinson, SP Semenza, GL Swartz, HM Vaupel, P Yang, D Croft, B Hoffman, J Liu, GY Stone, H Sullivan, D AF Tatum, James L. Kelloff, Gary J. Gillies, Robert J. Arbeit, Jeffrey M. Brown, J. Martin Chao, K. S. Clifford Chapman, J. Donald Eckelman, William C. Fyles, Anthony W. Giaccia, Amato J. Hill, Richard P. Koch, Cameron J. Krishna, Murali Cherukuri Krohn, Kenneth A. Lewis, Jason S. Mason, Ralph P. Melillo, Giovanni Padhani, Anwar R. Powis, Garth Rajendran, Joseph G. Reba, Richard Robinson, Simon P. Semenza, Gregg L. Swartz, Harold M. Vaupel, Peter Yang, David Croft, Barbara Hoffman, John Liu, Guoying Stone, Helen Sullivan, Daniel TI Hypoxia: Importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Review DE hypoxia; imaging; tumour physiology; tumour marker ID ENDOTHELIAL GROWTH-FACTOR; POSITRON-EMISSION-TOMOGRAPHY; CONTRAST-ENHANCED MRI; HUMAN BREAST-CANCER; ELECTRON-PARAMAGNETIC-RESONANCE; INDUCIBLE FACTOR 1-ALPHA; HIGH-SPATIAL-RESOLUTION; CELL LUNG-CANCER; PHASE-I TRIAL; CYTOTOXIC AGENT TIRAPAZAMINE AB Purpose: The Cancer Imaging Program of the National Cancer Institute convened a workshop to assess the current status of hypoxia imaging, to assess what is known about the biology of hypoxia as it relates to cancer and cancer therapy, and to define clinical scenarios in which in vivo hypoxia imaging could prove valuable. Results: Hypoxia, or low oxygenation, has emerged as an important factor in tumor biology and response to cancer treatment. It has been correlated with angiogenesis, tumor aggressiveness, local recurrence, and metastasis, and it appears to be a prognostic factor for several cancers, including those of the cervix, head and neck, prostate, pancreas, and brain. The relationship between tumor oxygenation and response to radiation therapy has been well established, but hypoxia also affects and is affected by some chemotherapeutic agents. Although hypoxia is an important aspect of tumor physiology and response to treatment, the lack of simple and efficient methods to measure and image oxygenation hampers further understanding and limits their prognostic usefulness. There is no gold standard for measuring hypoxia; Eppendorf measurement of pO(2) has been used, but this method is invasive. Recent studies have focused on molecular markers of hypoxia, such as hypoxia inducible factor 1 (HIF-1) and carbonic anhydrase isozyme IX (CA-IX), and on developing noninvasive imaging techniques. Conclusions: This workshop yielded recommendations on using hypoxia measurement to identify patients who would respond best to radiation therapy, which would improve treatment planning. This represents a narrow focus, as hypoxia measurement might also prove useful in drug development and in increasing our understanding of tumor biology. C1 NCI, Canc Imaging Program, DCTD, Rockville, MD 20852 USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Univ Texas, SW Med Ctr Dallas, Dallas, TX 75230 USA. Univ Penn, Philadelphia, PA 19104 USA. NCI, Ctr Canc Res, Rockville, MD 20852 USA. NCI, Dev Therapeut Program, DCTD, Rockville, MD 20852 USA. Washington Univ, Med Ctr, St Louis, MO 63130 USA. Georgetown Univ, Med Ctr, Washington, DC 20057 USA. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. Johannes Gutenberg Univ Mainz, D-6500 Mainz, Germany. NCI, Radiat Res Program, DCTD, Rockville, MD 20852 USA. RP Tatum, JL (reprint author), NCI, Canc Imaging Program, DCTD, Execut Plaza N,Room 6000,6130 Execut Blvd, Rockville, MD 20852 USA. EM tatumj@mail.nih.gov; arbeitj@wustl.edu; mbrown@stanford.edu; cchao@mdanderson.org; vinochapman@vip.net; weckelman@ucsd.edu; anthony.fyles@rmp.uhn.on.ca; giaccia@stanford.edu; hill@oci.utoronto.ca; kochc@mail.med.upenn.edu; murali@helix.nih.gov; kkrohn@u.washington.edu; lewisjas@mir.wustl.edu; ralph.mason@utsouthwestern.edu; ralph.mason@utsouthwestern.edu; anwar.padhani@synarc.com; gpowis@azcc.arizona.edu; rajan@u.washington.edu; rr68@gunet.georgetown.edu; gsemenza@jhmi.edu; harold.swartz@dartmouth.edu; vaupel@uni-mainz.de; dyang@mdanderson.org RI Croft, Barbara/D-1248-2013; Mason, Ralph/C-8472-2012; OI Croft, Barbara/0000-0003-2544-150X; Mason, Ralph/0000-0001-7517-3721; Gillies, Robert/0000-0002-8888-7747; Fyles, Anthony/0000-0002-3633-2483 FU NCI NIH HHS [P01 CA042045] NR 336 TC 352 Z9 360 U1 13 U2 82 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0955-3002 EI 1362-3095 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD OCT PY 2006 VL 82 IS 10 BP 699 EP 757 DI 10.1080/09553000601002324 PG 59 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 115VO UT WOS:000242762100001 PM 17118889 ER PT J AU Koturbash, I Baker, M Loree, J Kutanzi, K Hudson, D Pogribny, I Sedelnikova, O Bonner, W Kovalchuk, O AF Koturbash, Igor Baker, Mike Loree, Jonathan Kutanzi, Kristy Hudson, Darryl Pogribny, Igor Sedelnikova, Olga Bonner, William Kovalchuk, Olga TI Epigenetic dysregulation underlies radiation-induced transgenerational genome instability in vivo SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE radiation; transgeneration genome instability; epigenetics; DNA methylation; DNA damage ID METHYLATION PATTERNS; DNA-DAMAGE; EXPRESSION; EXPOSURE; GENE AB Purpose: Although modern cancer radiation therapy has led to increased patient survival rates, the risk of radiation treatment-related complications is becoming a growing problem. Among various complications, radiation also poses a threat to the progeny of exposed parents. It causes transgenerational genome instability that is linked to transgenerational carcinogenesis. Although the occurrence of transgenerational genome instability, which manifests as elevated delayed and nontargeted mutation, has been well documented, the mechanisms by which it arises remain obscure. We hypothesized that epigenetic alterations may play a pivotal role in the molecular etiology of transgenerational genome instability. Methods and Materials: We studied the levels of cytosine DNA methylation in somatic tissues or unexposed offspring upon maternal, paternal, or combined parental exposure. Results: We observed a significant loss of global cytosine DNA methylation in the thymus tissue of the offspring upon combined parental exposure. The loss of DNA methylation was paralleled by a significant decrease in the levels of maintenance (DNMT1) and de novo methyltransferases DNMT3a and 3b and methyl-CpG-binding protein MeCP2. Along with profound changes in DNA methylation, we noted a significant accumulation of DNA strand breaks in thymus, which is a radiation carcinogenesis target organ. Conclusion: The observed changes were indicative of a profound epigenetic dysregulation in the offspring, which in turn could lead to genome destabilization and possibly could serve as precursor for transgenerational carcinogenesis. Future studies are clearly needed to address the cellular and carcinogenic repercussions of those changes. (c) 2006 Elsevier Inc. C1 Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, 4401 Univ Dr, Lethbridge, AB T1K 3M4, Canada. EM olga.kovalchuk@uleth.ca NR 15 TC 66 Z9 70 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2006 VL 66 IS 2 BP 327 EP 330 DI 10.1016/j.ijrobp.2006.06.012 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 086UW UT WOS:000240699500004 PM 16965987 ER PT J AU Zeliadt, SB Potosky, AL Penson, DF Etzioni, R AF Zeliadt, Steven B. Potosky, Arnold L. Penson, David F. Etzioni, Ruth TI Survival benefit associated with adjuvant androgen deprivation therapy combined with radiotherapy for high- and low-risk patients with nonmetastatic prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate; prostatic neoplasms; adjuvant androgen deprivation therapy; LHRH agonists; SEER-Medicare; instrumental variables ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; LONG-TERM SURVIVAL; INSTRUMENTAL VARIABLES; RADIATION-THERAPY; UNITED-STATES; DEFINITIVE RADIOTHERAPY; HORMONAL-THERAPY; BREAST-CANCER; CLAIMS DATA AB Background: The use of adjuvant androgen deprivation therapy (ADT) combined with radiotherapy has become common in low-risk patients, although clinical trials have focused primarily on high-risk patients. This study examines the effectiveness of adjuvant ADT combined with radiotherapy for a wide range of patients treated in the 1990s. Methods and Materials: Prostate cancer survival was examined in a population based cohort of 31,643 patients aged 65 to 85 years who were diagnosed with nonmetastatic prostate cancer and treated with external beam radiotherapy and/or brachytherapy. Instrumental variable analysis methods were used to control for selection bias. Results: Patients with stage T3/T4 disease who received adjuvant ADT experienced improved 5-year and 8-year survival. No survival advantage was observed for men with T1/T2 disease during this interval. Conclusion: High-risk patients who receive primary radiotherapy have benefited from adjuvant ADT, whereas low-risk patients with disease confined to the prostate have not yet benefited from adjuvant therapy within the first 8 years after treatment. These findings are consistent with practice guidelines, which recommend adjuvant ADT for patients with high-risk disease. (c) 2006 Elsevier Inc. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ So Calif, Norris Canc Ctr, Dept Urol, Los Angeles, CA 90089 USA. Univ So Calif, Norris Canc Ctr, Dept Prevent Med, Los Angeles, CA 90089 USA. RP Zeliadt, SB (reprint author), Fred Hutchinson Canc Res Ctr, POB 19024,M2-230, Seattle, WA 98109 USA. EM szeliadt@fhcrc.org FU NCI NIH HHS [CA-88160, CA-92408] NR 41 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2006 VL 66 IS 2 BP 395 EP 402 DI 10.1016/j.ijrobp.2006.04.048 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 086UW UT WOS:000240699500015 PM 16904843 ER PT J AU Singh, AK Karimpour, SE Savani, BN Guion, P Hope, AJ Mansueti, JR Ning, H Altemus, RM Wu, CO Barrett, AJ AF Singh, Anurag K. Karimpour, Shervin E. Savani, Bipin N. Guion, Peter Hope, Andrew J. Mansueti, John R. Ning, Holly Altemus, Rosemary M. Wu, Colin O. Barrett, A. John TI Pretransplant pulmonary function tests predict risk of mortality following fractionated total body irradiation and allogeneic peripheral blood stem cell transplant SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE total body irradiation; peripheral blood stem cell transplantation; pulmonary function tests; lung shielding; dose reduction ID BONE-MARROW-TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; HEMATOLOGICAL MALIGNANCIES; MULTIPLE-MYELOMA; MULTICENTER AB Purpose: To determine the value of pulmonary function tests (PFTs) done before peripheral blood stem cell transplant (PBSCT) in predicting mortality after total body irradiation (TBI) performed with or without dose reduction to the lung. Methods and Materials: From 1997 to 2004, 146 consecutive patients with hematologic malignancies received fractionated TBI before BSCT. With regimen A (n = 85), patients were treated without lung dose reduction to 13.6 gray (Gy). In regimen B (n = 35), total body dose was decreased to 12 Gy (1.5 Gy twice per day for 4 days) and lung dose was limited to 9 Gy by use of lung shielding. In regimen C (n = 26), lung dose was reduced to 6 Gy. All patients received PFTs before treatment, 90 days after treatment, and annually. Results: Median follow-up was 44 months (range, 12-90 months). Sixty-one patients had combined ventilation/ diffusion capacity deficits defined as both a forced expiratory volume in the first second (FEV1) and a diffusion capacity of carbon dioxide (DLCO) < 100 % predicted. In this group, there was a 20% improvement in one-year overall survival with lung dose reduction (70 vs. 50%, log-rank test p = 0.042). Conclusion: Among those with combined ventilation/diffusion capacity deficits, lung dose reduction during TBI significantly improved survival. (c) 2006 Elsevier Inc. C1 NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Radiat Oncol, Mallinckrodt Inst Radiol,Siteman Canc Ctr, St Louis, MO USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Singh, AK (reprint author), NCI, Radiat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10-CRC,Room B2-3500 MSC 1642, Bethesda, MD 20892 USA. EM singan@mail.nih.gov FU Intramural NIH HHS NR 26 TC 15 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2006 VL 66 IS 2 BP 520 EP 527 DI 10.1016/j.ijrobp.2006.05.023 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 086UW UT WOS:000240699500032 PM 16965994 ER PT J AU Seshadri, S AF Seshadri, Sudha TI Methodology for measuring cerebrovascular disease burden SO INTERNATIONAL REVIEW OF PSYCHIATRY LA English DT Article ID WHITE-MATTER LESIONS; SILENT BRAIN INFARCTS; STROKE RISK PROFILE; ISCHEMIC VASCULAR DEMENTIA; CAROTID-ARTERY OCCLUSION; MIDLIFE BLOOD-PRESSURE; INTIMA-MEDIA THICKNESS; SMALL-VESSEL DISEASE; C-REACTIVE PROTEIN; CARDIOVASCULAR HEALTH AB Biological aging of the brain is partly attributable to aging of the cerebrovascular circulation and the effects of these vascular changes on the brain. A variety of techniques ranging from simple, clinical scores to complex radiological techniques have been used in an attempt to understand, describe and quantify this process. Simultaneously attempts have been made to relate these changes to cognitive and physical changes and the risk of dementia and stroke associated with brain aging. The most frequently used clinical scores are the Framingham Stroke Risk Profile and the Hachinski Ischemic Score for vascular dementia. Radiological techniques to estimate cerebrovascular burden include many varieties of ultrasonographic, computerized tomography (CT), magnetic resonance imaging (MRI) and nuclear medicine techniques. The radiological techniques evaluate the nature and extent of disease in the vessels supplying the brain and the pattern and extent of radiological evidence of damage to the brain both on static and dynamic imaging and are briefly outlined in this review. There are several studies using these techniques to study 'normal' aging populations, and the techniques used in the most widely known of these studies are briefly highlighted in this review. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. RP Seshadri, S (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St,B-605, Boston, MA 02118 USA. EM suseshad@bu.edu OI Seshadri, Sudha/0000-0001-6135-2622 NR 89 TC 11 Z9 11 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0261 J9 INT REV PSYCHIATR JI Int. Rev. Psych. PD OCT PY 2006 VL 18 IS 5 BP 409 EP 422 DI 10.1080/09540260600935413 PG 14 WC Psychiatry SC Psychiatry GA 110DO UT WOS:000242358700003 PM 17085360 ER PT J AU Newberg, AR Davydow, DS Lee, HB AF Newberg, Andrew R. Davydow, Dimitry S. Lee, Hochang B. TI Cerebrovascular disease basis of depression: Post-stroke depression and vascular depression SO INTERNATIONAL REVIEW OF PSYCHIATRY LA English DT Article ID WHITE-MATTER HYPERINTENSITIES; MRI SIGNAL HYPERINTENSITIES; GERIATRIC MAJOR DEPRESSION; RANDOMIZED CLINICAL-TRIAL; POST-STROKE DEPRESSION; PRIMARY-CARE PATIENTS; LATE-LIFE DEPRESSION; RISK-FACTORS; DOUBLE-BLIND; FOLLOW-UP AB The close association between cerebrovascular disease and depression has been known for more than a century, yet much of the progress in understanding the cerebrovascular basis of depression in late life has been spurred by development of two concepts: 'post-stroke depression' and 'vascular depression'. The purpose of this review is to examine the epidemiology, diagnostic features, course, pathophysiology and prognosis of post-stroke depression and vascular depression, to highlight their common features, and to contrast the distinct aspects of these two subtypes of geriatric depression. C1 Johns Hopkins Univ Hosp, Dept Psychiat, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. RP Newberg, AR (reprint author), NIMH, NIH, 10 Ctr Dr,MSC 1282,Bldg 10-CRC,Room 7-5545, Bethesda, MD 20892 USA. EM newberga@mail.nih.gov OI Newberg, Andrew/0000-0001-8230-1752 NR 87 TC 9 Z9 13 U1 8 U2 13 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0261 J9 INT REV PSYCHIATR JI Int. Rev. Psych. PD OCT PY 2006 VL 18 IS 5 BP 433 EP 441 DI 10.1080/09540260600935447 PG 9 WC Psychiatry SC Psychiatry GA 110DO UT WOS:000242358700005 PM 17085362 ER PT J AU Fautsch, MP Johnson, DH AF Fautsch, Michael P. Johnson, Douglas H. CA Second ARVOPfizer Res Inst Working TI Aqueous humor outflow: What do we know? Where will it lead us? SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPEN-ANGLE GLAUCOMA; INNER-WALL ENDOTHELIUM; HUMAN TRABECULAR MESHWORK; SCHLEMMS CANAL CELLS; INTRAOCULAR-PRESSURE; HUMAN EYES; FLUORESCENCE MICROSCOPY; CHONDROITINASE ABC; ANTERIOR SEGMENTS; INCREASED LEVEL C1 Mayo Clin & Mayo Fdn, Dept Ophthalmol, Coll Med, Rochester, MN 55905 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Tokyo, Tokyo, Japan. Univ Miami, Miami, FL 33152 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Nebraska, Med Ctr, Omaha, NE USA. Univ Penn, Philadelphia, PA 19104 USA. Alcon Res Inc, Ft Worth, TX USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Duke Univ, Ctr Eye, Durham, NC USA. Univ Toronto, Toronto, ON, Canada. Boston Univ, Sch Med, Boston, MA 02118 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Northwestern Univ, Evanston, IL USA. Univ Wisconsin, Madison, WI USA. Univ Erlangen Nurnberg, Erlangen, Germany. NEI, NIH, Bethesda, MD 20892 USA. Univ Arizona, Tucson, AZ USA. Univ Regensburg, D-8400 Regensburg, Germany. Univ Washington, Seattle, WA 98195 USA. Univ Penn, Philadelphia, PA 19104 USA. Weizmann Inst Sci, IL-76100 Rehovot, Israel. Univ Vienna, Vienna, Austria. NCI, NIH, Bethesda, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Queens Univ Belfast, Belfast, Antrim, North Ireland. Texas A&M Univ, Syst Hlth Sci Ctr, College Stn, TX USA. Pfizer Ophthalm, New York, NY USA. Aerie Pharmaceut, Res Triangle Pk, NC USA. Tufts Univ, Sch Med, Boston, MA USA. Univ Louisville, Louisville, KY 40292 USA. Harvard Univ, Cambridge, MA 02138 USA. Lexicon Genet, The Woodlands, TX USA. Indiana Univ, Sch Med, Indianapolis, IN USA. RP Fautsch, MP (reprint author), Mayo Clin & Mayo Fdn, Dept Ophthalmol, Coll Med, 200 1st St SW, Rochester, MN 55905 USA. EM fautsch@mayo.edu FU NEI NIH HHS [R01 EY015736, R01 EY015736-01A1] NR 77 TC 39 Z9 41 U1 1 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2006 VL 47 IS 10 BP 4181 EP 4187 DI 10.1167/iovs.06-0830 PG 7 WC Ophthalmology SC Ophthalmology GA 088AU UT WOS:000240784700001 PM 17003404 ER PT J AU Vasireddy, V Jablonski, MM Mandal, MNA Raz-Prag, D Wang, XFF Nizol, L Iannaccone, A Musch, DC Bush, RA Salem, N Sieving, PA Ayyagari, R AF Vasireddy, Vidyullatha Jablonski, Monica M. Mandal, Md Nawajes A. Raz-Prag, Dorit Wang, Xiaofei F. Nizol, Lesli Iannaccone, Alessandro Musch, David C. Bush, Ronald A. Salem, Norman, Jr. Sieving, Paul A. Ayyagari, Radha TI Elovl4 5-bp-deletion knock-in mice develop progressive photoreceptor degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; MACULAR DYSTROPHY; LIPOFUSCIN ACCUMULATION; CONE FUNCTION; MUTATION; PHENOTYPE; PROTEIN; FAMILY; LIPIDS; MOUSE AB PURPOSE. To develop and characterize a heterozygous knock-in mouse model carrying the 5-bp deletion in Elovl4 (E_mut(+/-)) and to study the pathology underlying Stargardt-like macular degeneration (STGD3). METHODS. E_mut(+/-) mice were generated by targeting a 5-bp deletion (AACTT) in the Elovl4 gene by homologous recombination. E_mut(+/-) mice of age 2 to 18 months and age-matched wild-type (Wt) littermate control animals were analyzed for the expression of Elovl4 transcript, ELOVL4 protein, photoreceptor-specific genes, and retinal fatty acid composition. Functional retinal changes were evaluated by electroretinography (ERG) and by morphologic and ultrastructural criteria. RESULTS. E_mut(+/-) mice retinas showed the presence of both Wt and mutant Elovl4 transcripts and proteins. Morphologic evaluation revealed cone photoreceptor ultrastructural abnormalities as early as 2 months of age, accumulation of lipofuscin in retinal pigment epithelium (RPE), and subretinal deposits at later ages. Shortening of rod outer segments (OS) was observed at similar to 10 months of age. Both cone and rod changes progressed with age. Unlike rod-specific genes, expression of selected cone specific genes was significantly reduced by 7 months of age. Mixed rod-cone and light-adapted b-waves were higher than normal at both 8 and 15 months. Levels of the fatty acids 20: 5 (P = 0.027), 22: 5 (P = 0.040) and 24: 6 (P = 0.005) were found to be significantly lower in the retinas of E_mut(+/-) mice than in retinas of control subjects. CONCLUSIONS. E_mut(+/-) animals display characteristic features associated with Stargardt-like macular degeneration and serve as a model for the study of the mechanism underlying STGD3. C1 Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. Univ Tennessee, Hamilton Eye Inst, Memphis, TN USA. NIDCD, Bethesda, MD USA. NEI, Bethesda, MD 20892 USA. NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. RP Ayyagari, R (reprint author), Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, 325,1000 Wall St, Ann Arbor, MI 48105 USA. EM ayyagari@umich.edu FU Intramural NIH HHS; NEI NIH HHS [EY13198, P30EY07060, P30EY007003, P30EY13080] NR 33 TC 42 Z9 46 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2006 VL 47 IS 10 BP 4558 EP 4568 DI 10.1167/iovs.06-0353 PG 11 WC Ophthalmology SC Ophthalmology GA 088AU UT WOS:000240784700050 PM 17003453 ER PT J AU Watts, DH Springer, G Minkoff, H Hillier, SL Jacobson, L Moxley, M Justman, J Cejtin, H O'Connell, C Greenblatt, RM AF Watts, D. Heather Springer, Gayle Minkoff, Howard Hillier, Sharon L. Jacobson, Lisa Moxley, Michael Justman, Jessica Cejtin, Helen O'Connell, Casey Greenblatt, Ruth M. TI The occurrence of vaginal infections among HIV-infected and high-risk HIV-uninfected women - Longitudinal findings of the women"s interagency HIV study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE bacterial vaginosis; HIV vaginitis; women ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEXUALLY-TRANSMITTED-DISEASE; GENITAL-TRACT INFECTIONS; BACTERIAL VAGINOSIS; TRICHOMONAS-VAGINALIS; EPIDEMIOLOGY RESEARCH; SERONEGATIVE WOMEN; PREGNANT-WOMEN; SEX WORKERS; TYPE-1 RNA AB Objectives: To evaluate changes over time in rates of bacterial vaginosis (BV), trichomoniasis (TV), and yeast vaginitis (YV) among HIV-infected and similar HIV-uninfected women. Methods: Two thousand fifty-six HIV-infected women and 554 HIV-uninfected women were evaluated semiannually from 1994 until March 2003 in a prospective cohort study. BV was diagnosed by Gram stain, TV by wet mount, and YV by symptoms with microscopically visible hyphae or positive culture. Trends were assessed using Poisson models. Results: At baseline, BV was present in 42.8% and 47.0% of HIV-infected and uninfected women (P = 0.21), TV in 6.1% and 7.8% (P = 0.17), and YV in 10.0% and 3.8% (P < 0.001). Over time, rates of BV and TV decreased significantly in both groups, whereas rates of YV declined only among HIV-infected women. Risk of BV was not associated with HIV status, whereas HIN-infected women had a lower risk of TV Highly active antiretroviral therapy (HAART) use was associated with decreased risk of all 3 infections. Conclusions: Declines in BV, TV, and YV represent decreased morbidity for HIV-infected women and, potentially, decreased risk of transmission of HIV because each has been associated with increased genital detection of HIV. C1 NICHD, Pediat Adolescent & Maternal AIDS Branch, CRMC, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA. Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. Georgetown Univ, Dept Obstet & Gynecol, Washington, DC USA. Columbia Univ, Ctr Infect Dis Epidemiol Res, New York, NY USA. John H Stroger Hosp Cook Cty, Dept Obstet Gynecol & Reprod Sci, Chicago, IL USA. Univ So Calif, Dept Med, Los Angeles, CA USA. Univ Calif San Francisco, Dept Med & Epidemiol, San Francisco, CA 94143 USA. RP Watts, DH (reprint author), NICHD, Pediat Adolescent & Maternal AIDS Branch, CRMC, NIH, 6100 Execut Blvd,Room 4B11, Bethesda, MD 20892 USA. EM wattsh@mail.nih.gov FU NCI NIH HHS [R01 CA85178-01]; NCRR NIH HHS [MO1 RR00079]; NIAID NIH HHS [U01-AI-31834, N01-AI-35161, U01-AI-34994, U01-AI-35004, U01-AI-42590, U01-AI-34989, U01-AI-34993]; NICHD NIH HHS [U01-HD-32632] NR 48 TC 23 Z9 24 U1 0 U2 2 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 OCT 1 PY 2006 VL 43 IS 2 BP 161 EP 168 DI 10.1097/01.qai.0000242448.90026.13 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 088VS UT WOS:000240839800005 PM 16951644 ER PT J AU Kaplan, JS Erickson, K Luckenbaugh, DA Weiland-Fiedler, P Geraci, M Sahakian, BJ Charney, D Drevets, WC Neumeister, A AF Kaplan, Johanna S. Erickson, Kristine Luckenbaugh, David A. Weiland-Fiedler, Petra Geraci, Marilla Sahakian, Barbara J. Charney, Dennis Drevets, Wayne C. Neumeister, Alexander TI Differential performance on tasks of affective processing and decision-making in patients with Panic Disorder and Panic Disorder with comorbid Major Depressive Disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE panic disorder; major depressive disorder; affective processing; decision-making ID FACIAL EXPRESSION; ATTENTIONAL BIAS; SEVERITY SCALE; DEFICITS; RECOGNITION; IMPAIRMENTS; COGNITION; ANXIETY; MANIA AB Background: Neuropsychological studies have provided evidence for deficits in psychiatric disorders, such as schizophrenia and mood disorders. However, neuropsychologicall function in Panic Disorder (PD) or PD with a comorbid diagnosis of Major Depressive Disorder (MDD) has not been comprehensively studied. The present study investigated neuropsychological functioning in patients with PD and PD + MDD by focusing on tasks that assess attention, psychomotor speed, executive function, decision-making, and affective processing. Methods: Twenty-two unmedicated patients with PD, eleven of whom had a secondary diagnosis of MDD, were compared to twenty-two healthy controls, matched for gender, age, and intelligence on tasks of attention, memory, psychomotor speed, executive function, decision-making, and affective processing from the Cambridge Neuropsychological Test Automated Battery (CANTAB), Cambridge Gamble Task, and Affective Go/No-go Task. Results: Relative to matched healthy controls, patients with PD + MDD displayed an attentional bias toward negatively-valenced verbal stimuli (Affective Go/No-go Task) and longer decision-making latencies (Cambridge Gamble Task). Furthermore, the PD + MDD group committed more errors on a task of memory and visual discrimination compared to their controls. In contrast, no group differences were found for PD patients relative to matched control subjects. Limitations: The sample size was limited, however, all patients were drug-free at the time of testing. Conclusions: The PD + MDD patients demonstrated deficits on a task involving visual discrimination and working memory, and an attentional bias towards negatively-valenced stimuli. In addition, patients with comorbid depression provided qualitatively different responses in the areas of affective and decision-making processes. Published by Elsevier B.V. C1 NIMH, Mood & Anxiety Disorders Program, NIH, DHHS, Bethesda, MD 20814 USA. Univ Cambridge, Dept Psychiat, Cambridge, England. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. Charite Univ Med, Dept Psychiat, Clin Psychiat & Psychotherapy, Berlin, Germany. RP Erickson, K (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, DHHS, 5413 W Cedar Lane,Suite 106-C,Rm 15,MSC 2606, Bethesda, MD 20814 USA. EM ericksok@intra.nimh.nih.gov FU Medical Research Council [G0001354] NR 34 TC 28 Z9 29 U1 3 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD OCT PY 2006 VL 95 IS 1-3 BP 165 EP 171 DI 10.1016/j.jad.2006.04.016 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 097VQ UT WOS:000241477700024 PM 16793143 ER PT J AU Salo, PM Arbes, SJ Sever, M Jaramillo, R Cohn, RD London, SJ Zeldin, DC AF Salo, Paivi M. Arbes, Samuel J., Jr. Sever, Michelle Jaramillo, Renee Cohn, Richard D. London, Stephanie J. Zeldin, Darryl C. TI Exposure to Alternaria alternata in US homes is associated with asthma symptoms SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE alternaria alternata; fungal allergen; antigen; indoor; exposure; asthma; allergy ID NUTRITION EXAMINATION SURVEY; FUNGAL ALLERGENS; INDOOR ALLERGENS; NATIONAL-HEALTH; AIRBORNE FUNGI; RISK-FACTOR; CHILDREN; OUTDOOR; SPORES; RHINITIS AB Background: Exposure to the fungus Alternaria alternata is a risk factor for asthma. Few studies have examined Alternaria exposures in indoor environments. Objective: We examined whether exposure to A alternata in US homes was associated with asthma-related outcomes. Methods: The data for this study were collected as part of the National Survey of Lead and Allergens in Housing. This cross-sectional study surveyed a nationally representative sample of 831 housing units inhabited by 2456 individuals in 75 different locations throughout the United States. An interviewer-administered questionnaire obtained information on demographics, household characteristics, and occupants' health status. Exposure to A alternata was assessed by measuring concentrations of A alternata antigens in vacuumed dust samples using a polyclonal anti-A alternata antibody assay. Dust samples were collected from a bed, a sofa, or a chair, and from bedroom, living room, and kitchen floors. Results: Lifetime prevalence of doctor-diagnosed asthma was 11.2%, and 6.9% of the study subjects reported active asthma symptoms in the past 12 months. The prevalence of current symptomatic asthma increased with increasing Alternaria concentrations in US homes; higher levels of A alternata antigens increased the odds of having asthma symptoms in the past year (relative to the lowest tertile, adjusted odds ratio was 1.52, 95% CI, 0.90-2.55 for the 2nd tertile; and 1.84, 95% Cl, 1.18-2.85 for the 3rd tertile). Conclusion: Exposure to A alternata in US homes is associated with active asthma symptoms. Clinical implications: Measures that reduce indoor exposure to A alternata may help control asthma exacerbations. C1 NIH, NIEHS, Res Triangle Pk, NC 27709 USA. Constella Grp LLC, Durham, NC USA. RP Zeldin, DC (reprint author), NIH, NIEHS, 111 Alexander Dr,Mail Drop D2-01, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov OI Sever, Michelle/0000-0002-2435-1214; London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS [Z01 ES025041-10] NR 47 TC 108 Z9 111 U1 0 U2 11 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 2006 VL 118 IS 4 BP 892 EP 898 DI 10.1016/j.jaci.2006.07.037 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 097GD UT WOS:000241434200017 PM 17030243 ER PT J AU Kolbrich, EA Barnes, AJ Gorelick, DA Boyd, SJ Cone, EJ Huestis, MA AF Kolbrich, Erin A. Barnes, Allan J. Gorelick, David A. Boyd, Susan J. Cone, Edward J. Huestis, Marilyn A. TI Major and minor metabolites of cocaine in human plasma following controlled subcutaneous cocaine administration SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID CHROMATOGRAPHY-MASS SPECTROMETRY; GAS-CHROMATOGRAPHY; DIFFERENT ROUTES; ORAL COCAINE; DISPOSITION; PHARMACOKINETICS; CODEINE; URINE; KINETICS; LIVER C1 NIDA, Off Sci Director, IRP, NIH, Baltimore, MD 21224 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Johns Hopkins Sch Med, Baltimore, MD 21205 USA. RP Huestis, MA (reprint author), NIDA, Off Sci Director, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS NR 39 TC 46 Z9 47 U1 1 U2 12 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 2006 VL 30 IS 8 BP 501 EP 510 PG 10 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 093NY UT WOS:000241176200003 PM 17132243 ER PT J AU Pirnay, SO Abraham, TT Lowe, RH Huestis, MA AF Pirnay, Stephane O. Abraham, Tsadik T. Lowe, Ross H. Huestis, Marilyn A. TI Selection and optimization of hydrolysis conditions for the quantification of urinary metabolites of MDMA SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; IDENTIFICATION; HUMANS; PLASMA C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS NR 10 TC 14 Z9 14 U1 1 U2 3 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 2006 VL 30 IS 8 BP 563 EP 569 PG 7 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 093NY UT WOS:000241176200013 PM 17132253 ER PT J AU Cowan, MJ Coll, T Shelhamer, JH AF Cowan, Mark J. Coll, Timothy Shelhamer, James H. TI Polyamine-mediated reduction in human airway epithelial migration in response to wounding is PGE(2) dependent through decreases in COX-2 and cPLA(2) protein levels SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE ornithine decarboxylase; putrescine; spermidine; spermine; restitution; airway epithelial cell; prostaglandin E-2; cytosolic phospholipase A(2); cyclooxygenase; asthma; chronic obstructive pulmonary disease ID CELL-MIGRATION; REPAIR; METABOLISM; ACTIVATION; EXPRESSION; INHIBITORS; DAMAGE; ACID AB Both ornithine decarboxylase inhibition to deplete polyamines and cyclooxygenase inhibition diminish the migration response to injury of human airway epithelial cells in tissue culture monolayers by similar to 75%. Restoration of normal migration responses is achieved in the polyamine depleted system either by exogenous reconstitution of polyamines or the addition of prostaglandin E-2 (PGE(2)). However, only PGE2 was able to restore migration in the cyclooxygenase-inhibited systems. Western blot for cyclooxygenase-2 and cytosolic phospholipase A(2) protein levels and ELISAs for PGE(2) secretion demonstrate dramatic increases over 24-48 h after monolayer wounding. These increases are completely abolished by polyamine depletion or cyclooxygenase inhibition. We conclude that polyamine inhibition decreases cellular migration in response to injury in airway epithelial cells at least in part through inhibiting normal PGE2 production in response to injury. This may be brought about by decreases in cytosolic phospholipase A2 and cyclooxygenase-2 protein levels. C1 Univ Maryland, Dept Med, Div Pulm & Crit Care Med, Sch Med, Baltimore, MD 21201 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Cowan, MJ (reprint author), Univ Maryland, Dept Med, Div Pulm & Crit Care Med, Sch Med, 10 N Greene St,Rm 3D122, Baltimore, MD 21201 USA. EM mcowan@medicine.umaryland.edu NR 29 TC 8 Z9 8 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD OCT PY 2006 VL 101 IS 4 BP 1127 EP 1135 DI 10.1152/japplphysiol.01287.2005 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 084CS UT WOS:000240510000019 PM 16741257 ER PT J AU Washburn, RS Court, DL Gottesman, ME AF Washburn, Robert S. Court, Donald L. Gottesman, Max E. TI Role of an RNase III binding site in transcription termination at lambda nutL by HK022 Nun protein SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI NUSA; BACTERIOPHAGE-LAMBDA; PHAGE-LAMBDA; ANTITERMINATION PROTEIN; COLIPHAGE-LAMBDA; POLYMERASE; REPRESSION; MUTATIONS; OPERON AB The phage HK022 Nun protein excludes phage lambda by binding nascent lambda P-L and P-R transcripts at nutL and nutR, respectively, and inducing transcription termination just downstream of these sites. Termination is more efficient at nutL than at nutR. One difference between nutL and nutR is the presence of RNase III processing sites (rIII) located immediately promoter distal to lambda nutL. We found that deletion of rIII dramatically reduced Nun transcription arrest in vitro but had little effect on termination in vivo. However, consistent with the in vitro results, overexpression of a transcript carrying nutL and rIII efficiently titrated Nun, allowing lambda to grow on a strain that expressed Nun, whereas a transcript carrying only nutL or nutL-rIII with nucleotides 97 to 141 deleted was ineffective. Rnc70, an RNase III mutant that binds but does not cleave rIII, also prevented Nun-mediated lambda exclusion. We propose that rIII enhances the on-rate of Nun at nutL, stimulating Nun-mediated arrest in vitro. We have shown that a specific element in rIII, i.e., box C (G(89)GUGUGUG), strongly enhances arrest on rIII(+) templates. Nun-rIII interactions do not stimulate Nun termination in vivo, presumably because formation of the Nuu-nutL complex is normally not rate-limiting in the cell. In contrast to Nun, N is not occluded by Rnc70 and is not efficiently titrated by a nutL-rIII transcript. C1 Columbia Univ, Med Ctr, Dept Microbiol, New York, NY 10032 USA. Columbia Univ, Med Ctr, Inst Canc Res, New York, NY 10032 USA. NCI, Mol Control & Genet Sect, NIH, Frederick, MD 21702 USA. RP Gottesman, ME (reprint author), Columbia Univ, Med Ctr, Dept Microbiol, New York, NY 10032 USA. EM gottesman@cuccfa.ccc.columbia.edu FU Intramural NIH HHS; NIGMS NIH HHS [GM37219, R01 GM037219, R56 GM037219] NR 28 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 2006 VL 188 IS 19 BP 6824 EP 6831 DI 10.1128/JB.00567-06 PG 8 WC Microbiology SC Microbiology GA 086ZN UT WOS:000240711900012 PM 16980485 ER PT J AU Zhou, YN Gottesman, S AF Zhou, YanNing Gottesman, Susan TI Modes of regulation of RpoS by H-NS SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; SIGMA(S) PROTEOLYSIS; SIGNAL-TRANSDUCTION; RSSB; DEGRADATION; CLPXP; STABILITY; PROTEINS; SPRE; RECOGNITION AB Regulated degradation of RpoS requires RssB and ClpXP protease. Mutations in hns increase both RpoS synthesis and stability, causing a twofold increase in synthesis and almost complete stabilization of RpoS, independent of effects on synthesis and independent of phosphorylation of RssB. This suggests that H-NS regulates an RssB inhibitor or inhibitors. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NIH, Bldg 37,Rm 5132, Bethesda, MD 20892 USA. EM susang@helix.nih.gov FU Intramural NIH HHS NR 24 TC 34 Z9 36 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 2006 VL 188 IS 19 BP 7022 EP 7025 DI 10.1128/JB.00687-06 PG 4 WC Microbiology SC Microbiology GA 086ZN UT WOS:000240711900032 PM 16980505 ER PT J AU Chill, JH Louis, JM Baber, JL Bax, A AF Chill, Jordan H. Louis, John M. Baber, James L. Bax, Ad TI Measurement of N-15 relaxation in the detergent-solubilized tetrameric KcsA potassium channel SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE backbone dynamics; cross correlation; diffusion anisotropy; micelle; relaxation interference; rotational correlation time; selectivity filter ID NUCLEAR-MAGNETIC-RESONANCE; CHEMICAL-SHIFT ANISOTROPY; 3D NMR EXPERIMENTS; BACKBONE DYNAMICS; PROTEIN DYNAMICS; SPIN RELAXATION; ROTATIONAL DIFFUSION; HETERONUCLEAR NMR; K+ CHANNEL; BIOLOGICAL MACROMOLECULES AB A set of TROSY-HNCO ( tHNCO)-based 3D experiments is presented for measuring N-15 relaxation parameters in large, membrane-associated proteins, characterized by slow tumbling times and significant spectral overlap. Measurement of backbone N-15 R-1, R-1p, N-15-{H-1} NOE, and N-15 CSA/dipolar cross correlation is demonstrated and applied to study the dynamic behavior of the homotetrameric KcsA potassium channel in SDS micelles under conditions where this channel is in the closed state. The micelle-encapsulated transmembrane domain, KcsA (TM), exhibits a high degree of order, tumbling as an oblate ellipsoid with a global rotational correlation time, tau(c) = 38 +/- 2.5 ns, at 50 degrees C and a diffusion anisotropy, D-parallel to/ D-perpendicular to = 0: 79 +/- 0: 05, corresponding to an aspect ratio a/b >= 1.4. The N- and C-terminal intracellular segments of KcsA exhibit considerable internal dynamics ( S-2 values in the 0.2 - 0.45 range), but are distinctly more ordered than what has been observed for unstructured random coils. Relaxation behavior in these domains confirms the position of the C- terminal helix, and indicates that in SDS micelles, this amphiphilic helix does not associate into a stable homotetrameric helical bundle. The relaxation data indicate the absence of elevated backbone dynamics on the ps-ns time scale for the 5-residue selectivity filter, which selects K+ ions to enter the channel. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Room 126,9000 Rockville Pike, Bethesda, MD 20892 USA. EM bax@nih.gov FU Intramural NIH HHS NR 64 TC 51 Z9 51 U1 1 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD OCT PY 2006 VL 36 IS 2 BP 123 EP 136 DI 10.1007/s10858-006-9071-4 PG 14 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 093KK UT WOS:000241167000004 PM 17013683 ER PT J AU Karadag, A Fisher, LW AF Karadag, Abdullah Fisher, Larry W. TI Bone sialoprotein enhances migration of bone marrow stromal cells through matrices by bridging MMP-2 to alpha(v)beta(3)-integrin SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE bone marrow stromal cells; bone sialoprotein; small integrin-binding ligand; N-linked glycoprotein; alpha(v)beta(3) integrin; matrix metalloproteinase 2 ID HUMAN BREAST-CANCER; INTEGRIN-BINDING LIGAND; SKELETAL STEM-CELLS; HUMAN LUNG-CANCER; EXPRESSION; METALLOPROTEINASES; PROMOTES; LOCALIZATION; PRECURSORS; INVASION AB BMSCs migrate through matrix barriers and differentiate into osteoblasts. BSP enhances osteogenic cell migration through basement membrane and collagen matrices in vitro by localizing MMP-2 on the cell surface through alpha(v)beta(3)-integrin. C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, DHHS, Bethesda, MD 20892 USA. Univ Sheffield, Sch Med, Div Clin Sci, Acad Unit Urol, Sheffield, S Yorkshire, England. RP Fisher, LW (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, DHHS, Bldg 30,Room 228,9000 Rockville Pike, Bethesda, MD 20892 USA. EM lfisher@dir.nidcr.nih.gov FU Intramural NIH HHS NR 45 TC 31 Z9 31 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2006 VL 21 IS 10 BP 1627 EP 1636 DI 10.1359/JBMR.060710 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 088KG UT WOS:000240810000015 PM 16995818 ER PT J AU Rao, HW Lu, GW Kajiya, H Garcia-Palacios, V Kurihara, N Anderson, J Patrene, K Sheppard, D Blair, HC Windle, JJ Choi, SJ Roodman, GD AF Rao, Honowei Lu, Ganwei Kajiya, Hiroshi Garcia-Palacios, Veronica Kurihara, Noriyoshi Anderson, Judy Patrene, Ken Sheppard, Dean Blair, Harry C. Windle, Jolene J. Choi, Sun Jin Roodman, G. David TI alpha(9)beta(1): A novel osteoclast integrin that regulates osteoclast formation and function SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE alpha(9)beta(1) integrin; osteoclast; ADAM8; alpha(9) knockout mice ID STIMULATING FACTOR; MICE LACKING; CELL; BONE; EXPRESSION; IDENTIFICATION; OSTEOPONTIN; MIGRATION; ADHESION; FAMILY AB We identified a previously unknown integrin, alpha(9)beta(1), on OCLs and their precursors. Antibody to alpha(9) inhibited OCL formation in human marrow cultures, and OCLs from alpha(9) knockout mice had a defect in actin ring reorganization and an impaired bone resorption capacity. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Pittsburgh, PA USA. Fukuoka Dent Coll, Sawara Ku, Fukuoka, Japan. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. RP Roodman, GD (reprint author), VA Pittsburgh Healthcare Syst, R&D 151C-U,Room 2E-113,Univ Dr, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu OI Windle, Jolene/0000-0001-6690-385X FU NIA NIH HHS [R01 AG012951-07, AG12951, R01 AG012951]; NIAMS NIH HHS [AR47700, R01 AR041336, R01 AR041336-15, R01 AR047700, R01 AR047700-05, R01-AR41336] NR 28 TC 49 Z9 53 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2006 VL 21 IS 10 BP 1657 EP 1665 DI 10.1359/JBMR.060718 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 088KG UT WOS:000240810000018 PM 16995821 ER PT J AU Kelly, TG Shattuck, TM Reyes-Mugica, M Stewart, AF Simonds, WF Udelsman, R Arnold, A Carpenter, TO AF Kelly, Thomas G. Shattuck, Trisha M. Reyes-Mugica, Miguel Stewart, Andrew F. Simonds, William F. Udelsman, Robert Arnold, Andrew Carpenter, Thomas O. TI Surveillance for early detection of aggressive parathyroid disease: Carcinoma and atypical adenoma in familial isolated hyperparathyroidism associated with a germline HRPT2 mutation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE CDC73; familial parathyroid disorders; genetics; hyperparathyroidism; parathyroid carcinoma; parathyroid tumorigenesis ID JAW TUMOR SYNDROME; HEREDITARY HYPERPARATHYROIDISM; GENE HRPT2; PARAFIBROMIN; MANAGEMENT; DISORDERS; DIAGNOSIS; 1Q21-Q32; LOCUS; MAPS AB Familial hyperparathyroid syndromes involving mutations of HRPT2 (also CDC73), a tumor suppressor, are important to identify because the relatively high incidence of parathyroid malignancy associated with such mutations warrants a specific surveillance strategy. However, there is a dearth of reports describing experience with surveillance and early detection informed by genetic insight into this disorder. C1 Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. Univ Connecticut, Sch Med, Ctr Mol Med, Farmington, CT USA. Univ Connecticut, Sch Med, Div Endocrinol & Metab, Farmington, CT USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. Univ Pittsburgh, Dept Internal Med Endocrinol, Pittsburgh, PA USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. RP Carpenter, TO (reprint author), Yale Univ, Sch Med, Dept Pediat Endocrinol, POB 208064, New Haven, CT 06520 USA. EM thomas.carpenter@yale.edu RI Reyes-Mugica, Miguel/C-2483-2008 FU NCRR NIH HHS [M01-RR000125]; NICHD NIH HHS [K24-HD01288] NR 35 TC 36 Z9 37 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2006 VL 21 IS 10 BP 1666 EP 1671 DI 10.1359/JBMR.060702 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 088KG UT WOS:000240810000019 PM 16995822 ER PT J AU Lakatta, EG AF Lakatta, Edward G. TI Aging of the heart and arteries: A set-up for cardiovascular disease leading to heart failure SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Japanese-Heart-Failure-Society CY OCT 13-15, 2006 CL Tokyo, JAPAN SP Japanese Heart Failure Soc C1 NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD OCT PY 2006 VL 12 IS 8 SU 2 BP S153 EP S153 DI 10.1016/j.cardfail.2006.08.040 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 100YP UT WOS:000241706400027 ER PT J AU Hu, G Tang, J Zhang, B Lin, YF Hanai, JI Galloway, J Bedell, V Bahary, N Han, Z Ramchandran, R Thisse, B Thisse, C Zon, LI Sukhatme, VP AF Hu, Guang Tang, Jian Zhang, Bo Lin, Yanfeng Hanai, Jun-ichi Galloway, Jenna Bedell, Victoria Bahary, Nathan Han, Zhihua Ramchandran, Ramani Thisse, Bernard Thisse, Christine Zon, Leonard I. Sukhatme, Vikas P. TI A novel endothelial-specific heat shock protein HspA12B is required in both zebrafish development and endothelial functions in vitro SO JOURNAL OF CELL SCIENCE LA English DT Article DE HspA12B; zebrafish; vascular development; endothelial cells; angiogenesis; Akt ID VASCULAR DEVELOPMENT; EXPRESSION; VIVO; HEAT-SHOCK-PROTEIN-70; HSP70; OVEREXPRESSION; ANGIOGENESIS; INCREASES; EMBRYOS; HSP-70 AB A zebrafish transcript dubbed GA2692 was initially identified via a whole-mount in situ hybridization screen for vessel specific transcripts. Its mRNA expression during embryonic development was detected in ventral hematopoietic and vasculogenic mesoderm and later throughout the vasculature up to 48 hours post fertilization. Morpholino-mediated knockdown of GA2692 in embryos resulted in multiple defects in vasculature, particularly, at sites undergoing active capillary sprouting: the intersegmental vessels, sub-intestinal vessels and the capillary sprouts of the pectoral fin vessel. During the course of these studies, a homology search indicated that GA2692 is the zebrafish orthologue of mammalian HspA12B, a distant member of the heat shock protein 70 (Hsp70) family. By a combination of northern blot and real-time PCR analysis, we showed that HspA12B is highly expressed in human endothelial cells in vitro. Knockdown of HspA12B by small interfering RNAs (siRNAs) in human umbilical vein endothelial cells blocked wound healing, migration and tube formation, whereas overexpression of HspA12B enhanced migration and accelerated wound healing - data that are consistent with the in vivo fish phenotype obtained in the morpholino-knockdown studies. Phosphorylation of Akt was consistently reduced by siRNAs against HspA12B. Overexpression of a constitutively active form of Akt rescued the inhibitory effects of knockdown of HspA12B on migration of human umbilical vein endothelial cells. Collectively, our data suggests that HspA12B is a highly endothelial-cell-specific distant member of the Hsp70 family and plays a significant role in endothelial cells during development and angiogenesis in vitro, partially attributable to modulation of Akt phosphorylation. C1 Beth Israel Deaconess Med Ctr, Dept Med, Ctr Study Tumor Microenvironm, Div Renal, Boston, MA 02215 USA. Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. NCI, NIH, Rockville, MD 20850 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA. E Tennessee State Univ, Dept Biochem & Mol Biol, Johnson City, TN 37614 USA. Univ Strasbourg 1, CNRS, INSERM, Inst Biol Mol & Cellulaire, F-67070 Strasbourg, France. Beth Israel Deaconess Med Ctr, Dept Med, Vasc Biol Res Ctr, Boston, MA 02215 USA. RP Sukhatme, VP (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Ctr Study Tumor Microenvironm, Div Renal, Boston, MA 02215 USA. EM vsukhatm@bidmc.harvard.edu NR 35 TC 41 Z9 44 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD OCT 1 PY 2006 VL 119 IS 19 BP 4117 EP 4126 DI 10.1242/jcs.03179 PG 10 WC Cell Biology SC Cell Biology GA 085UQ UT WOS:000240630300021 PM 16968741 ER PT J AU Hillion, JA Li, YX Maric, D Takanohashi, A Klimanis, D Barker, JL Hallenbeck, JM AF Hillion, Joelle A. Li, YiXin Maric, Dragan Takanohashi, Asako Klimanis, Dace Barker, Jeffrey L. Hallenbeck, John M. TI Involvement of Akt in preconditioning-induced tolerance to ischemia in PC12 cells SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE Akt; FoxO4; GSK-3; ischemic tolerance; MDM2; PC12 cells ID FORKHEAD TRANSCRIPTION FACTOR; PROTEIN-KINASE-B; FACTOR FOXO3A; ACTIVATION; APOPTOSIS; PHOSPHORYLATION; SURVIVAL; HYPOXIA; UBIQUITINATION; 3-KINASE AB The serine-threonine protein kinase Akt has been identified as an important mediator of cell survival able to counteract apoptotic stimuli. However, hibernation, a model of natural tolerance to cerebral ischemia, is associated with downregulation of Akt. We previously established a model of ischemic tolerance in a PC12 cell line and using this model we now addressed the question whether ischemic tolerance also downregulates Akt in PC12 cells. Kinetic studies showed decreased Akt phosphorylation in tolerized cells. Similarly, phosphorylated levels of three major targets of Akt and well-known proapoptotic factors, the glycogen synthase kinase 3 (GSK-3), a Forkhead family member, FoxO4, and the protein murine double minute 2 (MDM2), all inactivated upon phosphorylation by Akt, were decreased in preconditioned cells. In addition, pharmacological blockade of the phosphoinositide 3-kinase (PI3K)/Akt pathway reduced cell death induced by oxygen and glucose deprivation (OGD) and increased the protective effect of preconditioning (PC). Furthermore, decreasing availability of P-Akt by transfecting PC12 cells with constructs of inactive Akt also resulted in protection against OGD and potentiation of the protective effect of PC. Depending on the environment, GSK-3, FOXO-4, and MDM2 can trigger apoptotic responses or cell cycle arrest, and thus, in a situation of reduced energy, driving the cells into a state of quiescence might be neuroprotective. This work suggests that in the context of tolerance downregulation of Akt is beneficial. C1 NINDS, Stroke Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Hillion, JA (reprint author), NINDS, Stroke Branch, Dept Hlth & Human Serv, NIH, 49 Convent Dr MSC 4476,Bldg 49 Room 2A59, Bethesda, MD 20892 USA. EM hillionj@ninds.nih.gov OI Takanohashi, Asako/0000-0003-3292-1595 FU Intramural NIH HHS [Z99 NS999999] NR 37 TC 31 Z9 34 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2006 VL 26 IS 10 BP 1323 EP 1331 DI 10.1038/sj.jcbfm.9600286 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 087MO UT WOS:000240746700010 PM 16511503 ER PT J AU Scahill, L Aman, MG McDougle, CJ McCracken, JT Tierney, E Dziura, J Arnold, E Posey, D Young, C Shah, B Ghuman, J Ritz, L Vitiello, B AF Scahill, Lawrence Aman, Michael G. McDougle, Christopher J. McCracken, James T. Tierney, Elaine Dziura, James Arnold, Eugene Posey, David Young, Christopher Shah, Bhavik Ghuman, Jaswinder Ritz, Louise Vitiello, Benedetto TI A prospective open trial of guanfacine in children with pervasive developmental disorders SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID ABERRANT BEHAVIOR CHECKLIST; DEFICIT HYPERACTIVITY DISORDER; METHYLPHENIDATE; ADHD; ATOMOXETINE; COMMUNITY; AUTISM; NORMS; MTA AB Objective: A common complaint for children with pervasive developmental disorder (PDD) is hyperactivity. The purpose of this pilot study was to gather preliminary information on the efficacy of guanfacine in children with PDD and hyperactivity. Methods: Children with PDD accompanied by hyperactivity entered the open-label trial if there was a recent history of failed treatment with methylphenidate or the child did not improve on methylphenidate in a multisite, placebo-controlled trial. Results: Children (23 boys and 2 girls) with a mean age of 9.03 (+/- 3.14) years entered the open-label trial. After 8 weeks of treatment, the parent-rated Hyperactivity subscale of the Aberrant Behavior Checklist (ABC) went from a mean of 31.3 (+/- 8.89) at baseline to 18.9 (+/- 10.37) (effect size = 1.4; p < 0.001). The teacher-rated Hyperactivity subscale decreased from a mean of 29.9 (+/-\9.12) at baseline to 22.3 (+/- 9.44) (effect size = 0.83; p < 0.01). Twelve children (48%) were rated as Much Improved or Very Much Improved on the Clinical Global Impressions-Improvement. Doses ranged from 1.0 to 3.0 mg/day in two or three divided doses. Common adverse effects included irritability, sedation, sleep disturbance (insomnia or midsleep awakening), and constipation. Irritability led to discontinuation in 3 subjects. There were no significant changes in pulse, blood pressure, or electrocardiogram. Conclusions: Guanfacine may be useful for the treatment of hyperactivity in children with PDD. Placebo-controlled studies are needed to guide clinical practice. C1 Yale Univ, Yale Child Study Ctr, New Haven, CT 06520 USA. Ohio State Univ, Columbus, OH 43210 USA. Indiana Univ, Bloomington, IN 47405 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Kennedy Krieger Inst, Baltimore, MD USA. NIMH, Bethesda, MD 20892 USA. RP Scahill, L (reprint author), Yale Univ, Yale Child Study Ctr, POB 207900, New Haven, CT 06520 USA. EM lawrence.scahill@yale.edu OI Witwer, Andrea/0000-0002-1268-4222; Scahill, Lawrence/0000-0001-5073-1707 FU NCRR NIH HHS [M01 RR00034, M01 RR00052, M01 RR00750, M01 RR06022]; NIMH NIH HHS [N01MH80011, N01MH70010, N01MH70001, K23 MH001883-05, N01MH70009] NR 28 TC 59 Z9 60 U1 4 U2 10 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD OCT PY 2006 VL 16 IS 5 BP 589 EP 598 DI 10.1089/cap.2006.16.589 PG 10 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 109KT UT WOS:000242307600009 PM 17069547 ER PT J AU Pine, DS AF Pine, Daniel S. TI A primer on brain imaging in developmental psychopathology: What is it good for? SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article ID D-CYCLOSERINE; AMYGDALA AB This primer introduces a Special Section on brain imaging, which includes a commentary and 10 data papers presenting applications of brain imaging to questions on developmental psychopathology. This primer serves two purposes. First, the article summarizes the strength and weaknesses of various brain-imaging techniques typically employed in research on developmental psychopathology. Second, the article places research on brain imaging in a broader context by discussing particular limitations and utilities of imaging. Specifically, while brain imaging is currently of limited clinical utility, work in this area is beginning to shape clinical thinking. Brain-imaging research offers a unique opportunity to constrain theories of pathophysiology based on understandings of brain function. This effect promises to open avenues for novel treatments. C1 NIMH, Sect Dev Affect Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. RP Pine, DS (reprint author), NIMH, Sect Dev Affect Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. EM daniel.pine@nih.gov NR 5 TC 2 Z9 2 U1 2 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD OCT PY 2006 VL 47 IS 10 BP 983 EP 986 DI 10.1111/j.1469-7610.2006.01686.x PG 4 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 099VL UT WOS:000241625200002 PM 17073976 ER PT J AU Wallace, GL Schmitt, JE Lenroot, R Viding, E Ordaz, S Rosenthal, MA Molloy, EA Clasen, LS Kendler, KS Neale, MC Giedd, JN AF Wallace, Gregory L. Schmitt, J. Eric Lenroot, Rhoshel Viding, Essi Ordaz, Sarah Rosenthal, Michael A. Molloy, Elizabeth A. Clasen, Liv S. Kendler, Kenneth S. Neale, Michael C. Giedd, Jay N. TI A pediatric twin study of brain morphometry SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE brain development; brain imaging; pediatric; twin; behavioral genetics ID MRI DATA; SIZE; VARIABILITY; VARIANCE; MODELS AB Background: Longitudinal pediatric neuroimaging studies have demonstrated increasing volumes of white matter and regionally-specific inverted U shaped developmental trajectories of gray matter volumes during childhood and adolescence. Studies of monozygotic and dyzygotic twins during this developmental period allow exploration of genetic and non-genetic influences on these developmental trajectories. Method: Magnetic resonance imaging brain scans were acquired on a pediatric sample of 90 monozygotic twin pairs, 38 same-sex dyzygotic twin pairs, and 158 unrelated typically developing singletons. Structural equation modeling was used to estimate the additive genetic, common environment, and unique environment effects, as well as age by heritability interactions, on measures of brain volumes from these images. Results: Consistent with previous adult studies, additive genetic effects accounted for a substantial portion of variability in nearly all brain regions with the notable exception of the cerebellum. Significant age by heritability interactions were observed with gray matter volumes showing a reduction in heritability with increasing age, while white matter volume heritability increased with greater age. Conclusion: Understanding the relative contributions of genetic and nongenetic factors on developmental brain trajectories may have implications for better understanding brain-based disorders and typical cognitive development. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23284 USA. Virginia Commonwealth Univ, Dept Psychiat & Human Genet, Richmond, VA 23284 USA. Inst Psychiat, Social Genet & Dev Psychiat Ctr, London SE5, England. George Washington Univ, Sch Med, Washington, DC 20052 USA. RP Giedd, JN (reprint author), NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. EM jg@nih.gov RI Giedd, Jay/A-3080-2008; Wallace, Gregory/A-4789-2008; Neale, Michael/B-1418-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Wallace, Gregory/0000-0003-0329-5054 FU Intramural NIH HHS; NIMH NIH HHS [MH-20030, MH-65322] NR 23 TC 91 Z9 93 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD OCT PY 2006 VL 47 IS 10 BP 987 EP 993 DI 10.1111/j.1469-7610.2006.01676.x PG 7 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 099VL UT WOS:000241625200003 PM 17073977 ER PT J AU Greenstein, D Lerch, J Shaw, P Clasen, L Giedd, J Gochman, P Rapoport, J Gogtay, N AF Greenstein, Deanna Lerch, Jason Shaw, Philip Clasen, Liv Giedd, Jay Gochman, Peter Rapoport, Judith Gogtay, Nitin TI Childhood onset schizophrenia: cortical brain abnormalities as young adults SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE childhood onset schizophrenia; MRI; cortical thickness; development; neurodevelopment; schizophrenia ID 1ST EPISODE SCHIZOPHRENIA; AUTOMATED 3-D EXTRACTION; 1ST-EPISODE PSYCHOSIS; CEREBRAL-CORTEX; VOLUME CHANGES; MRI DATA; THICKNESS; ADOLESCENCE; CHILDREN; DISORDERS AB Background: Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset illness. Methods: Neuro-anatomic magnetic resonance scans were obtained prospectively from ages 7 through 26 in 70 children diagnosed with COS and age and sex matched healthy controls. Cortical thickness was measured at 40,962 points across the cerebral hemispheres using a novel, fully automated, validated method. Patterns of patient-control differences in cortical development were compared over a 19-year period. Results: Throughout the age range, the COS group had significantly smaller mean cortical thickness compared to controls. However, the COS brain developmental trajectory appeared to normalize in posterior (parietal) regions, and remained divergent in the anterior regions (frontal and temporal) regions, and the pattern of loss became more like that seen in adults. Conclusions: Cortical thickness loss in COS appears to localize with age to prefrontal and temporal regions that are seen for both medication naive and medicated adult onset patients. C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. Mouse Imaging Ctr, Toronto, ON, Canada. RP Greenstein, D (reprint author), NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. EM greenstd@mail.nih.gov RI Gogtay, Nitin/A-3035-2008; Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 57 TC 86 Z9 90 U1 7 U2 17 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD OCT PY 2006 VL 47 IS 10 BP 1003 EP 1012 DI 10.1111/j.1469-7610.2006.01685.x PG 10 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 099VL UT WOS:000241625200005 PM 17073979 ER PT J AU Krain, AL Hefton, S Pine, DS Ernst, M Castellanos, FX Klein, RG Milham, MP AF Krain, Amy L. Hefton, Sara Pine, Daniel S. Ernst, Monique Castellanos, F. Xavier Klein, Rachel G. Milham, Michael P. TI An fMRI examination of developmental differences in the neural correlates of uncertainty and decision-making SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE adolescence; anxiety; brain imaging; development ID VENTROMEDIAL PREFRONTAL CORTEX; STATE WORRY QUESTIONNAIRE; ANTERIOR CINGULATE CORTEX; MEDIAL FRONTAL-CORTEX; GAMBLING TASK; BRAIN IMAGES; ADOLESCENTS; ACTIVATION; ADULTS; OPTIMIZATION AB Background: Maturation of prefrontal circuits during adolescence contributes to the development of cognitive processes such as decision-making. Recent theories suggest that these neural changes also play a role in the shift from generalized anxiety disorder (GAD) to depression that often occurs during this developmental period. Cognitive models of the development of GAD highlight the role of intolerance of uncertainty (IU), which can be characterized behaviorally by impairments in decision-making. The present study examines potential developmental differences in frontal regions associated with uncertain decision-making, and tests the impact of IU on these circuits. Methods: Twelve healthy adults (ages 19-36) and 12 healthy adolescents (ages 13-17) completed a decision-making task with conditions of varied uncertainty while fMRI scans were acquired. They also completed measures of worry and IU, and a questionnaire about their levels of anxiety and certainty during the task. Results: Combined group analyses demonstrated significant linear effects of uncertainty on activity within anterior cingulate cortex (ACC). Region of interest (ROI)-based analysis found a significant interaction of group and IU ratings in ACC. Increased IU was associated with robust linear increases in ACC activity only in adolescents. An ROI analysis of feedback-related processing found that adolescents demonstrated greater activation during incorrect trials relative to correct trials, while the adults showed no difference in neural activity associated with incorrect and correct feedback. Conclusions: This decision-making task was shown to be effective at eliciting uncertainty-related ACC activity in adults and adolescents. Further, IU impacts ACC activity in adolescents during uncertain decision-making, providing preliminary support for a developmental model of GAD. C1 NYU, Sch Med, NYU Child Study Ctr, New York, NY 10012 USA. NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. RP Krain, AL (reprint author), NYU, Sch Med, NYU Child Study Ctr, 550 1St Ave, New York, NY 10012 USA. EM krain@med.nyu.edu RI Roy, Amy/J-7613-2013; OI Castellanos, Francisco/0000-0001-9192-9437 FU NIMH NIH HHS [K23MH074821] NR 52 TC 44 Z9 44 U1 1 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD OCT PY 2006 VL 47 IS 10 BP 1023 EP 1030 DI 10.1111/j.1469-7610.2006.01677.x PG 8 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 099VL UT WOS:000241625200007 PM 17073981 ER PT J AU Johnson, KA AF Johnson, Karen A. TI Editorial: The SERM of my dreams SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID ESTROGEN-RECEPTOR LIGANDS; DEVELOPING BREAST-CANCER; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; RALOXIFENE HYDROCHLORIDE; PREMENOPAUSAL WOMEN; HIGH-RISK; DISEASE; TRIAL; TAMOXIFEN C1 NCI, Div Canc Prevent, Breast & Gynecol Canc Res Grp, Bethesda, MD 20892 USA. RP Johnson, KA (reprint author), NCI, Div Canc Prevent, Breast & Gynecol Canc Res Grp, Bethesda, MD 20892 USA. EM kj80y@nih.gov NR 20 TC 8 Z9 9 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2006 VL 91 IS 10 BP 3754 EP 3756 DI 10.1210/jc.2006-1729 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 092ML UT WOS:000241100900007 PM 17028288 ER PT J AU Eng-Wong, J Reynolds, JC Venzon, D Liewehr, D Gantz, S Danforth, D Liu, ET Chow, C Zujewski, J AF Eng-Wong, J. Reynolds, J. C. Venzon, D. Liewehr, D. Gantz, S. Danforth, D. Liu, E. T. Chow, C. Zujewski, J. TI Effect of raloxifene on bone mineral density in premenopausal women at increased risk of breast cancer SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HEALTHY POSTMENOPAUSAL WOMEN; SURGICAL ADJUVANT BREAST; BOWEL PROJECT P-1; BIOCHEMICAL MARKERS; TAMOXIFEN; TRIAL; ESTROGEN; PREVENTION; PLACEBO; TURNOVER AB Context: Raloxifene is a promising breast cancer prevention agent in postmenopausal women at increased risk for breast cancer. The effects of raloxifene in premenopausal women are unknown. Objective: We evaluated the effect of raloxifene in premenopausal women at increased risk for breast cancer on bone mineral density (BMD). Design: This was a phase II clinical trial. Setting: This study was conducted at an academic medical center. Participants: Thirty-seven premenopausal women at increased risk for breast cancer enrolled in the trial. Thirty subjects began treatment and 27 were evaluable. Intervention: Raloxifene ( 60 mg daily) and elemental calcium ( 500 mg daily) were given for 2 yr. Subjects were followed up off medications for 1 yr. Main Outcome Measure: The primary end point was the intra-subject percent change in BMD at 1 yr measured by dual-energy x-ray absorptiometry. Results: The mean baseline lumbar spine density was 1.027 g/cm(2). Lumbar spine density decreased 2.3% at 1 yr ( P < 0.00001) and 3.5% at 2 yr ( P < .00001). Percent change from yr 2 to 3 was +1.4%. The mean baseline total hip bone density was 0.905 g/cm(2). Total hip density decreased 0.3% at 1 yr and 1.0% at 2 yr ( P = 0.033). Percent change from yr 2 to 3 was + 1.7%. Conclusions: Raloxifene use is associated with a decrease in BMD in premenopausal women at increased risk for breast cancer. The clinical significance of this decrease is unknown and is attenuated with stopping raloxifene. C1 NCI, Med Oncol Clin Res Unit, NIH, Bethesda, MD 20892 USA. NCI, Surg Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Genome Inst Singapore, Singapore 138672, Singapore. RP Eng-Wong, J (reprint author), NCI, Med Oncol Clin Res Unit, NIH, Bldg 10,Room 12N226,9000 Wisconsin Ave, Bethesda, MD 20892 USA. EM engwongj@mail.nih.gov RI Liu, Edison/C-4141-2008 FU Intramural NIH HHS NR 33 TC 21 Z9 21 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2006 VL 91 IS 10 BP 3941 EP 3946 DI 10.1210/jc.2005-2827 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 092ML UT WOS:000241100900038 PM 16868059 ER PT J AU Dorgan, JF McMahon, RP Aronson, L Van Horn, FL Snetselaar, LG Kwiterovich, PO Lauer, RM Lasser, NL Stevens, VJ Robson, A Cooper, SF Chandler, DW Franklin, FA Barton, BA Patterson, BH Taylor, PR Schatzkin, A AF Dorgan, Joanne F. McMahon, Robert P. Aronson, Lisa Van Horn, Friedman Linda Snetselaar, Linda G. Kwiterovich, Peter O., Jr. Lauer, Ronald M. Lasser, Norman L. Stevens, Victor J. Robson, Alan Cooper, Susan F. Chandler, D. Walt Franklin, Frank A. Barton, Bruce A. Patterson, Blossom H. Taylor, Philip R. Schatzkin, Arthur TI Diet and sex hormones in boys: Findings from the dietary intervention study in children SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; URINE ANDROGENS; BREAST-CANCER; SERUM; DISC; FAT; MEN; EFFICACY; SAFETY; PLASMA AB Context: Diet reportedly alters serum sex hormone concentrations in adults, but little is known about the influence of diet during puberty on these hormones. Objective: We aimed to determine whether an intervention to lower fat intake during adolescence alters serum sex hormone concentrations and progression through puberty. Design: In 1990 - 1997, we conducted an ancillary study to the Dietary Intervention Study in Children, a multicenter, randomized, controlled clinical trial to test the safety and efficacy of a cholesterol-lowering dietary intervention in children. Participants: Healthy, prepubertal, 8 to 10 yr olds with elevated low-density lipoprotein cholesterol were randomized to usual care or a behavioral intervention. Of 362 randomized Dietary Intervention Study in Children boys, 354 participated in the ancillary study. Eighty-four percent of boys attended last visits when their median time on trial was 7.1 yr. Intervention: The behavioral intervention continued throughout the duration of the trial and promoted a diet with 28% energy from total fat, less than 8% from saturated fat, 9% or less from polyunsaturated fat, and less than 75 mg cholesterol per 1000 kcal. Outcome Measures: The main outcome measure for boys formulated before study initiation was non-SHBG bound testosterone concentration. Secondary outcomes included serum total testosterone, dihydrotestosterone, androstenedione, estradiol, estrone, SHBG, and Tanner stage. Results: There were no significant treatment group differences in boys' serum hormone levels, SHBG, or Tanner stages at any individual visit or over the course of the trial when evaluated by longitudinal models. Conclusion: Modest reductions in total fat, saturated fat, and possibly energy intake do not alter progression through puberty or serum sex hormone concentrations in adolescent boys. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. Maryland Med Res Inst, Baltimore, MD 21210 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Univ Iowa, Iowa City, IA 52242 USA. Johns Hopkins Univ, Baltimore, MD 21205 USA. Univ Med & Dent New Jersey, Newark, NJ 07107 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR 97227 USA. Childrens Hosp, New Orleans, LA 70118 USA. Esoterix Endocrinol Inc, Calabasas Hills, CA 91301 USA. NIAID, Operat Off, Program Planning & Sci Informat, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Childrens Hosp, Birmingham, AL 35233 USA. RP Dorgan, JF (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM joanne.dorgan@fccc.edu RI McMahon, Robert/C-5462-2009; Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NHLBI NIH HHS [U01 HL 37948, U01 HL 37954, U01 HL 37947, U01 HL 37962, U01 HL 37966, U01 HL 37975, U01 HL 38110] NR 20 TC 15 Z9 15 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2006 VL 91 IS 10 BP 3992 EP 3996 DI 10.1210/jc.2005-0109 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 092ML UT WOS:000241100900045 PM 16868056 ER PT J AU Cataisson, C Pearson, AJ Tsien, MZ Mascia, F Gao, JL Pastore, S Yuspa, SH AF Cataisson, Christophe Pearson, Andrea J. Tsien, Margaret Z. Mascia, Francesca Gao, Ji-Liang Pastore, Saveria Yuspa, Stuart H. TI CXCR2 ligands and G-CSF mediate PKC alpha-induced intraepidermal inflammation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID COLONY-STIMULATING FACTOR; KINASE-C-ALPHA; IL-8 RECEPTOR HOMOLOG; SKIN TUMOR-PROMOTION; IN-VIVO; TRANSGENIC MICE; BONE-MARROW; TNF-ALPHA; NEUTROPHIL MIGRATION; MESSENGER-RNA AB Transgenic mice overexpressing PKC alpha in the epidermis (K5-PKC alpha mice) exhibit an inducible severe intraepi-dermal neutrophilic inflammation and systemic neutrophilia when PKCa is activated by topical 12-O-tetradecanoylphorbol-13-acetate (TPA). This inducible model of cutaneous inflammation was used to define mediators of skin inflammation that may have clinical relevance. Activation of cutaneous PKCa increased the production of the chemotactic factors cytokine-induced neutrophil chemoattractant (KC) and macrophage inflammatory protein 2 (MIP-2) in murine plasma. TPA treatment of cultured K5-PKC alpha keratinocytes also released KC and MIP-2 into culture supernatants through an NF-kappa B-dependent pathway. MIP-2 and KC mediated the infiltration of neutrophils into the epidermis, since this was prevented by ablating CXCR2 in K5-PKCa mice or administering neutralizing antibodies against KC or MIP-2. The neutrophilia resulted from PKC alpha-mediated upregulation of cutaneous G-CSF released into the plasma independent of CXCR2. These responses could be inhibited by topical treatment with a PKC alpha-selective inhibitor. Inhibiting PKCa also reduced the basal and TNF-alpha- or TPA-induced expression of CXCL8 in cultured psoriatic keratinocytes, suggesting that PKC alpha activity may contribute to psoriatic inflammation. Thus, skin can be the source of circulating factors that have both local and systemic consequences, and these factors, their receptors, and possibly PKC alpha could be therapeutic targets for inhibition of cutaneous inflammation. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Ist Dermopat Immacolata, Rome, Italy. RP Yuspa, SH (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Canc Res Ctr, 37 Convent Dr,MSC-4255,Bldg 37,Room 4068, Bethesda, MD 20892 USA. EM yuspas@mail.nih.gov FU Intramural NIH HHS NR 64 TC 49 Z9 49 U1 1 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2006 VL 116 IS 10 BP 2757 EP 2766 DI 10.1172/JC127514 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 090QK UT WOS:000240965700025 PM 16964312 ER PT J AU Altshuler, LL Post, RM Black, DO Keck, PE Nolen, WA Frye, MA Suppes, T Grunze, H Kupka, RW Leverich, GS McElroy, SL Walden, J Mintz, J AF Altshuler, Lori L. Post, Robert M. Black, David O. Keck, Paul E., Jr. Nolen, Willem A. Frye, Mark A. Suppes, Trisha Grunze, Heinz Kupka, Ralph W. Leverich, Gabriele S. McElroy, Susan L. Walden, Joerg Mintz, Jim TI Subsyndromal depressive symptoms are associated with functional impairment in patients with bipolar disorder: Results of a large, multisite study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID QUALITY-OF-LIFE; PROSPECTIVE FOLLOW-UP; SOCIAL-ADJUSTMENT; MAJOR DEPRESSION; SUBCLINICAL SYMPTOMS; GENERAL-POPULATION; SYMPTOMATOLOGY IDS; MEDICAL OUTCOMES; NATURAL-HISTORY; MOOD DISORDERS AB Objective: Studies of patients with unipolar depression have demonstrated a relationship between subthreshold depressive symptoms and impairment in role functioning. Research examining this relationship in persons with bipolar disorder is rare. This study sought to evaluate the association between subsyndromal depressive symptoms and role functioning in subjects with bipolar disorder. Method: 759 adult outpatients with a DSM-IV diagnosis of bipolar disorder were entered into this study at 7 different sites in the Stanley Foundation Bipolar Network (SFBN) beginning in March 1996 and ending in November 2002 and were followed longitudinally for assessment of their course of illness. Subsyndromal depression was operationalized using cutoff scores on the Inventory for Depressive Symptomatology-Clinician Rated (IDS-C), and patients were divided into 3 groups: not depressed (IDS-C score < 13), subsyndromally depressed (IDS-C score 13 to 27), and syndromally depressed (IDS-C score >= 28). Groups were compared using a series Of chi(2) analyses on degree of role function impairment across 4 role domains (work, home duties, family life, and friendships) from the Life Functioning Questionnaire. Logistic regression was used to estimate the probability of any impairment in life functioning based on severity of depressive symptoms. Results: Subsyndromally depressed patients were significantly more likely than those not depressed to report impairment in their work and home functioning roles, as well as impairment in relations with family and friends (p < .001). Across all domains of role function, the proportion of patients impaired in the subsyndromally depressed group was more similar to the syndromally depressed group than to the not depressed group. Conclusions: These findings clearly demonstrate the public health significance of subsyndromal depression in the bipolar population. The most appropriate interventions for subsyndromal depressive symptoms in patients with bipolar disorder remain to be determined. C1 Univ Calif Los Angeles, Dept Psychiat, VA Greater Los Angeles Heathcare Syst, W Los Angeles Healthcare, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, Cincinnati, OH USA. Vet Affairs Med Ctr, Mental Hlth Care Line & Gen Clin Res Ctr, Cincinnati, OH 45267 USA. Univ Groningen, Med Ctr, Dept Psychiat, Groningen, Netherlands. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Ludwig Maximilians Univ Munchen, Dept Psychiat, Munich, Germany. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. Univ Freiburg, Dept Psychiat, Freiburg, Germany. Univ Munster, Dept Psychiat, Munster, Germany. RP Altshuler, LL (reprint author), 300 UCLA Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu RI Nolen, Willem/E-9006-2014 NR 67 TC 114 Z9 119 U1 2 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2006 VL 67 IS 10 BP 1551 EP 1560 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 104NE UT WOS:000241964300009 PM 17107246 ER PT J AU Rickard, TC Verfaellie, M Grafman, J AF Rickard, Timothy C. Verfaellie, Mieke Grafman, Jordan TI Transverse patterning and human amnesia SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID CONFIGURAL ASSOCIATION THEORY; HIPPOCAMPAL-FORMATION; OLFACTORY CUES; MEMORY; ACQUISITION; RATS; LESIONS; DAMAGE; TASKS; DISCRIMINATIONS AB The transverse patterning (TP) task (A+ B-, B+ C-, C+ A-) has played a central role in testing the hypothesis that medial-temporal (and, in particular, hippocampal) brain damage selectively impairs learning on at least some classes of configural (i.e., nonlinear) learning tasks. Results in the animal and human literature generally support that hypothesis. Reed and Squire [Impaired transverse patterning in human amnesia is a special case of impaired memory for two-choice discrimination tasks. Behavioral Neuroscience, 113, 3-9, 1999], however, advanced an alternative account in which impaired TP performance in amnesia reflects a generic scaling artifact arising from the greater difficulty of the TP task compared to the elemental (i.e., linear) control task that is typically used. We begin with a critique of Reed and Squire, countering their conceptual arguments and showing that their results, when analyzed appropriately, support the configural deficit hypothesis. We then report results from eight new amnesic patients and controls oil an improved version of the TP task. Despite substantial practice, accuracy of patients with bilateral hippocampal damage clue to anoxia reached and maintained an asymptote of only 54% correct, well below the maximum accuracy obtainable (67%) in the absence of configural learning. A patient with selective bilateral damage to the anterior thalamic nuclei exhibited a TP accuracy asymptote that was near 67%, a pattern of two out of three correct consecutive trials, and a pattern of nearly always answering correctly for two of the three TP item pairs. These results are consistent with a set of unique and parameter-free predictions of the configural deficit hypothesis. C1 Univ Calif San Diego, Dept Psychol, La Jolla, CA 92093 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston VA Med Ctr, Boston, MA USA. Natl Inst Hlth, Bethesda, MD 20892 USA. RP Rickard, TC (reprint author), Univ Calif San Diego, Dept Psychol, La Jolla, CA 92093 USA. EM trickard@ucsd.edu OI Grafman, Jordan H./0000-0001-8645-4457 FU NIMH NIH HHS [R29 MH058202, R29 MH58202]; NINDS NIH HHS [P50 NS026985, NS26985] NR 28 TC 19 Z9 19 U1 0 U2 2 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD OCT PY 2006 VL 18 IS 10 BP 1723 EP 1733 DI 10.1162/jocn.2006.18.10.1723 PG 11 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 094ZR UT WOS:000241278500011 PM 17014376 ER PT J AU Sidorov, IA Dimitrov, DS AF Sidorov, I. A. Dimitrov, D. S. TI Nanobiology think tank: Computational and theoretical nanoscience is taking off at the National Cancer Institute SO JOURNAL OF COMPUTATIONAL AND THEORETICAL NANOSCIENCE LA English DT Editorial Material C1 NCI, Canc Res Ctr, Nanobiol Program, NIH, Frederick, MD 21702 USA. RP Sidorov, IA (reprint author), NCI, Canc Res Ctr, Nanobiol Program, NIH, POB 8,Miller Dr, Frederick, MD 21702 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SCIENTIFIC PUBLISHERS PI STEVENSON RANCH PA 25650 NORTH LEWIS WAY, STEVENSON RANCH, CA 91381-1439 USA SN 1546-1955 J9 J COMPUT THEOR NANOS JI J. Comput. Theor. Nanosci. PD OCT PY 2006 VL 3 IS 5 BP 599 EP 602 PG 4 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 100RD UT WOS:000241685400001 ER PT J AU McVeigh, E AF McVeigh, Elliot TI Measuring mechanical function in the failing heart SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article; Proceedings Paper CT 31st Annual Conference of the International-Society-for-Computerized-Electrocardiology CY APR 22-27, 2006 CL Ontario, CANADA SP Int Soc Computerized Electrocardiol, Draeger Med Syst, GE Med Syst Inc, Inovise Med Inc, MEDTRONIC, Mortara Instrument Inc, NE Montoring Inc, Philips Med Syst, Quinton Instrument Inc, Rozinn Elect Inc, St Jude Med, SCHILLER AG, SIGNALIFE Inc, Welch Allyn Inc DE heart failure; tagging; myocardium; function; MRI ID CARDIAC RESYNCHRONIZATION THERAPY; INTRAVENTRICULAR-CONDUCTION DELAY; HYPERTROPHIC CARDIOMYOPATHY; DILATED CARDIOMYOPATHY; DIASTOLIC DYSFUNCTION; MYOCARDIAL-INFARCTION; PACED HEART; MOTION; MRI; CONTRAST AB A common pathology in heart failure is a detrimental change in the mechanics of both contraction and filling. In familial hypertrophic cardiomyopathy, a genetic disease characterized by left ventricular hypertrophy and myofiber disarray, left ventricular diastolic dysfunction is common and contributes to congestive heart failure. In dilated cardiomyopathy, a common correlate to reduced wall thickening and increased chamber volume is an asynchronous activation of the left ventricle due to left bundle branch block. Local measures of the timing and magnitude of myocardial shortening and relaxation can be obtained with magnetic resonance (MR) tissue tagging, MR cine phase contrast, or MR cine displacement encoding. In familial hypertrophic cardiomyopathy, these methods have been shown to quantify the restrictive filling of the ventricle. Characterizing the regions of the failing heart which are activated late has allowed investigators to measure the change in protein expression in those regions compared to normal myocardium. Also, these MR imaging methods have led to a better quantification of the asynchronous activation in dilated cardiomyopathy, which can be used to predict response to resynchronization therapy with pacing. (C) 2006 Elsevier Inc. All rights reserved. C1 NHLBI, Cardiac Energet Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP McVeigh, E (reprint author), NHLBI, Cardiac Energet Lab, NIH, DHHS, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 HL004609-08] NR 37 TC 2 Z9 2 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD OCT PY 2006 VL 39 IS 4 SU S BP S24 EP S27 DI 10.1016/j.jelectrocard.2006.05.031 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 100YR UT WOS:000241706600006 PM 16963066 ER PT J AU Lindzey, J Jayes, FL Yates, MM Couse, JF Korach, KS AF Lindzey, Jonathan Jayes, Friederike L. Yates, Mariana M. Couse, John F. Korach, Kenneth S. TI The bi-modal effects of estradiol on gonadotropin synthesis and secretion in female mice are dependent on estrogen receptor-alpha SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; HORMONE-RELEASING-HORMONE; PITUITARY-GONADAL AXIS; LUTEINIZING-HORMONE; ER-BETA; RAT-BRAIN; OVARIECTOMIZED RATS; TISSUE DISTRIBUTION; CELLULAR-LEVELS; DISRUPTED MICE AB Depending on the estrous/menstrual cycle stage in females, ovarian-derived estrachol (E-2) exerts either a negative or a positive effect on the hypothalamic-pituitary axis to regulate the synthesis and secretion of pituitary gonadotropins, LH, and FSH. To study the role of estrogen receptor-alpha (ER alpha) mediating these effects, we assessed the relevant parameters in adult wild-type (WT) and ER alpha-null (alpha ERKO) female mice in vivo and in primary pituitary cell cultures. The ocERKO mice exhibited significantly higher plasma and pituitary LH levels relative to WT females despite possessing markedly high levels of circulating E-2. In contrast, hypothalamic GnRH content and circulating FSH levels were comparable between genotypes. Ovariectomy led to increased plasma LH in WT females but no further increase in ocERKO females, while plasma FSH levels increased in both genotypes. E-2 treatment suppressed the high plasma LH and pituitary Lhb mRNA expression in ovariectomized WT females but had no effect in ocERKO. In contrast, E-2 treatments only partially suppressed plasma FSH in ovariectomized WT females, but this too was lacking in alpha ERKO females. Therefore, negative feedback on FSH is partially E-2/ER alpha mediated but more dependent on ovarian-derived inhibin, which was increased threefold above normal in ocERKO females. Together, these data indicate that E-2-mediated negative feedback is dependent on functional ER alpha and acts to primarily regulate LH synthesis and secretion. Studies in primary cultures of pituitary cells from WT females revealed that E2 did not suppress basal or GnRH-incluced LH secretion but instead enhanced the latter response, indicating that the positive influence of E2 on gonadotropin secretion may occur at the level of the pituitary. Once again this effect was lacking in alpha ERKO gonadotropes in culture. These data indicate that the aspects of negative and positive effects of E-2 on gonadotropin secretion are ERa dependent and occur at the level of the hypothalamus and pituitary respectively. C1 NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. Lock Haven Univ, Dept Biol Sci, Lock Haven, PA 17745 USA. RP Korach, KS (reprint author), NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233,MD B3-02, Res Triangle Pk, NC 27709 USA. EM korach@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X FU Intramural NIH HHS NR 56 TC 26 Z9 27 U1 0 U2 2 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD OCT PY 2006 VL 191 IS 1 BP 309 EP 317 DI 10.1677/joe.1.06965 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 103YL UT WOS:000241923000031 PM 17065413 ER PT J AU Mash, C AF Mash, Clay TI Multidimensional shape similarity in the development of visual object classification SO JOURNAL OF EXPERIMENTAL CHILD PSYCHOLOGY LA English DT Article DE visual perception; attention; categorization; children; adults ID SUBORDINATE-LEVEL; PERCEPTUAL CLASSIFICATION; DIMENSIONAL SEPARABILITY; HIERARCHICAL PATTERNS; PRESCHOOL-CHILDREN; BASIC-LEVEL; PARTS; ATTENTION; CATEGORIES; ADULTS AB The current work examined age differences in the classification of novel object images that vary in continuous dimensions of structural shape. The structural dimensions employed are two that share a privileged status in the visual analysis and representation of objects: the shape of discrete prominent parts and the attachment positions of those parts. Experiment 1 involved a triad classification task in which participants at each of three different ages (5 years, 8 years, and adult) classified object images from two distinct stimulus sets. Across both sets, the youngest children demonstrated a systematic bias toward the shape of discrete parts during their judgments. With increasing age, participants increasingly came to select both the shape and the position of parts when classifying the images. The findings from Experiment 2 indicate that the local shape bias observed in young children's classifications is not merely a consequence of a discrimination advantage for that dimension. Results are discussed in relation to corresponding age-related changes in other functional contexts of visual processing. (c) 2006 Elsevier Inc. All rights reserved. C1 NICHHD, Bethesda, MD 20892 USA. RP Mash, C (reprint author), NICHHD, 6705 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA. EM mashe@mail.nih.gov FU Intramural NIH HHS NR 63 TC 20 Z9 20 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-0965 J9 J EXP CHILD PSYCHOL JI J. Exp. Child Psychol. PD OCT PY 2006 VL 95 IS 2 BP 128 EP 152 DI 10.1016/j.jecp.2006.04.002 PG 25 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 092UP UT WOS:000241123100004 PM 16793055 ER PT J AU Macrae, F Jones, IT Pizzey, C Bertagnolli, M Hawk, E Eagle, C AF Macrae, F. Jones, I. T. Pizzey, C. Bertagnolli, M. Hawk, E. Eagle, C. CA A P C Trial Investigators TI Celecoxib reduces formation of sporadic adenomas: results from the adenoma prevention with celecoxib (APC) trial SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Meeting Abstract C1 Royal Melbourne Hosp, Dept Colorectal Med, Melbourne, Vic, Australia. Royal Melbourne Hosp, Dept Genet, Melbourne, Vic, Australia. Royal Melbourne Hosp, Dept Colorectal Surg, Melbourne, Vic, Australia. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD OCT PY 2006 VL 21 SU 4 BP A264 EP A264 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 179WI UT WOS:000247320600035 ER PT J AU Zakhari, S AF Zakhari, Samir TI Special remarks from the national institute on alcohol abuse and alcoholism SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material C1 NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD 20892 USA. RP Zakhari, S (reprint author), NIAAA, Div Metab & Hlth Effects, NIH, 5635 Fishers Lane,Room 2031, Bethesda, MD 20892 USA. EM szakhari@mail.nih.gov 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 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD OCT PY 2006 VL 21 SU 3 BP CP3 EP CP3 DI 10.1111/j.1440-1746.2006.04599.x PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 075XC UT WOS:000239919600002 ER PT J AU Purohit, V AF Purohit, Vishnudutt TI International collaboration on alcoholic liver disease and pancreatitis: Opportunities SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article C1 NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD USA. RP Purohit, V (reprint author), 5635 Fishers Lane,Room 2035,MSC 9304, Bethesda, MD 20892 USA. EM vpurohit@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD OCT PY 2006 VL 21 SU 3 BP S107 EP S108 DI 10.1111/j.1440-1746.2006.04579.x PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 075XC UT WOS:000239919600028 PM 16958660 ER PT J AU Vasconcelos, OM Poehm, EH McCarter, RJ Campbell, WW Quezado, ZMN AF Vasconcelos, Olavo M. Poehm, Erika H. McCarter, Robert J. Campbell, William W. Quezado, Zenaide M. N. TI Potential outcome factors in subacute combined degeneration - Review of observational studies SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE subacute combined degeneration; SCD; nitrous oxide; cobalamin; vitamin B12; combined system degeneration ID NITROUS-OXIDE ANESTHESIA; TOTAL HOMOCYSTEINE CONCENTRATIONS; SPINAL-CORD; COBALAMIN DEFICIENCY; MAGNETIC-RESONANCE; MR FINDINGS; VITAMIN-B-12 DEFICIENCY; REVERSIBLE MYELOPATHY; METHYLMALONIC ACID; POSTERIOR COLUMNS AB BACKGROUND: Subacute combined degeneration is an acquired myelopathy caused by vitamin B12 deficiency. Therapy with B12 leads to improvement in most but to complete recovery in only a few patients. Prognostic indicators in subacute combined degeneration are unknown; therefore, predicting complete recovery of neurologic deficits is challenging. PURPOSE: To identify potential correlates of outcome and to generate hypotheses concerning predictors of complete resolution of neurologic deficits in subacute combined degeneration. DATA SOURCE: We searched EMBASE (1974 to October 2005), MEDLINE (1968 to October 2005), and references from identified reports. REPORTS SELECTION: Reports of patients with subacute combined degeneration containing results of magnetic resonance imaging (MRI) and description of outcome and 1 patient treated by the authors. DATA EXTRACTION, SYNTHESIS: We extracted data from 45 reports and 57 patients (36 males, 21 females; age range: 10 to 81) with a diagnosis of subacute combined degeneration, and estimated the strength of association between clinical, laboratory, and radiological factors and complete resolution of signs and symptoms. RESULTS: Eight patients (14%) achieved clinical resolution and 49 (86%) improved with B12 therapy. The absence of sensory dermatomal deficit, Romberg, and Babinski signs were associated with a higher complete resolution rate. Patients with MRI lesions in <= 7 segments and age less than 50 also appear to have higher rates of complete resolution. CONCLUSION: B12 therapy is reported to stop progression and improve neurologic deficits in most patients with subacute combined degeneration. However, complete resolution only occurs in a small percentage of patients and appears to be associated with factors suggestive of less severe disease at the time of diagnosis. C1 NIH, Ctr Clin, Dept Anesthesia & Surg Serv, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. George Washington Univ, Sch Med, Biostat & Informat Unit, Washington, DC USA. RP Quezado, ZMN (reprint author), NIH, Ctr Clin, Dept Anesthesia & Surg Serv, 10 Ctr Dr,MSC-1512,Bldg 10,Room 2C624, Bethesda, MD 20892 USA. EM zquezado@nih.gov RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 FU Intramural NIH HHS NR 63 TC 25 Z9 30 U1 2 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2006 VL 21 IS 10 BP 1063 EP 1068 DI 10.1111/j.1525-1497.2006.00525.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 081BH UT WOS:000240291700009 PM 16970556 ER PT J AU Gardener, EA Huppert, FA Guralnik, JM Melzer, D AF Gardener, Elizabeth A. Huppert, Felicia A. Guralnik, Jack M. Melzer, David TI Middle-aged and mobility-limited - Prevalence of disability and symptom attributions in a national survey SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE mobility-limited; middle-aged; symptoms ID OLD-AGE; FUNCTIONAL STATUS; HEALTH; MORTALITY; WOMEN; LIMITATION; MORBIDITY; COMMUNITY; DYNAMICS; DECLINE AB BACKGROUND: Lower limb mobility disabilities are well understood in older people, but the causes in middle age have attracted little attention. OBJECTIVES: To estimate the prevalence of mobility disabilities among noninstitutionalized adults in England and to compare the disabling symptoms reported by middle-aged and older people. DESIGN: Cross-sectional data from the 2002 English Longitudinal Study of Ageing (ELSA). Mobility disability was identified by level of reported difficulty walking a quarter mile. PARTICIPANTS: Eleven thousand two hundred sixteen respondents aged 50 years and older living in private households in 2002. RESULTS: The prevalence of difficulty walking a quarter mile increases sharply with age, but even in the middle-aged (50 to 64 years age-group) 18% (95% confidence interval [CI]: 16% to 19%) of men and 19% (95% CI: 17% to 20%) of women reported some degree of difficulty. Of the 16 main symptoms reported as causing mobility disability in middle age, 2 dominated: pain in the leg or the foot (43%; 95% CI: 40% to 46%) and shortness of breath/dyspnea (21%; 95% CI: 18% to 23%). Fatigue or tiredness, and stability problems were cited by only 5% and 6%, respectively. These proportions were slightly different from those in the 65 to 79-year age group: 40%, 23%, 6%, and 8%, respectively. CONCLUSIONS: Mobility (walking) disabilities in the middle-aged are relatively common. The symptoms reported as causes in this age group differ little from those reported by older groups, and are dominated by lower limb pain and shortness of breath. More clinical attention paid to disabling symptoms may lead to disability reductions in later life. C1 Peninsula Med Sch, Dept Epidemiol & Publ Hlth, Exeter EX2 5DW, Devon, England. Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England. Addenbrookes Hosp, Dept Psychiat, Cambridge, England. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Melzer, D (reprint author), Peninsula Med Sch, Dept Epidemiol & Publ Hlth, RD&E Wonford Site,Barrack Rd, Exeter EX2 5DW, Devon, England. EM david.melzer@pms.ac.uk OI Huppert, Felicia/0000-0003-2696-2286; Melzer, David/0000-0002-0170-3838 FU Intramural NIH HHS; NIA NIH HHS [R03 AG022912, R03-AG022912-01] NR 35 TC 26 Z9 28 U1 4 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2006 VL 21 IS 10 BP 1091 EP 1096 DI 10.1111/j.1525-1497.2006.00564.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 081BH UT WOS:000240291700014 PM 16970558 ER PT J AU Li, J Melenhorst, J Hensel, N Rezvani, K Sconocchia, G Kilical, Y Hou, J Curfman, B Major, E Barrett, AJ AF Li, Jongming Melenhorst, Jos Hensel, Nancy Rezvani, Katyoun Sconocchia, Giuseppe Kilical, Yasemin Hou, Jean Curfman, Blanche Major, Eugene Barrett, A. John TI T-cell responses to peptide fragments of the BK virus T antigen: implications for cross-reactivity of immune response to JC virus SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID DNA-SEQUENCES; TRANSPLANT RECIPIENTS; HEALTHY-INDIVIDUALS; RECEPTOR LIGAND; SIMIAN-VIRUS-40; POLYOMAVIRUS; RECOGNITION; EPITOPES; DISEASE; PROLIFERATION AB Infection with BK virus (BKV) induces both humoral and cellular immunity, but the viral antigens of T-antigen (T-ag) stimulating T-cell responses are largely unknown. To identify BKV-specific T cells in healthy individuals, peripheral blood lymphocytes were cultured with autologous dendritic cells (DCs) loaded with BKV lysate and T cells were screened for intracellular gamma interferon production after stimulation with an overlapping 15mer peptide library of the BKV T-ag. Among many immunogenic peptides identified, four T-ag peptides were identified as candidate major histocompatibility complex class I and 11 T-cell epitopes, restricted to human leukocyte antigen (HLA)-B*0702, -B*08, -DRB1*0301 and -DRB1*0901. Further, a candidate 9mer peptide, LPLMRKAYL, was confirmed to be restricted to HLA-B*0702 and -B*08. Because the polyomaviruses BKV, JC virus (JCV) and Simian virus 40 (SV40) share extensive sequence similarity in the immunogenic proteins T-ag and VP1, it was hypothesized that, in humans, these proteins contain conserved cytotoxic T-lymphocyte (CTL) target epitopes. Four HLA-restricted conserved epitopes of BKV, JCV and SV40 were identified: HLA-B*07, -B*08 and -DRB1*0901 for T-ag and -A*0201 for VP1. T cells cultured in vitro that were specific for one viral antigen recognized other conserved epitopes. CTLs generated from BKV T-ag and VP1 peptide were cytotoxic to DC targets pulsed with either BKV or JCV. Therefore, infection by one of the two viruses (BKV and JCV) could establish cross-immunity against the other. Although cross-cytotoxicity experiments were not performed with SV40, cross-recognition data from conserved antigen epitopes of polyomaviruses suggest strongly that cross-immunity might also exist among the three viruses. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Div Med Oncol, Philadelphia, PA 19107 USA. NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10 CRC,Room 3-5330,10 Ctr Dr, Bethesda, MD 20892 USA. EM barrettj@nih.gov NR 35 TC 45 Z9 45 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD OCT PY 2006 VL 87 BP 2951 EP 2960 DI 10.1099/vir.0.82094-0 PN 10 PG 10 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 094AC UT WOS:000241210400021 PM 16963754 ER PT J AU Jehn, ML Patt, MR Appel, LJ Miller, ER AF Jehn, M. L. Patt, M. R. Appel, L. J. Miller, E. R., III TI One year follow-up of overweight and obese hypertensive adults following intensive lifestyle therapy SO JOURNAL OF HUMAN NUTRITION AND DIETETICS LA English DT Article DE feeding trial; nutrition; weight loss; weight maintenance ID WEIGHT-LOSS; CLINICAL-TRIAL; UNITED-STATES; MAINTENANCE; EXERCISE; DIET; FAT AB Objective To examine the long-term effect on weight maintenance and dietary habits of participants in a clinical trial for weight loss. Setting Community-based residents living in Maryland. Participants Forty-four hypertensive, overweight adults who participated in a randomized clinical trial of weight loss. Participants were randomized to an intensive 'lifestyle' intervention or a 'monitoring' group. Main outcome measures Weight, self-reported current intake of fat and fruit/fibre and self-reported barriers to maintain weight loss were assessed 1 year after the completion of the Diet, Exercise and Weight-loss Intervention Trial (DEW-IT) trial. Analysis t-tests were used to compare groups for differences in continuous variables and chi-square tests were used to compare groups for categorical variables. Results Fourty-two of the 44 DEW-IT subjects participated in the follow-up study. Overall, 55% (12/19) of the lifestyle intervention group remained at or below their baseline weight at 1 year, compared with 48% (11/23) of the monitoring group (P = 0.32). However, during that year, 95% (18/19) of the lifestyle intervention group and 52% (12/23) of the monitoring group gained weight from the end of the study. Both groups reported similar intake of fruits/vegetables (servings day(-1)), dietary fibre (g day(-1)) and fat (g day(-1)). Conclusions and implications The majority of participants who lost weight during the trial regained weight during the course of 1 year. A successful intensive 2-month programme of lifestyle modification (DEW-IT) was ineffective for long-term maintenance of weight loss. C1 Arizona State Univ, Sch Hlth Management & Policy, Tempe, AZ 85287 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. NIA, NIH, Baltimore, MD 21224 USA. RP Jehn, ML (reprint author), Arizona State Univ, Sch Hlth Management & Policy, POB 874506, Tempe, AZ 85287 USA. EM megan.jehn@asu.edu NR 12 TC 17 Z9 17 U1 3 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0952-3871 J9 J HUM NUTR DIET JI J. Hum. Nutr. Diet. PD OCT PY 2006 VL 19 IS 5 BP 349 EP 354 DI 10.1111/j.1365-277X.2006.00711.x PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 082SI UT WOS:000240407100005 PM 16961681 ER PT J AU Gearhart, PJ AF Gearhart, Patricia J. TI Antibody wars: Extreme diversity SO JOURNAL OF IMMUNOLOGY LA English DT Editorial Material ID VARIABLE REGION; VARIABILITY; GENES; DNA C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Gearhart, PJ (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM gearhartp@grc.nia.nih.gov NR 9 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 OCT 1 PY 2006 VL 177 IS 7 BP 4235 EP 4236 PG 2 WC Immunology SC Immunology GA 088BV UT WOS:000240787400001 PM 16982852 ER PT J AU Leslie, A Price, DA Mkhize, P Bishop, K Rathod, A Day, C Crawford, H Honeyborne, I Asher, TE Luzzi, G Edwards, A Rosseau, CM Mullins, JI Tudor-Williams, G Novelli, V Brander, C Douek, DC Kiepiela, P Walker, BD Goulder, PJR AF Leslie, Alasdair Price, David A. Mkhize, Pamela Bishop, Karen Rathod, Almas Day, Cheryl Crawford, Hayley Honeyborne, Isobella Asher, Tedi E. Luzzi, Graz Edwards, Anne Rosseau, Christine M. Mullins, James I. Tudor-Williams, Gareth Novelli, Vas Brander, Christian Douek, Daniel C. Kiepiela, Photini Walker, Bruce D. Goulder, Philip J. R. TI Differential selection pressure exerted on HIV by CTL targeting identical epitopes but restricted by distinct HLA alleles from the same HLA supertype SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-LYMPHOCYTE RESPONSES; IMMUNODEFICIENCY-VIRUS TYPE-1; CELL RESPONSES; TRANSGENIC MICE; ESCAPE; RECOGNITION; IMMUNODOMINANCE; INFECTION; POLYMORPHISM; SPECIFICITY AB HLA diversity is seen as a major challenge to CTL vaccines against HIV. One current approach focuses on "promiscuous" epitopes, presented by multiple HLA alleles from within the same HLA supertype. However, the effectiveness of such supertype vaccines depends upon the functional equivalence of CTL targeting a particular epitope, irrespective of the restricting HLA. In this study, we describe the promiscuous HIV-specific CTL epitopes presented by alleles within the B7 supertype. Substantial differences were observed in the ability of CTL to select for escape mutation when targeting the same epitope but restricted by different HLA. This observation was common to all six promiscuous B7 epitopes identified. Moreover, with one exception, there were no significant differences in the frequency, magnitude, or immunodominance of the CTL responses restricted by different HLA alleles to explain these discrepancies. This suggests that the unique peptide/MHC complexes generated by even closely related HLA induce CTL responses that are qualitatively different. This hypothesis is supported by additional differences observed between CTL targeting identical epitopes but restricted by different HLA: first, the occurrence of distinct, HLA-specific escape mutation; second, the recruitment of distinct TCR repertoires by particular peptide/MHC complexes; and, third, significant differences in the functional avidity of CTL. Taken together, these data indicate that significant functional differences exist between CTL targeting identical epitopes but restricted by different, albeit closely related HLA. These findings are of relevance to vaccine approaches that seek to exploit HLA supertypes to overcome the problem of HLA diversity. C1 Nuffield Dept Med, Dept Paediat, Oxford, England. NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, ZA-4001 Durban, South Africa. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. High Wycombe Gen Hosp, Dept Genitourinary Med, High Wycombe, Bucks, England. Radcliffe Infirm Hosp, Harrison Clin, Oxford, England. Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. St Marys Hosp, Imperial Coll Sch Med, London, England. Great Ormond St Hosp Children, London WC1N 3JH, England. RP Leslie, A (reprint author), Univ Oxford, Dept Paediat, Peter Medawar Bldg,S Parks Rd, Oxford OX1 3SY, England. EM alleslie8@yahoo.co.uk RI Price, David/C-7876-2013; Day, Cheryl/J-9844-2012; OI Price, David/0000-0001-9416-2737; Bishop, Karen/0000-0003-4935-7708 FU Medical Research Council [G108/441]; NIAID NIH HHS [2R01 AI 46995-06, N01 AI 15422]; Wellcome Trust NR 49 TC 60 Z9 61 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 OCT 1 PY 2006 VL 177 IS 7 BP 4699 EP 4708 PG 10 WC Immunology SC Immunology GA 088BV UT WOS:000240787400058 PM 16982909 ER PT J AU Card, JW Carey, MA Bradbury, JA Graves, JP Lih, FB Moorman, MP Morgan, DL DeGraff, LM Zhao, Y Foley, JF Zeldin, DC AF Card, Jeffrey W. Carey, Michelle A. Bradbury, J. Alyce Graves, Joan P. Lih, Fred B. Moorman, Michael P. Morgan, Daniel L. DeGraff, Laura M. Zhao, Yun Foley, Julie F. Zeldin, Darryl C. TI Cyclooxygenase-1 overexpression decreases basal airway responsiveness but not allergic inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYNTHASE-DEFICIENT MICE; INHALED PGE(2); INDUCED BRONCHOCONSTRICTION; PROSTAGLANDIN E-2; LUNG; ASTHMA; LIPOPOLYSACCHARIDE; EXPRESSION; PROSTACYCLIN; INHIBITORS AB Pharmacological inhibition or genetic disruption of cyclooxygenase (COX)-1 or COX-2 exacerbates the inflammatory and functional responses of the lung to environmentally relevant stimuli. To further examine the contribution of COX-derived eicosanoids to basal lung function and to allergic lung inflammation, transgenic (Tr) mice were generated in which overexpression of human COX-1 was targeted to airway epithelium. Although no differences in basal respiratory or lung mechanical parameters were observed, COX-1 Tr mice had increased bronchoalveolar lavage fluid PGE(2) content compared with wild-type littermates (23.0 +/- 3.6 vs 8.4 +/- 1.4 pg/ml; p < 0.05) and exhibited decreased airway responsiveness to inhaled methacholine. In an OVA-induced allergic airway inflammation model, comparable up-regulation of COX-2 protein was observed in the lungs of allergic wild-type and COX-1 Tr mice. Furthermore, no genotype differences were observed in allergic mice in total cell number, eosinophil content (70 vs 76% of total cells, respectively), and inflammatory cytokine content of bronchoalveolar lavage fluid, or in airway responsiveness to inhaled methacholine (p > 0.05). To eliminate the presumed confounding effects of COX-2 up-regulation, COX-1 Tr mice were bred into a COX-2 null background. In these mice, the presence of the COX-1 transgene did not alter allergen-induced inflammation but significantly attenuated allergen-induced airway hyperresponsiveness, coincident with reduced airway leukotriene levels. Collectively, these data indicate that COX-1 overexpression attenuates airway responsiveness under basal conditions but does not influence allergic airway inflammation. C1 NIEHS, NIH, Div Intramural Res, Res Triangle Pk, NC 27709 USA. RP Zeldin, DC (reprint author), NIEHS, NIH, Div Intramural Res, 111 TW Alexander Dr,Bldg 101,Room D236, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov FU Intramural NIH HHS [Z01 ES025043-08]; NICHD NIH HHS [R03 HD053229, N01 HD 53229]; NIDCR NIH HHS [N01 DE 12634] NR 30 TC 16 Z9 16 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 OCT 1 PY 2006 VL 177 IS 7 BP 4785 EP 4793 PG 9 WC Immunology SC Immunology GA 088BV UT WOS:000240787400068 PM 16982919 ER PT J AU Meletiadis, J Petraitis, V Petraitiene, R Lin, P Stergiopoulou, T Kelaher, AM Sein, T Schaufele, RL Bacher, J Walsh, TJ AF Meletiadis, Joseph Petraitis, Vidmantas Petraitiene, Ruta Lin, Pengxin Stergiopoulou, Theodouli Kelaher, Amy M. Sein, Tin Schaufele, Robert L. Bacher, John Walsh, Thomas J. TI Triazole-polyene antagonism in experimental invasive pulmonary aspergillosis: In vitro and in vivo correlation SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID LIPOSOMAL AMPHOTERICIN-B; PERSISTENTLY NEUTROPENIC RABBITS; DRUG-INTERACTION MODELS; COMBINATION THERAPY; PLASMA PHARMACOKINETICS; ANTIFUNGAL THERAPY; ITRACONAZOLE; EFFICACY; RAVUCONAZOLE; AGENTS AB Combination antifungal therapy is increasingly used in the treatment of invasive aspergillosis. Whether the interaction between amphotericin B and triazoles is antagonistic against invasive aspergillosis is a controversial issue that is not likely to be resolved through a randomized clinical trial. Here, we found both in vitro and in vivo antagonism between liposomal amphotericin B and ravuconazole in simultaneous treatment of experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits. Bliss independence-based drug-interaction modeling showed significant antagonism in vitro and in vivo, with the observed drug effects being 20%-69% lower than would be expected if the drugs were acting independently. These in vitro and in vivo findings of antagonism were consistent with the findings from Loewe additivity-based drug-interaction modeling. No pharmacokinetic interaction was found. The combination of a triazole and polyene may be antagonistic in the treatment of invasive pulmonary aspergillosis. C1 NCI, Ctr Canc Res, Pediat Oncol Branch, Immunocompromised Host Sect,NIH, Bethesda, MD 20892 USA. NIH, Surg Serv, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Frederick, MD USA. RP Walsh, TJ (reprint author), NCI, Ctr Canc Res, Pediat Oncol Branch, Immunocompromised Host Sect,NIH, 1-5750, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov FU Intramural NIH HHS NR 45 TC 60 Z9 62 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 1 PY 2006 VL 194 IS 7 BP 1008 EP 1018 DI 10.1086/506617 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 081LE UT WOS:000240318300019 PM 16960790 ER PT J AU Hodge, DL Subleski, JJ Reynolds, DA Buschman, MD Schill, WB Burkett, MW Malyguine, AM Young, HA AF Hodge, Deborah L. Subleski, Jeff J. Reynolds, Della A. Buschman, Matthew D. Schill, William B. Burkett, Mark W. Malyguine, Anatoli M. Young, Howard A. TI The proinflammatory cytokine interleukin-18 alters multiple signaling pathways to inhibit natural killer cell death SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID GAMMA-INDUCING FACTOR; NF-KAPPA-B; NECROSIS-FACTOR RECEPTOR; HUMAN NK CELLS; GRANZYME-B; CYTOTOXIC LYMPHOCYTES; INTERFERON-GAMMA; FAS LIGAND; MEDIATED CYTOTOXICITY; DNA FRAGMENTATION AB The proinflammatory cytokine, interleukin-18 (IL-18), is a natural killer (NK) cell activator that induces NK cell cytotoxicity and interferon-gamma (IFN-gamma) expression. In this report, we define a novel role for IL-18 as an NK cell protective agent. Specifically, IL-18 prevents NK cell death initiated by different and distinct stress mechanisms. IL-18 reduces NK cell self-destruction during NK-targeted cell killing, and in the presence of staurosporin, a potent apoptotic inducer, IL-18 reduces caspase-3 activity. The critical regulatory step in this process is downstream of the mitochondrion and involves reduced cleavage and activation of caspase-9 and caspase-3. The ability of IL-18 to regulate cell survival is not limited to a caspase death pathway in that IL-18 augments tumor necrosis factor (TNF) signaling, resulting in increased and prolonged mRNA expression of c-apoptosis inhibitor 2 (cIAP2), a prosurvival factor and caspase-3 inhibitor, and TNF receptor-associated factor 1 (TRAF1), a prosurvival protein. The cumulative effects of IL-18 define a novel role for this cytokine as a molecular survival switch that functions to both decrease cell death through inhibition of the mitochondrial apoptotic pathway and enhance TNF induction of prosurvival factors. C1 NCI, Expt Immunol Lab, Canc Res Ctr, Frederick, MD 21702 USA. US Geol Survey, Natl Fish Hlth Res Lab, Leetown Sci Ctr, Kearneysville, WV 25430 USA. Sci Applicat Int Corp, Clin Serv Program, Ft Detrick, MD 21702 USA. RP Young, HA (reprint author), NCI, Expt Immunol Lab, Canc Res Ctr, 560 Chandler St,Room 31-93, Frederick, MD 21702 USA. EM youngh@ncifcrf.gov RI Young, Howard/A-6350-2008; OI Young, Howard/0000-0002-3118-5111; Schill, William/0000-0002-9217-984X FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 54 TC 15 Z9 18 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD OCT PY 2006 VL 26 IS 10 BP 706 EP 718 DI 10.1089/jir.2006.26.706 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 094XL UT WOS:000241272400002 PM 17032165 ER PT J AU Liang, C Morris, A Schlucker, S Imoto, K Price, VH Menefee, E Wincovitch, SM Levin, IW Tamura, D Strehle, KR Kraemer, KH DiGiovanna, JJ AF Liang, Christine Morris, Andrea Schluecker, Sebastian Imoto, Kyoko Price, Vera H. Menefee, Emory Wincovitch, Stephen M. Levin, Ira W. Tamura, Deborah Strehle, Katrin R. Kraemer, Kenneth H. DiGiovanna, John J. TI Structural and molecular hair abnormalities in trichothiodystrophy SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID DEFICIENT BRITTLE HAIR; BASAL TRANSCRIPTION; DIALKYL DISULFIDES; DNA-REPAIR; CONFORMATIONS; VIBRATIONS AB We examined hair from 15 patients with trichothiodystrophy (TTD), a rare inherited disorder with brittle, cystine-deficient hair. They had a wide variety of phenotypes, from brittle hair only to severe intellectual impairment and developmental delay. Polarizing light microscopic examination showed alternating light and dark (tiger tail) bands under polarizing microscopy. Confocal microscopy captured structural features of breaks in intact TTD hairs. The autofluorescent appearance was regular and smooth in normal donors and markedly irregular in sections of TTD hairs possibly reflecting abnormalities in melanin distribution. Scanning electron microscopy revealed numerous surface irregularities. All TTD hair samples had reduced sulfur content. We observed an inverse correlation (R-val=0.9) between sulfur content and percent of hairs with shaft abnormalities (trichoschisis, trichorrhexis nodosa, or ribbon/twist). There was no association between clinical disease severity and percent of abnormal hairs. Raman spectra of hairs from TTD patients and normal donors revealed a larger contribution of energetically less favored disulfide conformers in TTD hairs. Our data indicate that the brittleness of the TTD hair is dependent upon abnormalities at several levels of organization. These changes make TTD hairs excessively prone to breakage and weathering. C1 NCI, Basic Res Labs, DNA Repair Sect, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Brown Med Sch, Dept Dermatol, Div Dermatopathol, Providence, RI USA. Howard Hughes Med Inst, Res Scholars Program, NIH, Bethesda, MD 20817 USA. NIDDKD, Phys Chem Lab, NIH, Bethesda, MD USA. Univ Wurzburg, Inst Chem Phys, Wurzburg, Germany. Univ Calif San Francisco, Hair Res Ctr, Dept Dermatol, San Francisco, CA 94143 USA. NCI, CCR Confocal Microscopy Core Facil, Expt Carcinogenesis Lab, NIH, Bethesda, MD USA. RP Kraemer, KH (reprint author), NCI, Basic Res Labs, DNA Repair Sect, Ctr Canc Res,NIH, Bldg 37 Room 4002 MSC 4258, Bethesda, MD 20892 USA. EM kraemerk@nih.gov RI Schlucker, Sebastian/D-1031-2010 OI Schlucker, Sebastian/0000-0003-4790-4616 FU Intramural NIH HHS [Z01 BC004517-31] NR 18 TC 29 Z9 30 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2006 VL 126 IS 10 BP 2210 EP 2216 DI 10.1038/sj.jid.5700384 PG 7 WC Dermatology SC Dermatology GA 096EE UT WOS:000241359400012 PM 16728971 ER PT J AU Olasz, E Roh, J Yee, C Arita, K Akiyama, M Shimizu, H Vogel, J Yancey, KB AF Olasz, Edit Roh, Jooyoung Yee, Carole Arita, Ken Akiyama, Masashi Shimizu, Hiroshi Vogel, Jonathan Yancey, Kim B. TI Human bullous pemphigoid antigen 2 transgenic skin elicits specific IgG in wild type mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the European-Society-of-Dermatology-Research (ESDR) CY SEP 06-07, 2006 CL Paris, FRANCE SP European Soc Dermatol Res C1 Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA. NCI, DCS, Dermatol Branch, NIH, Bethesda, MD USA. Hokkaido Univ, Grad Sch Med, Dept Dermatol, Sapporo, Hokkaido, Japan. EM kyancey@mcw.edu NR 0 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2006 VL 126 IS 10 BP 2351 EP 2351 PG 1 WC Dermatology SC Dermatology GA 096EE UT WOS:000241359400037 ER PT J AU Rosenberg, HF Oppenheim, JJ AF Rosenberg, Helene F. Oppenheim, Joost J. TI Interview with Dr. Yoshiro Kobayashi regarding Pivotal Advance: A suppressive role of nitric oxide in MIP-2 production by macrophages upon coculturing with apoptotic cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material ID ACTIVATING FACTOR; HYBRIDOMA; IDENTIFICATION; LYMPHOTOXIN C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NCI, Mol Immunoregulat Lab, NIH, Frederick, MD 21701 USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov NR 10 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD OCT PY 2006 VL 80 IS 4 BP 742 EP 743 DI 10.1189/jlb.1306012 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 119MI UT WOS:000243016000013 ER PT J AU Someya, A Moss, J Nagaoka, I AF Someya, Akimasa Moss, Joel Nagaoka, Isao TI Involvement of a guanine nucleotide-exchange protein, ARF-GEP(100)/BRAG2a, in the apoptotic cell death of monocytic phagocytes SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE apoptosis; GEF; Sec7 domain; macrophages; siRNA ID ADP-RIBOSYLATION FACTOR; RECEPTOR-MEDIATED PHAGOCYTOSIS; HOMOLOGY DOMAINS; FACTOR ARF; SEC7; CYTOHESIN-1; MACROPHAGES; MEMBRANE; FACTOR-6; REQUIREMENT AB We previous identified adenosine 5'-diphosphate-ribosylation factor (ARF)-guanine nucleotide-exchange protein, 100 kDa (GEP(100)), as a novel GEP with a molecular size of similar to 100 kDa, which preferentially activates ARF6. In this study, we examined the effect of ARF-GEP(100) on monocytic cell apoptosis. Overexpression of ARF-GEP(100) in PMA-differentiated human monocyte-macrophage-like U937 cells and mouse macrophage RAW264.7 cells induced apoptotic cell death, which was detected by morphological changes (chromatin condensation, nucleus fragmentation, and shrinking of cytoplasm), annexin V-staining, and TUNEL assay. It is interesting that a mutant lacking the Sec7 domain, which is responsible for ARF activation, was able to induce apoptosis of the target cells to the level of that of a wild-type ARF-GEP(100). Furthermore, ARF-GEP(100)-silencing experiments indicated that the TNF-alpha-induced apoptosis was significantly suppressed among ARF-GEP(100)-depressed cells. These observations apparently suggest that ARF-GEP(100) is involved in the induction of apoptosis in monocytic phagocytes, possibly independent of ARF activation. C1 Juntendo Univ, Sch Med, Dept Host Def & Biochem Res, Bunkyo Ku, Tokyo 1138421, Japan. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Someya, A (reprint author), Juntendo Univ, Sch Med, Dept Host Def & Biochem Res, Bunkyo Ku, 2-1-1 Hongo, Tokyo 1138421, Japan. EM someya@med.juntendo.ac.jp NR 28 TC 3 Z9 3 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD OCT PY 2006 VL 80 IS 4 BP 915 EP 921 DI 10.1189/jlb.0106059 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 119MI UT WOS:000243016000032 PM 16877676 ER PT J AU Xu, S Shen, J AF Xu, Su Shen, Jun TI In vivo dynamic turnover of cerebral C-13 isotopomers from [U-(13) C]glucose SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE brain; C-13 MRS; isotopomer; INEPT; glutamate-glutamine cycle ID MAGNETIC-RESONANCE-SPECTROSCOPY; TRICARBOXYLIC-ACID CYCLE; RAT-BRAIN; NMR-SPECTROSCOPY; NEUROTRANSMITTER GLUTAMATE; ENERGY-METABOLISM; CARBON FLUX; 11.7 TESLA; MRS; HEART AB An INEPT-based C-13 MRS method and a cost-effective and widely available 11.7 Tesla 89-mm bore vertical magnet were used to detect dynamic C-13 isotopomer turnover from intravenously infused [U-C-13]glucose in a 211 mu L voxel located in the adult rat brain. The INEPT-based H-1 -> C-13 polarization transfer method is mostly adiabatic and therefore minimizes signal loss due to 131 inhomogeneity of the surface coils used. High quality and reproducible data were acquired as a result of combined use of outer volume suppression, ISIS, and the single-shot three-dimensional localization scheme built in the INEPT pulse sequence. Isotopomer patterns of both glutamate C4 at 34.00 ppm and glutamine C4 at 31.38 ppm are dominated first by a doublet originated from labeling at C4 and C5 but not at C3 (with (1)J(C4C5) = 51 Hz) and then by a quartet originated from labeling at C3, C4, and C5 (with (1)J(C3C4) = 35 Hz). A lag in the transition of glutamine C4 pattern from doublet-dominance to quartet dominance as compared to glutamate C4 was observed, which provides independent verification of the precursor-product relationship between neuronal glutamate and glial glutamine and a significant inter-compartmental cerebral glutamate-glutamine cycle between neurons and glial cells. Published by Elsevier Inc. C1 Natl Inst Mental Hlth, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Shen, J (reprint author), Natl Inst Mental Hlth, Mol Imaging Branch, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov FU Intramural NIH HHS NR 43 TC 18 Z9 18 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 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD OCT PY 2006 VL 182 IS 2 BP 221 EP 228 DI 10.1016/j.jmr.2006.07.003 PG 8 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 093XP UT WOS:000241203900006 PM 16859940 ER PT J AU Avdievich, NI Peshkovsky, AS Kennan, RP Hetherington, HP AF Avdievich, Nikolai I. Peshkovsky, Alexey S. Kennan, Richard P. Hetherington, Hoby P. TI SENSE imaging with a quadrature half-volume transverse electromagnetic (TEM) coil at 4T SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE SENSE imaging; half-volume coil; TEM coil; high-field MRI; reduction of power deposition ID ARRAY; MRI AB Purpose: To demonstrate the feasibility of high-field SENSE imaging of large objects, such as the human head, using a semicircular (half-volume) coil for both transmission and multi-channel reception. Materials and Methods: As a proof of concept, we present experimental data obtained using a seven-element half-volume (180 degrees of arc) transmit/receive quadrature transverse electromagnetic (TEM) coil. SENSE images of the human brain were acquired with a reduction factor of R = 2, using two degenerate linear modes of the same coil as independent receive channels at 4T. Since the need for additional hardware (i.e., a separate set of receive coils) is eliminated, the design can be substantially simplified. Results: The experimental data demonstrate that linear modes of the half-volume TEM coil have essentially no noise correlation, and their sensitivity profiles satisfy the requirement for small g-factors. Also, this type of coil provides efficient transmission with a relatively large uniform region and a reception profile that is more uniform than that of the surface coils. Conclusion: We demonstrate the feasibility of SENSE imaging using a half-volume coil. Half-volume coils allow reduced total power deposition compared to full-volume coils, and may replace the latter in body imaging applications in which the target region of interest (ROI) is smaller than the entire torso. C1 Albert Einstein Coll Med, NIA, Dept Radiol, Gruss MRRC, Bronx, NY 10461 USA. Gruss Magnet Resonance Res Ctr, Bronx, NY USA. Albert Einstein Coll Med, Dept Med, Div Hematol, Bronx, NY 10461 USA. RP Avdievich, NI (reprint author), Albert Einstein Coll Med, NIA, Dept Radiol, Gruss MRRC, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM navdievi@aecom.yu.edu FU NCRR NIH HHS [M01-RR12248]; NIBIB NIH HHS [R01-EB00473] NR 20 TC 1 Z9 1 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD OCT PY 2006 VL 24 IS 4 BP 934 EP 938 DI 10.1002/jmri.20714 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 089LL UT WOS:000240882000029 PM 16958065 ER PT J AU Espinoza, J Romero, R Nien, JK Kusanovic, JP Richani, K Gomez, R Kim, CJ Mittal, P Gotsh, F Erez, O Chaiworapongsa, T Hassan, S AF Espinoza, Jimmy Romero, Roberto Nien, Jyh Kae Kusanovic, Juan Pedro Richani, Karina Gomez, Ricardo Kim, Chong Jai Mittal, Pooja Gotsh, Francesca Erez, Offer Chaiworapongsa, Tinnakorn Hassan, Sonia TI A role of the anti-angiogenic factor sVEGFR-1 in the 'mirror syndrome' (Ballantyne's syndrome) SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE mirror syndrome; Ballantyne's syndrome; sVEGFR-1; preeclampsia; villous edema ID MATERNAL SYNDROME; ISO-IMMUNIZATION; HYDROPS FOETALIS; TRIPLE EDEMA; FETAL-DEATH; PREECLAMPSIA; PREGNANCY; REVERSAL; PATHOPHYSIOLOGY; HYPERTENSION AB Background. 'Mirror syndrome' (Ballantyne's syndrome) refers to the association of fetal hydrops with placentomegaly and severe maternal edema. Preeclampsia occurs in approximately 50% of these cases. Soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), an anti-angiogenic factor, has been implicated in the pathophysiology of preeclampsia ( PE). Objective. The objective of this study was to determine if the maternal plasma concentration of sVEGFR-1 is elevated in patients with mirror syndrome. Study design. This case-control study included patients with uncomplicated pregnancies (n = 40) and those with mirror syndrome ( n 4) matched for gestational age. Mirror syndrome was defined as fetal hydrops and severe maternal edema. Maternal plasma sVEGFR-1 concentrations were determined using specific enzyme-linked immunosorbent assays. Immunohistochemistry of sVEGFR-1 on villous trophoblasts was also performed in samples from one patient with mirror syndrome and compared with those from a patient with spontaneous preterm delivery matched for gestational age. Nonparametric statistics were used for analysis (p < 0.05). Results. ( 1) The median maternal plasma concentration of sVEGFR-1 was significantly higher in patients with mirror syndrome than in the control group ( median: 3974 pg/mL, range: 3083-10 780 vs. median: 824 pg/mL, range: 260-4712, respectively; p < 0.001). ( 2) All patients with mirror syndrome had sVEGFR-1 concentrations above the 95(th) percentile for gestational age. Syncytiotrophoblast, especially syncytial knots, showed strong staining with antibodies against sVEGFR-1 in placental samples from the patient with mirror syndrome, but not in those from the patient with spontaneous preterm delivery. Conclusion. High maternal plasma concentrations of sVEGFR-1 were observed in mirror syndrome. We propose that this anti-angiogenic factor may participate in the pathophysiology of this syndrome. Thus, maternal plasma determination of sVEGFR-1 may help to identify the hydropic fetus that places the mother at risk for preeclampsia. C1 Wayne State Univ, Sch Med, NICHD, Perinatol Res Branch,US Dept DHHS,NIH, Detroit, MI 48201 USA. NICHD, Perinatol Res Branch, US Dept HHS, NIH, Bethesda, MD USA. Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI USA. Wayne State Univ, Ctr Mol Med 7 Genet, Detroit, MI USA. Hosp Dr Sotero del Rio, Dept Obstet & Gynecol, CEDIP, Puente Alto, Chile. Wayne State Univ, Hutzel Womens Hosp, Dept Pathol, Detroit, MI USA. RP Romero, R (reprint author), Wayne State Univ, Sch Med, NICHD, Perinatol Res Branch,US Dept DHHS,NIH, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov FU Intramural NIH HHS NR 30 TC 53 Z9 58 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD OCT PY 2006 VL 19 IS 10 BP 607 EP 613 DI 10.1080/14767050600922677 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 119DI UT WOS:000242992000003 PM 17118734 ER PT J AU Pras, E Mahler, O Kumar, V Frydman, M Gefen, N Pras, E Hejtmancik, JF AF Pras, E. Mahler, O. Kumar, V. Frydman, M. Gefen, N. Pras, E. Hejtmancik, J. F. TI A new locus for autosomal dominant posterior polar cataract in Moroccan Jews maps to chromosome 14q22-23 SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID ALPHA-B-CRYSTALLIN; SUBCAPSULAR LENS OPACITIES; HEAT-SHOCK PROTEIN; TRANSCRIPTION FACTORS; EPITHELIAL-CELLS; MUTATION; ACTIN; EYE; HUMANS; GENES AB Background: Posterior polar cataract is a clinically distinctive opacity located at the back of the lens. It is commonly acquired in age related cataract, and may infrequently occur in pedigrees with congenital cataract. To date, five loci for autosomal dominant congenital posterior polar cataract have been identified. These include two genes, CRYAB and PITX3, on chromosomes 11q and 10q respectively, and three loci with as yet unknown genes on chromosomes 1p, 16q and 20p. Purpose: To find the chromosomal location of a gene causing autosomal dominant congenital posterior polar cataract in three Moroccan Jewish families. Methods: A whole genome scan was performed using microsatellite markers spaced at approximately 10 cM intervals. For fine mapping, five additional microsatellite markers were genotyped. Two-point lod scores were calculated using MLINK software, from the LINKAGE program package. After linkage was established, several positional candidate genes were assessed by PCR based DNA sequencing. Results: The new cataract locus was mapped to an 11.3 cM interval between D14S980 and D14S1069 on chromosome 14q22-23. A maximum two point lod score of 5.19 at h=0 was obtained with the markersD14S274. The positional and functional candidate genes SIX1, SIX4, SIX6, OTX2, and ARHJ were excluded as the cause of cataract in these families. Conclusion: An as yet unidentified gene associated with posterior polar cataract maps to the long arm of chromosome 14q22-23. C1 Kaplan Med Ctr, Dept Opthalmol, Rehovot, Israel. NEI, NIH, Ophtjal Genet & Vis Funct Branch, Bethesda, MD 20892 USA. Danek Gartener Inst Human Genet, Sheba Med Ctr, Tel Hashomer, Israel. Sapir Med Ctr, Dept Ophthalmol, Kefar Sava, Israel. RP Pras, E (reprint author), Assaf Harofeh Med Ctr, Dept Ophthalmol, IL-70300 Zerifin, Israel. EM eranpras@gmail.com NR 30 TC 7 Z9 8 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD OCT PY 2006 VL 43 IS 10 AR e50 DI 10.1136/jmg.2005.034876 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 100UD UT WOS:000241693600011 PM 17047090 ER PT J AU Kwak, J Lee, DH Park, YD Kim, SB Maeng, JS Oh, HW Park, HY Bae, KS AF Kwak, Jangyul Lee, Dong-Hun Park, Youn-Dong Kim, Seung Bum Maeng, Jin-Soo Oh, Hyun Woo Park, Ho-Yong Bae, Kyung Sook TI Polyphasic assignment of a highly proteolytic bacterium isolated from a spider to Serratia proteamaculans SO JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE Serratia proteamaculans; protease; phylogeny; spider ID ZEALAND GRASS GRUB; MOLECULAR CHARACTERIZATION; PHOTORHABDUS-LUMINESCENS; COSTELYTRA-ZEALANDICA; PHYLOGENETIC TREES; AMBER DISEASE; MARCESCENS; PURIFICATION; PROTEASE; GENE AB A bacterial strain named HY-3 that produces a highly active extracellular protease was isolated from the digestive tract of a spider, Nephila clavata. The bacterium was a Gram-negative, oxidase-negative, catalase-positive, nonhalophilic, nitrate-reducing, facultative anaerobe. Transmission and scanning electron microscopies demonstrated that the isolate was non-spore-forming, straight, rod-shaped, and motile by peritrichous flagella. The G+C content of the DNA was 57.0 mol%. The isoprenoid quinone type was ubiquinone with 8 isoprene units (Q-8). The morphological and biochemical characteristics including the predominant fatty acid and phospholipids profiles placed the isolate HY-3 in the family Enterobacteriaceae. Further biochemical characterization and phylogenetic studies including determination of an almost complete 16S ribosomal DNA sequence suggested that the bacterium was closely related to the genus Serratia. DNA-DNA hybridization analysis revealed that this extracellular protease-producing strain belongs to Serratia proteamaculans, which is also known for its association with insects. C1 Korea Res Inst Biosci & Biotechnol, Insect Resources Res Ctr, Taejon 305806, South Korea. Chungbuk Natl Univ, Sch Life Sci, Chungbuk 361763, South Korea. Chungnam Natl Univ, Dept Microbiol, Taejon 305764, South Korea. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Bae, KS (reprint author), Korea Res Inst Biosci & Biotechnol, Insect Resources Res Ctr, Taejon 305806, South Korea. EM ksbae@kribb.re.kr NR 46 TC 4 Z9 4 U1 1 U2 2 PU KOREAN SOC MICROBIOLOGY & BIOTECHNOLOGY PI SEOUL PA KOREA SCI TECHNOL CENTER #507, 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1017-7825 J9 J MICROBIOL BIOTECHN JI J. Microbiol. Biotechnol. PD OCT PY 2006 VL 16 IS 10 BP 1537 EP 1543 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 100QB UT WOS:000241682500008 ER PT J AU Yingling, YG Shapiro, BA AF Yingling, Yaroslava G. Shapiro, Bruce A. TI The prediction of the wild-type telomerase RNA pseudoknot structure and the pivotal role of the bulge in its formation SO JOURNAL OF MOLECULAR GRAPHICS & MODELLING LA English DT Article DE telomerase; RNA; molecular dynamics; theoretical prediction; pseudoknot ID MOLECULAR-DYNAMICS SIMULATIONS; EXPLICIT SOLVENT SIMULATIONS; GENERALIZED BORN MODELS; DYSKERATOSIS-CONGENITA; NUCLEIC-ACIDS; REVERSE-TRANSCRIPTASE; CONTINUUM SOLVENT; IN-VIVO; PROTEIN; MUTATIONS AB In this study, the three-dimensional structure of the wild-type human telomerase RNA pseudoknot was predicted via molecular modeling. The wild-type pseudoknot structure is then compared to the recent NMR solution structure of the telomerase pseudoknot, which does not contain the U177 bulge. The removal of the bulge from the pseudoknot structure results in higher stability and significant reduction of activity of telomerase. We show that the effect of the bulge on the structure results in a significant transformation of the pseudoknot junction region where the starting base pairs are disrupted and unique triple base pairs are formed. We found that the formation of the junction region is greatly influenced by interactions of the U177 bulge with loop residues and rotation of residue A174. Moreover, this is the first study to our knowledge where a structure as complex as the pseudoknot has been solved by purely theoretical methods. Published by Elsevier Inc. C1 NCI, Ctr Canc Res, Nanobiol Program, NIH, Frederick, MD 21702 USA. RP Shapiro, BA (reprint author), NCI, Ctr Canc Res, Nanobiol Program, NIH, Bldg 469,Room 150, Frederick, MD 21702 USA. EM bshapiro@ncifcrf.gov RI Yingling, Yaroslava/B-2901-2008 OI Yingling, Yaroslava/0000-0002-8557-9992 FU Intramural NIH HHS NR 55 TC 25 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1093-3263 J9 J MOL GRAPH MODEL JI J. Mol. Graph. PD OCT PY 2006 VL 25 IS 2 BP 261 EP 274 DI 10.1016/j.jmgm.2006.01.003 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Crystallography; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology GA 101BD UT WOS:000241713000010 PM 16481205 ER PT J AU Kanungo, J Li, BS Zheng, YL Pant, HC AF Kanungo, Jyotshnabala Li, Bing-Sheng Zheng, Yali Pant, Harish C. TI Cyclin-dependent kinase 5 influences Rohon-Beard neuron survival in zebrafish SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoptosis; cyclin-dependent kinase 5; Rohon-Beard neuron; siRNA; zebrafish ID PROGRAMMED CELL-DEATH; NERVOUS-SYSTEM; XENOPUS-LAEVIS; IN-VIVO; REGULATORY SUBUNIT; NEURITE OUTGROWTH; SUBSTANTIA-NIGRA; AXONAL-TRANSPORT; CDK5; P35 AB Cyclin-dependent kinase 5 (cdk5), a member of the cyclin-dependent kinase family, is expressed predominantly in post-mitotic cell populations. Unlike the other cdks, cdk5 is abundant and most active in differentiated neurons. Here, we describe the function of a cdk5 ortholog in zebrafish. Cdk5 catalytic activity is meager but present in early stages of development. However, at 24 h post-fertilization (hpf), the activity is remarkably higher and continues to be high through 48 and 72 hpf. Knocking down cdk5 by micro-injection of a specific siRNA resulted in decreased cdk5 protein level accompanied by reduced kinase activity. In the cdk5 siRNA-injected embryos, the number of primary sensory Rohon-Beard (RB) neurons was significantly reduced and there were more apoptotic cells in the brain. These phenotypes were rescued by co-injection of cdk5 mRNA. Within the first two days of development, RB neurons undergo apoptosis in zebrafish. To examine whether cdk5 has a role in RB neuron survival, cdk5 mRNA was injected into the one- to two-cell embryos. In these embryos, RB neuron apoptosis was inhibited compared with the uninjected control embryos. These results suggest that in zebrafish, cdk5 influences RB neuron survival and potentially regulates early neuronal development. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Pant, HC (reprint author), NINDS, Neurochem Lab, NIH, Bldg 49,Rm 2A28,9000 Rockville Pike, Bethesda, MD 20892 USA. EM panth@ninds.nih.gov FU Intramural NIH HHS NR 48 TC 13 Z9 14 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2006 VL 99 IS 1 BP 251 EP 259 DI 10.1111/j.1471-4159.2006.04114.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 084IW UT WOS:000240527600023 PM 16911583 ER PT J AU Kirvan, CA Swedo, SE Snider, LA Cunningham, MW AF Kirvan, Christine A. Swedo, Susan E. Snider, Lisa A. Cunningham, Madeleine W. TI Antibody-mediated neuronal cell signaling in behavior and movement disorders SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE streptococci; chorea; autoimmunity; behavior ID OBSESSIVE-COMPULSIVE SYMPTOMS; PROTEIN-KINASE-II; AUTOIMMUNE NEUROPSYCHIATRIC DISORDERS; STREPTOCOCCAL-M-PROTEINS; SYDENHAMS CHOREA; RHEUMATIC-FEVER; INTRAVENOUS IMMUNOGLOBULIN; PLASMA-EXCHANGE; BASAL GANGLIA; INFECTIONS AB Behavioral and movement disorders may have antibody responses where mimicry and signal transduction may lead to neuropsychiatric abnormalities. In our study, antibodies in pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS) reacted with the neuronal cell surface and caudate-putamen and induced calcium-calmodulin dependent protein (CaM) kinase II activity in neuronal cells. Depletion of serum IgG abrogated CaM kinase II cell signaling and reactivity of CSF was blocked by streptococcal antigen N-acetyl-beta-D-glucosamine (GlcNAc). Antibodies against GlcNAc in PANDAS sera were inhibited by lysoganglioside Gm,. Results suggest that antibodies from an infection may signal neuronal cells in some behavioral and movement disorders. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Oklahoma, Dept Microbiol & Immunol, HSC, Ctr Biomed Res, Oklahoma City, OK 73104 USA. Calif State Univ Sacramento, Dept Biol Sci, Sacramento, CA 95618 USA. NIMH, Pediat & Dev Neurospychiat Branch, NIH, US Dept HHS, Bethesda, MD 20814 USA. RP Cunningham, MW (reprint author), Univ Oklahoma, Dept Microbiol & Immunol, HSC, Ctr Biomed Res, 975 NE 10th St,Room 217, Oklahoma City, OK 73104 USA. EM madeleine-cunningham@ouhsc.edu FU NHLBI NIH HHS [HL56267, HL35280] NR 33 TC 78 Z9 79 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD OCT PY 2006 VL 179 IS 1-2 BP 173 EP 179 DI 10.1016/j.jneuroim.2006.06.017 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 102ON UT WOS:000241821800020 PM 16875742 ER PT J AU Griffith, C Bagnato, F Gupta, S Calabrese, A Oh, U Chiu, A Ohayon, JM McAuliffe, MJ Tasciyan, TA Jacobson, S AF Griffith, C. Bagnato, F. Gupta, S. Calabrese, A. Oh, U. Chiu, A. Ohayon, J. M. McAuliffe, M. J. Tasciyan, T. A. Jacobson, S. TI Brain volume measurements in patients with human T-cell lymphotropic virus-1-associated tropical spastic paraparesis SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE atrophy; brain; magnetic resonance imaging; spinal cord; tropical spastic paraparesis ID HTLV-1 ASSOCIATED MYELOPATHY; I-ASSOCIATED MYELOPATHY; MULTIPLE-SCLEROSIS; VIRUS TYPE-1; DISEASE; ATROPHY; ACCURATE; MRI; MS AB Human T-cell lymphotropic virus (HTLV)-1 is associated with a chronic progressive neurologic disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) that affects 0.2% to 3% of HTLV-1-infected people. The authors aimed at exploring, in vivo, whether brain volume reduction occurs in patients with HAM/TSP through the use of magnetic resonance imaging (MRI). T1 pre/postcontrast spin echo-weighted images (WIs) and T2WIs of the brain were obtained in 19 HAM/TSP patients and 14 age- and sex-matched healthy volunteers. Both patients and healthy individuals were imaged at a 1.5-Tesla magnet by employing a conventional head coil. Focal T1 and T2 abnormalities were calculated and two measurements of brain parenchyma fraction (BPF) were obtained by using SIENAx (Structural Image Evaluation, using Normalisation, of Atrophy; University of Oxford, Oxford, UK) and MIPAV (Medical Image Processing, Analysis, and Visualization; National Institutes of Health, Bethesda, USA) from T1WIs. No significant differences in BPF were found between patients and healthy subjects when using either SIENAx or MIPAV. Analysis of individual patients detected that BPF was lower by 1 standard deviation (SD) relative to patients' average BPF in one patient. The authors conclude that reductions in BPF do not occur frequently in patients with HAM/TSP. However, the authors believe that one individual case of significant brain atrophy raises the question as to whether atrophy selectively targets the spinal cord of HAM/TSP patients or may involve the brain as well. A larger patient population analyzing regional brain volume changes could be helpful in determining whether brain atrophy is a marker of disease in patients with HAM/TSP. C1 Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. New York Med Coll, Valhalla, NY USA. NIH, Biomed Imaging Res Serv Sect, Bethesda, MD 20892 USA. Med Numer Inc, Sterling, VA USA. RP Jacobson, S (reprint author), Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov NR 22 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2006 VL 12 IS 5 BP 349 EP 355 DI 10.1080/13550280600941665 PG 7 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 104VZ UT WOS:000241990000002 PM 17065127 ER PT J AU Khambalia, A Latulippe, ME Campos, C MerloS, C Villalpando, S Picciano, MF O'Connor, DL AF Khambalia, Amina Latulippe, Maria E. Campos, Cristina MerloS, Claide Villalpando, Salvador Picciano, Mary Frances O'Connor, Deborah L. TI Milk folate secretion is not impaired during iron deficiency in humans SO JOURNAL OF NUTRITION LA English DT Article ID SOLUBLE TRANSFERRIN RECEPTOR; QUALITY-OF-LIFE; LACTATING WOMEN; MATERNAL ANEMIA; PREGNANCY; INFANTS; FERRITIN; LEVEL; INDEX; RISK AB The purpose of this study was to examine whether maternal iron and/or folate status influences human milk folate secretion and is responsible for growth faltering of Otomi infants in Capulhuac, Mexico. Breast-feeding mothers (n = 71) were randomized at 22 +/- 13 d (baseline) postpartum to receive a daily multivitamin supplement containing folic acid (400 mu g) with and without iron (18 mg). Mothers provided blood and milk samples at baseline, and at 82 +/- 15 and 138 +/- 18 d postpartum. Iron supplementation significantly improved hematocrit and transferrin receptor concentrations but had no influence on maternal folate status or milk folate or iron concentrations. Forty-three percent of mothers (29/68) had low blood folate concentrations at baseline, whereas only 6% (4/66) had low blood folate concentrations at similar to 138 d postpartum. Milk folate concentrations did not differ between Fe-deficient and Fe-sufficient women and provided adequate levels of dietary folate by similar to 82 d postpartum. While milk iron concentrations were unrelated to maternal iron status, they decreased during lactation, and, by similar to 138 d, they provided only 55% of the current recommendation. In conclusion, milk folate concentrations appear to be well preserved during maternal iron deficiency; hence, faltering growth among infants in Capulhuac, Mexico is unlikely the result of reduced milk folate concentration secondary to maternal Fe deficiency. However, milk Fe concentrations showed a temporal decline. Whether the disjuncture between recommended and actual Fe intakes among infants born with low Fe reserves and weaned to foods low in bioavailable Fe has functional consequences is worthy of further investigation. C1 Hosp Sick Children, Dept Nutr Sci, Toronto, ON M5G 1X8, Canada. Univ Toronto, Toronto, ON M5G 1X8, Canada. Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP O'Connor, DL (reprint author), Hosp Sick Children, Dept Nutr Sci, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM deborah_l.o'connor@sickkids.ca OI Villalpando, Salvador/0000-0001-6429-3816 NR 49 TC 10 Z9 11 U1 0 U2 9 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD OCT PY 2006 VL 136 IS 10 BP 2617 EP 2624 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 089OH UT WOS:000240889600028 PM 16988136 ER PT J AU Kavanaugh, C Seifried, H Ellwood, K Yetley, E Swanson, C Milner, J AF Kavanaugh, Claudine Seifried, Harold Ellwood, Kathleen Yetley, Elizabeth Swanson, Christine Milner, John TI A research agenda for biomarkers as indicators of cancer risk reduction following dietary manipulation SO JOURNAL OF NUTRITION LA English DT Editorial Material C1 NCI, Div Canc Prevent, Rockville, MD 20852 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NIH, Off Dietary Supplements, Rockville, MD 20852 USA. RP Seifried, H (reprint author), NCI, Div Canc Prevent, Rockville, MD 20852 USA. EM hs41s@nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD OCT PY 2006 VL 136 IS 10 BP 2666S EP 2667S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 089OH UT WOS:000240889600034 PM 16988142 ER PT J AU Schatzkin, A AF Schatzkin, Arthur TI Promises and perils of validating biomarkers for cancer risk SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT Conference on the Use and Misuse of Biomarkers as Indicators of Cancer Risk Reduction Following Dietary Manipulation CY JUL 12-13, 2005 CL Bethesda, MD SP Ctr Food Safety * appl Nutr, FDA, US Dept HHS, NIH, NCI C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. EM schatzka@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD OCT PY 2006 VL 136 IS 10 BP 2671S EP 2672S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 089OH UT WOS:000240889600037 PM 16988144 ER PT J AU Wang, TTY Milner, MJ Milner, JA Kim, YS AF Wang, Thomas T. Y. Milner, Matthew J. Milner, John A. Kim, Young S. TI Estrogen receptor alpha as a target for indole-3-carbinol SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE indole-3-carbinol; 3,3 '-diindolylmethane; estrogen receptor alpha ID BREAST-CANCER CELLS; TRANSCRIPTION FACTOR; MAMMARY-GLAND; MESSENGER-RNA; TUMOR-CELLS; RISK; ACTIVATION; PREVENTION; MCF-7; GENE AB A wealth of preclinical evidence supports the antitumorigenic properties of indole-3-carbinol (I3C), which is a major bioactive food component in cruciferous vegetables. However, the underlying molecular mechanism(s) accounting for these effects remain unresolved. In the present study, estrogen receptor alpha (ER-alpha) was identified as a potential molecular target for I3C. Treating MCF-7 cells with 100 mu M I3C reduced ER-alpha mRNA expression by approximately 60% compared to controls. This reduction in ER-a transcript levels was confirmed using real-time polymerase chain reaction. The I3C dimer, 3,3'-diindolylmetbane (DIM), was considerably more effective in depressing ER-alpha mRNA in MCF-7 cells than the monomeric unit. The suppressive effects of 5 mu M DIM on ER-alpha mRNA was comparable to that caused by 100 mu M I3C. DIM is known to accumulate in the nucleus and is a preferred ligand for aryl hydrocarbon receptor (AhR) to 13C. The addition of other AhR ligands, alpha-naphthoflavone (alpha-NF, 10 mu M) and lutcolin (10 mu M), to the culture media resulted in a similar suppression in ER-alpha mRNA levels to that caused by 5 mu M DIM. Thus, it is likely that the binding of ligands to AhR inhibits nuclear ER-alpha transcript. The results from these experiments suggest that the antitumorigenic effects of I3C in MCF-7 human breast cancer cells may arise from its ability to reduce ER-alpha expression through the binding of its metabolite, DIM, to the nuclear AhR. (c) 2006 Elsevier Inc. All rights reserved. C1 USDA ARS, Beltsville Human Nutr Res Ctr, Phytonutirents Lab, Beltsville, MD 20705 USA. Penn State Univ, Dept Biol, University Pk, PA 16802 USA. NCI, Nutr Sci Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Wang, TTY (reprint author), USDA ARS, Beltsville Human Nutr Res Ctr, Phytonutirents Lab, Beltsville, MD 20705 USA. EM wangt@ba.ars.usda.gov NR 26 TC 41 Z9 41 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD OCT PY 2006 VL 17 IS 10 BP 659 EP 664 DI 10.1016/j.jnutbio.2005.10.012 PG 6 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 091CU UT WOS:000241004500002 PM 16488130 ER PT J AU Beseler, C Stallones, L Hoppin, JA Alavanja, MCR Blair, A Keefe, T Kamel, F AF Beseler, Cheryl Stallones, Lorann Hoppin, Jane A. Alavanja, Michael C. R. Blair, Aaron Keefe, Thomas Kamel, Freya TI Depression and pesticide exposures in female spouses of licensed pesticide applicators in the agricultural health study cohort SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CHRONIC NEUROLOGICAL SEQUELAE; NEUROPATHY TARGET ESTERASE; ORGANOPHOSPHATE PESTICIDES; OCCUPATIONAL-EXPOSURE; GENDER-DIFFERENCES; NERVOUS-SYSTEM; FARM RESIDENTS; WORK PRACTICES; PRIMARY-CARE; CHLORPYRIFOS AB Objective: This nested case-control study evaluated the association between depression and pesticide exposure among women. Methods: The study population included 29,074,female spouses of private pesticide applicators enrolled in the Agricultural Health Study between 1993 and 1997. Cases were women who had physician-diagnosed depression requiring medication. Lifetime pesticide use was categorized as never mixed/applied pesticides, low exposure (up to 225 days), high exposure (> 225 days), and a history of diagnosed pesticide poisoning. Results: After adjustment for state, age, race, off-farm work alcohol, cigarette smoking, physician visits, and solvent exposure, depression was significantly associated with a history of pesticide poisoning (odds ratio [OR] = 3.26; 95% confidence interval [G] = 1.72-619) but not low (OR = 1.09; CI = 0.91-1.31) or high (OR = 1.09; 95% CI = 0.91-1.31) cumulative pesticide exposure. Conclusion: Pesticide poisoning may contribute to risk of depression. C1 Colorado State Univ, Dept Psychol, Colorado Injury Control Res Ctr, Ft Collins, CO 80523 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. NIEHS, Epidemiol Branch, US Dept HHS, NIH, Res Triangle Pk, NC 27709 USA. NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Rockville, MD USA. Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. RP Beseler, C (reprint author), Colorado State Univ, Dept Psychol, Colorado Injury Control Res Ctr, Ft Collins, CO 80523 USA. EM cbeseler@lamar.colostate.edu OI Kamel, Freya/0000-0001-5052-6615 FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES044007-05] NR 48 TC 48 Z9 49 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD OCT PY 2006 VL 48 IS 10 BP 1005 EP 1013 DI 10.1097/01.jom.0000235938.70212.dd PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 095IJ UT WOS:000241301100009 PM 17033500 ER PT J AU Spinelli, HM Tabatabai, N Muzaffar, AR Isenberg, JS AF Spinelli, Henry M. Tabatabai, Nassim Muzaffar, Arshad R. Isenberg, Jeffrey S. TI Upper lip reconstruction with the alar crescent flap: A new approach SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID DEFECTS AB Purpose: The alar crescent advancement flap technique has been widely used for repair of large central defects of the upper lip and base of the nose because of its I-stage procedural simplicity and good results. Several more complicated and multiple staged procedures that respect either structure or function, often compromising one to achieve the other, have become popular and have recently taken its place. However, these procedures are more complex and in many cases require a staged approach. In this study, we present a series of 33 patients who underwent reconstruction of large upper lip defects utilizing alar crescent flaps between 1992 and 2002. Patients and Methods: A series of 20 patients underwent reconstruction of large upper lip defects using alar crescent flaps between 1992 and 2002. Malignant etiologies were responsible for the defect in all patients. Reconstruction was performed as a 1-staged procedure in 19 cases. In 1 patient with a total upper lip defect, bilateral alar crescent flaps were used in conjunction with a cross lip flap that was later divided in a second stage procedure. Results: All patients tolerated the procedure well with no major complications. Minor complications not requiring surgical intervention occurred in 5 patients. During the 12- to 60-month follow-up, all patients were found to be satisfied with the functional result. However, 7 patients underwent minor surgical procedures for esthetic improvement. There was no recurrence of disease in the 20 patients who underwent resection of malignancy. Conclusions: in these 20 cases, we have shown the utility of the alar crescent flap for varying length partial and full-thickness reconstruction of upper lip defects. This simple and straightforward technique provided good functional and esthetic results. The disadvantage of this procedure is the loss of philtral anatomic detail. Its primary advantage is that it is a single-stage procedure with a relatively low morbidity and patient inconvenience. As a single-stage technique it satisfies concerns over cost containment over more complex and staged procedures while still providing a good functional and cosmetic result. Furthermore, for those same reasons, this procedure is a good first choice in the elderly. (C) 2006 American Association of Oral and Maxillofacial Surgeons. C1 Cornell Univ, Weill Med Coll, Div Plast & Reconstruct Surg, New York, NY 10021 USA. Univ Washington, Med Ctr, Dept Plast Surg, Seattle, WA 98195 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Spinelli, HM (reprint author), Cornell Univ, Weill Med Coll, Div Plast & Reconstruct Surg, 875 5th Ave, New York, NY 10021 USA. EM hmspinelli@aol.com NR 17 TC 8 Z9 8 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD OCT PY 2006 VL 64 IS 10 BP 1566 EP 1570 DI 10.1016/j.joms.2005.12.031 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 090EF UT WOS:000240932700016 PM 16982318 ER PT J AU Liu, XD Zhao, SP Sun, LG Luo, HH Yin, XB Xie, ZQ Wang, YH Liu, KX Wu, XH Ding, XF Fu, DP AF Liu, X. D. Zhao, S. P. Sun, L. G. Luo, H. H. Yin, X. B. Xie, Z. Q. Wang, Y. H. Liu, K. X. Wu, X. H. Ding, X. F. Fu, D. P. TI Geochemical evidence for the variation of historical seabird population on Dongdao Island of the South China Sea SO JOURNAL OF PALEOLIMNOLOGY LA English DT Article DE Dongdao Island; Lacustrine sediments; sediment sequence affected by seabird feces; seabird population; elemental geochemistry; SST; South China Sea ID PAST 2,200 YEARS; FISHERIES RESOURCES; MARINE ECOSYSTEM; AGE CALIBRATION; PENGUIN COLONY; ORGANIC-MATTER; CLIMATE-CHANGE; HEAVY-METALS; SEDIMENTS; ANTARCTICA AB From a rare freshwater lake characteristic of alkalescence, named "Cattle Pond", on the Dongdao Island of South China Sea (16 degrees 39'-16 degrees 41'N, 112 degrees 43'-112 degrees 45'E), we collected two undisturbed sediment cores that contain seabird droppings. In this paper, we determined the concentration-versus-depth profiles of the geochemical elements in the ornithogenic sediment layers of the two cores, analyzed these profiles by various statistical methods, and studied their geochemical characteristics. The concentration profiles of As, Cd, Cu, Se, Zn, P and S are significantly correlated with each other and with loss on ignition (LOI) at 550 degrees C, the measure for the abundance of organic matter. Similar geochemical characteristics, however, were not observed in the upper sediment layer of the Cattle Pond notably affected by cattle excrements, as well as in the bottom sediment layer compositionally dominated by coral sand and gravel. This shows that these "bio-elements" are mainly derived from seabird feces and their geochemical composition is an important geochemical characteristic of the lacustrine ornithogenic sediments. By Q-mode factor analysis (QFA) on the concentration profiles of these bio-elements, we reconstructed the historical seabird population on Dongdao Island between 1350 and 350 year B.P., and observed significant fluctuations in the calculated population. The fluctuations seem to be related to the change of sea surface temperature (SST) in the Southern China Sea. This study provides new paleoenvironmental information of past seabird population changes in low latitude areas using an indirect geochemical method. C1 Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China. NIH, Bethesda, MD 20892 USA. Peking Univ, Sch Phys, Inst Heavy Ion Phys, Beijing 100871, Peoples R China. Peking Univ, Sch Archaeol & Museol, Beijing 100871, Peoples R China. RP Sun, LG (reprint author), Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China. EM slg@ustc.edu.cn RI Fu, Dongpo/C-2233-2014 OI Fu, Dongpo/0000-0001-9324-4247 NR 89 TC 29 Z9 39 U1 5 U2 19 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0921-2728 J9 J PALEOLIMNOL JI J. Paleolimn. PD OCT PY 2006 VL 36 IS 3 BP 259 EP 279 DI 10.1007/s10933-006-9006-9 PG 21 WC Environmental Sciences; Geosciences, Multidisciplinary; Limnology SC Environmental Sciences & Ecology; Geology; Marine & Freshwater Biology GA 092QR UT WOS:000241112900003 ER PT J AU Donenberg, GR Paikoff, R Pequegnat, W AF Donenberg, Geri R. Paikoff, Roberta Pequegnat, Willo TI Introduction to the special section on families, youth, and HIV: Family-based intervention studies SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Editorial Material ID HEALTH-RISK BEHAVIORS; ADOLESCENT SEXUAL-BEHAVIOR; COMMUNICATION; INTERCOURSE; ONSET; DEBUT C1 Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60608 USA. NIMH, Bethesda, MD 20892 USA. RP Donenberg, GR (reprint author), Univ Illinois, Dept Psychiat, Inst Juvenile Res, 1747 W Roosevelt Rd,Room 155 MC747, Chicago, IL 60608 USA. EM gdonenberg@psych.uic.edu FU NIMH NIH HHS [R01MH63008, R01MH58545, R01MH068225, R01MH65155] NR 30 TC 35 Z9 35 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD OCT PY 2006 VL 31 IS 9 BP 869 EP 873 DI 10.1093/jpepsy/jsj102 PG 5 WC Psychology, Developmental SC Psychology GA 085EM UT WOS:000240586200001 PM 16467312 ER PT J AU Russell, HF Wallis, D Mazzocco, MMM Moshang, T Zackai, E Zinn, AR Ross, JL Muenke, M AF Russell, Heather F. Wallis, Deeann Mazzocco, Michele M. M. Moshang, Thomas Zackai, Elaine Zinn, Andrew R. Ross, Judith L. Muenke, Maximilian TI Increased prevalence of ADHD in Turner syndrome with no evidence of imprinting effects SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE ADHD; imprinting; social cognition; Turner syndrome; X-inactivation ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; PSYCHOSOCIAL DEVELOPMENT; GENOMEWIDE SCAN; FRAGILE-X; CHILDREN; GIRLS; INTELLIGENCE; ADOLESCENTS; PHENOTYPE AB Background Turner syndrome (TS) results from the loss of part or all of one X chromosome in females. It can result in short stature, various dysmorphic findings, and difficulties with psychosocial adjustment. Girls with TS have previously been found to exhibit increased levels of hyperactivity and inattention. However, no studies have assessed whether individuals with TS meet strict (DSM-IV) criteria for attention-deficit/hyperactivity disorder (ADHD). Objective We looked at the prevalence of ADHD in girls with TS and evaluated the contribution of imprinting on cognitive performance (IQ) and ADHD. Methods We tested 50 girls with TS for ADHD, IQ, academic performance, and parental origin of the X chromosome. Results We report an 18-fold increase in the prevalence of ADHD in girls with TS (24%) compared with girls in the general population (1.3%) (p < .01) and a 4.8 fold increase when compared with boys and girls in the general population (5%) (p < .05). In contrast to previous reports, our molecular studies in females with 45,X also showed no association between IQ scores and the parental origin of the intact X chromosome. Conclusions We find an increased prevalence of ADHD in girls with TS but no evidence for imprinting effects for cognitive performance. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Childrens Hosp, Dept Pediat, Div Human & Mol Genet, Philadelphia, PA 19104 USA. Shriners Hosp Children, Philadelphia, PA USA. Johns Hopkins Univ, Kennedy Krieger Inst, Sch Med, Baltimore, MD 21218 USA. Childrens Hosp, Dept Pediat, Div Endocrinol, Philadelphia, PA 19104 USA. Thomas Jefferson Univ, Dept Pediat, Philadelphia, PA 19107 USA. DuPont Hosp Children, Wilmington, DE 19899 USA. RP Russell, HF (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mmuenke@nhgri.nih.gov OI Zinn, Andrew/0000-0002-4935-3291 FU Intramural NIH HHS; NINDS NIH HHS [NS32531, NS32532, NS35554, NS42777]; PHS HHS [34061] NR 63 TC 44 Z9 46 U1 6 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD OCT PY 2006 VL 31 IS 9 BP 945 EP 955 DI 10.1093/jpepsy/jsj106 PG 11 WC Psychology, Developmental SC Psychology GA 085EM UT WOS:000240586200008 PM 16524959 ER PT J AU Qian, L Block, ML Wei, SJ Lin, CF Reece, J Pang, H Wilson, B Hong, JS Flood, PM AF Qian, Li Block, Michelle L. Wei, Sung-Jen Lin, Chiou-Feng Reece, Jeffrey Pang, Hao Wilson, Belinda Hong, Jau-Shyong Flood, Patrick M. TI Interleukin-10 protects lipopolysaccharide-induced neurotoxicity in primary midbrain cultures by inhibiting the function of NADPH oxidase SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article; Proceedings Paper CT 16th International Congress on Parkinsons Disease and Related Disorders CY JUN 05-09, 2005 CL Berlin, GERMANY ID PARKINSONS-DISEASE; INFLAMMATORY RESPONSE; DOPAMINERGIC-NEURONS; TETRAZOLIUM SALT; NITRIC-OXIDE; CELL-DEATH; RAT-BRAIN; MICROGLIA; SUPEROXIDE; ACTIVATION AB The role of anti-inflammatory cytokines in Parkinson's disease is not completely understood. In this study, using mesencephalic neuron-glia cultures, we report that both pretreatment and post-treatment of rat mesencephalic neuron-glia cultures with interleukin (IL)-10, a natural immune modulator, reduced lipopolysaccharide (LPS)-induced DA neurotoxicity. The main purpose of this study was to elucidate the molecular mechanism underlying IL-10-elicited neuroprotection. IL-10 significantly inhibited LPS-induced production of tumor necrosis factor-alpha, nitric oxide, and extracellular superoxide in microglia cells. In addition, using reconstituted neuron and glia cell cultures, IL-10 was shown to be neuroprotective only in the presence of microglia. More importantly, IL-10 failed to protect DA neurons in cultures from mice lacking NADPH oxidase (PHOX), a key enzyme for extracellular superoxide production in immune cells, suggesting the critical role of PHOX in IL-10 neuroprotection. This conclusion was further supported by the finding that IL-10 inhibited LPS-induced translocation of the cytosolic subunit of NADPH oxidase p47(phox) to the membrane. When the Janus tyrosine kinase (JAK) 1 signaling pathway was blocked, IL-10 failed to attenuate LPS-induced superoxide production, indicating that the JAK1 signaling cascade mediates the inhibitory effect of IL-10. Together, our results suggest that IL-10 inhibits LPS-induced DA neurotoxicity through the inhibition of PHOX activity in a JAK1-dependent mechanism. C1 Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27599 USA. Natl Inst Environm Hlth Sci, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC USA. Natl Inst Environm Hlth Sci, Natl Ctr Toxicogenom, NIH, Res Triangle Pk, NC USA. Natl Inst Environm Hlth Sci, Confocal Microscopy Ctr, Lab Signal Transduct, NIH, Res Triangle Pk, NC USA. RP Flood, PM (reprint author), Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27599 USA. EM pat_flood@dentistry.unc.edu FU Intramural NIH HHS; NIDCR NIH HHS [DE-13079] NR 41 TC 76 Z9 76 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 2006 VL 319 IS 1 BP 44 EP 52 DI 10.1124/jpet.106.106351 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 087UK UT WOS:000240767800005 PM 16807359 ER PT J AU Partilla, JS Dempsey, AG Nagpal, AS Blough, BE Baumann, MH Rothman, RB AF Partilla, John S. Dempsey, Allison G. Nagpal, Ameet S. Blough, Bruce E. Baumann, Michael H. Rothman, Richard B. TI Interaction of amphetamines and related compounds at the vesicular monoamine transporter SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PRIMARY PULMONARY-HYPERTENSION; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; RAT-BRAIN; SEROTONIN NEUROTOXICITY; FENFLURAMINE; DOPAMINE; RELEASE; BINDING; MECHANISMS; AFFINITY AB Amphetamine-type agents interact with the vesicular monoamine transporter type 2 (VMAT(2)), promoting the release of intravesicular neurotransmitter and an increase in cytoplasmic neurotransmitter. Some compounds, such as reserpine, "release" neurotransmitter by inhibiting the ability of VMAT(2) to accumulate neurotransmitter in the vesicle, whereas other types of compounds can release neurotransmitter via a carrier-mediated exchange mechanism. The purpose of this study was to determine, for 42 mostly amphetamine-related compounds, their mode of interaction with the VMAT(2). We used a crude vesicular fraction prepared from rat caudate to assay VMAT(2) activity. Test compounds were assessed in several assays, including 1) inhibition of [H-3] dihydrotetrabenazine binding, 2) inhibition of vesicular [H-3] dopamine uptake, and 3) release of preloaded [H-3] dopamine and [H-3] tyramine. Several important findings derive from this comprehensive study. First, our work indicates that most agents are VMAT(2) substrates. Second, our data strongly suggest that amphetamine-type agents deplete vesicular neurotransmitter via a carrier-mediated exchange mechanism rather than via a weak base effect, although this conclusion needs to be confirmed via direct measurement of vesicular pH. Third, our data fail to reveal differential VMAT2 interactions among agents that do and do not produce long-term 5-hydroxytryptamine depletion. Fourth, the data reported revealed the presence of two pools of [H-3]amine within the vesicle, one pool that is free and one pool that is tightly associated with the ATP/protein complex that helps store amine. Finally, the VMAT(2) assays we have developed should prove useful for guiding the synthesis and evaluation of novel VMAT(2) agents as possible treatment agents for addictive disorders. C1 NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Res Triangle Inst Int, Chem & Life Sci Grp, Res Triangle Pk, NC USA. RP Rothman, RB (reprint author), NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rrothman@mail.nih.gov FU Intramural NIH HHS; NIDA NIH HHS [R01 DA12970] NR 33 TC 75 Z9 77 U1 1 U2 14 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 2006 VL 319 IS 1 BP 237 EP 246 DI 10.1124/jpet.106.103622 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 087UK UT WOS:000240767800024 PM 16835371 ER PT J AU Vyas, PM Roychowdhury, S Khan, FD Prisinzano, TE Lamba, J Schuetz, EG Blaisdell, J Goldstein, JA Munson, KL Hines, RN Svensson, CK AF Vyas, Piyush M. Roychowdhury, Sanjoy Khan, Farah D. Prisinzano, Thomas E. Lamba, Jatinder Schuetz, Erin G. Blaisdell, Joyce Goldstein, Joyce A. Munson, Kimber L. Hines, Ronald N. Svensson, Craig K. TI Enzyme-mediated protein haptenation of dapsone and sulfamethoxazole in human keratinocytes: I. Expression and role of cytochromes P450 SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; HUMAN EPIDERMAL-KERATINOCYTES; HUMAN SKIN; MESSENGER-RNA; COVALENT BINDING; DRUG-REACTIONS; METABOLITES; HYDROXYLAMINE; SULFONAMIDE; CYCLOOXYGENASE-2 AB Cutaneous drug reactions (CDRs) are among the most common adverse drug reactions and are responsible for numerous minor to life-threatening complications. Several arylamine drugs, such as sulfamethoxazole (SMX) and dapsone (DDS), undergo bioactivation, resulting in adduction to cellular proteins. These adducted proteins may initiate the immune response that ultimately results in a CDR. Recent studies have demonstrated that normal human epidermal keratinocytes (NHEKs) can bioactivate these drugs, resulting in protein haptenation. We sought to identify the enzyme(s) responsible for this bioactivation in NHEKs. Using immunofluorescence confocal microscopy and an adduct-specific enzyme-linked immunosorbent assay (ELISA), we found that N-acetylation of the primary amine of SMX and DDS markedly reduced the level of protein haptenation in NHEKs. Detection of mRNA and/or protein confirmed the presence of CYP3A4, CYP3A5, and CYP2E1 in NHEKs. In contrast, although a faint band suggestive of CYP2C9 protein was detected in one NHEK sample, a CYP2C9 message was not detectable. We also examined the ability of chemical inhibitors of cytochromes P450 (aminobenzotriazole and 1-dichloroethylene) and cyclooxygenase (indomethacin) to reduce protein haptenation when NHEKs were incubated with SMX or DDS by either confocal microscopy or ELISA. These inhibitors did not significantly attenuate protein adduction with either SMX or DDS, indicating that cytochromes P450 and cyclooxygenase do not play important roles in the bioactivation of these xenobiotics in NHEKs and thus suggesting the importance of other enzymes in these cells. C1 Univ Iowa, Coll Pharm, Div Pharmaceut, Iowa City, IA 52242 USA. Univ Iowa, Coll Pharm, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Med Coll Wisconsin, Dept Pediat & Pharmacol & Toxicol, Milwaukee, WI 53226 USA. Childrens Hosp Wisconsin, Childrens Res Inst, Milwaukee, WI 53201 USA. RP Svensson, CK (reprint author), Purdue Univ, Coll Pharm Nursing & Hlth Sci, W Lafayette, IN 47907 USA. EM svensson@purdue.edu RI Prisinzano, Thomas/B-7877-2010; Goldstein, Joyce/A-6681-2012; OI Hines, Ronald/0000-0002-3094-4200 FU NIAID NIH HHS [AI41395]; NIGMS NIH HHS [GM60346, GM63821] NR 35 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 2006 VL 319 IS 1 BP 488 EP 496 DI 10.1124/jpet.106.105858 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 087UK UT WOS:000240767800053 PM 16857728 ER PT J AU Jiang, H Joy, DA Furuya, T Su, XZ AF Jiang, H. Joy, D. A. Furuya, T. Su, X-Z TI Current understanding of the molecular basis of chloroquine-resistance in Plasmodium falciparum SO JOURNAL OF POSTGRADUATE MEDICINE LA English DT Article; Proceedings Paper CT National Consultation on Drug Resistance in Malaria - Tuberculosis and HIV/AIDS CY SEP 19-21, 2005 CL Bombay, INDIA DE chloroquine; chloroquine resistance; malaria; Plasmodium falciparum; pfcrt; pfmdr1 ID ANTIMALARIAL-DRUG-RESISTANCE; DIGESTIVE VACUOLAR PH; DRUG/METABOLITE TRANSPORTER SUPERFAMILY; TRANSMEMBRANE PROTEIN PFCRT; GENE HAPLOTYPE SVMNT; MULTIDRUG-RESISTANCE; IN-VITRO; MALARIA PARASITES; PFMDR1 GENE; QUININE RESISTANCE AB Chloroquine (CQ) is the most successful antimalarial drug ever discovered. Unfortunately, parasites resistant to the drug eventually emerged after its large scale use and are now widespread. Although great progress in our understanding of the mechanisms of CQ action and CQ resistance (COR) has been achieved over the past two decades, including the identification of the molecules responsible for CQR (e.g., Plasmodium falciparum chloroquine resistant transporter, PfCRT) many questions remain unanswered. Here we highlight recent advances in our understanding of the genetics and molecular mechanisms of CGR, with particular emphasis on the role of genes such as pfcrt and pfmdr1 in the resistance to CQ and other drugs. New drug development and applications will undoubtedly benefit from a better understanding of CQR, eventually leading to more effective malaria control measures. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM xsu@niaid.nih.gov RI Furuya, Tetsuya/J-5916-2013; Furuya, Tetsuya/H-2412-2013; OI Furuya, Tetsuya/0000-0003-3979-7072; Su, Xinzhuan/0000-0003-3246-3248 NR 88 TC 18 Z9 20 U1 1 U2 3 PU MEDKNOW PUBLICATIONS PI MUMBAI PA A-108-109 KANARA BUSINESS CENTRE, GHAKTOPAR, MUMBAI, 400075, INDIA SN 0022-3859 J9 J POSTGRAD MED JI J. Postgrad. Med. PD OCT-DEC PY 2006 VL 52 IS 4 BP 271 EP 276 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 113TA UT WOS:000242619100012 PM 17102545 ER PT J AU Moffett, A Hiby, S Carrington, M AF Moffett, Ashley Hiby, Sue Carrington, Mary TI Letter in response to article by Saito et al. SO JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Letter DE pre-eclampsia; KIR; HLA; Japanese; Caucasian C1 Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Moffett, A (reprint author), Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England. EM Am485@cam.ac.uk NR 2 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-0378 J9 J REPROD IMMUNOL JI J. Reprod. Immunol. PD OCT PY 2006 VL 71 IS 2 BP 132 EP 133 DI 10.1016/j.jri.2006.04.003 PG 2 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 087BA UT WOS:000240716000005 PM 16860398 ER PT J AU Ali, SO Thomassen, M Schulz, GM Hosey, LA Varga, M Ludlow, CL Braun, AR AF Ali, S. Omar Thomassen, Michael Schulz, Geralyn M. Hosey, Lara A. Varga, Mary Ludlow, Christy L. Braun, Allen R. TI Alterations in CNS activity induced by botulinum toxin treatment in spasmodic dysphonia: An (H2OPET)-O-15 study SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE adductor spasmodic dysphonia; botulinum toxin; CNS; rCBF; PET ID SUPPLEMENTARY MOTOR AREA; FOCAL HAND DYSTONIA; WRITERS CRAMP; BASAL GANGLIA; CORTICAL DYSFUNCTION; LARYNGEAL DYSTONIA; SPASTIC DYSPHONIA; ABNORMALITIES; SPEECH; ACTIVATION AB Speech-related changes in regional cerebral blood flow (rCBF) were measured using (H2O)-O-15 positron-emission tomography in 9 adults with adductor spasmodic dysphonia (ADSD) before and after botulinum toxin (BTX) injection and 10 age- and gender-matched volunteers without neurological disorders. Scans were acquired at rest and during production of continuous narrative speech and whispered speech. Speech was recorded during scan acquisition for offline quantification of voice breaks, pitch breaks, and percentage aperiodicity to assess correlations between treatment-related changes in rCBF and clinical improvement. Results demonstrated that speech-related responses in heteromodal sensory areas were significantly reduced in persons with ADSD, compared with volunteers, before the administration of BTX Three to 4 weeks after BTX injection, speech-related responses were significantly augmented in these regions and in left hemisphere motor areas commonly associated with oral-laryngeal motor control. This pattern of responses was most strongly correlated with the objective measures of clinical improvement (decreases in the frequency of voice breaks, pitch breaks, and percentage aperiodicity). These data suggest a pathophysiological model for ADSD in which BTX treatment results in more efficient cortical processing of sensory information, making this information available to motor areas that use it to more effectively regulate laryngeal movements. C1 Natl Tech Inst Deafness & Other Commun Disorders, Language Sect, Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Washington, DC USA. NINDS, Bethesda, MD 20892 USA. RP Braun, AR (reprint author), Natl Tech Inst Deafness & Other Commun Disorders, Language Sect, Voice Speech & Language Branch, NIH, Bldg 10,Room 8S235A,10 Ctr Dr, Bethesda, MD 20892 USA. EM brauna@nidcd.nih.gov OI Ali, Syed/0000-0003-3131-3299 FU Intramural NIH HHS [Z01 NS002980-09] NR 92 TC 29 Z9 29 U1 5 U2 8 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD OCT PY 2006 VL 49 IS 5 BP 1127 EP 1146 DI 10.1044/1092-4388(2006/081) PG 20 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 107YY UT WOS:000242208100016 PM 17077220 ER PT J AU Dong, DD Jewell, CM Bienstock, RJ Cidlowski, JA AF Dong, Diane D. Jewell, Christine M. Bienstock, Rachelle J. Cidlowski, John A. TI Functional analysis of the LXXLL motifs of the human glucocorticoid receptor: Association with altered ligand affinity SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE glucocorticoid receptor; ligand binding domain; LXXLL motif; transactivation; NF-kappa B; transrepression; molecular simulation ID FACTOR-KAPPA-B; NUCLEAR-RECEPTOR; BINDING DOMAIN; TRANSCRIPTIONAL ACTIVATION; DEXAMETHASONE 21-MESYLATE; CRYSTAL-STRUCTURE; STEROID-BINDING; HORMONE-BINDING; BETA-ISOFORM; AMINO-ACIDS AB Although LXXLL motifs in coactivators mediate binding to liganded nuclear receptors, the roles of comparable motifs within nuclear receptors are less understood. We investigated the role of the LXXLL motifs in the human glucocorticoid receptor both in transcriptional activation and repression of gene expression. The two conserved LXXLL motifs within the ligand binding domain of the receptor, amino acids 532-536 (helix 1) and 718-722 (helix 10), were characterized by evaluating LXXLL mutant receptors as well as comparable mutants in other helices of the ligand binding domain. All mutant receptors were expressed at comparable levels to wild type in COS-1 cells. Mutation of 532-536 LXXLL to LXXAA completely disrupted dexamethasone induced transcription, whereas the 718-722 LXXAA mutant fully activated reporter genes at high ligand concentrations. Ligand binding analysis demonstrated that both LXXLL motif mutations resulted in disruption of ligand binding capacity without altering their association with hsp90. Proteolytic cleavage studies suggested that mutations of the LXXLL motifs introduced changes in the receptor conformation. Interestingly, the 532-536 LXXAA mutant was not able to transrepress NF-kappa B activity, whereas the 718-722 LXXAA mutant did so in the presence of ligand. These data suggest that although LXXLL motifs in helices 1 and 10 appear to lie outside the predicted ligand binding pocket they may contribute to receptor ligand binding affinity. Published by Elsevier Ltd. C1 NIEHS, Lab Signal Transduct, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, US Dept HHS, POB 12233,MD F3-07, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov OI Bienstock, Rachelle/0000-0001-5228-3610 NR 38 TC 9 Z9 10 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD OCT PY 2006 VL 101 IS 2-3 BP 106 EP 117 DI 10.1016/j.jsbmb.2006.06.010 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 091RZ UT WOS:000241047300003 PM 16914312 ER PT J AU Ye, YH AF Ye, Yihong TI Diverse functions with a common regulator: Ubiquitin takes command of an AAA ATPase SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article; Proceedings Paper CT 6th International Conference on AAA(plus) Proteins CY SEP, 2005 CL Schloss Seggau, AUSTRIA DE ubiquitin; Cdc48/p97/VCP; AAA ATPase/chaperone; retro-translocation/ERAD; the proteasome ID VALOSIN-CONTAINING PROTEIN; ENDOPLASMIC-RETICULUM MEMBRANE; MITOTIC GOLGI FRAGMENTS; BOUND TRANSCRIPTION FACTOR; ER-ASSOCIATED DEGRADATION; RETRO-TRANSLOCATION; CELL-CYCLE; QUALITY-CONTROL; TYROSINE PHOSPHORYLATION; CONFORMATIONAL-CHANGES AB Cdc48/p97, a member of the AAA (ATPase associated with various cellular activities) ATPase family, participates in various cellular pathways including membrane fusion, protein folding/unfolding, proteolysis-dependent transcriptional control, protein degradation, and spindle disassembly. How Cdc48/p97 can perform such diverse functions is unclear, but the recently established connection between components of the ubiquitination system and various p97 activities suggests that these seemingly unrelated processes mediated by Cdc48/p97 may all be governed by ubiquitin. Published by Elsevier Inc. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ye, YH (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM yihongy@mail.nih.gov FU Intramural NIH HHS NR 109 TC 144 Z9 147 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD OCT PY 2006 VL 156 IS 1 BP 29 EP 40 DI 10.1016/j.jsb.2006.01.005 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 096RJ UT WOS:000241394200004 PM 16529947 ER PT J AU Szyk, A Maurizi, MR AF Szyk, Agnieszka Maurizi, Michael R. TI Crystal structure at 1.9 angstrom of E-coli ClpP with a peptide covalently bound at the active site SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article; Proceedings Paper CT 6th International Conference on AAA(plus) Proteins CY SEP, 2005 CL Schloss Seggau, AUSTRIA DE ClpP; Escherichia coli ClpP; peptide binding; chloromethyl ketone; chloromethyl ketone inhibitor; X-ray crystallography; beta-hairpin; axial channel ID ATP-DEPENDENT PROTEASES; CHAPERONE CLPA; PROTEIN; DEGRADATION; COMPLEXES; CRYSTALLOGRAPHY; SPECIFICITY; PROTEOLYSIS; TERMINUS; SEQUENCE AB ClpP, the proteolytic component of the ATP-dependent ClpAP and ClpXP chaperone/protease complexes, has 14 identical subunits organized in two stacked heptameric rings. The active sites are in an interior aqueous chamber accessible through axial channels. We have determined a 1.9 angstrom crystal structure of Escherichia coli ClpP with benzyloxycarbonyl-leucyltyrosine chloromethyl ketone (Z-LY-CMK) bound at each active site. The complex mimics a tetrahedral intermediate during peptide cleavage, with the inhibitor covalently linked to the active site residues, Ser97 and His122. Binding is further stabilized by six hydrogen bonds between backbone atoms of the peptide and ClpP as well as by hydrophobic binding of the phenolic ring of tyrosine in the S1 pocket. The peptide portion of Z-LY-CMK displaces three water molecules in the native enzyme resulting in little change in the conformation of the peptide binding groove, The heptameric rings of ClpP-CMK are slightly more compact than in native ClpP, but overall structural changes were minimal (rmsd similar to 0.5 angstrom). The side chain of Ser97 is rotated similar to 90 degrees in forming the covalent adduct with Z-LY-CMK, indicating that rearrangement of the active site residues to a active configuration occurs upon substrate binding. The N-terminal peptide of ClpP-CMK is stabilized in a P-hairpin conformation with the proximal N-terminal residues lining the axial channel and the loop extending beyond the apical surface of the heptameric ring. The lack of major substrate-induced conformational changes suggests that changes in ClpP structure needed to facilitate substrate entry or product release must be limited to rigid body motions affecting subunit packing or contacts between ClpP rings. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Maurizi, MR (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM mmaurizi@helix.nih.gov FU Intramural NIH HHS NR 46 TC 53 Z9 55 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD OCT PY 2006 VL 156 IS 1 BP 165 EP 174 DI 10.1016/j.jsb.2006.03.013 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 096RJ UT WOS:000241394200018 PM 16682229 ER PT J AU Fitch, WT Fritz, JB AF Fitch, W. Tecumseh Fritz, Jonathan B. TI Rhesus macaques spontaneously perceive formants in conspecific vocalizations SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID VENTROLATERAL PREFRONTAL CORTEX; MONKEYS CERCOPITHECUS-AETHIOPS; VOCAL-TRACT RESONANCES; HUMANS HOMO-SAPIENS; RED DEER STAGS; ALARM CALLS; VERVET MONKEYS; BODY-SIZE; ACOUSTIC CLASSIFICATION; COMMUNICATION SOUNDS AB We provide a direct demonstration that nonhuman primates spontaneously perceive changes in formant frequencies in their own species-typical vocalizations, without training or reinforcement. Formants are vocal tract resonances leading to distinctive spectral prominences in the vocal signal, and provide the acoustic determinant of many key phonetic distinctions in human languages. We developed algorithms for manipulating formants in rhesus macaque calls. Using the resulting computer-manipulated calls in a habituation/dishabituation paradigm, with blind video scoring, we show that rhesus macaques spontaneously respond to a change in formant frequencies within the normal macaque vocal range. Lack of dishabituation to a "synthetic replica" signal demonstrates that dishabituation was not due to an artificial quality of synthetic calls, but to the formant shift itself. These results indicate that formant perception, a significant component of human voice and speech perception, is a perceptual ability shared with other primates. (c) 2006 Acoustical Society of America. C1 Univ St Andrews, Sch Psychol, St Andrews KY16 9JP, Fife, Scotland. NIMH, Neuropsychol Lab, NIH, College Pk, MD 20742 USA. RP Fitch, WT (reprint author), Univ St Andrews, Sch Psychol, St Andrews KY16 9JP, Fife, Scotland. EM wtsf@st-andrews.ac.uk FU NIDCD NIH HHS [T32 DC00038] NR 86 TC 59 Z9 59 U1 3 U2 9 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD OCT PY 2006 VL 120 IS 4 BP 2132 EP 2141 DI 10.1121/1.2258499 PG 10 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 094SD UT WOS:000241258400041 PM 17069311 ER PT J AU Rothman, A Glenn, G Choyke, L Srinivasan, R Linehan, WM Cowen, EW AF Rothman, Anne Glenn, Gladys Choyke, Lynda Srinivasan, Ramaprasad Linehan, W. Marston Cowen, Edward W. TI Multiple painful cutaneous nodules and renal mass SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID CELL-CANCER; FUMARATE-HYDRATASE; HEREDITARY LEIOMYOMATOSIS; MUTATIONS; FAMILIES; SKIN; FH C1 NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Cowen, EW (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10,Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. EM cowene@mail.nih.gov NR 11 TC 8 Z9 8 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2006 VL 55 IS 4 BP 683 EP 686 DI 10.1016/j.jaad.2006.06.026 PG 4 WC Dermatology SC Dermatology GA 087OV UT WOS:000240752600016 PM 17010749 ER PT J AU Hudson, TS Forman, MR Cantwell, MM Schatzkin, A Albert, PS Lanza, E AF Hudson, Tamaro S. Forman, Michele R. Cantwell, Marie M. Schatzkin, Arthur Albert, Paul S. Lanza, Elaine TI Dietary fiber intake: Assessing the degree of agreement between food frequency questionnaires and 4-day food records SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE dietary fiber; dietary assessment; food frequency questionnaire; food records ID COLORECTAL-CANCER; COLON-CANCER; LIFE-STYLE; LOW-FAT; RISK; VALIDATION; VALIDITY; COHORT; TRIAL; REPRODUCIBILITY AB Objective: To assess the degree of agreement (comparability) between dietary fiber intakes reported on a food frequency questionnaire (FFQ) with 4-day food records (4DFR) and determine whether demographic, behavioral and biological factors influence comparability. Methods: At baseline and year one, all participants in the Polyp Prevention Trial (PPT), a multi-center randomized, clinical trial of a low-fat, high fiber, high fruit/vegetable eating plan and recurrence of large bowel adenomatous polyps were instructed in dietary assessment and completed a 106-item FFQ and 4DFR that trained nutritionists reviewed. A random sub-cohort of participants (n = 399) was selected from the intervention and control arms of the PPT for analysis of both FFQ and 4DFR. Results: Baseline crude and energy-adjusted fiber intakes were significantly higher in the 4DFR than the FFQ (P = 0.001). Using Bland-Altman statistics, the mean difference (FFQ-4DFR) was -0.11 g/MJ; while the limits of agreement were - 1.45, 1.23 g/MJ. The mean fiber difference increased with increasing average intake (FFQ + 4DFR)/2, (P = 0.004) for men, but not women (P = 0.10), suggesting that fiber intake was under-estimated in the FFQ, relative to the 4-DFR, for men with low fiber intakes and over-estimated for men with high intakes. Smoking and gender significantly influenced the average intake at baseline, whereas other demographic and behavioral factors did not. Education was significantly associated with average difference in fiber intake at baseline, but not at year 1. Conclusions: This study of clinical trial volunteers revealed differences in the ability to comparably report fiber intake across tools by gender, smoking, and education, however participants' repeated training in dietary assessment improved comparability in reporting over time. C1 NCI, Lab Canc Prevent, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Lab Biosyst & Canc, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Lanza, E (reprint author), NCI, Lab Canc Prevent, Canc Res Ctr, NIH, 6116 Execut Blvd, Bethesda, MD 20892 USA. EM el33t@nih.gov NR 48 TC 16 Z9 18 U1 1 U2 5 PU AMER COLLEGE NUTRITION PI CLEARWATER PA 300 SOUTH DUNCAN AVENUE, STE 225, CLEARWATER, FL 33755 USA SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD OCT PY 2006 VL 25 IS 5 BP 370 EP 381 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 094EN UT WOS:000241222400002 PM 17031005 ER PT J AU Barnett, ML Hyman, JJ AF Barnett, Michael L. Hyman, Jeffrey J. TI Challenges in interpreting study results - The conflict between appearance and reality SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE epidemiology; case-control studies; cohort studies; disease causation ID PERIODONTAL-DISEASE; CIGARETTE-SMOKING; SYSTEMIC-DISEASE; ASSOCIATIONS; CAUSATION; STRENGTH; BIAS AB Background. Many studies investigating the relationship between periodontal disease and systemic diseases have been reported; the majority of these have been epidemiologic (or observational) studies. The purpose of this article is to help readers understand the strengths and limitations of epidemiology for the purpose of being better able to interpret these studies. Findings. Epidemiologic studies include retrospective case-control studies and prospective cohort studies. While these studies cannot prove causality, they can provide strong evidence for and show the strength of an association between a disease and putative causative factors. Randomized controlled trials (RCTs) are used to test therapeutic and preventive measures and can provide presumptive evidence of disease causation in certain circumstances. Each of these study types has limitations that can distort the study results and, therefore, should be considered in study design and analysis. Conclusions and Clinical Implications. Epidemiologic studies conducted to date suggest an association between periodontal disease and a number of systemic diseases. However, the strength and nature of this association are not yet clear, because in some cases it might result from confounding by smoking or other variables. Additional well-designed observational studies and future RCTs should increase our understanding of the actual relationship between periodontal and systemic diseases. C1 SUNY Buffalo, Dept Periodont Endodont, Sch Dent Med, Buffalo, NY 14260 USA. Natl Inst Dent & Craniofacial Res, Off Sci Policy & Anal, Bethesda, MD USA. RP Barnett, ML (reprint author), 112 Hidden Ridge Common, Williamsville, NY 14221 USA. EM mlbgums@aol.com NR 19 TC 3 Z9 4 U1 0 U2 1 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD OCT PY 2006 VL 137 SU S BP 32S EP 36S PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 096JX UT WOS:000241374500006 PM 17012734 ER PT J AU Subar, AF Dodd, KW Guenther, PM Kipnis, V Midthune, D McDowell, M Tooze, JA Freedman, LS Krebs-Smith, SM AF Subar, Amy F. Dodd, Kevin W. Guenther, Patricia M. Kipnis, Victor Midthune, Douglas McDowell, Margaret Tooze, Janet A. Freedman, Laurence S. Krebs-Smith, Susan M. TI The Food Propensity Questionnaire: Concept, development, and validation for use as a covariate in a model to estimate usual food intake SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID DIETARY MEASUREMENT ERROR; FREQUENCY QUESTIONNAIRES; SAMPLE AB Objective Twenty-four- hour recalls capture rich information on food consumption, but suffer from inadequately measuring usual intakes of episodically consumed foods. We explore using food frequency questionnaire (FFQ) data as covariates in a statistical model to estimate individual usual intakes of episodically consumed foods and their distributions and describe the development of the Food Propensity Questionnaire, an FFQ introduced in the 2003-2004 National Health and Nutrition Examination Survey. Design We analyzed data from 965 adult participants in the Eating at America's Table Study who completed four 24-hour recalls and an FFQ. We assessed whether or not increasing FFQ-reported frequency was associated with both number of 24-hour recall consumption days and amounts reported. Results For 52 of 56 food groups (93%), and 218 of 230 individual foods (95%), there were significant monotonically increasing relationships between FFQ frequency and 24-hour recall probability of consumption. For 47 of 56 food groups (84%) and 55 of 230 (24%) individual foods, there were significant positive correlations between FFQ frequencies and consumption-day mean intake. Conclusions We found strong and consistent relationships between reported FFQ frequency of food and food-group consumption and probability of consumption on 24-hour recalls. This supports the premise that frequency data may offer important covariate information in supplementing multiple recalls for estimating usual intake of food groups. C1 NCI, Bethesda, MD 20892 USA. USDA, Ctr Nutr Policy & Promot, Washington, DC 20250 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Biostat Sect, Winston Salem, NC USA. Chaim Sheba Med Ctr, Gertner Inst Epidemiol & Hlth Policy Res, Biostat Unit, IL-52621 Tel Hashomer, Israel. RP Subar, AF (reprint author), NCI, 6130 Execut Blvd,EPN 4005,MSC 7344, Bethesda, MD 20892 USA. EM subara@mail.nih.gov NR 23 TC 79 Z9 80 U1 1 U2 14 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD OCT PY 2006 VL 106 IS 10 BP 1556 EP 1563 DI 10.1016/j.jada.2006.07.002 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 090BI UT WOS:000240925200012 PM 17000188 ER PT J AU Tooze, JA Midthune, D Dodd, KW Freedman, LS Krebs-Smith, SM Subar, AF Guenther, PM Carroll, RJ Kipnis, V AF Tooze, Janet A. Midthune, Douglas Dodd, Kevin W. Freedman, Laurence S. Krebs-Smith, Susan M. Subar, Amy F. Guenther, Patricia M. Carroll, Raymond J. Kipnis, Victor TI A new statistical method for estimating the usual intake of episodically consumed foods with application to their distribution SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID DOUBLY LABELED WATER; CONSUMPTION AB Objective We propose a new statistical method that uses information from two 24-hour recalls to estimate usual intake of episodically consumed foods. Statistical analyses performed The method developed at the National Cancer Institute (NCI) accommodates the large number of nonconsumption days that occur with foods by separating the probability of consumption from the consumption-day amount, using a two-part model. Covariates, such as sex, age, race, or information from a food frequency questionnaire, may supplement the information from two or more 24-hour recalls using correlated mixed model regression. The model allows for correlation between the probability of consuming a food on a single day and the consumption-day amount. Percentiles of the distribution of usual intake are computed from the estimated model parameters. Results The Eating at America's Table Study data are used to illustrate the method to estimate the distribution of usual intake for whole grains and dark-green vegetables for men and women and the distribution of usual intakes of whole grains by educational level among men. A simulation study indicates that the NCI method leads to substantial improvement over existing methods for estimating the distribution of usual intake of foods. Conclusions The NCI method provides distinct advantages over previously proposed methods by accounting for the correlation between probability of consumption and amount consumed and by incorporating covariate information. Researchers interested in estimating the distribution of usual intakes of foods for a population or subpopulation are advised to work with a statistician and incorporate the NCI method in analyses. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA. NCI, Bethesda, MD 20892 USA. Chaim Sheba Med Ctr, Gertner Inst Epidemiol & Hlth Policy Res, Biostat Unit, IL-52621 Tel Hashomer, Israel. USDA, Ctr Nutr Policy & Promot, Alexandria, VA USA. Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. RP Tooze, JA (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM jtooze@wfubmc.edu FU NCI NIH HHS [R37 CA057030, CA-57030, R37 CA057030-19]; NIEHS NIH HHS [P30 ES009106, P30 ES009106-04, P30-ES09106] NR 15 TC 206 Z9 212 U1 1 U2 25 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD OCT PY 2006 VL 106 IS 10 BP 1575 EP 1587 DI 10.1016/j.jada.2006.07.003 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 090BI UT WOS:000240925200014 PM 17000190 ER PT J AU Dodd, KW Guenther, PM Freedman, LS Subar, AF Kipnis, V Midthune, D Tooze, JA Krebs-Smith, SM AF Dodd, Kevin W. Guenther, Patricia M. Freedman, Laurence S. Subar, Amy F. Kipnis, Victor Midthune, Douglas Tooze, Janet A. Krebs-Smith, Susan M. TI Statistical methods for estimating usual intake of nutrients and foods: A review of the theory SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Review ID DIETARY RECALL DATA; INTAKE DISTRIBUTIONS; QUESTIONNAIRE; POPULATION; NUTRITION; VARIANCE; DESIGN AB Although 24-hour recalls are fiequently used in dietary assessment, intake on a single day is a poor estimator of long-term usual intake. Statistical modeling mitigates this limitation more effectively than averaging multiple 24-hour recalls per respondent. In this article, we describe the statistical theory that underlies the four major modeling methods developed to date, then review the strengths and limitations of each method. We focus on the problem of estimating the distribution of usual intake for a population from 24-hour recall data, giving special attention to the problems inherent in modeling usual intake for foods or food groups that a proportion of the population does not consume every day (ie, episodically consumed foods). All four statistical methods share a common framework. Differences between the methods arise from different assumptions about the measurement characteristics of 24-hour recalls and from the fact that more recently developed methods build upon their predecessor(s). These differences can result in estimated usual intake distributions that differ from one another. We also demonstrate the need for an improved method for estimating usual intake distributions for episodically consumed foods. C1 NCI, Bethesda, MD 20892 USA. USDA, Ctr Nutr Policy & Promot, Alexandria, VA USA. Chaim Sheba Med Ctr, Gertner Inst Epidemiol & Hlth Policy Res, Biostat Unit, IL-52621 Tel Hashomer, Israel. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Biostat Sect, Winston Salem, NC 27103 USA. RP Dodd, KW (reprint author), NCI, 6116 Execut Blvd,MSC 8317, Bethesda, MD 20892 USA. EM doddk@mail.nih.gov NR 28 TC 239 Z9 252 U1 6 U2 38 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD OCT PY 2006 VL 106 IS 10 BP 1640 EP 1650 DI 10.1016/j.jada.2006.07.011 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 090BI UT WOS:000240925200021 PM 17000197 ER PT J AU Hoggle, LB Michael, MA Houston, SM Ayres, EJ AF Hoggle, Lindsey B. Michael, Madeline A. Houston, Susan M. Ayres, Elaine J. TI Electronic health record: Where does nutrition fit in? SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Editorial Material ID AMERICAN-DIETETIC-ASSOCIATION; PHYSICIAN ORDER ENTRY; INFORMATION-TECHNOLOGY; PATIENT OUTCOMES; CARE PROCESS; SYSTEMS; COSTS; MODEL; PERFORMANCE; STANDARDS C1 NIH, Clin Nutr Serv, Bethesda, MD 20892 USA. RP Hoggle, LB (reprint author), 13501 Haddonfield, Gaithersburg, MD 20878 USA. EM Lindseyhoggle@comcast.net NR 40 TC 3 Z9 4 U1 1 U2 1 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD OCT PY 2006 VL 106 IS 10 BP 1688 EP 1695 DI 10.1016/j.jada.2006.07.031 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 090BI UT WOS:000240925200028 PM 17000204 ER PT J AU Hofman, K Ryce, A Prudhomme, W Kotzin, S AF Hofman, Karen Ryce, Andrea Prudhomme, Wendy Kotzin, Sheldon TI Reporting of non-communicable disease research in low- and middle-income countries: a pilot bibliometric analysis SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB Objective: The paper identifies the relative amount of research devoted to non-communicable disease in low- and middle-income countries (LMICs). Design: A bibliometric analysis of a subset of journals published in LMICs was performed. Measurements: Seventy-six peer-reviewed journals focused on general medicine or public health published in 46 LMICs and indexed from 1998 to 2003 in MEDLINE. A total of 24 journals were selected, 4 journals from each of 6 LMIC regions. Searches were refined using 18 non-communicable disease topics with 7,012 articles identified for analysis. Results: More than 40% of articles in LMIC regions focused on non-communicable disease research. The percentage was highest in Eastern Europe/Central Asia (47%) and lowest in Latin America (36%). The percentage of articles published in Sub-Saharan Africa (38%) did not differ significantly from that of Latin America or South Asia. Cardiovascular disease and cancer led the list of the top ten most-indexed published topics by region. Conclusions: Even in regions rampant with infectious diseases, some capability exists to conduct research on non-communicable diseases. Greater attention should be paid to the conduct and support of such research in LMICs, which will benefit these countries and may yield clues to lower-cost solutions to the burden of these diseases worldwide. C1 NIH, Div Adv Studies & Policy Anal, Fogarty Int Ctr, Bethesda, MD 20892 USA. NIH, Natl Lib Med, Bibliog Serv Div, Bethesda, MD 20892 USA. RP Hofman, K (reprint author), NIH, Div Adv Studies & Policy Anal, Fogarty Int Ctr, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM hofmank@mail.nih.gov; rycea@u.washington.edu; wp65h@nih.gov; kotzin@nlm.nih.gov RI Ryce, Andrea/C-5587-2014 OI Ryce, Andrea/0000-0001-9709-2156 NR 15 TC 20 Z9 20 U1 0 U2 3 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD OCT PY 2006 VL 94 IS 4 BP 415 EP 420 PG 6 WC Information Science & Library Science SC Information Science & Library Science GA 100QH UT WOS:000241683100009 PM 17082833 ER PT J AU Locatis, C Gaines, C Liu, WL Gill, M Carney, J Foster, J McCall, V Woods, M AF Locatis, Craig Gaines, Cynthia Liu, Wei-Li Gill, Michael Carney, John Foster, Jamelia McCall, Valerie Woods, Michelle TI A blended training approach using videoconferencing for distance education SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article C1 Natl Lib Med, Bethesda, MD 20894 USA. Charles R Drew Univ Med & Sci, King Drew Hlth Sci Lib, Los Angeles, CA 90059 USA. King Drew Med Magnet High Sch, Los Angeles, CA USA. RP Locatis, C (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM locatis@nlm.nih.gov; gainesc@mail.nlm.nih.gov; wliu@mail.nih.gov; mgill@mail.nih.gov; jocarney@cdrewu.edu; jafoster@cdrewu.edu NR 20 TC 3 Z9 3 U1 1 U2 3 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD OCT PY 2006 VL 94 IS 4 BP 464 EP 468 PG 5 WC Information Science & Library Science SC Information Science & Library Science GA 100QH UT WOS:000241683100021 PM 17082845 ER PT J AU Burvall, A Barrett, HH Dainty, C Myers, KJ AF Burvall, Anna Barrett, Harrison H. Dainty, Christopher Myers, Kyle J. TI Singular-value decomposition for through-focus imaging systems SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID SPHEROIDAL WAVE-FUNCTIONS; FOURIER-ANALYSIS; FRESNEL ZONE; UNCERTAINTY; RESOLUTION; MODES AB Singular-value decomposition (SVD) of a linear imaging system gives information on the null and measurement components of object and image and provides a method for object reconstruction from image data. We apply SVD to through-focus imaging systems that produce several two-dimensional images of a three-dimensional object. Analytical expressions for the singular functions are derived in the geometrical approximation for a telecentric, laterally shift-invariant system linear in intensity. The modes are evaluated numerically, and their accuracy confirmed. Similarly, the modes are derived and evaluated for a continuous image representing the limit of a large number of image planes. (c) 2006 Optical Society of America. C1 Natl Univ Ireland Univ Coll Galway, Dept Expt Phys, Galway, Ireland. Univ Arizona, Coll Opt Sci, Tucson, AZ 85724 USA. Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. US FDA, Natl Inst Biomed Imaging & Bioengn, US Nalt Inst Hlth, Ctr Devices & Radiol Hlth,Lab Assessement Med Ima, Rockville, MD 20850 USA. RP Burvall, A (reprint author), Natl Univ Ireland Univ Coll Galway, Dept Expt Phys, Galway, Ireland. EM anna.burvall@nuigalway.ie NR 16 TC 2 Z9 2 U1 1 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 EI 1520-8532 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD OCT PY 2006 VL 23 IS 10 BP 2440 EP 2448 DI 10.1364/JOSAA.23.002440 PG 9 WC Optics SC Optics GA 089CU UT WOS:000240858500008 PM 16985529 ER PT J AU Saha, A Liang, H Badano, A AF Saha, Anindita Liang, Hongye Badano, Aldo TI Color measurement methods for medical displays SO JOURNAL OF THE SOCIETY FOR INFORMATION DISPLAY LA English DT Article DE medical display; color measurement; color uniformity; luminance uniformity ID PERFORMANCE AB The effect of different measurement methods on the characterization of display color, maximum color difference, and luminance uniformity of medical liquid-crystal displays are reported. We use a telescopic colorimeter and a custom-designed collimated probe with an internal lens attached to a spectrometer. The maximum color-difference variations were found to be between 0.0047 to 0.0073, in the same range as variations among methods, displays, and screen locations. C1 US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math,Off Sci & Engn Labs, CDRH NIBIB Lab Assessment Med Imaging Syst, Rockville, MD 20952 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math,Off Sci & Engn Labs, CDRH NIBIB Lab Assessment Med Imaging Syst, 12720 Twinbrook Pkwy, Rockville, MD 20952 USA. EM aldo.badano@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 10 TC 4 Z9 4 U1 0 U2 2 PU SOC INFORMATION DISPLAY PI SAN JOSE PA 610 S SECOND STREET, SAN JOSE, CA 95112 USA SN 1071-0922 J9 J SOC INF DISPLAY JI J. Soc. Inf. Disp. PD OCT-DEC PY 2006 VL 14 IS 10-12 BP 979 EP 985 DI 10.1889/1.2393035 PG 7 WC Engineering, Electrical & Electronic; Materials Science, Multidisciplinary; Optics; Physics, Applied SC Engineering; Materials Science; Optics; Physics GA 129LO UT WOS:000243731200021 ER PT J AU Setse, RW Cutts, F Monze, M Ryon, JJ Quinn, TC Griffin, DE Moss, WJ AF Setse, Rosanna W. Cutts, Felicity Monze, Mwaka Ryon, Judith J. Quinn, Thomas C. Griffin, Diane E. Moss, William J. TI HIV-1 infection as a risk factor for incomplete childhood immunization in Zambia SO JOURNAL OF TROPICAL PEDIATRICS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MORTALITY; CHILDREN; COVERAGE; AFRICA; DETERMINANTS; INFANTS; MOTHERS; IMPACT; GHANA AB Immunizations are of particular importance for human immunodeficiency virus type 1(HIV-1)-infected children as they are at increased risk of severe disease and death from several vaccine-preventable diseases. Outside the United States, however, research on the impact of the HIV-1 epidemic on childhood immunization coverage is sparse. We conducted a nested case-control study in hospitalized children with measles to assess whether HIV-1 infection was a risk factor for incomplete immunization with diphtheria-tetanus-pertussis vaccine (DTP) and oral polio vaccine (OPV). Of 473 children, whose immunization status was determined from the immunization record or maternal recall, 23% were incompletely immunized and 19% were HIV-1 infected. After adjusting for age, sex, and measles vaccination status, HIV-1 infection was significantly associated with incomplete immunization with DTP and OPV (adjusted OR 1.9; 95% CI 1.1, 3.3). In a subset of children for whom information on maternal education was available, less than 7 years of school education was a risk factor for incomplete immunization (adjusted OR 3.7; 95% CI 1.8. 7.5). Children from homes with more than three children were twice as likely to be incompletely immunized as those from homes with one to three children. Our findings suggest that HIV-1-infected children are at increased risk of vaccine-preventable diseases not only because of impaired immune responses but because of lower rates of vaccine coverage. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1, England. Univ Teaching Hosp, Virol Lab, Lusaka, Zambia. Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Moss, WJ (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. EM wmoss@jhsph.edu NR 23 TC 17 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0142-6338 J9 J TROP PEDIATRICS JI J. Trop. Pediatr. PD OCT PY 2006 VL 52 IS 5 BP 324 EP 328 DI 10.1093/tropej/fmk002 PG 5 WC Pediatrics; Tropical Medicine SC Pediatrics; Tropical Medicine GA 090DV UT WOS:000240931700005 PM 16401614 ER PT J AU Brown, E Senkevich, TG Moss, B AF Brown, Erica Senkevich, Tatiana G. Moss, Bernard TI Vaccinia virus F9 virion membrane protein is required for entry but not virus assembly, in contrast to the related L1 protein SO JOURNAL OF VIROLOGY LA English DT Article ID INTRACELLULAR MATURE VIRIONS; CELL-CELL FUSION; OPEN READING FRAME; ESSENTIAL COMPONENT; EARLY STEP; GENE; MORPHOGENESIS; EXPRESSION; RECOMBINANT; ANTIBODIES AB All sequenced poxviruses encode orthologs of the vaccinia virus L1 and F9 proteins, which are structurally similar and share about 20% amino acid identity. We found that F9 further resembles L1 as both proteins are membrane components of the mature virion with similar topologies and induce neutralizing antibodies. In addition, a recombinant vaccinia virus that inducibly expresses F9, like a previously described L1 mutant, had a conditional-lethal phenotype: plaque formation and replication of infectious virus were dependent on added inducer. However, only immature virus particles are made when L1 is repressed, whereas normal-looking intracellular and extracellular virions formed in the absence of F9. Except for the lack of F9, the polypeptide components of such virions were indistinguishable from those of wild-type virus. These F9-deficient virions bound to cells, but their cores did not penetrate into the cytoplasm. Furthermore, cells infected with F9-negative virions did not fuse after a brief low-pH treatment, as did cells infected with virus made in the presence of inducer. In these respects, the phenotype associated with F9 deficiency was identical to that produced by the lack of individual components of a previously described poxvirus entry/fusion complex. Moreover, F9 interacted with proteins of that complex, supporting a related role. Thus, despite the structural relationships of L1 and F9, the two proteins have distinct functions in assembly and entry, respectively. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Intramural NIH HHS; NIAID NIH HHS [U54 AI057168, U54-AI57168] NR 42 TC 51 Z9 54 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2006 VL 80 IS 19 BP 9455 EP 9464 DI 10.1128/JVI.01149-06 PG 10 WC Virology SC Virology GA 086BD UT WOS:000240647200011 PM 16973551 ER PT J AU McPhillips, MG Oliveira, JG Spindler, JE Mitra, R McBride, AA AF McPhillips, M. G. Oliveira, J. G. Spindler, J. E. Mitra, R. McBride, A. A. TI Brd4 is required for E2-mediated transcriptional activation but not genome partitioning of all papillomaviruses SO JOURNAL OF VIROLOGY LA English DT Article ID BROMODOMAIN PROTEIN BRD4; VIRAL E2 PROTEIN; HPV18 REGULATORY REGION; MITOTIC CHROMOSOMES; GENE-PRODUCT; DNA-REPLICATION; EPISOMAL MAINTENANCE; COACTIVATOR HCF-1; E6 PROMOTER; CELL-LINES AB Bromodomain protein 4 (Brd4) has been identified as the cellular binding target through which the E2 protein of bovine papillomavirus type I links the viral genome to mitotic chromosomes. This tethering ensures retention and efficient partitioning of genomes to daughter cells following cell division. E2 is also a regulator of viral gene expression and a replication factor, in association with the viral El protein. In this study, we show that E2 proteins from a wide range of papillomaviruses interact with Brd4, albeit with variations in efficiency. Moreover, disruption of the E2-Brd4 interaction abrogates the transactivation function of E2, indicating that Brd4 is required for E2-mediated transactivation of all papillomaviruses. However, the interaction of E2 and Brd4 is not required for genome partitioning of all papillomaviruses since a number of papillomavirus E2 proteins associate with mitotic chromosomes independently of Brd4 binding. Furthermore, mutations in E2 that disrupt the interaction with Brd4 do not affect the ability of these E2s to associate with chromosomes. Thus, while all papillomaviruses attach their genomes to cellular chromosomes to facilitate genome segregation, they target different cellular binding partners. In summary, the E2 proteins from many papillomaviruses, including the clinically important alpha genus human papillomaviruses, interact with Brd4 to mediate transcriptional activation function but not all depend on this interaction to efficiently associate with mitotic chromosomes. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP McBride, AA (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 137,4 Ctr Dr,MSC 0455, Bethesda, MD 20892 USA. EM amcbride@nih.gov OI McBride, Alison/0000-0001-5607-5157 FU Intramural NIH HHS NR 63 TC 101 Z9 102 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2006 VL 80 IS 19 BP 9530 EP 9543 DI 10.1128/JVI.01105-06 PG 14 WC Virology SC Virology GA 086BD UT WOS:000240647200017 PM 16973557 ER PT J AU Chen, JB Powell, D Hu, WS AF Chen, Jianbo Powell, Douglas Hu, Wei-Shau TI High frequency of genetic recombination is a common feature of primate lentivirus replication SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; MONKEYS CERCOPITHECUS-LHOESTI; HIGH NEGATIVE INTERFERENCE; RETROVIRAL RECOMBINATION; VIRAL REPLICATION; IN-VIVO; REVERSE TRANSCRIPTION; PACKAGING SIGNAL; TARGET-CELLS AB Recent studies indicate that human immunodeficiency virus type 1 (HIV-1) recombines at exceedingly high rates, approximately 1 order of magnitude more frequently than simple gammaretroviruses such as murine leukemia virus and spleen necrosis virus. We hypothesize that this high frequency of genetic recombination is a common feature of primate lentiviruses. Alternatively, it is possible that HIV-1 is unique among primate lentiviruses in possessing high recombination rates. Among other primate lentiviruses, only the molecular mechanisms of HIV-2 replication have been extensively studied. There are reported differences between the replication mechanisms of HIV-1 and those of HIV-2, such as preferences for RNA packaging in cis and properties of reverse transcriptase and RNase H activities. These biological disparities could lead to differences in recombination rates between the two viruses. Currently, HIV-1 is the only primate lentivirus in which recombination rates have been measured. To test our hypothesis, we established recombination systems to measure the recombination rates of two other primate lentiviruses, HIV-2 and simian immunodeficiency virus from African green monkeys (SIVagm), in one round of viral replication. We determined that, for markers separated by 588, 288, and 90 bp, HIV-2 recombined at rates of 7.4%, 5.5%, and 2.4%, respectively, whereas SIVagm recombined at rates of 7.8%, 5.6%, and 2.7%, respectively. These high recombination rates are within the same range as the previously measured HIV-1 recombination rates. Taken together, our results indicate that HIV-1, HIV-2, and SIVagm all possess high recombination frequencies; hence, the high recombination potential is most likely a common feature of primate lentivirus replication. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. NCI, Data Management Serv Inc, Frederick, MD 21702 USA. RP Hu, WS (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 535,Room 336, Frederick, MD 21702 USA. EM whu@ncifcrf.gov RI Chen, Jianbo/N-3737-2014 OI Chen, Jianbo/0000-0001-6491-6577 FU Intramural NIH HHS NR 64 TC 28 Z9 31 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2006 VL 80 IS 19 BP 9651 EP 9658 DI 10.1128/JVI.00936-06 PG 8 WC Virology SC Virology GA 086BD UT WOS:000240647200029 PM 16973569 ER PT J AU Ojeda, S Domi, A Moss, B AF Ojeda, Suany Domi, Arban Moss, Bernard TI Vaccinia virus G9 protein is an essential component of the poxvirus entry-fusion complex SO JOURNAL OF VIROLOGY LA English DT Article ID INTRACELLULAR MATURE VIRION; CELL-CELL FUSION; BACTERIAL ARTIFICIAL CHROMOSOME; SURFACE HEPARAN-SULFATE; MEMBRANE-PROTEIN; ENVELOPE PROTEIN; ESCHERICHIA-COLI; MAMMALIAN-CELLS; A27L PROTEIN; IDENTIFICATION AB The vaccinia virus G9R gene (VACWR087) encodes a protein of 340 amino acids with the following structural features that are conserved in all poxviruses: a site for N-terminal myristoylation, 14 cysteines, and a C-terminal transmembrane domain. Previous studies showed that G9 is one of eight proteins associated in a putative entry-fusion complex. Our attempt to isolate a mutant without the G9R gene was unsuccessful, suggesting that it is essential for virus replication. To further investigate its role, we constructed a recombinant vaccinia virus in which G9R is regulated by addition of an inducer. Induced G9 protein was associated with mature infectious virions and could be labeled with a membrane-impermeant biotinylation reagent, indicating surface exposure. Omission of inducer reduced the infectious-virus yield by about 1.5 logs; nevertheless, all stages of virus morphogenesis appeared normal and extracellular virions were present on the cell surface. Purified virions assembled without inducer had a specific infectivity of less than 5% of the normal level and a comparably small amount of G9, whereas their overall polypeptide composition, including other components of the entry-fusion complex, was similar to that of virions made in the presence of inducer or of wild-type virions. G9-deficient virions bound to cells, but penetration of cores into the cytoplasm and early viral RNA synthesis were barely detected, and cell-cell fusion was not triggered by low pH. Of the identified components of the multiprotein complex, G9 is the sixth that has been shown to be required for entry and membrane fusion. RP Moss, B (reprint author), NIAID, NIH, Viral Dis Lab, 4 Mem Dr, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Intramural NIH HHS NR 43 TC 39 Z9 40 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2006 VL 80 IS 19 BP 9822 EP 9830 DI 10.1128/JVI.00987-06 PG 9 WC Virology SC Virology GA 086BD UT WOS:000240647200046 PM 16973586 ER PT J AU Shackelton, LA Rambaut, A Pybus, OG Holmes, EC AF Shackelton, Laura A. Rambaut, Andrew Pybus, Oliver G. Holmes, Edward C. TI JC virus evolution and its association with human populations SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN POLYOMAVIRUS JC; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; HUMAN MIGRATIONS; VIRAL EVOLUTION; DNA; INDIVIDUALS; PHYLOGENY; DIVERSITY; SEQUENCES; COEVOLUTION AB The ubiquitous human polyomavirus JC (JCV) is a small double-stranded DNA virus that establishes a persistent infection, and it is often transmitted from parents to children. There are at least 14 subtypes of the virus associated with different human populations. Because of its presumed codivergence with humans, JCV has been used as a genetic marker for human evolution and migration. Codivergence has also been used as a basis for estimating the rate of nucleotide substitution in JCV. We tested the hypothesis of host-virus codivergence by (i) performing a reconciliation analysis of phylogenetic trees of human and JCV populations and (ii) providing the first estimate of the evolutionary rate of JCV that is independent from the assumption of codivergence. Strikingly, our comparisons of JCV and human phylogenies provided no evidence for codivergence, suggesting that this virus should not be used as a marker for human population history. Further, while the estimated nucleotide substitution rate of JCV has large confidence intervals due to limited sampling, our analysis suggests that this virus may evolve nearly two orders of magnitude faster than predicted under the codivergence hypothesis. C1 Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. Univ Oxford, Dept Zool, Oxford OX1 3PS, England. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Holmes, EC (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. EM ech15@psu.edu RI pybus, oliver/B-2640-2012; OI Pybus, Oliver/0000-0002-8797-2667; Rambaut, Andrew/0000-0003-4337-3707; Holmes, Edward/0000-0001-9596-3552 NR 41 TC 43 Z9 44 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2006 VL 80 IS 20 BP 9928 EP 9933 DI 10.1128/JVI.00441-06 PG 6 WC Virology SC Virology GA 091RU UT WOS:000241046800001 PM 17005670 ER PT J AU Jeong, SJ Lu, HX Cho, WK Park, HU Pise-Masison, C Brady, JN AF Jeong, Soo-Jin Lu, Hanxin Cho, Won-Kyung Park, Hyeon Ung Pise-Masison, Cynthia Brady, John N. TI Coactivator-associated arginine methyltransferase 1 enhances transcriptional activity of the human T-cell lymphotropic virus type 1 long terminal repeat through direct interaction with tax SO JOURNAL OF VIROLOGY LA English DT Article ID CREB BINDING-PROTEIN; RNA-POLYMERASE-II; HTLV-I; GENE-EXPRESSION; 21-BASE-PAIR REPEATS; TRANSACTIVATOR TAX; COMPLEX-FORMATION; HISTONE H3; LEUKEMIA; METHYLATION AB In this study, we demonstrate that the coactivator-associated arginine methyltransferase 1 (CARM1), which methylates histone H3 and other proteins such as p300/CBP, is positively involved in the regulation of Tax transactivation. First, transfection studies demonstrated that overexpression of CARM1 wild-type protein resulted in increased Tax transactivation of the human T-cell lymphotropic virus type 1 (HTLV-1) long terminal repeat (LTR). In contrast, transfection of a catalytically inactive CARM1 methyltransferase mutant did not enhance Tax transactivation. CARM1 facilitated Tax transactivation of the CREB-dependent cellular GEM promoter. A direct physical interaction between HTLV-1 Tax and CARM1 was demonstrated using in vitro glutathione S-transferase-Tax binding assays, in vivo coinummoprecipitation, and confocal microscopy experiments. Finally, chromatin inummoprecipitation analysis of the activated HTLV-1 LTR promoter showed the association of CARM1 and methylated histone H3 with the template DNA. In vitro, Tax facilitates the binding of CARM1 to the transcription complex. Together, our data provide evidence that CARM1 enhances Tax transactivation of the HTLV-1 LTR through a direct interaction between CARM1 and Tax and this binding promotes methylation of histone H3 (R2, R17, and R26). C1 NCI, Tumor Virus Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Brady, JN (reprint author), NCI, Tumor Virus Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, 41 Medlars Dr,Bldg 41,Room B302, Bethesda, MD 20892 USA. EM bradyj@mail.nih.gov FU Intramural NIH HHS NR 55 TC 19 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2006 VL 80 IS 20 BP 10036 EP 10044 DI 10.1128/JVI.00186-06 PG 9 WC Virology SC Virology GA 091RU UT WOS:000241046800012 PM 17005681 ER PT J AU Oh, J Chang, KW Alvord, WG Hughes, SH AF Oh, Jangsuk Chang, Kevin W. Alvord, W. Gregory Hughes, Stephen H. TI Alternate polypurine tracts affect Rous sarcoma virus integration in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; RNASE-H CLEAVAGE; REPLICATION; MUTATIONS; SEQUENCES; SPECIFICITY; DNA AB When the endogenous polypurine tract (PPT) of the Rous sarcoma virus (RSV)-derived vector RSVP(A)Z was replaced with alternate retroviral PPTs, the fraction of unintegrated viral DNA with the normal consensus ends significantly decreased and the retention of part of the PPT significantly increased. If the terminus of the U3 long terminal repeat (LTR) is aberrant, RSV integrase can correctly process and integrate the normal U5 LTR into the host genome. However, the canonical CA is not involved in joining the aberrant U3 LTR to the host DNA, generating either large duplications or deletions of the host sequences instead of the normal 5- or 6-bp duplication. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. NCI, Data Management Serv, Frederick, MD 21702 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 539,Rm 130A, Frederick, MD 21702 USA. EM Hughes@ncifcrf.gov FU Intramural NIH HHS NR 12 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2006 VL 80 IS 20 BP 10281 EP 10284 DI 10.1128/JVI.00361-06 PG 4 WC Virology SC Virology GA 091RU UT WOS:000241046800039 PM 17005708 ER PT J AU Goodpaster, BH Park, SW Harris, TB Kritchevsky, SB Nevitt, M Schwartz, AV Simonsick, EM Tylavsky, FA Visser, M Newman, AB AF Goodpaster, Bret H. Park, Seok Won Harris, Tamara B. Kritchevsky, Steven B. Nevitt, Michael Schwartz, Ann V. Simonsick, Eleanor M. Tylavsky, Frances A. Visser, Marjolein Newman, Anne B. CA Hlth ABC Study TI The loss of skeletal muscle strength, mass, and quality in older adults: The health, aging and body composition study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID X-RAY ABSORPTIOMETRY; GRIP STRENGTH; WOMEN; MEN; AGE; MORTALITY; COHORT; ATTENUATION; PERFORMANCE; POPULATION AB Background. The loss of muscle mass is considered to be a major determinant of strength loss in aging. However, large-scale longitudinal studies examining the association between the loss of mass and strength in older adults are lacking. Methods. Three-year changes in muscle mass and strength were determined in 1880 older adults in the Health, Aging and Body Composition Study. Knee extensor strength was measured by isokinetic dynamometry. Whole body and appendicular lean and fat mass were assessed by dual-energy x-ray absorptiometry and computed tomography. Results. Both men and women lost strength, with men losing almost twice as much strength as women. Blacks lost about 28% more strength than did whites. Annualized rates of leg strength decline (3.4% in white men, 4.1% in black men, 2.6% in white women, and 3.0% in black women) were about three times greater than the rates of loss of leg lean mass (-1% per year). The loss of lean mass, as well as higher baseline strength, lower baseline leg lean mass, and older age, was independently associated with strength decline in both men and women. However, gain of lean mass was not accompanied by strength maintenance or gain (beta coefficients; men, -0.48 +/- 4.6 1, p = .92, women, -1.68 +/- 3.57, p = .64). Conclusions. Although the loss of muscle mass is associated with the decline in strength in older adults, this strength decline is much more rapid than the concomitant loss of muscle mass, suggesting a decline in muscle quality. Moreover, maintaining or gaining muscle mass does not prevent aging-associated declines in muscle strength. C1 Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Sticht Ctr Aging, Dept Internal Med, Winston Salem, NC 27109 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. NIA, Clin Res Branch, Baltimore, MD 21224 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN 38163 USA. Vrije Univ Amsterdam, Inst Res Extramural Med, Amsterdam, Netherlands. RP Goodpaster, BH (reprint author), Univ Pittsburgh, Med Ctr, Dept Med, MUH-N809, Pittsburgh, PA 15213 USA. EM bgood@pitt.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU Intramural NIH HHS NR 40 TC 611 Z9 632 U1 6 U2 65 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD OCT PY 2006 VL 61 IS 10 BP 1059 EP 1064 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 102CL UT WOS:000241788300008 PM 17077199 ER PT J AU Waldman, M Appel, GB AF Waldman, M. Appel, G. B. TI Update on the treatment of lupus nephritis SO KIDNEY INTERNATIONAL LA English DT Review DE lupus nephritis; mycophenolate mofetil; membranous lupus; rituximab; cytotoxic agents ID B-CELL DEPLETION; MONOCLONAL-ANTIBODY RITUXIMAB; PERIPHERAL-BLOOD LYMPHOCYTES; PLACEBO-CONTROLLED TRIAL; MOLECULE CD40 LIGAND; REGULATORY T-CELLS; OPEN-LABEL TRIAL; SYSTEMIC-LUPUS; MYCOPHENOLATE-MOFETIL; LONG-TERM AB Lupus nephritis (LN) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus. Although the use of aggressive immunosuppression has improved both patient and renal survival over the past several decades, the optimal treatment of LN remains challenging. Improved outcomes have come at the expense of significant adverse effects owing to therapy. Moreover with long-term survival, the chronic adverse effects of effective therapies including risk of malignancy, atherosclerosis, infertility, and bone disease all become more important. Finally, some patients fail to achieve remission with standard cytotoxic therapy and others relapse when therapy is reduced. For these reasons, recent clinical trials have attempted to define alternate treatment protocols that appear to be efficacious in achieving and maintaining remission, but with less toxicity than standard regimens. This paper discusses established and newer treatment options for patients with proliferative and membranous LN, with an emphasis on the results of these recent clinical trials. We also review the experimental and human data regarding some of the novel targeted forms of therapy that are under investigation and in different phases of clinical trials. C1 NIDDK, NIH, Kidney Dis Sect, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, Dept Med, Div Nephrol, New York, NY 10032 USA. RP Waldman, M (reprint author), NIDDK, NIH, Kidney Dis Sect, Clin Res Bldg,Rm 5-2551,10 Ctr Dr, Bethesda, MD 20892 USA. EM waldmanm@niddk.nih.gov NR 149 TC 54 Z9 58 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2006 VL 70 IS 8 BP 1403 EP 1412 DI 10.1038/sj.ki.5001777 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 092MX UT WOS:000241102300007 PM 16929249 ER PT J AU Ondrey, FG Moldestad, E Mastroianni, MA Pikus, A Sklare, D Vernon, E Nusenblatt, R Smith, J AF Ondrey, Frank G. Moldestad, Eric Mastroianni, Mary Ann Pikus, Anita Sklare, Daniel Vernon, Estelle Nusenblatt, Robert Smith, Janine TI Sensorineural hearing loss in Vogt-Koyanagi-Harada syndrome SO LARYNGOSCOPE LA English DT Article DE Vogt Koyanagi Harada syndrome; VKH syndrome; SNHL ID EAR IMMUNE-RESPONSES; DISEASE; CRITERIA; TRIAL AB Background: Vogt-Koyanagi-Harada (VKH) syndrome is a systemic condition characterized by ocular inflammatory disease as well as skin, ear, and meningeal manifestations. Patients with VKH often report tinnitus and hearing loss, but these symptoms tend to be given secondary consideration because most undergo treatment with steroids to prevent blindness resulting from granulomatous uveitis, exudative retinal detachment, and optic nerve inflammation. Methods/Study Design: In the current retrospective review, 24 patients with this syndrome were screened for auditory system abnormalities. All patients denied history of noise exposure or ototoxic agent exposure. The age range of the patients was 13 to 42 years. Results. Three patients reported tinnitus and two patients reported sudden hearing loss. One patient experienced vertigo and aural fullness. Eight of 24 patients had pure-tone thresholds greater than 25 dB hearing loss at two or more frequencies. Five of 24 of these patients experienced hearing loss outside of the 95% confidence interval for published age-matched control populations. There was sloping sensorineural hearing loss at 4 kHz and above in five of 24 patients. All eight patients with hearing loss experienced some degree of hearing loss at 4 kHz or above. Three patients had mild to moderate low-frequency sensorineural hearing loss. There were no tympanometric abnormalities suggestive of conductive involvement. Abnormal acoustic reflex decay was observed in one patient. Conclusions. We conclude that a significant number of patients with VKH experience sensorineural hearing loss and that every patient with VKH should undergo a review of systems for auditory abnormalities and referral for audiologic testing if symptomatic. It is possible that untreated patients may experience worse symptoms. C1 Univ Minnesota, Dept Otolaryngol, Minneapolis, MN 55455 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. NIH, Off Rare Dis, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Ondrey, FG (reprint author), Univ Minnesota, Dept Otolaryngol, Box 396,420 Delaware St SE, Minneapolis, MN 55455 USA. EM ondre002@umn.edu NR 18 TC 16 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2006 VL 116 IS 10 BP 1873 EP 1876 DI 10.1097/01.mlg.0000234946.31603.fe PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 090ER UT WOS:000240933900030 PM 17003710 ER PT J AU Barrett, AJ Savani, BN AF Barrett, A. J. Savani, B. N. TI Stem cell transplantation with reduced-intensity conditioning regimens: a review of ten years experience with new transplant concepts and new therapeutic agents SO LEUKEMIA LA English DT Review DE reduced-intensity; myeloablative; non-myeloablative; stem cell transplantation ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; TOTAL-BODY IRRADIATION; ACUTE MYELOID-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; REFRACTORY HEMATOLOGIC MALIGNANCIES; CHRONIC MYELOGENOUS LEUKEMIA; TREATMENT-RELATED MORTALITY; DAILY INTRAVENOUS BUSULFAN; METASTATIC BREAST-CANCER AB The realization in the 1990s that allogeneic stem cell transplants ( SCT) have a potentially curative graft-versus-leukemia ( GVL) effect in addition to the antileukemic action of myeloablative conditioning regimens was a major stimulus for the development of reduced-intensity conditioning ( RIC) regimens, aimed primarily at securing engraftment to provide the GVL effect, while minimizing regimen-related toxicity. It is now over 10 years since RIC regimens were heralded as a new direction in the field of SCT. Over the last decade much has been learned about the ways in which the conditioning regimen can be tailored to provide adequate immunosuppression, and modulated to deliver a chosen degree of antimalignant treatment. The huge literature of clinical data with RIC transplantation now permits us to more clearly define the success and limitations of the approach. This review examines the origins of RIC SCT, explores the degree to which the initial expectations and purpose of the approach have been realized, and outlines some ways forward for the field. C1 NHLBI, Stem Cell Allogen Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Stem Cell Allogen Transplantat Sect, Hematol Branch, NIH, Bldg 10,Hatfield CRC,Room 3-5330,10 Ctr Dr MSC 12, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov NR 125 TC 75 Z9 78 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 2006 VL 20 IS 10 BP 1661 EP 1672 DI 10.1038/sj.leu.2404334 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA 096MK UT WOS:000241381000004 PM 16871277 ER PT J AU Abdelaziz, A Dakhil, N Elbaz, T Shehab, H Zekri, A Bisceglie, AD AF Abdelaziz, A. Dakhil, N. Elbaz, T. Shehab, H. Zekri, A. Bisceglie, A. D. TI Smoking increases the risk of hepatocellular carcinoma in cirrhosis SO LIVER INTERNATIONAL LA English DT Meeting Abstract C1 Cairo Univ, Cairo, Egypt. St Louis Univ, Ctr Liver, St Louis, MO 63103 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1478-3223 J9 LIVER INT JI Liver Int. PD OCT PY 2006 VL 26 SU 1 BP 63 EP 63 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 076EC UT WOS:000239938800191 ER PT J AU Hassan, R AF Hassan, R. TI Multi-center clinical trials for peritoneal mesothelioma: Can they be done and what are the questions to be answered? SO LUNG CANCER LA English DT Meeting Abstract C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD OCT PY 2006 VL 54 SU 1 MA 129 BP S32 EP S32 DI 10.1016/S0169-5002(07)70205-2 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 103PY UT WOS:000241900400130 ER PT J AU Hassan, R AF Hassan, R. TI Mesotheliomas of the pericardium and tunica vaginalis SO LUNG CANCER LA English DT Meeting Abstract C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD OCT PY 2006 VL 54 SU 1 MA 107 BP S27 EP S27 DI 10.1016/S0169-5002(07)70183-6 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 103PY UT WOS:000241900400108 ER PT J AU Hassan, R Zhang, J Pastan, I AF Hassan, R. Zhang, J. Pastan, I. TI Antibody-based treatment for mesothelioma: Clinical trials and laboratory studies SO LUNG CANCER LA English DT Meeting Abstract C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD OCT PY 2006 VL 54 SU 1 MA 50 BP S13 EP S13 DI 10.1016/S0169-5002(07)70126-5 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 103PY UT WOS:000241900400051 ER PT J AU Pingpank, J AF Pingpank, J. TI Aggressive surgical cytoreduction with hyperthermic intrapernonew chemoperfusion for patients with malignant mesothelioma SO LUNG CANCER LA English DT Meeting Abstract C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD OCT PY 2006 VL 54 SU 1 MA 110 BP S27 EP S28 DI 10.1016/S0169-5002(07)70186-1 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 103PY UT WOS:000241900400111 ER PT J AU Varghese, S Pingpank, J Xu, H Cox, D Alexander, HR AF Varghese, S. Pingpank, J. Xu, H. Cox, D. Alexander, H. R. TI Gene expression profiling of malignant peritoneal mesothelioma identifies novel targets for therapeutic intervention SO LUNG CANCER LA English DT Meeting Abstract C1 Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD OCT PY 2006 VL 54 SU 1 MA 62 BP S15 EP S16 DI 10.1016/S0169-5002(07)70138-1 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 103PY UT WOS:000241900400063 ER PT J AU Fukunaga, M Horovitz, SG van Gelderen, P de Zwart, JA Jansma, JM Ikonomidou, VN Chu, RX Deckers, RHR Leopold, DA Duyn, JH AF Fukunaga, Masaki Horovitz, Silvina G. van Gelderen, Peter de Zwart, Jacco A. Jansma, J. Martijn Ikonomidou, Vasiliki N. Chu, Renxin Deckers, Roel H. R. Leopold, David A. Duyn, Jeff H. TI Large-amplitude, spatially correlated fluctuations in BOLD fMRI signals during extended rest and early sleep stages SO MAGNETIC RESONANCE IMAGING LA English DT Article DE BOLD; fMRI; fluctuation; resting state; connectivity ID CEREBRAL-BLOOD-FLOW; INDEPENDENT COMPONENT ANALYSIS; SLOW-WAVE SLEEP; FUNCTIONAL CONNECTIVITY; DEFAULT-MODE; ALPHA-RHYTHM; BRAIN-FUNCTION; VISUAL-CORTEX; BASAL GANGLIA; OSCILLATIONS AB A number of recent studies of human brain activity using blood-oxygen-level-dependent (BOLD) fMRI and EEG have reported the presence of spatiotemporal patterns of correlated activity in the absence of external stimuli. Although these patterns have been hypothesized to contain important information about brain architecture, little is known about their origin or about their relationship to active cognitive processes such as conscious awareness and monitoring of the environment. In this study, we have investigated the amplitude and spatiotemporal characteristics of resting-state activity patterns and their dependence on the subjects' alertness. For this purpose, BOLD fMRI was performed at 3.0 T on 12 normal subjects using a visual stimulation protocol, followed by a 27 min rest period, during which subjects were allowed to fall asleep. In subjects who were asleep at the end of the scan, we found (a) a higher amplitude of BOLD signal fluctuation during rest compared with subjects who were awake at the end of the scan; (b) spatially independent patterns of correlated activity that involve all of gray matter, including deep brain nuclei; (c) many patterns that were consistent across subjects; (d) that average percentage levels of fluctuation in visual cortex (VC) and whole brain were higher in subjects who were asleep (up to 1.71% and 1.16%, respectively) than in those who were awake (up to 1.15% and 0.96%) at the end of the scan and were comparable with those levels evoked by intense visual stimulation (up to 1.85% and 0.76% for two subject groups); (e) no confirmation of correlation, positive or negative, between thalamus and VC found in earlier studies. These findings suggest that resting-state activity continues during sleep and does not require active cognitive processes or conscious awareness. (C) 2006 Elsevier Inc. All rights reserved. C1 NINDS, ADV MRI, LFMI, NIH, Bethesda, MD 20892 USA. NIMH, Unit Cognit Neurophysiol & Imaging, NIH, Bethesda, MD 20892 USA. RP Fukunaga, M (reprint author), NINDS, ADV MRI, LFMI, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM fukunagm@mail.nih.gov RI Duyn, Jozef/F-2483-2010; Fukunaga, Masaki/F-6441-2013; Deckers, Roel/J-7749-2015; OI Fukunaga, Masaki/0000-0003-1010-2644; Deckers, Roel/0000-0001-5281-2949; Leopold, David/0000-0002-1345-6360 NR 74 TC 168 Z9 173 U1 1 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD OCT PY 2006 VL 24 IS 8 BP 979 EP 992 DI 10.1016/j.mri.2006.04.018 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 094QG UT WOS:000241253500001 PM 16997067 ER PT J AU Umegaki, H Yamaguchi, Y Ishiwata, K Ingram, DK Roth, GS Iguchi, A AF Umegaki, Hiroyuki Yamaguchi, Yoko Ishiwata, Kiichi Ingram, Donald K. Roth, George S. Iguchi, Akihisa TI Functional recovery of the striatal cholinergic system in aged rats by adenoviral vector-mediated gene transfer of dopamine D-2 receptor SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE microdialysis; quinpirole; acetylcholine; dopamine D-2 receptor; gene transfer ID D-2 RECEPTOR; MESSENGER-RNA; NEURONS AB We previously reported that the striatal dopamine-acetylcholine (ACh) interaction was affected by the aging process, possibly via a decrease of the striatal D2R expression. In the current study, the ACh responses to the infusion of 0.1 mu M of the D2R agonist quinpirole were measured with microdialysis techniques after adenoviral vector-mediated gene transfer of D2R into the striatum of 25-month-old rats. The D2R gene-transferred rats showed significantly stronger responses of the striatal cholinergic neurons to the infusion of the D2R agonist than did control vector-transferred rats. The current study suggests that age-associated functional decline with decreased gene expression of the receptor may be restored by intervention. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Nagoya Univ, Grad Sch Med, Dept Geriatr, Showa Ku, Nagoya, Aichi 4668550, Japan. Tokyo Metropolitan Inst Gerontol, Positron Med Ctr, Itabashi Ku, Tokyo 1730022, Japan. NIA, Gerontol Res Ctr, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. RP Umegaki, H (reprint author), Nagoya Univ, Grad Sch Med, Dept Geriatr, Showa Ku, 65 Tsuruma Cho, Nagoya, Aichi 4668550, Japan. EM umegaki@med.nagoya-u.ac.jp NR 16 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD OCT PY 2006 VL 127 IS 10 BP 813 EP 815 DI 10.1016/j.mad.2006.07.007 PG 3 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 095DO UT WOS:000241288600009 PM 16939687 ER PT J AU Klabunde, CN Harlan, LC Warren, JL AF Klabunde, Carrie N. Harlan, Linda C. Warren, Joan L. TI Data sources for measuring comorbidity - A comparison of hospital records and medicare claims for cancer patients SO MEDICAL CARE LA English DT Article DE comorbidity; medical record; claims data; cancer; health services research; SEER; Medicare ID CO-MORBIDITY; ADMINISTRATIVE DATA; CLINICAL-DATA; PREVALENCE; OUTCOMES; HEALTH; VALIDATION; ACCURACY; SURGERY; TRENDS AB Background: Identifying appropriate comorbidity data sources is a key consideration in health services and outcomes research. Objective: Using cancer patients as an example, we compared comorbid conditions identified: 1) on the discharge facesheet versus full hospital medical record and 2) in the hospital record versus Medicare claims, both precancer diagnosis and associated with a cancer treatment-related index hospitalization. Methods: We used data from 1995 Surveillance, Epidemiology and End Results patterns of care studies for 1382 patients. Comorbid conditions were ascertained from the hospital record associated with the most definitive cancer treatment and Medicare claims. We calculated the prevalence for and assessed concordances among 12 conditions derived from the hospital record facesheet; full hospital record; Medicare claims precancer diagnosis, with and without a rule-out algorithm applied; and Medicare claims associated with an index hospitalization. Results: The proportion of patients with one or more comorbid conditions varied by data source, from 21% for the facesheet to 85% for prediagnosis Medicare claims without the rule-out algorithm. Condition prevalences were substantially lower for the facesheet compared with the full hospital record. For prediagnosis Medicare claims, condition prevalences were more than 1.7 times greater in the absence of an algorithm to screen for rule-out diagnoses. Measures assessing concordance between the full hospital record and prediagnosis Medicare claims (rule-out algorithm applied) showed modest agreement. Conclusions: The hospital record and Medicare claims are complementary data sources for identifying comorbid conditions. Comorbidity is greatly underascertained when derived only from the facesheet of the hospital record. Investigators using Part B Medicare claims to measure comorbidity should remove conditions that are listed for purposes of generating bills but are not true comorbidities. C1 NCI, Hlth Serv & Econ Branch, Appl Res Program, Bethesda, MD 20892 USA. RP Klabunde, CN (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Execut Pl N Room 4005,6130 Execut Blvd, Bethesda, MD 20892 USA. EM klabundc@mail.nih.gov FU NCI NIH HHS [N01-PC-35143, N01-PC-35133, N01-PC-35135, N01-PC-35136, N01-PC-35138, N01-PC-35139, N01-PC-35142, N01-PC-35145] NR 29 TC 91 Z9 91 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD OCT PY 2006 VL 44 IS 10 BP 921 EP 928 DI 10.1097/01.mlr.0000223480.52713.b9 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 092RR UT WOS:000241115500006 PM 17001263 ER PT J AU Bunnell, SC Singer, AL Hong, DI Jacque, BH Jordan, MS Seminario, MC Barr, VA Koretzky, GA Samelson, LE AF Bunnell, Stephen C. Singer, Andrew L. Hong, David I. Jacque, Berri H. Jordan, Martha S. Seminario, Maria-Cristina Barr, Valarie A. Koretzky, Gary A. Samelson, Lawrence E. TI Persistence of cooperatively stabilized signaling clusters drives T-cell activation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PHOSPHOLIPASE C-GAMMA-1 PLC-GAMMA-1; HEMATOPOIETIC PROGENITOR KINASE-1; FC-EPSILON-RI; ANTIGEN RECEPTOR; IMMUNOLOGICAL SYNAPSE; MEMBRANE MICRODOMAINS; ACTIN CYTOSKELETON; TYROSINE RESIDUES; ADAPTER PROTEINS; LINKER PROTEIN AB Antigen recognition triggers the recruitment of the critical adaptor protein SLP-76 to small macromolecular clusters nucleated by the T-cell receptor (TCR). These structures develop rapidly, in parallel with TCR-induced increases in tyrosine phosphorylation and cytosolic calcium, and are likely to contribute to TCR-proximal signaling. Previously, we demonstrated that these SLP-76-containing clusters segregate from the TCR and move towards the center of the contact interface. Neither the function of these clusters nor the structural requirements governing their persistence have been examined extensively. Here we demonstrate that defects in cluster assembly and persistence are associated with defects in T-cell activation in the absence of Lck, ZAP-70, or LAT. Clusters persist normally in the absence of phospholipase C-gamma 1, indicating that in the absence of a critical effector, these structures are insufficient to drive T-cell activation. Furthermore, we show that the critical adaptors LAT and Gads localize with SLP-76 in persistent clusters. Mutational analyses of LAT, Gads, and SLP-76 indicated that multiple domains within each of these proteins contribute to cluster persistence. These data indicate that multivalent cooperative interactions stabilize these persistent signaling clusters, which may correspond to the functional complexes predicted by kinetic proofreading models of T-cell activation. C1 Tufts Univ, Sch Med, Dept Pathol, Program Immunol, Boston, MA 02111 USA. NCI, Mol & Cellular Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Penn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. RP Bunnell, SC (reprint author), Tufts Univ, Sch Med, Dept Pathol, Program Immunol, Jaharis Bldg,Rm 512,150 Harrison Ave, Boston, MA 02111 USA. EM Stephen.Bunnell@tufts.edu FU Intramural NIH HHS; NCI NIH HHS [P01 CA093615, P01-CA93615]; NIDDK NIH HHS [F32 DK009969, F32-DK09969] NR 62 TC 84 Z9 86 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2006 VL 26 IS 19 BP 7155 EP 7166 DI 10.1128/MCB.00507-06 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 087KB UT WOS:000240740200012 PM 16980618 ER PT J AU Kohno, M Momoi, M Oo, ML Paik, JH Lee, YM Venkataraman, K Ai, Y Ristimaki, AP Fyrst, H Sano, H Rosenberg, D Saba, JD Proia, RL Hla, T AF Kohno, Masataka Momoi, Michiko Oo, Myat Lin Paik, Ji-Hye Lee, Yong-Moon Venkataraman, Krishnan Ai, Youxi Ristimaki, Ari P. Fyrst, Henrik Sano, Hajime Rosenberg, Daniel Saba, Julie D. Proia, Richard L. Hla, Timothy TI Intracellular role for sphingosine kinase 1 in intestinal adenoma cell proliferation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SPHINGOLIPID METABOLISM; TUMOR ANGIOGENESIS; KNOCKOUT MICE; IN-VIVO; 1-PHOSPHATE; SUPPRESSION; POLYPOSIS; GROWTH; CYCLOOXYGENASE-2; DROSOPHILA AB Sphingosine kinase (Sphk) enzymes are important in intracellular sphingolipid metabolism as well as in the biosynthesis of sphingosine 1-phosphate (S1P), an extracellular lipid mediator. Here, we show that Sphk1 is expressed and is required for small intestinal tumor cell proliferation in Ape(Min/+) mice. Adenoma size but not incidence was dramatically reduced in Apc(Min/+) Sphk(-/-) mice. Concomitantly, epithelial cell proliferation in the polyps was significantly attenuated, suggesting that Sphk1 regulates adenoma progression. Although the SIP receptors (S1P1R, S1P2R, and S1P3R) are expressed, polyp incidence or size was unaltered in Apc(Min/+) S1p2r(-/-), Apc(4Min/+) S1p3r(-/-), and Apc(Min/+) S1p1r(+/-) bigenic mice. These data suggest that extracellular SIP signaling via its receptors is not involved in adenoma cell proliferation. Interestingly, tissue sphingosine content was elevated in the adenomas of Apc(Min/+) Sphk1(-/-) mice, whereas S1P levels were not significantly altered. Concomitantly, epithelial cell proliferation and the expression of the G(1)/S cell cycle regulator CDK4 and c-myc were diminished in the polyps of Apc(Min/+) Sphk1(-/-) mice. In rat intestinal epithelial (RIE) cells in vitro, Sphk1 overexpression enhanced cell cycle traverse at the G(1)/S boundary. In addition, RIE cells treated with sphingosine but not C6-ceramide exhibited reduced cell proliferation, reduced retinoblastoma protein phosphorylation, and cyclin-dependent kinase 4 (Cdk4) expression. Our findings suggest that Sphk1 plays a critical role in intestinal tumor cell proliferation and that inhibitors of Sphk1 may be useful in the control of intestinal cancer. C1 Univ Connecticut, Ctr Hlth, Dept Cell Biol, Ctr Vasc Biol, Farmington, CT 06030 USA. Univ Connecticut, Ctr Hlth, Ctr Mol Med, Farmington, CT 06030 USA. Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland. Univ Helsinki, Biomedicum Helsinki, Mol & Canc Biol Res Program, Helsinki, Finland. Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA. Hyogo Med Univ, Dept Internal Med, Nishinomiya, Hyogo 6638501, Japan. NIDDK, Genet Dis & Dev Branch, NIH, Bethesda, MD 20892 USA. RP Hla, T (reprint author), Univ Connecticut, Ctr Hlth, Dept Cell Biol, Ctr Vasc Biol, Farmington, CT 06030 USA. EM hla@nso2.uchc.edu RI Proia, Richard/A-7908-2012; Hla, Timothy/G-5873-2012 OI Hla, Timothy/0000-0001-8355-4065 FU NCI NIH HHS [R01 CA077528, CA77528, CA77839, P01 CA077839]; NHLBI NIH HHS [HL67330, HL70694, P01 HL070694, R01 HL067330, R37 HL067330] NR 42 TC 138 Z9 147 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2006 VL 26 IS 19 BP 7211 EP 7223 DI 10.1128/MCB.02341-05 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 087KB UT WOS:000240740200017 PM 16980623 ER PT J AU Storici, F Snipe, JR Chan, GK Gordenin, DA Resnick, MA AF Storici, Francesca Snipe, Joyce R. Chan, Godwin K. Gordenin, Dmitry A. Resnick, Michael A. TI Conservative repair of a chromosomal double-strand break by single-strand DNA through two steps of annealing SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; SACCHAROMYCES-CEREVISIAE; HOMOLOGOUS RECOMBINATION; DEINOCOCCUS-RADIODURANS; MAMMALIAN-CELLS; GENE DISRUPTION; RAD52 PROTEIN; YEAST; OLIGONUCLEOTIDES; ENDONUCLEASE AB The repair of chromosomal double-strand breaks (DSBs) is essential to normal cell growth, and homologous recombination is a universal process for DSB repair. We explored DSB repair mechanisms in the yeast Saccharomyces cerevisiae using single-strand oligonucleotides with homology to both sides of a DSB. Oligonucleotide-directed repair occurred exclusively via Rad52- and Rad59-mediated single-strand annealing (SSA). Even the SSA domain of human Rad52 provided partial complementation for a null rad52 mutation. The repair did not involve Rad51-driven strand invasion, and moreover the suppression of strand invasion increased repair with oligonucleotides. A DSB was shown to activate targeting by oligonucleotides homologous to only one side of the break at large distances (at least 20 kb) from the break in a strand-biased manner, suggesting extensive 5' to 3' resection, followed by the restoration of resected DNA to the double-strand state. We conclude that long resected chromosomal DSB ends are repaired by a single-strand DNA oligonucleotide through two rounds of annealing. The repair by single-strand DNA can be conservative and may allow for accurate restoration of chromosomal DNAs with closely spaced DSBs. C1 NIEHS, Genet Mol Lab, Head Chromosome Stabil Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Resnick, MA (reprint author), NIEHS, Genet Mol Lab, Head Chromosome Stabil Sect, NIH, Res Triangle Pk, NC 27709 USA. EM Resnick@niehs.nih.gov OI Gordenin, Dmitry/0000-0002-8399-1836 FU Intramural NIH HHS NR 47 TC 49 Z9 49 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2006 VL 26 IS 20 BP 7645 EP 7657 DI 10.1128/MCB.00672-06 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 094PU UT WOS:000241252300025 PM 16908537 ER PT J AU Tsuduki, T Nakano, M Yasuoka, N Yamazaki, S Okada, T Okamoto, Y Masumoto, H AF Tsuduki, Tomohiro Nakano, Megumi Yasuoka, Nao Yamazaki, Saeko Okada, Teruaki Okamoto, Yasuhide Masumoto, Hiroshi TI An artificially constructed de novo human chromosome behaves almost identically to its natural counterpart during metaphase and anaphase in living cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ALPHA-SATELLITE DNA; MAMMALIAN TISSUE-CELLS; B NULL MICE; CENP-B; CENTROMERIC CHROMATIN; FUNCTIONAL-ANALYSIS; FISSION YEAST; HETEROCHROMATIN; GENE; GENERATION AB Human artificial chromosomes (HACs) are promising reagents for the analysis of chromosome function. While HACs are maintained stably, the segregation mechanisms of HACs have not been investigated in detail. To analyze HACs in living cells, we integrated 256 copies of the Lac operator into a precursor yeast artificial chromosome (YAC) containing alpha-satellite DNA and generated green fluorescent protein (GFP)-tagged HACs in HT1080 cells expressing a GFP-Lac repressor fusion protein. Time-lapse analyses of GFP-RACs and host centromeres in living mitotic cells indicated that the HAC was properly aligned at the spindle midzone and that sister chromatids of the HAC separated with the same timing as host chromosomes and moved to the spindle poles with mobility similar to that of the host centromeres. These results indicate that a HAC composed of a multimer of input alpha-satellite YACs retains most of the functions of the centromeres on natural chromosomes. The only difference between the HAC and the host chromosome was that the HAC oscillated more frequently, at higher velocity, across the spindle midzone during metaphase. However, this provides important evidence that an individual HAC has the capacity to maintain tensional balance in the pole-to-pole direction, thereby stabilizing its position around the spindle midzone. C1 Nagoya Univ, Grad Sch Sci, Div Biol Sci, Chikusa Ku, Nagoya, Aichi 4648602, Japan. Shinshu Univ, Grad Sch Agr, Nagano 3994598, Japan. NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. RP Masumoto, H (reprint author), Nagoya Univ, Grad Sch Sci, Div Biol Sci, Chikusa Ku, Nagoya, Aichi 4648602, Japan. EM g44478a@nucc.cc.nagoya-u.ac.jp NR 63 TC 7 Z9 10 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2006 VL 26 IS 20 BP 7682 EP 7695 DI 10.1128/MCB.00355-06 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 094PU UT WOS:000241252300028 PM 17015481 ER PT J AU Nakatake, Y Fukui, N Iwamatsu, Y Masui, S Takahashi, K Yagi, R Yagi, K Miyazaki, J Matoba, R Ko, MSH Niwa, H AF Nakatake, Yuhki Fukui, Nobutaka Iwamatsu, Yuko Masui, Shinji Takahashi, Kadue Yagi, Rika Yagi, Kiyohito Miyazaki, Jun-ichi Matoba, Ryo Ko, Minoru S. H. Niwa, Hitoshi TI Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID KRUPPEL-LIKE FACTOR; TRANSCRIPTION FACTOR KLF4; SELF-RENEWAL; MOUSE DEVELOPMENT; GENE-EXPRESSION; GROWTH-FACTOR; OCT-3/4; DIFFERENTIATION; TRANSACTIVATION; COACTIVATOR AB Although the POU transcription factor Oct3/4 is pivotal in maintaining self renewal of embryonic stem (ES) cells, little is known of its molecular mechanisms. We previously reported that the N-terminal transactivation domain of Oct3/4 is required for activation of Lefty1 expression (H. Niwa, S. Masui, I. Chambers, A. G. Smith, and J. Miyazaki, Mol. Cell. Biol. 22:1526-1536, 2002). Here we test whether Lefty1 is a direct target of Oct3/4. We identified an ES cell-specific enhancer upstream of the Lefty1 promoter that contains binding sites for Oct3/4 and Sox2. Unlike other known Oct3/4-Sox2-dependent enhancers, however, this enhancer element could not be activated by Oct3/4 and Sox2 in differentiated cells. By functional screening of ES-specific transcription factors, we found that Kruppel-like factor 4 (KIN) cooperates with Oct3/4 and Sox2 to activate Lefty1 expression, and that KIN acts as a mediating factor that specifically binds to the proximal element of the Lefty1 promoter. DNA microarray analysis revealed that a subset of putative Oct3/4 target genes may be regulated in the same manner. Our findings shed light on a novel function of Oct3/4 in ES cells. C1 RIKEN, Ctr Dev Biol, Lab Pluripotent Cell Studies, Chuo Ku, Kobe, Hyogo 6500047, Japan. Osaka Univ, Grad Sch Pharmaceut Sci, Suita, Osaka 5650871, Japan. Osaka Univ, Grad Sch Med, Course Adv Med, Area Mol Therapeut, Suita, Osaka 5650871, Japan. NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. Kobe Univ, Grad Sch Med, Lab Dev & Regenerat Med, Chuo Ku, Kobe, Hyogo 6500017, Japan. RP Niwa, H (reprint author), RIKEN, Ctr Dev Biol, Lab Pluripotent Cell Studies, Chuo Ku, Minatojima Minamimachi 2-2-3, Kobe, Hyogo 6500047, Japan. EM niwa@cdb.riken.jp RI Ko, Minoru/B-7969-2009; Nakatake, Yuhki/K-5405-2013; Miyazaki, Jun-ichi/N-1976-2015 OI Ko, Minoru/0000-0002-3530-3015; Miyazaki, Jun-ichi/0000-0003-2475-589X FU Intramural NIH HHS NR 48 TC 165 Z9 184 U1 0 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2006 VL 26 IS 20 BP 7772 EP 7782 DI 10.1128/MCB.00468-06 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 094PU UT WOS:000241252300035 PM 16954384 ER PT J AU Brzostowski, JA Kimmel, AR AF Brzostowski, Joseph A. Kimmel, Alan R. TI Nonadaptive regulation of ERK2 in Dictyostelium: Implications for mechanisms of cAMP relay SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; ADENYLYL-CYCLASE; PROTEIN-KINASE; SIGNALING PATHWAYS; MAP KINASE; DISCOIDEUM; CHEMOATTRACTANT; CHEMOTAXIS; RECEPTOR; GENE AB It is assumed that ERK2 in Dictyostelium is subject to adaptive regulation in response to constant extracellular ligand stimulation. We now show, to the contrary, that ERK2 remains active under continuous stimulation, differing from most ligand-activated pathways in chemotactically competent Dictyostelium and other cells. We show that the upstream phosphorylation pathway, responsible for ERK2 activation, transiently responds to receptor stimulation, whereas ERK2 dephosphorylation (deactivation) is inhibited by continuous stimulation. We argue that the net result of these two regulatory actions is a persistently active ERK2 pathway when the extracellular ligand (i.e., cAMP) concentration is held constant and that oscillatory production/destruction of secreted cAMP in chemotaxing cells accounts for the observed oscillatory activity of ERK2. We also show that pathways controlling seven-transmembrane receptor (7-TMR) ERK2 activation/deactivation function independently of G proteins and ligand-induced production of intracellular cAMP and the consequent activation of PKA. Finally, we propose that this regulation enables ERK2 to function both in an oscillatory manner, critical for chemotaxis, and in a persistent manner, necessary for gene expression, as secreted ligand concentration increases during later development. This work redefines mechanisms of ERK2 regulation by 7-TMR signaling in Dictyostelium and establishes new implications for control of signal relay during chemotaxis. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Kimmel, AR (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM ark1@helix.nih.gov FU Intramural NIH HHS NR 39 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD OCT PY 2006 VL 17 IS 10 BP 4220 EP 4227 DI 10.1091/mbc.E06-05-0376 PG 8 WC Cell Biology SC Cell Biology GA 092HJ UT WOS:000241087300007 PM 16870702 ER PT J AU Pani, B Cornatzer, E Cornatzer, W Shin, DM Pittelkow, MR Hovnanian, A Ambudkar, IS Singh, BB AF Pani, Biswaranjan Cornatzer, Eric Cornatzer, William Shin, Dong-Min Pittelkow, Mark R. Hovnanian, Alain Ambudkar, Indu S. Singh, Brij B. TI Up-regulation of transient receptor potential canonical 1 (TRPC1) following sarco(endo)plasmic reticulum Ca2+ ATPase 2 gene silencing promotes cell survival: A potential role for TRPC1 in Darier's disease SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID NF-KAPPA-B; CAPACITATIVE CALCIUM-ENTRY; NERVOUS-SYSTEM; NIGRAL NEURONS; CHANNELS; PROLIFERATION; MUTATIONS; GROWTH; ACTIVATION; MECHANISM AB The mechanism(s) involved in regulation of store operated calcium entry in Darier's disease (DD) is not known. We investigated the distribution and function of transient receptor potential canonical (TRPQ in epidermal skin cells. DD patients demonstrated up-regulation of TRPC1, but not TRPC3, in the squamous layers. Ca2+ influx was significantly higher in keratinocytes obtained from DD patients and showed enhanced proliferation compared with normal keratinocytes. Similar up-regulation of TRPC1 was also detected in epidermal layers of SERCA2(+/-) mice. HaCaT cells expressed TRPC1 in the plasma membrane. Expression of sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA)2 small interfering RNA (siRNA) in HaCaT cells increased TRPC1 levels and thapsigargin-stimulated Ca2+ influx, which was blocked by store-operated calcium entry inhibitors. Thapsigargin-stimulated intracellular Ca2+ release was decreased in DD cells. DD keratinocytes exhibited increased cell survival upon thapsigargin treatment. Alternatively, overexpression of TRPC1 or SERCA2-siRNA in HaCaT cells demonstrated resistance to thapsigargin-induced apoptosis. These effects were dependent on external Ca2+ and activation of nuclear factor-kappa B. Isotretinoin reduced Ca2+ entry in HaCaT cells and decreased survival of HaCaT and DD keratinocytes. These findings put forward a novel consequence of compromised SERCA2 function in DD wherein up-regulation of TRPC1 augments cell proliferation and restrict apoptosis. We suggest that the anti-apoptotic effect of TRPC1 could potentially contribute to abnormal keratosis in DD. C1 Univ N Dakota, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Grand Forks, ND 58202 USA. Univ N Dakota, Sch Med & Hlth Sci, Dept Internal Med, Grand Forks, ND 58202 USA. Yonsei Univ, Coll Dent, Dept Oral Biol, Korea 21 Project Med Sci, Seoul 120752, South Korea. Mayo Clin, Coll Med, Dept Dermatol, Rochester, MN 55905 USA. INSERM U563, Dept Funct Genet Epithelial Dis, F-31024 Toulouse 3, France. Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Singh, BB (reprint author), Univ N Dakota, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Grand Forks, ND 58202 USA. EM bsingh@medicine.nodak.edu OI Singh, Brij/0000-0003-0535-5997 FU NCRR NIH HHS [5P20RR017699, P20 RR017699, P20 RR017699-077011]; NIDCR NIH HHS [R01 DE017102-01A1, DE 017102, R01 DE017102, R01 DE017102-02, R01 DE017102-03] NR 50 TC 45 Z9 46 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD OCT PY 2006 VL 17 IS 10 BP 4446 EP 4458 DI 10.1091/mbc.E06-03-0251 PG 13 WC Cell Biology SC Cell Biology GA 092HJ UT WOS:000241087300026 PM 16899508 ER PT J AU Seamon, JA Rugg, CA Emanuel, S Calcagno, AM Ambudkar, SV Middleton, SA Butler, J Borowski, V Greenberger, LM AF Seamon, Jennifer A. Rugg, Catherine A. Emanuel, Stuart Calcagno, Anna Maria Ambudkar, Suresh V. Middleton, Steven A. Butler, Jeannene Borowski, Virna Greenberger, Lee M. TI Role of the ABCG2 drug transporter in the resistance and oral bioavailability of a potent cyclin-dependent kinase/Aurora kinase inhibitor SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID BREAST-CANCER CELLS; NORMAL HUMAN TISSUES; MULTIDRUG-RESISTANCE; HALF-TRANSPORTER; ACQUIRED MUTATIONS; PROTEIN BCRP/ABCG2; FUMITREMORGIN-C; HUMAN PLACENTA; IN-VITRO; GENE AB Cell cycle kinase inhibitors have advanced into clinical trials in oncology. One such molecule, JNJ-7706621, is a broad-spectrum inhibitor of the cyclin-dependent kinises and Aurora kinases that mediate G(2)-M arrest and inhibits tumor growth in xenograft models. To determine the putative mechanisms of resistance to JNJ-7706621 that might be encountered in the clinic, the human epithelial cervical carcinoma cell line (HeLa) was exposed to incrementally increasing concentrations of JNJ-7706621. The resulting resistant cell population, designated HeLa-6621, was 16-fold resistant to JNJ-7706621, cross-resistant to mitoxantrone (15-fold) and topotecan (6-fold), and exhibited reduced intracellular drug accumulation of JNJ-7706621. ABCG2 was highly overexpressed at both the mRNA (similar to 163-fold) and protein levels. The functional role of ABCG2 in mediating resistance to JNJ-7706621 was consistent with the following findings: (a) an ABCG2 inhibitor, fumitremorgin C, restored the sensitivity of HeLa-6621 cells to JNJ-7706621 and to mitoxantrone; (b) human embryonic kidney-293 cells transfected with ABCG2 were resistant to both JNJ-7706621 and mitoxantrone; and (c) resistant cells that were removed from the drug for 12 weeks and reverted to susceptibility to JNJ-7706621 showed near-normal ABCG2 RNA levels. ABCG2 is likely to limit the bioavailability of JNJ-7706621 because oral administration of JNJ-7706621 to Bcrp (the murine homologue of ABCG2) knockout mice resulted in an increase in the plasma concentration of JNJ-7706621 compared with wild-type mice. These findings indicate that ABCG2 mediates the resistance to JNJ-7706621 and alters the absorption of the compound following administration. C1 Johnson & Johnson Pharmaceut Res & Dev, Canc Therapeut Res, Raritan, NJ USA. NCI, Cell Biol Lab, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. RP Seamon, JA (reprint author), Johnson & Johnson Pharmaceut Res & Dev LLC, 1125 Trenton Harbourton Rd,POB 200, Titusville, NJ 08560 USA. EM jseamon@prdus.jnj.com RI Calcagno, Anna Maria/A-5617-2012; OI Calcagno, Anna Maria/0000-0002-0804-2753 FU Intramural NIH HHS NR 39 TC 40 Z9 42 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD OCT PY 2006 VL 5 IS 10 BP 2459 EP 2467 DI 10.1158/1535-7163.MCT-06-0339 PG 9 WC Oncology SC Oncology GA 095VE UT WOS:000241335600004 PM 17041089 ER PT J AU Wang, JH He, LS Combs, CA Roderiquez, G Norcross, MA AF Wang, Jinhai He, Liusheng Combs, Christian A. Roderiquez, Gregory Norcross, Michael A. TI Dimerization of CXCR4 in living malignant cells: control of cell migration by a synthetic peptide that reduces homologous CXCR4 interactions SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEIN-COUPLED RECEPTORS; COLONY-STIMULATING FACTOR; HUMAN PRIMARY MONOCYTES; ENERGY-TRANSFER FRET; HIV-1 INFECTION; CHEMOKINE SDF-1-ALPHA; CANCER METASTASIS; TUMOR PROGRESSION; CCR5 AB Chemokine receptor CXCR4 (CD184) may play a role in cancer metastasis and is known to form homodimers. However, it is not clear how transmembrane regions (TM) of CXCR4 and receptor homotypic interactions affect the function of CXCR4 in living cells. Using confocal microscopy and flow cytometric analysis, we showed that high levels of CXCR4 are present in the cytoplasm, accompanied by lower expression on the cell surface in CXCR4 transfectants, tumor cells, and normal peripheral blood lymphocytes. CXCR4 homodimers were detected in tumor cells, both on the cell surface membrane and in the cytoplasm using fluorescence resonance energy transfer and photo-bleaching fluorescence resonance energy transfer to measure energy transfer between CXCR4-CFP and CXCR4-YFP constructs. Disruption of lipid rafts by depletion of cholesterol with methyl-beta-cyclodextrin reduced the interaction between CXCR4 molecules and inhibited malignant cell migration to CXCL12/SDF-1 alpha. A synthetic peptide of TM4 of CXCR4 reduced energy transfer between molecules of CXCR4, inhibited CXCL12-induced actin polymerization, and blocked chemotaxis of malignant cells. TM4 also inhibited migration of normal monocytes toward CXCL12. Reduction of CXCR4 energy transfer by the TM4 peptide and methyl-beta-cyclodextrin indicates that interactions between CXCR4s may play important roles in cell migration and suggests that cell surface and intracellular receptor dimers are appropriate targets for control of tumor cell spread. Targeting chemokine receptor oligomerization and signal transduction for the treatment of cancer, HIV-1 infections, and other CXCR4 mediated inflammatory conditions warrants further investigation. C1 US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Wang, JH (reprint author), US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bldg 29B,Room 4E12,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Jinhai.wang@fda.hhs.gov; michael.norcross@fda.hhs.gov NR 41 TC 61 Z9 61 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD OCT PY 2006 VL 5 IS 10 BP 2474 EP 2483 DI 10.1158/1535-7163.MCT-05-0261 PG 10 WC Oncology SC Oncology GA 095VE UT WOS:000241335600006 PM 17041091 ER PT J AU Abi-Habib, RJ Singh, R Liu, SH Bugge, TH Leppla, SH Frankel, AE AF Abi-Habib, Ralph J. Singh, Ravibhushan Liu, Shihui Bugge, Thomas H. Leppla, Stephen H. Frankel, Arthur E. TI A urokinase-activated recombinant anthrax toxin is selectively cytotoxic to many human tumor cell types SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ABL-POSITIVE CELLS; PLASMINOGEN-ACTIVATOR; ANTITUMOR-ACTIVITY; TYROSINE KINASE; RECEPTOR; INVASION; GROWTH; METASTASIS; INHIBITOR; PROTEIN AB Urokinase plasminogen activator (uPA) is a tumor-specific protease highly expressed in several types of solid tumors and rarely present on normal cells under physiologic conditions. Due to its high expression on metastatic tumors, several different strategies have been used to target the urokinase system. These have mostly led to tumor growth inhibition rather than tumor regression. A different approach was adopted by replacing the furin activation site on a recombinant anthrax toxin with a urokinase activation site. The resulting toxin, PrAgU2/FP59, was highly potent against tumors both in vitro and in vivo. In this study, we show that PrAgU2/FP59 is toxic to a wide range of tumor cell lines, including non-small cell lung cancer, pancreatic cancer, and basal-like breast cancer cell lines. Of the few cell lines found to be resistant to PrAgU2/FP59, most became sensitive upon addition of exogenous pro-uPA. PrAgU2/FP59 was much less toxic to normal human cells. The potency of PrAgU2/FP59 was dependent on anthrax toxin receptor, uPA receptor, and uPA levels but not on total plasminogen activator inhibitor-1 levels. In this study, we show that PrAgU2/FP59 is a wide-range, highly potent, and highly selective toxin that is capable of specifically targeting uPA-expressing tumor cells, independently of the tissue of origin of these cells. Furthermore, we identify three molecular markers, anthrax toxin receptor, uPA, and uPA receptor, which can be used as predictors of tumor cell sensitivity to PrAgU2/FP59. C1 Scott & White Mem Hosp & Clin, Canc Res Inst, Temple, TX 76502 USA. NIAID, Bacterial Toxins & Therapeut Sect, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD USA. RP Frankel, AE (reprint author), Scott & White Mem Hosp & Clin, Canc Res Inst, 5701 S Airport Rd, Temple, TX 76502 USA. EM afrankel@swmail.sw.org FU Intramural NIH HHS NR 27 TC 33 Z9 34 U1 3 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD OCT PY 2006 VL 5 IS 10 BP 2556 EP 2562 DI 10.1158/1535-7163.MCT-06-0315 PG 7 WC Oncology SC Oncology GA 095VE UT WOS:000241335600015 PM 17041100 ER PT J AU Lee, CH Kakinuma, T Wang, J Zhang, H Palmer, DC Restifo, NP Hwang, ST AF Lee, Chih-hung Kakinuma, Takashi Wang, Julia Zhang, Hong Palmer, Douglas C. Restifo, Nicholas P. Hwang, Sam T. TI Sensitization of B16 tumor cells with a CXCR4 antagonist increases the efficacy of immunotherapy for established lung metastases SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID REGULATORY T-CELLS; CHEMOKINE RECEPTOR CXCR4; ANTIGEN-4 BLOCKADE; MELANOMA-CELLS; LYMPHOCYTE ANTIGEN-4; IN-VIVO; CANCER; CYCLOPHOSPHAMIDE; AUTOIMMUNITY; COMBINATION AB Expression of the chemokine receptor CXCR4 by tumor cells promotes metastasis, possibly by activating pro-survival signals that render cancer cells resistant to immune attack. Inhibition of CXCR4 with a peptide antagonist, T22, blocks metastatic implantation of CXCR4-transduced B16 (CXCR4-luc-B16) melanoma cells in lung, but not the outgrowth of established metastases, raising the question of how T22 can best be used in a clinical setting. Herein, whereas the treatment of CXCR4-luc-B16 cells in vitro with the CXCR4 ligand CXCL12 did not reduce killing induced by cisplatin or cyclophosphamide, CXCL12 markedly reduced Fas-dependent killing by gp100-specific (pmel-1) CD8(+) T cells. T22 pretreatment restored sensitivity of CXCR4-luc-B16 cells to pmel-1 killing, even in the presence of CXCL12. Two immune-augmenting regimens were used in combination with T22 to treat experimental lung metastases. First, low-dose cyclophosphamide treatment (100 mg/kg) on day 5 in combination with T22 (days 4-7) yielded a similar to 70% reduction of B16 metastatic tumor burden in the lungs compared with cyclophosphamide treatment alone (P < 0.001). Furthermore, whereas anti-CTL antigen 4 (CTLA4) monoclonal antibody (mAb; or T22 treatment) alone had little effect on established B16 metastases, pretreatment with T22 (in combination with anti-CTLA4 mAb) resulted in a 50% reduction in lung tumor burden (P = 0.02). Thus, in vitro, CXCR4 antagonism with T22 renders B16 cells susceptible to killing by antigen-specific T cells. In vivo, T22 synergizes with cyclophosphamide or anti-CTLA4 mAb in the treatment of established lung metastases, suggesting a novel strategy for augmenting the efficacy of immunotherapy. C1 NCI, Dermatol Branch, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Hwang, ST (reprint author), NCI, Dermatol Branch, NIH, Ctr Canc Res, Bldg 10 Room 12N246,10 Ctr Dr, Bethesda, MD 20892 USA. EM hwangs@mail.nih.gov RI Palmer, Douglas/B-9454-2008; Restifo, Nicholas/A-5713-2008; Lee, Chih-Hung /B-4081-2010; OI Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 41 TC 36 Z9 37 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD OCT PY 2006 VL 5 IS 10 BP 2592 EP 2599 DI 10.1158/1535-7163.MCT-06-0310 PG 8 WC Oncology SC Oncology GA 095VE UT WOS:000241335600019 PM 17041104 ER PT J AU Pisitkun, T Johnstone, R Knepper, MA AF Pisitkun, Trairak Johnstone, Rose Knepper, Mark A. TI Discovery of urinary biomarkers SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Review ID DIFFERENCE GEL-ELECTROPHORESIS; RENAL-ALLOGRAFT REJECTION; ACID-BINDING PROTEIN; PROTEOMIC ANALYSIS; BLADDER-CANCER; MASS-SPECTROMETRY; DIABETIC-NEPHROPATHY; PROXIMAL TUBULE; 2-DIMENSIONAL ELECTROPHORESIS; RETICULOCYTE MATURATION AB A myriad of proteins and peptides can be identified in normal human urine. These are derived from a variety of sources including glomerular filtration of blood plasma, cell sloughing, apoptosis, proteolytic cleavage of cell surface glycosylphosphatidylinositol-linked proteins, and secretion of exosomes by epithelial cells. Mass spectrometry-based approaches to urinary protein and peptide profiling can, in principle, reveal changes in excretion rates of specific proteins/peptides that can have predictive value in the clinical arena, e. g. in the early diagnosis of disease, in classification of disease with regard to likely therapeutic responses, in assessment of prognosis, and in monitoring response to therapy. These approaches have potential value, not only in diseases of the kidney and urinary tract but also in systemic diseases that are associated with circulating small protein and peptide markers that can pass the glomerular filter. Most large scale biomarker discovery studies reported thus far have used one of two approaches to identify proteins and peptides whose excretion in urine changes in specific disease states: 1) two-dimensional electrophoresis with mass spectrometric and/or immunochemical identification of proteins and 2) top-down mass spectrometric methods (SELDI-TOF-MS and capillary electrophoresis-MS). These studies have been chiefly in the areas of nephrology, urology, and oncology. We review these applications, focusing on two areas of progress, viz. in bladder cancer and in acute rejection of renal transplants. Progress has been limited so far. However, with the advent of powerful LC-MS/MS methods along with methods for quantifying LC-MS/MS output, there is hope for an accelerated discovery and validation of disease biomarkers in urine. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov FU Intramural NIH HHS [Z99 HL999999, Z01 HL001285-21] NR 77 TC 220 Z9 234 U1 6 U2 63 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 BP 1760 EP 1771 DI 10.1074/mcp.R60004-MCP200 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098KL UT WOS:000241519300005 PM 16837576 ER PT J AU Krueger, KE Srivastava, S AF Krueger, Karl E. Srivastava, Sudhir TI Posttranslational protein modifications - Current implications for cancer detection, prevention, and therapeutics SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Review ID CELL LUNG-CANCER; GROWTH-FACTOR-RECEPTOR; INTEGRIN-LINKED KINASE; ENZYME-ACTIVITY PROFILES; PANCREATIC-CANCER; UBIQUITIN LIGASES; BREAST-CANCER; PROTEOMIC ANALYSIS; DOUBLE-BLIND; IN-VIVO C1 NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Srivastava, S (reprint author), NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, 6130 Execut Blvd,MSC 7362, Bethesda, MD 20892 USA. EM srivasts@mail.nih.gov NR 75 TC 92 Z9 93 U1 1 U2 14 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 BP 1799 EP 1810 DI 10.1074/mcp.R600009-MCP200 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098KL UT WOS:000241519300008 PM 16844681 ER PT J AU Azad, NS Rasool, N Annunziata, CM Minasian, L Whiteley, G Kohn, EC AF Azad, Nilofer S. Rasool, Nabila Annunziata, Christina M. Minasian, Lori Whiteley, Gordon Kohn, Elise C. TI Proteomics in clinical trials and practice - Present uses and future promise SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Review ID NIPPLE ASPIRATE FLUID; SELDI-TOF-MS; BREAST-CANCER; MASS-SPECTROMETRY; PROSTATE-CANCER; CEREBROSPINAL-FLUID; OVARIAN-CANCER; KINASE INHIBITORS; PROTEIN PROFILES; CELLULAR TARGETS AB The study of clinical proteomics is a promising new field that has the potential to have many applications, including the identification of biomarkers and monitoring of disease, especially in the field of oncology. Expression proteomics evaluates the cellular production of proteins encoded by a particular gene and exploits the differential expression and post-translational modifications of proteins between healthy and diseased states. These biomarkers may be applied towards early diagnosis, prognosis, and prediction of response to therapy. Functional proteomics seeks to decipher protein-protein interactions and biochemical pathways involved in disease biology and targeted by newer molecular therapeutics. Advanced spectrometry technologies and new protein array formats have improved these analyses and are now being applied prospectively in clinical trials. Further advancement of proteomics technology could usher in an era of personalized molecular medicine, where diseases are diagnosed at earlier stages and where therapies are more effective because they are tailored to the protein expression of a patient's malignancy. C1 NCI, Pathol Lab, NIH, Ctr Canc Res,Mol Singaling Sect, Bethesda, MD 20892 USA. RP Azad, NS (reprint author), NCI, Pathol Lab, NIH, Ctr Canc Res,Mol Singaling Sect, 10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. EM azadn@mail.nih.gov; kohne@mail.nih.gov FU Intramural NIH HHS NR 65 TC 52 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 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 BP 1819 EP 1829 DI 10.1074/mcp.R600008-MCP200 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098KL UT WOS:000241519300010 PM 16737951 ER PT J AU Haab, BB Paulovich, AG Anderson, NL Clark, AM Downing, GJ Hermjakob, H LaBaer, J Uhlen, M AF Haab, Brian B. Paulovich, Amanda G. Anderson, N. Leigh Clark, Adam M. Downing, Gregory J. Hermjakob, Henning LaBaer, Joshua Uhlen, Mathias TI A reagent resource to identify proteins and peptides of interest for the cancer community - A workshop report SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Editorial Material ID MONOCLONAL-ANTIBODIES; PLASMA-PROTEOME; GLOBAL ANALYSIS; BREAST-CANCER; MICROARRAYS; GENERATION; TISSUE; DISCOVERY; BIOMARKER; CAPTURE AB On the basis of discussions with representatives from all sectors of the cancer research community, the National Cancer Institute (NCI) recognizes the immense opportunities to apply proteomics technologies to further cancer research. Validated and well characterized affinity capture reagents (e. g. antibodies, aptamers, and affibodies) will play a key role in proteomics research platforms for the prevention, early detection, treatment, and monitoring of cancer. To discuss ways to develop new resources and optimize current opportunities in this area, the NCI convened the "Proteomic Technologies Reagents Resource Workshop" in Chicago, IL on December 12-13, 2005. The workshop brought together leading scientists in proteomics research to discuss model systems for evaluating and delivering resources for reagents to support MS and affinity capture platforms. Speakers discussed issues and identified action items related to an overall vision for and proposed models for a shared proteomics reagents resource, applications of affinity capture methods in cancer research, quality control and validation of affinity capture reagents, considerations for target selection, and construction of a reagents database. The meeting also featured presentations and discussion from leading private sector investigators on state-of-the-art technologies and capabilities to meet the user community's needs. This workshop was developed as a component of the NCI's Clinical Proteomics Technologies Initiative for Cancer, a coordinated initiative that includes the establishment of reagent resources for the scientific community. This workshop report explores various approaches to develop a framework that will most effectively fulfill the needs of the NCI and the cancer research community. C1 Van Andel Res Inst, Grand Rapids, MI 49503 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Plasma Proteome Inst, Washington, DC 20009 USA. NCI, Off Technol & Ind Relat, NIH, Bethesda, MD 20892 USA. European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England. Harvard Univ, Harvard Inst Proteom, Cambridge, MA 02141 USA. Royal Inst Technol, S-10691 Stockholm, Sweden. RP Downing, GJ (reprint author), Van Andel Res Inst, Grand Rapids, MI 49503 USA. EM downingg@mail.nih.gov OI Hermjakob, Henning/0000-0001-8479-0262 NR 38 TC 56 Z9 56 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 BP 1996 EP 2007 DI 10.1074/mcp.T600020-MCP200 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098KL UT WOS:000241519300026 PM 16867976 ER PT J AU Clark, AM Rodriguez, H Downing, GJ AF Clark, A. M. Rodriguez, H. Downing, G. J. TI Proteomic technologies for cancer research; Technology assessment and resource development SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 NIH, Natl Canc Inst, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 SU S MA 484 BP S118 EP S118 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506400267 ER PT J AU Elliott, ST Olsson, A Sheng, S Boheler, KR Forsstrom-Olsson, O Van Eyk, JE AF Elliott, S. T. Olsson, A. Sheng, S. Boheler, K. R. Forsstrom-Olsson, O. Van Eyk, J. E. TI Two-dimensional liquid chromatography analysis software; Maximizing the potential of a powerful proteomic tool SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. Ludesi AB, Lund, Sweden. NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 SU S MA 925 BP S239 EP S239 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506401129 ER PT J AU Gonzales, DA Ying, S Hoehn, G Petraitiene, R Munson, PJ Walsh, TJ Suffredini, AF AF Gonzales, D. A. Ying, S. Hoehn, G. Petraitiene, R. Munson, P. J. Walsh, T. J. Suffredini, A. F. TI SELDI distinguishes infectious etiologies in neutropenic rabbit models of Aspergillus fumigatus and Pseudomonas aeruginosa pneumonias SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Computercraft, Mclean, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 SU S MA 1404 BP S372 EP S372 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506401436 ER PT J AU Jacobowitz, DM Zhang, X Eudy, YK Adimi, N Ji, X Mccue, J Yuan, PX Chen, G Eidelman, O Jozwik, C Pollard, HB Manji, H AF Jacobowitz, D. M. Zhang, X. Eudy, Y. K. Adimi, N. Ji, X. McCue, J. Yuan, P. X. Chen, G. Eidelman, O. Jozwik, C. Pollard, H. B. Manji, H. TI Discovery of platelet proteomic biomarkers in patients with bipolar depression after acute and chronic treatment with lithium SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIMH, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 SU S MA 752 BP S197 EP S197 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506401027 ER PT J AU Jozwik, CE Eudy, Y Zhang, X Ji, X Adimi, N Eidelman, O Srivastava, M Huang, W Jacobowitz, DM Pollard, HB AF Jozwik, C. E. Eudy, Y. Zhang, X. Ji, X. Adimi, N. Eidelman, O. Srivastava, M. Huang, W. Jacobowitz, D. M. Pollard, H. B. TI Dysfunctional kinase-driven signaling pathways in cystic fibrosis lung epithelial cells SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 SU S MA 723 BP S189 EP S189 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506401006 ER PT J AU Krizman, DB Hood, BL Darfler, MM Guiel, TG Conrads, TP Veenstra, TD AF Krizman, D. B. Hood, B. L. Darfler, M. M. Guiel, T. G. Conrads, T. P. Veenstra, T. D. TI Quantitative proteomics of formalin-fixed archival tissue SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 Express Pathol Inc, Gaithersburg, MD USA. SAIC NCI Frederick, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 SU S MA 766 BP S200 EP S200 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506401035 ER PT J AU Kulikowicz, T Cheng, WH Saxena, S Bohr, VA AF Kulikowicz, T. Cheng, W. -H. Saxena, S. Bohr, V. A. TI Post-translational modifications of human premature aging proteins SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 SU S MA 1237 BP S335 EP S335 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506401348 ER PT J AU Kulikowicz, T Cheng, WH Saxena, S Bohr, VA AF Kulikowicz, T. Cheng, W. -H. Saxena, S. Bohr, V. A. TI Post-translational modifications of human premature aging proteins SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 Nat Inst Aging, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 SU S MA 1021 BP S273 EP S273 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506401208 ER PT J AU Kuzdzal, SA Lopez, MF Mikulskis, A Sarracino, D O'Gorman, M Patton, W Rosenblatt, K Gurnani, P Nandi, A Whiteley, G Petricoin, EF Liotta, L Fishman, D AF Kuzdzal, S. A. Lopez, M. F. Mikulskis, A. Sarracino, D. O'Gorman, M. Patton, W. Rosenblatt, K. Gurnani, P. Nandi, A. Whiteley, G. Petricoin, E. F. Liotta, L. Fishman, D. TI Identification of a four marker biomarker panel from the serum fragmentome for classification of stage 1 ovarian cancer SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 Perkin Elmer Life & Analyt Sci, Boston, MA USA. Harvard Partners Ctr Genet & Genom, Cambridge, MA USA. Nonlinear Dynam, Newcastle Upon Tyne, Tyne & Wear, England. SW Texas State Univ, Dallas, TX USA. Natl Canc Inst, Frederick, MD USA. George Mason Univ, Fairfax, VA 22030 USA. NYU, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 SU S MA 95 BP S18 EP S18 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506400039 ER PT J AU Lustig, A Saxena, A Wu, CH Saxena, S Taub, DD AF Lustig, A. Saxena, A. Wu, C. H. Saxena, S. Taub, D. D. TI Molecular alterations in thymocytes with progressive aging SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RI Crozier, Laura/A-4821-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 SU S MA 1236 BP S335 EP S335 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506401347 ER PT J AU Meetel, AR Yin, J Medhurst, A Ling, C Xue, Y Saxena, S Hoatlin, M Joenje, H de Winter, J Wang, W AF Meetel, A. R. Yin, J. Medhurst, A. Ling, C. Xue, Y. Saxena, S. Hoatlin, M. Joenje, H. de Winter, J. Wang, W. TI Identification of new genes involved in genomic instability diseases by protein complex purification and mass spectrometry SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. VU Univ Med Ctr, Amsterdam, Netherlands. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 SU S MA 1243 BP S337 EP S337 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506401352 ER PT J AU Pollard, HB Eidelman, O Jozwik, C Mueller, G Rothwell, S Zeitlin, PL Guggino, WB Jacobowitz, DM Srivastava, M AF Pollard, H. B. Eidelman, O. Jozwik, C. Mueller, G. Rothwell, S. Zeitlin, P. L. Guggino, W. B. Jacobowitz, D. M. Srivastava, M. TI Antibody microarray analysis of the human platelet signaling proteome; Evidence for gender specificity SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Johns Hopkins Univ, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 SU S MA 1036 BP S277 EP S277 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506401216 ER PT J AU Savas, JN Makusky, A Markey, SP Tanese, N AF Savas, J. N. Makusky, A. Markey, S. P. Tanese, N. TI A proteomic approach to elucidate wild type huntingtin function(s) and Huntington's disease pathological mechanisms SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 NYU, Sch Med, NIH GPP, New York, NY USA. NIMH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 SU S MA 770 BP S201 EP S201 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506401038 ER PT J AU Saxena, SP AF Saxena, S. P. TI Proteomic strategies for aging and age-related disorders SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 SU S MA 1232 BP S334 EP S334 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506401345 ER PT J AU Sun, QF Gao, Y Liu, XL Chi, J Gao, JE Liu, XB Sun, QH Wang, SL AF Sun, Q. -F. Gao, Y. Liu, X. -L. Chi, J. Gao, J. -E. Liu, X. -B. Sun, Q. -H. Wang, S. -L. TI Preparation, characterization, and application of antibodies against human CLCN5 SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 Capital Med Univ, Sch Stomatol, Beijing, Peoples R China. Beijing Proteome Res Ctr, Beijing, Peoples R China. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 SU S MA 169 BP S38 EP S38 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506400084 ER PT J AU Whiteley, GR Fishman, D Huang, S Cowan, E Mikulskis, A Lopez, M Ross-Rucker, S Russo, P Shea, N Harvey, L Liu, C AF Whiteley, G. R. Fishman, D. Huang, S. Cowan, E. Mikulskis, A. Lopez, M. Ross-Rucker, S. Russo, P. Shea, N. Harvey, L. Liu, C. TI Identification of proteomic patterns using ion distance ratios to classify disease states SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 SAIC Frederick, NCI Frederick, Gaithersburg, MD USA. PerkinElmer Life & Analytical Sci, Boston, MA USA. NYU, New York, NY USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 SU S MA 446 BP S103 EP S103 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506400236 ER PT J AU Yeung, A Patel, B Li, XM Paterson, M Blagoi, E Seeholzer, S Chen, Y He, A Chaudhry, A Ke, E Coundry, R Cooper, H Bellacosa, A Clapper, M Boman, B Zhang, T Ross, E Litwin, S Conrad, P Crowell, J Kopelovich, L Knudson, A AF Yeung, A. Patel, B. Li, X-M. Paterson, M. Blagoi, E. Seeholzer, S. Chen, Y. He, A. Chaudhry, A. Ke, E. Coundry, R. Cooper, H. Bellacosa, A. Clapper, M. Boman, B. Zhang, T. Ross, E. Litwin, S. Conrad, P. Crowell, J. Kopelovich, L. Knudson, A. TI Heterozygous Adenomatous Polyposis Coli mutation in human colon crypt alters the proteome SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2006 VL 5 IS 10 SU S MA 213 BP S47 EP S47 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506400110 ER PT J AU Leung, MYK Steinbach, PJ Bear, D Baxendale, V Fechner, PY Rennert, OM Chan, WY AF Leung, Michael Yiu-Kwong Steinbach, Peter J. Bear, Deborah Baxendale, Vanessa Fechner, Patricia Y. Rennert, Owen M. Chan, Wai-Yee TI Biological effect of a novel mutation in the third leucine-rich repeat of human luteinizing hormone receptor SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID LEYDIG-CELL HYPOPLASIA; HORMONE/CHORIONIC GONADOTROPIN RECEPTOR; FOLLICLE-STIMULATING-HORMONE; HUMAN CHORIONIC-GONADOTROPIN; MALE PSEUDOHERMAPHRODITISM; HOMOZYGOUS MUTATION; EXTRACELLULAR DOMAIN; OVARIAN RESISTANCE; SURFACE EXPRESSION; BINDING EXODOMAIN AB A novel heterozygous mutation A340T leading to the substitution of Phe for the conserved amino acid IIe114 was identified by nucleotide sequencing of the human LH/chorionic gonadotropin receptor (hLHR) of a patient with Leydig cell hypoplasia. This mutation is located in the third leucine-rich repeat in the ectodomain of the hLHR. In vitro expression studies demonstrated that this mutation results in reduced ligand binding and signal transduction of the receptor. Studies of hLHR constructs in which various amino acids were substituted for the conserved Ile114 showed that receptor activity is sensitive to changes in size, shape, and charge of the side chain. A homology model of the wild-type hLHR ectodomain was made, illustrating the packing of conserved hydrophobic side chains in the protein core. Substitution of Ile114 by Phe might disrupt intermolecular contacts between hormone and receptor. This mutation might also affect an LHR-dimer interaction. Thus, the I114F mutation reduces ligand binding and signal transduction by the hLHR, and it is partially responsible for Leydig cell hypoplasia in the patient. C1 Natl Inst Child Hlth & Human Dev, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. Ctr Informat Technol, Div Compuatat Biosci, NIH, Bethesda, MD 20892 USA. Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. Georgetown Univ, Dept Pediat, Washington, DC 20007 USA. RP Chan, WY (reprint author), Natl Inst Child Hlth & Human Dev, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. EM chanwy@mail.nih.gov FU Intramural NIH HHS NR 48 TC 9 Z9 10 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 2006 VL 20 IS 10 BP 2493 EP 2503 DI 10.1210/me.2005-0510 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 088AY UT WOS:000240785100019 PM 16709601 ER PT J AU Vortherms, TA Roth, BL AF Vortherms, Timothy A. Roth, Bryan L. TI Salvinorin A - From natural product to human therapeutics SO MOLECULAR INTERVENTIONS LA English DT Review ID KAPPA-OPIOID-RECEPTOR; PLANT-DERIVED HALLUCINOGEN; MINT SALVIA-DIVINORUM; NEOCLERODANE DITERPENES; DRUG DISCOVERY; SALVINICIN-B; JATIVA-M; AGONIST; ANALOGS; RATS AB The hallucinogenic plant Salvia divinorum, a member of the mint family, has traditionally been used by the Mazatec natives of southern Mexico to induce ritual visions and is increasingly used in the US for recreational purposes. The main active ingredient in the plant is the diterpene salvinorin A, which is structurally distinct from other chemical classes of hallucinogens. In recent high-throughput screening experiments, salvinorin A was found to bind to the kappa-opioid receptor (KOR) with high specificity. Chemical analogs of the compound are now under study, in concert with functional characterization of KOR, to determine whether modulation of KOR activity could provide a basis for new psychotropic: medications. Indeed, there are indications that salvinorin A or its congeners may prove useful in both psychiatric and non-psychiatric diseases. C1 Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. NIMH, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA. RP Roth, BL (reprint author), Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. EM bryan_roth@med.unc.edu RI Roth, Bryan/F-3928-2010 FU NIDA NIH HHS [1F32 DA 022188, R01 DA 017204]; NIMH NIH HHS [N01 MH 80004] NR 49 TC 50 Z9 53 U1 1 U2 16 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 1534-0384 J9 MOL INTERV JI Mol. Interv. PD OCT PY 2006 VL 6 IS 5 BP 257 EP + DI 10.1124/mi.6.5.7 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 099YO UT WOS:000241634000005 PM 17035666 ER PT J AU Nielsen, HJ Ottesen, JR Youngren, B Austin, SJ Hansen, FG AF Nielsen, Henrik J. Ottesen, Jesper R. Youngren, Brenda Austin, Stuart J. Hansen, Flemming G. TI The Escherichia coli chromosome is organized with the left and right chromosome arms in separate cell halves SO MOLECULAR MICROBIOLOGY LA English DT Article ID REPLICATION FORKS; SEGREGATION; COHESION; TERMINUS; PLASMID; FAMILY; ORIGIN AB We have developed a system for the simultaneous labelling of two specific chromosomal sites using two different fluorescent ParB/parS systems. Using this, we demonstrate that the two chromosome arms are spatially arranged in newborn cells such that markers on the left arm of the chromosome lie in one half of the cell and markers on the right arm of the chromosome lie in the opposite half. This is achieved by reorganizing the chromosome arms of the two nucleoids in pre-division cells relative to the cell quarters. The spatial reorganization of the chromosome arms ensures that the two replication forks remain in opposite halves of the cell during replication. The relative orientation of the two reorganized nucleoids in pre-division cells is not random. Approximately 80% of dividing cells have their nucleoids oriented in a tandem configuration. C1 Tech Univ Denmark, BioCentrum, DK-2800 Lyngby, Denmark. NCI, Gene Regulat & Chromosome Biol Lab, CCR, Frederick, MD 21701 USA. RP Hansen, FG (reprint author), Tech Univ Denmark, BioCentrum, DK-2800 Lyngby, Denmark. EM fgh@biocentrum.dtu.dk NR 12 TC 92 Z9 93 U1 0 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 2006 VL 62 IS 2 BP 331 EP 338 DI 10.1111/j.1365-2958.2006.05346.x PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 088TM UT WOS:000240834000004 PM 17020576 ER PT J AU Yahiro, K Morinaga, N Satoh, M Matsuura, G Tomonaga, T Nomura, F Moss, J Noda, M AF Yahiro, Kinnosuke Morinaga, Naoko Satoh, Mamoru Matsuura, Gen Tomonaga, Takeshi Nomura, Fumio Moss, Joel Noda, Masatoshi TI Identification and characterization of receptors for vacuolating activity of subtilase cytotoxin SO MOLECULAR MICROBIOLOGY LA English DT Article ID ENTEROHEMORRHAGIC ESCHERICHIA-COLI; HEMOLYTIC-UREMIC SYNDROME; H+-ATPASE; 3-DIMENSIONAL COLLAGEN; INTEGRIN ALPHA-2-BETA-1; BETA(1) INTEGRIN; GENE-EXPRESSION; 16-KDA SUBUNIT; CELL-ADHESION; SHIGA TOXIN AB Some shiga toxin-producing Escherichia coli secrete a novel AB5 cytotoxin, named subtilase cytotoxin (SubAB), which induces vacuole formation in addition to cytotoxicity in susceptible cells. By immunoprecipitation with SubAB from Vero cells, we discovered proteins of 100 kDa, 135 kDa and 155 kDa as potential candidates for its receptor. These proteins were N-glycosylated in their extracellular domains, a modification that was necessary for interaction with SubAB. Biotinylated receptors were partially purified by Datura stramonium agglutinin affinity chromatography and avidin-agarose and analysed by TOF mass spectroscopy. The peptide sequences of p135 were identical to beta 1 integrin, and its identification was confirmed with anti-integrin beta 1 antibody. The p155 protein was identified as alpha 2 integrin using anti-integrin alpha 2 antibody. In addition, treatment of Vero cells with beta 1 integrin RNAi before exposure to SubAB prevented vacuolating activity. These results suggested that SubAB recognizes alpha 2 beta 1 integrin as a functional receptor; this first interaction may be an important key step leading to the SubAB-induced morphological changes in Vero cells. C1 Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chiba 2608670, Japan. Chiba Univ, Grad Sch Med, Dept Mol Diag, Chiba 2608670, Japan. Chiba Univ, Grad Sch Med, Dept Pediat Surg, Chiba 2608670, Japan. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Morinaga, N (reprint author), Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chiba 2608670, Japan. EM nmorinaga@faculty.chiba-u.jp NR 33 TC 27 Z9 27 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 2006 VL 62 IS 2 BP 480 EP 490 DI 10.1111/j.1365-2958.2006.05379.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 088TM UT WOS:000240834000015 PM 16965518 ER PT J AU Walker, NJ Wyde, ME Fischer, LJ Nyska, A Bucher, JR AF Walker, Nigel J. Wyde, Michael E. Fischer, Lawrence J. Nyska, Abraham Bucher, John R. TI Comparison of chronic toxicity and carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in 2-year bioassays in female Sprague-Dawley rats SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article DE carcinogenicity; mixtures; polychlorinated biphenyls; risk assessment; toxic equivalency factor ID DIOXIN-LIKE COMPOUNDS; SUBCHRONIC EXPOSURE; OXIDATIVE STRESS; ORAL TREATMENT; BRAIN-TISSUES; AH RECEPTOR; PATHOLOGY; 3,3',4,4',5-PENTACHLOROBIPHENYL; CLASSIFICATION; INDUCTION AB The cancer bioassay for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) conducted by the Dow Chemical company in the mid 70s has been used extensively for conducting quantitative cancer risk assessments for human exposure to TCDD. More recently the National Toxicology Program (NTP) conducted a cancer bioassay of similar design as part of its evaluation of the dioxin toxic equivalency factor methodology. This report compares the design and the results of these two cancer bioassays. This comparison confirms, in most cases, previously published and widely used carcinogenic response characteristics with respect to dose, time course, organ selectivity, tumor type and maximum intensity of TCDD-induced carcinogenicity and toxicity in the Sprague-Dawley rat. Specifically, increases in the incidences of neoplasms were seen in both studies in the liver, lung and oral mucosa. The most notable difference was the significant increase in the incidence of cholangiocarcinoma of the liver seen in the NTP study but not in the Dow study. The experimental designs for the two studies are similar but some protocol parameters differed, such as vehicle, dosing schedule, diet and rat sub-strain utilized. Differences in the shapes of the dose response curves for several neoplasms were noted between the studies, with the NTP study showing non-linearity for all neoplasms. This may result from differences in the experimental protocols as well as divergence in the biological behavior of the different stocks of Sprague-Dawley rat strains used. C1 NIEHS, Environm Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. Michigan State Univ, Ctr Integrat Toxicol, E Lansing, MI 48824 USA. RP Walker, NJ (reprint author), NIEHS, Environm Toxicol Program, NIH, 79 Alexander Dr,Bldg 4401,POB 12233,MD EC-34, Res Triangle Pk, NC 27709 USA. EM walker3@niehs.nih.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 FU Intramural NIH HHS [Z99 ES999999] NR 34 TC 20 Z9 20 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD OCT PY 2006 VL 50 IS 10 BP 934 EP 944 DI 10.1002/mnfr.200600031 PG 11 WC Food Science & Technology SC Food Science & Technology GA 098MZ UT WOS:000241528200007 PM 16977594 ER PT J AU Bauer, B Yang, XD Hartz, AMS Olson, ER Zhao, R Kalvass, JC Pollack, GM Miller, DS AF Bauer, Bjorn Yang, Xiaodong Hartz, Anika M. S. Olson, Emily R. Zhao, Rong Kalvass, J. Cory Pollack, Gary M. Miller, David S. TI In vivo activation of human pregnane X receptor tightens the blood-brain barrier to methadone through P-glycoprotein up-regulation SO MOLECULAR PHARMACOLOGY LA English DT Article ID DRUG EFFLUX TRANSPORTERS; XENOBIOTIC RECEPTOR; ANALGESIC ACTIVITY; ELECTRICAL METHOD; MICE; MODULATION; RIFAMPIN; DISEASES AB The ATP-driven drug export pump, P-glycoprotein, is a primary gatekeeper of the blood-brain barrier and a major impediment to central nervous system (CNS) pharmacotherapy. Reducing P-glycoprotein activity dramatically increases penetration of many therapeutic drugs into the CNS. Previous studies in rat showed that brain capillary P-glycoprotein was transcriptionally up-regulated by the pregnane X receptor (PXR), a xenobiotic-activated nuclear receptor. Here we used a transgenic mouse expressing human PXR (hPXR) to determine the consequences of increased blood-brain barrier P-glycoprotein activity. P-glycoprotein expression and transport activity in brain capillaries from transgenic mice was significantly increased when capillaries were exposed to the hPXR ligands, rifampin and hyperforin, in vitro and when the mice were dosed with rifampin in vivo. Plasma rifampin levels in induced mice were comparable with literature values for patients. We also administered methadone, a CNS-acting, P-glycoprotein substrate, to control and rifampin-induced transgenic mice and measured the drug's antinociceptive effect. In rifampin-induced mice, the methadone effect was reduced by approximately 70%, even though plasma methadone levels were similar to those found in transgenic controls not exposed to rifampin. Thus, hPXR activation in vivo increased P-glycoprotein activity and tightened the blood-brain barrier to methadone, reducing the drug's CNS efficacy. This is the first demonstration of the ability of bloodbrain barrier PXR to alter the efficacy of a CNS-acting drug. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Pharm, Div Drug Delivery & Disposit, Chapel Hill, NC USA. RP Miller, DS (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM miller@niehs.nih.gov FU Intramural NIH HHS; NIGMS NIH HHS [GM61191] NR 28 TC 113 Z9 115 U1 1 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 2006 VL 70 IS 4 BP 1212 EP 1219 DI 10.1124/mol.106.023796 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 086QN UT WOS:000240688200009 PM 16837625 ER PT J AU Shin, M Kim, I Inoue, Y Kimura, S Gonzalez, FJ AF Shin, Mariko Kim, Insook Inoue, Yusuke Kimura, Shioko Gonzalez, Frank J. TI Regulation of mouse hepatic alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase, a key enzyme in the tryptophan-nicotinamide adenine dinucleotide pathway, by hepatocyte nuclear factor 4 alpha and peroxisome proliferator-activated receptor alpha SO MOLECULAR PHARMACOLOGY LA English DT Article ID NUCLEAR FACTOR 4-ALPHA; POLYUNSATURATED FATTY-ACIDS; CLOFIBRATE-CONTAINING DIET; ACYL-COA THIOESTERS; HIGH-PROTEIN DIET; GENE-EXPRESSION; PICOLINIC CARBOXYLASE; DNA-BINDING; LIVER; FACTOR-4-ALPHA AB Nicotinamide adenine dinucleotide (NAD) plays a critical role in the maintenance of cellular energy homeostasis. alpha-Amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) is the key enzyme regulating de novo synthesis of NAD from L-tryptophan (Trp), designated the Trp-NAD pathway. Acmsd gene expression was found to be under the control of both hepatocyte nuclear factor 4 alpha (HNF4 alpha) and peroxisome proliferator-activated receptor alpha(PPAR alpha). Constitutive expression of ACMSD mRNA levels were governed by HNF4 alpha and downregulated by activation of PPAR alpha by the ligand Wy-14,643 ([4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid]), as revealed by studies with hepatic HNF4 alpha-null mice and PPAR alpha-null mice, respectively. Transient transfection and electrophoretic mobility shift analyses showed an HNF4 alpha binding site in the Acmsd gene promoter that directed transactivation of reporter gene constructs by HNF4 alpha. The Acmsd promoter was not responsive to PPAR alpha in transactivation assays. Wy-14,643 treatment decreased HNF4 alpha protein levels in wild-type, but not PPAR alpha-null, mouse livers, with no changes in HNF4 alpha mRNA. These results show that Wy-14,643, through PPAR alpha, posttranscriptionally down-regulates HNF4 alpha protein levels, leading to reduced expression of the HNF4 alpha target gene Acmsd. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov FU Intramural NIH HHS NR 41 TC 24 Z9 25 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 2006 VL 70 IS 4 BP 1281 EP 1290 DI 10.1124/mol.106.026294 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 086QN UT WOS:000240688200017 PM 16807375 ER PT J AU Navarro, S Meza, NW Quintana-Bustamante, O Casado, JA Jacome, A McAllister, K Puerto, S Surralles, J Segovia, JC Bueren, JA AF Navarro, Susana Meza, Nestor W. Quintana-Bustamante, Oscar Casado, Jos A. Jacome, Ariana McAllister, Kimberly Puerto, Silvia Surralles, Jordi Segovia, Jose C. Bueren, Juan A. TI Hematopoietic dysfunction in a mouse model for Fanconi anemia group D1 SO MOLECULAR THERAPY LA English DT Article DE Fanconi anemia; Brca2; Fancd1; genetic instability; DNA repair; mitomycin C; hernatopoietic stem cells; self-renewal; competitive repopulation ability; hernatopoiesis ID LYMPHOHEMATOPOIETIC STEM-CELLS; CANCER SUSCEPTIBILITY; TARGETED DISRUPTION; REVERSE MOSAICISM; HELICASE BRIP1; KNOCKOUT MICE; BREAST-CANCER; BRCA2; REPAIR; DEFECT AB We have investigated the hematopoietic phenotype of mice with a hypomorphic mutation in the Brca2/Fancd1 gene (Brca2(Delta 27/Delta 27) mutation). In contrast to observations made in other Fanconi anemia (FA) mouse models, low numbers of hematopoietic colony-forming cells (CFCs) were noted in Brca2(Delta 27/Delta 27) mice, either young or adult. Additionally, a high incidence of spontaneous chromosomal instability was observed in Brca2(Delta 27/Delta 27) bone marrow (BM) cells, but not in Brca2(+/Delta 27) or Fanca(-/-) BM cells. Although Brca2(Delta 27/Delta 27) CFCs were not hypersensitive to ionizing radiation, a very severe hematopoietic syndrome was observed in irradiated Brca2(Delta 27/Delta 27) mice. Conventional BM competition experiments showed a marked repopulation defect in Brca2(Delta 27/Delta 27) hematopoietic stem cells (HSCs), compared to wild-type HSCs. Moreover, we have observed for the first time in a DNA repair disease model a very significant proliferation defect in Brca2(Delta 27/Delta 27) HSCs maintained in their natural physiological environment. The progressive repopulation of wild-type HSCs transplanted into unconditioned Brca2(A27/Delta 27) recipients is reminiscent of the somatic mosaicism phenomenon observed in a number of genetic diseases, including FA. The hematopoietic phenotype associated with the Brca2(Delta 27/Delta 27) mutation suggests that this FA-D1 mouse model will constitute an important tool for the development of new therapies for FA, including gene therapy. C1 Marcelino Botin Fdn, CIEMAT, Hematopoiesis & Gene Therapy Div, Madrid 28040, Spain. Natl Inst Environm Hlth Sci, NIH, Bethesda, MD 20892 USA. Univ Autonoma Barcelona, Dept Genet, E-08193 Barcelona, Spain. RP Bueren, JA (reprint author), Marcelino Botin Fdn, CIEMAT, Hematopoiesis & Gene Therapy Div, Ave Complutense 22, Madrid 28040, Spain. EM juan.bueren@ciemat.es RI Navarro, Susana/L-9300-2014; Casado, Jose/H-5077-2015; Bueren, Juan/L-6112-2014; Quintana, Oscar/M-1724-2014; OI Navarro, Susana/0000-0002-0764-5384; Casado, Jose/0000-0003-2479-1508; Bueren, Juan/0000-0002-3228-7013; Quintana, Oscar/0000-0002-6869-7006; Surralles, Jordi/0000-0002-4041-7519; Jacome de Azevedo, Ariana/0000-0002-2980-7399; Segovia, Jose C/0000-0003-4101-6124 NR 45 TC 59 Z9 59 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 1525-0016 J9 MOL THER JI Mol. Ther. PD OCT PY 2006 VL 14 IS 4 BP 525 EP 535 DI 10.1016/j.ymthe.2006.05.018 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 087KF UT WOS:000240740600011 PM 16859999 ER PT J AU Bankiewicz, KS Forsayeth, J Eberling, JL Sanchez-Pernaute, R Pivirotto, P Bringas, J Herscovitch, P Carson, RE Eckelman, W Reutter, B Cunningham, J AF Bankiewicz, Krystof S. Forsayeth, John Eberling, Jamie L. Sanchez-Pernaute, Rosario Pivirotto, Philip Bringas, John Herscovitch, Peter Carson, Richard E. Eckelman, William Reutter, Bryan Cunningham, Janet TI Long-term clinical improvement in MPTP-lesioned primates after gene therapy with AAV-hAADC SO MOLECULAR THERAPY LA English DT Article DE Parkinson, primate; clinical; L-dopa; AADC; PET imaging; FMT ID CONVECTION-ENHANCED DELIVERY; PARKINSONS-DISEASE; ADENOASSOCIATED VIRUS; MONKEYS; DOPAMINE; STRIATUM; VECTOR; EXPRESSION; INFUSION; NEURONS AB Dopamine, the major neurotransmitter depleted in Parkinson disease, can be synthesized and regulated in vivo with a combination of intrastriatal AAV-hAADC gene therapy and administration of the dopamine precursor L-Dopa. When tested in MPTP-lesioned monkeys, this approach resulted in long-term improvement in clinical rating scores, significantly lowered L-Dopa requirements, and a reduction in L-Dopa-induced side effects. Positron emission tomography with [F-18]FMT confirmed persistent AADC activity, demonstrating for the first time that infusion of AAV vector into primate brain results in at least 6 years of transgene expression. AAV-hAADC restores the ability of the striatum to convert L-Dopa into dopamine efficiently. Introduction of this therapy into the clinic holds promise for Parkinson patients experiencing the motor complications that result from escalating L-Dopa requirements against a background of disease progression. C1 Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94103 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Ctr Funct Imaging, Berkeley, CA 94720 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Bankiewicz, KS (reprint author), Univ Calif San Francisco, Dept Neurosurg, Room MCB 226,1855 Folsom St, San Francisco, CA 94103 USA. EM kbank@itsa.ucsf.edu RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 FU Intramural NIH HHS NR 33 TC 160 Z9 170 U1 2 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD OCT PY 2006 VL 14 IS 4 BP 564 EP 570 DI 10.1016/j.ymthe.2006.05.005 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 087KF UT WOS:000240740600015 PM 16829205 ER PT J AU Rehner, SA De Muro, MA Bischoff, JF AF Rehner, Stephen A. De Muro, Marilena Aquino Bischoff, Joseph F. TI Description and phylogenetic placement of Beauveria malawiensis sp nov (Clavicipitaceae, Hypocreales) SO MYCOTAXON LA English DT Article DE Cordyceps; fungal entomopathogen; new species; taxonomy ID EVOLUTION; FUNGI AB A new entomopathogenic species, Beauveria malawiensis, is described. Beauveria malawiensis was isolated from a cadaver of Phoracantha semipunctata (Coleoptera: Cerambycidae) collected in Zomba, Malawi. Morphologically, B. malawiensis is distinguished by its pink colony color, the terminal and intercalary clusters of inflated conidiophores that each gives rise to multiple rachiform conidiogenous cells, and holoblastic cylindrical conidia. Phylogenetic analysis of nuclear ribosomal internal transcribed spacer and translation elongation factor-1 alpha sequences place B. malawiensis apart from other species in the genus that also produce cylindrical conidia, supporting its proposed species status. C1 USDA ARS, Insect Biocontrol Lab, Beltsville, MD 20705 USA. CABI Biosci, Egham TW20 9TY, Surrey, England. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Rehner, SA (reprint author), USDA ARS, Insect Biocontrol Lab, Beltsville, MD 20705 USA. EM rehners@ba.ars.usda.gov NR 17 TC 9 Z9 12 U1 0 U2 8 PU MYCOTAXON LTD PI ITHACA PA PO BOX 264, ITHACA, NY 14851-0264 USA SN 0093-4666 J9 MYCOTAXON JI Mycotaxon PD OCT-DEC PY 2006 VL 98 BP 137 EP 145 PG 9 WC Mycology SC Mycology GA 153GM UT WOS:000245420200005 ER PT J AU Bray, F Ferlay, J Devesa, SS McGlynn, KA Moller, H AF Bray, Freddie Ferlay, Jacques Devesa, Susan S. McGlynn, Katherine A. Moller, Henrik TI Interpreting the international trends in testicular seminoma and nonseminoma incidence SO NATURE CLINICAL PRACTICE UROLOGY LA English DT Review DE epidemiology; germ cell; seminoma; testicular cancer; trends ID GERM-CELL TUMORS; CANCER INCIDENCE; CARCINOMA-INSITU; HISTOPATHOLOGICAL ABNORMALITIES; POLYCHLORINATED-BIPHENYLS; PERINATAL CHARACTERISTICS; DESCRIPTIVE EPIDEMIOLOGY; EUROPEAN COUNTRIES; RISK; MEN AB There are considerable geographic, ethnic and temporal variations in the global incidence of testicular cancer. The disease mainly affects Western populations, with average rates in developed areas of the world six times higher than those in developing areas. About 500,000 new cases were diagnosed worldwide in 2002, with the vast majority being germ cell tumors and occurring in young adult males. Traditionally, these tumors are further classified into seminoma and nonseminoma. In this Review, trends in the incidence of germ cell tumors are examined using high-quality cancer-registry data from 41 populations within 14 countries worldwide. To assess whether trends of seminoma and nonseminoma incidence are similar, data were analyzed by birth cohort. These analyses should reveal similar trends if the 10-year difference in the clinical manifestation of cancer between subtypes is caused by differences in the speed of progression from the same early rate-limiting step to the onset of symptomatic disease. In each country, incidence has uniformly increased in successive generations born from around 1920 until very recently. Cohort-specific trends in seminoma incidence are similar to cohort-specific trends in nonseminoma incidence, lending support to the conclusion that the subtypes are epidemiologically and etiologically comparable. The findings presented are related to current theories and evidence regarding the determinants of testicular germ cell cancer. C1 Canc Registry Norway, Inst Populat Based Canc Res, N-0310 Oslo, Norway. Int Agcy Res Canc, F-69372 Lyon, France. NCI, Bethesda, MD 20892 USA. Kings Coll London, London WC2R 2LS, England. London Sch Hyg & Trop Med, London WC1, England. RP Bray, F (reprint author), Canc Registry Norway, Inst Populat Based Canc Res, N-0310 Oslo, Norway. EM freddie.bray@kreftregisteret.no OI Moller, Henrik/0000-0001-8200-5929 NR 52 TC 69 Z9 70 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4270 J9 NAT CLIN PRACT UROL JI Nat. Clin. Pract. Urol. PD OCT PY 2006 VL 3 IS 10 BP 532 EP 543 DI 10.1038/ncpuro0606 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 090GI UT WOS:000240938400010 PM 17031378 ER PT J AU Padiath, QS Saigoh, K Schiffmann, R Asahara, H Yamada, T Koeppen, A Hogan, K Ptacek, LJ Fu, YH AF Padiath, Quasar S. Saigoh, Kazumasa Schiffmann, Raphael Asahara, Hideaki Yamada, Takeshi Koeppen, Anulf Hogan, Kirk Ptacek, Louis J. Fu, Ying-Hui TI Lamin B1 duplications cause autosomal dominant leukodystrophy SO NATURE GENETICS LA English DT Article ID PROGRESSIVE MULTIPLE-SCLEROSIS; DREIFUSS MUSCULAR-DYSTROPHY; PELIZAEUS-MERZBACHER-DISEASE; NUCLEAR LAMINS; PARTIAL LIPODYSTROPHY; GENE-EXPRESSION; DNA-SEQUENCES; HUMAN TISSUES; DROSOPHILA; PROTEIN AB Adult-onset autosomal dominant leukodystrophy (ADLD) is a slowly progressive neurological disorder characterized by symmetrical widespread myelin loss in the central nervous system, with a phenotype similar to chronic progressive multiple sclerosis. In this study, we identify a genomic duplication that causes ADLD. Affected individuals carry an extra copy of the gene for the nuclear laminar protein lamin B1, resulting in increased gene dosage in brain tissue from individuals with ADLD. Increased expression of lamin B1 in Drosophila melanogaster resulted in a degenerative phenotype. In addition, an abnormal nuclear morphology was apparent when cultured cells overexpressed this protein. This is the first human disease attributable to mutations in the gene encoding lamin B1. Antibodies to lamin B are found in individuals with autoimmune diseases, and it is also an antigen recognized by a monoclonal antibody raised against plaques from brains of individuals with multiple sclerosis. This raises the possibility that lamin B may be a link to the autoimmune attack that occurs in multiple sclerosis. C1 Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Kyushu Univ, Fac Med, Dept Neurol, Fukuoka 812, Japan. Iizuka Hosp, Dept Neurol, Iizuka, Fukuoka, Japan. Albany Med Coll, Vet Adm Med Ctr, Albany, NY 12208 USA. Albany Med Coll, Dept Neurol, Albany, NY 12208 USA. Univ Wisconsin, Dept Anesthesiol, Madison, WI 53792 USA. Howard Hughes Med Inst, San Francisco, CA 94158 USA. RP Fu, YH (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA. EM yhf@neugenes.org FU NINDS NIH HHS [NS41331] NR 50 TC 193 Z9 200 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2006 VL 38 IS 10 BP 1114 EP 1123 DI 10.1038/ng1872 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 094PJ UT WOS:000241251100010 PM 16951681 ER PT J AU de Bakker, PIW McVean, G Sabeti, PC Miretti, MM Green, T Marchini, J Ke, XY Monsuur, AJ Whittaker, P Delgado, M Morrison, J Richardson, A Walsh, EC Gao, XJ Galver, L Hart, J Hafler, DA Pericak-Vance, M Todd, JA Daly, MJ Trowsdale, J Wijmenga, C Vyse, TJ Beck, S Murray, SS Carrington, M Gregory, S Deloukas, P Rioux, JD AF de Bakker, Paul I. W. McVean, Gil Sabeti, Pardis C. Miretti, Marcos M. Green, Todd Marchini, Jonathan Ke, Xiayi Monsuur, Alienke J. Whittaker, Pamela Delgado, Marcos Morrison, Jonathan Richardson, Angela Walsh, Emily C. Gao, Xiaojiang Galver, Luana Hart, John Hafler, David A. Pericak-Vance, Margaret Todd, John A. Daly, Mark J. Trowsdale, John Wijmenga, Cisca Vyse, Tim J. Beck, Stephan Murray, Sarah Shaw Carrington, Mary Gregory, Simon Deloukas, Panos Rioux, John D. TI A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC SO NATURE GENETICS LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; NONCODING SEQUENCE POLYMORPHISMS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; HUMAN GENOME; LINKAGE-DISEQUILIBRIUM; CELIAC-DISEASE; REGION; RISK AB The proteins encoded by the classical HLA class I and class II genes in the major histocompatibility complex (MHC) are highly polymorphic and are essential in self versus non-self immune recognition. HLA variation is a crucial determinant of transplant rejection and susceptibility to a large number of infectious and autoimmune diseases(1). Yet identification of causal variants is problematic owing to linkage disequilibrium that extends across multiple HLA and non-HLA genes in the MHC(2,3). We therefore set out to characterize the linkage disequilibrium patterns between the highly polymorphic HLA genes and background variation by typing the classical HLA genes and > 7,500 common SNPs and deletion-insertion polymorphisms across four population samples. The analysis provides informative tag SNPs that capture much of the common variation in the MHC region and that could be used in disease association studies, and it provides new insight into the evolutionary dynamics and ancestral origins of the HLA loci and their haplotypes. C1 Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Ctr Human Genet, Boston, MA 02114 USA. Univ Oxford, Dept Stat, Oxford OX1 2JD, England. Wellcome Trust Sanger Inst, Hinxton, England. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England. Univ Utrecht, Med Ctr, Dept Med Genet, Complex Genet Sect, NL-3508 TC Utrecht, Netherlands. SAIC Frederick Inc, Lab Genom Divers, Frederick, MD USA. NCI, Frederick, MD 21701 USA. Illumina Inc, San Diego, CA USA. Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC 27706 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Cambridge, Inst Med Res, Wellcome Trust Diabet & Inflammat Lab, Juventil Diabet Res Fdn, Cambridge CB2 1TN, England. Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge, England. Imperial Coll Sch Med, London, England. Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. RP Rioux, JD (reprint author), Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. EM rioux@broad.mit.edu RI Ke, Xiayi/C-7674-2009; Todd, John/A-3542-2010; Deloukas, Panos/B-2922-2013; de Bakker, Paul/B-8730-2009; Wijmenga, Cisca/D-2173-2009; Rioux, John/A-9599-2015; OI Deloukas, Panos/0000-0001-9251-070X; de Bakker, Paul/0000-0001-7735-7858; Rioux, John/0000-0001-7560-8326; Wijmenga, Cisca/0000-0002-5635-1614 FU Intramural NIH HHS; Medical Research Council [G9800943]; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [U19 AI050864]; Wellcome Trust [, 077011] NR 29 TC 409 Z9 417 U1 2 U2 30 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2006 VL 38 IS 10 BP 1166 EP 1172 DI 10.1038/ng1885 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 094PJ UT WOS:000241251100016 PM 16998491 ER PT J AU Siegel, RM AF Siegel, Richard M. TI A new web resource for NIH immunology SO NATURE IMMUNOLOGY LA English DT Letter C1 NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Siegel, RM (reprint author), NIAMSD, Autoimmun Branch, NIH, Bldg 10,Rm 9N238, Bethesda, MD 20892 USA. EM rsiegel@nih.gov RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 NR 0 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 2006 VL 7 IS 10 BP 1007 EP 1007 DI 10.1038/ni1006-1007 PG 1 WC Immunology SC Immunology GA 097HE UT WOS:000241437100002 PM 16985492 ER PT J AU Choi, KC Lee, YS Lim, S Choi, HK Lee, CH Lee, EK Hong, S Kim, IH Kim, SJ Park, SH AF Choi, Kyung-Chul Lee, Youn Sook Lim, Seunghwan Choi, Hyo Kyoung Lee, Chang-Hun Lee, Eun-Kyung Hong, Suntaek Kim, In-Hoo Kim, Seong-Jin Park, Seok Hee TI Smad6 negatively regulates interleukin 1-receptor Toll-like receptor signaling through direct interaction with the adaptor Pellino-1 SO NATURE IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; TGF-BETA; INHIBITORY SMADS; CELL ACTIVATION; INNATE IMMUNITY; HUMAN-DISEASE; HOST-DEFENSE; PROTEIN; MECHANISM; MICE AB Transforming growth factor-beta 1 (TGF-beta 1) is a potent cytokine with pleiotropic effects, including anti-inflammatory activity. Here we show that the signaling protein Smad6 bound to Pellino-1, an adaptor protein of mammalian interleukin 1 receptor (IL-1R) associated kinase 1 ( IRAK1), and thereby promoted TGF-beta-mediated anti-inflammatory effects. Smad6-Pellino-1 interaction abrogated signaling mediated by a complex of IRAK1, Pellino-1 and adaptor protein TRAF6 that formed after stimulation by IL-1 beta treatment. Blockade of IRAK1-Pellino-1-TRAF6 signaling prevented degradation of the inhibitor I kappa B alpha and subsequent nuclear translocation of transcription factor NF-kappa B and thus expression of proinflammatory genes. 'Knockdown' of endogenous Smad6 expression by RNA interference reduced anti-inflammatory activity mediated by TGF-beta 1 or the TGF-beta family member BMP-4. Thus Smad6 is a critical mediator of the TGF-beta-BMP pathway that mediates anti-inflammatory activity and negatively regulates IL-1R-Toll-like receptor signals. C1 Inha Univ, Coll Med, Dept Pathol, BK Project 21,Ctr Adv Med Educ, Inchon 400712, South Korea. Inha Univ, Coll Med, Inha Res Inst Med Sci, Inchon 400712, South Korea. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Natl Canc Ctr, Res Inst, Goyang 411769, Gyeonggi, South Korea. RP Park, SH (reprint author), Inha Univ, Coll Med, Dept Pathol, BK Project 21,Ctr Adv Med Educ, Inchon 400712, South Korea. EM kims@mail.nih.gov; parksh@inha.ac.kr FU Intramural NIH HHS NR 56 TC 72 Z9 85 U1 1 U2 5 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 OCT PY 2006 VL 7 IS 10 BP 1057 EP 1065 DI 10.1038/ni1383 PG 9 WC Immunology SC Immunology GA 097HE UT WOS:000241437100011 PM 16951688 ER PT J AU Minetti, GC Colussi, C Adami, R Serra, C Mozzetta, C Parente, V Fortuni, S Straino, S Sampaolesi, M Di Padova, M Illi, B Gallinari, P Steinkuhler, C Capogrossi, MC Sartorelli, V Bottinelli, R Gaetano, C Puri, PL AF Minetti, G. C. Colussi, C. Adami, R. Serra, C. Mozzetta, C. Parente, V. Fortuni, S. Straino, S. Sampaolesi, M. Di Padova, M. Illi, B. Gallinari, P. Steinkuehler, C. Capogrossi, M. C. Sartorelli, V. Bottinelli, R. Gaetano, C. Puri, P. L. TI Functional and morphological recovery of dystrophic muscles in mice treated with deacetylase inhibitors SO NATURE MEDICINE LA English DT Article ID MUSCULAR-DYSTROPHY; MYOSTATIN BLOCKADE; DEFICIENT MICE; MDX MICE; EXPRESSION; SEVERITY AB Pharmacological interventions that increase myofiber size counter the functional decline of dystrophic muscles(1,2). We show that deacetylase inhibitors increase the size of myofibers in dystrophin-deficient (MDX) and alpha-sarcoglycan (alpha-SG)-deficient mice by inducing the expression of the myostatin antagonist follistatin(3) in satellite cells. Deacetylase inhibitor treatment conferred on dystrophic muscles resistance to contraction-coupled degeneration and alleviated both morphological and functional consequences of the primary genetic defect. These results provide a rationale for using deacetylase inhibitors in the pharmacological therapy of muscular dystrophies. C1 Fdn A Cesalpino, Dulbecco Telethon Inst, Inst Cell Biol & Tissue Engn, San Raffaele Biomed Sci Pk Rome, I-00128 Rome, Italy. IRCCS, Ist Dermatopat Immacolata, Lab Vasc Pathol, I-00167 Rome, Italy. Univ Pavia, Dept Expt Med, Human Physiol Unit, I-27100 Pavia, Italy. Univ Pavia, Interuniv Inst Mycol, I-27100 Pavia, Italy. Burnham Inst, La Jolla, CA 92037 USA. Hosp San Raffaele, Stem Cell Res Inst, I-20132 Milan, Italy. NIAMSD, Muscle Gene Express Grp, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA. IRCCS, Lab Vasc Biol & Gene Therapy, Ctr Cardiol Monzino, I-20138 Milan, Italy. Ist Ric Biol Mol P Angeletti, I-00040 Rome, Italy. RP Puri, PL (reprint author), Fdn A Cesalpino, Dulbecco Telethon Inst, Inst Cell Biol & Tissue Engn, San Raffaele Biomed Sci Pk Rome, Via Castel Romano 100, I-00128 Rome, Italy. EM plpuri@dti.telethon.it RI Sampaolesi, Maurilio/H-6509-2013; Parente, Valeria/H-7817-2016; Minetti, Giampaolo/F-2385-2012; OI Gaetano, Carlo/0000-0002-5238-1832; Puri, Pier Lorenzo/0000-0003-4964-0095; Sampaolesi, Maurilio/0000-0002-2422-3757; Parente, Valeria/0000-0001-6559-9817; Minetti, Giampaolo/0000-0003-3063-4613; DI PADOVA, Monica/0000-0003-3808-7159; Mozzetta, Chiara/0000-0002-7147-7266 FU Intramural NIH HHS; Telethon [GGP02284] NR 15 TC 168 Z9 171 U1 5 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2006 VL 12 IS 10 BP 1147 EP 1150 DI 10.1038/nm1479 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 092MW UT WOS:000241102200030 PM 16980968 ER PT J AU Pommier, Y AF Pommier, Yves TI Topoisomerase I inhibitors: camptothecins and beyond SO NATURE REVIEWS CANCER LA English DT Review ID DOUBLE-STRAND BREAKS; MEDIATED DNA-DAMAGE; MOLECULAR INTERACTION MAPS; DEPENDENT PROTEIN-KINASE; COLON-CARCINOMA CELLS; RNA-POLYMERASE-II; CANCER-CELLS; S-PHASE; POLY(ADP-RIBOSE) POLYMERASE; GENOMIC INSTABILITY AB Nuclear DNA topoisomerase I (TOP1) is an essential human enzyme. It is the only known target of the alkaloid camptothecin, from which the potent anticancer agents irinotecan and topotecan are derived. As camptothecins bind at the interface of the TOP1-DNA complex, they represent a paradigm for interfacial inhibitors that reversibly trap macromolecular complexes. Several camptothecin and non-camptothecin derivatives are being developed to further increase anti-tumour activity and reduce side effects. The mechanisms and molecular determinants of tumour response to TOP1 inhibitors are reviewed, and rational combinations of TOP1 inhibitors with other drugs are considered based on current knowledge of repair and checkpoint pathways that are associated with TOP1-mediated DNA damage. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. EM pommier@nih.gov FU Intramural NIH HHS NR 152 TC 907 Z9 931 U1 19 U2 148 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD OCT PY 2006 VL 6 IS 10 BP 789 EP 802 DI 10.1038/nrc1977 PG 14 WC Oncology SC Oncology GA 095JC UT WOS:000241303000015 PM 16990856 ER PT J AU Shoemaker, RH AF Shoemaker, Robert H. TI The NCI60 human tumour cell line anticancer drug screen SO NATURE REVIEWS CANCER LA English DT Article ID NATIONAL-CANCER-INSTITUTE; ANTHRAX LETHAL FACTOR; CYTO-TOXICITY ASSAYS; HALICHONDRIN-B; IN-VITRO; 9-CHLORO-2-METHYLELLIPTICINIUM ACETATE; DIFFERENTIAL CYTOTOXICITY; PROTEOLYTIC INACTIVATION; MOLECULAR PHARMACOLOGY; SALICYLIHALAMIDE-A AB The US National Cancer Institute (NCl) 60 human tumour cell line anticancer drug screen (NCl60) was developed in the late 1980s as an in vitro drug-discovery tool intended to supplant the use of transplantable animal tumours in anticancer drug screening. This screening model was rapidly recognized as a rich source of information about the mechanisms of growth inhibition and tumour-cell kill. Recently, its role has changed to that of a service screen supporting the cancer research community. Here I review the development, use and productivity of the screen, highlighting several outcomes that have contributed to advances in cancer chemotherapy. C1 NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diagnosis, Frederick, MD 21702 USA. RP Shoemaker, RH (reprint author), NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diagnosis, Frederick, MD 21702 USA. EM shoemaker@dtpax2.ncifcrf.gov RI han, chao/B-6245-2011 NR 92 TC 933 Z9 947 U1 19 U2 95 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD OCT PY 2006 VL 6 IS 10 BP 813 EP 823 DI 10.1038/nrc1951 PG 11 WC Oncology SC Oncology GA 095JC UT WOS:000241303000017 PM 16990858 ER PT J AU Scripture, CD Figg, WD AF Scripture, Charity D. Figg, William D. TI Epidemiology of drug interactions in cancer patients - Reply SO NATURE REVIEWS CANCER LA English DT Letter C1 NCI, Canc Res Ctr, Bethesda, MD 20892 USA. RP Scripture, CD (reprint author), NCI, Canc Res Ctr, 9000 Rockville Pike,Bldg 10,Room 5A01,MSC1910, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD OCT PY 2006 VL 6 IS 10 PG 1 WC Oncology SC Oncology GA 095JC UT WOS:000241303000019 ER PT J AU Kouprina, N Larionov, V AF Kouprina, Natalay Larionov, Vladimir TI Innovation - TAR cloning: insights into gene function, long-range haplotypes and genome structure and evolution SO NATURE REVIEWS GENETICS LA English DT Review ID TRANSFORMATION-ASSOCIATED RECOMBINATION; HUMAN ARTIFICIAL CHROMOSOMES; COPY-NUMBER VARIATION; PROSTATE-CANCER; HUMAN DNA; ENGINEERED CHROMOSOMES; SELECTIVE ISOLATION; ASPM GENE; YEAST; SEQUENCE AB The structural and functional analysis of mammalian genomes would benefit from the ability to isolate from multiple DNA samples any targeted chromosomal segment that is the size of an average human gene. A cloning technique that is based on transformation-associated recombination ( TAR) in the yeast Saccharomyces cerevisiae satisfies this need. It is a unique tool to selectively recover chromosome segments that are up to 250 kb in length from complex genomes. In addition, TAR cloning can be used to characterize gene function and genome variation, including polymorphic structural rearrangements, mutations and the evolution of gene families, and for long-range haplotyping. C1 NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. RP Kouprina, N (reprint author), NCI, Lab Biosyst & Canc, NIH, Bldg 37,Room 5032,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kouprinn@mail.nih.gov NR 53 TC 46 Z9 48 U1 4 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD OCT PY 2006 VL 7 IS 10 BP 805 EP 812 DI 10.1038/nrg1943 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 093HJ UT WOS:000241158700016 PM 16983376 ER PT J AU Manolio, TA Bailey-Wilson, JE Collins, FS AF Manolio, Teri A. Bailey-Wilson, Joan E. Collins, Francis S. TI Opinion - Genes, environment and the value of prospective cohort studies SO NATURE REVIEWS GENETICS LA English DT Review ID CORONARY-HEART-DISEASE; DIETARY-FAT INTAKE; HUMAN GENOME; EPIDEMIOLOGIC RESEARCH; ATHEROSCLEROSIS RISK; CHOLESTEROL LEVELS; COMPLEX DISEASES; POLYMORPHISM; MARKERS; DESIGN AB Case-control studies have many advantages for identifying disease-related genes, but are limited in their ability to detect gene-environment interactions. The prospective cohort design provides a valuable complement to case-control studies. Although it has disadvantages in duration and cost, it has important strengths in characterizing exposures and risk factors before disease onset, which reduces important biases that are common in case-control studies. This and other strengths of prospective cohort studies make them invaluable for understanding gene-environment interactions in complex human disease. C1 NHGRI, Bethesda, MD 20892 USA. NHGRI, Inherited Dis Res Branch, Baltimore, MD 21224 USA. RP Manolio, TA (reprint author), NHGRI, 31 Ctr Dr,Room 4B-09, Bethesda, MD 20892 USA. EM manolio@nih.gov NR 58 TC 178 Z9 192 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD OCT PY 2006 VL 7 IS 10 BP 812 EP 820 DI 10.1038/nrg1919 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 093HJ UT WOS:000241158700017 PM 16983377 ER PT J AU Meyer-Lindenberg, A Weinberger, DR AF Meyer-Lindenberg, Andreas Weinberger, Daniel R. TI Intermediate phenotypes and genetic mechanisms of psychiatric disorders SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID CATECHOL-O-METHYLTRANSFERASE; DORSOLATERAL PREFRONTAL CORTEX; MEDIAL TEMPORAL-LOBE; LONG-TERM-MEMORY; SEROTONIN TRANSPORTER; HUMAN BRAIN; FUNCTIONAL POLYMORPHISM; HIPPOCAMPAL-FORMATION; AMYGDALA INTERACTIONS; COMPLEX DISEASES AB Genes are major contributors to many psychiatric diseases, but their mechanisms of action have long seemed elusive. The intermediate phenotype concept represents a strategy for characterizing the neural systems affected by risk gene variants to elucidate quantitative, mechanistic aspects of brain function implicated in psychiatric disease. Using imaging genetics as an example, we illustrate recent advances, challenges and implications of linking genes to structural and functional variation in brain systems related to cognition and emotion. C1 NIMH, Unit Syst Neurosci Psychiat, Clin Brain Disorders Branch, Gene Cognit & Psychosis Program,NIH,Dept Hlth & H, Bethesda, MD 20892 USA. RP Meyer-Lindenberg, A (reprint author), NIMH, Unit Syst Neurosci Psychiat, Clin Brain Disorders Branch, Gene Cognit & Psychosis Program,NIH,Dept Hlth & H, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM andreasml@nih.gov; weinberd@mail.nih.gov RI Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 FU Intramural NIH HHS NR 94 TC 645 Z9 667 U1 4 U2 65 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 OCT PY 2006 VL 7 IS 10 BP 818 EP 827 DI 10.1038/nrn1993 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 093TH UT WOS:000241191800014 PM 16988657 ER PT J AU Nakahara, H Nakamura, K Hikosaka, O AF Nakahara, Hiroyuki Nakamura, Kae Hikosaka, Okihide TI Extended LATER model can account for trial-by-trial variability of both pre- and post-processes SO NEURAL NETWORKS LA English DT Review DE saccadic eye movement; caudate nucleus; reward; rise-to-threshold model; motivation; decision making ID SACCADIC EYE-MOVEMENTS; PRIMATE ORBITOFRONTAL CORTEX; MONKEY CAUDATE NEURONS; NIGRA PARS RETICULATA; PREDICTABLE ENVIRONMENTAL EVENTS; PERCEPTUAL DECISION-MAKING; SUPPLEMENTARY MOTOR AREA; SUPERIOR COLLICULUS; REACTION-TIME; RHESUS-MONKEYS AB We present a new decision-making model that can account for trial-by-trial variability induced by a process ("pre-process") that occurs before an explicit sensory signal specifying a later motor response. A process after explicit sensory signals, referred to herein as the "post-process", has been investigated by a variety of so-called rise-to-threshold models including the LATER model. The LATER model formulates post-process variability but treats the pre-process as fixed within a block of an experiment. We propose an extension of the LATER model, which we call the extended LATER (ELATER) model, to account for trial-by-trial variability of both pre- and post-processes together. We present the mathematical formulation of the ELATER model and analyze its characteristics, including numerical examples and an example of saccade latency data in reward-manipulated conditions with caudate activity. The ELATER model is useful for investigating decision making by taking account of trial-by-trial variability of both pre- and post-processes. (c) 2006 Elsevier Ltd. All rights reserved. C1 RIKEN, Brain Sci Inst, Lab Integrated Theoret Neurosci, Wako, Saitama 3510198, Japan. RIKEN, Brain Sci Inst, Lab Math Neurosci, Wako, Saitama 3510198, Japan. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Nakahara, H (reprint author), RIKEN, Brain Sci Inst, Lab Integrated Theoret Neurosci, 2-1 Hirosawa, Wako, Saitama 3510198, Japan. EM hn@brain.riken.jp; kae@lsr.nei.nih.gov; oh@lsr.nei.nih.gov RI Nakahara, Hiroyuki/N-5411-2015 OI Nakahara, Hiroyuki/0000-0001-6891-1175 NR 112 TC 29 Z9 31 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0893-6080 J9 NEURAL NETWORKS JI Neural Netw. PD OCT PY 2006 VL 19 IS 8 BP 1027 EP 1046 DI 10.1016/j.neunet.2006.07.001 PG 20 WC Computer Science, Artificial Intelligence; Neurosciences SC Computer Science; Neurosciences & Neurology GA 101RU UT WOS:000241758900004 PM 16971090 ER PT J AU Synowitz, M Glass, R Farber, K Kronenberg, G Schnerman, J Kettenmann, H AF Synowitz, M. Glass, R. Farber, K. Kronenberg, G. Schnerman, J. Kettenmann, H. TI A1 adenosine receptor deficiency in the host brain promotes the growth of inoculated glioblastoma cells SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Dept Neurosurg, Berlin, Germany. MDC Berlin Buch, Berlin, Germany. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 315 EP 315 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877300086 ER PT J AU Bassiri, D Luther, N Dunkel, IJ Edgar, MA Cheung, NK Wang, QC Pastan, I Gutin, PH Souweidane, MM AF Bassiri, D. Luther, N. Dunkel, I. J. Edgar, M. A. Cheung, N. K. Wang, Q. C. Pastan, I. Gutin, P. H. Souweidane, M. M. TI Successful treatment of a human glioma xenograft using the immunotoxin 8H9scFv-PE38 by interstitial infusion SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Cornell Univ, Weill Med Coll, New York, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 425 EP 425 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301134 ER PT J AU Nakada, M Drake, KL Demuth, T Reavie, LB Nakada, S Zenklusen, JC Fine, HA Mikkelsen, T Berens, ME AF Nakada, Mitsutoshi Drake, Kelsey L. Demuth, Tim Reavie, Linsey B. Nakada, Satoko Zenklusen, Jean-Claude Fine, Howard A. Mikkelsen, Tom Berens, Michael E. TI Ephrin-B2 ligand tyrosine kinase promotes glioma invasion and predicts survival SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Translat Genom Res Inst, Phoenix, AZ USA. NCI, Bethesda, MD 20892 USA. Henry Ford Hosp, Detroit, MI 48202 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 435 EP 435 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301170 ER PT J AU Reavie, LB Demuth, T Hoelzinger, DB Rennert, JL Bristol, R Nakada, S Zenklusen, JC Fine, HA Mikkelsen, T Berens, ME AF Reavie, L. B. Demuth, T. Hoelzinger, D. B. Rennert, J. L. Bristol, R. Nakada, S. Zenklusen, J. C. Fine, H. A. Mikkelsen, T. Berens, M. E. TI Glioma invadomics - Identification and validation of novel targets for glioma invasion in vivo SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Translat Genom Res Inst, Phoenix, AZ USA. NCI, Bethesda, MD 20892 USA. Henry Ford Hosp, Detroit, MI 48202 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 435 EP 436 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301173 ER PT J AU Wen, PY Yung, WKA Lamborn, K Cloughesy, T DeAngelis, LM Fine, HA Chang, SM Robins, HI Fink, K Abrey, LE Lassman, AB Mehta, M Kesari, S Kim, L Stiles, C Egorin, M Kaplan, R Murgo, A Prados, MD AF Wen, P. Y. Yung, W. K. A. Lamborn, K. Cloughesy, T. DeAngelis, L. M. Fine, H. A. Chang, S. M. Robins, H. I. Fink, K. Abrey, L. E. Lassman, A. B. Mehta, M. Kesari, S. Kim, L. Stiles, C. Egorin, M. Kaplan, R. Murgo, A. Prados, M. D. TI Phase II study of imatinib mesylate (ST1571) for patients with recurrent meningiomas (NABTC 01-08) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 N Amer Brain Tumor Consortium, Boston, MA USA. Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. Univ Pittsburgh, Pittsburgh, PA USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RI Kesari, Santosh/E-8461-2013; Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 0 TC 6 Z9 6 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 454 EP 454 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301243 ER PT J AU Wen, PY Chang, SM Kuhn, J Lamborn, K Robins, HI Cloughesy, T Gilbert, MR Yung, WKA Mehta, M DeAngelis, LM Abrey, LE Kesari, S Drappatz, J Lassman, AB Dancey, J Prados, MD AF Wen, P. Y. Chang, S. M. Kuhn, J. Lamborn, K. Robins, H. I. Cloughesy, T. Gilbert, M. R. Yung, W. K. A. Mehta, M. DeAngelis, L. M. Abrey, L. E. Kesari, S. Drappatz, J. Lassman, A. B. Dancey, J. Prados, M. D. TI Phase I study of erlotinib (tarceva) and temsirolimus (CCI-779) for patients with recurrent malignant gliomas (NABTC 04-02) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 N Amer Brain Tumor Consortium, Bethesda, MD USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RI Kesari, Santosh/E-8461-2013; Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 0 TC 6 Z9 6 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 454 EP 454 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301242 ER PT J AU Hunt, MA Muldoon, LL Palmieri, D Steeg, PS Neuwelt, EA AF Hunt, M. A. Muldoon, L. L. Palmieri, D. Steeg, P. S. Neuwelt, E. A. TI HER-2 status influences survival in a rat model of brain metastasis from breast cancer SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Natl Canc Inst, Ctr Canc Res, Womens Canc Sect, Mol Pharmacol Lab, Bethesda, MD USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 97201 USA. RI Palmieri, Diane/B-4258-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 472 EP 472 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301311 ER PT J AU Victorson, D Royce, C Draper, D Haggarty, I Garren, N Kim, L Beaumont, JL Cella, D Liepa, AM Thornton, DE Fine, HA AF Victorson, David Royce, Cheryl Draper, David Haggarty, Irene Garren, Nancy Kim, Lyndon Beaumont, Jennifer L. Cella, David Liepa, Astra M. Thornton, Donald E. Fine, Howard A. TI Health-related quality of life in patients with recurrent high-grade gliomas treated with enzastaurin SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Evanston NW Healthcare, Ctr Outcomes Res & Educ, Evanston, IL USA. NIH, Natl Inst Neurol Disorders & Stroke, Natl Canc Inst, Neuro Oncol Branch, Bethesda, MD USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 483 EP 483 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301352 ER PT J AU Cohen, RM Szczepanik, J McManus, M Mirza, N Putnam, K Levy, J Sunderland, T AF Cohen, Robert M. Szczepanik, Joanna McManus, Michael Mirza, Nadeem Putnam, Karen Levy, Jim Sunderland, Trey TI Hippocampal atrophy in the healthy is initially linear and independent of age SO NEUROBIOLOGY OF AGING LA English DT Article DE aging; memory; hippocampus; Alzheimer's disease; MCl ID MEDIAL TEMPORAL-LOBE; MILD COGNITIVE IMPAIRMENT; APOLIPOPROTEIN-E GENOTYPE; FAMILIAL ALZHEIMERS-DISEASE; ENTORHINAL CORTEX; MEMORY PERFORMANCE; BRAIN ATROPHY; NEURONAL LOSS; VOLUME LOSS; MRI AB Patients with minimal cognitive impairment (MCI) or Alzheimer's disease (AD) have smaller hippocampal volumes (HV) and increased rates of HV loss (rHVL). A 6-year study was conducted to assess rHVL in healthy aging subjects (HQ in which four MRI scans, each 2 years apart, were obtained on 26 HC with a mean age of 58.8 years when entering the study. rHVLs were linear and significantly differed among subjects, even those sharing an identical apoliporotein E genotype, ranging from .027 to .191 cc/year (S.D.=.022 cc/year), and were not affected by age or sex. rHVL, but not HV, at time of subject entry, was found to predict performance on the delayed recall measure of the Selective Reminder Task obtained 6 years after subject entry into study. Although the molecular events underlying rHVL are unclear, the significance of rHVL in subjects in their sixth and seventh decades of life for predicting age-related cognitive trajectories and whether changes in rHVLs foreshadow the development of MCI are the subject of ongoing study. (c) 2005 Elsevier Inc. All rights reserved. C1 NIMH, Geriatr Psychiat Branch, Clin Res Ctr 2 5362, NIH, Bethesda, MD 20892 USA. RP Cohen, RM (reprint author), Cedars Sinai Med Ctr, Thalians Bldg,Rm E101,8730 Alden Dr, Los Angeles, CA 90048 USA. EM rcn1946@mac.com NR 72 TC 9 Z9 9 U1 0 U2 1 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 OCT PY 2006 VL 27 IS 10 BP 1385 EP 1394 DI 10.1016/j.neurobiolaging.2005.07.018 PG 10 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 084MN UT WOS:000240537200003 PM 16168525 ER PT J AU Adighibe, O Arepalli, S Duckworth, J Hardy, J Wavrant-De Vrieze, F AF Adighibe, Omanma Arepalli, Sampath Duckworth, Jaime Hardy, John Wavrant-De Vrieze, Fabienne TI Genetic variability at the LXR gene (NR1H2) may contribute to the risk of Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; genetics; cholesterol; LXR gene ID APOLIPOPROTEIN-E; TOTAL CHOLESTEROL; GENOME SCREEN; CELLS; ASSOCIATION; EXPRESSION; SECRETION; FAMILIES; EFFLUX; ALLELE AB We have initiated a systematic analysis of the role of cholesterol metabolizing genes as risk factors for Alzheimer's disease pathogenesis. As part of this analysis, we have assessed the NR1H2 gene on chromosome 19 and report here a modest association with the locus in sibpairs with late onset disease. (c) 2005 Elsevier Inc. All rights reserved. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Wavrant-De Vrieze, F (reprint author), NIA, Neurogenet Lab, NIH, Porter Neurosci Bldg,35 Convent Dr, Bethesda, MD 20892 USA. EM wavrant@mail.nih.gov RI Hardy, John/C-2451-2009 FU NIA NIH HHS [U24 AG021886] NR 23 TC 20 Z9 22 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 OCT PY 2006 VL 27 IS 10 BP 1431 EP 1434 DI 10.1016/j.neurobiolaging.2005.08.010 PG 4 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 084MN UT WOS:000240537200008 PM 16207502 ER PT J AU Winterer, G Musso, F Vucurevic, G Stoeter, P Konrad, A Seker, B Gallinat, J Dahmen, N Weinberger, DR AF Winterer, Georg Musso, Francesco Vucurevic, Goran Stoeter, Peter Konrad, Andreas Seker, Berna Gallinat, Juergen Dahmen, Norbert Weinberger, Daniel R. TI COMT genotype predicts BOLD signal and noise characteristics in prefrontal circuits SO NEUROIMAGE LA English DT Article DE dopamine; COMT; prefrontal; attention; fMRI ID CATECHOL-O-METHYLTRANSFERASE; CORTICAL PYRAMIDAL NEURONS; VAL(108/158) MET GENOTYPE; DOPAMINE D1 RECEPTORS; EVENT-RELATED FMRI; WORKING-MEMORY; VAL(158)MET POLYMORPHISM; PARKINSONS-DISEASE; FUNCTIONAL POLYMORPHISM; COGNITIVE FUNCTION AB Objective: Prefrontal dopamine (DA) is catabolized by the COMT (catechol-O-methyltransferase) enzyme. Literature suggests that the Val/Met single nucleotide polymorphism (SNP) in the COMT gene predicts executive cognition in humans with Val carriers showing poorer performance due to less available synaptic DA. Recent fMRI studies are thought to agree with these studies having demonstrated prefrontal hyperactivation during n-back and attention-requiring tasks. This was interpreted as "less efficient" processing due to impaired signal-to-noise ratio (SNR) of neuronal activity. However, electrophysiological studies of neuronal SNR in primates and humans imply that prefrontal cortex should show a diminished prefrontal BOLD response in Val carriers. In the present study, we addressed the question of whether the prefrontal SNR of the BOLD response is decreased in Val carriers using a visual oddball task and an approach to analysis of fMRI data that maximizes noise characterization. Methods: We investigated N=17 homozygous Met carriers compared with N=24 Val carriers matched for age, sex, education, IQ, reaction time (variability) and head motion. Event-related fMRI was conducted presenting 160 visual stimuli (40 targets, checkerboard reversal). Subjects had to respond as quickly as possible to targets by button press. In the fMRI GLM [y(t)=beta* x(t)+c+e(t)] analysis, voxel-by-voxel 'activation' [y(t)] as well as residual noise variance [e(t)=sigma(2)] were calculated using a conservative full-width half maximum (FWHM=6 mm). Results: As compared to Val carriers, we observed a stronger and more extended BOLD responses in homozygous Met carriers in left supplementary motor area (SMA) extending to ACC and dorsolateral prefrontal cortex. Vice versa, increased levels of noise were seen in Val carriers surrounding the peak activation maximum. Discussion: In line with our expectations from prior electrophysiological studies, we observed a diminished BOLD response and increased noise in Val carriers. This suggests that the DA stabilizes cortical microcircuits by sharpening the signal and suppressing surrounding noise. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Dusseldorf, Dept Psychiat, D-40629 Dusseldorf, Germany. Univ Mainz, Inst Neuroradiol, D-6500 Mainz, Germany. Univ Mainz, Dept Psychiat, D-6500 Mainz, Germany. Charite Berlin, Berlin, Germany. NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. RP Winterer, G (reprint author), Univ Dusseldorf, Dept Psychiat, Bergische Landstr 2, D-40629 Dusseldorf, Germany. EM georg.winterer@uni-duesseldorf.de NR 80 TC 70 Z9 71 U1 3 U2 3 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 OCT 1 PY 2006 VL 32 IS 4 BP 1722 EP 1732 DI 10.1106/j.neuroimage.2006.05.058 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 090RR UT WOS:000240969200018 PM 16884927 ER PT J AU Volkow, ND Wang, GJ Ma, YM Fowler, JS Wong, C Jayne, M Telang, F Swanson, JM AF Volkow, Nora D. Wang, Gene-Jack Ma, Yeming Fowler, Joanna S. Wong, Christopher Jayne, Millard Telang, Frank Swanson, James M. TI Effects of expectation on the brain metabolic responses to methylphenidate and to its placebo in non-drug abusing subjects SO NEUROIMAGE LA English DT Article DE imaging; FDG; dopamine; reinforcement; methylphenidate; placebo; cingulate gyrus; nucleus accumbens ID ORBITOFRONTAL CORTEX; COCAINE ABUSERS; FUNCTIONAL NEUROANATOMY; DOPAMINE CONCENTRATIONS; THREO-METHYLPHENIDATE; REWARD ANTICIPATION; GLUCOSE-UTILIZATION; NEURONAL-ACTIVITY; NEURAL RESPONSES; HUMAN AMYGDALA AB The response to drugs is affected by expectation, which in turn is sensitive to prior drug experiences. Here, we evaluate the effects of expectation on the responses to intravenous methylphenidate (0.5 mg/ kg) in fifteen subjects who had minimal experience with stimulant drugs. We used positron emission tomography to measure brain glucose metabolism, which we used as a marker of brain function and tested them under four randomized conditions (1) expecting placebo and receiving placebo; (2) expecting placebo and receiving methylphenidate; (3) expecting methylphenidate and receiving methylphenidate; (4) expecting methylphenidate, and receiving placebo. We show that methylphenidate-induced decreases in striatum were greater when subjects expected to receive methylphenidate than when they were not expecting it. We also show that the subjects' expectations affected their responses to placebo. That is, when subjects expected to receive methylphenidate but received placebo there were significant increases in ventral cingulate gyros (BA 25) and nucleus accumbens (regions involved with emotional reactivity and reward). The effect was largest in subjects who, because of experimental randomization, had not experienced methylphenidate. Because subjects were told that methylphenidate could be experienced as pleasant, unpleasant or devoid of subjective effects these results suggest the involvement of the ventral cingulate and of the nucleus accumbens in processing expectation for "uncertain drug effects". Thus, the state of expectation needs to be considered as a variable modulating the reinforcing and therapeutic effects of drugs even in subjects who have no prior experience with the drug. Published by Elsevier Inc. C1 Natl Inst Drug Abuse, Bethesda, MD 20892 USA. NIAAA, Lab Neuroimaging, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. Univ Calif Irvine, Child Dev Ctr, Irvine, CA 92612 USA. RP Volkow, ND (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov FU Intramural NIH HHS NR 65 TC 55 Z9 55 U1 2 U2 8 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 OCT 1 PY 2006 VL 32 IS 4 BP 1782 EP 1792 DI 10.1016/j.neuroimage.2006.04.192 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 090RR UT WOS:000240969200023 PM 16757181 ER PT J AU Pluta, RM AF Pluta, Ryszard M. TI Dysfunction of nitric oxide synthases as a cause and therapeutic target in delayed cerebral vasospasm after SAH SO NEUROLOGICAL RESEARCH LA English DT Review DE nitric oxide; NO donors; SAH; vasospasm; PDE; ADMA; nitrite ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; INTRAVENTRICULAR SODIUM-NITROPRUSSIDE; CONTROLLED-RELEASE POLYMER; CHILDHOOD BRAIN-TUMORS; DIMETHYL-L-ARGININE; PRIMATE MODEL; BLOOD-FLOW; CEREBROSPINAL-FLUID; ENDOTHELIAL-CELLS; INTRAVENOUS NITROGLYCERIN AB Nitric oxide (NO), also known as endothelium-derived relaxing factor, is produced by endothelial nitric oxide synthase (eNOS) in the intima and by neuronal nitric oxide synthase (nNOS) in the adventitia of cerebral vessels. It dilates the arteries in response to shear stress, metabolic demands, pterygopalatine ganglion stimulation and chemoregulation. Subarachnoid hemorrhage (SAH) interrupts this regulation of cerebral blood flow. Hemoglobin, gradually released from erythrocytes in the subarachnoid space, destroys nNOS-containing neurons in the conductive arteries. This deprives the arteries of NO, leading to initiation of delayed vasospasm. But such vessel narrowing increases shear stress, which stimulates eNOS. This mechanism normally would lead to increased production of NO and dilation of arteries. However, a transient eNOS dysfunction evoked by an increase in the endogenous competitive NOS inhibitor, asymmetric dimethylarginine (ADMA), prevents this vasodilation. eNOS dysfunction has been recently shown to be evoked by increased levels of ADMA in cerebrospinal fluid (CSF) in response to the presence of bilirubin-oxidized fragments (BOXes). A direct cause of the increased ADMA CSF level is most likely decreased ADMA elimination owing to disappearance of ADMA-hydrolyzing enzyme [dimethylarginine dimethylaminohydrolase II (DDAH II)] immunoreactivity in the arteries in spasm. This eNOS dysfunction sustains vasospasm. CSF ADMA levels are closely associated with the degree and time course of vasospasm; when CSF ADMA levels decrease, vasospasm resolves. Thus, exogenous delivery of NO, inhibiting the L-arginine-methylating enzyme or stimulating DDAH II, may provide new therapeutic modalities to prevent and treat vasospasm. This paper will present results of pre-clinical studies supporting the NO-based hypothesis of delayed cerebral vasospasm development and its prevention by increased NO availability. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Pluta, RM (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Room 5D37, Bethesda, MD 20892 USA. EM rysiek@ninds.nih.gov FU Intramural NIH HHS NR 114 TC 31 Z9 36 U1 1 U2 3 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 0161-6412 J9 NEUROL RES JI Neurol. Res. PD OCT PY 2006 VL 28 IS 7 BP 730 EP 737 DI 10.1179/016164106X152052 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 102CD UT WOS:000241787500006 PM 17164036 ER PT J AU Schmidt, J Raju, R Salajegheh, M Rakocevic, G Dalakas, MC AF Schmidt, J. Raju, R. Salajegheh, M. Rakocevic, G. Dalakas, M. C. TI Specific interrelationship between inflammation and (beta-amyloid-related degeneration in sporadic inclusion body myositis (sIBM) SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 11th International Congress of the World-Muscle-Society CY OCT 04-07, 2006 CL Bruges, BELGIUM SP World Muscle Soc C1 NIH, Neuromuscular Dis Sect, Bethesda, MD 20892 USA. Univ Gottingen, Dept Neuroimmunol & Neurol, D-3400 Gottingen, Germany. RI Raju, Raghavan/E-9219-2011 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 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2006 VL 16 IS 9-10 BP 657 EP 658 DI 10.1016/j.nmd.2006.05.057 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 096HY UT WOS:000241369400054 ER PT J AU Li, J Yin, C Okamoto, H Jaffe, H Oldfield, EH Zhuang, Z Vortmeyer, AO Rushing, EJ AF Li, J. Yin, C. Okamoto, H. Jaffe, H. Oldfield, E. H. Zhuang, Z. Vortmeyer, A. O. Rushing, E. J. TI Proteomic analysis of inclusion body myositis SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 11th International Congress of the World-Muscle-Society CY OCT 04-07, 2006 CL Bruges, BELGIUM SP World Muscle Soc C1 Armed Forces Inst Pathol, Washington, DC 20306 USA. Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, Bethesda, 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 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2006 VL 16 IS 9-10 BP 658 EP 659 DI 10.1016/j.nmd.2006.05.060 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 096HY UT WOS:000241369400057 ER PT J AU Poitelon, Y Hamadouche, T De Sandre-Giovannoli, A Kozlov, S Serradj, N Tazir, M Chaouch, M Grid, D Stewart, C Jamon, M Delague, V Levy, N AF Poitelon, Y. Hamadouche, T. De Sandre-Giovannoli, A. Kozlov, S. Serradj, N. Tazir, M. Chaouch, M. Grid, D. Stewart, C. Jamon, M. Delague, V. Levy, N. TI Pathophysiological mechanisms of lamin A/C associated Charcot-Marie-Tooth disease (CMT2B1/ARCMT2) SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 11th International Congress of the World-Muscle-Society CY OCT 04-07, 2006 CL Bruges, BELGIUM SP World Muscle Soc C1 Fac Med Timone, INSERM, U491, Marseille, France. Hop Enfants La Timone, Dept Med Genet, Marseille, France. NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA. CNRS, Marseille, France. Ctr Hosp Univ Mustaphe, Algiers, Algeria. Ctr Hosp Univ Ben Aknoun, Algiers, Algeria. Genethon III, Evry, France. 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 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2006 VL 16 IS 9-10 BP 675 EP 675 DI 10.1016/j.nmd.2006.05.110 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 096HY UT WOS:000241369400107 ER PT J AU Hayashi, YK Astejada, MN Ozawa, R Fujita, M Noguchi, S Nonaka, I Stewart, CL Nishino, I AF Hayashi, Y. K. Astejada, M. N. Ozawa, R. Fujita, M. Noguchi, S. Nonaka, I. Stewart, C. L. Nishino, I. TI Three kinds of model mice for nuclear envelopathy SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 11th International Congress of the World-Muscle-Society CY OCT 04-07, 2006 CL Bruges, BELGIUM SP World Muscle Soc C1 NCNP, Natl Inst Neurosci, Tokyo, Japan. NCI, Bethesda, MD 20892 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 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2006 VL 16 IS 9-10 BP 677 EP 677 DI 10.1016/j.nmd.2006.05.116 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 096HY UT WOS:000241369400113 ER PT J AU Sarkozy, A Goldfarb, L Charlton, R Eagle, M Chinnery, PM Straub, V Bushby, K AF Sarkozy, A. Goldfarb, L. Charlton, R. Eagle, M. Chinnery, P. M. Straub, V. Bushby, K. TI Phenotypic variability associated with desmin gene mutations SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 11th International Congress of the World-Muscle-Society CY OCT 04-07, 2006 CL Bruges, BELGIUM SP World Muscle Soc C1 Int Ctr Life, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England. IRCCS, CSS Mendel Inst, Rome, Italy. NINDS, NIH, Bethesda, MD 20892 USA. Univ Newcastle Upon Tyne, Dept Neurol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. 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 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2006 VL 16 IS 9-10 BP 708 EP 708 DI 10.1016/j.nmd.2006.05.209 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 096HY UT WOS:000241369400205 ER PT J AU Caldwell, HK Stewart, J Wiedholz, LM Millstein, RA Iacangelo, A Holmes, A Young, WS Wersinger, SR AF Caldwell, Heather K. Stewart, John Wiedholz, Lisa M. Millstein, Rachel A. Iacangelo, Anna Holmes, Andrew Young, W. Scott, III Wersinger, Scott R. TI The acute intoxicating effects of ethanol are not dependent on the vasopressin 1a or 1b receptors SO NEUROPEPTIDES LA English DT Article DE vasopressin; vasopressin 1a receptor; vasopressin 1b receptor; ethanol; voluntary ethanol consumption; anxiety-like behavior; hypothermia; motor coordination; knockout mice ID CORTICOTROPIN-RELEASING FACTOR; SCOPOLAMINE-INDUCED IMPAIRMENTS; LATERAL SEPTAL VASOPRESSIN; ACUTE ALCOHOL-INTOXICATION; ANXIETY-RELATED BEHAVIOR; PITUITARY-ADRENAL AXIS; PARAVENTRICULAR NUCLEUS; ARGININE-VASOPRESSIN; V-1A RECEPTOR; V1B RECEPTOR AB Studies of the role of vasopressin (Avp) in mediating the effects of ethanol have focused on Avp's role in altering kidney function via its action through the vasopressin 2 receptor. However, alcohol consumption also has central effects that are poorly understood. There is evidence that Avp may mediate ethanol consumption as well as some of ethanol's behavioral effects. Centrally only two Avp receptor subtypes are expressed: the la receptor (Avpr1a) and the 1b receptor (Avpr1b). To determine the extent to which these receptors mediate the behavioral effects of alcohol, we used mice with targeted disruptions of either their Avpr1a or Avpr1b. gene. We examined the effects of genotype on the acute intoxicating effects of ethanol as well as on voluntary ethanol consumption. Surprisingly, our findings indicate that there is no interaction between either the Avpr1a or Avpr1b and ethanol on motor coordination, hypothermia, mood, or voluntary ethanol consumption. C1 NIMH, Sect Neural Gene Express, NIH, DHHS, Bethesda, MD 20892 USA. NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH,DHHS, Bethesda, MD 20892 USA. SUNY Buffalo, Dept Psychol, Rochester, NY 14620 USA. RP Caldwell, HK (reprint author), NIMH, Sect Neural Gene Express, NIH, DHHS, 9000 Rockville Pike,Bldg 49,Room 5A51, Bethesda, MD 20892 USA. EM heathercaldwell@mail.nih.gov RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU Intramural NIH HHS NR 84 TC 28 Z9 31 U1 0 U2 7 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD OCT PY 2006 VL 40 IS 5 BP 325 EP 337 DI 10.1016/j.npep.2006.08.001 PG 13 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 109HC UT WOS:000242297700004 PM 17049983 ER PT J AU Gardner, EL Liu, XH Paredes, W Giordano, A Spector, J Lepore, M Wu, KM Froimowitz, M AF Gardner, Eliot L. Liu, Xinhe Paredes, William Giordano, Anthony Spector, Jordan Lepore, Marino Wu, Kuo-Ming Froimowitz, Mark TI A slow-onset, long-duration indanamine monoamine reuptake inhibitor as a potential maintenance pharmacotherapy for psychostimulant abuse: Effects in laboratory rat models relating to addiction SO NEUROPHARMACOLOGY LA English DT Article DE addiction; cocaine; drug abuse; indanamine; reuptake blockade ID EXTRACELLULAR DOPAMINE LEVELS; NUCLEUS-ACCUMBENS; BRAIN-STIMULATION; SELF-STIMULATION; COCAINE-SEEKING; WITHDRAWAL; MICRODIALYSIS; REINFORCEMENT; SENSITIZATION; PERFORMANCE AB Slow-onset, long-lasting dopamine reuptake blockers with reduced abuse potential have been suggested as maintenance therapies for cocaine addiction. We have synthesized a series of 3-(3,4'-dichlorophenyl)-1-indanamine monoamine reuptake inhibitors as candidates for such maintenance pharmacotherapy. The initial lead compound, the N,N-dimethyl analogue 30,640 was then subjected to testing in addiction-relevant animal models. Compound 30,640 (2 mg/kg i.p.) produced a pronounced slow-onset, long-lasting increase (300-400%) in extracellular nucleus accumbens dopamine levels, as measured by in vivo brain microdialysis in awake laboratory rats. Slow-onset, long-lasting decreases (40-80%) in the dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid, and the serotonin metabolite 5-hydroxyindoleacetic acid were also seen. Compound 30,640 (3 or 5 mg/kg i.p.) also produced a significant (similar to 30%) slow-onset, long-lasting enhancement of electrical brain-stimulation reward, which was additive with that of cocaine (5 mg/kg i.p.). When given to cocaine-administering rats, 30,640 (2.5, 3, 5, or 10 mg/kg i.p.) significantly inhibited (30-60%) intravenous cocaine self-administration, with a pronounced long-lasting profile. In sum, 30,640 showed cocaine-like effects, but with a marked slow-onset, long-lasting profile. We conclude that the prodrug strategy employed in the design of 30,640 achieved its goal. We suggest that such compounds may be useful as maintenance pharmacotherapies for psychostimulant addiction. (c) 2006 Elsevier Ltd. All rights reserved. C1 NIDA, Neuropsychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA. SUNY Stony Brook, Stony Brook Univ Hosp, Dept Neurol, Stony Brook, NY 11794 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Pharmasci Inc, Montreal, PQ H4P 2T4, Canada. Pharm Eco Labs, Devens, MA 01432 USA. Eisai Res Inst, Andover, MA 01810 USA. Massachusetts Coll Pharm & Hlth Sci, Boston, MA 02115 USA. RP Gardner, EL (reprint author), NIDA, Neuropsychopharmacol Sect, Intramural Res Program, NIH, Bldg C,Room 393,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM egardner@intra.nida.nih.gov FU Intramural NIH HHS; NIDA NIH HHS [N01 DA-4-8313, R01 DA-15795] NR 43 TC 10 Z9 11 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 OCT PY 2006 VL 51 IS 5 BP 993 EP 1003 DI 10.1016/j.neuropharm.2006.06.009 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 104XT UT WOS:000241994600006 PM 16901516 ER PT J AU Yamashita, M Fukushima, S Shen, HW Hall, FS Uhl, GR Numachi, Y Kobayashi, H Sora, I AF Yamashita, Motoyasu Fukushima, Setsu Shen, Hao-wei Hall, F. Scott Uhl, George R. Numachi, Yohtaro Kobayashi, Hideaki Sora, Ichiro TI Norepinephrine transporter blockade can normalize the prepulse inhibition deficits found in dopamine transporter knockout mice SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE dopamine transporter; norepinephrine transporter; serotonin transporter; knockout mice; prepulse inhibition; startle ID MEDIAL PREFRONTAL CORTEX; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; ACOUSTIC STARTLE RESPONSE; IN-VIVO MICRODIALYSIS; HYPERACTIVITY DISORDER; EXTRACELLULAR DOPAMINE; ANTIDEPRESSANT DRUGS; LATENT INHIBITION; RAT; HABITUATION AB Dopamine transporter knockout (DAT KO) mice display deficits in sensorimotor gating that are manifested by reduced prepulse inhibition (PPI) of the acoustic startle reflex. Since PPI deficits may model some of the cognitive dysfunctions identified in certain neuropsychiatric patients, we have studied the effects of transporter blockers on PPI in wild-type and DAT KO mice. Treatments with High dose psychostimulants that block DAT as well as the norepinephrine (NET) and serotonin (SERT) transporters (60 mg/kg cocaine or methylphenidate) significantly impaired PPI in wild-type mice. By contrast, these treatments significantly ameliorated the PPI deficits observed in untreated DAT KO mice. In studies with more selective transport inhibitors, the selective NET inhibitor nisoxetine ( 10 or 30 mg/kg) also significantly reversed PPI deficits in DAT KO mice. By contrast, while the SERT inhibitor fluoxetine (30 mg/kg) normalized these PPI deficits in DAT KO mice, citalopram (30 or 100 mg/kg) failed to do so. The 'paradoxical' effects of cocaine and methylphenidate in DAT KO mice are thus likely to be mediated, at least in part by the ability of these drugs to block NET, although serotonin systems may also have some role. Together with recent microdialysis data, these results support the hypothesis that prefrontal cortical NET blockade and consequent enhancement of prefrontal cortical extracellular dopamine mediates the reversal of PPI deficits in DAT KO mice. C1 Tohoku Univ, Dept Psychobiol, Grad Sch Med, Sendai, Miyagi 9808574, Japan. Tokyo Inst Psychiat, Dept Mol Psychiat, Tokyo, Japan. Natl Inst Drug Abuse, Mol Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD USA. RP Sora, I (reprint author), Tohoku Univ, Dept Psychobiol, Grad Sch Med, 1-1 Seiryomachi, Sendai, Miyagi 9808574, Japan. EM isora@mail.tains.tohoku.ac.jp RI Kobayashi, Hideaki/C-8617-2009; Hall, Frank/C-3036-2013; OI Kobayashi, Hideaki/0000-0003-3599-0465; Hall, Frank/0000-0002-0822-4063; Shen, Hao-wei/0000-0002-2766-5139 NR 44 TC 44 Z9 45 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 2006 VL 31 IS 10 BP 2132 EP 2139 DI 10.1038/sj.npp.1301009 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 090HX UT WOS:000240942900004 PM 16407898 ER PT J AU Karcz-Kubicha, M Ferre, S Diaz-Ruiz, O Quiroz-Molina, C Goldberg, SR Hope, BT Morales, M AF Karcz-Kubicha, Marzena Ferre, Sergi Diaz-Ruiz, Oscar Quiroz-Molina, Cesar Goldberg, Steven R. Hope, Bruce T. Morales, Marisela TI Stimulation of adenosine receptors selectively activates gene expression in striatal enkephalinergic neurons SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE adenosine A(1) receptor; adenosine A(2A) receptor; c-Fos; enkephalin; dynorphin; striatum ID MESSENGER-RNA EXPRESSION; DOPAMINE-RECEPTOR; C-FOS; ADENYLYL-CYCLASE; A(2A) RECEPTORS; RAT STRIATUM; GABAERGIC NEURONS; NERVOUS-SYSTEM; A(1) RECEPTORS; MODULATION AB In the striatum, adenosine A(2A) and dopamine D-2 receptors exert reciprocal antagonistic interactions that modulate the function of GABAergic enkephalinergic neurons. We have previously shown that stimulation of adenosine A(1) receptors allows the stimulation of A(2A) receptors to overcome a tonic inhibitory effect of D-2 receptors and induce striatal expression of c-fos. In the present work, by studying co-localization of c-Fos immunoreactivity and preproenkephalin and preprodynorphin transcripts, we show that co-administration of the A(1) receptor agonist CPA and the A(2A) receptor agonist CGS 21680 increases the striatal expression of c-fos in GABAergic enkephalinergic but not in GABAergic dynorphinergic neurons. Co-administration of CPA and CGS 21680 also induced a significant increase in the striatal expression of preproenkephalin. The results underscore the role of adenosine in the activation of gene expression in the GABAergic enkephalinergic neuron. C1 Natl Inst Drug Abuse, Preclin Pharmacol Sect, IRP, NIH,DHHS,Behav Neurosci Branch, Baltimore, MD 21224 USA. Natl Inst Drug Abuse, Cellular Neurobiol Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP Ferre, S (reprint author), Natl Inst Drug Abuse, Preclin Pharmacol Sect, IRP, NIH,DHHS,Behav Neurosci Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sferre@intra.nida.nih.gov RI Diaz-Ruiz, Oscar/F-3162-2010; Hope, Bruce/A-9223-2010; Ferre, Sergi/K-6115-2014 OI Hope, Bruce/0000-0001-5804-7061; Ferre, Sergi/0000-0002-1747-1779 FU Intramural NIH HHS NR 41 TC 15 Z9 15 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 2006 VL 31 IS 10 BP 2173 EP 2179 DI 10.1038/sj.npp.1301035 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 090HX UT WOS:000240942900008 PM 16452987 ER PT J AU Ghitza, UE Gray, SM Epstein, DH Rice, KC Shaham, Y AF Ghitza, Udi E. Gray, Sarah M. Epstein, David H. Rice, Kenner C. Shaham, Yavin TI The anxiogenic drug yohimbine reinstates palatable food seeking in a rat relapse model: a role of CRF1 receptors SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE corticotropin; releasing factor; extinction; noradrenaline; palatable food; relapse; reinstatement; stress ID CORTICOTROPIN-RELEASING-FACTOR; STRESS-INDUCED REINSTATEMENT; SOCIAL-INTERACTION TEST; ANXIETY-LIKE BEHAVIOR; COCAINE-SEEKING; STRIA TERMINALIS; BED NUCLEUS; LOCUS-COERULEUS; ALCOHOL-SEEKING; NORADRENERGIC MECHANISMS AB The major problem in treating excessive eating is high rates of relapse to maladaptive eating habits during diet treatments; this relapse is often induced by stress or anxiety states. Preclinical studies have not explored this clinical problem. Here, we adapted a reinstatement model ( commonly used to study relapse to abused drugs) to examine the role of stress and anxiety in relapse to palatable food seeking during dieting. Rats were placed on restricted diet (75-80% of daily standard food) and for 12 intermittent training days (9 h/day, every other day) lever-pressed for palatable food pellets (25% fat, 48% carbohydrate) under a fixed ratio 1 (20-s timeout) reinforcement schedule. Subsequently, the rats were given 10 daily extinction sessions during which lever presses were not reinforced, and were then injected with yohimbine (an alpha-2 adrenoceptor antagonist that induces stress and anxiety in humans and non-humans) or given a single food pellet to assess reinstatement of food seeking. The rats rapidly learned to lever press for the palatable pellets and across the training days the ratio of timeout nonreinforced lever presses to reinforced lever presses progressively increased more than three-fold, suggesting the development of compulsive eating behavior. After extinction, yohimbine injections and pellet priming reliably reinstated food seeking. The corticotropin-releasing factor(1) (CRF1) receptor antagonist antalarmin attenuated the reinstatement induced by yohimbine, but not pellet priming. Antalarmin also reversed yohimbine's anxiogenic effects in the social interaction test. These data suggest that CRF is involved in stress-induced relapse to palatable food seeking, and that CRF1 antagonists should be considered for the treatment of maladaptive eating habits. C1 NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. NIDA, Clin Pharmacol & Therapeut Res Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. NIDDK, Med Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM yshaham@intra.nida.nih.gov RI shaham, yavin/G-1306-2014 FU Intramural NIH HHS; NIDA NIH HHS [Z01 DA000434-06] NR 80 TC 99 Z9 100 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 2006 VL 31 IS 10 BP 2188 EP 2196 DI 10.1038/sj.npp.1300964 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 090HX UT WOS:000240942900010 PM 16341025 ER PT J AU Bossert, JM Gray, SM Lu, L Shaham, Y AF Bossert, Jennifer M. Gray, Sarah M. Lu, Lin Shaham, Yavin TI Activation of group II metabotropic glutamate receptors in the nucleus accumbens shell attenuates context-induced relapse to heroin seeking SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE drug environment; extinction; nucleus accumbens core; opiate self-administration; reinstatement; relapse ID VENTRAL TEGMENTAL AREA; CONDITIONED PLACE PREFERENCE; CENTRAL-NERVOUS-SYSTEM; STRESS-INDUCED RELAPSE; CUE-INDUCED REINSTATEMENT; COCAINE-SEEKING; DRUG-SEEKING; BASOLATERAL AMYGDALA; PREFRONTAL CORTEX; AGONIST LY379268 AB Using a rat relapse model, we previously reported that re-exposing rats to a drug-associated context, following extinction of operant responding in a different context, reinstates heroin seeking. In an initial pharmacological characterization, we found that the mGluR(2/3) agonist LY379268, which acts centrally to reduce evoked glutamate release, attenuates context-induced reinstatement of heroin seeking when injected systemically or into the ventral tegmental area, the cell body region of the mesolimbic dopamine system. Here, we tested whether injections of LY379268 into the nucleus accumbens (NAc), a terminal region of the mesolimbic dopamine system, would also attenuate context-induced reinstatement of heroin seeking. Rats were trained to self-administer heroin; drug infusions were paired with a discrete tone-light cue. Subsequently, lever pressing was extinguished in the presence of the discrete cue in a context that differed from the drug self-administration context in terms of visual, auditory, tactile, and circadian cues. After extinction of responding, LY379268 was injected to different groups of rats into the NAc core or shell or into the caudate-putamen, a terminal region of the nigrastriatal dopamine system. Injections of LY379268 into the NAc shell (0.3 or 1.0 mu g) dose-dependently attenuated context-induced reinstatement of heroin seeking. Injections of 1.0 mg of LY379268 into the NAc core had no effect, while a higher dose (3.0 mu g) decreased this reinstatement. Injections of LY379268 (3.0 mu g) 1.5mm dorsal from the NAc core into the caudate-putamen were ineffective. Results suggest an important role of glutamate transmission in the NAc shell in context-induced reinstatement of heroin seeking. C1 NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP Bossert, JM (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jbossert@intra.nida.nih.gov RI shaham, yavin/G-1306-2014 FU Intramural NIH HHS; NIDA NIH HHS [Z01 DA000434-06] NR 107 TC 123 Z9 129 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 2006 VL 31 IS 10 BP 2197 EP 2209 DI 10.1038/sj.npp.1300977 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 090HX UT WOS:000240942900011 PM 16341024 ER PT J AU Ebmeier, K Rose, E Steele, D AF Ebmeier, Klaus Rose, Emma Steele, Douglas TI Cognitive impairment and fMRI in major depression SO NEUROTOXICITY RESEARCH LA English DT Article; Proceedings Paper CT Meeting of the Fundacion-Cerebro-and-Mente CY 2005 CL SPAIN SP Fund Cerebro Mente DE functional magnetic resonance imaging; depression; working memory; SSRI ID EVENT-RELATED FMRI; N-BACK TASK; UNIPOLAR DEPRESSION; PREFRONTAL CORTEX; MOOD DISORDERS; WORKING-MEMORY; VERBAL MEMORY; REWARD; PERFORMANCE; ACTIVATION AB Cognitive impairment in depression may be one of the more practically important aspects of the illness, responsible for much of its morbidity. It also is at the heart of its psychopathology, may contribute to strategies of treatment, and may give us a more easily quantifiable measure of impaired function to correlate with brain activity. Functional magnetic resonance imaging (fMRI) is ideally suited to examine brain function in depression. It has the correct time window to repeatedly sample cognitive task performance; it does not require exposure to radioactive tracers and can therefore be repeated many times; it also can be linked with high resolution structural images acquired in the same imaging session that help identify the regions of activation and support the spatial transformation necessary to compare the scans of different subjects. fMRI has already produced a series of consistent results in depression, identifying increased activity of rostral anterior cingulate and other medial prefrontal structures during effortful tasks and on occasion also increased dorsolateral prefrontal activity, suggesting increased possibly compensatory activity to maintain task performance. Investigating the interplay between limbic (orbitomedial) and 'cognitive' dorsolateral structures clearly has the potential to clarify important illness mechanisms of depressive illness. C1 Univ Edinburgh, Sch Mol & Clin Med, Div Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland. Univ Aberdeen, Dept Mental Hlth, Aberdeen AB9 1FX, Scotland. NIDA, Baltimore, MD USA. RP Ebmeier, K (reprint author), Univ Edinburgh, Sch Mol & Clin Med, Div Psychiat, Kennedy Tower, Edinburgh EH10 5HF, Midlothian, Scotland. EM k.ebmeier@ed.ac.uk RI Rose, Emma/A-9960-2010; OI Rose, Emma/0000-0001-5365-4794; Ebmeier, Klaus/0000-0002-5190-7038 NR 46 TC 21 Z9 25 U1 3 U2 16 PU F P GRAHAM PUBLISHING CO PI MOUNTAIN HOME PA PO BOX 370, MOUNTAIN HOME, TN 37684 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PD OCT PY 2006 VL 10 IS 2 BP 87 EP 92 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 104XM UT WOS:000241993900002 PM 17062370 ER PT J AU Simpson, NR Souza, F Witkowski, P Maffei, A Raffo, A Herron, A Kilbourn, M Jurewicz, A Herold, K Liu, E Hardy, MA Van Heertum, R Harris, PE AF Simpson, Norman Ray Souza, Fabiola Witkowski, Piotr Maffei, Antonella Raffo, Anthony Herron, Alan Kilbourn, Michael Jurewicz, Agata Herold, Kevan Liu, Eric Hardy, Mark Adam Van Heertum, Ronald Harris, Paul Emerson TI Visualizing pancreatic-cell mass with [C-11]DTBZ SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE diabetes; VMAT2; [C-11]DTBZ ID VESICULAR MONOAMINE TRANSPORTER; BOVINE CHROMAFFIN GRANULES; DIABETIC RATS; BETA-CELLS; ENDOCRINE PANCREAS; SEX-DIFFERENCES; BLOOD-GLUCOSE; REAL-TIME; ISLETS; EXPRESSION AB beta-Cell mass (BCM) influences the total amount of insulin secreted, varies by individual and by the degree of insulin resistance, and is affected by physiologic and pathologic conditions. The islets of Langerhans, however, appear to have a reserve capacity of insulin secretion and, overall, assessments of insulin and blood glucose levels remain poor measures of BCM, beta-cell function and progression of diabetes. Thus, novel noninvasive determinations of BCM are needed to provide a quantitative endpoint for novel therapies of diabetes, islet regeneration and transplantation. Built on previous gene expression studies, we tested the hypothesis that the targeting of vesicular monoamine transporter 2 (VMAT2), which is expressed by beta cells, with [C-11]dihydrotetrabenazine ([C-11]DTBZ), a radioligand specific for VMAT2, and the use of positron emission tomography (PET) can provide a measure of BCM. In this report, we demonstrate decreased radioligand uptake within the pancreas of Lewis rats with streptozotocin-induced diabetes relative to their euglycemic historical controls. These studies suggest that quantitation of VMAT2 expression in cells with the use of [C-11]DTBZ and PET represents a method for noninvasive longitudinal estimates of changes in BCM that may be useful in the study and treatment of diabetes. (c) 2006 Elsevier Inc. All rights reserved. C1 Columbia Univ, Sch Med, Dept Radiol, New York, NY 10032 USA. Columbia Univ, Sch Med, Dept Med, New York, NY 10032 USA. Columbia Univ, Sch Med, Dept Surg, New York, NY 10032 USA. CNR, Inst Genet & Biophys Adriano Buzzati Traverso, I-80131 Naples, Italy. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Ctr Comparat Med, Houston, TX 77030 USA. Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. NIDDK, Diabet Branch, NIH, Bethesda, MD 20854 USA. RP Harris, PE (reprint author), Coll Phys & Surg, Dept Med, BB 20-06, New York, NY 10032 USA. EM peh1@columbia.edu RI Maffei, Antonella/C-1181-2015 OI Maffei, Antonella/0000-0001-5637-6523 FU NCRR NIH HHS [U42 RR016629, 1 U42 RR016629-04]; NIDDK NIH HHS [2 R01 DK63567-03, P30 DK063608, 5 P30 DK063608-02, R01 DK063567, R01 DK077493] NR 61 TC 89 Z9 93 U1 0 U2 3 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 OCT PY 2006 VL 33 IS 7 BP 855 EP 864 DI 10.1016/j.nucmedbio.2006.07.002 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 098NR UT WOS:000241530100005 PM 17045165 ER PT J AU Zhong, XJ Garg, P Stith, CM McElhinny, SAN Kissling, GE Burgers, PMJ Kunkel, TA AF Zhong, Xuejun Garg, Parie Stith, Carrie M. McElhinny, Stephanie A. Nick Kissling, Grace E. Burgers, Peter M. J. Kunkel, Thomas A. TI The fidelity of DNA synthesis by yeast DNA polymerase zeta alone and with accessory proteins SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; DOUBLE-STRAND-BREAK; DEPENDENT TRANSLESION SYNTHESIS; THYMINE DIMER BYPASS; SACCHAROMYCES-CEREVISIAE; REV1 PROTEIN; FRAMESHIFT MUTATIONS; INDUCED MUTAGENESIS; ACTIVE-SITE; POL-ETA AB DNA polymerase zeta (pol zeta) participates in several DNA transactions in eukaryotic cells that increase spontaneous and damage-induced mutagenesis. To better understand this central role in mutagenesis in vivo, here we report the fidelity of DNA synthesis in vitro by yeast pol zeta alone and with RFC, PCNA and RPA. Overall, the accessory proteins have little effect on the fidelity of pol zeta. Pol zeta is relatively accurate for single base insertion/deletion errors. However, the average base substitution fidelity of pol zeta is substantially lower than that of homologous B family pols alpha, delta and epsilon. Pol zeta is particularly error prone for substitutions in specific sequence contexts and generates multiple single base errors clustered in short patches at a rate that is unprecedented in comparison with other polymerases. The unique error specificity of pol zeta in vitro is consistent with Pol zeta-dependent mutagenic specificity reported in vivo. This fact, combined with the high rate of single base substitution errors and complex mutations observed here, indicates that pol zeta contributes to mutagenesis in vivo not only by extending mismatches made by other polymerases, but also by directly generating its own mismatches and then extending them. C1 Natl Inst Enviorm Hlth Sci, Mol Genet Lab, DHHS, NIH, Res Triangle Pk, NC 27709 USA. Natl Inst Enviorm Hlth Sci, Struct Biol Lab, DHHS, NIH, Res Triangle Pk, NC 27709 USA. Natl Inst Enviorm Hlth Sci, Biostat Branch, DHHS, NIH, Res Triangle Pk, NC 27709 USA. Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. RP Kunkel, TA (reprint author), Bldg 101,Room E342B,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov FU Intramural NIH HHS; NIGMS NIH HHS [GM3243, R01 GM032431] NR 68 TC 74 Z9 74 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT PY 2006 VL 34 IS 17 BP 4731 EP 4742 DI 10.1093/nar/gkl465 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 097DR UT WOS:000241427300014 PM 16971464 ER PT J AU Marchand, C Krajewski, K Lee, HF Antony, S Johnson, AA Amin, R Roller, P Kvaratskhelia, M Pommier, Y AF Marchand, Christophe Krajewski, Krzysztof Lee, Hsiu-Fang Antony, Smitha Johnson, Allison A. Amin, Ronak Roller, Peter P. Kvaratskhelia, Mamuka Pommier, Yves TI Covalent binding of the natural antimicrobial peptide indolicidin to DNA abasic sites SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; REPLICATION-PROTEIN-A; TOPOISOMERASE-I; MASS-SPECTROMETRY; PWWP DOMAIN; INTEGRASE; IDENTIFICATION; INHIBITORS; MECHANISM; VIRUS AB Indolicidin is a host defense tridecapeptide that inhibits the catalytic activity of HIV-1 integrase in vitro. Here we have elucidated its mechanism of integrase inhibition. Using crosslinking and mass spectrometric footprinting approaches, we found that indolicidin interferes with formation of the catalytic integrase-DNA complex by directly binding DNA. Further characterization revealed that the peptide forms covalent links with abasic sites. Indolicidin crosslinks single- or double-stranded DNAs and various positions of the viral cDNA with comparable efficiency. Using truncated and chemically modified peptides, we show that abasic site crosslinking is independent of the PWWP motif but involves the indolicidin unique lysine residue and the N- and C- terminal NH2 groups. Because indolicidin can also inhibit topoisomerase I, we believe that multiple actions at the level of DNA might be a common property of antimicrobial peptides. C1 NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Canc Res Ctr, Frederick, MD 21702 USA. Ohio State Univ, Coll Pharm, Ctr Retrovirus Res, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Hlth Sci Ctr, Columbus, OH 43210 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Marchand, Christophe/D-8559-2016 FU Intramural NIH HHS; NIAID NIH HHS [R01 AI062520] NR 34 TC 48 Z9 51 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT PY 2006 VL 34 IS 18 BP 5157 EP 5165 DI 10.1093/nar/gkl667 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 104JQ UT WOS:000241955100023 PM 16998183 ER PT J AU Huang, TTK Goran, MI Spruijt-Metz, D AF Huang, Terry T. -K. Goran, Michael I. Spruijt-Metz, Donna TI Associations of adiposity with measured and self-reported academic performance in early adolescence SO OBESITY LA English DT Article DE overweight; adiposity; physical activity; school performance; academic performance ID BODY-MASS INDEX; PHYSICAL-ACTIVITY; OBESITY; CHILDREN; OVERWEIGHT; SCHOOL; ACHIEVEMENT; PREVALENCE; FITNESS; GROWTH AB Objective: To examine the associations of adiposity with measured and self-reported academic performance independently of demographics and physical activity among U.S. adolescents. Research Methods and Procedures: We surveyed 666 students 11 to 14 years old from seven middle schools in Los Angeles, CA. Weight and height were measured. Actual grade point average was obtained from school records. Self-reported school grades and physical activity time were measured by questionnaire. Adiposity measures included BMI, BMI percentile (>= 85th percentile defined as at-riskof-overweight), and percentage body fat (bioimpedance). Results: After adjusting for gender, ethnicity, age, and physical activity time, overweight at-risk status, BMI, and percentage body fat were negatively related to only Selfreported (p < 0.01) but not measured, grades. Level of moderate-to-vigorous physical activity time was negatively related to measured and self-reported grades, independently of adiposity (p < 0.01). Discussion: To our knowledge, this is the first study to examine both body mass and body fat in relation to measured and self-reported school grades. Adiposity did not relate to actual academic performance in a sample of predominantly Latino and Asian-American adolescents. The use of measured vs. self-reported academic outcomes may represent different constructs and influence study conclusions. Cultural factors may also play a role in our findings, but this requires further study. C1 NICHHD, Endocrinol Nutr & Growth Branch, NIH, Bethesda, MD 20892 USA. Univ So Calif, Dept Prevent Med, Inst Hlth Promot & Dis Prevent Res, Keck Sch Med, Los Angeles, CA 90089 USA. RP Huang, TTK (reprint author), NICHHD, Endocrinol Nutr & Growth Branch, 6100 Execut Blvd,4B11, Rockville, MD 20852 USA. EM huangter@mail.nih.gov FU NIDDK NIH HHS [1-K01DK59293-01] NR 29 TC 27 Z9 27 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD OCT PY 2006 VL 14 IS 10 BP 1839 EP 1845 DI 10.1038/oby.2006.212 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 212OE UT WOS:000249605900021 PM 17062815 ER PT J AU Borello-France, D Burgio, KL Richter, HE Zyczynski, H FitzGerald, MP Kitehead, W Fine, P Nygaard, I Handa, VL Visco, AG Weber, AM Brown, MB AF Borello-France, Diane Burgio, Kathryn L. Richter, Holly E. Zyczynski, Halina FitzGerald, Mary Pat Kitehead, William Fine, Paul Nygaard, Ingrid Handa, Victoria L. Visco, Anthony G. Weber, Anne M. Brown, Morton B. CA Pelvic Floor Disorders Network TI Fecal and urinary incontinence in primiparous women SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID ANAL-SPHINCTER RUPTURE; VAGINAL DELIVERY; POSTPARTUM URINARY; CESAREAN DELIVERY; PREVALENCE; RISK; SYMPTOMS; DISRUPTION; INCREASE; DAMAGE AB OBJECTIVE: To prospectively investigate the relationship between anal sphincter tears and postpartum fecal and urinary incontinence. METHODS: The Childbirth and Pelvic Symptoms study was a prospective cohort study performed by the Pelvic Floor Disorders Network to estimate the prevalence of postpartum fecal and urinary incontinence in primiparous women: 407 with clinically recognized anal sphincter tears during vaginal delivery, 390 without recognized sphincter tears (vaginal controls), and 124 delivered by cesarean before labor. Women were recruited postpartum while hospitalized and interviewed by telephone 6 weeks and 6 months postpartum. We assessed fecal and urinary incontinence symptoms using the Fecal Incontinence Severity Index and the Medical, Epidemiological, and Social Aspects of Aging Questionnaire, respectively. Odds ratios were adjusted for age, race, and clinical site. RESULTS: Compared with the vaginal control group, women in the sphincter tear cohort reported more fecal incontinence (6 weeks, 26.6% versus 11.2%; adjusted odds ratio [AOR] 2.8, 95% confidence interval [CI] 1.84.3; 6 months, 17.0% versus 8.2%; AOR 1.9, 95% CI 1.2-3.2), more fecal urgency and flatal incontinence, and greater fecal incontinence severity at both times. Urinary incontinence prevalence did not differ between the sphincter tear and vaginal control groups. Six months postpartum, 22.9% of women delivered by cesarean reported urinary incontinence, whereas 7.6% reported fecal incontinence. CONCLUSION: Women with clinically recognized anal sphincter tears are more than twice as likely to report postpartum fecal incontinence than women without sphincter tears. Cesarean delivery before labor is not entirely protective against pelvic floor disorders. C1 Duquesne Univ, Dept Phys Therapy, Pittsburgh, PA 15282 USA. Birmingham VA Med Ctr, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Iowa, Iowa City, IA 52242 USA. Johns Hopkins Univ, Baltimore, MD USA. Natl Inst Child Hlth & Human Dev, NIH, Bethesda, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Borello-France, D (reprint author), Duquesne Univ, Dept Phys Therapy, 111 Hlth Sci Bldg, Pittsburgh, PA 15282 USA. EM borellofrance@duq.edu FU NICHD NIH HHS [U01 HD41249, U10 HD041261, U10 HD041263, U10 HD41248, U10 HD41250, U10 HD41261, U10 HD41263, U10 HD41267, U10 HD41268, U10 HD41269] NR 43 TC 132 Z9 135 U1 0 U2 11 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 OCT PY 2006 VL 108 IS 4 BP 863 EP 872 DI 10.1097/01.AOG.0000232504.32589.3b PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171XS UT WOS:000246769300007 PM 17012447 ER PT J AU Alexander, JM Leveno, KJ Hauth, J Landon, MB Thom, E Spong, CY Varner, MW Moawad, AH Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M O'Sullivan, MJ Sibai, BM Langer, O Gabbe, SG AF Alexander, James M. Leveno, Kenneth J. Hauth, John Landon, Mark B. Thom, Elizabeth Spong, Catherine Y. Varner, Michael W. Moawad, Atef H. Caritis, Steve N. Harper, Margaret Wapner, Ronald J. Sorokin, Yoram Miodovnik, Menachem O'Sullivan, Mary J. Sibai, Baha M. Langer, Oded Gabbe, Steven G. CA Natl I Child Hlth Human Dev Matern TI Fetal injury associated with Cesarean delivery SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PREDISPOSING FACTORS; SECTION; FRACTURES; TRIAL; BIRTH; TERM AB OBJECTIVE: To describe the incidence and type of fetal injury identified in women undergoing cesarean delivery. METHODS: Between January 1, 1999, and December 31, 2000, a prospective cohort study of all cesarean deliveries was conducted at 13 university centers. Information regarding maternal and infant outcomes was abstracted directly from hospital charts. RESULTS: A total of 37,110 cesarean deliveries were included in the registry, and 418 (1.1%) had an identified fetal injury. The most common injury was skin laceration (n=272, 0.7%). Other injuries included cephalohema-toma (n=88), clavicular fracture (n=11), brachial plexus (n=9), skull fracture (n=6), and facial nerve palsy (n=11). Among primary cesarean deliveries, deliveries with a failed forceps or vacuum attempt had the highest rate of injuries (6.9%). In women with a prior cesarean delivery, the highest rate of injury also occurred in the unsuccessful trial of forceps or vacuum (1.7%), and the lowest rate occurred in the elective repeat cesarean group (0.5%). The type of uterine incision was associated with fetal injury, 3.4% "T" or "J" incision, 1.4% for vertical incision, and 1.1% for a low transverse (P=.003), as was a skin incision-to-delivery time of 3 minutes or less. Fetal injury did not vary in frequency with the type of skin incision, preterm delivery, maternal body mass index, or infant birth weight greater than 4,000 g. CONCLUSION: Fetal injuries complicate 1.1% of cesarean deliveries. The frequency of fetal injury at cesarean delivery varies with the indication for surgery as well as with the duration of the skin incision-to-delivery interval and the type of uterine incision. C1 Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX 75235 USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. George Washington Univ, Ctr Biostat, Dept Obstet & Gynecol, Washington, DC 20052 USA. NICHHD, Dept Obstet & Gynecol, Bethesda, MD 20892 USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT 84112 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA 15260 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Obstet & Gynecol, Winston Salem, NC USA. Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH 45221 USA. Univ Miami, Dept Obstet & Gynecol, Miami, FL 33152 USA. Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, San Antonio, TX USA. Vanderbilt Univ, Dept Obstet & Gynecol, Nashville, TN USA. RP Alexander, JM (reprint author), Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. EM james.alexander@utsouthwestern.edu RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973 FU NICHD NIH HHS [HD27869, HD21410, HD21414, HD27860, HD27861, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD36801] NR 15 TC 61 Z9 66 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 2006 VL 108 IS 4 BP 885 EP 890 DI 10.1097/01.AOG.0000237116.72011.f3 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171XS UT WOS:000246769300010 PM 17012450 ER PT J AU Rouse, DJ MacPherson, C Landon, M Varner, MW Leveno, KJ Moawad, AH Spong, CY Caritis, SN Meis, PJ Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M Peaceman, AM O'Sullivan, MJ Sibai, BM Langer, O Thorp, JM Ramin, SM Mercer, BM AF Rouse, Dwight J. MacPherson, Cora Landon, Mark Varner, Michael W. Leveno, Kenneth J. Moawad, Atef H. Spong, Catherine Y. Caritis, Steve N. Meis, Paul J. Wapner, Ronald J. Sorokin, Yoram Miodovnik, Menachem Carpenter, Marshall Peaceman, Alan M. O'Sullivan, Mary Jo Sibai, Baha M. Langer, Oded Thorp, John M. Ramin, Susan M. Mercer, Brian M. CA Natl I Child Hlth Human Dev Matern TI Blood transfusion and Cesarean delivery SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 22-25, 2006 CL Toronto, CANADA SP Soc Gynecol Invest ID SECTION AB OBJECTIVE: To evaluate risks for intraoperative or postoperative packed red blood cell transfusion in women who underwent cesarean delivery. METHODS: This was a 19-university prospective observational study. All primary cesarean deliveries from January 1, 1999, to December 31, 2000, and all repeat cesareans from January 1, 1999, to December 31, 2002, were included. Trained, certified research nurses performed systematic data abstraction. Primary and repeat cesarean deliveries were analyzed separately. Univariable analyses were used to inform multivariable analyses. RESULTS: A total of 23,486 women underwent primary cesarean delivery, of whom 762 (3.2%) were transfused (median 2 units, 25th% to 75th% 2-3 units). A total of 33,683 women underwent primary cesarean delivery, and 735 (2.2%) were transfused (median 2 units, 25th% to 75th% 2-4 units). Among primary cesareans, general anesthesia (odds ratio [OR] 4.2, 95% confidence interval [CI] 3.5-5.0), placenta previa (OR 4.8, CI 3.5-6.5) and severe (hematocrit less than 25%) preoperative anemia (OR 17.0, CI 12.4-23.3) increased the odds of transfusion. Among repeat cesareans, the risk was increased by general anesthesia (OR 7.2, CI 5.9-8.7), a history of five or more prior cesareans (OR 7.6, CI 4.0-14.3), placenta previa (OR 15.9, CI 12.0-21.0), and severe preoperative anemia (OR 19.9, CI 14.5-27.2). CONCLUSION: Overall, the risk of transfusion in association with cesarean is low. However, both severe preoperative maternal anemia and placenta previa are associated with markedly increased risks. The former argues for optimizing maternal antenatal iron status to avoid severe anemia and the latter for careful perioperative planning when previa complicates cesarean. C1 Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35249 USA. George Washington Univ, Ctr Biostat, Dept Obstet & Gynecol, Washington, DC 20052 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Utah, Salt Lake City, UT 84112 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. NICHHD, Dept Obstet & Gynecol, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA 15260 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Thomas Jefferson Univ, Sch Med, Philadelphia, PA 19107 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH 45221 USA. Brown Univ, Dept Obstet & Gynecol, Providence, RI 02912 USA. Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. Univ Miami, Dept Obstet & Gynecol, Miami, FL 33152 USA. Univ Tennessee, Dept Obstet & Gynecol, Knoxville, TN 37996 USA. Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, San Antonio, TX 78284 USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC 27515 USA. Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, Houston, TX USA. Case Western Reserve Univ, Dept Obstet & Gynecol, Cleveland, OH 44106 USA. RP Rouse, DJ (reprint author), Univ Alabama, Dept Obstet & Gynecol, 619 19th St South,OHB 457, Birmingham, AL 35249 USA. EM drouse@uab.edu RI Varner, Michael/K-9890-2013; OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973; Peaceman, Alan/0000-0002-4515-4850 FU NICHD NIH HHS [HD27861, HD21410, HD21414, HD27860, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD36801, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560] NR 10 TC 55 Z9 62 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 2006 VL 108 IS 4 BP 891 EP 897 DI 10.1097/01.AOG.0000236547.35234.8c PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171XS UT WOS:000246769300011 PM 17012451 ER PT J AU Minkoff, H Xian, LS Watts, DH Leighty, R Hershow, R Palefsky, J Tuomala, R Neu, N Zorrilla, CD Paul, M Strickler, H AF Minkoff, Howard Xian, Lin Shen Watts, D. Heather Leighty, Robert Hershow, Ron Palefsky, Joel Tuomala, Ruth Neu, Natalie Zorrilla, Carmen D. Paul, Mary Strickler, Howard TI Relationship of pregnancy to human papillornavirus among human immunodeficiency virus-infected women SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID HUMAN-PAPILLOMAVIRUS INFECTION; UNINFECTED WOMEN; NATURAL-HISTORY; POSITIVE WOMEN; RISK-FACTORS; YOUNG-WOMEN; HIV; PREVALENCE; PERSISTENCE; INFANTS AB OBJECTIVE: Because parity is a reported risk factor for cervical cancer, we sought to estimate the effects of pregnancy on the prevalence, incident detection, and copy number of human papillomavirus (HPV) among human immunodeficiency virus (HIV)-infected women, patients at high risk for cervical cancer. METHODS: Human immunodeficiency virus-infected women who had a pregnancy in the Women's Interagency HIV Study (n=178) and the Women and Infants Transmission Study (n=450) underwent serial type-specific HPV DNA testing using MY09/MY11 polymerase chain reaction. During pregnancy and during the prepregnancy and postpregnancy periods, we assessed HPV prevalence, incident detection, and HPV copy number (estimated using hybridization signal strength) of both oncogenic and nononcogenic HPV. All binary-regression analyses incorporated generalized estimating equations to address the repeated observations of the same women over time, and were further adjusted for parity, gestational age, smoking, antiretroviral use, number of lifetime sexual partners, and oral contraceptive use. RESULTS: The prevalence and copy number of oncogenic and nononcogenic HPV did not significantly differ between pregnancy and either the prepregnancy or postpregnancy periods. Incident HPV detection was significantly lower for both oncogenic and nononcogenic HPV during pregnancy compared with the postpregnancy period (relative risk 0.534, 95% confidence interval 0.390-0.732, P <.001 and relative risk 0.577, 95% confidence interval 0.428-0.779, P <.001, respectively), but not compared with the prepregnancy period CONCLUSION: Among HIV-infected women, the incident detection of HPV is lower during pregnancy compared with postpregnancy, while prevalence and copy number do no differ between pregnancy and either prepregnancy or postpregnancy. C1 Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY USA. Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. Clin Trials & Surveys Corp, Baltimore, MD USA. NICHHD, Pediat Adolescent & Maternal Acquired Immunodefic, Bethesda, MD USA. Univ Illinois, Dept Internal Med, Chicago, IL 60680 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Columbia Univ, Dept Pediat, New York, NY 10027 USA. Univ Puerto Rico, Dept Obstet & Gynecol, San Juan, PR USA. Baylor Coll Med, Dept Family & Community Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Minkoff, H (reprint author), Maimonides Hosp, Dept Obstet & Gynecol, 967 48th St, Brooklyn, NY USA. EM Hminkoff@maimonidesmed.org RI Palefsky, Joel/A-7128-2009 FU NCI NIH HHS [CA85178-06]; NCRR NIH HHS [M01-RR-00071, M01-RR-00083, RR000645, M01-RR-00079, RR000188]; NIAID NIH HHS [U01-AI-31834, U01-AI-34993, U01-AI-34989, U01-AI-35004, U01-AI-34994, U01-AI-42590]; NICHD NIH HHS [U01-HD-32632] NR 30 TC 7 Z9 7 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 2006 VL 108 IS 4 BP 953 EP 960 DI 10.1097/01.AOG.0000236447.81813.c3 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171XS UT WOS:000246769300019 PM 17012459 ER PT J AU Araki-Sasaki, K Tanaka, T Ebisuno, Y Kanda, H Umemoto, E Hayashi, K Miyasaka, M AF Araki-Sasaki, Kaoru Tanaka, Toshiyuki Ebisuno, Yukihiko Kanda, Hidenobu Umemoto, Eiji Hayashi, Kozaburo Miyasaka, Masayuki TI Dynamic expression of chemokines and the infiltration of inflammatory cells in the HSV-infected cornea and its associated tissues SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE HSK (herpetic stromal keratitis); chemokine; cornea; lymph nodes; trigeminal ganglion ID HERPES-SIMPLEX-VIRUS; TRIGEMINAL GANGLION; STROMAL KERATITIS; TYPE-1; CYTOKINE; NEUTROPHIL; REPLICATION; KERATOCYTES; SUPPRESSION; SYSTEM AB Background: The chemotactic signals regulating cell trafficking in the herpes simplex virus type 1 (HSV-1) infected cornea are well documented, however, those in the cornea-associated tissues, such as the trigeminal ganglion (TG) and draining lymph nodes (LNs), are largely unknown. Objectives: To examine chemokine expression and subsequent cell infiltration in the HSV-1 infected cornea and its associated tissues. Study design: Eight-week-old female BALB/c mice were infected with 10 mu l HSV-1 (CHR3 strain: 5 x 10(6) PFU/ml) by corneal scarification. Total RNAs were extracted from the corneas, TGs, and LNs at pre-inoculation, 3 days post-inoculation (P.I.) and 7 days P. I. The mRNA for 28 different chemokines in the extracts was amplified by RT-PCR. Infiltrating cells were identified by immunohistochemistry. Result: After the HSV-1 infection, the corneal stroma became edematous by infiltrated cells under the eroded epithelium. The TG and LNs were markedly swollen. The cornea was infiltrated with granulocytes and CD11b(+) cells at 3 days P. I., followed by CD4(+) and CD8(+) T cells at 12 days P. I. In the TG, CD11b+ cells, but no granulocytes, infiltrated throughout the observation period. T cells migrated into the TG earlier than into the cornea. Gene expressions of neutrophil-attracting chemokines (CXCL1, 2, 3, and 5) increased in the cornea, but they did not enhance in the TG or LNs. On the other hand, gene expressions of chemokines which attract CD11b+ cells such as CCL2, 8, 7, 12, CCL3, 4, and CCL5, increased in the cornea and TG with its peak at 3 days P. I. Gene expressions of chemokines those work on T cells and B cells, such as CCL19, CCL21, CXCL9, CXCL13, CXCL10, XCL1, and CXCL16, were up-regulated and peaked at 3 days P. I. in the cornea and in the TG. Thus, pattern of chemokine gene expression was similar in the cornea and in the TG. On the contrary, gene expressions of chemokines in the draining LNs affecting CD11b+ cells and T cells were temporarily down-regulated. Conclusion: Upon HSV-1 infection, dynamic gene expression of chemokines was observed not only in the inoculated cornea but also in its associated tissues. C1 Ideta Eye Hosp, Kumamoto 8600035, Japan. Osaka Univ, Grad Sch Med, Osaka, Japan. NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Araki-Sasaki, K (reprint author), Ideta Eye Hosp, 1-35 Gofukumachi, Kumamoto 8600035, Japan. EM sasakis@sa2.so-net.ne.jp RI Tanaka, Toshiyuki/D-1193-2010 NR 22 TC 12 Z9 12 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD OCT PY 2006 VL 14 IS 5 BP 257 EP 266 DI 10.1080/09273940600943581 PG 10 WC Ophthalmology SC Ophthalmology GA 097GP UT WOS:000241435500001 PM 17056459 ER PT J AU Moon, HE Cheon, H Chun, KH Lee, SK Kim, YS Jung, BK Park, JA Kim, SH Jeong, JW Lee, MS AF Moon, Hyo-Eun Cheon, Hwanju Chun, Kwang-Hoon Lee, Seung Ki Kim, Yong-Sik Jung, Bo-Kyung Park, Jeong Ae Kim, Se-Hee Jeong, Joo-Won Lee, Myung-Shik TI Metastasis-associated protein 1 enhances angiogenesis by stabilization of HIF-1 alpha SO ONCOLOGY REPORTS LA English DT Article DE MTA1; HIF-1 alpha; stabilization; angiogenesis ID HYPOXIA; INVASION; MTA1; STABILITY; COMPLEXES; GROWTH; ALPHA; GENE; HIF AB Metastasis-associated protein 1 (MTA1) is highly upregulated in cancer cells with metastatic potential; however, the molecular mechanism by which MTA1 increases the metastatic potential of cancer cells is unknown. We characterized the functional consequences of NITA I overexpression in cancer cells with an emphasis on its potential role as a deacetylator of hypoxia-inducible factor-1 alpha (HIF-1 alpha). MTA1 increased the expression of HIF-1 alpha protein, but did not increase the expression of its mRNA. Glutathione S-transferase pull-down and coimmunoprecipitation assays demonstrated direct interaction of MTA1 with HIF-1 alpha both in vitro and in vivo. Immunoprecipitation and acetylation assays also showed that MTA1 has deacetylation activity on HIF-1 alpha in vivo. Moreover, MTA1 increased the transcriptional activity of HIF-1 alpha and enhanced the expression of vascular endothelial growth factor, a target molecule of HIF-1 alpha. Conditioned medium collected from MTA1 transfectants also increased angiogenesis in vitro and in vivo, probably through enhanced HIF-1 alpha stabilization. These results indicate that MTA1 enhances angiogenesis by stabilization of the HIF-1 alpha protein, which is closely related to the increased metastatic potential of cancer cells with high MTA1 expression. C1 Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med, Seoul 135710, South Korea. Seoul Natl Univ, Coll Pharm, Div Pharmaceut Biosci, Seoul 151, South Korea. NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. Kyung Hee Univ, Sch Med, MRC, ROS,Dept Anat, Seoul, South Korea. RP Lee, MS (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med, 50 Irwon Dong, Seoul 135710, South Korea. EM mslee@smc.samsung.co.kr RI Lee, Myung Shik/C-9606-2011 NR 23 TC 41 Z9 53 U1 0 U2 5 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 OCT PY 2006 VL 16 IS 4 BP 929 EP 935 PG 7 WC Oncology SC Oncology GA 089KI UT WOS:000240879000042 PM 16969516 ER PT J AU Kump, LI Castaneda, RAC Androudi, SN Reed, GF Foster, CS AF Kump, Leila I. Cervantes Castaneda, Rene A. Androudi, Sofia N. Reed, George F. Foster, C. Stephen TI Visual outcomes in children with juvenile idiopathic arthritis-associated uveitis SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 109th Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 15-18, 2005 CL Chicago, IL SP Amer Acad Ophthalmol ID RHEUMATOID-ARTHRITIS; PEDIATRIC UVEITIS; PREVALENCE; CHILDHOOD; PROGNOSIS AB Purpose: To analyze visual outcomes in children affected by juvenile idiopathic arthritis (JIA)-associated uveitis. Design: Retrospective interventional case series. Participants: Eighty-nine children with JIA-associated uveitis. Methods: Charts of children with JIA-associated uveitis were reviewed. Main Outcome Measure: Change in patients' visual acuities (VAs). Results: Of 269 children with uveitic syndromes referred, 89 (33%) had JIA-associated uveitis. The process was bilateral in 76 children. Seventy-three patients were female, and 84% of patients were Caucasian. Mean age of onset of uveitis was 5.7 years. Mean follow-up was 2.96 years. Antinuclear antibody positivity was detected in 56 patients, 44 of them female. Patients with JIA-associated uveitis developed numerous complications in the course of their disease: of 165 affected eyes, 105 (64%) developed cataracts, 33 (20%) developed increased intraocular pressure, and 76 (46%) developed band keratopathy; posterior synechiae were present in 96 (58%). Of 89 children, 73% were treated with immunomodulators, 40% were treated with nonsteroidal antiinflammatory agents alone or in combination with immunomodulators, and 21% were treated with topical and/or systemic steroids. Of 65 children who required immunomodulation, only one chemotherapeutic agent was used in 30, two agents in 21, and >= 3 in 14. Visual acuities of 65 children (122 eyes) were documented and compared at standard intervals. By mixed-models linear regression, improvement in VA of 0.03 logarithm of the minimum angle of resolution units per year was not found to be statistically significant (standard error, 0.02, P = 0.089). Conclusions: Juvenile idiopathic arthritis-associated uveitis is a sight-threatening disease. However, much of the children's vision can be preserved if patients are treated appropriately. (c) 2006 by the American Academy of Ophthalmology. C1 Massachusetts Eye Res & Surg Inst, Cambridge Ctr 5, Cambridge, MA 02142 USA. NEI, NIH, Bethesda, MD 20892 USA. Ocular Immunol & Uveitis Fdn, Cambridge, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Foster, CS (reprint author), Massachusetts Eye Res & Surg Inst, Cambridge Ctr 5, Cambridge, MA 02142 USA. EM fosters@uveitis.org NR 20 TC 41 Z9 43 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 2006 VL 113 IS 10 BP 1874 EP 1877 DI 10.1016/j.ophtha.2006.05.016 PG 4 WC Ophthalmology SC Ophthalmology GA 092HO UT WOS:000241087800031 PM 16884776 ER PT J AU Pinn, VW AF Pinn, Vivian W. TI Past and future: Sex and gender in health research, the aging experience, and implications for musculoskeletal health SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article ID HIP FRACTURE; MORTALITY AB The statistics about common musculoskeletal disorders describe a few of the many health conditions that affect men and women. For such disorders and conditions, there are differences in incidence, predisposition, and therapeutic and preventive strategies for managing them. Although we have made progress in women's health research, many challenges remain, including those related to conditions and diseases of the musculoskeletal system that may affect women and men differentially. Research is needed to identify genetic, hormonal, environmental, and societal factors that contribute to these sex and gender differences and to understand when appropriate clinical applications should differ or be the same. C1 Off Res Womens Hlth, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Pinn, VW (reprint author), Off Res Womens Hlth, Natl Inst Hlth, Dept Hlth & Human Serv, 6707 Democracy Blvd,Suite 400,MSC 5484, Bethesda, MD 20892 USA. EM pinn@od1th1.od.nih.gov NR 23 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-5898 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD OCT PY 2006 VL 37 IS 4 BP 513 EP + DI 10.1016/j.ocl.2006.09.006 PG 10 WC Orthopedics SC Orthopedics GA 123WV UT WOS:000243328400002 PM 17141007 ER PT J AU Pereira, MJR Rebelo, H Teeling, EC O'Brien, SJ Mackie, I Bu, SSH Swe, KM Mie, KM Bates, PJJ AF Ramos Pereira, Maria Joao Rebelo, Hugo Teeling, Emma C. O'Brien, Stephen J. Mackie, Iain Hla Bu, Si Si Swe, Khin Maung Mie, Khin Mie Bates, Paul J. J. TI Status of the world's smallest mammal, the bumble-bee bat Craseonycteris thonglongyai, in Myanmar SO ORYX LA English DT Article DE bumble-bee bat; Craseonycteris thonglongyai; Chiroptera; cytochrome b; distribution; echolocation; genetics; Myanmar ID CYTOCHROME-B; ECHOLOCATION; CHIROPTERA; SEQUENCE AB The bumble-bee bat Craseonycteris thonglongyai of the monospecific family Craseonycteridae is categorized as Endangered on the IUCN Red List. First discovered in 1973, it was until recently only known from a small population of approximately 2,300 individuals restricted to the catchment area of the River Kwai, Thailand. However, in 2001 a single craseonycterid was discovered in Mon State, Myanmar, extending its geographical range by approximately 250 km. In October and November 2002 a survey was undertaken to examine the status of C. thonglongyai in Myanmar and assess its geographical distribution and population size. C. thonglongyai calls were recorded from bats emerging from nine of 19 caves surveyed; the population size was estimated to be 1,500. The phylogenetic relationships between the Thai and Myanmar populations were investigated using molecular, morphological and acoustic data. Morphologically, the two populations are indistinguishable. However, there is an 8-10 kHz echolocation call divergence between the populations. Cytochrome b data suggest that the two populations are similar and that the Myanmar population may be monophyletic. Annual surveys of the known bat roosts and in situ education programmes for local people are recommended together with the establishment of an integrated, transboundary Myanmar/Thai conservation strategy. C1 Harrison Inst, Sevenoaks TN13 3AQ, Kent, England. Fac Ciencias Lisboa, Ctr Biol Ambiental, Dept Biol Anim, P-1749016 Lisbon, Portugal. Univ Porto, CIBIO, P-4485661 Vairao, Portugal. Univ Coll Dublin, Dept Zool, Dublin 4, Ireland. NCI, Lab Genom Divers, Frederick, MD 21702 USA. Univ Aberdeen, Dept Zool, Aberdeen AB24 2TZ, Scotland. RP Bates, PJJ (reprint author), Harrison Inst, Bowerwood House,St Botolphs Rd, Sevenoaks TN13 3AQ, Kent, England. EM hzm@btinternet.com RI Rebelo, Hugo/C-9005-2009; Ramos Pereira, Maria Joao/F-5644-2011; Ramos Pereira, Maria Joao/P-6221-2014 OI Rebelo, Hugo/0000-0002-7118-4068; Ramos Pereira, Maria Joao/0000-0002-9365-5166 NR 21 TC 3 Z9 4 U1 0 U2 17 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0030-6053 J9 ORYX JI Oryx PD OCT PY 2006 VL 40 IS 4 BP 456 EP 463 DI 10.1017/S0030605306001268 PG 8 WC Ecology SC Environmental Sciences & Ecology GA 130XU UT WOS:000243833100019 ER PT J AU Limb, CJ Carey, JP Srireddy, S Minor, LB AF Limb, Charles J. Carey, John P. Srireddy, Sharmila Minor, Lloyd B. TI Auditory function in patients with surgically treated superior semicircular canal dehiscence SO OTOLOGY & NEUROTOLOGY LA English DT Article DE canal plugging; canal resurfacing; hearing; middle fossa approach; superior semicircular canal dehiscence syndrome; surgical repair ID CONDUCTIVE HEARING-LOSS; VERTIGO; OTOSCLEROSIS AB Objective: To characterize preoperative and postoperative audiologic findings in patients with superior semicircular canal dehiscence syndrome. Study Design: Retrospective case review. Setting: Tertiary referral center. Patients: Patients with documented superior semicircular canal dehiscence syndrome (according to history, vestibular testing, and high-resolution computed tomography imaging) who underwent surgical repair of their dehiscence. Intervention: Middle fossa craniotomy for superior semicircular canal plugging and/or resurfacing. Main Outcome Measures: Audiologic testing both before and after surgery with pure-tone threshold measurements of air and bone conduction. Results: Twenty-nine subjects underwent surgical repair of superior semicircular canal dehiscence. Overall, there were no statistically significant differences by paired t test in hearing before or after surgery, in either air-conduction or bone-conduction thresholds, for 19 patients that had no previous surgical history. At least partial closure of air-bone gap was achieved in five patients. One patient with previous stapes surgery had significantly worse hearing both before and after canal repair compared with those without previous surgery. Two patients who had undergone previous middle fossa surgery with incomplete resolution of symptoms developed sensorineural hearing loss after revision surgery. Previous middle-ear exploration and tympanostomy tube placement did not seem to affect audiologic outcomes. Surgical hearing results did not differ according to method of canal repair (plugging versus resurfacing). Conclusion: Primary middle fossa repair of superior semicircular canal dehiscence is not associated with sensorineural hearing loss and, in some cases, can lead to normalization of conductive hearing loss. Revision middle fossa repair or previous stapes surgery may be associated with postoperative sensorineural hearing loss. C1 Johns Hopkins Univ Hosp, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. RP Limb, CJ (reprint author), Johns Hopkins Univ Hosp, Dept Otolaryngol Head & Neck Surg, 601 N Caroline St,6th Floor, Baltimore, MD 21287 USA. EM climb@jhmi.edu NR 19 TC 53 Z9 54 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD OCT PY 2006 VL 27 IS 7 BP 969 EP 980 DI 10.1097/01.mao.0000235376.70492.8e PG 12 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 089XN UT WOS:000240915300012 PM 17006348 ER PT J AU So, K Tamura, G Honda, T Homma, N Endoh, M Togawa, N Nishizuka, S Motoyama, T AF So, Kanji Tamura, Gen Honda, Teiichiro Homma, Naoyuki Endoh, Makoto Togawa, Naoyuki Nishizuka, Satoshi Motoyama, Teiichi TI Quantitative assessment of RUNX3 methylation in neoplastic and non-neoplastic gastric epithelia using a DNA microarray SO PATHOLOGY INTERNATIONAL LA English DT Article DE DNA microarray; gastric cancer; hypermethylation; RUNX3 ID CPG-ISLAND METHYLATION; CANCER; EXPRESSION; PROMOTER; GENES; AGE AB Silencing of the RUNX3 gene by hypermethylation of its promoter CpG island plays a major role in gastric carcinogenesis. To quantitatively evaluate RUNX3 methylation, a fiber-type DNA microarray was used on which methylated and unmethylated sequence probes were mounted. After bisulfite modification, a part of the RUNX3 promoter CpG island, at which methylation is critical for gene silencing, was amplified by polymerase chain reaction using a Cy5 end-labeled primer. Methylation rates (MR) were calculated as the ratio of the fluorescence intensity of a methylated sequence probe to the total fluorescence intensity of methylated and unmethylated probes. Five gastric cancer cell lines were analyzed, as well as 26 primary gastric cancers and their corresponding non-neoplastic gastric epithelia. MR in four of the cancer cell lines that lost RUNX3 mRNA ranged from 99.0% to 99.7% (mean, 99.4%), whereas MR in the remaining cell line that expressed RUNX3 mRNA was 0.6%. In primary gastric cancers and their corresponding non-neoplastic gastric epithelia, MR ranged from 0.2% to 76.5% (mean, 22.7%) and from 0.7% to 25.1% (mean, 5.5%). Ten (38.5%) of the 26 gastric cancers and none of their corresponding non-neoplastic gastric epithelia had MR > 30%. Most of the samples with MR > 10% tested methylation-positive by conventional methylation-specific polymerase chain reaction (MSP). This microarray-based methylation assay is a promising method for the quantitative assessment of gene methylation. C1 Yamagata Prefectural Cent Hosp, Div Pathol, Yamagata 9902292, Japan. Yamagata Univ, Sch Med, Dept Pathol, Yamagata 990, Japan. Mitsubishi Rayon, Yokohama Res Labs, Genom Device Project, Yokohama, Kanagawa, Japan. NCI, Mol Therapeut Program, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. SAIC Frederick, Lab Proteom & Analyt Technol, Frederick, MD USA. RP Tamura, G (reprint author), Yamagata Prefectural Cent Hosp, Div Pathol, 1800 O Aza Aoyagi, Yamagata 9902292, Japan. EM gtamura@ypch.gr.jp FU NCI NIH HHS [N01-CO-12400] NR 14 TC 22 Z9 23 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1320-5463 J9 PATHOL INT JI Pathol. Int. PD OCT PY 2006 VL 56 IS 10 BP 571 EP 575 DI 10.1111/j.1440-1827.2006.02010.x PG 5 WC Pathology SC Pathology GA 085MC UT WOS:000240607200001 PM 16984612 ER PT J AU Zapka, JG Geller, BM Bulliard, JL Jacques, F Helene, SG Ballard-Barbash, R AF Zapka, Jane G. Geller, Berta M. Bulliard, Jean-Luc Jacques, Fracheboud Helene, Sancho-Garnier Ballard-Barbash, Rachel CA IBSN Commun Working Grp TI Print information to inform decisions about mammography screening participation in 16 countries with population-based programs SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE mammography; decision-making; health communication ID BREAST-CANCER; QUALITY ASSURANCE; WOMENS PERCEPTION; FOLLOW-UP; BENEFITS; RISKS; CONSEQUENCES; MORTALITY; SERVICES; INSIGHT AB Objective: To profile and compare the content and presentation of written communications related to informed decision-making about mammography. Methods: Materials from 16 screening programs organized at the national or regional level were analyzed according to five major information domains suggested by the international literature. Results: A majority of countries provided information on the program (interval, cost and quality). There was considerable variability in comprehensiveness of elements in the domains, e.g., test characteristics (false positive/negative) and pros and cons of screening. The majority noted the likelihood of recall for further tests, few commented on the risks of additional tests or finding unimportant tumors. The audit also found variation in presentation (words and pictures). Conclusions: Presentation of comprehensive, but balanced information on screening benefits and risks is complex and daunting. Issues such as framing effects, coupled with debate about screening efficacy are challenging to the design of effective information tools. The objective of increasing screening prevalence at the population level must be balanced with objectively presenting complete and clear information. Additional research is needed on how information (and mode of presentation) impact screening decisions. Practice implications: Public health officials need to articulate their objectives and review written communication according to important decision-making domains. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. Univ Vermont, Hlth Promot Res, Burlington, VT 05405 USA. Univ Lausanne, Inst Social & Prevent Med, Canc Epidemiol Unit, Lausanne, Switzerland. Univ Rotterdam, Med Ctr, Dept Publ Hlth, Erasmus MC, Rotterdam, Netherlands. Epidaure, CRLC, Montpellier, France. NCI, Appl Res Program, Bethesda, MD 20892 USA. RP Zapka, JG (reprint author), Univ Massachusetts, Sch Med, 55 Lake Ave N, Worcester, MA 01655 USA. EM jane.zapka@umassmed.edu NR 50 TC 25 Z9 26 U1 5 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD OCT PY 2006 VL 63 IS 1-2 BP 126 EP 137 DI 10.1016/j.pec.2005.09.012 PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 093LP UT WOS:000241170100017 PM 16962910 ER PT J AU Lin, FYC Troendle, JF AF Lin, Feng Ying C. Troendle, James F. TI Neonotol respiratory distress may be related to asymptomatic colonization with group B streptococci SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE group B streptococci; colonization; respiratory distress; intrapartum penicillin ID EARLY-ONSET DISEASE; MUTANS BHT; INTRAPARTUM CHEMOPROPHYLAXIS; PULMONARY-HYPERTENSION; VERTICAL TRANSMISSION; TRANSIENT TACHYPNEA; EXCRETION; MULTICENTER; INHIBITION; AMPICILLIN AB Background: Phospholipids from the group B streptococcal (GBS) cell wall cause pulmonary hypertension in experimental animals. When exposed to penicillin, Streptococcus mutans releases phospholipids immediately. We hypothesize that newborns colonized with GBS receive bacterial phospholipids leading to pulmonary hypertension and respiratory distress, especially in the situation of newborns of penicillin-treated mothers. We examined clinical and epidemiologic data on these relations. Methods: We used data from a prospective multicenter GBS study conducted from 1995 to 1999 in which 1674 of 17,690 newborns cultured at 4 sites were colonized with GBS. Our analyses included 1610 colonized newborns >= 32 weeks gestation without early-onset disease. Clinical features were compared between 1003 lightly colonized (GBS positive at :52 sites) and 607 heavily colonized (positive at 3 or 4 sites) newborns. The rates of respiratory distress were compared between colonized newborns of penicillin-treated mothers and those of untreated mothers. Results: Of the 16 10 colonized newborns, 8.8% had signs of respiratory distress within 48 hours after birth (cases). Oxygen supplementation was used in 60% of the cases, mechanical ventilation was required in 5% and persistent pulmonary hypertension was diagnosed in 2%. Compared with light colonization, heavy colonization increased the rate of respiratory distress 1.73-fold (95% CI, 1.26-2.38), a discharge diagnosis of respiratory disorder 2.02-fold (95% CI, 1.16-3.52), a blood/cerebrospinal fluid obtained for culture 1.54-fold (95% CI, 1.241.93) and antibiotic administration after birth 1.87-fold (95% CI, 1.342.61). Penicillin use during labor was associated with a 2.62-fold (95% CI, 1.79-3.83) increase in respiratory distress in the colonized newbom. Conclusions: Our findings support the association of neonatal respiratory distress with asymptomatic GBS colonization and with penicillin use during labor. These data require confirmation. C1 NICHHD, Dev & Mol Immun Lab, NIH, Dept Hlth & Human Serv,Div Epidemiol Stat & Preve, Bethesda, MD 20892 USA. RP Lin, FYC (reprint author), NICHHD, Dev & Mol Immun Lab, NIH, Dept Hlth & Human Serv,Div Epidemiol Stat & Preve, Room 2A27,Bldg 31,31 Ctr Dr, Bethesda, MD 20892 USA. EM Link@mail.nih.gov FU NICHD NIH HHS [HD-43215, HD-43217, HD-43218, HD-53223, HD-43214, HD-43219, HD-43220] NR 30 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD OCT PY 2006 VL 25 IS 10 BP 884 EP 888 DI 10.1097/01.inf.0000239322.58890.94 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 093WJ UT WOS:000241200700006 PM 17006281 ER PT J AU Bondy, CA Ceniceros, I Van, PL Bakalov, VK Rosing, DR AF Bondy, Carolyn A. Ceniceros, Irene Van, Phillip L. Bakalov, Vladimir K. Rosing, Douglas R. TI Prolonged rate-corrected QT interval and other electrocardiogram abnormalities in girls with Turner syndrome SO PEDIATRICS LA English DT Article DE electrophysiology; Turner syndrome; heart disease; long QT ID LEFT-VENTRICULAR HYPERTROPHY; CONGENITAL HEART-DISEASE; RISK; REPOLARIZATION; ASSOCIATION; PREVALENCE; MORTALITY; PROFILE; HEALTH; DEATH AB BACKGROUND. We recently reported that electrocardiographic abnormalities are common in adults with monosomy X (Turner syndrome), but this issue has not been investigated in girls with Turner syndrome. PATIENTS AND METHODS. We analyzed electrocardiograms in 78 girls with Turner syndrome and 50 age-matched control girls. The girls with Turner syndrome had additional cardiac and metabolic evaluations. RESULTS. Girls with Turner syndrome were more likely to demonstrate >= 1 electrocardiographic findings including right axis deviation, right ventricular hypertrophy, accelerated atrioventricular conduction, T-wave abnormalities, and a prolonged rate-corrected QT interval. The right-sided findings were associated with partial anomalous pulmonary venous connection, but the etiology of the other findings remains unknown. The rate-corrected QT interval was significantly longer in girls with Turner syndrome (431 +/- 22 vs 407 +/- 21 milliseconds). Twenty-eight girls with Turner syndrome but only 2 controls had a rate-corrected QT interval above the reference range. We found no correlation between body habitus, cardiac dimensions, or metabolic parameters and the rate- corrected QT interval duration in girls with Turner syndrome. CONCLUSIONS. Cardiac conduction and repolarization abnormalities seem to affect both young girls and adults with Turner syndrome equally, suggesting that electrophysiologic defects are intrinsic to the syndrome and indicating that electrocardiogram analysis should be included in evaluating and monitoring even the youngest patients with Turner syndrome. Attention to the rate-corrected QT interval is important, because some common medications may further prolong this interval and increase the risk of arrhythmias. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD USA. RP Bondy, CA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10 CRC,Room 1-3330, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov FU Intramural NIH HHS NR 28 TC 14 Z9 15 U1 1 U2 1 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 OCT PY 2006 VL 118 IS 4 BP E1220 EP E1225 DI 10.1542/peds.2006-0776 PG 6 WC Pediatrics SC Pediatrics GA 090NZ UT WOS:000240959300107 PM 17015510 ER PT J AU Freeman, AF Davis, J Anderson, VL Barson, W Darnell, DN Puck, JM Holland, SM AF Freeman, Alexandra F. Davis, Joie Anderson, Victoria L. Barson, William Darnell, Dirk N. Puck, Jennifer M. Holland, Steven M. TI Pneumocystis jiroveci infection in patients with hyper-immunoglobulin E syndrome SO PEDIATRICS LA English DT Article DE hyper-IgE syndrome; Pneumocystis jiroveci; immunodeficiency ID CARINII-PNEUMONIA; IGE SYNDROME; HYPERIMMUNOGLOBULINEMIA-E; HIV-INFECTION; T-CELLS; IMMUNODEFICIENCY; GAMMA; PCR AB The hyper-immunoglobulin E syndrome is a primary immunodeficiency characterized by recurrent pyogenic skin and lung abscesses, dermatitis, and elevated serum immunoglobulin E levels. Pneumocystis jiroveci (formerly Pneumocystis carinii) is not typically associated with hyper-immunoglobulin E syndrome. We identified 7 patients with hyper-immunoglobulin E syndrome with P jiroveci detected in respiratory or pulmonary pathology specimens. In 5 patients it was the sole pathogen, and in 2 other patients it contributed to a polymicrobial etiology. No consistent prophylaxis was given, and there have been no recurrences on long-term follow-up. Our experience suggests that P jiroveci can cause pneumonia in patients with hyper-immunoglobulin E syndrome both with and without chronic lung disease. C1 NIAID, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Coll Med, Infect Dis Sect, Columbus Childrens Hosp, Columbus, OH 43210 USA. RP Freeman, AF (reprint author), NIAID, NIH, Bldg 10,Room 10S255,9000 Rockville Pike, Bethesda, MD 20892 USA. EM freemaal@mail.nih.gov FU Intramural NIH HHS NR 24 TC 22 Z9 22 U1 1 U2 1 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 OCT PY 2006 VL 118 IS 4 BP E1271 EP E1275 DI 10.1542/peds.2006-0311 PG 5 WC Pediatrics SC Pediatrics GA 090NZ UT WOS:000240959300115 PM 16940164 ER PT J AU Fleisher, TA AF Fleisher, Thomas A. TI Primary immune deficiencies: Windows into the immune system SO PEDIATRICS IN REVIEW LA English DT Review ID PRIMARY IMMUNODEFICIENCY; ANTIBODY DEFICIENCY; DISEASES; DEFECTS C1 NIH, Dept Lab Med, Ctr Clin, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Fleisher, TA (reprint author), NIH, Dept Lab Med, Ctr Clin, Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 15 TC 5 Z9 5 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 0191-9601 J9 PEDIATR REV JI Pediatr. Rev. PD OCT PY 2006 VL 27 IS 10 BP 363 EP 372 DI 10.1542/pir.27-10-363 PG 10 WC Pediatrics SC Pediatrics GA 107MW UT WOS:000242176700001 PM 17012486 ER PT J AU Dalakas, MC AF Dalakas, Marinos C. TI B cells in the pathophysiology of autoimmune neurological disorders: A credible therapeutic target SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE B cells; autoantibodies; autoimmune neurological disorders; B cell depletion; rituximab ID GUILLAIN-BARRE-SYNDROME; MULTIPLE-SCLEROSIS PATIENTS; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; STIFF-PERSON-SYNDROME; INFLAMMATORY DEMYELINATING POLYNEUROPATHY; MONOCLONAL-ANTIBODY RITUXIMAB; OPSOCLONUS-MYOCLONUS SYNDROME; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CENTRAL-NERVOUS-SYSTEM; CEREBROSPINAL-FLUID AB There is evidence that B cells are involved in the pathophysiology of many neurological diseases, either in a causative or contributory role, via production of autoantibodies, cytokine secretion, or by acting as antigen-presenting cells leading to T cell activation. Clonal expansion of B cells either in situ or intrathecally and circulating autoantibodies are critical elements in multiple sclerosis (MS), Devic's disease, paraneoplastic central nervous system disorders, stiff-person syndrome, myasthenia gravis, autoimmune demyelinating neuropathies and dermatomyositis. The pathogenic role of B cells and autoantibodies in central and peripheral nervous system disorders, as reviewed here, provides a rationale for investigating whether depletion of B cells with new agents can improve clinical symptomatology and, potentially, restore immune function. Preliminary results from several clinical studies and case reports suggest that B cell depletion may become a viable alternative approach to the treatment of autoimmune neurological disorders. Published by Elsevier Inc. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248, Bethesda, MD 20892 USA. EM DalakasM@ninds.nih.gov NR 143 TC 26 Z9 28 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD OCT PY 2006 VL 112 IS 1 BP 57 EP 70 DI 10.1016/j.pharmthera.2006.03.005 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 086YF UT WOS:000240708400004 PM 16644016 ER PT J AU Parnes, HL Figg, WD AF Parnes, Howard L. Figg, William D. TI Chemoprevention in prostate cancer SO PHARMACOTHERAPY LA English DT Editorial Material DE prostate cancer; chemoprevention; finasteride C1 NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. NCI, Prostate & Urol Canc Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 2 TC 1 Z9 2 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2006 VL 26 IS 10 BP 1533 EP 1533 DI 10.1592/phco.26.10.1533 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 090RE UT WOS:000240967800020 PM 16999665 ER PT J AU dos Santos, CAM Neumeier, JJ Yu, YK Bollinger, RK Jin, R Mandrus, D Sales, BC AF dos Santos, C. A. M. Neumeier, J. J. Yu, Yi-Kuo Bollinger, R. K. Jin, R. Mandrus, D. Sales, B. C. TI Thermodynamic nature of the antiferromagnetic transition in NaxCoO2 SO PHYSICAL REVIEW B LA English DT Article AB High-resolution thermal expansion measurements of single-crystalline Na0.80CoO2 reveal continuous behavior of the paramagnetic-antiferromagnetic phase transition at T-M=21.7(1) K with critical exponent alpha=0.18(2). The thermal expansion is found to be highly anisotropic. Thermodynamic analysis provides the hydrostatic pressure derivative dT(M)/dP=+4.6(2) K/GPa. Similar measurements and analysis are presented for Na0.75CoO2. C1 Montana State Univ, Dept Phys, Bozeman, MT 59717 USA. USP, Escola Engn Lorena, BR-12602810 Lorena, SP, Brazil. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Oak Ridge Natl Lab, Div Mat Sci & Technol, Oak Ridge, TN 37831 USA. RP dos Santos, CAM (reprint author), Montana State Univ, Dept Phys, POB 173840, Bozeman, MT 59717 USA. RI Mandrus, David/H-3090-2014; dos Santos, Carlos/C-1619-2012 NR 31 TC 11 Z9 11 U1 0 U2 9 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1098-0121 J9 PHYS REV B JI Phys. Rev. B PD OCT PY 2006 VL 74 IS 13 AR 132402 DI 10.1103/PhysRevB.74.132402 PG 4 WC Physics, Condensed Matter SC Physics GA 101EY UT WOS:000241723200010 ER PT J AU Silva, HS Martins, ML Vilela, MJ Jaeger, R Kachar, B AF Silva, H. S. Martins, M. L. Vilela, M. J. Jaeger, Ruy Kachar, B. TI 1/f ruffle oscillations in plasma membranes of amphibian epithelial cells under normal and inverted gravitational orientations SO PHYSICAL REVIEW E LA English DT Article ID ACTIN; MIGRATION; FLUCTUATIONS; ERYTHROCYTES; MACROPHAGES; LOCOMOTION; DYNAMICS AB Membrane ruffle fluctuations of amphibian epithelial cells A6 (CCL102) cultured in normal and upside down oriented plates have been analyzed through video microscopy. Our results reveal that their edge ruffle fluctuations exhibit a stochastic dynamics with 1/f(alpha) power spectrum over at least two decades at low frequencies and long range correlated, self-affine lateral border profiles. In a few and small areas of the membrane, probably nearby focal contacts, we found periodic oscillations which could be induced by myosin driven contraction of stress fibers. Furthermore, whereas the different gravitational orientations had none or little effect on the structure (power spectra and surface roughness) of these membrane ruffle fluctuations, their dynamic parameters were differentially affected. Indeed, the decay time of ruffles remained unchanged, but the period of lamellipodia oscillations near the focal adhesion points was significantly altered in A6 cells cultured upside down. C1 Univ Fed Pernambuco, Dept Fis, BR-50670901 Recife, PE, Brazil. Univ Fed Vicosa, Dept Fis, BR-36570000 Vicosa, MG, Brazil. Univ Fed Vicosa, Dept Biol Anim, BR-36570000 Vicosa, MG, Brazil. Univ Sao Paulo, Inst Ciencias Biomed, Dept Biol Celular & Desenvolvimento, BR-05508900 Sao Paulo, Brazil. NIDCD, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. RP Silva, HS (reprint author), Univ Fed Pernambuco, Dept Fis, BR-50670901 Recife, PE, Brazil. EM mmartins@mail.ufv.br RI Martins, Marcelo/G-3868-2012; Jaeger, Ruy/G-8230-2011 FU Intramural NIH HHS NR 31 TC 4 Z9 4 U1 1 U2 3 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD OCT PY 2006 VL 74 IS 4 AR 041903 DI 10.1103/PhysRevE.74.041903 PN 1 PG 8 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 101EV UT WOS:000241722900086 PM 17155092 ER PT J AU Bharti, K Nguyen, MTT Skuntz, S Bertuzzi, S Arnheiter, H AF Bharti, Kapil Nguyen, Minh-Thanh T. Skuntz, Susan Bertuzzi, Stefano Arnheiter, Heinz TI The other pigment cell: specification and development of the pigmented epithelium of the vertebrate eye SO PIGMENT CELL RESEARCH LA English DT Review DE Mitf; Otx; Chx10; Pax6; activin; sonic hedgehog/fibroblast growth factor; neuroepithelial domain specification; evolution ID VITILIGO MUTANT MICE; ADULT MAMMALIAN EYE; RETINAL STEM-CELLS; SONIC HEDGEHOG; NEURAL RETINA; TRANSCRIPTION FACTOR; OPTIC VESICLE; CHICK EYE; MICROPHTHALMIA GENE; LENS MORPHOGENESIS AB Vertebrate retinal pigment epithelium (RPE) cells are derived from the multipotent optic neuroepithelium, develop in close proximity to the retina, and are indispensible for eye organogenesis and vision. Recent advances in our understanding of RPE development provide evidence for how critical signaling factors operating in dorso-ventral and distal-proximal gradients interact with key transcription factors to specify three distinct domains in the budding optic neuroepithelium: the distal future retina, the proximal future optic stalk/optic nerve, and the dorsal future RPE. Concomitantly with domain specification, the eye primordium progresses from a vesicle to a cup, RPE pigmentation extends towards the ventral side, and the future ciliary body and iris form from the margin zone between RPE and retina. While much has been learned about the molecular networks controlling RPE cell specification, key questions concerning the cell proliferative parameters in RPE and the subsequent morphogenetic events still need to be addressed in greater detail. C1 NINDS, Mammalian Dev Sect, NIH, Bethesda, MD 20892 USA. RP Arnheiter, H (reprint author), NINDS, Mammalian Dev Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM ha3p@nih.gov FU Intramural NIH HHS; NINDS NIH HHS [Z01 NS002790-17] NR 101 TC 87 Z9 92 U1 1 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD OCT PY 2006 VL 19 IS 5 BP 380 EP 394 DI 10.1111/j.1600-0749.2006.00318.x PG 15 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 079AG UT WOS:000240147300002 PM 16965267 ER PT J AU Jordens, I Westbroek, W Marsman, M Rocha, N Mommaas, M Huizing, M Lambert, J Naeyaert, JM Neefjes, J AF Jordens, Ingrid Westbroek, Wendy Marsman, Marije Rocha, Nuno Mommaas, Mieke Huizing, Marjan Lambert, Jo Naeyaert, Jean M. Neefjes, Jacques TI Rab7 and Rab27a control two motor protein activities involved in melanosomal transport SO PIGMENT CELL RESEARCH LA English DT Article DE melanosomes; motor proteins; dynein; dynactin; myosin Va; Rab7-interacting lysosomal protein; Rab7; Rab27a ID NORMAL HUMAN MELANOCYTES; TYROSINASE-RELATED PROTEIN-1; MYOSIN-VA; GRISCELLI-SYNDROME; CYTOPLASMIC DYNEIN; INTRACELLULAR-TRANSPORT; XENOPUS MELANOPHORES; ENDOCYTIC PATHWAY; MEMBRANE DYNAMICS; DYNACTIN COMPLEX AB Melanosomes are lysosome-related organelles that synthesize, store and transport melanin. In epidermal melanocytes, melanosomes mature and are transferred to surrounding keratinocytes, which is essential for skin and coat colour. Mouse coat colour mutants reveal a critical role for the small GTPase Rab27a, which recruits myosin Va through its effector protein melanophilin/Slac2a. Here we have studied how two different Rab GTPases control two motor proteins during subsequent phases in transport of melanosomes. We show that the small GTPase Rab7 mainly associates with early and intermediate stage melanosomes and Rab27a to intermediate and mature melanosomes. Rab27a is found in an active state on mature melanosomes in the tips of the dendrites. The Rab7-Rab7-interacting lysosomal protein-dynein pathway only controls early and intermediate stage melanosomes because the mature melanosomes lack Rab7 and associate with the actin network through Rab27a recruited MyoVa. Thus two Rab proteins regulate two different motor proteins, thereby controlling complementary phases in melanosome biogenesis: Rab7 controls microtubule-mediated transport of early and Rab27a the subsequent actin-dependent transport of mature melanosomes. C1 Netherlands Canc Inst, Dept Tumor Biol, Amsterdam, Netherlands. NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Leiden Univ, Med Ctr, Ctr Electron Microscopy, Dept Mol Cell Biol, NL-2300 RA Leiden, Netherlands. State Univ Ghent Hosp, Dept Dermatol, B-9000 Ghent, Belgium. RP Neefjes, J (reprint author), Netherlands Canc Inst, Dept Tumor Biol, Plesmanlaan 121, Amsterdam, Netherlands. EM j.neefjes@nki.nl FU Intramural NIH HHS NR 63 TC 54 Z9 57 U1 3 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD OCT PY 2006 VL 19 IS 5 BP 412 EP 423 DI 10.1111/j.1600-0749.2006.00329.x PG 12 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 079AG UT WOS:000240147300005 PM 16965270 ER PT J AU Gibbs, JR Singleton, A AF Gibbs, J. Raphael Singleton, Andrew TI Application of genome-wide single nucleotide polymorphism typing: Simple association and beyond SO PLOS GENETICS LA English DT Review ID GENETIC ASSOCIATION; HUMAN-POPULATIONS; HAPMAP PROJECT; STRATIFICATION; HOMOZYGOSITY; MAP AB T he International HapMap Project and the arrival of technologies that type more than 100,000 SNPs in a single experiment have made genome-wide single nucleotide polymorphism (GW-SNP) assay a realistic endeavor. This has sparked considerable debate regarding the promise of GW-SNP typing to identify genetic association in disease. As has already been shown, this approach has the potential to localize common genetic variation underlying disease risk. The data provided from this technology also lends itself to several other lines of investigation; autozygosity mapping in consanguineous families and outbred populations, direct detection of structural variation, admixture analysis, and other population genetic approaches. In this review we will discuss the potential uses and practical application of GW-SNP typing including those above and beyond simple association testing. C1 NIA, Mol Genet Unit, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. NIA, Computat Biol Core, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. RP Singleton, A (reprint author), NIA, Mol Genet Unit, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. EM singleta@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Gibbs, J. Raphael/A-3984-2010 FU Intramural NIH HHS NR 20 TC 70 Z9 70 U1 2 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2006 VL 2 IS 10 BP 1511 EP 1517 AR e150 DI 10.1371/journal.pgen.0020150 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 103YD UT WOS:000241922200001 PM 17029559 ER PT J AU Aslanukov, A Bhowmick, R Guruju, M Oswald, J Raz, D Bush, RA Sieving, PA Lu, XR Bock, CB Ferreira, PA AF Aslanukov, Azamat Bhowmick, Reshma Guruju, Mallikarjuna Oswald, John Raz, Dorit Bush, Ronald A. Sieving, Paul A. Lu, Xinrong Bock, Cheryl B. Ferreira, Paulo A. TI RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism SO PLOS GENETICS LA English DT Article ID NUCLEAR-PORE COMPLEX; UBIQUITIN-PROTEIN LIGASE; PIGMENTOSA GTPASE REGULATOR; BINDING PROTEIN-2; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; CELL-DEATH; SUBCELLULAR-LOCALIZATION; RAT-BRAIN; PARKIN; MICE AB The Ran-binding protein 2 (RanBP2) is a large multimodular and pleiotropic protein. Several molecular partners with distinct functions interacting specifically with selective modules of RanBP2 have been identified. Yet, the significance of these interactions with RanBP2 and the genetic and physiological role(s) of RanBP2 in a whole-animal model remain elusive. Here, we report the identification of two novel partners of RanBP2 and a novel physiological role of RanBP2 in a mouse model. RanBP2 associates in vitro and in vivo and colocalizes with the mitochondrial metallochaperone, Cox11, and the pacemaker of glycolysis, hexokinase type I (HKI) via its leucine-rich domain. The leucine-rich domain of RanBP2 also exhibits strong chaperone activity toward intermediate and mature folding species of Cox11 supporting a chaperone role of RanBP2 in the cytosol during Cox11 biogenesis. Cox11 partially colocalizes with HKI, thus supporting additional and distinct roles in cell function. Cox11 is a strong inhibitor of HKI, and RanBP2 suppresses the inhibitory activity of Cox11 over HKI. To probe the physiological role of RanBP2 and its role in HKI function, a mouse model harboring a genetically disrupted RanBP2 locus was generated. RanBP2(-/-) are embryonically lethal, and haploinsufficiency of RanBP2 in an inbred strain causes a pronounced decrease of HKI and ATP levels selectively in the central nervous system. Inbred RanBP2(+/-) mice also exhibit deficits in growth rates and glucose catabolism without impairment of glucose uptake and gluconeogenesis. These phenotypes are accompanied by a decrease in the electrophysiological responses of photosensory and postreceptoral neurons. Hence, RanBP2 and its partners emerge as critical modulators of neuronal HKI, glucose catabolism, energy homeostasis, and targets for metabolic, aging disorders and allied neuropathies. C1 Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA. Med Coll Wisconsin, Dept Anat Cell Biol & Neurobiol, Milwaukee, WI 53226 USA. Third Wave Technol, Madison, WI USA. NEI, NIH, Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. RP Ferreira, PA (reprint author), Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA. EM ferre044@mc.duke.edu RI Ferreira, Paulo/A-3893-2008; Ferreira, Paulo/S-4209-2016 OI Ferreira, Paulo/0000-0003-4585-1717 FU NEI NIH HHS [R01 EY012665, 2P30-EY005722-21, EY012665, EY11993, P30 EY005722, R01 EY011993] NR 67 TC 46 Z9 47 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2006 VL 2 IS 10 BP 1653 EP 1665 AR e177 DI 10.1371/journal.pgen.0020177 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 103YD UT WOS:000241922200015 PM 17069463 ER PT J AU Altfeld, M Kalife, ET Qi, Y Streeck, H Lichterfeld, M Johnston, MN Burgett, N Swartz, ME Yang, A Alter, G Yu, XG Meier, A Rockstroh, JK Allen, TM Jessen, H Rosenberg, ES Carrington, M Walker, BD AF Altfeld, Marcus Kalife, Elizabeth T. Qi, Ying Streeck, Hendrik Lichterfeld, Mathias Johnston, Mary N. Burgett, Nicole Swartz, Martha E. Yang, Amy Alter, Galit Yu, Xu G. Meier, Angela Rockstroh, Juergen K. Allen, Todd M. Jessen, Heiko Rosenberg, Eric S. Carrington, Mary Walker, Bruce D. TI HLA alleles associated with delayed progression to AIDS contribute strongly to the initial CD8(+) T cell response against HIV-1 SO PLOS MEDICINE LA English DT Article ID IMMUNODEFICIENCY VIRUS-INFECTION; LYMPHOCYTE RESPONSES; TYPE-1 INFECTION; IMMUNE-RESPONSES; DISEASE PROGRESSION; RHESUS MACAQUES; ESCAPE; VIREMIA; IMMUNODOMINATION; EXPRESSION AB Background Very little is known about the immunodominance patterns of HIV-1-specific T cell responses during primary HIV-1 infection and the reasons for human lymphocyte antigen (HLA) modulation of disease progression. Methods and Findings In a cohort of 104 individuals with primary HIV-1 infection, we demonstrate that a subset of CD8(+) T cell epitopes within HIV-1 are consistently targeted early after infection, while other epitopes subsequently targeted through the same HLA class I alleles are rarely recognized. Certain HLA alleles consistently contributed more than others to the total virus-specific CD8(+) T cell response during primary infection, and also reduced the absolute magnitude of responses restricted by other alleles if coexpressed in the same individual, consistent with immunodomination. Furthermore, individual HLA class I alleles that have been associated with slower HIV-1 disease progression contributed strongly to the total HIV-1-specific CD8(+) T cell response during primary infection. Conclusions These data demonstrate consistent immunodominance patterns of HIV-1-specific CD8(+) T cell responses during primary infection and provide a mechanistic explanation for the protective effect of specific HLA class I alleles on HIV-1 disease progression. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA. SAIC Frederick, Basic Res Program, Lab Gen Divers, NCI, Frederick, MD USA. Gemeinschaftspraxis Jessen, Berlin, Germany. Univ Bonn, Dept Internal Med, D-5300 Bonn, Germany. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Infect Dis Unit, Boston, MA 02114 USA. EM maltfeld@partners.org RI Allen, Todd/F-5473-2011 FU NCI NIH HHS [N01CO12400]; NIAID NIH HHS [R01 AI050429, U01 AI052403] NR 53 TC 198 Z9 201 U1 2 U2 8 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 OCT PY 2006 VL 3 IS 10 BP 1851 EP 1864 AR e403 DI 10.1371/journal.pmed.0030403 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 103YU UT WOS:000241923900033 PM 17076553 ER PT J AU Emanuel, EJ AF Emanuel, Ezekiel J. TI Research ethics boards - Reply SO PLOS MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM eemanuel@mail.cc.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2006 VL 3 IS 10 BP 1970 EP 1970 AR e460 DI 10.1371/journal.pmed.0030460 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 103YU UT WOS:000241923900049 ER PT J AU Reis, LC Hibbeln, JR AF Reis, L. C. Hibbeln, J. R. TI Cultural symbolism of fish and the psychotropic properties of omega-3 fatty acids SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID MAJOR DEPRESSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; N-6 FATTY-ACIDS; DOUBLE-BLIND; SEAFOOD CONSUMPTION; POPULATION AB Fish is a food with unique psychotropic properties. Consumption of long-chain omega-3 fatty acids, rich in seafood, reduces depression, aggression and anger while improving mental well-being. We posit that symbols of fish have become linked to the emotional states induced by long-chain fatty acid by associative pairings, both conscious and unconscious. The limbic and hippocampal activity necessary for memory formation containing emotional content and the labeling of social context by cortical processes appears to be optimized by diets rich in long-chain omega-3 fatty acid. In this critical literature survey, we find that fish have been culturally labeled as symbols of emotional well-being and social healing in religious and medical practices among independent cultures, for at least six millennia. This understanding of the perception of fish as a symbolically healing or purifying food can assist current messages improving public health. (c) 2006 Elsevier Ltd. All rights reserved. C1 NIAAA, Sect Nutr Neurosci, Lab Membrane Biophys & Biochem, NIH, Rockville, MD 20852 USA. RP Hibbeln, JR (reprint author), 31 Ctr Dr 31-1B58, Bethesda, MD USA. EM jhibbeln@mail.nih.gov FU Intramural NIH HHS NR 63 TC 15 Z9 18 U1 0 U2 7 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD OCT-NOV PY 2006 VL 75 IS 4-5 BP 227 EP 236 DI 10.1016/j.plefa.2006.07.014 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 097CG UT WOS:000241423400003 PM 16962306 ER PT J AU Fedorova, I Salem, N AF Fedorova, Irina Salem, Norman, Jr. TI Omega-3 fatty acids and rodent behavior SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Review ID POLYUNSATURATED FATTY-ACIDS; ALPHA-LINOLENIC ACID; BRAIN DOCOSAHEXAENOIC ACID; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; N-6 DOCOSAPENTAENOIC ACID; SPATIAL TASK-PERFORMANCE; BLOOD-PRESSURE LATER; MALE WISTAR RATS; LEARNING-ABILITY; DEFICIENT RATS AB This paper reviews the role of the n-3 fatty acids in the regulation of cognitive functions, locomotor and exploratory activity and emotional status in rodents. There are disparate data on the performance of n-3 fatty acid deficient animals in the open field test and elevated plus maze. Results obtained in our laboratory indicated slower habituation to the open field in deficient mice, which affects total locomotor and exploratory parameters. We also observed no change in plus maze performance of deficient mice under low-stress but elevated anxiety under high-stress conditions. There is some evidence of elevated aggression and increased immobility time in the forced swimming test caused by n-3 fatty acid deficiency in rodents. Effects of n-3 fatty acid deficiency and supplementation on learning in several tests such as the Morris water maze, two odor olfactory discriminations, radial arm maze performance and avoidance tasks are reviewed in detail. There is some evidence of an enhanced vulnerability to stress of n-3 fatty acid deficient animals and this factor can influence performance in a variety of tests. Thus, behavioral tasks that involve a higher level of stress may better differentiate behavioral effects related to brain docosahexaenoic acid (DHA) status. It is suggested that a fruitful area for future investigations of functional alterations related to brain DHA status will be the delineation of the factors underlying changes in performance in behavioral tasks. The possible role of non-cognitive factors like emotionality and attention in the impaired performance of n-3 fatty acid deficient animals also requires further investigation. (c) 2006 Elsevier Ltd. All rights reserved. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Salem, N (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, 5625 Fishers Lane,Room 3N-07,MSC 9410, Bethesda, MD 20892 USA. EM nsalem@niaaa.nih.gov RI Wilkinson, Stuart/C-2802-2013 FU Intramural NIH HHS NR 144 TC 152 Z9 154 U1 2 U2 26 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 EI 1532-2823 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD OCT-NOV PY 2006 VL 75 IS 4-5 BP 271 EP 289 DI 10.1016/j.plefa.2006.07.006 PG 19 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 097CG UT WOS:000241423400006 PM 16973342 ER PT J AU Nieminen, LRG Makino, KK Mehta, N Virkkunen, M Kim, HY Hibbeln, JR AF Nieminen, L. R. G. Makino, K. K. Mehta, N. Virkkunen, M. Kim, H. Y. Hibbeln, J. R. TI Relationship between omega-3 fatty acids and plasma neuroactive steroids in alcoholism, depression and controls SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; GABA(A) RECEPTOR FUNCTION; RAT-BRAIN; DOCOSAHEXAENOIC ACID; MAJOR DEPRESSION; STRESS; NEUROSTEROIDS; THDOC; GENE; PROGESTERONE AB Deficiency in the long-chain omega-3 fatty acid, docosahexaenoic acid (DHA) has been associated with increased corticotropin releasing hormone and may contribute to hypothalamic pituitary axis (HPA) hyperactivity. Elevated levels of the neuroactive steroids, allopregnanolone (3 alpha,5 alpha-THP) and 3 alpha,5 alpha-tetrahydrodeoxycorticosterone (THDOC) appear to counter-regulate HPA hyperactivity. Plasma essential fatty acids and neurosteroids were assessed among 18 male healthy controls and among 34 male psychiatric patients with DSM-III alcoholism, depression, or both. Among all subjects, lower plasma DHA was correlated with higher plasma THDOC (r = -0.3, P < 0.05) and dihydroprogesterone (DHP) (r = -0.52, P < 0.05). Among psychiatric patients lower DHA was correlated with higher DHP (r = -0.60, P < 0.01), and among healthy controls lower plasma DHA was correlated with higher THDOC (r = -0.83, P < 0.01) and higher isopregnanolone (3 beta,5 alpha-THP) (r = -0.55, P < 0.05). In this pilot observational study, lower long-chain omega-3 essential fatty acid status was associated with higher neuroactive steroid concentrations, possibly indicating increased feedback inhibition of the HPA axis. (c) 2006 Elsevier Ltd. All rights reserved. C1 NIAAA, NIH, Lab Membrane Biophys & Biochem, Bethesda, MD 20892 USA. Univ Helsinki, Cent Hosp, Dept Psychiat, FIN-00014 Helsinki, Finland. RP Hibbeln, JR (reprint author), NIAAA, NIH, Lab Membrane Biophys & Biochem, 31 Ctr Dr,31-1B 58, Bethesda, MD 20892 USA. EM jhibbeln@mail.nih.gov FU Intramural NIH HHS NR 34 TC 14 Z9 14 U1 0 U2 8 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD OCT-NOV PY 2006 VL 75 IS 4-5 BP 309 EP 314 DI 10.1016/j.plefa.2006.07.012 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 097CG UT WOS:000241423400009 PM 16959481 ER PT J AU Boeshans, KM Liu, F Peng, G Idler, W Jang, SI Marekov, L Black, L Ahvazi, B AF Boeshans, Karen M. Liu, Fang Peng, Guihong Idler, William Jang, Shyh-Ing Marekov, Lyuben Black, Lindsay Ahvazi, Bijan TI Purification, crystallization and preliminary X-ray diffraction analysis of the phage T4 vertex protein gp24 and its mutant forms SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE bacteriophage T4; capsid protein gp24; mutations; crystallization; surface entropy reduction; reductive methylation ID LYSINE RESIDUES; REDUCTIVE METHYLATION; BACTERIOPHAGE-T4; MUTATIONS; REQUIREMENT; RESOLUTION; ENTROPY; RHOGDI; HEAD; T4 AB The study of bacteriophage T4 assembly has revealed regulatory mechanisms pertinent not only to viruses but also to macromolecular complexes. The capsid of bacteriophage T4 is composed of the major capsid protein gp23, and a minor capsid protein gp24, which is arranged as pentamers at the vertices of the capsid. In this study the T4 capsid protein gp24 and its mutant forms were overexpressed and purified to homogeneity. The overexpression from plasmid vectors of all the constructs in Escherichia coli yields biologically active protein in vivo as determined by assembly of active virus following infection with inactivated gene 24 mutant viruses. The gp24 mutant was subjected to surface entropy reduction by mutagenesis and reductive alkylation in order to improve its crystallization properties and diffraction quality. To determine if surface mutagenesis targeting would result in diffractable crystals, two glutamate to alanine mutations (E89A,E90A) were introduced. We report here the biochemical observations and consequent mutagenesis experiment that resulted in improvements in the stability, crystallizability and crystal quality of gp24 without affecting the overall folding. Rational modification of the protein surface to achieve crystallization appears promising for improving crystallization behavior and crystal diffracting qualities. The crystal of gp24(E89A,E90A) diffracted to 2.6 angstrom resolution compared to wild-type gp24 at 3.80 angstrom resolution under the same experimental conditions. Surface mutation proved to be a better method than reductive methylation for improving diffraction quality of the gp24 crystals. Published by Elsevier Inc. C1 NIAMSD, NIH, Xray Crystalog Facil, Off Sci & Technol, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. RP Ahvazi, B (reprint author), NIAMSD, NIH, Xray Crystalog Facil, Off Sci & Technol, MSC 8024,50 S Dr,Bldg 50,Room 1345, Bethesda, MD 20892 USA. EM ahvazib@mail.nih.gov FU Intramural NIH HHS NR 29 TC 4 Z9 4 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD OCT PY 2006 VL 49 IS 2 BP 235 EP 243 DI 10.1016/j.pep.2006.05.021 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 093YK UT WOS:000241206000012 PM 16884923 ER PT J AU Chakkaravarthi, S Babu, MM Gromiha, MM Jayaraman, G Sethumadhavan, R AF Chakkaravarthi, S. Babu, M. Madan Gromiha, M. Michael Jayaraman, G. Sethumadhavan, R. TI Exploring the environmental preference of weak interactions in (alpha/beta)(8) barrel proteins SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE accessible surface area; amino acid preference; secondary structure; sequential separation; stabilizing residues; TIM-barrel; weak interactions ID CATION-PI INTERACTIONS; O HYDROGEN-BOND; LONG-RANGE INTERACTIONS; DATABASE-DERIVED POTENTIALS; DIFFERENT FOLDING TYPES; C-H; CRYSTALLOGRAPHIC EVIDENCE; STRUCTURAL-ANALYSIS; AMIDE INTERACTIONS; MEMBRANE-PROTEINS AB The environmental preference for the occurrence of noncanonical hydrogen bonding and cation-pi interactions, in a data set containing 71 nonredundant (alpha/beta)(8) barrel proteins, with respect to amino acid type, secondary structure, solvent accessibility, and stabilizing residues has been performed. Our analysis reveals some important findings, which include (a) higher contribution of weak interactions mediated by main-chain atoms irrespective of the amino acids involved; (b) domination of the aromatic amino acids among interactions involving side-chain atoms; (c) involvement of strands as the principal secondary structural unit, accommodating cross strand ion pair interaction and clustering of aromatic amino acid residues; (d) significant contribution to weak interactions occur in the solvent exposed areas of the protein; (e) majority of the interactions involve long-range contacts; (f) the preference of Arg is higher than Lys to form cation-pi interaction; and (g) probability of theoretically predicted stabilizing amino acid residues involved in weak interaction is higher for polar amino acids such as Trp, Glu, and Gln. On the whole, the present study reveals that the weak interactions contribute to the global stability of (alpha/beta)(8) TIM-barrel proteins in an environment-specific manner, which can possibly be exploited for protein engineering applications. C1 Vellore Inst Technol, Sch Biotechnol & Chem Engn, Vellore 632014, Tamil Nadu, India. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD USA. Natl Inst Adv Ind Sci & Technol, CBRC, Tokyo, Japan. RP Jayaraman, G (reprint author), Vellore Inst Technol, Sch Biotechnol & Chem Engn, Vellore 632014, Tamil Nadu, India. EM raman291068@yahoo.com; sethu_rao@sancharnet.in FU Medical Research Council [MC_U105185859] NR 68 TC 16 Z9 16 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD OCT 1 PY 2006 VL 65 IS 1 BP 75 EP 86 DI 10.1002/prot.21067 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 080PN UT WOS:000240260100009 PM 16835922 ER PT J AU Ravichandran, V Major, EO AF Ravichandran, Veerasamy Major, Eugene O. TI Viral proteomics: A promising approach for understanding JC virus tropism SO PROTEOMICS LA English DT Review DE Anchored-JCV-promoter; JC virus; proteomics technologies ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; HUMAN POLYOMAVIRUS-JC; NUCLEAR FACTOR-I; TRANSCRIPTIONAL CONTROL REGION; HEMATOPOIETIC PROGENITOR CELLS; LARGE-T-ANTIGEN; CEREBROSPINAL-FLUID; REGULATORY REGION; BINDING-SITES; HUMAN BRAIN AB The human polyomaviras JC virus (JCV) is responsible for the CNS demyelination observed in cases of progressive multifocal leukoencephalopathy. The JCV regulatory region (promoter) is a hypervariable, noncoding, nucleotide sequence positioned between the early and late protein-coding regions in the viral genome. Selective binding of cellular transcription factors to this promoter region participates in the control of viral tropism. Hence, further study of these proteins might provide new insights into JCV tropism and associated pathogenesis. This review gives an overview of viral proteomics - the study of all proteins expressed from the viral gene transcripts, and all the cellular proteins that play a role in JCV tropism. It also describes a new biochemical approach for studying relevant JCV promoter-binding proteins, which is an anchored-JCV transcriptional promoter (ATP) assay. An ATP assay utilizes the product of PCR-amplified JCV promoter sequences coupled with Sepharose beads in order to capture and isolate cellular nuclear proteins with specific promoter-binding affinity for analysis. Proteins that bind to JCV-ATPs can be eluted and subjected to proteomic analysis. Insights from this approach may improve the understanding of viral and cellular parameters that control JCV tropism. C1 NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, 10 Ctr Dr,Bldg 10,Room 3B14,MSC1296, Bethesda, MD 20892 USA. EM majorg@ninds.nih.gov FU Intramural NIH HHS NR 65 TC 12 Z9 13 U1 0 U2 0 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 OCT PY 2006 VL 6 IS 20 BP 5628 EP 5636 DI 10.1002/pmic.200600261 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 101ZT UT WOS:000241781100019 PM 16991198 ER PT J AU Wiener, L Battles, H Bernstein, D Long, L Derdak, J Mackall, CL Mansky, PJ AF Wiener, Lori Battles, Haven Bernstein, Donna Long, Lauren Derdak, Joanne Mackall, Crystal L. Mansky, Patrick J. TI Persistent psychological distress in long-term survivors of pediatric sarcoma: The experience at a single institution SO PSYCHO-ONCOLOGY LA English DT Article DE psychological distress; posttraumatic stress; pediatric sarcoma; long-term survivors; intensive treatment; cancer; oncology ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD-CANCER SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; QUALITY-OF-LIFE; STRUCTURED CLINICAL INTERVIEW; YOUNG-ADULT SURVIVORS; DSM-III-R; EWINGS-SARCOMA; ADOLESCENT CANCER; PSYCHOSOCIAL SEQUELAE AB Background: The long-term psychological impact of pediatric sarcoma is largely unknown. As part of a cross-sectional study examining the late effects of pediatric sarcoma therapy, we examined whether psychological distress or posttraumatic stress symptoms are present in an adult cohort of pediatric sarcoma survivors. Method: Thirty-four patients participated in the study, an average of 17 years after their treatment ended, each completing the SCID module for Posttraumatic Stress Disorder, Impact of Events Scale, Brief Symptom Inventory (BSI) and a questionnaire assessing sociodemographic variables and psychosocial issues. Results: Significant persistent psychological distress characterized this cohort of patients. Seventy-seven percent scored in the clinical range on the BSI. Twelve percent met diagnostic criteria for PTSD. Current psychological distress was associated with intrusive thoughts and avoidant behaviors, male gender, employment, difficulty readjusting to work/school after treatment, and enduring worries about health. No differences were found based on age, presence of metastatic disease or time since diagnosis. Conclusions: This is the first report of a clinical evaluation of psychological distress in a cohort of pediatric sarcoma survivors treated with intensive multimodal cancer therapy. The results suggest that survivors of pediatric sarcoma might be at high risk for adverse psychological outcomes. Appropriate interventions are proposed. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 NCI, Pediat Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Wiener, L (reprint author), 9000 Rockville Pike,10-10S255, Bethesda, MD 20892 USA. EM wienerl@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 78 TC 26 Z9 29 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD OCT PY 2006 VL 15 IS 10 BP 898 EP 910 DI 10.1002/pon.1024 PG 13 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 109LK UT WOS:000242309400006 PM 16402373 ER PT J AU Back, A Bakos, A Harris, L Lannamann, J McNamee, S AF Back, A. Bakos, A. Harris, L. Lannamann, J. McNamee, S. TI An interdisciplinary dialogue on the end of life impasse SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Washington Univ, Fred Hutchinson Canc Res Ctr, Washington, DC USA. NINR, Bethesda, MD 20892 USA. Natl Canc Inst, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. Univ New Hampshire, Dept Commun, Durham, NH 03824 USA. St Louis Univ, Hlth Commun Res Lab, St Louis, MO 63103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2006 VL 15 IS 2 SU S MA 616 BP S262 EP S263 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 110XF UT WOS:000242413901062 ER PT J AU Bellizzi, K AF Bellizzi, K. TI The application of developmental/aging theories to cancer survivorship research SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2006 VL 15 IS 2 SU S MA 141 BP S61 EP S61 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 110XF UT WOS:000242413900142 ER PT J AU Costantini, M Morasso, G Beccaro, M AF Costantini, M. Morasso, G. Beccaro, M. TI High prevalence of depressive symptoms among Italian surviving caregivers. Results from the Italian survey of the dying of cancer (ISDOC) SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Natl Canc Inst, Genoa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2006 VL 15 IS 2 SU S MA 297 BP S126 EP S126 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 110XF UT WOS:000242413900298 ER PT J AU Finney, RLJ AF Finney, Rutten L. J. TI The role of health communication theory in cancer treatment and survival SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Natl Canc Inst, SAIC Frederick, Div Canc Control & Populat Sci, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2006 VL 15 IS 2 SU S MA 142 BP S61 EP S61 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 110XF UT WOS:000242413900143 ER PT J AU Jeffery, D AF Jeffery, D. TI The application of psychosocial theories to cancer survivorship research SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2006 VL 15 IS 2 SU S MA 143 BP S61 EP S62 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 110XF UT WOS:000242413900144 ER PT J AU Ka'opua, LSI Kaluai, RK Meighen, P Mitchske, D Phosena, A AF Ka'opua, L. S., I Kaluai, R. K. Meighen, P. Mitchske, D. Phosena, A. TI Developing breast cancer screening education for native Hawaiian women: Use of 'talk story' dialogues SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Univ Hawaii, Sch Social Work, Honolulu, HI 96822 USA. Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. Natl Canc Inst, Canc Informat Serv, Honolulu, HI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2006 VL 15 IS 2 SU S MA 664 BP S283 EP S283 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 110XF UT WOS:000242413901110 ER PT J AU Morasso, G Costantini, M Di Leo, S Roma, S Miccinesi, G AF Morasso, G. Costantini, M. Di Leo, S. Roma, S. Miccinesi, G. TI End-of-life care in Italy: Understanding family dynamics. A qualitative study from the Italian survey of the Dying of Cancer (ISDOC) SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Natl Canc Inst, Unit Psycho Oncol, Genoa, Italy. Natl Canc Inst, Unit Clin Epidemiol, Genoa, Italy. CSPO, Florence, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2006 VL 15 IS 2 SU S MA 41 BP S18 EP S19 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 110XF UT WOS:000242413900042 ER PT J AU Herrell, R Henter, ID Mojtabai, R Bartko, JJ Venable, D Susser, E Merikangas, KR Wyatt, RJ AF Herrell, Richard Henter, Ioline D. Mojtabai, Ramin Bartko, John J. Venable, Diane Susser, Ezra Merikangas, Kathleen R. Wyatt, Richard J. TI First psychiatric hospitalizations in the US military: the National Collaborative Study of Early Psychosis and Suicide (NCSEPS) SO PSYCHOLOGICAL MEDICINE LA English DT Article ID EARLY-ONSET SCHIZOPHRENIA; HEALTH-CARE UTILIZATION; SOCIAL-CLASS; RISK-FACTORS; SOCIOECONOMIC-STATUS; MENTAL-DISORDERS; AFRICAN-AMERICAN; PERSIAN-GULF; ARMED-FORCES; COHORT AB Background. Military samples provide an excellent context to systematically ascertain hospitalization for severe psychiatric disorders. The National Collaborative Study of Early Psychosis and Suicide (NCSEPS), a collaborative study of psychiatric disorders in the US Armed Forces, estimated rates of first hospitalization in the military for three psychiatric disorders: bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia. Method. First hospitalizations for BD, MDD and schizophrenia were ascertained from military records for active duty personnel between 1992 and 1996. Rates were estimated as dynamic incidence (using all military personnel on active duty at the midpoint of each year as the denominator) and cohort incidence (using all military personnel aged 18-25 entering active duty between 1992 and 1996 to estimate person-years at risk). Results. For all three disorders, 8723 hospitalizations were observed in 8 120 136 person-years for a rate of 10(.)7/10 000 [95 % confidence interval (CI) 10(.)5-11(.)0]. The rate for BD was 2(.)0 (95 % CI 1(.)9-2(.)1), for MDD, 7(.)2 (95 % CI 7(.)0-7(.)3), and for schizophrenia, 1(.)6 (95 % CI 1(.)5-1(.)7). Rates for BD and MDD were greater in females than in males [for BD, rate ratio (RR) 2(.)0, 95 % CI 1(.)7-2(.)2; for MDD, RR 2(.)9, 95% CI 2(.)7-3(.)1], but no sex difference was found for schizophrenia. Blacks had lower rates than whites of BD (RR 0(.)8, 95 % CI 0(.)7-0(.)9) and MDD (RR 0(.)8, 95 % CI 0(.)8-0(.)9), but a higher rate of schizophrenia (RR 1(.)5, 95 % CI 1(.)3-1(.)7). Conclusions. This study underscores the human and financial burden that psychiatric disorders place on the US Armed Forces. C1 NIMH, Sect Dev Genet Epidemiol, Mood & Anxiety Disorders Program, NIH,DHHS, Bethesda, MD 20892 USA. NIMH, Neuropsychiat Branch, DDHS, NIH, New York, NY USA. Beth Israel Med Ctr, Dept Psychiat, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. New York State Psychiat Inst & Hosp, New York, NY 10027 USA. Columbia Univ, Coll Phys & Surg, Joseph L Mailman Sch Publ Hlth, New York, NY 10027 USA. RP Merikangas, KR (reprint author), NIMH, Sect Dev Genet Epidemiol, Mood & Anxiety Disorders Program, NIH,DHHS, 35 Convent Dr IA-201,MSC 3270, Bethesda, MD 20892 USA. EM merikank@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 77 TC 6 Z9 6 U1 5 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD OCT PY 2006 VL 36 IS 10 BP 1405 EP 1415 DI 10.1017/S0033291706008348 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 100LY UT WOS:000241671800007 PM 16879759 ER PT J AU Stinson, FS Ruan, WJ Pickering, R Grant, BF AF Stinson, Frederick S. Ruan, W. June Pickering, Roger Grant, Bridget F. TI Cannabis use disorders in the USA: prevalence, correlates and co-morbidity SO PSYCHOLOGICAL MEDICINE LA English DT Article ID NATIONAL EPIDEMIOLOGIC SURVEY; ALCOHOL-USE DISORDER; DRUG-USE DISORDERS; DSM-IV ALCOHOL; SUBSTANCE USE DISORDERS; COMORBIDITY SURVEY REPLICATION; INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; AGE-OF-ONSET; UNITED-STATES AB Background. The purpose of this study was to present 12-month and lifetime estimates of the prevalence, sociodemographic and clinical correlates, and psychiatric co-morbidity of DSM-IV cannabis abuse and dependence. Method. Data were derived from a large nationally representative survey (n = 43 093) of US adults. Results. The prevalence of 12-month and lifetime DSM-IV cannabis abuse (1(.)1% and 7(.)2%) exceeded the corresponding rates of cannabis dependence (0(.)3% and 1(.)3%). Being male, Native American, widowed/separated/divorced, and residing in the West increased the odds whereas being Black, Asian or Hispanic decreased the odds of cannabis abuse and dependence. Cannabis dependence was significantly associated with low income. Ages of onset for both cannabis use disorders occurred in adolescence and the majority of individuals with these disorders remained untreated. Co-morbidity was high between cannabis use disorders and other Axis I and II disorders. Conclusions. Cannabis use disorders continue to present a widespread and serious personal and public health problem. Native Americans were found to have high rates of cannabis use disorders, warranting closer attention to the mental health needs of this subgroup. Associations between cannabis abuse and dependence and Axis I and II disorders were strong, signaling the need for more comprehensive assessment of individuals with cannabis use disorders. Further controlled treatment studies are needed, especially among co-morbid individuals, in view of growing evidence of the adverse personal, medical and societal impacts of cannabis use disorders in the USA. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, MS 9304,5635 Fishers Lane,Room 3077, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov FU Intramural NIH HHS NR 92 TC 191 Z9 191 U1 9 U2 27 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD OCT PY 2006 VL 36 IS 10 BP 1447 EP 1460 DI 10.1017/S0033291706008361 PG 14 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 100LY UT WOS:000241671800011 PM 16854249 ER PT J AU Chemel, BR Roth, BL Armbruster, B Watts, VJ Nichols, DE AF Chemel, Benjamin R. Roth, Bryan L. Armbruster, Blaine Watts, Val J. Nichols, David E. TI WAY-100635 is a potent dopamine D-4 receptor agonist SO PSYCHOPHARMACOLOGY LA English DT Article DE WAY-100635; WAY-100634; 5-HT1A; D-4; D-2; receptor selectivity ID 5-HT1A RECEPTOR; ADENYLATE-CYCLASE; HUMAN BRAIN; ANTAGONIST; PET; SENSITIZATION; DELINEATION; NAD-299 AB Rationale and objectives WAY-100635 is a prototypical 5-HT1A receptor antagonist and has been used widely as a pharmacological probe to investigate the distribution and function of 5-HT1A receptors. Results from our studies suggested that WAY-100635 was potently inducing effects unrelated to its 5-HT1A receptor affinity. In the present work, we evaluated the in vitro pharmacology of this compound at two D-2-like receptor subtypes. Method The functional properties and binding affinities of WAY-100635 were evaluated in HEK 293 cells stably expressing dopamine D-2L or D-4.4 receptors. Results Initial screens performed by the NIMH Psychoactive Drug Screening Program indicated that WAY-100635 displayed 940, 370, and 16 nM binding affinities at D-2L, D-3, and D-4.2 receptors, respectively. Subsequent saturation analyses demonstrated that the K-d of [H-3]WAY-100635 at D-4.2 receptors was 2.4 nM, only tenfold higher than 5-HT1A. WAY-100635 and its major metabolite, WAY-100634, were potent agonists in HEK-D-4.4 cells (EC50=9.7 +/- 2.2 and 0.65 +/- 0.2 nM, respectively). WAY-100635 behaved as a full agonist, and WAY-100634 was a nearly full agonist. In HEK-D-2L cells, WAY-100635 weakly antagonized the effects of 300 nM quinpirole. Subsequent radioligand binding studies confirmed that WAY-100635 possesses high affinity for D-4.4 receptors but binds weakly to D-2L receptors (3.3 +/- 0.6 and 420 +/- 11 nM, respectively). Conclusions This study demonstrates that WAY-100635 is not a "selective" 5-HT1A receptor antagonist, as previously reported, and conclusions drawn from studies that employed WAY-100635 as a selective 5-HT1A antagonist may need to be reevaluated. C1 Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, NIMH Psychoact Drug Screening Program, Cleveland, OH 44106 USA. RP Nichols, DE (reprint author), Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, 575 Stadium Mall Dr, W Lafayette, IN 47907 USA. EM drdave@pharmacy.purdue.edu RI Roth, Bryan/F-3928-2010; Watts, Val/A-4633-2012 FU NIDA NIH HHS [DA02189]; NIMH NIH HHS [MH60397, K02MH01366]; PHS HHS [C06-14499] NR 17 TC 88 Z9 89 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 2006 VL 188 IS 2 BP 244 EP 251 DI 10.1007/s00213-006-0490-4 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 082IN UT WOS:000240380000012 PM 16915381 ER PT J AU Ronckers, CM Sigurdson, AJ Stovall, M Smith, SA Mertens, AC Liu, Y Hammond, S Land, CE Neglia, JP Donaldson, SS Meadows, AT Sklar, CA Robison, LL Inskip, PD AF Ronckers, Cecile M. Sigurdson, Alice J. Stovall, Marilyn Smith, Susan A. Mertens, Ann C. Liu, Yan Hammond, Sue Land, Charles E. Neglia, Joseph P. Donaldson, Sarah S. Meadows, Anna T. Sklar, Charles A. Robison, Leslie L. Inskip, Peter D. TI Thyroid cancer in childhood cancer survivors: A detailed evaluation of radiation dose response and its modifiers SO RADIATION RESEARCH LA English DT Article ID HODGKINS-DISEASE; POOLED ANALYSIS; BOMB SURVIVORS; RISK; FALLOUT; IRRADIATION; POPULATION; NEOPLASMS; EXPOSURE; THERAPY AB Radiation exposure at a young age is a strong risk factor for thyroid cancer. We conducted a nested case-control study of 69 thyroid cancer cases and 265 controls from a cohort of 14,054 childhood cancer survivors to evaluate the shape of the radiation dose-response relationship, in particular at high doses, and to assess modification of the radiation effects by patient and treatment characteristics. We considered several types of statistical models to estimate the excess relative risk (ERR), mainly guided by radiobiological models. A two-parameter model with a term linear in dose and a negative exponential in dose squared provided the best parsimonious description with an ERR of 1.3 per gray (95% confidence interval 0.4-4.1) at doses below 6 Gy and a relative decrease in ERR of 0.2% per unit dose squared with increasing dose, that is, decreases in the ERR/Gy of 53% at 20 Gy and 95% at 40 Gy. Further analyses using spline models suggested that the significant nonlinearity at high doses was characterized most appropriately as a true downturn rather than a flattening of the dose-response curve. We found no statistically significant modification of the dose-response relationship by patient characteristics; however, the linear parameter (i.e., the ERR/Gy at doses less than 6 Gy) did decrease consistently and linearly with increasing age at childhood cancer diagnosis, from 4.45 for 0-1-year-olds to 0.48 for 15-20-year-olds. In summary, we applied models derived from radiobiology to describe the radiation dose-response curve for thyroid cancer in an epidemiological study and found convincing evidence for a downturn in risk at high doses. (c) 2006 by Radiation Research Society C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98104 USA. Childrens Hosp, Dept Lab Med & Pathol, Columbus, OH 43205 USA. Ohio State Univ, Coll Med, Columbus, OH 43210 USA. Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. RP Ronckers, CM (reprint author), Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, Dept Pediat Oncol, POB 22660, NL-1100 DD Amsterdam, Netherlands. EM c.m.ronckers@amc.uva.nl FU Intramural NIH HHS; NCI NIH HHS [CA 55727] NR 42 TC 65 Z9 70 U1 0 U2 1 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD OCT PY 2006 VL 166 IS 4 BP 618 EP 628 DI 10.1667/RR3605.1 PG 11 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 089LV UT WOS:000240883000007 PM 17007558 ER PT J AU Sedelnikova, OA Nakamura, A Kovalchuk, O Koturbash, I Mitchell, SA Marino, SA Brenner, DJ Bonner, WM AF Sedelnikova, O. A. Nakamura, A. Kovalchuk, O. Koturbash, I. Mitchell, S. A. Marino, S. A. Brenner, D. J. Bonner, W. M. TI Long-term biological bystander effects of microbeam irradiation in 3D human tissue models SO RADIATION RESEARCH LA English DT Meeting Abstract CT 7th International Workshop on Microbeam Probes of Cellular Radiation Response CY MAR 15-17, 2006 CL Columbia Univ, New York, NY HO Columbia Univ ID DOUBLE-STRAND BREAKS C1 NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Lethbridge, Dept Sci Biol, Lethbridge, AB T1K 3M4, Canada. Columbia Univ, Ctr Radiol Res, Radiat Accelerator Res Facil, New York, NY 10032 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD OCT PY 2006 VL 166 IS 4 BP 687 EP 687 PG 1 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 089LV UT WOS:000240883000055 ER PT J AU Rosenberg, RD Yankaskas, BC Abraham, LA Sickles, EA Lehman, CD Geller, BM Carney, PA Kerlikowske, K Buist, DSM Weaver, DL Barlow, WE Ballard-Barbash, R AF Rosenberg, Robert D. Yankaskas, Bonnie C. Abraham, Linn A. Sickles, Edward A. Lehman, Constance D. Geller, Berta M. Carney, Patricia A. Kerlikowske, Karla Buist, Diana S. M. Weaver, Donald L. Barlow, William E. Ballard-Barbash, Rachel TI Performance benchmarks for screening mammography SO RADIOLOGY LA English DT Article ID BREAST-CANCER; DIAGNOSTIC MAMMOGRAPHY; QUALITY ASSURANCE; AMERICAN-COLLEGE; FAMILY HISTORY; MEDICAL AUDIT; UNITED-STATES; DATA SYSTEM; RADIOLOGISTS; VARIABILITY AB Purpose: To retrospectively evaluate the range of performance outcomes of the radiologist in an audit of screening mammography by using a representative sample of U. S. radiologists to allow development of performance benchmarks for screening mammography. Materials and Methods: Institutional review board approval was obtained, and study was HIPAA compliant. Informed consent was or was not obtained according to institutional review board guidelines. Data from 188 mammographic facilities and 807 radiologists obtained between 1996 and 2002 were analyzed from six registries from the Breast Cancer Surveillance Consortium (BCSC). Contributed data included demographic information, clinical findings, mammographic interpretation, and biopsy results. Measurements calculated were positive predictive values (PPVs) from screening mammography (PPV1), biopsy recommendation (PPV2), biopsy performed (PPV3), recall rate, cancer detection rate, mean cancer size, and cancer stage. Radiologist performance data are presented as 50th ( median), 10th, 25th, 75th, and 90th percentiles and as graphic presentations by using smoothed curves. Results: There were 2 580 151 screening mammographic studies from 1 117 390 women (age range, < 30 to >= 80 years). The respective means and ranges of performance outcomes for the middle 50% of radiologists were as follows: recall rate, 9.8% and 6.4% - 13.3%; PPV1, 4.8% and 3.4% - 6.2%; and PPV2, 24.6% and 18.8% - 32.0%. Mean cancer detection rate was 4.7 per 1000, and the mean size of invasive cancers was 13 mm. The range of performance outcomes for the middle 80% of radiologists also was presented. Conclusion: Community screening mammographic performance measurements of cancer outcomes for the majority of radiologists in the BCSC surpass performance recommendations. Recall rate for almost half of radiologists, however, is higher than the recommended rate. C1 1 Univ New Mexico, Dept Radiol, Hlth Sci Ctr, Albuquerque, NM 87131 USA. Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. Grp Hlth Ctr Hlth Studies, Seattle, WA USA. Canc Res & Biostat, Seattle, WA USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. Univ Vermont, Off Hlth Promot Res, Dept Pathol, Burlington, VT USA. Univ Vermont, Vermont Canc Ctr, Burlington, VT USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Hanover, NH USA. Univ Calif San Francisco, Gen Internal Med Sect, Dept Vet Affairs, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Rosenberg, RD (reprint author), 1 Univ New Mexico, Dept Radiol, Hlth Sci Ctr, MSC10 5530, Albuquerque, NM 87131 USA. EM rrosenb@unm.edu FU NCI NIH HHS [U01CA86076, U01 CA086082, U01CA63731, U01CA63740, U01CA70013, U01CA70040, U01CA86082-01]; PHS HHS [U0169976] NR 45 TC 171 Z9 174 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2006 VL 241 IS 1 BP 55 EP 66 DI 10.1148/radiol.2411051504 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 087TK UT WOS:000240765100008 PM 16990671 ER PT J AU Geller, BM Ichikawa, LE Buist, DSM Sickles, EA Carney, PA Yankaskas, BC Dignan, M Kerlikowske, K Yabroff, KR Barlow, W Rosenberg, RD AF Geller, Berta M. Ichikawa, Laura E. Buist, Diana S. M. Sickles, Edward A. Carney, Patricia A. Yankaskas, Bonnie C. Dignan, Mark Kerlikowske, Karla Yabroff, K. Robin Barlow, William Rosenberg, Robert D. CA Breast Canc Surveillance Consortiu TI Improving the concordance of mammography assessment and management recommendations SO RADIOLOGY LA English DT Article AB Purpose: To retrospectively compare the concordance of initial and final assessment categories for mammograms with management recommendations made before and after the final rules of the Mammography Quality Standards Act (MQSA) were in effect for screening and diagnostic mammography. Materials and Methods: The study included mammograms from 1996 to 2001 from the seven mammography registries of the Breast Cancer Surveillance Consortium (BCSC). The authors defined the pre-MQSA period as January 1, 1996 - April 27, 1999, and the post-MQSA period as April 28, 1999 - December 31, 2001 ( 2 470 151 screening and 194 199 diagnostic mammograms). Assessment was cross-classified according to management recommendation. Changes in concordance between assessment and recommendation were evaluated by year and by period (before and after MQSA) for computer-linked data and for all data by using Pearson chi(2) test to evaluate differences. Mantel-Haenszel chi(2) test was used to measure change in concordance over time. Each registry and the BCSC Statistical Coordinating Center had a Federal Certificate of Confidentiality and approval from each institution's review board for protection of human subjects to collect and send data to coordinating center and conduct research with these data. Active consent was required at only one site in this HIPAA-compliant study. Results: Concordance increased significantly in the post-MQSA period for Breast Imaging Reporting and Data System categories 3 - 5 assessments at both screening and diagnostic mammography. The most substantial improvements were in the use of the management recommendation for "additional imaging," which decreased from 41% in 1996 to 15% in 2001 for screening mammograms with an initial assessment of category 4 (P < .001). Recommendation for short-interval follow-up in women with screening mammograms with a category 3 final assessment increased from 51% in 1996 to 76% in 2001 (P < .001). Concordance for diagnostic mammograms assigned category 0 improved from 65% in the pre-MQSA period to 81% in the post-MQSA period (P < .001). Conclusion: This analysis demonstrates that over a relatively short period of time, major improvement in radiology reporting has occurred. C1 Univ Vermont, Off Hlth Promot Res, Burlington, VT 05401 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Dartmouth Coll Sch Med, Norris Cotton Canc Ctr, Lebanon, NH USA. Univ N Carolina, Chapel Hill, NC USA. Cooper Inst, Denver, CO USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ New Mexico, Albuquerque, NM 87131 USA. RP Geller, BM (reprint author), Univ Vermont, Off Hlth Promot Res, 1 S Prospect St,Rm 4427D, Burlington, VT 05401 USA. EM berta.geller@uvm.edu OI Yabroff, K. Robin/0000-0003-0644-5572 FU NCI NIH HHS [U01CA70013, U01 CA086082, U01CA63731, U01CA63736, U01CA63740, U01CA69976, U01CA70040, U01CA86076, U01CA86082] NR 7 TC 20 Z9 20 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2006 VL 241 IS 1 BP 67 EP 75 DI 10.1148/radiol.2411051375 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 087TK UT WOS:000240765100009 PM 16990672 ER PT J AU Wang, T Bar-Sela, G Huang, L Sun, L Nguyen, P Pennington, J Gius, D AF Wang, T. Bar-Sela, G. Huang, L. Sun, L. Nguyen, P. Pennington, J. Gius, D. TI Boris epigenetically influences survival transcription factors SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT Conference of the Spanish-Portuguese-and -Latin-American-Association CY OCT 09, 2006 CL Leipzig, GERMANY SP Spainsh Portuguese & Latin- Amer Assoc C1 Natl Canc Inst, Radiat Oncol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2006 VL 81 SU 1 MA 1179 BP S479 EP S479 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 115FB UT WOS:000242719101488 ER PT J AU Becker, RA Borgert, CJ Webb, S Ansell, J Amundson, S Portier, CJ Goldberg, A Bruner, LH Rowan, A Curren, RD Stott, WT AF Becker, Richard A. Borgert, Christopher J. Webb, Simon Ansell, Jay Amundson, Sara Portier, Christopher J. Goldberg, Alan Bruner, Leon H. Rowan, Andrew Curren, Rodger D. Stott, William T. TI Report of an ISRTP Workshop: Progress and barriers to incorporating alternative toxicological methods in the US SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE alternative testing methods; animal testing; regulatory toxicology AB The workshop objectives were to explore progress in implementing new, revised and alternative toxicological test methods across regulatory evaluation frameworks and decision-making programs in the United States, to identify barriers and to develop recommendations to further promote adoption of approaches that reduce, refine, or replace the use of animal methods. The workshop included sessions on: (1) current research, development, and validation of alternative methods within the U.S. federal government; (2) emerging alternative methodologies with potential applications to a broad spectrum of toxicity evaluation strategies; (3) tiered evaluation ("intelligent testing") strategies; and (4) identification of, and recommendations to address, critical barriers that affect adoption and use of new, revised alternative toxicological test methods by U.S. regulatory agencies. Through facilitated discussion, a list of barriers and recommendations were developed and grouped into categories of economic/financial, scientific/technical, and regulatory/policy. Overall, participants from all sectors collectively supported catalyzing actions to promote more meaningful and rapid progress for research to develop alternative methods focused for use in regulatory programs, accelerated lab investigations to validate such alternative methods and adoption of regulatory frameworks which embrace and incorporate these validated alternatives. Published by Elsevier Inc. C1 Amer Chem Council, Arlington, VA USA. Appl Pharmacol & Toxicol Inc, Gainesville, FL USA. Procter & Gamble Co, Strombeek Bever, Belgium. Yves Rocher N Amer Inc, Exton, PA USA. Doris Day Anim League, Washington, DC USA. NIEHS, Res Triangle Pk, NC 27709 USA. Johns Hopkins Univ, Ctr Alternat Anim Testing, Baltimore, MD USA. Gillette Co, Needham, MA USA. Humane Soc United States, Washington, DC USA. In Vitro Sci Inc, Gaithersburg, MD USA. Dow Chem Co USA, Midland, MI 48674 USA. RP Becker, RA (reprint author), Amer Chem Council, Arlington, VA USA. EM Rick_Becker@americanchemistry.com RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 0 TC 18 Z9 18 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD OCT PY 2006 VL 46 IS 1 BP 18 EP 22 DI 10.1016/j.yrtph.2006.06.001 PG 5 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 086WH UT WOS:000240703200002 PM 16876299 ER PT J AU Cadenhead, K Addington, J Cannon, T Cornblatt, B Heinssen, R McGlashan, TH Perkins, D Seidman, L Tsuang, M Walker, E Woods, S AF Cadenhead, K. Addington, J. Cannon, T. Cornblatt, B. Heinssen, R. McGlashan, Th. H. Perkins, D. Seidman, L. Tsuang, M. Walker, E. Woods, S. TI The development of the NAPLS dataset and baseline sample characteristics SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 5th International Conference on Early Psychosis CY OCT 04-06, 2006 CL Birmingham, ENGLAND C1 Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Toronto, Toronto, ON, Canada. Univ Calif Los Angeles, Los Angeles, CA USA. Zucker Hillside Hosp, Glen Oaks, NY USA. Yale Univ, New Haven, CT USA. Univ N Carolina, Chapel Hill, NC USA. Harvard Univ, Boston, MA 02115 USA. Emory Univ, Atlanta, GA 30322 USA. NIMH, Bethesda, MD 20892 USA. EM kcadenhead@ucsd.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2006 VL 86 SU S MA WC8D BP S18 EP S18 DI 10.1016/S0920-9964(06)70053-6 PG 1 WC Psychiatry SC Psychiatry GA 095RM UT WOS:000241325600053 ER PT J AU Cornblatt, B Addington, J Cadenhead, K Cannon, T Perkins, D Seidman, L Walker, E Woods, S McGlashan, TH Tsaung, M Heinssen, R AF Cornblatt, B. Addington, J. Cadenhead, K. Cannon, T. Perkins, D. Seidman, L. Walker, E. Woods, S. McGlashan, Th. H. Tsaung, M. Heinssen, R. TI NAPLS consortium: Impaired social, school, and work functioning characterizes prodromal individuals prior to emergence of psychosis SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 5th International Conference on Early Psychosis CY OCT 04-06, 2006 CL Birmingham, ENGLAND C1 Zucker Hillside Hosp, New York, NY USA. Univ Toronto, Toronto, ON, Canada. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Emory Univ, Atlanta, GA 30322 USA. Harvard Univ, Boston, MA 02115 USA. Yale Univ, New Haven, CT USA. Univ N Carolina, Chapel Hill, NC USA. NIMH, Washington, DC USA. EM cornblat@lij.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2006 VL 86 SU S MA WC8C BP S18 EP S18 DI 10.1016/S0920-9964(06)70052-4 PG 1 WC Psychiatry SC Psychiatry GA 095RM UT WOS:000241325600052 ER PT J AU Seidman, LJ Cornblatt, B Addington, J Cadenhead, K Cannon, T McGlashan, TH Perkins, DO Walker, E Woods, SW Tsuang, MT Heinssen, RK AF Seidman, L. J. Cornblatt, B. Addington, J. Cadenhead, K. Cannon, T. McGlashan, Th. H. Perkins, D. O. Walker, E. Woods, S. W. Tsuang, M. T. Heinssen, R. K. TI Neurocognitive functioning in the prodrome to psychosis from the NAPLS collaboration SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 5th International Conference on Early Psychosis CY OCT 04-06, 2006 CL Birmingham, ENGLAND C1 Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Albert Einstein Coll Med, Long Isl Jewish Med Ctr, Hillside Hosp, New York, NY USA. Univ Toronto, Dept Psychiat, Toronto, ON, Canada. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Yale Univ, Sch Med, Yale Psychiat Inst, New Haven, CT USA. Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Univ Calif San Diego, Dept Psychiat, Inst Behav Genom, San Diego, CA 92103 USA. NIMH, Div Mental Disorders, Bethesda, MD 20892 USA. NIMH, Div Behav Res, Bethesda, MD 20892 USA. NIMH, Div Aids, Bethesda, MD 20892 USA. EM Iseidman@bidmc.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2006 VL 86 SU S MA WC8B BP S17 EP S17 DI 10.1016/S0920-9964(06)70051-2 PG 1 WC Psychiatry SC Psychiatry GA 095RM UT WOS:000241325600051 ER PT J AU Woods, SW Addington, J Cadenhead, KS Cannon, TD Cornblatt, BA Perkins, DO Seidman, LJ Walker, EF Tsuang, MT McGlashan, TH Heinssen, RK AF Woods, S. W. Addington, J. Cadenhead, K. S. Cannon, T. D. Cornblatt, B. A. Perkins, D. O. Seidman, L. J. Walker, E. F. Tsuang, M. T. McGlashan, T. H. Heinssen, R. K. TI The criteria of prodromal syndromes and alternate prodromal diagnostic criteria in NAPLS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 5th International Conference on Early Psychosis CY OCT 04-06, 2006 CL Birmingham, ENGLAND C1 Yale Univ, New Haven, CT USA. Univ Toronto, Toronto, ON, Canada. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Zucker Hillside Hosp, New York, NY USA. Univ N Carolina, Chapel Hill, NC USA. Harvard Univ, Boston, MA 02115 USA. Emory Univ, Atlanta, GA 30322 USA. NIMH, Bethesda, MD 20892 USA. EM scott.woods@yale.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2006 VL 86 SU S MA WC8A BP S17 EP S17 DI 10.1016/S0920-9964(06)70050-0 PG 1 WC Psychiatry SC Psychiatry GA 095RM UT WOS:000241325600050 ER PT J AU Yamamoto, J Ikeda, A Kinoshita, M Matsumoto, R Satow, T Takeshita, K Matsuhashi, M Mikuni, N Miyamoto, S Hashimoto, N Shibasaki, H AF Yamamoto, Junichi Ikeda, Akio Kinoshita, Masako Matsumoto, Riki Satow, Takeshi Takeshita, Kazuhide Matsuhashi, Masao Mikuni, Nobuhiro Miyamoto, Susumu Hashimoto, Nobuo Shibasaki, Hiroshi TI Low-frequency electric cortical stimulation decreases interictal and ictal activity in human epilepsy SO SEIZURE-EUROPEAN JOURNAL OF EPILEPSY LA English DT Article DE low-frequency electric cortical stimulation; interictal epileptiform discharge; ictal activity ID TRANSCRANIAL MAGNETIC STIMULATION; CORTEX EXCITABILITY; LOBE EPILEPSY; SEIZURES AB We previously reported that low-frequency electric cortical stimulation (LFECS) directly applied to the epileptic focus by means of subdural electrodes decreased the number of interictal epileptiform discharges in patients with intractable partial epilepsy. In the present study, LFECS was applied to the epileptic foci directly in four patients with medically intractable partial epilepsy through subdural. electrodes and evaluated its effect on the number of interictal epileptiform discharges as well as simple partial seizures. We used alternating electric current of 0.3 ms duration presented at 0.9 Hz frequency for 250 s. LFECS did not induce seizures in any of the four patients. In one patient, the number of interictal epileptiform discharge decreased significantly by LFECS, which is in conformity with our previous report. In addition, LFECS applied to the seizure onset zone decreased the frequency of simple partial seizures in one patient. These results suggest that LFECS has an inhibitory effect not only on the interictal but also the ictal activities in patients with intractable partial epilepsy. Further study is required to determine the inhibitory effect of LFECS more in details. (C) 2006 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. C1 Kyoto Univ, Grad Sch Med, Human Brain Res Ctr, Sakyo Ku, Kyoto 6068507, Japan. Kyoto Univ, Grad Sch Med, Dept Neurol, Sakyo Ku, Kyoto 6068507, Japan. Kyoto Univ, Grad Sch Med, Dept Neurosurg, Sakyo Ku, Kyoto 6068507, Japan. Natl Cardiovasc Ctr, Dept Neurosurg, Osaka 5658565, Japan. NINDS, NIH, Bethesda, MD 20892 USA. RP Ikeda, A (reprint author), Kyoto Univ, Grad Sch Med, Human Brain Res Ctr, Sakyo Ku, Kyoto 6068507, Japan. EM akio@kuhp.kyoto-u.ac.jp RI Matsumoto, Riki/I-8397-2016; OI Matsumoto, Riki/0000-0003-3985-9210; Ikeda, Akio/0000-0002-0790-2598 NR 14 TC 31 Z9 35 U1 0 U2 4 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1059-1311 J9 SEIZURE-EUR J EPILEP JI Seizure PD OCT PY 2006 VL 15 IS 7 BP 520 EP 527 DI 10.1016/j.seizure.2006.06.004 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 089FC UT WOS:000240864700007 PM 16908203 ER PT J AU Romero, R Espinoza, J Goncalves, LF Kusanovic, JP Friel, LA Nien, JK AF Romero, Roberto Espinoza, Jimmy Goncalves, Luis F. Kusanovic, Juan Pedro Friel, Lara A. Nien, Jyh Kae TI Inflammation in preterm and term labour and delivery SO SEMINARS IN FETAL & NEONATAL MEDICINE LA English DT Article DE cytokines; preterm premature rupture of membranes; microbial invasion of the amniotic cavity; fetal inflammatory response syndrome; innate immunity; chemokines ID POLYMERASE-CHAIN-REACTION; TUMOR-NECROSIS-FACTOR; AMNIOTIC-FLUID INFECTION; INTRAUTERINE VIRAL-INFECTION; INTRAAMNIOTIC INFECTION; CLINICAL-SIGNIFICANCE; CHORIOAMNIOTIC MEMBRANES; PREMATURE LABOR; FACTOR-ALPHA; UREAPLASMA-UREALYTICUM AB Inflammation has been implicated in the mechanisms responsible for preterm and term parturition, as well as fetal injury. Out of all of the suspected causes of preterm labour and delivery, infection and/or inflammation is the only pathological process for which both a firm causal link with preterm birth has been established and a molecular pathophysiology defined. Inflammation has also been implicated in the mechanism of spontaneous parturition at term. Most cases of histopathological inflammation and histological chorioamnionitis, both in preterm and term labour, are sub-clinical in nature. The isolation of bacteria in the amniotic fluid, known as microbial invasion of the amniotic cavity, is a pathological finding; the frequency of which is dependent upon the clinical presentation and gestational age. There is a window of time during which it may be possible to detect a 'molecular signature of inflammation' by analysis of the transcriptome before histological evidence is observed. This article reviews the role of inflammation in preterm and term parturition. It is possible that modulation of inflammation using anti-inflammatory cytokines, corticoids, antioxidants and/or other factors may complement antibiotic therapy and limit fetal injury. Published by Elsevier Ltd. C1 NICHD, Perinatol Res Branch, DHHS, Hutzel Womens Hosp,NIH, Detroit, MI 48201 USA. NICHD, Perinatol Res Branch, DHHS, NIH, Detroit, MI USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, DHHS, Hutzel Womens Hosp,NIH, Box 4,3990 John R, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov FU Intramural NIH HHS NR 56 TC 272 Z9 278 U1 4 U2 24 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1744-165X J9 SEMIN FETAL NEONAT M JI Semin. Fetal Neonatal Med. PD OCT PY 2006 VL 11 IS 5 BP 317 EP 326 DI 10.1016/j.siny.2006.05.001 PG 10 WC Pediatrics SC Pediatrics GA 090QJ UT WOS:000240965600006 PM 16839830 ER PT J AU Wilson, WH AF Wilson, Wyndham H. TI Drug resistance in diffuse large B-cell lymphoma SO SEMINARS IN HEMATOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; SOUTHWEST-ONCOLOGY-GROUP; HIGH-DOSE THERAPY; PROGNOSTIC-SIGNIFICANCE; MULTIDRUG-RESISTANCE; AGGRESSIVE LYMPHOMA; EPOCH CHEMOTHERAPY; INDUCED APOPTOSIS; EXPRESSION; GENE C1 NCI, Ctr Canc Treatment, Bethesda, MD 20892 USA. RP Wilson, WH (reprint author), NCI, Ctr Canc Treatment, Bldg 10,Room 4N115,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov NR 56 TC 10 Z9 10 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2006 VL 43 IS 4 BP 230 EP 239 DI 10.1053/j.seminhematol.2006.07.005 PG 10 WC Hematology SC Hematology GA 094JE UT WOS:000241234900005 PM 17027657 ER PT J AU Sadarshan, S Linehan, WM AF Sadarshan, Sunil Linehan, W. Marston TI Genetics basis of cancer of the kidney SO SEMINARS IN ONCOLOGY LA English DT Review ID TUMOR-SUPPRESSOR GENE; RENAL-CELL CARCINOMA; HIPPEL-LINDAU-DISEASE; HOGG-DUBE-SYNDROME; PARENCHYMAL SPARING SURGERY; RADIO-FREQUENCY ABLATION; TYROSINE KINASE DOMAIN; GERMLINE MUTATIONS; VHL GENE; MET PROTOONCOGENE C1 NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, 10 Ctr Dr,MSC 1107,Bldg 10 CRC Room 1-5940, Bethesda, MD 20892 USA. EM linehanm@mail.nih.gov NR 86 TC 4 Z9 4 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 2006 VL 33 IS 5 BP 544 EP 551 DI 10.1053/j.seminoncol.2006.06.008 PG 8 WC Oncology SC Oncology GA 098RP UT WOS:000241540800004 ER PT J AU Signore, C Hemachandra, A Klebanoff, M AF Signore, Caroline Hemachandra, Anusha Klebanoff, Mark TI Neonatal mortality and morbidity after elective cesarean delivery versus routine expectant management: A decision analysis SO SEMINARS IN PERINATOLOGY LA English DT Review DE cesarean delivery; neonatal mortality; perinatal mortality; decision analysis; trial of labor ID RESPIRATORY-DISTRESS-SYNDROME; CEREBRAL-PALSY; NULLIPAROUS WOMEN; GESTATIONAL-AGE; RISK-FACTOR; TERM; SECTION; LABOR; MODE; INJURY C1 NICHD, DESPR, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Klebanoff, M (reprint author), NICHD, DESPR, NIH, Dept Hlth & Human Serv, 6100 Bldg,Room 7B05, Bethesda, MD 20892 USA. EM mk90h@nih.gov FU Intramural NIH HHS NR 60 TC 15 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0146-0005 J9 SEMIN PERINATOL JI Semin. Perinatol. PD OCT PY 2006 VL 30 IS 5 BP 288 EP 295 DI 10.1053/j.semperi.2006.07.010 PG 8 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 097LP UT WOS:000241449600011 PM 17011401 ER PT J AU Potter, D Goldenberg, RL Read, JS Wang, J Hoffman, IF Saathoff, E Kafulafula, G Aboud, S Martinson, FEA Dahab, M Vermund, SH AF Potter, Dara Goldenberg, Robert L. Read, Jennifer S. Wang, Jing Hoffman, Irving F. Saathoff, Elmar Kafulafula, George Aboud, Said Martinson, Francis E. A. Dahab, Maysoon Vermund, Sten H. TI Correlates of syphilis seroreactivity among pregnant women: The HIVNET 024 trial in Malawi, Tanzania, and Zambia SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID SEXUALLY-TRANSMITTED-DISEASES; IMMUNODEFICIENCY-VIRUS INFECTION; TO-CHILD TRANSMISSION; SUB-SAHARAN AFRICA; CONGENITAL-SYPHILIS; HIV-INFECTION; RISK-FACTORS; EPIDEMIOLOGIC SYNERGY; ANTENATAL SYPHILIS; MATERNAL SYPHILIS AB Objectives: The objectives of this cross-sectional study were to determine correlates of syphilis seroprevallence among HIV-infected and -uninfected antenatal attendees in an African multisite clinical trial, and to improve strategies for maternal syphilis prevention. Results: A total of 2270 (86%) women were HIV-infected and 366 (14%) were HIV-uninfected. One hundred seventy-five (6.6%) were syphillis-seropositive (7.3% among HIV-infected and 2.6% HIV-uninfected women). Statistically significant correlates included geographic site (odds ratio [OR] = 4.5, Blantyre; OR = 3.2, Lilongwe; OR = 9.0, Lusaka vs. Dar es Salaam referent); HIV infection (OR = 3.3); age 20 to 24 years (OR = 2.5); being divorced, widowed, or separated (OR = 2.9); genital ulcer treatment in the last year (OR = 2.9); history of stillbirth (OR = 2.8, one stillbirth; OR = 4.3, 2-5 stillbirths); and history of preterm delivery (OR = 2.7, one preterm delivery). Conclusion: Many women without identified risk factors were syphilis-seropositive. Younger HIV-infected women were at highest risk. Universal integrated antenatal HIV and syphilis screening and treatment is essential in sub-Saharan African settings. C1 Ctr Infect Dis Res Zambia, Lusaka, Zambia. Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA. Univ Alabama, Sch Med, Birmingham, AL 35294 USA. NICHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD USA. FHCRC, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA USA. Univ N Carolina, Chapel Hill, NC USA. UNC Project, Lilongwe, Malawi. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Malawi, Coll Med, Blantyre, Malawi. Muhimbili Univ, Coll Hlth Sci, Dar Es Salaam, Tanzania. Johns Hopkins Coll, Med Res Project, Blantyre, Malawi. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. RP Potter, D (reprint author), Ctr Infect Dis Res Zambia, Box 34681,5977 Benekale & Mwembeshi Rd, Lusaka, Zambia. EM dara@cidrz.org OI Vermund, Sten/0000-0001-7289-8698 FU FIC NIH HHS [D43 TW001035, D43 TW001035-07, D43 TW01035-07]; NIAID NIH HHS [U01 AI047972, N01 AI035173, N01 AI045200, N01-AI-35173-117/412, U01 AI047972-04, U01 AI048005, U01 AI048005-01, U01 AI048006, U01 AI048006-01, U01-AI-47972, U01-AI-480006, U01-AI-48005]; NICHD NIH HHS [1 F31 HD 046415-01, F31 HD046415, F31 HD046415-01] NR 49 TC 17 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD OCT PY 2006 VL 33 IS 10 BP 604 EP 609 DI 10.1097/01.olq.0000216029.00424.ae PG 6 WC Infectious Diseases SC Infectious Diseases GA 104ZK UT WOS:000241998900005 PM 16601659 ER PT J AU Klebanoff, MA Andrews, WW Yu, KF Brotman, RM Nansel, TR Zhang, J Cliver, SP Schwebke, JR AF Klebanoff, Mark A. Andrews, William W. Yu, Kai Fun Brotman, Rebecca M. Nansel, Tonja R. Zhang, Jun Cliver, Suzanne P. Schwebke, Jane R. TI A pilot study of vaginal flora changes with randomization to cessation of douching SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID BACTERIAL VAGINOSIS; GRAM STAIN; WOMEN; LACTOBACILLI AB Objectives: The objectives of this study were to determine whether women who douche regularly would enter a randomized trial of douching cessation or continuation, whether they would adhere to the assigned behavior, and whether there was a dramatic impact on vaginal flora. Goal: The goal of this study was to determine the feasibility of a large, definitive trial of douching cessation. Study Design: Women who douched at least weekly and who had either bacterial vaginosis or normal flora by Gram stain were assigned at random either to continue douching or to stop for 8 weeks. Vaginal Gram stains were obtained every 7 days from each woman. Results: Forty-eight women were randomized. Those assigned to continue reported douching during 77% of study weeks; those assigned to stop denied douching in 94% of weeks. No dramatic differences in flora were observed between women in the continue versus stop groups. Conclusion: A large randomized trial of douching cessation is feasible. C1 NICHD, DESPR, NIH, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. RP Klebanoff, MA (reprint author), NICHD, DESPR, NIH, 6100 Bldg,Room 7B05, Bethesda, MD 20892 USA. EM mk90h@nih.gov RI Brotman, Rebecca/H-5442-2011; OI Nansel, Tonja/0000-0002-8298-7595 FU NICHD NIH HHS [N0-1-HD-8-3293] NR 15 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD OCT PY 2006 VL 33 IS 10 BP 610 EP 613 DI 10.1097/01.olq.000021050.41305.c1 PG 4 WC Infectious Diseases SC Infectious Diseases GA 104ZK UT WOS:000241998900006 PM 16614585 ER PT J AU Patwardhan, AA Larson, MG Levy, D Benjamin, EJ Leip, EP Keyes, MJ Wang, TJ Gottlieb, DJ Vasan, RS AF Patwardhan, Anjali A. Larson, Martin G. Levy, Daniel Benjamin, Emelia J. Leip, Eric P. Keyes, Michelle J. Wang, Thomas J. Gottlieb, Daniel J. Vasan, Ramachandran S. TI Obstructive sleep apnea and plasma natriuretic peptide levels in a community-based sample SO SLEEP LA English DT Article DE sleep apnea syndromes; natriuretic peptides; cohort studies ID POSITIVE AIRWAY PRESSURE; HEART-FAILURE; BLOOD-PRESSURE; HEALTH; EXPRESSION; SECRETION; THERAPY; HORMONE; HYPOXIA; RELEASE AB Study Objectives: We hypothesized that alterations in cardiac hemodynamics associated with obstructive sleep apnea-hypopnea (OSAH) would be reflected in higher natriuretic peptide levels. We examined the association of OSAH with natriuretic peptides in a community-based sample. Design: Cross-sectional, retrospective, observational study. Setting: Framingham Heart Study Offspring Cohort and Sleep Heart Health Study. Participants: Community-based sample of 623 individuals. Measurements: Full-montage home polysomnography was used to determine apnea-hypopnea index (AHI) and percentage of time with an oxyhemoglobin saturation < 90% (PctLt90). Sensitive immunoradiometric assays were used to measure plasma B-type (BNP) and N-terminal pro-atrial natriuretic peptide (NT-ANP). Multivariable regression was used to examine the relations between natriuretic peptides and indicators of OSAH, adjusting for age, sex, body mass index, and clinical covariates. Results: No statistically significant relations between OSAH indices and BNP were observed in the multivariable model. Compared with an AHI < 5, relative levels of 1.20, 0.88, and 0.91 were observed for AHI categories 5-15, 15-30, > 30 events per hour, respectively. For NT-ANP, no significant relations were seen with AHI in the multivariable model (relative levels of 0.98, 0.91, and 0.90). An inverse association was observed between NT-ANP and PctLt90 in age- and sex-adjusted models (relative levels of 0,93, 0.87, and 0.80), although this association became statistically nonsignificant after adjusting for body mass index. Conclusion: Lack of association of natriuretic peptides with OSAH indices suggests that undiagnosed OSAH may not be associated with major alterations in left ventricular function, as reflected in morning natriuretic peptide levels. C1 Boston Univ, Sch Med, Boston, MA 02118 USA. VA Boston Healthcare Syst, W Roxbury, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. RP Gottlieb, DJ (reprint author), Boston Univ, Sch Med, Room R-304,715 Albany St, Boston, MA 02118 USA. EM dgottlieb@lung.bumc.bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970 NR 36 TC 24 Z9 24 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD OCT 1 PY 2006 VL 29 IS 10 BP 1301 EP 1306 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 100FL UT WOS:000241653400006 PM 17068983 ER PT J AU Chen, SX Qin, J AF Chen, Song Xi Qin, Jing TI An empirical likelihood method in mixture models with incomplete classifications SO STATISTICA SINICA LA English DT Article DE auxiliary information; empirical likelihood; genetic studies; mixture model; survey sampling; tax-auditing problem AB In studying the relationship between a binary variable and a covariate, it is very common that the value of the binary variable is missing for some observations, and subsequently those observations are uncategorised. In this paper we show that the uncategorised data can be treated as auxiliary information, as in survey sampling literature. We establish a framework of parametric and nonparametric estimation by the empirical likelihood. The proposed empirical likelihood estimators improve the efficiency of estimators based on the categorised samples in the leading order. In a comparative study with the ratio estimator, we show the reveal robust performance of the empirical likelihood estimators. Applications to tax-auditing and to genetic studies are discussed. C1 Iowa State Univ, Dept Stat, Ames, IA 50010 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Chen, SX (reprint author), Iowa State Univ, Dept Stat, Ames, IA 50010 USA. EM songchen@iastate.edu; jingqin@niaid.nih.gov OI Chen, Song Xi/0000-0002-2338-0873 NR 16 TC 2 Z9 2 U1 0 U2 1 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 J9 STAT SINICA JI Stat. Sin. PD OCT PY 2006 VL 16 IS 4 BP 1101 EP 1115 PG 15 WC Statistics & Probability SC Mathematics GA 108ZE UT WOS:000242276900003 ER PT J AU Milhavet, O Casanova, D Chevallier, N McKay, RDG Lehmann, S AF Milhavet, Ollivier Casanova, Danielle Chevallier, Nathalie McKay, Ronald D. G. Lehmann, Sylvain TI Neural stem cell model for prion propagation SO STEM CELLS LA English DT Article DE neural stem cells; prions; neural differentiation; diagnosis ID CENTRAL-NERVOUS-SYSTEM; SCRAPIE AGENT; NEUROBLASTOMA-CELLS; CNS NEURONS; IN-VITRO; PROTEIN; INFECTION; PRP; RESISTANT; DIFFERENTIATION AB The study of prion transmission and targeting is a major scientific issue with important consequences for public health. Only a few cell culture systems that are able to convert the cellular isoform of the prion protein into the pathologic scrapie isoform of the prion protein (PrPs) have been described. We hypothesized that central nervous system neural stem cells (NSCs) could be the basis of a new cell culture model permissive to prion infection. Here, we report that monolayers of differentiated fetal NSCs and adult multipotent progenitor cells isolated from mice were able to propagate prions. We also demonstrated the large influence of neural cell fate on the production of PrPSc, allowing the molecular study of prion neuronal targeting in relation with strain differences. This new stem cell-based model, which is applicable to different species and to transgenic mice, will allow thoughtful investigations of the molecular basis of prion diseases, and will open new avenues for diagnostic and therapeutic research. C1 CNRS, Inst Genet Humaine, UPR1142, F-34396 Montpellier 5, France. Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD USA. RP Milhavet, O (reprint author), CNRS, Inst Genet Humaine, UPR1142, 141 Rue Cardonille, F-34396 Montpellier 5, France. EM Ollivier.Milhavet@igh.cnrs.fr; Sylvain.Lehmann@igh.cnrs.fr NR 40 TC 23 Z9 24 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD OCT PY 2006 VL 24 IS 10 BP 2284 EP 2291 DI 10.1634/stemcells.2006-0088 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 090QM UT WOS:000240965900016 PM 16741225 ER PT J AU Hale, DA AF Hale, Douglas A. TI Basic transplantation immunology SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article ID DONOR BONE-MARROW; REGULATORY T-CELLS; RENAL-ALLOGRAFT SURVIVAL; ANTITHYMOCYTE GLOBULINS; KIDNEY-TRANSPLANTATION; HETEROLOGOUS IMMUNITY; HLA ANTIBODIES; HOMEOSTATIC PROLIFERATION; ORGAN-TRANSPLANTATION; MONOCLONAL-ANTIBODIES AB Humans are protected from a daily onslaught of pathogenic organisms by an immune system that provides multiple layers of protection. Until solid organ transplantation became technically feasible in the early twentieth century, this constant state of surveillance for foreign cells that are associated with the immune response mostly was viewed as advantageous. Unfortunately for patients who have end-stage failure of the heart, lungs, kidney, liver, and pancreas, the immune system is incapable of distinguishing between the presence of beneficial foreign tissue and harmful foreign pathogens; it mounts an effective attack against both. Improving our understanding of the factors that initiate and perpetuate the alloimmune response will result in the development of more refined and better tolerated immunosuppressive strategies. C1 NIDDKD, Transplantat Branch, NIH, Bethesda, MD 20892 USA. RP Hale, DA (reprint author), Univ Florida, Jacksonville Transplant Ctr Shands, 580 W 8th St,8000, Jacksonville, FL 32209 USA. EM Douglas.Hale@jax.ufl.edu FU Intramural NIH HHS NR 81 TC 12 Z9 12 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD OCT PY 2006 VL 86 IS 5 BP 1103 EP + DI 10.1016/j.suc.2006.06.015 PG 24 WC Surgery SC Surgery GA 093EB UT WOS:000241149500003 PM 16962404 ER PT J AU Becker, DV Braverman, LE Delange, F Dunn, JT Franklyn, JA Hollowell, JG Lamm, SH Mitchell, ML Pearce, E Robbins, J Rovet, JF AF Becker, David V. Braverman, Lewis E. Delange, Francois Dunn, John T. Franklyn, Jayne A. Hollowell, Joseph G. Lamm, Steven H. Mitchell, Marvin L. Pearce, Eizabeth Robbins, Jacob Rovet, Joanne F. CA Public Hlth Comm Amer Thyroid Asso TI Iodine supplementation for pregnancy and lactation - United States and Canada: Recommendations of the American Thyroid Association SO THYROID LA English DT Article ID NATIONAL-HEALTH; NUTRITION; MILK AB The fetus is totally dependent in early pregnancy on maternal thyroxine for normal brain development. Adequate maternal dietary intake of iodine during pregnancy is essential for maternal thyroxine production and later for thyroid function in the fetus. If iodine insufficiency leads to inadequate production of thyroid hormones and hypothyroidism during pregnancy, then irreversible fetal brain damage can result. In the United States, the median urinary iodine (UI) was 168 mu g/L in 2001-2002, well within the range of normal established by the World Health Organization (WHO), but whereas the UI of pregnant women (173 mu g/L; 95% CI 75-229 mu g/L) was within the range recommended by WHO (150-249 mu g/L), the lower 95% CI was less than 150 mu g/L. Therefore, until additional physiologic data are available to make a better judgment, the American Thyroid Association recommends that women receive 150 mu g iodine supplements daily during pregnancy and lactation and that all prenatal vitamin/mineral preparations contain 150 mu g of iodine. C1 New York Presbyterian Hosp, New York, NY USA. Boston Med Ctr, Boston, MA USA. Univ Birmingham, Queen Elizabeth Hosp, Div Med Sci, Birmingham B15 2TH, W Midlands, England. Univ Massachusetts, Sch Med, New England Newborn Screening Program, Boston, MA 02125 USA. NIH, Bethesda, MD 20892 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. RP Hollowell, JG (reprint author), 435 N 1500 Rd, Lawrence, KS 66049 USA. EM jgh3@mindspring.com NR 14 TC 117 Z9 124 U1 0 U2 7 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 OCT PY 2006 VL 16 IS 10 BP 949 EP 951 DI 10.1089/thy.2006.16.949 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 104TI UT WOS:000241981900002 ER PT J AU Chen, Q Zou, H Xu, XH Luo, M Wang, J Zuo, YQ Chen, YH Chen, XH Chen, XL Yao, ZQ Song, N Zeng, J Mi, XY Sun, SX Wang, JX Zhao, TM AF Chen, Q. Zou, H. Xu, X. H. Luo, M. Wang, J. Zuo, Y. Q. Chen, Y. H. Chen, X. H. Chen, X. L. Yao, Z. Q. Song, N. Zeng, J. Mi, X. Y. Sun, S. X. Wang, J. X. Zhao, T. M. TI Characterization of HLA-B*5516, -B*1313, -B*9512, and-DRB1*1457 alleles identified in a southwest Chinese population SO TISSUE ANTIGENS LA English DT Article DE DNA sequencing; HLA-B; DRB1 alleles; PCR-SSP; SNP ID HLA-B; DIVERSITY; ASSOCIATIONS; SEQUENCE; DRB3 AB The human leukocyte antigen (HLA)-B*5516 allele differs from the B*5502 by a single 97 T -> C substitution (His to Tyr at position 33) in exon 2. The B*1313 allele results from 419 T -> A and 420 A -> C substitutions, encoding a Leu to Tyr substitution at 140 in exon 2 of the B*1301 allele. The B*9512 allele differs from B*1502 by a single 360 G -> C substitution (Gln to His at 120) in exon 3. The DRB1*1457 allele appears to be a hybrid molecule generated by recombination between the DRB1*13 and DRB1*14 alleles. The serological equivalents of these new alleles are HLA-B22, -B13, -B15, and DR13, respectively. Family studies detected two rare haplotypes: A*11, B*9512, DRB1*14 and A*24, B*52, Cw*07, DRB1*1457, DRB3*020201, DQB1*050301. The gene frequencies of these alleles in the Chinese population are less than 0.0001. C1 Chinese Acad Med Sci, Inst Blood Transfus, Chengdu, Peoples R China. Sichuan Umbilical Cord Blood Bank, Chengdu, Peoples R China. NIH, Bethesda, MD 20892 USA. RP Zhao, TM (reprint author), NIAID, Mol & Cellular Immunogenet Sect, Bldg 50,Room 5511,50 S Dr, Bethesda, MD 20892 USA. EM tzhao@niaid.nih.gov NR 9 TC 2 Z9 3 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD OCT PY 2006 VL 68 IS 4 BP 339 EP 343 DI 10.1111/j.1399-0039.2006.00669.x PG 5 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 092PP UT WOS:000241110100012 PM 17026471 ER PT J AU Zhang, WB Walboomers, XF Shi, ST Fan, MW Jansen, JA AF Zhang, Weibo Walboomers, X. Frank Shi, Songtao Fan, Mingwen Jansen, John A. TI Multilineage differentiation potential of stem cells derived from human dental pulp after cryopreservation SO TISSUE ENGINEERING LA English DT Article ID BONE-MARROW; PROGENITOR CELLS; GENE-EXPRESSION; ADIPOSE-TISSUE; IN-VITRO; MUSCLE; LINEAGE; BLOOD; MICE AB The current study aimed to prove that human dental pulp stem cells (hDPSCs) isolated from the pulp of third molars can show multilineage differentiation after cryopreservation. First, hDPSC were isolated via enzymatic procedures, and frozen in liquid nitrogen until use. After defrosting, cells were analyzed for proliferative potential and the expression of the stem cell marker STRO-1. Subsequently, cells were cultured in neurogenic, osteogenic/odontogenic, adipogenic, myogenic, and chondrogenic inductive media, and analyzed on basis of morphology, immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR) for specific marker genes. All data were replicated, and the results of the primary cells were compared to similar tests with an additional primary dental pulp stem cell strain, obtained from the National Institutes of Health (NIH). Results showed that our cell population could be maintained for at least 25 passages. The existence of stem/progenitor cells in both cell strains was proven by the STRO-1 staining. Under the influence of the 5 different media, both cell strains were capable to advance into all 5 differentiation pathways. Still differences between both strains were found. In general, our primary culture performed better in myogenic differentiation, while the externally obtained cells were superior in the odontogenic/osteogenic and chondrogenic differentiation pathways. In conclusion, the pulp tissue of the third molar may serve as a suitable source of multipotent stem cells for future tissue engineering strategies and cell-based therapies, even after cryopreservation. C1 Radboud Univ Nijmegen, Med Ctr, Dept Peridontol & Biomat, NL-6500 HB Nijmegen, Netherlands. NIDCR, NIH, Bethesda, MD USA. Wuhan Univ, Sch Stomatol, Wuhan 430072, Peoples R China. RP Jansen, JA (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Peridontol & Biomat, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM J.Jansen@dent.umcn.nl RI Zhang, Weibo/S-1546-2016; Walboomers, X.Frank/B-3692-2013; Jansen, J.A./H-8055-2014 OI Zhang, Weibo/0000-0001-6246-2487; NR 41 TC 163 Z9 175 U1 2 U2 26 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD OCT PY 2006 VL 12 IS 10 BP 2813 EP 2823 DI 10.1089/ten.2006.12.2813 PG 11 WC Cell & Tissue Engineering SC Cell Biology GA 105PU UT WOS:000242045600011 PM 17518650 ER PT J AU Tran, SD Sugito, T Dipasquale, G Cotrim, AP Bandyopadhyay, BC Riddle, K Mooney, D Kok, MR Chiorini, JA Baum, BJ AF Tran, Simon D. Sugito, Takayuki Dipasquale, Giovanni Cotrim, Ana P. Bandyopadhyay, Bidhan C. Riddle, Kathryn Mooney, David Kok, Marc R. Chiorini, John A. Baum, Bruce J. TI Re-engineering primary epithelial cells from rhesus monkey parotid glands for use in developing an artificial salivary gland SO TISSUE ENGINEERING LA English DT Article ID GENE-TRANSFER; SJOGRENS-SYNDROME; MEDIATED TRANSFER; TIGHT JUNCTIONS; ORAL-CAVITY; IN-VIVO; FLUID; SECRETION; RADIATION; MODEL AB There is no satisfactory conventional treatment for patients who experience irreversible salivary gland damage after therapeutic radiation for head and neck cancer or because of Sjogren's syndrome. Additionally, if most parenchyma is lost, these patients also are not candidates for evolving gene transfer strategies. To help such patients, several years ago we began to develop an artificial salivary gland. In the present study, we used a non-human primate tissue source, parotid glands from rhesus monkeys, to obtain potential autologous graft cells for development of a prototype device for in situ testing. Herein, we present 3 major findings. First, we show that primary cultures of rhesus parotid gland (RPG) cells are capable of attaining a polarized orientation, with Na+/K+-adenosine triphosphatase, zonula occludens-1, and claudin-1 distributed in specific domains appropriate for epithelial cells. Second, we show that RPG cells exhibit 2 essential epithelial functions required for graft cells in an artificial salivary gland device (i.e., an effective barrier to paracellular water flow and the generation of a moderate transepithelial electrical resistance). Third, we show that RPG cells can express functional water channels, capable of mediating directional fluid movement, after transduction by adenoviral and adeno-associated virus type 2 vectors. Together these results demonstrate that it is feasible to individually prepare RPG cells for eventual use in a prototype artificial salivary gland. C1 NIDCR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD USA. McGill Univ, Fac Dent, Montreal, PQ, Canada. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. Harvard Univ, Div Engn & Appl Sci, Cambridge, MA 02138 USA. Univ Amsterdam, Acad Med Ctr, Dept Clin Immunol & Rheumatol, NL-1105 AZ Amsterdam, Netherlands. RP Baum, BJ (reprint author), NIDCR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD USA. EM bbaum@dir.nidcr.nih.gov FU Intramural NIH HHS NR 30 TC 25 Z9 27 U1 1 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD OCT PY 2006 VL 12 IS 10 BP 2939 EP 2948 DI 10.1089/ten.2006.12.2939 PG 10 WC Cell & Tissue Engineering SC Cell Biology GA 105PU UT WOS:000242045600022 PM 17518661 ER PT J AU McCardle, P Leung, CYY AF McCardle, Peggy Leung, Christy Y. Y. TI Foreword SO TOPICS IN LANGUAGE DISORDERS LA English DT Editorial Material C1 NICHHD, Ctr Res Mothers & Children, Rockville, MD USA. Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. RP McCardle, P (reprint author), NICHHD, Ctr Res Mothers & Children, Rockville, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-8294 J9 TOP LANG DISORD JI Top. Lang. Disord. PD OCT-DEC PY 2006 VL 26 IS 4 BP 300 EP 301 PG 2 WC Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA 105WZ UT WOS:000242064300002 ER PT J AU McCardle, P Leung, CYY AF McCardle, Peggy Leung, Christy Y. Y. TI English language learners: Development an intervention - An introduction SO TOPICS IN LANGUAGE DISORDERS LA English DT Editorial Material C1 NICHHD, Ctr Res Mothers & Children, Rockville, MD USA. Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. RP McCardle, P (reprint author), NICHHD, Ctr Res Mothers & Children, Rockville, MD USA. NR 11 TC 3 Z9 3 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-8294 J9 TOP LANG DISORD JI Top. Lang. Disord. PD OCT-DEC PY 2006 VL 26 IS 4 BP 302 EP 304 PG 3 WC Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA 105WZ UT WOS:000242064300003 ER PT J AU Van den Berg, M Birnbaum, LS Denison, M De Vito, M Farland, W Feeley, M Fiedler, H Hakansson, H Hanberg, A Haws, L Rose, M Safe, S Schrenk, D Tohyama, C Tritscher, A Tuomisto, J Tysklind, M Walker, N Peterson, RE AF Van den Berg, Martin Birnbaum, Linda S. Denison, Michael De Vito, Mike Farland, William Feeley, Mark Fiedler, Heidelore Hakansson, Helen Hanberg, Annika Haws, Laurie Rose, Martin Safe, Stephen Schrenk, Dieter Tohyama, Chiharu Tritscher, Angelika Tuomisto, Jouko Tysklind, Mats Walker, Nigel Peterson, Richard E. TI The 2005 World Health Organization reevaluation of human and mammalian toxic equivalency factors for dioxins and dioxin-like compounds SO TOXICOLOGICAL SCIENCES LA English DT Review DE dioxins; dibenzofurans; PCBs; TEFs; reevaluation; WHO ID DIBENZO-P-DIOXINS; ARYL-HYDROCARBON RECEPTOR; SPRAGUE-DAWLEY RATS; BROMINATED FLAME RETARDANTS; INDIVIDUAL POLYCHLORINATED NAPHTHALENES; POLYBROMINATED DIPHENYL ETHERS; SUBCHRONIC DIETARY EXPOSURE; DOSE-RESPONSE RELATIONSHIPS; TUMOR PROMOTING ACTIVITY; CYP1A2 ENZYME-ACTIVITY AB In June 2005, a World Health Organization (WHO)-International Programme on Chemical Safety expert meeting was held in Geneva during which the toxic equivalency factors (TEFs) for dioxin-like compounds, including some polychlorinated biphenyls (PCBs), were reevaluated. For this reevaluation process, the refined TEF database recently published by Haws et al. (2006, Toxicol. Sci. 89, 4-30) was used as a starting point. Decisions about a TEF value were made based on a combination of unweighted relative effect potency (REP) distributions from this database, expert judgment, and point estimates. Previous TEFs were assigned in increments of 0.01, 0.05, 0.1, etc., but for this reevaluation, it was decided to use half order of magnitude increments on a logarithmic scale of 0.03, 0.1, 0.3, etc. Changes were decided by the expert panel for 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) (TEF = 0.3), 1,2,3,7,8-pentachlorodibenzofuran (PeCDF) (TEF = 0.03), octachlorodibenzo-p-dioxin and octachlorodibenzofuran (TEFs = 0.0003), 3,4,4',5-tetrachlorbiphenyl (PCB 81) (TEF = 0.0003), 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169) (TEF = 0.03), and a single TEF value (0.00003) for all relevant mono-ortho-substituted PCBs. Additivity, an important prerequisite of the TEF concept was again confirmed by results from recent in vivo mixture studies. Some experimental evidence shows that non-dioxin-like aryl hydrocarbon receptor agonists/antagonists are able to impact the overall toxic potency of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds, and this needs to be investigated further. Certain individual and groups of compounds were identified for possible future inclusion in the TEF concept, including 3,4,4'-TCB (PCB 37), polybrominated dibenzo-p-dioxins and dibenzofurans, mixed polyhalogenated dibenzo-p-dioxins and dibenzofurans, polyhalogenated naphthalenes, and polybrominated biphenyls. Concern was expressed about direct application of the TEF/total toxic equivalency (TEQ) approach to abiotic matrices, such as soil, sediment, etc., for direct application in human risk assessment. This is problematic as the present TEF scheme and TEQ methodology are primarily intended for estimating exposure and risks via oral ingestion (e.g., by dietary intake). A number of future approaches to determine alternative or additional TEFs were also identified. These included the use of a probabilistic methodology to determine TEFs that better describe the associated levels of uncertainty and "systemic" TEFs for blood and adipose tissue and TEQ for body burden. C1 Univ Utrecht, Fac Vet Med, Collaborating Ctr Res Environm Hlth Risk Assessme, WHO, NL-3508 TD Utrecht, Netherlands. Univ Utrecht, Fac Vet Med, Inst Risk Assessment Sci, NL-3508 TD Utrecht, Netherlands. Univ Utrecht, Med Ctr, NL-3508 TD Utrecht, Netherlands. US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27709 USA. Univ Calif Davis, Dept Environm Toxicol, Davis, CA 95616 USA. US EPA, Off Res & Dev, Washington, DC 20460 USA. Hlth Canada, Bur Chem Safety, Chem Hlth Hazard Assessment Div, Ottawa, ON K1A 0L2, Canada. UN, Environm Program Chem, Int Environm House, CH-1219 Chatelaine, GE, Switzerland. Karolinska Inst, Inst Environm Med, Unit Environm Hlth Risk Assessment, S-17177 Stockholm, Sweden. ChemRisk, Austin, TX USA. Cent Sci Lab, York YO41 1LZ, N Yorkshire, England. Texas A&M Univ, College Stn, TX 77843 USA. Univ Kaiserslautern, Dept Food Chem & Environm Toxicol, D-67663 Kaiserslautern, Germany. Univ Tokyo, Grad Sch Med, Ctr Dis Biol & Integrat Med, Div Environm Hlth Sci,Bunkyo Ku, Tokyo 1130033, Japan. WHO, Int Programme Chem Safety, CH-1211 Geneva 27, Switzerland. Dept Environm Hlth, Natl Publ Hlth Inst, FI-70701 Kuopio, Finland. Umea Univ, SE-90187 Umea, Sweden. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA. Univ Wisconsin, Mol & Environm Toxicol Ctr, Madison, WI 53705 USA. RP Van den Berg, M (reprint author), Univ Utrecht, Fac Vet Med, Collaborating Ctr Res Environm Hlth Risk Assessme, WHO, POB 80177, NL-3508 TD Utrecht, Netherlands. EM m.vandenberg@iras.uu.nl RI Tuomisto, Jouko/J-7450-2012; Walker, Nigel/D-6583-2012; Fiedler, Heidelore/P-6115-2015; OI Walker, Nigel/0000-0002-9111-6855; Fiedler, Heidelore/0000-0003-1496-9245; Hanberg, Annika/0000-0001-7255-9856; Rose, Martin/0000-0001-7071-180X FU Intramural NIH HHS [Z99 ES999999] NR 129 TC 1556 Z9 1609 U1 43 U2 390 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 2006 VL 93 IS 2 BP 223 EP 241 DI 10.1093/toxsci/kfl055 PG 19 WC Toxicology SC Toxicology GA 084NM UT WOS:000240540000001 PM 16829543 ER PT J AU Cover, C Liu, J Farhood, A Malle, E Waalkes, MP Bajt, ML Jaeschke, H AF Cover, Cathleen Liu, Jie Farhood, Anwar Malle, Ernst Waalkes, Michael P. Bajt, Mary Lynn Jaeschke, Hartmut TI Pathophysiological role of the acute inflammatory response during acetaminophen hepatotoxicity SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE neutrophils; inflammation; cytokines; oxidant stress; hypochlorite; NAPDH oxidase ID ISCHEMIA-REPERFUSION INJURY; INDUCED LIVER-INJURY; INTERCELLULAR-ADHESION MOLECULE-1; HYPOCHLORITE-MODIFIED PROTEINS; DUCT-LIGATED MICE; OXIDANT STRESS; RAT-LIVER; KUPFFER CELLS; IN-VIVO; FUNCTIONAL-SIGNIFICANCE AB Neutrophils are recruited into the liver after acetaminophen (AAP) overdose but the pathophysiological relevance of this acute inflammatory response remains unclear. To address this question, we compared the time course of liver injury, hepatic neutrophil accumulation and inflammatory gene mRNA expression for up to 24 h after treatment with 300 mg/kg AAP in C3Heb/FeJ and C57BL/6 mice. Although there was no relevant difference in liver injury (assessed by the increase of plasma alanine aminotransferase activities and the areas of necrosis), the number of neutrophils and the expression of several pro-inflammatory genes (e.g., tumor necrosis factor-alpha, interleukin-1 beta and macrophage inflammatory protein-2) was higher in C3Heb/FeJ than in C57BL/6 mice. In contrast, the expression of the anti-inflammatory genes interieukin-10 and heme oxygenase-1 was higher in C57BL/6 mice. Despite substantial hepatic neutrophil accumulation, none of the liver sections from both strains stained positive for hypochlorite-modified proteins, a specific marker for a neutrophil-induced oxidant stress. In addition, treatment with the NADPH oxidase inhibitors diphenyleneiodonium, chloride or apocynin or the anti-neutrophil antibody Gr-1 did not protect against AAP hepatotoxicity. Furthermore, although intercellular adhesion molecule-1 (ICAM-1) was previously shown to be important for neutrophil extravasation and tissue injury in several models, ICAM-1-deficient mice were not protected against AAP-mediated liver injury. Together, these data do not support the hypothesis that neutrophils aggravate liver injury induced by AAP overdose. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Arizona, Coll Med, Liver Res Inst, Tucson, AZ 85724 USA. NIEHS, Inorgan Carcinogenesis Sect, Lab Comparat Carcinogenesis, NCI, Res Triangle Pk, NC 27709 USA. Brackenridge Hosp, Dept Pathol, Austin, TX 78701 USA. Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, A-8010 Graz, Austria. RP Jaeschke, H (reprint author), Univ Arizona, Coll Med, Liver Res Inst, 1501 N Campbell Ave,Room 6309, Tucson, AZ 85724 USA. EM jaeschke@email.arizona.edu RI Malle, Ernst/D-3071-2013 FU Intramural NIH HHS; NIAAA NIH HHS [R01 AA 12916]; NIDDK NIH HHS [R01 DK 070195] NR 62 TC 74 Z9 75 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT 1 PY 2006 VL 216 IS 1 BP 98 EP 107 DI 10.1016/j.taap.2006.04.010 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 091CZ UT WOS:000241005100011 PM 16781746 ER PT J AU Hsia, CC Purcell, RH Farshid, M Lachenbruch, PA Yu, MYW AF Hsia, Chu Chieh Purcell, Robert H. Farshid, Mahmood Lachenbruch, Peter A. Yu, Mei-ying W. TI Quantification of hepatitis B virus genomes and infectivity in human serum samples SO TRANSFUSION LA English DT Article ID NUCLEIC-ACID AMPLIFICATION; REAL-TIME PCR; HBV-DNA; BLOOD-DONATIONS; DETECTION SYSTEM; COMPETITIVE PCR; HBSAG SUBTYPES; TAQMAN PCR; QUANTITATION; ASSAY AB Hepatitis B virus (HBV) infections are still a major health issue, with approximately 350 million people chronically infected with HBV worldwide. Information about the minimum copy number of HBV genomes required for infection would be useful as a reference for drug and vaccine development; for monitoring HBV patients during treatment; for screening of blood, organ, and tissue donors; and for regulating nucleic acid amplification assays for HBV. Serum samples from chronic carriers (hepatitis B surface antigen-positive and antibody to HBV core antigen-positive) of the three most common subtypes of HBV were studied; their infectivity titers had been evaluated previously in chimpanzees. The genotypes of the HBV samples were determined by DNA sequences and type-specific amino acids of the S gene of HBV. Copy numbers of HBV DNA were quantified by real-time TaqMan polymerase chain reaction (PCR) and by nested PCR applied to limiting dilutions. The copy number determined for each inoculum was compared with previously defined chimpanzee infectivity titers. The genotypes of the HBV adw, ayw, and adr inocula were A, D, and C, respectively. The concentration of HBV DNA was determined to be 5.4 x 10(9), 2.5 x 10(9), and 3.1 x 10(8) genome equivalents (geq) per mL for serum samples containing the adw, ayw, and adr, respectively. The chimpanzee infectivity titers per milliliter of these initial HBV-containing serum samples were previously determined to be 10(7.5) for adw, 10(7.5) for ayw (MS-2 strain), and 10(8) for adr. The minimal copy number of HBV DNA in chronic carriers of HBV that can infect the chimpanzee model was estimated to be from 3 to 169 geq based upon the three well-characterized inocula. C1 US FDA, Div Emerging & Transfus Transmitted Dis, CBER, Bethesda, MD 20014 USA. US FDA, Div Biostat, CBER, Bethesda, MD 20014 USA. US FDA, Div Hematol, CBER, Bethesda, MD 20014 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Hsia, CC (reprint author), Bldg 29,Room 222,HFM 310,29 Lincoln Dr, Bethesda, MD 20892 USA. EM chuchieh.hsia@fda.hhs.gov NR 46 TC 29 Z9 33 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 2006 VL 46 IS 10 BP 1829 EP 1835 DI 10.1111/j.1537-2995.2006.00974.x PG 7 WC Hematology SC Hematology GA 086NT UT WOS:000240681000023 PM 17002641 ER PT J AU Feng, ML Liu, DZ Shen, W Wang, JL Guo, ZH Zhang, X Du, KM Qian, KC Zhao, TM AF Feng, M. L. Liu, D. Z. Shen, W. Wang, J. L. Guo, Z. H. Zhang, X. Du, K. M. Qian, K. C. Zhao, T. M. TI Establishment of an HPA-1-to-16-typed platelet donor registry in China SO TRANSFUSION MEDICINE LA English DT Article DE Chinese; gene frequency; human platelet antigens; PCR-SSP; platelet donor registry ID PCR-SSP; POPULATIONS; ALLOANTIGENS; ANTIGENS; TRANSFUSIONS; POLYMORPHISM; ANTIBODIES; INTEGRIN; ALLELES; HPA-1 AB In order to determine gene frequencies of human platelet antigen (HPA) and establish a panel of accredited HPA-1a, -2a, -4a, -5a and -6a-negative donors as well as an HPA-typed platelet donor registry, a total of 1000 Chinese donors of Han nationality (500 from north China and 500 from south China) were typed for HPA-1 through -16 using a DNA-based polymerase chain reaction with sequence-specific primers genotyping method. The gene frequencies of HPA-1b, -2b, -3b, -4b, -5b, -6bw, -10bw and -15b were 0.0060, 0.0485, 0.4055, 0.0045, 0.0140, 0.0135, 0.0005 and 0.4680, respectively. The HPA-7bw, -8bw, -9bw, -11bw, -12bw, -13bw, -14bw and -16bw alleles were not found. The HPA-2b and -5b homozygous donors were detected at low frequencies. The HPA mismatch probabilities potentially leading to alloimmunization in random platelet transfusion vary with a region from 0.1% to 37% depending on the distribution patterns of common and less common alleles in each system. This study provides a useful HPA-typed plateletpheresis donor registry in China and could improve platelet antibody detection and HPA-matched platelet transfusion in alloimmune thrombocytopenic patients. C1 Shanghai Blood Ctr, Shanghai 200051, Peoples R China. NIH, Bethesda, MD 20892 USA. RP Liu, DZ (reprint author), Shanghai Blood Ctr, 1191 Hong Qiao Rd, Shanghai 200051, Peoples R China. EM fengml@sh163.net NR 24 TC 33 Z9 61 U1 2 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0958-7578 J9 TRANSFUSION MED JI Transfus. Med. PD OCT PY 2006 VL 16 IS 5 BP 369 EP 374 DI 10.1111/j.1365-3148.2006.00687.x PG 6 WC Hematology SC Hematology GA 087IN UT WOS:000240736200010 PM 16999761 ER PT J AU Hinnebusch, AG AF Hinnebusch, Alan G. TI eIF3: a versatile scaffold for translation initiation complexes SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID VIRAL REINITIATION FACTOR; RNA RECOGNITION MOTIF; FACTOR 3 SUBUNITS; FACTOR 4G EIF4G; EUKARYOTIC TRANSLATION; SACCHAROMYCES-CEREVISIAE; PREINITIATION COMPLEX; RIBOSOMAL-SUBUNIT; IN-VIVO; MULTIFACTOR COMPLEX AB Translation initiation in eukaryotes depends on many eukaryotic initiation factors (elFs) that stimulate Met both recruitment of the initiator tRNA, Met-tRNAi, and mRINA to the 40S ribosomal subunit and subsequent scanning of the mRNA for the AUG start codon. The largest of these initiation factors, the eIF3 complex, organizes a web of interactions among several elFs that assemble on the 40S subunit and participate in the different reactions involved in translation. Structural analysis suggests that eIF3 performs this scaffolding function by binding to the 40S subunit on its solvent-exposed surface rather than on its interface with the 60S subunit, where the decoding sites exist. This location of eIF3 seems ideally suited for its other proposed regulatory functions, including reinitiating translation on polycistronic mRNAs and acting as a receptor for protein kinases that control protein synthesis.. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM alanh@mail.nih.gov FU Intramural NIH HHS NR 83 TC 215 Z9 224 U1 2 U2 18 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD OCT PY 2006 VL 31 IS 10 BP 553 EP 562 DI 10.1016/j.tibs.2006.08.005 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 102VN UT WOS:000241841500004 PM 16920360 ER PT J AU Hegde, RS Bernstein, HD AF Hegde, Ramanujan S. Bernstein, Harris D. TI The surprising complexity of signal sequences SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID ENDOPLASMIC-RETICULUM MEMBRANE; POSTTRANSLATIONAL PROTEIN-TRANSPORT; VIRUS PRECORE PROTEIN; CELL-MEDIATED LYSIS; HLA-E BINDS; ESCHERICHIA-COLI; RECOGNITION PARTICLE; PRION PROTEIN; ER MEMBRANE; SACCHAROMYCES-CEREVISIAE AB Most secreted and many membrane proteins contain cleavable N-terminal signal sequences that mediate their targeting to and translocation across the endoplasmic reticulum or bacterial cytoplasmic membrane. Recent studies have identified many exceptions to the widely held view that signal sequences are simple, degenerate and interchangeable. Growing evidence indicates that signal sequences contain information that specifies the choice of targeting pathway, the efficiency of translocation, the timing of cleavage and even postcleavage functions. As a consequence, signal sequences can have important roles in modulating protein blogenesis. Based on a synthesis of studies in numerous experimental systems, we propose that substrate-specific sequence elements embedded in a conserved domain structure impart unique and physiologically important functionality to signal sequences. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Hegde, RS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM hegder@mail.nih.gov; harris_bernstein@nih.gov OI Hegde, Ramanujan/0000-0001-8338-852X FU Intramural NIH HHS NR 79 TC 173 Z9 180 U1 3 U2 39 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD OCT PY 2006 VL 31 IS 10 BP 563 EP 571 DI 10.1016/j.tibs.2006.08.004 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 102VN UT WOS:000241841500005 PM 16919958 ER PT J AU Tsai, CJ Zheng, J Aleman, C Nussinov, R AF Tsai, Chung-Jung Zheng, Jie Aleman, Carlos Nussinov, Ruth TI Structure by design: from single proteins and their building blocks to nanostructures SO TRENDS IN BIOTECHNOLOGY LA English DT Editorial Material ID PEPTIDE-NANOTUBE; CRYSTAL-STRUCTURE; AMYLOID FIBERS; DYNAMICS; FLEXIBILITY; ASSEMBLIES; NANOWIRES; DRIVEN AB Nanotechnology realizes the advantages of naturally occurring biological macromolecules and their building-block nature for design. Frequently, assembly starts with the choice of a 'good' molecule that is synthetically optimized towards the desired shape. By contrast, we propose starting with a pre-specified nanostructure shape, selecting candidate protein building blocks from a library and mapping them onto the shape and, finally, testing the stability of the construct. Such a shape-based, part-assembly strategy is conceptually similar to protein design through the combinatorial assembly of building blocks. If the conformational preferences of the building blocks are retained and their interactions are favorable, the nanostructure will be stable. The richness of the conformations, shapes and chemistries of the protein building blocks suggests a broad range of potential applications; at the same time, it also highlights their complexity. In this Opinion article, we focus on the first step: validating such a strategy against experimental data. C1 NCI, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. Univ Politecn Cataluna, ETS Engn Ind Barcelona, Dept Engn Quim, E-08028 Barcelona, Spain. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov RI Zheng, Jie/B-5057-2013 OI Zheng, Jie/0000-0003-1547-3612 FU NCI NIH HHS [N01 CO 12400] NR 50 TC 22 Z9 25 U1 0 U2 8 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD OCT PY 2006 VL 24 IS 10 BP 449 EP 454 DI 10.1016/j.tibtech.2006.08.004 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 094QZ UT WOS:000241255400004 PM 16935374 ER PT J AU Lark, KG Chase, K Sutter, NB AF Lark, Karl G. Chase, Kevin Sutter, Nathan B. TI Genetic architecture of the dog: sexual size dimorphism and functional morphology SO TRENDS IN GENETICS LA English DT Review ID QUANTITATIVE TRAIT LOCI; CANINE GENOME; DOMESTIC DOG; LINKAGE ANALYSIS; COMPLEX TRAITS; HIP-DYSPLASIA; RENSCHS RULE; EVOLUTION; SELECTION; FAMILIARIS AB Purebred dogs are a valuable resource for genetic analysis of quantitative traits. Quantitative traits are complex, controlled by many genes that are contained within regions of the genome known as quantitative trait loci (QTL). The genetic architecture of quantitative traits is defined by the characteristics of these genes: their number, the magnitude of their effects, their positions in the genome and their interactions with each other. QTL analysis is a valuable tool for exploring genetic architecture, and highlighting regions of the genome that contribute to the variation of a trait within a population. C1 Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Lark, KG (reprint author), Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA. EM lark@bioscience.utah.edu FU FIC NIH HHS [R03 TW007056, TW 07056]; NIGMS NIH HHS [R01 GM063056, R01 GM063056-05, GM 063056] NR 53 TC 21 Z9 22 U1 1 U2 11 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD OCT PY 2006 VL 22 IS 10 BP 537 EP 544 DI 10.1016/j.tig.2006.08.009 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 094VX UT WOS:000241268400005 PM 16934357 ER PT J AU Crawford, NPS Hunter, KW AF Crawford, Nigel P. S. Hunter, Kent W. TI New perspectives on hereditary influences in metastatic progression SO TRENDS IN GENETICS LA English DT Review ID BREAST-CANCER METASTASIS; TRANSGENIC MOUSE MODEL; GENE-EXPRESSION; IMPORTANT DETERMINANT; TUMOR PROGRESSION; CELLS; DISEASE; SIGNATURE; SUSCEPTIBILITY; DISSEMINATION AB Metastasis, the process by which cancer cells spread to distant sites and form secondary tumors, depends upon the ability of cells to escape the primary tumor, and colonize and proliferate in a novel microenvironment. Many mechanisms have been proposed to explain this phenomenon although no theory has comprehensively explained all biological observations. There is growing evidence that host hereditary factors modulate the ability of tumor cells to form metastatic lesions, and host genetic polymorphism could be a significant variable in this process. This review is intended to illustrate the role of hereditary variation in metastatic progression, how this integrates with currently proposed metastatic mechanisms, and the potential clinical impact on this frequently fatal consequence of cancer. C1 NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. RP Hunter, KW (reprint author), NCI, Lab Populat Genet, NIH, Bldg 41,Room D702,41 Lib Dr, Bethesda, MD 20892 USA. EM hunterk@mail.nih.gov NR 45 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD OCT PY 2006 VL 22 IS 10 BP 555 EP 561 DI 10.1016/j.tig.2006.07.009 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 094VX UT WOS:000241268400007 PM 16889869 ER PT J AU Provenzano, M Panelli, MC Mocellin, S Bracci, L Sais, G Stroncek, DF Spagnoli, GC Marincola, FM AF Provenzano, Maurizio Panelli, Monica C. Mocellin, Simone Bracci, Laura Sais, Giovanni Stroncek, David F. Spagnoli, Giulio C. Marincola, Francesco M. TI MHC-peptide specificity and T-cell epitope mapping: where immunotherapy starts SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID REAL-TIME PCR; BLOOD MONONUCLEAR-CELLS; EX-VIVO STIMULATION; PERIPHERAL-BLOOD; HUMAN CYTOMEGALOVIRUS; METASTATIC MELANOMA; DENDRITIC CELLS; COSTIMULATORY MOLECULES; LYMPHOCYTE EPITOPE; GENE-EXPRESSION AB The evaluation and characterization of epitope-specific human leukocyte antigen (HLA)-restricted memory T-cell reactivity is an important step for the development of preventive vaccines and peptide-based immunotherapies for viral and tumor diseases. The past decade has witnessed the use of HLA-restricted peptides as tools to activate strong immune responses of naive or memory T cells specifically. This has fuelled an active search for methodological approaches focusing on HLA and peptide associations. Here, we outline new perspective on the emerging opportunity of evaluating HLA and peptide restriction by using novel approaches, such as quantitative real-time PCR, that can identify epitope specificities that are potentially useful in clinical settings. C1 Univ Basel, Inst Surg Res & Hosp Management, CH-4031 Basel, Switzerland. NIH, Ctr Clin, Dept Transfus Med, Immunogenet Sect, Bethesda, MD 20892 USA. Univ Padua, Dept Oncol & Surg Sci, Surg Branch, I-35128 Padua, Italy. RP Provenzano, M (reprint author), Univ Basel, Inst Surg Res & Hosp Management, CH-4031 Basel, Switzerland. EM mprovenzano@uhbs.ch RI BRACCI, LAURA/J-8777-2016 OI BRACCI, LAURA/0000-0002-2535-4353 NR 74 TC 16 Z9 16 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD OCT PY 2006 VL 12 IS 10 BP 465 EP 472 DI 10.1016/j.molmed.2006.08.008 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 102NH UT WOS:000241818400005 PM 16962375 ER PT J AU Sheliga, BM FitzGibbon, EJ Miles, FA AF Sheliga, B. M. FitzGibbon, E. J. Miles, F. A. TI Short-latency disparity vergence eye movements: A response to disparity energy SO VISION RESEARCH LA English DT Article DE disparity energy; missing fundamental; spatiotemporal filtering ID OCULAR-FOLLOWING RESPONSES; RANDOM-DOT STEREOGRAMS; TRANSIENT-STEREOPSIS SYSTEM; OPPOSITE-CONTRAST STIMULI; RADIAL OPTIC FLOW; CORTICAL AREA MST; BINOCULAR DISPARITY; MOTION PERCEPTION; DEPTH-PERCEPTION; VISUAL-CORTEX AB Vergence eye movements were elicited in human subjects by applying disparities to square-wave gratings lacking the fundamental ("missing fundamental", mf). Using a dichoptic arrangement, subjects viewed gratings that were identical at the two eyes except for a phase difference of 1/4 wavelength so that, based on the nearest-neighbor matches, the features and the 4n+1 harmonics (5th, 9th, etc.) all had binocular disparities of one sign, whereas the 4n - 1 harmonics (3rd, 7th, etc.) all had disparities of the opposite sign. Further, the amplitude of the ith harmonic was proportional to 1/i. Using the electromagnetic search coil technique to record the positions of both eyes indicated that the earliest vergence eye movements elicited by these disparity stimuli had ultra-short latencies (minimum, < 65 ms) and were always in the direction of the most prominent harmonic, the 3rd, but their magnitudes fell short of those elicited when the same disparities were applied to pure sinusoids whose spatial frequency and contrast matched those of the 3rd harmonic. This shortfall was evident in both the horizontal vergence responses recorded with vertical grating stimuli and the vertical vergence responses recorded with horizontal grating stimuli. When the next most prominent harmonic, the 5th, was removed from the mf stimulus (creating the "mf-5" stimulus) the vertical vergence responses showed almost no shortfall-indicating that it had been almost entirely due to that 5th harmonic-but the horizontal vergence responses still showed a small shortfall, at least with higher contrast stimuli. This small shortfall might represent a very minor contribution from higher harmonics and/or distortion products and/or a feature-based mechanism. We conclude that the earliest disparity vergence responses-especially vertical-were strongly dependent on the major Fourier components of the binocular images, consistent with early spatial filtering of the monocular visual inputs prior to their binocular combination as in the disparity-energy model of complex cells in striate cortex [Ohzawa, I., DeAngelis, G. C., & Freeman, R. D. (1990). Stereoscopic depth discrimination in the visual cortex: neurons ideally suited as disparity detectors. Science, 249, 1037-1041]. Published by Elsevier Ltd. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Sheliga, BM (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50,49 Convent Dr, Bethesda, MD 20892 USA. EM bms@lsr.nei.nih.gov FU Intramural NIH HHS [Z01 EY000153-24] NR 86 TC 14 Z9 14 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 J9 VISION RES JI Vision Res. PD OCT PY 2006 VL 46 IS 21 BP 3723 EP 3740 DI 10.1016/j.visres.2006.04.020 PG 18 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 095NG UT WOS:000241314000018 PM 16765403 ER PT J AU Tien, ES Negishi, M AF Tien, E. S. Negishi, M. TI Nuclear receptors CAR and PXR in the regulation of hepatic metabolism SO XENOBIOTICA LA English DT Article DE CAR; PXR; gene regulation ID CONSTITUTIVE ANDROSTANE RECEPTOR; PREGNANE-X-RECEPTOR; THYROID-HORMONE METABOLISM; SULFOTRANSFERASE SULT1A1 GENE; RESPONSIVE ENHANCER MODULE; BILE-ACID; CYP2B10 GENE; BILIRUBIN DETOXIFICATION; INTERACTING PROTEIN-1; ACTIVATED RECEPTOR AB The nuclear receptors CAR and PXR were first characterized as xenosensing transcription factors regulating the induction of phase I and II xenobiotic-metabolizing enzymes as well as transporters in response to exogenous stimuli. It has now become clear, however, that these receptors cross-talk with endogenous stimuli as well, which extends their regulation to various physiological processes such as energy metabolism and cell growth. As recognition of the function of these receptors has widened, the molecular mechanism of their regulation has evolved from simple protein-DNA binding to regulation by complex protein-protein interactions. Novel mechanisms as to how xenobiotic exposure alters hepatic metabolic pathways such as gluconeogenesis and beta-oxidation have emerged. At the same time, the molecular mechanism of how endogenous stimuli, such as insulin, regulate xenobiotc metabolism via CAR and PXR have also become evident. C1 NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, POB 12233, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov FU Intramural NIH HHS [001-1877-254, , NIH0011877254]; PHS HHS [NIH0011877254, 001-1877-254] NR 77 TC 52 Z9 56 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD OCT-NOV PY 2006 VL 36 IS 10-11 BP 1152 EP 1163 DI 10.1080/00498250600861827 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 116KK UT WOS:000242801300012 PM 17118922 ER PT J AU Zhu, JL Basso, O Obel, C Bille, C Olsen, J AF Zhu, Jin Liang Basso, Olga Obel, Carsten Bille, Camilla Olsen, Jorn TI Infertility, infertility treatment, and congenital malformations: Danish national birth cohort SO BRITISH MEDICAL JOURNAL LA English DT Article ID IN-VITRO FERTILIZATION; RISK; REGISTRY; CHILDREN; SWEDEN; IVF AB Objectives To examine whether infertile couples (with a time to pregnancy of >12 months), who conceive naturally or after treatment, give birth to children with an increased prevalence of congenital malformations. Design Longitudinal study. Setting Danish national birth cohort. Participants Three groups of liveborn children and their mothers: 50 897 singletons and 1366 twins born to fertile couples (time to pregnancy : 12 months), 5764 singletons and 100 twins born to infertile couples who conceived naturally (time to pregnancy >12 months), and 4588 singletons and 1690 twins born after infertility treatment. Main outcome measures Prevalence of congenital malformations determined from hospital discharge diagnoses. Results Compared with singletons born to fertile couples, singletons born to infertile couples who conceived naturally or after treatment had a higher prevalence of congenital malformations-hazard ratios 1.20 (95% confidence interval 1.07 to 1.35) and 1.39 (1.23 to 1.57). The overall prevalence of congenital malformations increased with increasing time to pregnancy. When the analysis was restricted to singletons born to infertile couples, babies born after treatment had an increased prevalence of genital organ malformations (hazard ratio 2.32, 1.24 to 4.35) compared with babies conceived naturally. No significant differences existed in the overall prevalence of congenital malformations among twins. Conclusions Hormonal treatment for infertility may be related to the occurrence of malformations of genital organs, but our results suggest that the reported increased prevalence of congenital malformations seen in singletons born after assisted reproductive technology is partly the result of the underlying infertility or its determinants. The association between untreated infertility and congenital malformations warrants further examination. C1 Aarhus Univ, Danish Epidemiol Sci Ctr, Dept Epidemiol, Inst Publ Hlth, DK-8000 Aarhus C, Denmark. NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC USA. Aarhus Univ Hosp, Dept Obstet & Gynaecol, Perinatal Epidemiol Res Unit, DK-8200 Aarhus, Denmark. Univ So Denmark, Ctr Prevent Congenital Malformat, Inst Publ Hlth, DK-5000 Odense C, Denmark. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. RP Zhu, JL (reprint author), Aarhus Univ, Danish Epidemiol Sci Ctr, Dept Epidemiol, Inst Publ Hlth, DK-8000 Aarhus C, Denmark. EM zjl@soci.au.dk RI Basso, Olga/E-5384-2010; Olsen, Jorn/F-8801-2015 OI Basso, Olga/0000-0001-9298-4921; Olsen, Jorn/0000-0001-7462-5140 FU Intramural NIH HHS NR 19 TC 159 Z9 160 U1 1 U2 12 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD SEP 30 PY 2006 VL 333 IS 7570 BP 679 EP + DI 10.1136/bmj.38919.495718.AE PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 092AA UT WOS:000241068200017 PM 16893903 ER PT J AU Walbridge, S Murad, GJA Heiss, JD Oldfield, EH Lonser, RR AF Walbridge, Stuart Murad, Gregory J. A. Heiss, John D. Oldfield, Edward H. Lonser, Russell R. TI Technique for enhanced accuracy and reliability in non-human primate stereotaxy SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE accuracy; magnetic resonance imaging; primate; stereotaxy; surgery; technique ID RHESUS-MONKEY; GUIDANCE; SURGERY; BRAIN AB Despite the importance of enhancing the accuracy and reliability of non-human primate stereotaxy, a number of limitations exist using currently described techniques. To overcome these problems, we present a simple universally available approach that combines pre-operative magnetic resonance imaging and the non-surgical creation of reference points (teeth marking). We have found that this approach improves stereotaxic targeting reliability and permits accurate reproducible stereotaxic localization at time points distant from the pre-operative imaging. Published by Elsevier B.V. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 5D37, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov OI Heiss, John/0000-0002-3890-0165 FU Intramural NIH HHS [Z99 NS999999] NR 9 TC 2 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD SEP 30 PY 2006 VL 156 IS 1-2 BP 310 EP 313 DI 10.1016/j.jneumeth.2006.01.025 PG 4 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 092WA UT WOS:000241126800039 PM 16516975 ER PT J AU Rosenberg, PS Che, A Chen, BE AF Rosenberg, Philip S. Che, Anney Chen, Bingshu E. TI Multiple hypothesis testing strategies for genetic case-control association studies SO STATISTICS IN MEDICINE LA English DT Article DE statistics and numerical data; research design; epidemiology; case-control studies; human genome; polymorphism; single nucleotide; haplotypes ID FALSE DISCOVERY RATE; SINGLE-NUCLEOTIDE POLYMORPHISMS; IMPROVED BONFERRONI PROCEDURE; UNPHASED GENOTYPE DATA; LINKAGE DISEQUILIBRIUM; TEST STATISTICS; HUMAN GENOME; ALZHEIMERS-DISEASE; HAPLOTYPE BLOCKS; COMPLEX DISEASE AB The genetic case-control association study of unrelated subjects is a leading method to identify single nucleotide polymorphisms (SNPs) and SNP haplotypes that modulate the risk of complex diseases. Association studies often genotype several SNPs in a number of candidate genes; we propose a two-stage approach to address the inherent statistical multiple comparisons problem. In the first stage, each gene's association with disease is summarized by a single p-value that controls a familywise error rate. In the second stage, summary p-values are adjusted for multiplicity using a false discovery rate (FDR) controlling procedure. For the first stage, we consider marginal and joint tests of SNPs and haplotypes within genes, and we construct an omnibus test that combines SNP and haplotype analysis. Simulation studies show that when disease susceptibility is conferred by a SNP, and all common SNPs in a gene are genotyped, marginal analysis of SNPs using the Simes test has similar or higher power than marginal or joint haplotype analysis. Conversely, haplotype analysis can be more powerful when disease susceptibility is conferred by a haplotype. The omnibus test tracks the more powerful of the two approaches, which is generally unknown. Multiple testing balances the desire for statistical power against the implicit costs of false positive results, which up to now appear to be common in the literature. Published in 2005 by John Wiley & Sons, Ltd. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Sci, Rockville, MD 20852 USA. RP Rosenberg, PS (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Sci, 6120 Execut Blvd,Execut Plaza S 8022, Rockville, MD 20852 USA. EM rosenbep@mail.nih.gov; chea@mail.nih.gov; cheneric@mail.nih.gov OI Chen, Bingshu/0000-0001-6139-0696 FU Intramural NIH HHS NR 46 TC 29 Z9 29 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 30 PY 2006 VL 25 IS 18 BP 3134 EP 3149 DI 10.1002/sim.2407 PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 084XQ UT WOS:000240568100006 PM 16252274 ER PT J AU Zheng, G Gastwirth, JL AF Zheng, Gang Gastwirth, Joseph L. TI On estimation of the variance in Cochran-Armitage trend tests for genetic association using case-control studies SO STATISTICS IN MEDICINE LA English DT Article DE biased estimate; efficiency robust test; genetic models; MAX; mode of inheritance; power ID EFFICIENCY ROBUST-TESTS; SAMPLE-SIZE; SURVIVAL; MARKERS; POWER AB The Cochran-Armitage trend test has been used in case-control studies for testing genetic association. As the variance of the test statistic is a function of unknown parameters, e.g. disease prevalence and allele frequency, it must be estimated. The usual estimator combining data for cases and controls assumes they follow the same distribution under the null hypothesis. Under the alternative hypothesis, however, the cases and controls follow different distributions. Thus, the power of the trend tests may be affected by the variance estimator used. In particular, the usual method combining both cases and controls is not an asymptotically unbiased estimator of the null variance when the alternative is true. Two different estimates of the null variance are available which are consistent under both the null and alternative hypotheses. In this paper, we examine sample size and small sample power performance of trend tests, which are optimal for three common genetic models as well as a robust trend test based on the three estimates of the variance and provide guidelines for choosing an appropriate test. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. George Washington Univ, Dept Stat, Washington, DC 20052 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, Room 8223,6701 Rockledge Dr,MSC 7938, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov NR 11 TC 26 Z9 26 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 30 PY 2006 VL 25 IS 18 BP 3150 EP 3159 DI 10.1002/sim.2250 PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 084XQ UT WOS:000240568100007 PM 16397860 ER PT J AU Zheng, G Tian, X AF Zheng, Gang Tian, Xin CA ACCESS Res Grp TI Robust trend tests for genetic association using matched case-control design SO STATISTICS IN MEDICINE LA English DT Article DE case-control study; MAX; MERT; score test; variable matching ID GENOMIC CONTROL; SAMPLE-SIZE; CONTINGENCY-TABLES; SCORES; POWER; SARCOIDOSIS; STATISTICS; SURVIVAL; MARKERS; CHOICE AB Trend tests for genetic association using a matched case-control design are studied, which allows for a variable number of controls per case. However, the tests depend on the scores based on the underlying genetic model, thus it may result in substantial loss of power when the model is misspecified. Since the mode of inheritance may be unknown for complex diseases, robust trend tests in matched case-control studies are developed. Simulation is conducted to compare the trend tests and the robust trend tests under various genetic models. The results are applied to detect candidate-gene association using an example from a case-control aetiologic study of sarcoidosis. Published in 2005 by John Wiley & Sons, Ltd. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, Room 8223,6701 Rockledge Dr,MSC 7938, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov OI Strange, Charlie/0000-0002-8109-8067; Judson, Marc/0000-0002-4663-7985 FU NHLBI NIH HHS [N01-HR-56070, N01-HR-56065, N01-HR-56066, N01-HR-56067, N01-HR-56068, N01-HR-56069, N01-HR-56071, N01-HR-56072, N01-HR-56073, N01-HR-56074, N01-HR-56075] NR 28 TC 12 Z9 13 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 30 PY 2006 VL 25 IS 18 BP 3160 EP 3173 DI 10.1002/sim.2278 PG 14 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 084XQ UT WOS:000240568100008 PM 16196079 ER PT J AU Liao, HX Sutherland, LL Xia, SM Brock, ME Scearce, RM Vanleeuwen, S Alam, SM McAdams, M Weaver, EA Camacho, ZT Ma, BJ Li, YY Decker, JM Nabel, GJ Montefiori, DC Hahn, BH Korber, BT Gao, F Haynes, BF AF Liao, Hua-Xin Sutherland, Laura L. Xia, Shi-Mao Brock, Mary E. Scearce, Richard M. Vanleeuwen, Stacie Alam, S. Munir McAdams, Mildred Weaver, Eric A. Camacho, Zenaido T. Ma, Ben-Jiang Li, Yingying Decker, Julie M. Nabel, Gary J. Montefiori, David C. Hahn, Beatrice H. Korber, Bette T. Gao, Feng Haynes, Barton F. TI A group M consensus envelope glycoprotein induces antibodies that neutralize subsets of subtype B and CHIV-1 primary viruses SO VIROLOGY LA English DT Article DE HIV-1; vaccine; neutralization antibody; consensus inummogens ID HUMAN-IMMUNODEFICIENCY-VIRUS; FUSION INHIBITOR T-20; TYPE-1 ENVELOPE; HIV TYPE-1; V3 LOOP; MONOCLONAL-ANTIBODIES; RHESUS MACAQUES; GP120; IMMUNOGENICITY; IMMUNIZATION AB HIV-1 subtype C is the most common HIV-1 group M subtype in Africa and many parts of Asia. However, to date HIV-1 vaccine candidate immunogens have not induced potent and broadly neutralizing antibodies against subtype C primary isolates. We have used a centralized gene strategy to address HIV-1 diversity and generated a group M consensus envelope gene with shortened consensus variable loops (CON-S) for comparative studies with wild-type (WT) Env immunogens. Our results indicate that the consensus HIV-1 group M CON-S Env elicited cross-subtype neutralizing antibodies of similar or greater breadth and titer than the WT Envs tested, indicating the utility of a centralized gene strategy. Our study also shows the feasibility of iterative improvements in Env immunogenicity by rational design of centralized genes. (c) 2006 Published by Elsevier Inc. C1 Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC 27710 USA. Duke Univ, Sch Med, Dept Med, Durham, NC 27710 USA. Duke Univ, Sch Med, Dept Surg, Durham, NC 27710 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Med, Birmingham, AL 35203 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35203 USA. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Santa Fe Inst, Santa Fe, NM 87501 USA. RP Liao, HX (reprint author), Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC 27710 USA. EM hilao@acpub.duke.edu OI Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [N01 AI085338, P01 AI 28147, P01 AI046023, P01 AI061734, P30 AI051445, P30 AI51445, P01 AI52816, R21AI55386, R21 AI055386, P01 AI052816, P0-1, AI061734, N01 AI085338-002, N01 AI 85338, P01 AI028147] NR 58 TC 125 Z9 129 U1 1 U2 9 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 SEP 30 PY 2006 VL 353 IS 2 BP 268 EP 282 DI 10.1016/j.virol.2006.04.043 PG 15 WC Virology SC Virology GA 090DN UT WOS:000240930900003 PM 17039602 ER PT J AU Zhang, FW Hatziioannou, T Perez-Caballero, D Derse, D Bieniasz, PD AF Zhang, Fengwen Hatziioannou, Theodora Perez-Caballero, David Derse, David Bieniasz, Paul D. TI Antiretroviral potential of human tripartite motif-5 and related proteins SO VIROLOGY LA English DT Article DE HIV-1; SIV; MLV; TRIM5; TRIM genes; retrovirus; intrinsic immunity ID IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; SIMIAN IMMUNODEFICIENCY; RETROVIRUS RESTRICTION; MONKEY TRIM5-ALPHA; CYCLOPHILIN-A; HUMAN-CELLS; POSTENTRY RESTRICTION; CYTOPLASMIC BODIES; LENTIVIRAL VECTOR AB TRIM5 alpha is a potent inhibitor of infection by diverse retroviruses and is encoded by one of a large family of TRIM genes. We found that several TRIM motifs among a panel of selected human TRIM proteins (TRIM1, 5, 6, 18, 19, 2122, 34) could inhibit infection when artificially targeted to an incoming HIV-1 capsid. Conversely, when ectopically expressed as authentic full-length proteins, most lacked activity against a panel of retroviruses. The exceptions were TRIM1, TRIM5 and TRIM34 proteins. Weak but specific inhibition of HIV-2/SIVMAc and EIAV by TRIM34 was noted, and human TRIM5 a modestly, but specifically, inhibited an HIV-I strain carrying a mutation in the cyclophilin binding loop (G89V). Restriction activity observed in ectopic expression assays was sometimes not detectable in corresponding RNAi-based knockdown experiments. However, endogenous owl monkey TRIMCyp potently inhibited an SIVAGM strain. Overall, sporadic examples of intrinsic antiretroviral activity exist in this panel of TRIM proteins. (c) 2006 Elsevier Inc. All rights reserved. C1 Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. Rockefeller Univ, Lab Retrovirol, New York, NY 10016 USA. NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. RP Bieniasz, PD (reprint author), Rockefeller Univ, Aaron Diamond AIDS Res Ctr, 455 1st Ave, New York, NY 10016 USA. EM pbienias@adarc.org FU NIAID NIH HHS [R01AI064003] NR 70 TC 78 Z9 82 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 SEP 30 PY 2006 VL 353 IS 2 BP 396 EP 409 DI 10.1016/j.virol.2006.05.035 PG 14 WC Virology SC Virology GA 090DN UT WOS:000240930900015 PM 16828831 ER PT J AU Pinto, LA Viscidi, R Harro, CD Kemp, TJ Garcia-Pineres, AJ Trivett, M Demuth, F Lowy, DR Schiller, JT Berzofsky, JA Hildesheim, A AF Pinto, Ligia A. Viscidi, Raphael Harro, Clayton D. Kemp, Troy J. Garcia-Pineres, Alfonso J. Trivett, Matthew Demuth, Franklin Lowy, Douglas R. Schiller, John T. Berzofsky, Jay A. Hildesheim, Allan TI Cellular immune responses to HPV-18, -31, and -53 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles SO VIROLOGY LA English DT Article DE T cells; cytokines; vaccination; infectious diseases ID HUMAN-PAPILLOMAVIRUS TYPE-16; CERVICAL-CANCER; YOUNG-WOMEN; IMMUNOLOGICAL MEMORY; ADULT VOLUNTEERS; CONTROLLED-TRIAL; IN-VITRO; VACCINE; INFECTION; CD4(+) AB Human papillomavirus-like particles (HPV VLP) are candidate vaccines that have shown to be efficacious in reducing infection and inducing robust antiviral immunity. Neutralizing antibodies generated by vaccination are largely type-specific, but little is known about the type-specificity of cellular immune responses to VLP vaccination. To determine whether vaccination with HPV-16 L1VLP induces cellular immunity to heterologous HPV types (HPV-18, HPV-31, and HPV-53), we examined proliferative and cytokine responses in vaccine (n=11) and placebo (n=5) recipients. Increased proliferative and cytokine responses to heterologous types were observed postvaccination in some individuals. The proportion of women responding to heterologous types postvaccination (36%-55%) was lower than that observed in response to HPV-16 (73%). Response to HPV-16 VLP predicted response to other types. The strongest correlations in response were observed between HPV-16 and HPV-31, consistent with their phylogenetic relatedness. In summary, PBMC from HPV-16 VLP vaccine recipients can respond to L1VLP from heterologous HPV types, suggesting the presence of conserved T cell epitopes. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, HPV Immunol Lab, SAIC Frederick, Frederick, MD 21702 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Informat Management Serv Inc, Silver Spring, MD USA. NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Pinto, LA (reprint author), NCI, HPV Immunol Lab, SAIC Frederick, Frederick Bldg 469,Room 120, Frederick, MD 21702 USA. EM lpinto@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 37 TC 30 Z9 30 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 SEP 30 PY 2006 VL 353 IS 2 BP 451 EP 462 DI 10.1016/j.virol.2006.06.021 PG 12 WC Virology SC Virology GA 090DN UT WOS:000240930900020 PM 16863657 ER PT J AU Chang, KO Sosnovtsev, SV Belliot, G King, AD Green, KY AF Chang, Kyeong-Ok Sosnovtsev, Stanislav V. Belliot, Gael King, Adriene D. Green, Kim Y. TI Stable expression of a Norwalk virus RNA replicon in a human hepatoma cell line SO VIROLOGY LA English DT Article DE Norwalk virus; replicon-bearing cells; Huh-7; interferon; RNA replication ID HEPATITIS-C VIRUS; PORCINE ENTERIC CALICIVIRUS; FELINE CALICIVIRUS; MAMMALIAN-CELLS; INNATE IMMUNITY; UNITED-STATES; REPLICATION; INTERFERON; PROTEIN; GENOME AB Norwalk virus (NV) is a prototype strain of the genus Norovirus in the family Caliciviridae. The human noroviruses have emerged as major agents of acute gastroenteritis in all age groups, but there are no vaccines or antiviral agents partly due to the absence of a cell culture system. We report the generation of cells expressing self-replicating NV RNA (NV replicon) following transfection of NV RNA bearing an engineered neomycin resistance gene into cell lines of human (Huh-7) or hamster (BHK21) origin. Expression of replicon RNA was significantly reduced in the presence of interferon (IFN)-alpha in a dose-dependent manner in the NV replicon-bearing cells, suggesting a role for innate immunity in the control of human norovirus replication. This stable NV replicon system should lead to new insights into norovirus replication, virus-host interactions, and approaches for the treatment of norovirus disease. (c) 2006 Elsevier Inc. All rights reserved. C1 Kansas State Univ, Coll Vet Med, Dept Diagnost Med & Pathobiol, Manhattan, KS 66506 USA. NIAID, Infect Dis Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Chang, KO (reprint author), Kansas State Univ, Coll Vet Med, Dept Diagnost Med & Pathobiol, 1800 Denison Ave, Manhattan, KS 66506 USA. EM kchang@vet.ksu.edu NR 38 TC 84 Z9 87 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 30 PY 2006 VL 353 IS 2 BP 463 EP 473 DI 10.1016/j.virol.2006.06.006 PG 11 WC Virology SC Virology GA 090DN UT WOS:000240930900021 PM 16843517 ER PT J AU Hama, Y Urano, Y Koyama, Y Choyke, PL Kobayashi, H AF Hama, Yukihiro Urano, Yasuteru Koyama, Yoshinori Choyke, Peter L. Kobayashi, Hisataka TI Targeted optical imaging of cancer cells using lectin-binding BODIPY conjugated avidin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE D-galactose receptor; molecular imaging; neoplasms; peritoneal metastasis; surgery; flow cytometry; optical imaging; endoscopy ID TUMOR AB Lectins (asialo-receptor family) are expressed on a number of tumors that develop peritoneal metastases. To demonstrate that fluorescence imaging based on lectin binding is applicable for a variety of tumors, we conjugated BODIPY to avidin (avidin-BODIPY), and studied the efficacy of tumor targeting in 9 cancer cell lines in vitro and an ovarian cancer cell line in vivo using a murine peritoneal cancer model. All 9 cell lines showed specific intracellular accumulation with avidin-BODIPY on fluorescence microscopy and flow cytometry. In vivo spectral molecular imaging clearly visualized the peritoneal tumor foci with avidin-BODIPY, whereas, deglycosylated avidin-BODIPY (neutravidin-BODIPY) showed only minimal fluorescence from the tumor foci and was accompanied by higher background signals. These results suggest the lectin-targeted molecular imaging technique using a targeted green fluorescence probe is potentially useful in a wide variety of cancers with a proclivity for dissemination in the peritoneal space. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Ctr Canc REs, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan. RP Kobayashi, H (reprint author), NCI, Ctr Canc REs, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov RI Urano, Yasuteru/H-1380-2012 FU Intramural NIH HHS NR 14 TC 32 Z9 33 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 29 PY 2006 VL 348 IS 3 BP 807 EP 813 DI 10.1016/j.bbrc.2006.07.169 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 079HM UT WOS:000240166500005 PM 16904640 ER PT J AU Choudhry, V Zhang, MY Harris, I Sidorov, IA Vu, B Dimitrov, AS Fouts, T Dimitrov, DS AF Choudhry, Vidita Zhang, Mei-Yun Harris, Ilia Sidorov, Igor A. Vu, Bang Dimitrov, Antony S. Fouts, Timothy Dimitrov, Dimiter S. TI Increased efficacy of HIV-1 neutralization by antibodies at low CCR5 surface concentration SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE HIV; antibody; X5; 2F5; 4E10; CCR5; envelope glycoprotein; neutralization ID IMMUNODEFICIENCY-VIRUS TYPE-1; CORECEPTOR-BINDING-SITE; RECEPTOR DENSITY; BETA-CHEMOKINES; T-CELLS; MACROPHAGES; CXCR4; CD4; GLYCOPROTEIN; GP120 AB It has been observed that some antibodies, including the CD4-induced (CD4i) antibody IgG X5 and the gp41-specific antibody IgG 2F5. exhibit higher neutralizing activity in PBMC-based assays than in cell line based assays [J.M. Binley, T. Wrin, B. Korber, M.B. Zwick, M. Wang, C. Chappey, G. Stiegler, R. Kunert, S. Zolla-Pazner, H. Katinger, C.J. Petropoulos, D.R. Burton, Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type I monoclonal antibodies, J. Virol. 78 (2004) 13232-13252]. It has been hypothesized that the lower CCR5 concentration on the surface of the CD4 T lymphocytes compared to that on cell lines used for the neutralization assays could be a contributing factor to the observed differences in neutralizing activity. To test this hypothesis and to further elucidate the contribution of CCR5 concentration differences on antibody neutralizing activity, we used a panel of HeLa cell lines with well-defined and differential surface concentrations of CCR5 and CD4 in a pseudovirus-based assay. We observed that the CCR5 cell surface concentration but not the CD4 concentration had a significant effect on the inhibitory activity of X5 and several other CD4i antibodies including 1713 and m9, as well as that of the gp41-specifc antibodies 2F5 and 4E10 but not on that of the CD4 binding site antibody (CD4bs), b12. The 50% inhibitory concentration (IC50) decreased up to two orders of magnitude in cell lines with low CCR5 concentration corresponding to that in CD4 T cells used in PBMC-based assays (about 10(3) per cell) compared to cell lines with high CCR5 concentration (about 10(4) or more). Our results suggest that the CCR5 cell surface concentration could be a contributing factor to the high neutralizing activities of some antibodies in PBMC-based-assays but other factors could also play an important role. These findings could have implications for development of vaccine immunogens based on the epitopes of X5 and other CD4i antibodies, for elucidation of the mechanisms of HIV-1 neutralization by antibodies, and for design of novel therapeutic approaches. Published by Elsevier Inc. C1 NCI, Prot Interact Grp, CCRNP, CCR,NIH, Frederick, MD 21702 USA. SAIC Frederick Inc, NCI Frederick, BRP, Frederick, MD 21702 USA. Profectus BioSci Inc, Baltimore, MD 21227 USA. RP Choudhry, V (reprint author), NCI, Prot Interact Grp, CCRNP, CCR,NIH, Bldg 320,Room 8,POB B,Miller Dr, Frederick, MD 21702 USA. EM vchoudhry@ncifcrf.gov; dimitrov@nciferf.gov OI Fouts, Timothy/0000-0002-2429-2859; Sidorov, Igor/0000-0001-6519-4983 FU NCI NIH HHS [N01 CO12400/CO/NCI, N01-CO-12400] NR 22 TC 53 Z9 54 U1 2 U2 5 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 SEP 29 PY 2006 VL 348 IS 3 BP 1107 EP 1115 DI 10.1016/j.bbrc.2006.07.163 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 079HM UT WOS:000240166500045 PM 16904645 ER PT J AU Cohen, RA McComb, ME AF Cohen, Richard A. McComb, Mark E. TI Preconditioning enters the era of "physiological proteomics" SO CIRCULATION RESEARCH LA English DT Editorial Material DE preconditioning; proteomics; ischemia; mitochondria; mass spectrometry ID MYOCARDIUM; ISCHEMIA; INJURY C1 Boston Univ, Sch Med, Vasc Biol Univ, Boston, MA 02118 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, NIH,NHLBI Cardiovasc Proteom Ctr, Boston, MA 02118 USA. Boston Univ, Sch Med, Mass Spectrometry Resource Ctr, Boston, MA 02118 USA. RP Cohen, RA (reprint author), Boston Univ, Sch Med, Vasc Biol Univ, 650 Albany St,X720, Boston, MA 02118 USA. EM racohen@bu.edu OI Cohen, Richard/0000-0002-1070-6408; McComb, Mark/0000-0002-4249-485X FU NCRR NIH HHS [P41RR10888-6]; NHLBI NIH HHS [N01-HV-28178] NR 13 TC 1 Z9 1 U1 0 U2 2 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 SEP 29 PY 2006 VL 99 IS 7 BP 663 EP 665 DI 10.1161/01.RES.0000245431.16226.c6 PG 3 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 088YK UT WOS:000240846800001 PM 17008594 ER PT J AU Waheed, AA Ablan, SD Mankowski, MK Cummins, JE Ptak, RG Schaffner, CP Freed, EO AF Waheed, Abdul A. Ablan, Sherimay D. Mankowski, Marie K. Cummins, James E. Ptak, Roger G. Schaffner, Carl P. Freed, Eric O. TI Inhibition of HIV-1 replication by amphotericin B methyl ester - Selection for resistant variants SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRION-ASSOCIATED CHOLESTEROL; GP41 CYTOPLASMIC TAIL; CELL-SURFACE EXPRESSION; TYROSINE-BASED SIGNAL; ENVELOPE GLYCOPROTEIN; LIPID RAFTS; ANTIRETROVIRAL THERAPY; MEMBRANE CHOLESTEROL; CLATHRIN ADAPTER AB Membrane cholesterol plays an important role in human immunodeficiency virus type 1 (HIV-1) particle production and infectivity. Here, we have investigated the target and mechanism of action of a cholesterol-binding compound, the polyene antifungal antibiotic amphotericin B methyl ester (AME). We found that AME potently inhibited the replication of a highly divergent panel of HIV-1 isolates in various T-cell lines and primary cells irrespective of clade or target cell tropism. The defects in HIV-1 replication caused by AME were due to profoundly impaired viral infectivity as well as a defect in viral particle production. To elucidate further the mechanism of action of AME, we selected for and characterized AME-resistant HIV-1 variants. Mutations responsible for AME resistance mapped to a highly conserved and functionally important endocytosis motif in the cytoplasmic tail of the transmembrane glycoprotein gp41. Interestingly, truncation of the gp41 cytoplasmic tail in the context of either HIV-1 or rhesus macaque simian immunodeficiency virus also conferred resistance to AME. The infectivity of HIV-1 virions bearing murine leukemia virus or vesicular stomatitis virus glycoproteins was unaffected by AME. Our data define the target and mechanism of action of AME and provide support for the concept that cholesterol-binding compounds should be pursued as antiretroviral drugs to disrupt HIV-1 replication. C1 NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. So Res Inst, Infect Dis Res Dept, Frederick, MD 21701 USA. Rutgers State Univ, Waksman Inst, Dept Microbiol & Biochem, New Brunswick, NJ 08903 USA. RP Freed, EO (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, NIH, Bldg 535,Rm 108, Frederick, MD 21702 USA. EM efreed@mail.nih.gov FU Intramural NIH HHS NR 73 TC 34 Z9 36 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 SEP 29 PY 2006 VL 281 IS 39 BP 28699 EP 28711 DI 10.1074/jbc.M603609200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 086NO UT WOS:000240680500023 PM 16882663 ER PT J AU Joe, YS Jeong, JH Yang, S Kang, H Motoyama, N Pandolfi, PP Chung, JH Kim, MK AF Joe, YeonSoo Jeong, Jae-Hoon Yang, Shutong Kang, Hyeog Motoyama, Noburu Pandolfi, Pier Paolo Chung, Jay H. Kim, Myung K. TI ATR, PML, and CHK2 play a role in arsenic trioxide-induced apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; DEPENDENT PROTEIN-KINASE; DNA-DAMAGE CHECKPOINT; ATAXIA-TELANGIECTASIA; HISTONE H2AX; CELL-LINES; ACTIVATION; PHOSPHORYLATION; PATHWAY; P53 AB Arsenic trioxide (ATO) is a potent anti-leukemic chemotherapeutic agent for acute promyelocytic leukemia (APL) that results from a t (15, 17) chromosomal translocation that produces PML-RAR alpha, a fusion protein between a tumor suppressor PML and the retinoic acid receptor RAR alpha. APL patients are initially treated with retinoic acid, but most develop resistance and relapse. In contrast, ATO induces prolonged remissions even in the relapsed cases. However, the molecular mechanisms by which ATO kills the leukemic cells are not fully understood. We find that ATO induces apoptosis, at least in part, by activating proapoptotic kinase Chk2. ATO does this by stimulating ATR (ataxia telangiectasia mutated and Rad3-related) kinase, a Chk2-activating kinase. In conjunction, ATO degrades PML-RAR alpha, resulting in the restoration of PML, which is required for autophosphorylation and full activation of Chk2. As a result, the p53-dependent apoptosis pathway is activated. Based on this, we propose that a pathway composed of ATR, PML, Chk2, and p53 plays a role in ATO-mediated apoptosis, a notion that is consistent with the observation that Chk2 is genetically intact and mutations in the p53 gene are extremely rare in APL. C1 Natl Inst Hlth, NHLBI, Lab Biochem Genet, Bethesda, MD 20892 USA. Natl Inst Longev Sci, Dept Geriatr Res, Obu, Aichi 4748522, Japan. Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Chung, JH (reprint author), Natl Inst Hlth, NHLBI, Lab Biochem Genet, Bldg 10,Rm 7D14,10 Ctr Dr, Bethesda, MD 20892 USA. EM ChungJ@nhlbi.nih.gov; KimM@nhlbi.nih.gov FU Intramural NIH HHS NR 38 TC 29 Z9 31 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 SEP 29 PY 2006 VL 281 IS 39 BP 28764 EP 28771 DI 10.1074/jbc.M604392200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 086NO UT WOS:000240680500030 PM 16891316 ER PT J AU Kim, SY Nguyen, AD Gao, JL Murphy, PM Mansfield, BC Chou, JY AF Kim, So Youn Nguyen, Andrew D. Gao, Ji-Liang Murphy, Philip M. Mansfield, Brian C. Chou, Janice Yang TI Bone marrow-derived cells require a functional glucose 6-phosphate transporter for normal myeloid functions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DISEASE TYPE 1B; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; PHOSPHOHISTIDINE-ENZYME INTERMEDIATE; LIVER-TRANSPLANTATION; HEXOSE-6-PHOSPHATE DEHYDROGENASE; NEUTROPHIL RECRUITMENT; MICE LACKING; CATALYSIS; IB AB Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the ubiquitously expressed glucose 6-phosphate transporter (Glc-6-PT). Glc-6-PT activity has been shown to be critical in the liver and kidney where a deficiency disrupts glucose homeostasis. GSD-Ib patients also have defects in the neutrophil respiratory burst, chemotaxis, and calcium flux. They also manifest neutropenia, but whether Glc-6-PT deficiency in the bone marrow underlies myeloid dysfunctions in GSD-Ib remains controversial. To address this, we transferred bone marrow from Glc-6-PT-deficient (Glc-6-PT-/-) mice to wild-type mice to generate chimeric mice (BM-Glc-6-PT-/-). As a control, we also transferred bone marrow between wild-type mice (BM-Glc-6-PT+/+). While BM-Glc-6-PT+/+ mice have normal myeloid functions, BM-Glc-6-PT-/- mice manifest myeloid abnormalities characteristic of Glc-6-PT-/- mice. Both have impairments in their neutrophil respiratory burst, chemotaxis response, and calcium flux activities and exhibit neutropenia. In the bone marrow of BM-Glc-6-PT-/- and Glc-6-PT-/- mice, the numbers of myeloid progenitor cells are increased, while in the serum there is an increase in granulocyte colony-stimulating factor and chemokine KC levels. Moreover, in an experimental model of peritoneal inflammation, local production of KC and the related chemokine macrophage inflammatory protein-2 is decreased in both BM-Glc-6-PT-/- and Glc-6-PT-/- mice along with depressed peritoneal neutrophil accumulation. The neutrophil recruitment defect was less severe in BM-Glc-6-PT-/- mice than in Glc-6-PT-/- mice. These findings demonstrate that Glc-6-PT expression in bone marrow and neutrophils is required for normal myeloid functions and that non-marrow Glc-6-PT activity also influences some myeloid functions. C1 NICHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NIAID, Lab Mol Immunol, Mol Signaling Sect, NIH, Bethesda, MD 20892 USA. Correlog Syst Inc, Rockville, MD 20850 USA. RP Chou, JY (reprint author), NICHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bldg 10,Rm 9D42, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov OI Mansfield, Brian/0000-0002-8533-2789 FU Intramural NIH HHS NR 27 TC 23 Z9 23 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 SEP 29 PY 2006 VL 281 IS 39 BP 28794 EP 28801 DI 10.1074/jbc.M604964200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 086NO UT WOS:000240680500033 PM 16891306 ER PT J AU Donaldson, JR Courcelle, CT Courcelle, J AF Donaldson, Janet R. Courcelle, Charmain T. Courcelle, Justin TI RuvABC is required to resolve Holliday junctions that accumulate following replication on damaged templates in Escherichia coli SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECOMBINATION-DEFICIENT MUTANTS; INDUCED DNA-DAMAGE; ULTRAVIOLET-LIGHT; LAGGING-STRAND; IN-VITRO; GENETIC-RECOMBINATION; FORK REVERSAL; LESION BYPASS; POL-V; POSTREPLICATION REPAIR AB RuvABC is a complex that promotes branch migration and resolution of Holliday junctions. Although ruv mutants are hypersensitive to UV irradiation, the molecular event(s) that necessitate RuvABC processing in vivo are not known. Here, we used a combination of two-dimensional gel analysis and electron microscopy to reveal that although ruvAB and ruvC mutants are able to resume replication following arrest at UV-induced lesions, molecules that replicate in the presence of DNA damage accumulate unresolved Holliday junctions. The failure to resolve the Holliday junctions on the fully replicated molecules correlates with a delayed loss of genomic integrity that is likely to account for the loss of viability in these cells. The strand exchange intermediates that accumulate in ruv mutants are distinct from those observed at arrested replication forks and are not subject to resolution by RecG. These results indicate that the Holliday junctions observed in ruv mutants are intermediates of a repair pathway that is distinct from that of the recovery of arrested replication forks. A model is proposed in which RuvABC is required to resolve junctions that arise during the repair of a subset of nonarresting lesions after replication has passed through the template. C1 Portland State Univ, Dept Biol, Portland, OR 97207 USA. RP Donaldson, JR (reprint author), Natl Inst Hlth, NIDDK, GBB 5 Mem Dr,MSC 0538, Bethesda, MD 20892 USA. EM donaldsonjr@niddk.nih.gov FU NIGMS NIH HHS [F32 GM068566] NR 74 TC 27 Z9 27 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 SEP 29 PY 2006 VL 281 IS 39 BP 28811 EP 28821 DI 10.1074/jbc.M603933200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 086NO UT WOS:000240680500035 PM 16895921 ER PT J AU Botta, D Shi, S White, CC Dabrowski, MJ Keener, CL Srinouanprachanh, SL Farin, FM Ware, CB Ladiges, WC Pierce, RH Fausto, N Kavanagh, TJ AF Botta, Dianne Shi, Shengli White, Collin C. Dabrowski, Michael J. Keener, Cassie L. Srinouanprachanh, Sengkeo L. Farin, Federico M. Ware, Carol B. Ladiges, Warren C. Pierce, Robert H. Fausto, Nelson Kavanagh, Terrance J. TI Acetaminophen-induced liver injury is attenuated in male glutamate-cysteine ligase transgenic mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; HAMSTER V79 CELLS; MITOCHONDRIAL PERMEABILITY TRANSITION; INDUCED HEPATIC NECROSIS; MODIFIER SUBUNIT GENE; NITRIC-OXIDE SYNTHASE; INDUCED HEPATOTOXICITY; GLUTATHIONE SYNTHESIS; CATALYTIC SUBUNIT; PEROXYNITRITE FORMATION AB Acetaminophen overdose is a leading cause of drug-related acute liver failure in the United States. Glutathione, a tripeptide antioxidant protects cells against oxidative damage from reactive oxygen species and plays a crucial role in the detoxification of xenobiotics, including acetaminophen. Glutathione is synthesized in a two-step enzymatic reaction. Glutamate-cysteine ligase carries out the rate-limiting and first step in glutathione synthesis. We have generated C57Bl/6 mice that conditionally overexpress glutamate-cysteine ligase, and report here their resistance to acetaminophen-induced liver injury. Indices of liver injury included histopathology and serum alanine aminotransferase activity. Male transgenic mice induced to overexpress glutamate-cysteine ligase exhibited resistance to acetaminophen-induced liver injury when compared with acetaminophen-treated male mice carrying, but not expressing glutamate-cysteine ligase transgenes, or to female glutamate-cysteine ligase transgenic mice. We conclude that glutamate-cysteine ligase activity is an important factor in determining acetaminophen-induced liver injury in C57Bl/6 male mice. Because people are known to vary in their glutamate-cysteine ligase activity, this enzyme may also be an important determinant of sensitivity to acetaminophen-induced liver injury in humans. C1 Univ Washington, NIEHS, Ctr Ecogenet & Environm Hlth, Seattle, WA 98105 USA. Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98105 USA. Univ Washington, Dept Comparat Med, Seattle, WA 98105 USA. Univ Washington, Dept Pathol, Seattle, WA 98105 USA. Univ Rochester, Sch Med & Dent, Dept Pathol & Lab Med, Rochester, NY 14642 USA. RP Kavanagh, TJ (reprint author), Univ Washington, Box 354695, Seattle, WA 98195 USA. EM tjkav@u.washington.edu FU NIA NIH HHS [5P01AG001751]; NIEHS NIH HHS [5P42ES004696, 2P30ES007033, 5R01ES010849] NR 56 TC 31 Z9 33 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 29 PY 2006 VL 281 IS 39 BP 28865 EP 28875 DI 10.1074/jbc.M605143200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 086NO UT WOS:000240680500041 PM 16840778 ER PT J AU Dobi, A Szemes, M Lee, C Palkovits, M Lim, F Gyorgy, A Mahan, MA Agoston, DV AF Dobi, Albert Szemes, Marianna Lee, Cheol Palkovits, Miklos Lim, Francis Gyorgy, Andrea Mahan, Mark A. Agoston, Denes V. TI AUF1 ls expressed in the developing brain, binds to AT-rich double-stranded DNA, and regulates enkephalin gene expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN; MESSENGER-RNA DECAY; TRANSCRIPTION FACTORS; CHROMATIN DOMAINS; PROTEIN ISOFORMS; HNRNP PROTEINS; ARID PROTEINS; IN-VIVO; MATRIX; REGION AB During our search for transcriptional regulators that control the developmentally regulated expression of the enkephalin (ENK) gene, we identified AUF1. ENK, a peptide neurotransmitter, displays precise cell-specific expression in the adult brain. AUF1 (also known as heterogeneous nuclear ribonucleoprotein D) has been known to regulate gene expression through altering the stability of AU-rich mRNAs. We show here that in the developing brain AUF1 proteins are expressed in a spatiotemporally defined manner, and p37 and p40/42 isoforms bind to an AT-rich double-stranded (ds) DNA element of the rat ENK (rENK) gene. This AT-rich dsDNA sequence acts as a cis-regulatory DNA element and is involved in regulating the cell-specific expression of the ENK gene in primary neuronal cultures. The AT-rich dsDNA elements are present at similar to 2.5 kb 5' upstream of the rat, human, and mouse ENK genes. AUF1 proteins are shown here to provide direct interaction between these upstream AT-rich DNA sequences and the TATA region of the rENK gene. Double immunohistochemistry demonstrated that in the developing brain AUF1 proteins are expressed by proliferating neural progenitors and by differentiating neurons populating brain regions, which will not express the ENK gene in the adult, suggesting a repressor role for AUF1 proteins during enkephalinergic differentiation. Their subnuclear distribution and interactions with AT-rich DNA suggest that in the developing brain they can be involved in complex nuclear regulatory mechanisms controlling the development- and cell-specific expression of the ENK gene. C1 Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. NIMH, Bethesda, MD 20892 USA. Univ New Mexico, Dept Biochem, Albuquerque, NM 87131 USA. Columbia Univ, Dept Neurol, New York, NY 10027 USA. RP Agoston, DV (reprint author), Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, B2036, Bethesda, MD 20814 USA. EM vagoston@usuhs.mil RI Palkovits, Miklos/F-2707-2013 NR 65 TC 20 Z9 21 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 29 PY 2006 VL 281 IS 39 BP 28889 EP 28900 DI 10.1074/jbc.M511858200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 086NO UT WOS:000240680500043 PM 16769718 ER PT J AU Jothi, R Cherukuri, PF Tasneem, A Przytycka, TM AF Jothi, Raja Cherukuri, Praveen F. Tasneem, Asba Przytycka, Teresa M. TI Co-evolutionary analysis of domains in interacting proteins reveals insights into domain-domain interactions mediating protein-protein interactions SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE co-evolution; protein-protein interaction; domain-domain interaction ID SACCHAROMYCES-CEREVISIAE; INTERACTION NETWORK; PHYLOGENETIC PROFILES; INTERACTION MAP; COEVOLUTION; COMPLEXES; SEQUENCE; CONSERVATION; DATABASE; PAIRS AB Recent advances in functional genomics have helped generate large-scale high-throughput protein interaction data. Such networks, though extremely valuable towards molecular level understanding of cells, do not provide any direct information about the regions (domains) in the proteins that mediate the interaction. Here, we performed co-evolutionary analysis of domains in interacting proteins in order to understand the degree of coevolution of interacting and non-interacting domains. Using a combination of sequence and structural analysis, we analyzed protein-protein interactions in F1-ATPase, Sec23p/Sec24p, DNA-directed RNA polymerase and nuclear pore complexes, and found that interacting domain pair(s) for a given interaction exhibits higher level of co-evolution than the non-interacting domain pairs. Motivated by this finding, we developed a computational method to test the generality of the observed trend, and to predict large-scale domain-domain interactions. Given a protein-protein interaction, the proposed method predicts the domain pair(s) that is most likely to mediate the protein interaction. We applied this method on the yeast interactome to predict domain-domain interactions, and used known domain-domain interactions found in PDB crystal structures to validate our predictions. Our results show that the prediction accuracy of the proposed method is statistically significant. Comparison of our prediction results with those from two other methods reveals that only a fraction of predictions are shared by all the three methods, indicating that the proposed method can detect known interactions missed by other methods. We believe that the proposed method can be used with other methods to help identify previously unrecognized domain-domain interactions on a genome scale, and could potentially help reduce the search space for identifying interaction sites. Published by Elsevier Ltd. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Boston Univ, Bioinformat Program, Boston, MA 02215 USA. Booz Allen Hamilton Inc, Rockville, MD 20852 USA. RP Jothi, R (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM jothi@ncbi.nlm.nih.gov; przytyck@ncbi.nlm.nih.gov RI Jothi, Raja/G-3780-2015 NR 74 TC 68 Z9 76 U1 2 U2 8 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 SEP 29 PY 2006 VL 362 IS 4 BP 861 EP 875 DI 10.1016/j.jmb.2006.07.072 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 095RE UT WOS:000241324700019 PM 16949097 ER PT J AU Wendler, D AF Wendler, D. TI Three steps to protecting pediatric research participation from excessive risks SO PLOS CLINICAL TRIALS LA English DT Editorial Material ID DEVELOPING-COUNTRIES; CLINICAL-TRIALS; MINIMAL RISK; STANDARD; BIASES C1 NIH, Unit Vulnerable Populat, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Unit Vulnerable Populat, Dept Clin Bioeth, Bldg 10, Bethesda, MD 20892 USA. NR 24 TC 3 Z9 3 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1555-5887 J9 PLOS CLIN TRIALS JI PLos Clin. Trials PD SEP 29 PY 2006 VL 1 IS 5 AR e25 DI 10.1371/journal.pctr.0010025 PG 5 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 150SQ UT WOS:000245238700001 PM 17016542 ER PT J AU Hudson, KL AF Hudson, Kathy L. TI Genetic testing oversight SO SCIENCE LA English DT Editorial Material C1 Genet & Publ Policy Ctr, Washington, DC USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Hudson, KL (reprint author), Genet & Publ Policy Ctr, Washington, DC USA. EM khudson5@jhu.edu NR 0 TC 17 Z9 17 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 SEP 29 PY 2006 VL 313 IS 5795 BP 1853 EP 1853 DI 10.1126/science.1134996 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 088SU UT WOS:000240832200001 PM 17008491 ER PT J AU Pletnev, AG Swayne, DE Speicher, J Rumyantsev, AA Murphy, BR AF Pletnev, Alexander G. Swayne, David E. Speicher, Jim Rumyantsev, Alexander A. Murphy, Brian R. TI Chimeric West Nile/dengue virus vaccine candidate: Preclinical evaluation in mice, geese and monkeys for safety and immunogenicity SO VACCINE LA English DT Article DE West Nile virus; live virus vaccine ID LIVE-ATTENUATED VACCINE; ANSER-ANSER-DOMESTICUS; TICK-BORNE FLAVIVIRUS; HUMAN NEURO-BLASTOMA; NILE-VIRUS; RHESUS-MONKEYS; ENVELOPE GLYCOPROTEIN; IMMUNODEFICIENT MICE; VERO CELLS; SCID MICE AB A live attenuated virus vaccine is being developed to protect against West Nile virus (WN) disease in humans. Previously, it was found that chimeric West Nile/dengue viruses (WN/DEN4 and WN/DEN4 Delta 30) bearing the membrane precursor and envelope protein genes of WN on a backbone of dengue type 4 virus (DEN4) with or without a deletion of 30 nucleotides (Delta 30) in the 3' noncoding region of the DEN4 part of the chimeric genome were attenuated and efficacious in mice and monkeys against WN challenge. Here, we report the generation of a clinical lot of WN/DEN4 Delta 30 virus and its further preclinical evaluation for safety and immunogenicity in mice, geese and monkeys. The vaccine candidate had lost neuroinvasiveness in highly sensitive immunodeficient mice inoculated intraperitoneally and had greatly reduced neurovirulence in suckling mice inoculated intracerebrally (IC). Compared to the wild-type WN parent, the chimeric virus was highly restricted in replication in both murine and human neuroblastoma cells as well as in brains of suckling mice. The WN/DEN4 Delta 30 virus failed to infect geese, indicating that chimerization of WN with DEN4 completely attenuated WN for this avian host. This observation suggests that the WN/DEN4 chimeric viruses would be restricted in their ability to be transmitted from vaccinees to domestic or wild birds. In monkeys, the WN/DEN4 Delta 30 vaccine candidate was highly immunogenic despite its low level of replication with undetectable viremia. Furthermore, the WN/DEN4 Delta 30 vaccine virus was safe and readily induced neutralizing antibodies against WN in monkeys immune to each of the four serotypes of dengue virus. These studies confirm the attenuation of WN/DEN4 Delta 30 for non-human primates, including dengue-immune monkeys, and demonstrate both a highly restricted replication (> 10(8)-fold decrease) in the brain of mice inoculated IC and an absence of infectivity for birds, findings that indicate this vaccine should be safe for both the recipient and the environment. (c) 2006 Elsevier Ltd. All rights reserved. C1 NIAID, NIH, Infect Dis Lab, Bethesda, MD 20892 USA. USDA ARS, SE Poultry Res Lab, Athens, GA 30605 USA. RP Pletnev, AG (reprint author), NIAID, NIH, Infect Dis Lab, 12735 Twinbrook Pkwy,Twinbrook 3,Room 3W13,MSC 81, Bethesda, MD 20892 USA. EM apletnev@niaid.nih.gov FU Intramural NIH HHS NR 33 TC 55 Z9 56 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD SEP 29 PY 2006 VL 24 IS 40-41 BP 6392 EP 6404 DI 10.1016/j.vaccine.2006.06.008 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 093OU UT WOS:000241178400005 PM 16831498 ER PT J AU Takada, Y Fariss, R Muller, M Bush, R Rushing, E Sieving, P AF Takada, Yuichiro Fariss, Robert N. Mueller, Morten Bush, Ronald A. Rushing, Elisabeth J. Sieving, Paul A. TI Retinoschisin expression and localization in rodent and human pineal and consequences of mouse RS1 gene knockout SO MOLECULAR VISION LA English DT Article ID LINKED JUVENILE RETINOSCHISIS; S-ANTIGEN; PARENCHYMAL TUMORS; IMMUNOCYTOCHEMICAL DEMONSTRATION; S-100 PROTEIN; CELLS; GLAND; PHOTORECEPTORS; LIGHT; MICE AB PURPOSE: The pineal gland shares a common neuroectoderm origin with the retina, and like the retina, regulates circadian rhythms through melatonin secretion. Recent expressed tag sequence (EST) analysis showed that several gene mutations, including RS1, which cause retinal degeneration, are also expressed in the pineal gland. Mutations in RS1 result in structural delamination of the neural retinal layers, leading to formation of schisis cavities in men affected with "X-linked retinoschisis" (XLRS). In this study, we evaluated RS1 expression in the rat and mouse as well as in human pineal and looked for morphological changes in the pineal of the RS1 knockout (RS1(-/Y)) mouse. METHODS: We analyzed rat and mouse pineal for RS1 expression by Northern blot and in situ hybridization. RS protein, synaptophysin, S-100, and GFAP localization in the pineal of rat and mouse and RS protein in human pineal were evaluated immunohistochemically. Morphological studies were performed using transmission electron microscopy and light microscopy comparing wild-type to the RS1(-/Y) mouse. RESULTS: RS1 expression was detected in RNA isolated from both the pineal and retina as a single major band migrating at about 5.5 kbp in Northern blots. RS1 riboprobe in situ hybridization demonstrated message in rat and mouse pineal, and immunohistochemistry showed RS protein in pinealocytes expressing synaptophysin but not in interstitial GFAP- and S100-positive glial cells. RS protein was present in many pinealocytes in human pineal. In light and electron microscopic examination of the pineal gland from RS1(-/Y) mice none of the structural changes found in the retina, such as cavity formation and loosening of the tissue, were seen. CONCLUSIONS: This study demonstrates that RS protein is expressed in the pinealocytes but not in interstitial glial cells. The lack of structural abnormalities in the RS1(-/Y) mice suggests that RS serves a different function in the pineal gland than in the retina. C1 NEI, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. Univ Copenhagen, Panum Inst, Inst Med Anat, Copenhagen, Denmark. Armed Forces Inst Pathol, Dept Neuropathol & Ophthalm Pathol, Washington, DC 20306 USA. RP Sieving, P (reprint author), NEI, NIH, 31 Ctr Dr,Bldg 31,Room 6A03,MSC 2510, Bethesda, MD 20892 USA. EM paulsieving@nei.nih.gov FU Intramural NIH HHS NR 44 TC 24 Z9 27 U1 0 U2 1 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD SEP 28 PY 2006 VL 12 IS 125 BP 1108 EP 1116 PG 9 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 103CW UT WOS:000241864300001 PM 17093404 ER PT J AU Anderson, LM AF Anderson, Lucy M. TI Environmental genotoxicants/carcinogens and childhood cancer: Bridgeable gaps in scientific knowledge SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the European-Environmental-Mutagen-Society CY JUL 03-07, 2005 CL Kos Isl, GREECE DE childhood cancer; perinatal; environmental; genotoxicants/carcinogens; DNA repair enzymes; carcinogen metabolism ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GLUTATHIONE-S-TRANSFERASE; DNA-REPAIR GENES; POLYCYCLIC AROMATIC-HYDROCARBONS; HUMAN-FETAL TISSUES; PARENTAL CIGARETTE-SMOKING; DRUG-METABOLIZING-ENZYMES; HUMAN EMBRYONIC-TISSUES; MALIGNANT BRAIN-TUMORS; HUMAN-LIVER MICROSOMES AB Cancer in children is a major concern in many countries. An important question is whether these childhood cancers are caused by something, or are just tragic random events. Causation of at least some children's cancers is suggested by direct and indirect evidence, including epidemiological data, and animal studies that predict early life sensitivity of humans to carcinogenic effects. Candidate risk factors include genotoxic agents (chemicals and radiation), but also diet/nutrition, and infectious agents/immune responses. With regard to likelihood of risks posed by genotoxicants, there are pros and cons. The biological properties of fetuses and infants are consistent with sensitivity to preneoplastic genotoxic damage. Recent studies of genetic polymorphisms in carcinogen-metabolizing enzymes confirm a role for chemicals. On the other hand, in numerous epidemiological studies, associations between childhood cancers and exposure to genotoxicants, including tobacco smoke, have been weak and hard to reproduce. Possibly, sensitive genetic or ontogenetic subpopulations, and/or co-exposure situations need to be discovered to allow identification of susceptible individuals and their risk factors. Among the critical knowledge gaps needing to be bridged to aid in this effort include detailed tissue and cellular ontogeny of carcinogen metabolism and DNA repair enzymes, and associations of polymorphisms in DNA repair enzymes with childhood cancers. Perinatal bioassays in animals of specific environmental candidates, for example, benzene, could help guide epidemiology. Genetically engineered animal models could be useful for identification of chemical effects on specific genes. Investigations of interactions between factors may be key to understanding risk. Finally, fathers and newborn infants should receive more attention as especially sensitive targets. Published by Elsevier B.V. C1 NCI, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. RP Anderson, LM (reprint author), NCI, Lab Comparat Carcinogenesis, Bldg 538, Frederick, MD 21702 USA. EM Andersol@mail.ncifcrf.gov NR 245 TC 18 Z9 21 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD SEP 28 PY 2006 VL 608 IS 2 SI SI BP 136 EP 156 DI 10.1016/j.mrgentox.2006.02.016 PG 21 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 088TY UT WOS:000240835200006 PM 16829162 ER PT J AU Edgar, R AF Edgar, Ron TI Challenge of choosing right level of microarray detail SO NATURE LA English DT Letter C1 NIH, Gene Express Grp, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Edgar, R (reprint author), NIH, Gene Express Grp, Natl Ctr Biotechnol Informat, Natl Lib Med, 45 Ctr Dr,MSC6511, Bethesda, MD 20892 USA. NR 1 TC 2 Z9 3 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 28 PY 2006 VL 443 IS 7110 BP 394 EP 394 DI 10.1038/443394b PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 088FY UT WOS:000240798800020 PM 17006493 ER PT J AU Shapiro, AMJ Ricordi, C Hering, BJ Auchincloss, H Lindblad, R Robertson, P Secchi, A Brendel, MD Berney, T Brennan, DC Cagliero, E Alejandro, R Ryan, EA DiMercurio, B Morel, P Polonsky, KS Reems, JA Bretzel, RG Bertuzzi, F Froud, T Kandaswamy, R Sutherland, DER Eisenbarth, G Segal, M Preiksaitis, J Korbutt, GS Barton, FB Viviano, L Seyfert-Margolis, V Bluestone, J Lakey, JRT AF Shapiro, A. M. James Ricordi, Camillo Hering, Bernhard J. Auchincloss, Hugh Lindblad, Robert Robertson, Paul Secchi, Antonio Brendel, Mathias D. Berney, Thierry Brennan, Daniel C. Cagliero, Enrico Alejandro, Rodolfo Ryan, Edmond A. DiMercurio, Barbara Morel, Philippe Polonsky, Kenneth S. Reems, Jo-Anna Bretzel, Reinhard G. Bertuzzi, Federico Froud, Tatiana Kandaswamy, Raja Sutherland, David E. R. Eisenbarth, George Segal, Miriam Preiksaitis, Jutta Korbutt, Gregory S. Barton, Franca B. Viviano, Lisa Seyfert-Margolis, Vicki Bluestone, Jeffrey Lakey, Jonathan R. T. TI International trial of the edmonton protocol for islet transplantation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DIABETES-MELLITUS; INSULIN-SECRETION; HUMAN-PANCREAS; TISSUE FACTOR; RECIPIENTS; ALLOTRANSPLANTATION; IMMUNOSUPPRESSION; AUTOGRAFTS; TOLERANCE; ANTIBODY AB Background: Islet transplantation offers the potential to improve glycemic control in a subgroup of patients with type 1 diabetes mellitus who are disabled by refractory hypoglycemia. We conducted an international, multicenter trial to explore the feasibility and reproducibility of islet transplantation with the use of a single common protocol (the Edmonton protocol). Methods: We enrolled 36 subjects with type 1 diabetes mellitus, who underwent islet transplantation at nine international sites. Islets were prepared from pancreases of deceased donors and were transplanted within 2 hours after purification, without culture. The primary end point was defined as insulin independence with adequate glycemic control 1 year after the final transplantation. Results: Of the 36 subjects, 16 (44%) met the primary end point, 10 (28%) had partial function, and 10 (28%) had complete graft loss 1 year after the final transplantation. A total of 21 subjects (58%) attained insulin independence with good glycemic control at any point throughout the trial. Of these subjects, 16 (76%) required insulin again at 2 years; 5 of the 16 subjects who reached the primary end point (31%) remained insulin-independent at 2 years. Conclusions: Islet transplantation with the use of the Edmonton protocol can successfully restore long-term endogenous insulin production and glycemic stability in subjects with type 1 diabetes mellitus and unstable control, but insulin independence is usually not sustainable. Persistent islet function even without insulin independence provides both protection from severe hypoglycemia and improved levels of glycated hemoglobin. (ClinicalTrials.gov number, NCT00014911.) C1 Univ Alberta, Clin Islet Transplant Program, Edmonton, AB T6G 2C8, Canada. Univ Miami, Miami, FL 33152 USA. Univ Minnesota, Minneapolis, MN USA. Harvard Univ, Sch Med, Boston, MA USA. Emmes Corp, Rockville, MD USA. Univ Washington, Seattle, WA 98195 USA. San Raffaele Sci Inst, I-20132 Milan, Italy. Univ Giessen, Giessen, Germany. Univ Geneva, CH-1211 Geneva 4, Switzerland. Washington Univ, St Louis, MO 63130 USA. NIAID, Rockville, MD USA. Univ Colorado, Barbara Davis Ctr, Boulder, CO 80309 USA. Immune Tolerance Network, San Francisco, CA USA. Immune Tolerance Network, Bethesda, MD USA. RP Shapiro, AMJ (reprint author), Univ Alberta, Clin Islet Transplant Program, 2000 Coll Plaza,8215 112th St, Edmonton, AB T6G 2C8, Canada. EM shapiro@islet.ca OI Ricordi, Camillo/0000-0001-8092-7153 NR 42 TC 991 Z9 1059 U1 4 U2 55 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 SEP 28 PY 2006 VL 355 IS 13 BP 1318 EP 1330 DI 10.1056/NEJMoa061267 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 088EF UT WOS:000240793600005 PM 17005949 ER PT J AU Yarchoan, R AF Yarchoan, Robert TI Key role for a viral lytic gene in Kaposi's sarcoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Yarchoan, R (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 5 TC 12 Z9 12 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 28 PY 2006 VL 355 IS 13 BP 1383 EP 1385 DI 10.1056/NEJMcibr063911 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 088EF UT WOS:000240793600018 PM 17005960 ER PT J AU Shimura, T Toyoshima, M Adiga, SK Kunoh, T Nagai, H Shimizu, N Inoue, M Niwa, O AF Shimura, T. Toyoshima, M. Adiga, S. K. Kunoh, T. Nagai, H. Shimizu, N. Inoue, M. Niwa, O. TI Suppression of replication fork progression in low-dose-specic p53-dependent S-phase DNA damage checkpoint SO ONCOGENE LA English DT Article DE p53; PCNA; ATM; S-phase DNA damage checkpoint; replication fork progression ID CELL NUCLEAR ANTIGEN; ATM GENE-PRODUCT; MAMMALIAN-CELLS; HOMOLOGOUS RECOMBINATION; REPLICON INITIATION; IONIZING-RADIATION; MOUSE ZYGOTES; STRAND BREAKS; BLM HELICASE; P53 AB The S-phase DNA damage checkpoint is activated by DNA damage to delay DNA synthesis allowing time to resolve the replication block. We previously discovered the p53-dependent S-phase DNA damage checkpoint in mouse zygotes fertilized with irradiated sperm. Here, we report that the same p53 dependency holds in mouse embryonic fibroblasts (MEFs) at low doses of irradiation. DNA synthesis in p53 wild-type (WT) MEFs was suppressed in a biphasic manner in which a sharp decrease below 2.5 Gy was followed by a more moderate decrease up to 10 Gy. In contrast, p53-/- MEFs exhibited radioresistant DNA synthesis below 2.5 Gy whereas the cells retained the moderate suppression above 5 Gy. DNA fiber analysis revealed that 1 Gy irradiation suppressed replication fork progression in p53 WT MEFs, but not in p53-/- MEFs. Proliferating cell nuclear antigen (PCNA), clamp loader of DNA polymerase, was phosphorylated in WT MEFs after 1 Gy irradiation and redistributed to form foci in the nuclei. In contrast, PCNA was not phosphorylated and dissociated from chromatin in 1 Gy-irradiated p53-/- MEFs. These results demonstrate that the novel low-dosespecific p53-dependent S-phase DNA damage checkpoint is likely to regulate the replication fork movement through phosphorylation of PCNA. C1 Kyoto Univ, Dept Late Effect Studies, Radiat Biol Ctr, Sakyo Ku, Kyoto, Japan. Kyoto Univ, Dept Radiat Syst Biol, Radiat Biol Ctr, Sakyo Ku, Kyoto, Japan. Hiroshima Univ, Grad Sch Biosphere Sci, Hiroshima, Japan. Kanazawa Med Univ, Med Res Inst, Uchinada, Ishikawa 92002, Japan. RP Shimura, T (reprint author), NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH Bldg 37,Rm 5056 37 Convent Dr, Bethesda, MD 20892 USA. EM shimurat@mail.nih.gov NR 57 TC 18 Z9 19 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 28 PY 2006 VL 25 IS 44 BP 5921 EP 5932 DI 10.1038/sj.onc.1209624 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 088QN UT WOS:000240826300001 PM 16682953 ER PT J AU Singh, SR Zhen, W Zheng, Z Wang, H Oh, SW Liu, W Zbar, B Schmidt, LS Hou, SX AF Singh, S. R. Zhen, W. Zheng, Z. Wang, H. Oh, S-W Liu, W. Zbar, B. Schmidt, L. S. Hou, S. X. TI The Drosophila homolog of the human tumor suppressor gene BHD interacts with the JAK-STAT and Dpp signaling pathways in regulating male germline stem cell maintenance SO ONCOGENE LA English DT Article DE tumor suppressor; Drosophila BHD homolog; male germline stem cell; stem cell maintenance; JAK/STAT signaling pathway; Dpp signaling pathway ID HOGG-DUBE-SYNDROME; SELF-RENEWAL; SPONTANEOUS PNEUMOTHORAX; RENAL TUMORS; DIFFERENTIATION; SPERMATOGENESIS; PROTEIN; MUTATIONS; FOLLICLE; ENCODES AB Birt-Hogg-Dube syndrome (BHD) is a rare, inherited genodermatosis characterized by hair follicle hamartomas, kidney tumors and spontaneous pneumothorax. The BHD locus was mapped to chromosome 17p11.2 by linkage analysis, and germ line mutations in a novel gene ( BHD) were identified in a panel of BHD families. Using RNA interference to decrease expression of the Drosophila BHD homolog (DBHD), we have demonstrated that DBHD is required for male germline stem cell (GSC) maintenance in the fly testis. Reduction of DBHD gene activity suppresses the GSC overproliferation phenotype associated with overexpression of either unpaired (upd) or decapentaplegic (dpp). Further genetic interaction experiments suggest that DBHD regulates GSC maintenance downstream or in parallel of the JAK/STAT and Dpp signal-transduction pathways. These findings suggest that the BHD protein may regulate tumorigenesis through modulating stem cells in human. C1 NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. NCI, Immunobiol Lab, NIH, Frederick, MD 21702 USA. NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Singh, SR (reprint author), NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. EM sshreeram@ncifcrf.gov; shou@mail.ncifcrf.gov RI Singh, Shree Ram/B-7614-2008 OI Singh, Shree Ram/0000-0001-6545-583X FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [N01-CO-12400] NR 29 TC 35 Z9 37 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 28 PY 2006 VL 25 IS 44 BP 5933 EP 5941 DI 10.1038/sj.onc.1209593 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 088QN UT WOS:000240826300002 PM 16636660 ER PT J AU McNeill-Blue, C Wetmore, BA Sanchez, JF Freed, WJ Merrick, BA AF McNeill-Blue, Charlesene Wetmore, Barbara A. Sanchez, Joseph F. Freed, William J. Merrick, B. Alex TI Apoptosis mediated by p53 in rat neural AF5 cells following treatment with hydrogen peroxide and staurosporine SO BRAIN RESEARCH LA English DT Article DE apoptosis; hydrogen peroxide; neural cells; p53; rat; staurosporine; neurodegeneration ID SV40 LARGE-T; OXIDATIVE STRESS; PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; DNA-DAMAGE; PC12 CELLS; STEM-CELLS; NEURODEGENERATIVE DISEASES; SIGNALING PATHWAYS; CASPASE ACTIVATION AB AF5 neural cells derived from fetal rat mesencephalic tissue were immortalized with a truncated SV40 LT vector lacking the p53-inactivating domain to maintain long-term cultures with a p53-responsive phenotype. This study examined p53 function in producing programmed cell death in propagating AFS neural cells after exposure to hydrogen peroxide (H(2)O(2)) and the kinase inhibitor staurosporine (STSP). Concentration-dependent exposure of AF5 cells to 0-800 mM H(2)O(2) and STSP at 0-1000 nM revealed increasing cytotoxicity from MTS cell viability assays. Apoptosis occurred at 400 mM H(2)O(2) as evidenced by subG(1) DNA and Annexin V flow cytometry analyses and cellular immunofluorescence staining with propidium iodide, anti-Annexin V and DAPI. DNA fragmentation, caspase-3/7 activity and cytochrome c release into cytosol also confirmed H(2)O(2)-mediated apoptotic events. p53 protein levels were increased over 24 h by H(2)O(2) in a coordinated fashion with mdm2 expression. pS3 activation by H(2)O(2) was evidenced by elevated Ser15 phosphorylation, increased luciferase p53 reporter activity and upregulation of the downstream p53 targets p21(waf1) and apoptotic proteins, bax, Noxa and PUMA. STSP exposure produced apoptosis demonstrated by DNA fragmentation, caspase-3/7 activity, cytochrome c release and over 24 h was accompanied by sustained increase in p53 and Ser15 phosphorylation, rise in p21(wafl) and bax and a transient increase in p53 reporter activity but without Annexin V binding. These findings demonstrate that AF5 cells undergo apoptosis in response to H(2)O(2)-mediated oxidative stress and signal pathway disruption by STSP that therefore would be useful in studies related to p53-dependent neuronal cell death and neuro degeneration. Published by Elsevier B.V. C1 NIEHS, NIH, Proteom Grp, Natl Ctr Toxicogen,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIDA, Cellular Neurobiol Res Branch, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Merrick, BA (reprint author), NIEHS, NIH, Proteom Grp, Natl Ctr Toxicogen,Dept Hlth & Human Serv, D2-04,POB 12233, Res Triangle Pk, NC 27709 USA. EM merrick@niehs.nih.gov NR 90 TC 32 Z9 36 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 27 PY 2006 VL 1112 BP 1 EP 15 DI 10.1016/j.brainres.2006.07.024 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 092XC UT WOS:000241129900001 PM 16901471 ER PT J AU Lindor, NM Petersen, GM Hadley, DW Kinney, AY Miesfeldt, S Lu, KH Lynch, P Burke, W Press, N AF Lindor, Noralane M. Petersen, Gloria M. Hadley, Donald W. Kinney, Anita Y. Miesfeldt, Susan Lu, Karen H. Lynch, Patrick Burke, Wylie Press, Nancy TI Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome - A systematic review SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID NONPOLYPOSIS COLORECTAL-CANCER; DNA-MISMATCH-REPAIR; MICROSATELLITE INSTABILITY; COLON-CANCER; GERMLINE MUTATIONS; ENDOMETRIAL CARCINOMA; FOLLOW-UP; EXTRACOLONIC CANCER; SCREENING PRACTICES; FAMILY-HISTORY AB Context About 2% of all colorectal cancer occurs in the context of the autosomal dominantly inherited Lynch syndrome, which is due to mutations in mismatch repair genes. Potential risk-reducing interventions are recommended for individuals known to have these mutations. Objectives To review cancer risks and data on screening efficacy in the context of Lynch syndrome (hereditary nonpolyposis colorectal cancer) and to provide recommendations for clinical management for affected families, based on available evidence and expert opinion. Data Sources and Study Selection A systematic literature search using PubMed and the Cochrane Database of Systematic Reviews, reference list review of retrieved articles, manual searches of relevant articles, and direct communication with other researchers in the field. Search terms included hereditary non-polyposis colon cancer, Lynch syndrome, microsatellite instability, mismatch repair genes, and terms related to the biology of Lynch syndrome. Only peer-reviewed, full-text, English-language articles concerning human subjects published between January 1, 1996, and February 2006 were included. The US Preventive Services Task Force's 2-tier system was adapted to describe the quality of evidence and to assign strength to the recommendations for each guideline. Evidence Synthesis The evidence supports colonoscopic surveillance for individuals with Lynch syndrome, although the optimal age at initiation and frequency of examinations is unresolved. Colonoscopy is recommended every 1 to 2 years starting at ages 20 to 25 years (age 30 years for those with MSH6 mutations), or 10 years younger than the youngest age of the person diagnosed in the family. While fully acknowledging absence of demonstrated efficacy, the following are also recommended annually: endometrial sampling and transvaginal ultrasound of the uterus and ovaries (ages 30-35 years); urinalysis with cytology (ages 25-35 years); history, examination, review of systems, education and genetic counseling regarding Lynch syndrome (age 21 years). Regular colonoscopy was favored for at-risk persons without colorectal neoplasia. For individuals who will undergo surgical resection of a colon cancer, subtotal colectomy is favored. Evidence supports the efficacy of prophylactic hysterectomy and oophorectomy. Conclusions The past 10 years have seen major advances in the understanding of Lynch syndrome. Current recommendations regarding cancer screening and prevention require careful consultation between clinicians, clinical cancer genetic services, and well-informed patients. C1 Oregon Hlth & Sci Univ, Sch Nursing, Portland, OR 97239 USA. Mayo Clin, Coll Med, Dept Med Genet, Rochester, MN USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. NHGRI, Social & Behav Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Utah, Dept Med, Salt Lake City, UT 84112 USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Vet Affairs Med Ctr, Salt Lake City, UT 84148 USA. Maine Ctr Canc Med & Blood Disorders, Portland, ME USA. Maine Med Ctr, Portland, ME 04102 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med & Nutr, Houston, TX 77030 USA. Univ Washington, Dept Med Hist & Eth, Seattle, WA 98195 USA. Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97239 USA. RP Press, N (reprint author), Oregon Hlth & Sci Univ, Sch Nursing, 3455 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM pressn@ohsu.edu FU Intramural NIH HHS; NCI NIH HHS [U01 CA074800]; NHGRI NIH HHS [3R01HG001885-03S2] NR 105 TC 355 Z9 361 U1 0 U2 30 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 27 PY 2006 VL 296 IS 12 BP 1507 EP 1517 DI 10.1001/jama.296.12.1507 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 087VD UT WOS:000240770000027 PM 17003399 ER PT J AU Henry, WK Tebas, P Lane, HC AF Henry, W. Keith Tebas, Pablo Lane, H. Clifford TI Explaining, predicting, and treating HIV-associated CD4 cell loss - After 25 years still a puzzle SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTION; DISEASE; PLASMA; PROGRESSION; AIDS; RESTRICTION; PROGNOSIS; VARIANTS; GENE C1 Hennepin Cty Med Ctr, HIV Program, Minneapolis, MN 55415 USA. Univ Minnesota, Minneapolis, MN USA. Univ Penn, Div Infect Dis, Philadelphia, PA USA. NIAID, Div Clin Res, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Henry, WK (reprint author), Hennepin Cty Med Ctr, HIV Program, 701 Pk Ave R7, Minneapolis, MN 55415 USA. EM keithh6680@aol.com RI Tebas, Pablo/A-7061-2008 NR 27 TC 13 Z9 14 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 27 PY 2006 VL 296 IS 12 BP 1523 EP 1525 DI 10.1001/jama.296.12.1523 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 087VD UT WOS:000240770000030 PM 17003402 ER PT J AU Nielsen, JA Maric, D Lau, P Barker, JL Hudson, LD AF Nielsen, Joseph A. Maric, Dragan Lau, Pierre Barker, Jeffery L. Hudson, Lynn D. TI Identification of a novel oligodendrocyte cell adhesion protein using gene expression profiling SO JOURNAL OF NEUROSCIENCE LA English DT Article DE oligodendrocyte; microarray; myelination; adhesion; cytoskeleton; actin ID NEURAL STEM-CELLS; PERIPHERAL-NERVE MYELINATION; RHO-FAMILY GTPASES; MONOCLONAL-ANTIBODY; DIFFERENTIATION; MEMBRANE; NEURONS; GROWTH; LINEAGE; CHOLESTEROL AB Oligodendrocytes undergo extensive changes as they differentiate from progenitors into myelinating cells. To better understand the molecular mechanisms underlying this transformation, we performed a comparative analysis using gene expression profiling of A2B5 (+) oligodendrocyte progenitors and O4 (+) oligodendrocytes. Cells were sort-purified ex vivo from postnatal rat brain using flow cytometry. Using Affymetrix microarrays, 1707 transcripts were identified with a more than twofold increase in expression in O4 (+) oligodendrocytes. Many genes required for oligodendrocyte differentiation were upregulated in O4 (+) oligodendrocytes, including numerous genes encoding myelin proteins. Transcriptional changes included genes required for cell adhesion, actin cytoskeleton regulation, and fatty acid and cholesterol biosynthesis. At the O4 (+) stage, there was an increase in expression of a novel proline-rich transmembrane protein (Prmp). Localized to the plasma membrane, Prmp displays adhesive properties that may be important for linking the extracellular matrix to the actin cytoskeleton. Together, our results highlight the usefulness of this discovery-driven experimental strategy to identify genes relevant to oligodendrocyte differentiation and myelination. C1 NINDS, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Hudson, LD (reprint author), Bldg 49,Room 5A82,49 Convent Dr, Bethesda, MD 20892 USA. EM hudsonl1@od.nih.gov FU Intramural NIH HHS NR 41 TC 52 Z9 53 U1 0 U2 2 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 SEP 27 PY 2006 VL 26 IS 39 BP 9881 EP 9891 DI 10.1523/JNEUROSCI.2246-06.2006 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 088QH UT WOS:000240825700008 PM 17005852 ER PT J AU Acharya, A Rishi, V Vinson, C AF Acharya, Asha Rishi, Vikas Vinson, Charles TI Stability of 100 homo and heterotypic coiled-coil a-a ' pairs for ten amino acids ( A, L, I, V, N, K, S, T, E, and R) SO BIOCHEMISTRY LA English DT Article ID GCN4 LEUCINE-ZIPPER; AMINO-ACID; ELECTROSTATIC INTERACTIONS; OLIGOMERIZATION STATE; PROTEIN STABILITY; CRYSTAL-STRUCTURE; DNA-BINDING; SPECIFICITY; POSITION; HELIX AB We present the thermal stability monitored by circular dichroism (CD) spectroscopy at 222 nm of 100 heterodimers that contain all possible coiled-coil a-a' pairs for 10 amino acids (I, V, L, N, A, K S, T, E, and R). This includes the stability of 36 heterodimers for 6 amino acids (I, V, L, N, A, and K) previously described (1) and 64 new heterodimers including the 4 amino acids (S, T, E, and R). We have calculated a double mutant alanine thermodynamic cycle to determine a-a' pair coupling energies to evaluate which a-a' pairs encourage specific dimerization partners. The four new homotypic a-a' pairs (T-T, S-S, R-R, E-E) are repulsive relative to A-A and have destabilizing coupling energies. Among the 90 heterotypic a-a' pairs, the stabilizing coupling energies contain lysine or arginine paired with either an aliphatic or a polar amino acid. The range in coupling energies for each amino acid reveals its potential to regulate dimerization specificity. The a-a' pairs containing isoleucine and asparagine have the greatest range in coupling energies and thus contribute dramatically to dimerization specificity, which is to encourage homodimerization. In contrast, the a-a' pairs containing charged amino acids (K, R, and E) show the least range in coupling energies and promiscuously encourage heterodimerization. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Vinson, C (reprint author), NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. EM Vinsonc@mail.nih.gov NR 41 TC 61 Z9 61 U1 2 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 26 PY 2006 VL 45 IS 38 BP 11324 EP 11332 DI 10.1021/bi060822u PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 085AQ UT WOS:000240575900008 PM 16981692 ER PT J AU Wagner, W Fodor, E Ginsburg, A Hammer, JA AF Wagner, Wolfgang Fodor, Elfrieda Ginsburg, Ann Hammer, John A., III TI The binding of DYNLL2 to myosin Va requires alternatively spliced exon B and stabilizes a portion of the myosin's coiled-coil domain SO BIOCHEMISTRY LA English DT Article ID DYNEIN LIGHT-CHAIN; NITRIC-OXIDE SYNTHASE; CYTOPLASMIC DYNEIN; UNCONVENTIONAL MYOSIN; PROTEIN COMPLEX; MOTOR COMPLEX; CARGO-BINDING; TAIL DOMAIN; FAMILY; LC8 AB The myosin Va light chain DYNLL2 has been proposed to function as an adaptor to link the myosin to certain cargo. Here, we mapped the binding site for DYNLL2 within the myosin Va heavy chain. Copurification and pull-down experiments showed that the heavy chain contains a single DYNLL2 binding site and that this site resides within a discontinuity in the myosin's central coiled-coil domain. Importantly, exon B, an alternatively spliced, three-amino acid exon, is a part of this binding site, and we show in the context of full-length myosin Va that this exon is required for DYNLL2-myosin Va interaction. We investigated the effect of DYNLL2 binding on the structure of a myosin Va heavy chain fragment that contains the DYNLL2 binding site and flanking sequence, only parts of which are strongly predicted to form a coiled coil. Circular dichroism measurements revealed a DYNLL2- induced change in the secondary structure of this dimeric myosin fragment that is consistent with an increase in alpha-helical coiled-coil content. Moreover, the binding of DYNLL2 considerably stabilizes this heavy chain fragment against thermal denaturation. Analytical ultracentrifugation yielded an apparent association constant of similar to 3 x 10(6) M(-1) for the interaction of DYNLL2 with the dimeric myosin fragment. Together, these data show that alternative splicing of the myosin Va heavy chain controls DYNLL2- myosin Va interaction and that DYNLL2 binding alters the structure of a portion of the myosin's coiled-coil domain. These results suggest that exon B could have a significant impact on the conformation and regulatory folding of native myosin Va, as well as on its interaction with certain cargos. C1 NHLBI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. NHLBI, NIH, Biochem Lab, Bethesda, MD 20892 USA. RP Hammer, JA (reprint author), NHLBI, NIH, Cell Biol Lab, Bldg 50,Room 2523,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hammerj@nhlbi.nih.gov FU Intramural NIH HHS NR 66 TC 38 Z9 38 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 26 PY 2006 VL 45 IS 38 BP 11564 EP 11577 DI 10.1021/bi061142u PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 085AQ UT WOS:000240575900032 PM 16981716 ER PT J AU Adair, JC Rudnicki, SA Boudreau, E Weiner, WJ Coyle, PK Corboy, JR AF Adair, J. C. Rudnicki, S. A. Boudreau, E. Weiner, W. J. Coyle, P. K. Corboy, J. R. TI Survey of training programs' means for promoting neurology and attracting trainees SO NEUROLOGY LA English DT Article ID MEDICAL-STUDENTS; LIFE-STYLE; RESIDENCY; COMMITTEE; WORKFORCE; CHOICE AB Objective: To determine neurology training opportunities available to medical students and to define factors that influence program choice. Methods: All neurology residency program directors and a random sample of residents were surveyed. Resident questions related to application, interview, and training experience. Directors' questions focused on ways their department generated interest in clinical neurosciences. Results: Medical schools introduce students to clinical neurology primarily through required clerkships. Contact time averages less than 4 weeks and emphasizes inpatient encounters. Preceptorships with neurology faculty do not exist at almost 40% of schools and only 14% have neuroscience tracks. Nearly all residency applicants matched their first or second choice. The majority declined at least one interview and 39% failed to rank at least one site they visited. When choosing where to apply, the programs' reputation and geographic considerations were paramount. When making a rank list, interactions with faculty and residents at interview were most important. Residents generally reported satisfaction with their programs and attribute morale to supportive relationships with faculty and residents. Conclusions: Neurology programs may be able to enhance students' impression of neurology through changes in their clinical experience and development of venues for more meaningful relationships with faculty. Attention to the residents' personal needs may increase the likelihood of matching the best available candidates and ensuring their satisfaction. C1 Univ New Mexico, Hlth Sci Ctr, Dept Neurol, Albuquerque, NM 87131 USA. New Mexico Vet Healthcare Syst, Albuquerque, NM USA. Univ Arkansas Med Sci, Dept Neurol, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Neurol, College Pk, MD 20742 USA. SUNY Stony Brook, Dept Neurol, Stony Brook, NY 11794 USA. Univ Colorado, Dept Neurol, Denver, CO 80202 USA. Hlth Sci Ctr, Denver, CO USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Adair, JC (reprint author), Univ New Mexico Hosp, Dept Neurol, ACC 2nd Floor,2211 Lomas Blvd NE, Albuquerque, NM 87131 USA. EM John.Adair@med.va.gov NR 14 TC 9 Z9 9 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 SEP 26 PY 2006 VL 67 IS 6 BP 936 EP 939 DI 10.1212/01.wnl.0000237324.47522.24 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 087NU UT WOS:000240749900004 PM 17000957 ER PT J AU Rakocevic, G Raju, R Semino-Mora, C Dalakas, MC AF Rakocevic, Goran Raju, Raghavan Semino-Mora, Cristina Dalakas, Marinos C. TI Stiff person syndrome with cerebellar disease and high-titer anti-GAD antibodies SO NEUROLOGY LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; ATAXIA; AUTOANTIBODIES; PATIENT AB We report five of 38 patients with stiff person syndrome (SPS), who also had cerebellar disease, gait ataxia, dysarthria, and oculomotor dysfunction (SPS-Cer). Cerebellar manifestations either preceded SPS or occurred concurrently. Brain MRI was normal. The intrathecal production of glutamic acid decarboxylase antibodies was elevated. gamma-Aminobutyric acid-enhancing drugs and immunotherapies improved only the stiffness. SPS-Cer is a distinct subset of SPS causing a more severe and complex clinical phenotype. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Gastrointestinal & Liver Studies Lab, Bethesda, MD 20814 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr,MSC 1382, Bethesda, MD 20892 USA. EM dalakasm@ninds.nih.gov RI Raju, Raghavan/E-9219-2011 FU Intramural NIH HHS NR 10 TC 38 Z9 40 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 26 PY 2006 VL 67 IS 6 BP 1068 EP 1070 DI 10.1212/01.wnl.0000237558.83349.d0 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 087NU UT WOS:000240749900031 PM 17000981 ER PT J AU Salajegheh, M Bryan, WW Dalakas, MC AF Salajegheh, Mohammad Bryan, Wilson W. Dalakas, Marinos C. TI The challenge of diagnosing ALS in patients with prior poliomyelitis SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; POLIO AB Four patients with postpolio syndrome ( PPS) developed ALS. Weakness and atrophy started from previously unaffected extremities but, contrary to PPS, spread to all muscles leading to death within 0.4 to 8 ( mean 3.9) years. Upper motor neuron signs were absent in the atrophic limbs. Abundant spontaneous activity and group atrophy in newly affected muscles were prominent. ALS can rarely occur in the postpolio population starting de novo rather than as evolution of PPS. C1 NINDS, NDS, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Dalakas, MC (reprint author), NINDS, NDS, NIH, Bldg 10,Room 4N248,10 Ctr Dr, Bethesda, MD 20892 USA. EM dalakasm@ninds.nih.gov FU Intramural NIH HHS NR 10 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 26 PY 2006 VL 67 IS 6 BP 1078 EP 1079 DI 10.1212/01.wnl.0000237342.73436.f6 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 087NU UT WOS:000240749900034 PM 17000983 ER PT J AU Sloand, EM Yong, ASM Ramkissoon, S Solomou, E Bruno, TC Kim, S Fuhrer, M Kajigaya, S Barrett, AJ Young, NS AF Sloand, Elaine M. Yong, Agnes S. M. Ramkissoon, Shakti Solomou, Elena Bruno, Tullia C. Kim, Sonnie Fuhrer, Monika Kajigaya, Sachiko Barrett, A. John Young, Neal S. TI Granulocyte colony-stimulating factor preferentially stimulates proliferation of monosomy 7 cells bearing the isoform IV receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hematopoiesis; myelodysplasia; clonal evolution; leukemia; marrow failure ID ACUTE MYELOID-LEUKEMIA; G-CSF RECEPTOR; SEVERE CONGENITAL NEUTROPENIA; SEVERE APLASTIC-ANEMIA; DISTINCT CYTOPLASMIC REGIONS; ACUTE MYELOGENOUS LEUKEMIA; MYELODYSPLASTIC SYNDROME; CYTOGENETIC ABNORMALITIES; EXPRESSION; GENE AB Granulocyte colony-stimulating factor (GCSF) administration has been linked to the development of monosomy 7 in severe congenital neutropenia and aplastic anemia. We assessed the effect of pharmacologic doses of GCSF on monosomy 7 cells to determine whether this chromosomal abnormality developed de novo or arose as a result of favored expansion of a preexisting clone. Fluorescence in situ hybridization (FISH) of chromosome 7 was used to identify small populations of aneuploid cells. When bone marrow mononuclear cells from patients with monosomy 7 were cultured with 400 ng/ml GCSF, all samples showed significant increases in the proportion of monosomy 7 cells. In contrast, bone marrow from karyotypically normal aplastic anemia, myelodysplastic syndrome, or healthy individuals did not show an increase in monosomy 7 cells in culture. In bone marrow CD34 cells of patients with myelodysplastic syndrome and monosomy 7, GCSF receptor (GCSFR) protein was increased. Although no mutation was found in genomic GCSFR DNA, CD34 cells showed increased expression of the GCSFR class IV mRNA isoform, which is defective in signaling cellular differentiation. GCSFR signal transduction via the Jak/Stat system was abnormal in monosomy 7 CD34 cells, with increased phosphorylated signal transducer and activation of transcription protein, STAT1-P, and increased STAT5-P relative to STAT3-P. Our results suggest that pharmacologic doses of GCSF increase the proportion of preexisting monosomy 7 cells. The abnormal response of monosomy 7 cells to GCSF would be explained by the expansion of undifferentiated monosomy 7 clones expressing the class IV GCSFR, which is defective in signaling cell maturation. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Sloand, EM (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM sloande@nih.gov NR 38 TC 60 Z9 71 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 SEP 26 PY 2006 VL 103 IS 39 BP 14483 EP 14488 DI 10.1073/pnas.0605245103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 090RG UT WOS:000240968100042 PM 16980411 ER PT J AU Peruzzi, B Athauda, G Bottaro, DP AF Peruzzi, Benedetta Athauda, Gagani Bottaro, Donald P. TI The von Hippel-Lindau tumor suppressor gene product represses oncogenic beta-catenin signaling in renal carcinoma cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE c-Met; hepatocyte growth factor; renal cell carcinoma ID HEPATOCYTE GROWTH-FACTOR; VON-HIPPEL-LINDAU; POLYCYSTIC KIDNEY-DISEASE; HYPOXIA-INDUCIBLE FACTOR; TYROSINE PHOSPHORYLATION; BRANCHING MORPHOGENESIS; INVASIVE GROWTH; C-MET; EXPRESSION; CANCER AB Loss of von Hippel-Lindau (VHL) tumor suppressor gene function occurs in familial and most sporadic clear cell renal cell carcinoma (RCC), resulting in the aberrant expression of genes that control cell proliferation, invasion, and angiogenesis. The molecular mechanisms by which VHL loss leads to tumorigenesis are not yet fully defined. VHL loss has been shown to allow robust RCC cell motility, invasiveness, and morphogenesis in response to hepatocyte growth factor (HGF) stimulation, processes that are known to contribute to tumor invasiveness and metastatic potential. Among the most likely intracellular mediators of these HGF-driven activities is ss-catenin, a structural link between cadherens and the actin cytoskeleton, as well as a gene transactivator. We show that reconstitution of VHL expression in RCC cells repressed HGF-stimulated ss-catenin tyrosyl phosphorylation, adherens junction disruption, cytoplasmic ss-catenin accumulation, and reporter gene transactivation in RCC cells. Ectopic expression of a ubiquitinationresistant ss-catenin mutant specifically restored HGF-stimulated invasion and morphogenesis in VHL-transfected RCC cells. VHL gene silencing in non-RCC renal epithelial cells phenotypically mimicked VHL loss in RCC, and HGF-driven invasiveness was blocked by the expression of a dominant-negative mutant of Tcf. We conclude that, unlike many other cancers, where HGF pathway activation contributes to malignancy through the acquisition of autocrine signaling, receptor overexpression, or mutation, in RCC cells VHL loss enables HGF-driven oncogenic ss-catenin signaling. These findings identify P-catenin as a potential target in biomarker and drug development for RCC. C1 NCI, Canc Res Ctr, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Bottaro, DP (reprint author), NCI, Canc Res Ctr, Urol Oncol Branch, NIH, Bldg 10,Room 1-3961,10 Ctr Dr,Mail Stop Code 1107, Bethesda, MD 20892 USA. EM dbottaro@helix.nih.gov RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 FU Intramural NIH HHS NR 58 TC 66 Z9 70 U1 2 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 SEP 26 PY 2006 VL 103 IS 39 BP 14531 EP 14536 DI 10.1073/pnas.0606850103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 090RG UT WOS:000240968100050 PM 16983094 ER PT J AU Checroun, C Wehrly, TD Fischer, ER Hayes, SF Celli, J AF Checroun, Claire Wehrly, Tara D. Fischer, Elizabeth R. Hayes, Stanley F. Celli, Jean TI Autophagy-mediated reentry of Francisella tularensis into the endocytic compartment after cytoplasmic replication SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE macrophage; pathogenesis; tularemia; trafficking ID HUMAN MACROPHAGES; MATURATION; PHAGOSOME; ESCAPE; GROWTH; TULAREMIA; MECHANISM; VACUOLES; CELLS; LIFE AB Intracellular bacterial pathogens evade the bactericidal functions of mammalian cells by physical escape from their phagosome and replication into the cytoplasm or through the modulation of phagosome maturation and biogenesis of a membrane-bound replicative organelle. Here, we detail in murine primary macrophages the intracellular life cycle of Francisella tularensis, a highly infectious bacterium that survives and replicates within mammalian cells. After transient interactions with the endocytic pathway, bacteria escaped from their phagosome by 1 h after infection and underwent replication in the cytoplasm from 4 to 20 h after infection. Unexpectedly, the majority of bacteria were subsequently found to be enclosed within large, juxtanuclear, LAMP-1-positive vacuoles called Franciselia-containing vacuoles (FCVs). FCV formation required intracytoplasmic replication of bacteria. Using electron and fluorescence microscopy, we observed that the FCVs contained morphologically intact bacteria, despite fusing with lysosomes. FCVs are multimembranous structures that accumulate monodansylcadaverine and display the autophagy-specific protein LC3 on their membrane. Formation of FCVs was significantly inhibited by 3-methyladenine, confirming a role for the autophagic pathway in the biogenesis of these organelles. Taken together, our results demonstrate that, via autophagy, F. tularensis reenters the endocytic pathway after cytoplasmic replication, a process thus far undescribed for intracellular pathogens. C1 NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Tularemia Pathogeneis Sect,NIH, Hamilton, MT 59840 USA. NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Microscopy Core Unit,NIH, Hamilton, MT 59840 USA. RP Celli, J (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Tularemia Pathogeneis Sect,NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM jcelli@niaid.nih.gov FU Intramural NIH HHS NR 26 TC 222 Z9 223 U1 0 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 SEP 26 PY 2006 VL 103 IS 39 BP 14578 EP 14583 DI 10.1073/pnas.0601838103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 090RG UT WOS:000240968100058 PM 16983090 ER PT J AU Parikh, NI Hwang, SJ Larson, MG Meigs, JB Levy, D Fox, CS AF Parikh, Nisha I. Hwang, Shih-Jen Larson, Martin G. Meigs, James B. Levy, Daniel Fox, Caroline S. TI Cardiovascular disease risk factors in chronic kidney disease - Overall burden and rates of treatment and control SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CHRONIC RENAL-INSUFFICIENCY; GLOMERULAR-FILTRATION-RATE; CORONARY-HEART-DISEASE; BLOOD-PRESSURE; SERUM CREATININE; SYSTOLIC HYPERTENSION; MYOCARDIAL-INFARCTION; DIALYSIS PATIENTS; ELDERLY PROGRAM; UNITED-STATES AB Background: Mild to moderate chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease. The burden of cardiovascular disease risk factors in this setting is not well described. Methods: We compared the age- and sex-adjusted prevalence of cardiovascular disease risk factors and their treatment and control among persons with and without CKD in 3258 Framingham offspring cohort members who attended the seventh examination cycle (1998-2001). Glomerular filtration rate (GFR) was estimated using the simplified Modification of Diet in Renal Disease Study equation. We defined CKD as a GFR of less than 59 mL/min per 1.73 m(2) in women and less than 64 mL/min per 1.73 m(2) in men. Results: Those with CKD were older, more likely to be obese (33.5% vs 29.3%; P=.02), and more likely to have low levels of high-density lipoprotein cholesterol (45.2% vs 29.4%; P <.001) and high triglyceride levels (39.9% vs 29.8%; P <.001). Those with CKD had a higher prevalence of hypertension (71.2% vs 42.7%; P <.001) and hypertension treatment (86.0% vs 72.5%; P <.001), but were less likely to achieve optimal blood pressure control ( 27.0% vs 45.5%; P <. 001). Participants with CKD had a higher prevalence of elevated low-density lipoprotein cholesterol levels (60.5% vs 44.7%; P=.06) and lipid-lowering therapy (57.1% vs 42.6%; P=.09), although this was not statistically significant. A greater proportion of individuals with CKD than those without had diabetes (23.5% vs 11.9%; P=.02) and were receiving diabetes treatment (63.6% vs 46.9%; P=.05), but were less likely to achieve a hemoglobin A(1c) level of less than 7% (43.8% vs 59.4%; P=.03). Conclusions: Chronic kidney disease is associated with a significant burden of cardiovascular disease risk factors in the community. The diagnosis of CKD should alert the practitioner to look for potentially modifiable cardiovascular risk factors. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Endocrinol Diabet & Hypertens, Brigham & Womens Hosp, Boston, MA 02115 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov FU NHLBI NIH HHS [N01-HC-25195] NR 57 TC 116 Z9 120 U1 2 U2 5 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 SEP 25 PY 2006 VL 166 IS 17 BP 1884 EP 1891 DI 10.1001/archinte.166.17.1884 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 087GI UT WOS:000240730500014 PM 17000946 ER PT J AU Csordas, G Renken, C Varnai, P Walter, L Weaver, D Buttle, KF Balla, T Mannella, CA Hajnoczky, G AF Csordas, Gyorgy Renken, Christian Varnai, Peter Walter, Ludivine Weaver, David Buttle, Karolyn F. Balla, Tamas Mannella, Carmen A. Hajnoczky, Gyorgy TI Structural and functional features and significance of the physical linkage between ER and mitochondria SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ROUGH ENDOPLASMIC-RETICULUM; CALCIUM SIGNAL TRANSMISSION; RAT-LIVER MITOCHONDRIA; LIGAND-BINDING; CHANNEL; CA2+; CELLS; ASSOCIATION; TOMOGRAPHY; EXPRESSION AB The role of mitochondria in cell metabolism and survival is controlled by calcium signals that are commonly transmitted at the close associations between mitochondria and endoplasmic reticulum (ER). However, the physical linkage of the ER-mitochondria interface and its relevance for cell function remains elusive. We show by electron tomography that ER and mitochondria are adjoined by tethers that are similar to 10 nm at the smooth ER and similar to 25 nm at the rough ER. Limited proteolysis separates ER from mitochondria, whereas expression of a short "synthetic linker" (< 5 nm) leads to tightening of the associations. Although normal connections are necessary and sufficient for proper propagation of ER-derived calcium signals to the mitochondria, tightened connections, synthetic or naturally observed under apoptosis-inducing conditions, make mitochondria prone to Ca2+ overloading and ensuing permeability transition. These results reveal an unexpected dependence of cell function and survival on the maintenance of proper spacing between the ER and mitochondria. C1 Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. Wadsworth Ctr, Albany, NY 12201 USA. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Hajnoczky, G (reprint author), Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. EM gyorgy.hajnoczky@jefferson.edu OI Balla, Tamas/0000-0002-9077-3335 FU Intramural NIH HHS; NCRR NIH HHS [P41 RR001219, RR01219]; NIDDK NIH HHS [DK51526, R01 DK051526, R29 DK051526] NR 36 TC 461 Z9 470 U1 2 U2 26 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 SEP 25 PY 2006 VL 174 IS 7 BP 915 EP 921 DI 10.1083/jcb.200604016 PG 7 WC Cell Biology SC Cell Biology GA 090JD UT WOS:000240946400002 PM 16982799 ER PT J AU Mukhopadhyay, D Ayaydin, F Kolli, N Tan, SH Anan, T Kametaka, A Azuma, Y Wilkinson, KD Dasso, M AF Mukhopadhyay, Debaditya Ayaydin, Ferhan Kolli, Nagamalleswari Tan, Shyh-Han Anan, Tadashi Kametaka, Ai Azuma, Yoshiaki Wilkinson, Keith D. Dasso, Mary TI SUSP1 antagonizes formation of highly SUMO2/3-conjugated species SO JOURNAL OF CELL BIOLOGY LA English DT Article ID UBIQUITIN-LIKE PROTEINS; SUMO-1 MODIFICATION; SEQUENCE ALIGNMENT; PROTEASE; IDENTIFICATION; CONJUGATION; COMPLEX; RANGAP1; CHAINS; YEAST AB Small ubiquitin-related modifier (SUMO) processing and deconjugation are mediated by sentrin-specific proteases/ubiquitin-like proteases (SENP/Ulps). We show that SUMO-specific protease 1 (SUSP1), a mammalian SENP/Ulp, localizes within the nucleoplasm. SUSP1 depletion within cell lines expressing enhanced green fluorescent protein (EGFP) fusions to individual SUMO paralogues caused redistribution of EGFP-SUMO2 and -SUMO3, particularly into promyelocytic leukemia (PML) bodies. Further analysis suggested that this change resulted primarily from a deficit of SUMO2/3-deconjugation activity.Under these circumstances, PML bodies became enlarged and increased in number. We did not observe a comparable redistribution of EGFP-SUMO1. We have investigated the specificity of SUSP1 using vinyl sulfone inhibitors and model substrates. We found that SUSP1 has a strong paralogue bias toward SUMO2/3 and that it acts preferentially on substrates containing three or more SUMO2/3 moieties. Together, our findings argue that SUSP1 may play a specialized role in dismantling highly conjugated SUMO2 and -3 species that is critical for PML body maintenance. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. Emory Univ, Dept Biochem, Atlanta, GA 30322 USA. Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA. RP Dasso, M (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM mdasso@helix.nih.gov RI Ayaydin, Ferhan/C-4849-2011; Tan, Shyh-Han/I-7037-2013; OI Tan, Shyh-Han/0000-0001-8250-7005; Dasso, Mary/0000-0002-5410-1371 FU Intramural NIH HHS [Z01 HD001902-13]; NIGMS NIH HHS [GM66355, R01 GM066355] NR 37 TC 100 Z9 110 U1 1 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 SEP 25 PY 2006 VL 174 IS 7 BP 939 EP 949 DI 10.1083/jcb.200510103 PG 11 WC Cell Biology SC Cell Biology GA 090JD UT WOS:000240946400005 PM 17000875 ER PT J AU Wang, QY Li, LY Ye, YH AF Wang, Qiuyan Li, Lianyun Ye, Yihong TI Regulation of retrotranslocation by p97-associated deubiquitinating enzyme ataxin-3 SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM MEMBRANE; ER-ASSOCIATED DEGRADATION; PROTEIN ATAXIN-3; POLYUBIQUITIN CHAINS; MISFOLDED PROTEINS; JOSEPHIN DOMAIN; AAA-ATPASE; UBIQUITIN; PROTEASOME; COMPLEX AB Misfolded proteins of the endoplasmic reticulum undergo retrotranslocation to enter the cytosol where they are degraded by the proteasome. Retrotranslocation of many substrates requires an ATPase complex consisting of the p97 ATPase and a dimeric cofactor, Ufd1-Npl4. We report that efficient elimination of misfolded ER proteins also involves ataxin-3 (atx3), a p97-associated deubiquitinating enzyme mutated in type-3 spinocerebellar ataxia. Overexpression of an atx3 mutant defective in deubiquitination inhibits the degradation of misfolded ER proteins and triggers ER stress. Misfolded polypeptides stabilized by mutant atx3 are accumulated in part as polyubiquitinated form, suggesting an involvement of its deubiquitinating activity in ER-associated protein degradation regulation. We demonstrate that atx3 transiently associates with the ER membrane via p97 and the recently identified Derlin-VIMP complex, and its release from the membrane appears to be governed by both the p97 ATPase cycle and its own deubiquitinating activity. We present evidence that atx3 may promote p97-associated deubiquitination to facilitate the transfer of polypeptides from p97 to the proteasome. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ye, YH (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM yihongy@mail.nih.gov FU Intramural NIH HHS NR 36 TC 106 Z9 107 U1 0 U2 12 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 SEP 25 PY 2006 VL 174 IS 7 BP 963 EP 971 DI 10.1083/jcb.200605100 PG 9 WC Cell Biology SC Cell Biology GA 090JD UT WOS:000240946400007 PM 17000876 ER PT J AU Birchenall-Roberts, MC Fu, T Kim, SG Huang, YK Dambach, M Resau, JH Ruscetti, FW AF Birchenall-Roberts, Maria C. Fu, Tao Kim, Soo-Gyung Huang, Ying K. Dambach, Michael Resau, James H. Ruscetti, Francis W. TI K-Ras4B proteins are expressed in the nucleolus: Interaction with nucleolin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE K-Ras4B; nucleolin; interaction; oncogenic ID PLASMA-MEMBRANE; LOCALIZATION SIGNALS; CELL-PROLIFERATION; CAAX MOTIF; RAS-FAMILY; NUCLEAR; GENE; SITE; IDENTIFICATION; CARCINOMAS AB Kirsten Ras4B (K-Ras4B) is a potent onco-protein that is expressed in the majority of human cell types and is frequently mutated in carcinomas. K-Ras4B, like other members of the Ras family of proteins, is considered to be a cytoplasmic protein that must be localized to the plasma membrane for activation. Here, using confocal microscopy and biochemical analysis, we show that K-Ras4B, but not H-Ras or the closely related K-Ras4A, is also present in the nucleoli of normal and transformed cells. Subcellular fractionation and immunostaining show that K-Ras4B is located not only in the cytoplasm, but also in the nucleolar compartment. Modification of a C-terminal hexa-lysine motif unique to K-Ras4B results in exclusively cytoplasmic forms of the protein. Nucleolin, a pleiotropic regulator of cellular processes, including transcriptional regulation, is also characterized by a nucleolar-like nuclear appearance. We show that K-Ras4B and nucleolin co-localize within the nucleus and that nucleolin physically associates with K-Ras4B. Inhibition of K-Ras4B/nucleolin association blocked nucleolar localization of K-Ras4B. Using siRNA to knockdown the expression of nucleolin eliminated the nucleolar localization of K-Ras4B and significantly repressed the activation of the well-characterized K-Ras4B transcriptional target Ap-1, but stimulated Elk1. These data provide evidence of a nucleolar localization of K-Ras4B and describe a functional association between K-Ras4B and nucleolin. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Canc Res Ctr, Frederick, MD 21702 USA. Van Andel Inst, Grand Rapids, MI 49506 USA. RP Birchenall-Roberts, MC (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM birchena@mail.ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 38 TC 15 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 22 PY 2006 VL 348 IS 2 BP 540 EP 549 DI 10.1016/j.bbrc.2006.07.094 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 080UW UT WOS:000240275000030 PM 16889753 ER PT J AU Wang, CY Kong, QP Yao, YG Zhang, YP AF Wang, Cheng-Ye Kong, Qing-Peng Yao, Yong-Gang Zhang, Ya-Ping TI mtDNA mutation C1494T, haplogroup A, and hearing loss in Chinese SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE mtDNA; C1494T; haplogroup A; aminoglycoside-induced and nonsyndromic hearing loss; phylogeny; Chinese ID HEREDITARY OPTIC NEUROPATHY; MITOCHONDRIAL-DNA; ETHNIC POPULATIONS; PHYLOGEOGRAPHIC ANALYSIS; SEQUENCE; REAPPRAISAL; PENETRANCE; PHYLOGENY; DEAFNESS; FAMILY AB Mutation C1494T in mitochondrial 12S rRNA gene was recently reported in two large Chinese families with aminoglycoside-induced and nonsyndromic hearing loss (AINHL) and was claimed to be pathogenic. This mutation, however, was first reported in a sample from central China in our previous study that was aimed to reconstruct East Asian mtDNA phylogeny. All these three mtDNAs formed a subclade defined by mutation C1494T in mtDNA haplogroup A. It thus seems that mutation C1494T is a haplogroup A-associated mutation and this matrilineal background may contribute a high risk for the penetrance of mutation C1494T in Chinese with AINHL. To test this hypothesis, we first genotyped mutation C1494T in 553 unrelated individuals from three regional Chinese populations and performed an extensive search for published complete or near-complete mtDNA data sets (> 3000 mtDNAs), we then screened the C1494T mutation in 111 mtDNAs with haplogroup A status that were identified from 1823 subjects across China. The search for published mtDNA data sets revealed no other mtDNA besides the above-mentioned three carrying mutation C1494T. None of the 553 randomly selected individuals and the 111 haplogroup A mtDNAs was found to bear this mutation. Therefore, our results suggest that C1494T is a very rare event. The mtDNA haplogroup A background in general is unlikely to play an active role in the penetrance of mutation C1494T in AINHL. (c) 2006 Elsevier Inc. All rights reserved. C1 Chinese Acad Sci, Kunming Inst Zool, Lab Cellular & Mol Evolut & Mol Biol Domest Anim, Kunming 650223, Peoples R China. Yunnan Univ, Lab Conservat & Utilizat Bioresource, Kunming 650091, Peoples R China. Grad Univ, Chinese Acad Sci, Beijing 100039, Peoples R China. RP Yao, YG (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Rm 3-5216,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ygyaozh@yahoo.com NR 25 TC 8 Z9 15 U1 0 U2 6 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 SEP 22 PY 2006 VL 348 IS 2 BP 712 EP 715 DI 10.1016/j.bbrc.2006.07.119 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 080UW UT WOS:000240275000053 PM 16890911 ER PT J AU Wakabayashi, Y Kipp, H Arias, IM AF Wakabayashi, Yoshiyuki Kipp, Helmut Arias, Irwin M. TI Transporters on demand: Intracellular reservoirs and cycling of bile canalicular ABC transporters SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID POLARIZED HEPATIC CELLS; CANINE KIDNEY-CELLS; PLASMA-MEMBRANE PROTEINS; SALT EXPORT PROTEIN; WIF-B CELLS; RAT-LIVER; PHOSPHOINOSITIDE 3-KINASE; SUBAPICAL COMPARTMENT; ACID SECRETION; MYOSIN VB C1 NICHD, CBMB, Unit Cellular Polar, NIH, Bethesda, MD 20892 USA. Tufts Univ, Sch Med, Dept Physiol & Med, Boston, MA 02111 USA. Univ Wurzburg, Dept Anat & Cell Biol, D-97070 Wurzburg, Germany. RP Arias, IM (reprint author), NICHD, CBMB, Unit Cellular Polar, NIH, Bldg 32T,Rm 101, Bethesda, MD 20892 USA. EM ariasi@mail.nih.gov FU NIDDK NIH HHS [DK 35652] NR 48 TC 41 Z9 41 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 SEP 22 PY 2006 VL 281 IS 38 BP 27669 EP 27673 DI 10.1074/jbc.R600013200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 084LM UT WOS:000240534400002 PM 16737964 ER PT J AU Bennasser, Y Yeung, ML Jeang, KT AF Bennasser, Yamina Yeung, Man Lung Jeang, Kuan-Teh TI HIV-1 TAR RNA subverts RNA interference in transfected cells through sequestration of TAR RNA-binding protein, TRBP SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; MICRORNA BIOGENESIS; VIRAL SUPPRESSOR; EXPRESSION; DICER; KINASE; PKR; RECOGNITION; INHIBITION AB TAR RNA-binding protein, TRBP, was recently discovered to be an essential partner for Dicer and a crucial component of the RNA-induced silencing complex ( RISC), a critical element of the RNA interference (RNAi) of the cell apparatus. Human TRBP was originally characterized and cloned 15 years ago based on its high affinity for binding the HIV-1 encoded leader RNA, TAR. RNAi is used, in part, by cells to defend against infection by viruses. Here, we report that transfected TAR RNA can attenuate the RNAi machinery in human cells. Our data suggest that TAR RNA sequesters TRBP rendering it unavailable for downstream Dicer-RISC complexes. TAR-induced inhibition of Dicer-RISC activity in transfected cells was partially relieved by exogenous expression of TRBP. C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bldg 4,Rm 306,Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 FU Intramural NIH HHS NR 42 TC 82 Z9 91 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 SEP 22 PY 2006 VL 281 IS 38 BP 27674 EP 27678 DI 10.1074/jbc.C6000722200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 084LM UT WOS:000240534400003 PM 16887810 ER PT J AU Dash, C Fisher, TS Prasad, VR Le Grice, SFJ AF Dash, Chandravanu Fisher, Timothy S. Prasad, Vinayaka R. Le Grice, Stuart F. J. TI Examining interactions of HIV-1 reverse transcriptase with single-stranded template nucleotides by nucleoside analog interference SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PRIMER GRIP REGION; SUBUNIT-SELECTIVE MUTAGENESIS; DIFFERENT SEQUENCE CONTEXTS; POLYMERASE ACTIVE-SITE; T7 DNA-POLYMERASE; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; TRANSLESION SYNTHESIS; FINGERS SUBDOMAIN AB Crystallographic studies have implicated several residues of the p66 fingers subdomain of human immunodeficiency virus type-1 reverse transcriptase in contacting the single-stranded template overhang immediately ahead of the DNA polymerase catalytic center. This interaction presumably assists in inducing the appropriate geometry on the template base for efficient and accurate incorporation of the incoming dNTP. To investigate this, we introduced nucleoside analogs either individually or in tandem into the DNA template ahead of the catalytic center and investigated whether they induce pausing of the replication machinery before serving as the template base. Analogs included abasic tetrahydrofuran linkages, neutralizing methylphosphonate linkages, and conformationally locked nucleosides. In addition, several Phe-61 mutants were included in our analysis, based on previous data indicating that altering this residue affects both strand displacement synthesis and the fidelity of DNA synthesis. We demonstrate here that altering the topology of the template strand two nucleotides ahead of the catalytic center can interrupt DNA synthesis. Mutating Phe-61 to either Ala or Leu accentuates this defect, whereas replacement with an aromatic residue (Trp) allows the mutant enzyme to bypass the template analogs with relative ease. C1 NCI, Frederick Canc Res & Dev Ctr, Resistance Mechanisms Lab, HIV Drug Resistance Program,NIH, Frederick, MD 21702 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. RP Le Grice, SFJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Resistance Mechanisms Lab, HIV Drug Resistance Program,NIH, Frederick, MD 21702 USA. EM slegrice@ncifcrf.gov FU Intramural NIH HHS; NIAID NIH HHS [R37 AI030861]; NIDA NIH HHS [R00 DA024558, K99 DA024558] NR 56 TC 10 Z9 10 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 SEP 22 PY 2006 VL 281 IS 38 BP 27873 EP 27881 DI 10.1074/jbc.M603970200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 084LM UT WOS:000240534400023 PM 16867979 ER PT J AU Majerciak, V Yamanegi, K Nie, SH Zheng, ZM AF Majerciak, Vladimir Yamanegi, Koji Nie, Sarah H. Zheng, Zhi-Ming TI Structural and functional analyses of Kaposi sarcoma-associated herpesvirus ORF57 nuclear localization signals in living cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REGULATORY PROTEIN ICP27; MESSENGER-RNA EXPORT; OPEN READING FRAME; VIRUS SM PROTEIN; MULTICENTRIC CASTLEMANS-DISEASE; PRIMARY EFFUSION LYMPHOMA; SIMPLEX-VIRUS; GENE-EXPRESSION; IN-VIVO; POSTTRANSCRIPTIONAL REGULATOR AB Kaposi sarcoma-associated herpesvirus (KSHV) ORF57 is a multifunctional, nuclear protein involved in post-transcriptional regulation of a subset of viral genes during lytic replication. Three nuclear localization signals (NLSs), NLS1 (amino acids (aa 101 - 107), NLS2 (aa 121 - 130), and NLS3 (aa 143 - 152), were identified in the N terminus of the ORF57 protein, and each of the three represents a short stretch of basic amino acid residues. Disruption of all three NLSs prevented localization of ORF57 in the nucleus. Insertion of individual NLSs into a heterologous cytoplasmic protein converted it into a nuclear protein, confirming that each NLS functions independently and is sufficient to promote protein nuclear localization. Although it exhibits a function similar to that of Epstein-Barr virus EB2 in promoting KSHV ORF59 expression, KSHV ORF57 differs from the herpes simplex virus ICP27 protein, and its function could be disrupted by point mutations of single or two NLSs in random combination, despite the proper localization of the mutant protein in the nucleus. The dysfunctional ORF57 containing NLS mutations also had low affinity with ORF59 RNA and the RNA export factor REF. However, the REF binding of ORF57 in vivo appeared to have no effect on ORF57-mediated enhancement of ORF59 expression. Thus, the three NLSs identified in ORF57 provide at least two functions, nuclear localization of ORF57 and up-regulation of ORF59 expression. C1 NCI, HIV & AIDS Malignancy Branch, Canc Res Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), NCI, HIV & AIDS Malignancy Branch, Canc Res Ctr, Natl Inst Hlth, 10 Ctr Dr,Rm 10 S255,MSC-1868, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov FU Intramural NIH HHS NR 52 TC 44 Z9 44 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 SEP 22 PY 2006 VL 281 IS 38 BP 28365 EP 28378 DI 10.1074/jbc.M603095200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 084LM UT WOS:000240534400074 PM 16829516 ER PT J AU Carpio, RVD Gonzalez-Nilo, FD Riadi, G Taraporewala, ZF Patton, JT AF Carpio, Rodrigo Vasquez-Del Gonzalez-Nilo, Fernando D. Riadi, Gonzalo Taraporewala, Zenobia F. Patton, John T. TI Histidine triad-like motif of the rotavirus NSP2 octamer mediates both RTPase and NTPase activities SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE rotavirus replication; viroplasm formation; NSP2; RTPase activity; NTPase activity ID NONSTRUCTURAL PROTEIN NSP2; DOUBLE-STRANDED-RNA; NUCLEOSIDE TRIPHOSPHATE PHOSPHOHYDROLASE; LAMBDA 1 PROTEIN; 5'-TRIPHOSPHATASE ACTIVITIES; CAPPING APPARATUS; BINDING ACTIVITY; INFECTED-CELLS; IN-VIVO; MECHANISM AB Rotavirus NSP2 is an abundant non-structural RNA-binding protein essential for forming the viral factories that support replication of the double-stranded RNA genome. NSP2 exists as stable doughnut-shaped octamers within the infected cell, representing the tail-to-tail interaction of two tetramers. Extending diagonally across the surface of each octamer are four highly basic grooves that function as binding sites for single-stranded RNA. Between the N and C-terminal domains of each monomer is a deep electropositive cleft containing a catalytic site that hydrolyzes the gamma-beta phosphoanhydride bond of any NTP. The catalytic site has similarity to those of the histidine triad (HIT) family of nucleotide-binding proteins. Due to the close proximity of the grooves and clefts, we investigated the possibility that the RNA-binding activity of the groove promoted the insertion of the 5'-triphosphate moiety of the RNA into the cleft, and the subsequent hydrolysis of its gamma-beta phosphoanhydride bond. Our results show that NSP2 hydrolyzes the gamma P from RNAs and NTPs through Mg2+ -dependent activities that proceed with similar reaction velocities, that require the catalytic His225 residue, and that produce a phosphorylated intermediate. Competition assays indicate that although both substrates enter the active site, RNA is the preferred substrate due to its higher affinity for the octamer. The RNA triphosphatase (RTPase) activity of NSP2 may account for the absence of the 5'-terminal gamma P on the (-) strands of the double-stranded RNA genome segments. This is the first report of a HIT-like protein with a multifunctional catalytic site, capable of accommodating both NTPs and RNAs during gamma P hydrolysis. Published by Elsevier Ltd. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Talca, CBSM, Talca, Chile. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jpatton@niaid.nih.gov RI Gonzalez-Nilo, Fernando/M-5671-2016 OI Gonzalez-Nilo, Fernando/0000-0001-6857-3575 NR 54 TC 3 Z9 3 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 SEP 22 PY 2006 VL 362 IS 3 BP 539 EP 554 DI 10.1016/j.jmb.2006.07.050 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 089MD UT WOS:000240883800013 ER PT J AU Gil-da-Costa, R Hauser, MD AF Gil-da-Costa, Ricardo Hauser, Marc D. TI Vervet monkeys and humans show brain asymmetries for processing conspecific vocalizations, but with opposite patterns of laterality SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE brain evolution; primate; communication; vocalizations; functional asymmetry ID HEMISPHERIC-SPECIALIZATION; RHESUS-MONKEYS; CALLS; COMMUNICATION; DOMINANCE; MACAQUES; LESIONS AB A robust finding in the human neurosciences is the observation of a left hemisphere specialization for processing spoken language. Previous studies suggest that this auditory specialization and brain asymmetry derive from a primate ancestor. Most of these studies focus on the genus Macaca and all demonstrate a left hemisphere bias. Due to the narrow taxonomic scope, however, we lack a sense of the distribution of this asymmetry among primates. Further, although the left hemisphere bias appears mediated by conspecific calls, other possibilities exist including familiarity, emotional relevance and more general acoustic properties of the signal. To broaden the taxonomic scope and test the specificity of the apparent hemisphere bias, we conducted an experiment on vervets (Cercopithecus aethiops)-a different genus of old world monkeys and implemented the relevant acoustic controls. Using the same head orienting procedure tested with macaques, results show a strong left ear/right hemisphere bias for conspecific vocalizations (both familiar and unfamiliar), but no asymmetry for other primate vocalizations or non-biological sounds. These results suggest that although auditory asymmetries for processing species-specific vocalizations are a common feature of the primate brain, the direction of this asymmetry may be relatively plastic. This finding raises significant questions for how ontogenetic and evolutionary forces have impacted on primate brain evolution. C1 Harvard Univ, Dept Psychol Organism & Evolut Biol, Cognit Evolut Lab, Cambridge, MA 02138 USA. Harvard Univ, Dept Biol Anthropol, Cognit Evolut Lab, Cambridge, MA 02138 USA. Gulbenkian Inst Sci, Program Biol & Med, P-2780 Oeiras, Portugal. RP Gil-da-Costa, R (reprint author), NIMH, Lab Brain & Cognit, NIH, 10 Ctr Dr,MSC 1366,Bldg 10,Room 4C103, Bethesda, MD 20892 USA. EM rcosta@helix.nih.gov NR 21 TC 25 Z9 25 U1 5 U2 8 PU ROYAL SOCIETY PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8452 J9 P R SOC B JI Proc. R. Soc. B-Biol. Sci. PD SEP 22 PY 2006 VL 273 IS 1599 BP 2313 EP 2318 DI 10.1098/rspb.2006.3580 PG 6 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA 082QC UT WOS:000240400800008 PM 16928633 ER PT J AU Nabel, EG AF Nabel, Elizabeth G. TI The Women's Health Initiative SO SCIENCE LA English DT Editorial Material C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. EM nabele@nhlbi.nih.gov NR 0 TC 6 Z9 7 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 SEP 22 PY 2006 VL 313 IS 5794 BP 1703 EP 1703 DI 10.1126/science.1134995 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 086ED UT WOS:000240655700001 PM 16990517 ER PT J AU Jiao, D King, C Grossfield, A Darden, TA Ren, PY AF Jiao, Dian King, Christopher Grossfield, Alan Darden, Thomas A. Ren, Pengyu TI Simulation of Ca2+ and Mg2+ solvation using polarizable atomic multipole potential SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID MOLECULAR-DYNAMICS SIMULATION; HYDRATION FREE-ENERGY; X-RAY-DIFFRACTION; AB-INITIO; AQUEOUS-SOLUTION; FORCE-FIELDS; CALCIUM-ION; WATER; NA+; REPRESENTATION C1 Univ Texas, Dept Biomed Engn, Austin, TX 78712 USA. IBM Corp, Thomas J Watson Res Ctr, Yorktown Hts, NY 10598 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Ren, PY (reprint author), Univ Texas, Dept Biomed Engn, Austin, TX 78712 USA. EM pren@mail.utexas.edu RI Jiao, Dian/E-5814-2011; Jiao, Dian/F-4337-2011; OI Grossfield, Alan/0000-0002-5877-2789 FU Intramural NIH HHS [, NIH0011757912]; PHS HHS [NIH0011757912] NR 40 TC 135 Z9 136 U1 5 U2 29 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD SEP 21 PY 2006 VL 110 IS 37 BP 18553 EP 18559 DI 10.1021/jp062230r PG 7 WC Chemistry, Physical SC Chemistry GA 083YR UT WOS:000240496500072 PM 16970483 ER PT J AU Grigorenko, B Savitsky, A Topol, I Burt, S Nemukhin, A AF Grigorenko, Bella Savitsky, Alexander Topol, Igor Burt, Stanley Nemukhin, Alexander TI Ground-state structures and vertical excitations for the kindling fluorescent protein asFP595 SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID ELECTRONIC EXCITATIONS; CHROMOPHORE ENVIRONMENT; MOLECULAR-DYNAMICS; PROTONATION STATES; ANEMONIA-SULCATA; GFP CHROMOPHORE; QM/MM METHOD; RED; ISOMERIZATION; CHROMOPROTEIN C1 Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119991, Russia. Russian Acad Sci, AN Bach Inst Biochem, Moscow 119071, Russia. Natl Canc Inst, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. RP Nemukhin, A (reprint author), Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119991, Russia. EM anem@lcc.chem.msu.ru RI Savitsky, Alexander/O-9799-2015; Nemukhin, Alexander/P-9662-2015 FU PHS HHS [N01 C0 12400] NR 44 TC 24 Z9 24 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD SEP 21 PY 2006 VL 110 IS 37 BP 18635 EP 18640 DI 10.1021/jp060124j PG 6 WC Chemistry, Physical SC Chemistry GA 083YR UT WOS:000240496500082 PM 16970493 ER PT J AU Voronin, YA Sidorov, IA Pathak, VK AF Voronin, Yegor A. Sidorov, Igor A. Pathak, Vinay K. TI A probability model predicting initiation efficiency of retroviral vectors with two primer-binding sites SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE reverse transcription; probability model; retrovirus; initiation ID MURINE LEUKEMIA-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; DEPENDENT DNA POLYMERASE; ROUS-SARCOMA VIRUS; REVERSE TRANSCRIPTION; VIRAL-RNA; GENETIC-RECOMBINATION; INTEGRATION SITE; TUMOR-VIRUSES; AVIAN-SARCOMA AB Initiation of reverse transcription in retroviruses occurs at a specific point in the viral genome, called the primer-binding site (PBS). The efficiency of reverse transcription initiation is not known. We previously published a paper describing reverse transcription of the retroviral vector S-2PBS containing two PBSs. Reverse transcription of this vector results in a provirus with one of four possible structures, depending, in part, on the PBSs used to initiate reverse transcription. Using Southern blotting analyses of DNA from infected cells, we measured the relative proportions of proviruses with different structures. Although the analysis allowed us to detect multiple initiation events occurring in a single virion, the measurement of frequency of such events was not possible. In this paper, we have built a probability model, which describes the reverse transcription process and predicts the outcomes of different initiation scenarios. By fitting the predicted outcomes to the observed data, we have been able to estimate the initiation efficiency in this system as similar to 0.4 initiation per PBS. In addition, we show that even though multiple models of reverse transcription can explain the observed data, all of these models predict approximately the same initiation efficiency. This initiation efficiency is discussed in relation to general replication strategies of retroviruses. Published by Elsevier Ltd. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. NCI, Canc Res Ctr, Nanobiol Program, Frederick, MD 21702 USA. RP Voronin, YA (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N, Seattle, WA 98109 USA. EM yvoronin@fhcrc.org OI Sidorov, Igor/0000-0001-6519-4983 FU Intramural NIH HHS NR 22 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD SEP 21 PY 2006 VL 242 IS 2 BP 347 EP 355 DI 10.1016/j.jtbi.2006.03.003 PG 9 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 086AN UT WOS:000240645600009 PM 16631208 ER PT J AU Meshorer, E AF Meshorer, Eran TI Iran is sixth, not second, in Middle East publication list SO NATURE LA English DT Letter C1 NCI, NIH, Bethesda, MD 20892 USA. RP Meshorer, E (reprint author), NCI, NIH, 41 Lib Dr, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 21 PY 2006 VL 443 IS 7109 BP 271 EP 271 DI 10.1038/443271c PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 085RL UT WOS:000240622000018 PM 16988686 ER PT J AU Thrasher, AJ Gaspar, HB Baum, C Modlich, U Schambach, A Candotti, F Otsu, M Sorrentino, B Scobie, L Cameron, E Blyth, K Neil, J Abina, SHB Cavazzana-Calvo, M Fischer, A AF Thrasher, Adrian J. Gaspar, H. Bobby Baum, Christopher Modlich, Ute Schambach, Axel Candotti, Fabio Otsu, Makoto Sorrentino, Brian Scobie, Linda Cameron, Ewan Blyth, Karen Neil, Jim Abina, Salima Hacein-Bey Cavazzana-Calvo, Marina Fischer, Alain TI Gene therapy - X-SCID transgene leukaemogenicity SO NATURE LA English DT Letter ID SEVERE COMBINED IMMUNODEFICIENCY; INSERTIONAL MUTAGENESIS; MICE C1 UCL, Inst Child Hlth, Mol Immunol Unit, London WC1N 1EH, England. Great Ormond St Hosp Sick Children, London WC1N 3JH, England. Hannover Med Sch, Dept Expt Hematol, D-30625 Hannover, Germany. Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol, Cincinnati, OH 45229 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Ctr Med Expt, Tokyo 1088639, Japan. St Jude Childrens Hosp, Dept Hematol Oncol, Div Expt Hematol, Memphis, TN 38105 USA. Univ Glasgow, Fac Vet Med, Inst Comparat Med, Div Pathol Sci, Glasgow G61 1QH, Lanark, Scotland. Assistance Publ Hop Paris, Hop Necker, INSERM, U768, F-75743 Paris, France. Assistance Publ Hop Paris, Dept Biotherapies, F-75743 Paris, France. Assistance Publ Hop Paris, Unite Immunohematol, F-75743 Paris, France. Univ Paris 05, Fac Med, F-75270 Paris, France. RP Thrasher, AJ (reprint author), UCL, Inst Child Hlth, Mol Immunol Unit, London WC1N 1EH, England. EM a.thrasher@ich.ucl.ac.uk RI Schambach, Axel/C-5491-2011; OI Otsu, Makoto/0000-0002-9769-0217; Blyth, Karen/0000-0002-9304-439X NR 10 TC 94 Z9 96 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 21 PY 2006 VL 443 IS 7109 BP E5 EP E6 DI 10.1038/nature05219 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 085RL UT WOS:000240622000034 PM 16988659 ER PT J AU Kobayashi, S Nomoto, K Watanabe, M Hikosaka, O Schultz, W Sakagami, M AF Kobayashi, Shunsuke Nomoto, Kensaku Watanabe, Masataka Hikosaka, Okihide Schultz, Wolfram Sakagami, Masamichi TI Influences of rewarding and aversive outcomes on activity in macaque lateral prefrontal cortex SO NEURON LA English DT Article ID SINGLE NEURON RESPONSES; ORBITOFRONTAL CORTEX; EXPECTED REWARD; MONKEY; ATTENTION; STIMULI; AMYGDALA; ENCODE; MECHANISMS; AVOIDANCE AB Both appetitive and aversive outcomes can reinforce animal behavior. It is not clear, however, whether the opposing kinds of reinforcers are processed by specific or common neural mechanisms. To investigate this issue, we studied macaque monkeys that performed a memory-guided saccade task for three different outcomes, namely delivery of liquid reward, avoidance of air puff, and feedback sound only. Animals performed the task best in rewarded trials, intermediately in aversive trials, and worst in sound-only trials. Most task-related activity in lateral prefrontal cortex was differentially influenced by the reinforcers. Aversive avoidance had clear effects on some prefrontal neurons, although the effects of rewards were more common. We also observed neurons modulated by both positive and negative reinforcers, reflecting reinforcement or attentional processes. Our results demonstrate that information about positive and negative reinforcers is processed differentially in prefrontal cortex, which could contribute to the role of this structure in goal-directed behavior. C1 Tamagawa Univ, Res Inst, Brain Sci Res Ctr, Tokyo 1940041, Japan. Tokyo Metropolitan Inst Neurosci, Dept Psychol, Tokyo 1838526, Japan. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3DY, England. Univ Tokyo, Sch Med, Dept Psychiat, Tokyo 1138655, Japan. RP Kobayashi, S (reprint author), Tamagawa Univ, Res Inst, Brain Sci Res Ctr, Tokyo 1940041, Japan. EM skoba-tky@umin.ac.jp RI Kobayashi, Shunsuke/C-2551-2008; OI Nomoto, Kensaku/0000-0003-2953-4594 FU Medical Research Council [G0001354]; Wellcome Trust [, 095495] NR 41 TC 57 Z9 61 U1 2 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP 21 PY 2006 VL 51 IS 6 BP 861 EP 870 DI 10.1016/j.neuron.2006.08.031 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 091AM UT WOS:000240997900022 PM 16982429 ER PT J AU Hillmen, P Young, NS Schubert, J Brodsky, RA Socie, G Muus, P Roth, A Szer, J Elebute, MO Nakamura, R Browne, P Risitano, AM Hill, A Schrezenmeier, H Fu, C Maciejewski, J Rollins, SA Mojcik, CF Rother, RP Luzzatto, L AF Hillmen, Peter Young, Neal S. Schubert, Joerg Brodsky, Robert A. Socie, Gerard Muus, Petra Roeth, Alexander Szer, Jeffrey Elebute, Modupe O. Nakamura, Ryotaro Browne, Paul Risitano, Antonio M. Hill, Anita Schrezenmeier, Hubert Fu, Chieh-Lin Maciejewski, Jaroslaw Rollins, Scott A. Mojcik, Christopher F. Rother, Russell P. Luzzatto, Lucio TI The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PIG-A GENE; DEFICIENCY; MECHANISM; PLATELETS; HEMOLYSIS; FATIGUE; ANCHOR; C5B-9 AB BACKGROUND: We tested the safety and efficacy of eculizumab, a humanized monoclonal antibody against terminal complement protein C5 that inhibits terminal complement activation, in patients with paroxysmal nocturnal hemoglobinuria (PNH). METHODS: We conducted a double-blind, randomized, placebo-controlled, multicenter, phase 3 trial. Patients received either placebo or eculizumab intravenously; eculizumab was given at a dose of 600 mg weekly for 4 weeks, followed 1 week later by a 900-mg dose and then 900 mg every other week through week 26. The two primary end points were the stabilization of hemoglobin levels and the number of units of packed red cells transfused. Biochemical indicators of intravascular hemolysis and the patients' quality of life were also assessed. RESULTS: Eighty-seven patients underwent randomization. Stabilization of hemoglobin levels in the absence of transfusions was achieved in 49% (21 of 43) of the patients assigned to eculizumab and none (0 of 44) of those assigned to placebo (P<0.001). During the study, a median of 0 units of packed red cells was administered in the eculizumab group, as compared with 10 units in the placebo group (P<0.001). Eculizumab reduced intravascular hemolysis, as shown by the 85.8% lower median area under the curve for lactate dehydrogenase plotted against time (in days) in the eculizumab group, as compared with the placebo group (58,587 vs. 411,822 U per liter; P<0.001). Clinically significant improvements were also found in the quality of life, as measured by scores on the Functional Assessment of Chronic Illness Therapy-Fatigue instrument (P<0.001) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Of the 87 patients, 4 in the eculizumab group and 9 in the placebo group had serious adverse events, none of which were considered to be treatment-related; all these patients recovered without sequelae. CONCLUSIONS: Eculizumab is an effective therapy for PNH. C1 Gen Infirm, Dept Haematol, Leeds LS1 3EX, W Yorkshire, England. NHLBI, Bethesda, MD 20892 USA. Univ Saarland, Sch Med, D-6650 Homburg, Germany. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Hop St Louis, Paris, France. INSERM, Paris, France. Radboud Univ Med Ctr, Nijmegen, Netherlands. Univ Hosp Essen, Essen, Germany. Royal Melbourne Hosp, Melbourne, Vic, Australia. Univ London St Georges Hosp, London, England. City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. Univ Dublin Trinity Coll, St James Hosp, Dublin 2, Ireland. Univ Naples Federico II, Naples, Italy. Univ Hosp, Inst Transfus Med, Ulm, Germany. Cleveland Clin Florida, Weston, FL USA. Cleveland Clin Fdn, Taussig Canc Ctr, Cleveland, OH 44195 USA. Alex Pharmaceut, Cheshire, CT USA. Ist Toscano Tumori, Florence, Italy. RP Hillmen, P (reprint author), Gen Infirm, Dept Haematol, Great George St, Leeds LS1 3EX, W Yorkshire, England. EM peter.hillmen@nhs.net RI Muus, P./L-4539-2015; OI Browne, Paul/0000-0001-5310-1487; Szer, Jeff/0000-0001-6783-2301 NR 21 TC 430 Z9 447 U1 2 U2 12 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 SEP 21 PY 2006 VL 355 IS 12 BP 1233 EP 1243 DI 10.1056/NEJMoa061648 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 085IT UT WOS:000240598500007 PM 16990386 ER PT J AU Dudko, OK Weiss, GH Chernomordik, V AF Dudko, Olga K. Weiss, George H. Chernomordik, Victor TI Mean time-of-flight of photons in transillumination measurements of optically anisotropic tissue with an inclusion SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RANDOM-WALK DESCRIPTION; FLUORESCENCE-LIFETIME; SCALING RELATIONSHIPS; LIGHT-PROPAGATION; SLAB GEOMETRY; SCATTERING; MEDIA; ABNORMALITIES; TOMOGRAPHY; ABSORPTION AB We study the effect of optical anisotropy on the mean time-of-flight of photons in a slab of turbid medium containing an inclusion whose optical properties differ from those of the bulk. For this analysis the difference in the mean time for a photon introduced into the slab to reach a specified target point with and without the inclusion is calculated. This difference is defined to be a measure of the contrast. The theoretical model is based on a continuous-time random walk on a lattice, which can be solved exactly and furnishes an exact expression for the contrast. Qualitative and quantitative characteristics of the contrast are analysed as functions of the geometric configuration of the system components ( locations of the source, the inclusion and the detector), parameters that specify the optical anisotropy of the medium, and either the scattering properties of the inclusion or the lifetime of the small fluorophore in the case of the time-resolved fluorescence experimental configuration. C1 NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Innovat Technol, Bethesda, MD 20892 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Dudko, OK (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Innovat Technol, Bldg 10, Bethesda, MD 20892 USA. FU CIT NIH HHS [Z01 CT000014-39]; Intramural NIH HHS NR 37 TC 2 Z9 2 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD SEP 21 PY 2006 VL 51 IS 18 BP 4719 EP 4733 DI 10.1088/0031-9155/51/18/017 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 091SR UT WOS:000241049100017 PM 16953052 ER PT J AU Basso, O Rasmussen, S Weinberg, CR Wilcox, AJ Irgens, LM Skjaerven, R AF Basso, Olga Rasmussen, Svein Weinberg, Clarice R. Wilcox, Allen J. Irgens, Lorentz M. Skjaerven, Rolv TI Trends in fetal and infant survival following preeclampsia SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID EPIDEMIOLOGIC RESEARCH; PRETERM BIRTH; MANAGEMENT; SMOKING; PATHOGENESIS; MORTALITY AB Context Management of preeclampsia often culminates in induced delivery of a very preterm infant. While early termination protects the fetus from an intrauterine death, the newborn then faces increased risks associated with preterm delivery. This practice has increased in recent decades, but its net effect on fetal and infant survival has not been assessed. Objective To assess the effect on fetal and infant survival of increased rates of early delivery of preeclamptic pregnancies. Design, Setting, and Participants Population-based observational longitudinal study using registry data from 804 448 singleton first-born infants with Norwegian-born mothers and registered in the Medical Birth Registry of Norway between 1967 and 2003. Main Outcome Measures Odds ratio ( OR) of fetal and early childhood death in relation to preeclampsia. Results Among preeclamptic pregnancies, inductions before 37 weeks increased from 8% in 1967- 1978 to nearly 20% in 1991- 2003. During this period, the adjusted OR for stillbirth decreased from 4.2 (95% confidence interval [CI], 3.8-4.7) to 1.3 ( 95% CI, 1.1-1.7) for preeclamptic compared with nonpreeclamptic pregnancies. During the same period, the OR for neonatal death after preeclamptic pregnancy remained relatively stable (1.7 in 1967- 1978 vs 2.0 in 1991- 2003). Later infant and childhood mortality also showed little change. Conclusions Fetal survival in preeclamptic pregnancies has vastly improved over the past 35 years in Norway, presumably because of more aggressive clinical management. However, the relative risk of neonatal death following a preeclamptic pregnancy has not changed over time. C1 NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Univ Bergen, Locus Registry Based Epidemiol, Med Birth Registry Norway, Bergen, Norway. Norwegian Inst Publ Hlth, Bergen, Norway. Univ Bergen, Dept Obstet & Gynaecol, Inst Clin Med, N-5020 Bergen, Norway. RP Basso, O (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, MD A3-05,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM bassoo2@niehs.nih.gov RI Basso, Olga/E-5384-2010; OI Basso, Olga/0000-0001-9298-4921; Wilcox, Allen/0000-0002-3376-1311 FU Intramural NIH HHS NR 18 TC 70 Z9 73 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 20 PY 2006 VL 296 IS 11 BP 1357 EP 1362 DI 10.1001/jama.296.11.1357 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 085HS UT WOS:000240595800022 PM 16985227 ER PT J AU Agrawal, M Grady, C Fairclough, DL Meropol, NJ Maynard, K Emanuel, EJ AF Agrawal, Manish Grady, Christine Fairclough, Diane L. Meropol, Neal J. Maynard, Kim Emanuel, Ezekiel J. TI Patients' decision-making process regarding participation in phase I oncology research SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADVANCED CANCER-PATIENTS; INFORMED-CONSENT; CLINICAL-TRIALS; THERAPEUTIC MISCONCEPTION; PERCEPTIONS; ETHICS; EXPECTATIONS; PHYSICIANS; INFORMATION; MOTIVATION AB Purpose This study assesses the decision-making process of patients enrolling in phase I oncology studies. Patients and Methods Participants were eligible if they had consented to participate in a phase I cancer study at one of five cancer centers, understood English, and were older than 18 years. Trained interviewers conducted structured in-person interviews. Results Of the 163 participants, 88% were white, 96% had health insurance, and 51% were college graduates or post graduates. Overall, 81% were aware of hospice, but only 6% had seriously considered hospice for themselves; 84% were aware of palliative care and 10% seriously considered it for themselves; and 7% considered getting no treatment at all. Overall, 75% reported moderate or a lot of pressure to participate in the phase I study because their cancer was growing, whereas 7% reported such pressure from the study investigators and 9% felt such pressure from their families. For 63% of patients, the most important information for decision making was that the phase I drug killed cancer cells; only 12% reported that the adverse effects of the drug(s) was the most useful information. More than 90% of patients said they would still participate in the study even if the experimental drug caused serious adverse effects, including a 10% chance of dying. Conclusion Patients are aware of many alternatives to phase I studies, but do not seriously consider them. Very few experience pressure from family or researchers to participate in research. Their main goal is to fight their cancer, and almost no adverse effect, including death, would dissuade them from enrolling. C1 NCI, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Med Oncol Clin Res Unit,Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Colorado Hlth Outcomes Program, Dept Prevent Med & Biometr, Denver, CO USA. Fox Chase Canc Ctr, Div Med Sci, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. RP Agrawal, M (reprint author), NCI, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Med Oncol Clin Res Unit,Ctr Canc Res,NIH, Bldg 10,Room 1C118,10 Ctr Dr, Bethesda, MD 20892 USA. EM agrawalm@mail.nih.gov FU PHS HHS [R0182085] NR 37 TC 77 Z9 77 U1 0 U2 8 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 SEP 20 PY 2006 VL 24 IS 27 BP 4479 EP 4484 DI 10.1200/JCO.2006.06.0269 PG 6 WC Oncology SC Oncology GA 086YD UT WOS:000240708200018 PM 16983117 ER PT J AU Dobolyi, A Wang, J Irwin, S Usdin, TB AF Dobolyi, Arpad Wang, Jing Irwin, Sarah Usdin, Ted Bjorn TI Postnatal development and gender-dependent expression of TIP39 in the rat brain SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE tuberoinfundibular peptide of 39 residues; parathyroid hormone 2 receptor; in situ hybridization; immunocytochemistry; quantitative real-time RT-PCR; transient expression; ontogeny; puberty; sexual dimorphism; gonadectomy ID HORMONE-RECEPTOR FAMILY; TUBEROINFUNDIBULAR PEPTIDE; 39 RESIDUES; PARATHYROID-HORMONE; MATERNAL-BEHAVIOR; NERVOUS-SYSTEM; LACTATING RATS; PTH2 RECEPTOR; FEMALE RAT; C-FOS AB Tuberoinfundibular peptide of 39 residues (TIP39) is a selective agonist of the parathyroid hormone 2 (PTH2) receptor. The topographical distributions of TIP39 and the PTH2 receptor in the brain, described for young male rats, suggested that TIP39 has limbic and endocrine functions. In the present study, we investigated the expression of TIP39 and the PTH2 receptor in male and female rat brain during postnatal development by means of in situ hybridization histochemistry, quantitative RT-PCR, and immunocytochemistry. TIP39's distribution and expression levels are similar in young female and male brains. TIP39 mRNA levels peak at postnatal day 14 and subsequently decline both in the subparafascicular area and in the medial paralemniscal nucleus, the two major sites where TIP39 is synthesized. A greater developmental decrease in TIP39 expression in males leads to greater levels in older females than older males. The decrease is partially reversed by prepubertal but not postpubertal gonadectomy. TIP39 peptide levels in cell bodies change in parallel with mRNA levels, whereas TIP39 appears and disappears somewhat later in nerve fibers. In addition, TIP39 peptide levels are also sexually dimorphic in older rats. In contrast, PTH2 receptor expression in the brain does not decrease during puberty and is not sexually dimorphic even in old animals. The appearance of TIP39 during early, and decline during late, postnatal development together with the gender-dependent levels in mature animals suggests that TIP39 may play a role in sexual maturation or gender-specific functions. C1 NIMH, Genet Lab, Bethesda, MD 20892 USA. Semmelweis Univ, Lab Neuromorpol, H-1904 Budapest, Hungary. Hungarian Acad Sci, H-1904 Budapest, Hungary. RP Usdin, TB (reprint author), NIMH, Genet Lab, 35 Convent Dr, Bethesda, MD 20892 USA. EM usdint@mail.nih.gov RI Dobolyi, Arpad/B-9089-2008 FU Intramural NIH HHS [Z01 MH002685-14] NR 49 TC 11 Z9 11 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 20 PY 2006 VL 498 IS 3 BP 375 EP 389 DI 10.1002/cne.21063 PG 15 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 074FB UT WOS:000239797000005 PM 16871538 ER PT J AU Brown, P Gerfen, CR AF Brown, Pierre Gerfen, Charles R. TI Plasticity within striatal direct pathway neurons after neonatal dopamine depletion is mediated through a novel functional coupling of serotonin 5-HT2 receptors to the ERK 1/2 map kinase pathway SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE striatum; receptor coupling; serotonin ID PREPROTACHYKININ MESSENGER-RNA; CENTRAL-NERVOUS-SYSTEM; C-FOS GENE; 6-HYDROXYDOPAMINE-LESIONED RATS; SYNAPTIC PLASTICITY; PARKINSONS-DISEASE; HYPERINNERVATED NEOSTRIATUM; NUCLEUS-ACCUMBENS; BRAIN DOPAMINE; ANIMAL-MODELS AB Dysfunction within the striatal direct and indirect projecting systems arises after 6-hydroxydopamine (6-OHDA)-induced dopamine depletion, highlighting the central regulatory function of dopamine in motor systems. However, the striatal 5-hydroxytryptamine (5-HT) innervation remains intact after 6-OHDA lesions, suggesting that the 5-HT system may contribute to the lesion-induced dysfunction, or alternatively, it may adapt and compensate for the dopamine deficit. Neonatal 6-OHDA lesions actually give rise to a 5-HT axonal hyperinnervation within the dorsal striatum, further reinforcing the idea that the 5-HT system plays a central role in striatal function after dopamine depletion. Here we show that neonatal but not adult 6-OHDA lesions result in a novel coupling of 5-HT, receptors to the ERK1/2/MAP Kinase pathway, a signaling cascade known to regulate neuronal plasticity. Chloroamphetamine-induced 5-HT release or direct stimulation of striatal 5-HT, receptors via the 5-HT, agonist DOI, produced robust ERK1/2 phosphorylation throughout the dorsal striatum of neonatal lesioned animals, a response not observed within the intact striatum. Pretreatment with the select 5-HT, receptor antagonist Ketanserin blocked DOI-induced ERK1/2 phosphorylation. This drug-induced ERK1/2 phosphorylation was subsequently shown to be restricted to direct pathway striatal neurons. Our data show that adaptation of direct pathway neurons after neonatal 6-OHDA lesions involves coupling of 5-HT, receptors to the ERK1/2/MAP Mnase cascade, a pathway not typically active in these neurons. Because dopamine-mediated signaling is redundant after 6-OHDA lesions, 5-HT-mediated stimulation of the ERK1/2/MAP Mnase pathway may provide an alternative signaling route allowing the regulation of neuronal gene expression and neuronal plasticity in the absence of dopamine. C1 NIMH, Lab Syst Neurosci, NIH, Bethesda, MD 20892 USA. RP Gerfen, CR (reprint author), NIMH, Lab Syst Neurosci, NIH, Bldg 35,Room 3A-1000,35 Convent Dr, Bethesda, MD 20892 USA. EM gerfenc@mail.nih.gov FU Intramural NIH HHS [Z01 MH002497-16, Z01 MH002497-18] NR 68 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 20 PY 2006 VL 498 IS 3 BP 415 EP 430 DI 10.1002/cne.21034 PG 16 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 074FB UT WOS:000239797000008 PM 16871540 ER PT J AU Murase, S Mckay, RD AF Murase, Sachiko McKay, Ronald D. TI A specific survival response in dopamine neurons at most risk in Parkinson's disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Parkinson's disease; fibroblast growth factor 20; dopamine; calbindin; midbrain; neurotrophic factor ID FIBROBLAST-GROWTH-FACTOR; VESICULAR MONOAMINE TRANSPORTER-2; MESSENGER-RNA LEVELS; FACTOR GENE-THERAPY; NEUROTROPHIC FACTOR; SUBSTANTIA-NIGRA; TYROSINE-HYDROXYLASE; OXIDATIVE DAMAGE; FACTOR RECEPTORS; RAT STRIATUM AB The specific expression of fibroblast growth factor 20 (FGF-20) in the adult substantia nigra and the association between FGF-20 mutations and Parkinson's disease provoked exploration of the function of this growth factor. We show by gain- and loss-of-function in vitro experiments that FGF-20 promotes survival and stimulates dopamine (DA) release in a calbindin-negative subset of cells that are preferentially lost in Parkinson's disease. FGF-20 selectively activates tyrosine hydroxylase in calbindin-negative neurons. In the adult substantia nigra, calbindin-negative neurons specifically express high levels of FGFR1 (FGF receptor 1). These data show that FGF signals to elevate DA levels and protect the specific midbrain neuron type at most risk in Parkinson's patients. C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Mckay, RD (reprint author), 35 Convent Dr,MSC 4092, Bethesda, MD 20892 USA. EM mckay@codon.nih.gov FU Intramural NIH HHS NR 79 TC 56 Z9 59 U1 0 U2 1 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 SEP 20 PY 2006 VL 26 IS 38 BP 9750 EP 9760 DI 10.1523/JNEUROSCI.2745-06.2006 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 086CN UT WOS:000240650800017 PM 16988046 ER PT J AU Longo, DL AF Longo, Dan L. TI Idiotype vaccination in follicular lymphoma: Knocking on the doorway to cure SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; ANTI-IDIOTYPE; IMMUNE-RESPONSES C1 NIA, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Longo, DL (reprint author), NIA, NIH, Intramural Res Program, Rm 1E07,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM longod@grc.nia.nih.gov NR 16 TC 17 Z9 18 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 20 PY 2006 VL 98 IS 18 BP 1263 EP 1265 DI 10.1093/jnci/djj371 PG 3 WC Oncology SC Oncology GA 101EG UT WOS:000241721100002 PM 16985240 ER PT J AU Messina, M McCaskill-Stevens, W Lampe, JW AF Messina, Mark McCaskill-Stevens, Worta Lampe, Johanna W. TI Addressing the soy and breast cancer relationship: Review, commentary, and workshop proceedings SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID ESTROGEN-RECEPTOR-BETA; HORMONE-REPLACEMENT THERAPY; OVARIECTOMIZED ATHYMIC MICE; CELLS IN-VITRO; MAMMALIAN LIGNANS ENTEROLACTONE; FOOD FREQUENCY QUESTIONNAIRE; DIETARY PHYTOESTROGEN INTAKE; CARDIOVASCULAR-DISEASE RISK; RANDOMIZED CONTROLLED-TRIAL; MAMMARY-GLAND DEVELOPMENT AB The impact of soyfood intake on breast cancer risk has been investigated extensively. Much of this focus can be attributed to the soybean being a dietary source that is uniquely rich in isoflavones. The chemical structure of isoflavones is similar to that of estrogen, and isoflavones bind to both estrogen receptors (ER alpha and ER beta) (although they preferentially bind to and activate ER beta) and exert estrogen-like effects under some experimental conditions. Isoflavones also possess nonhormonal properties that are associated with the inhibition of cancer cell growth. Thus, there are several possible mechanisms by which soy may reduce the risk of breast cancer. However, the role of isoflavones in breast cancer has become controversial because, in contrast to the possible beneficial effects, some data from in vitro and animal studies suggest that isoflavones, especially genistein, the aglycone of the main soybean isoflavone genistin, may stimulate the growth of estrogen-sensitive tumors. Limited human data directly address the tumor-promoting effects of isoflavones and soy. Because the use of soyfoods and isoflavone supplements is increasing, it is important from a public health perspective to understand the impact of these products on breast cancer risk in women at high risk of the disease and on the survival of breast cancer patients. To this end, a workshop was held in November 2005 to review the existing literature and to make research recommendations. This paper summarizes the workshop findings and recommendations. The primary research recommendation is that the impact of isoflavones on breast tissue needs to be evaluated at the cellular level in women at high risk for breast cancer. C1 Nutr Matters Inc, Port Townsend, WA 98368 USA. Loma Linda Univ, Sch Publ Hlth, Dept Nutr, Loma Linda, CA 92350 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Messina, M (reprint author), Nutr Matters Inc, 439 Calhoun St, Port Townsend, WA 98368 USA. EM market@olympus.net NR 157 TC 185 Z9 190 U1 0 U2 20 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 SEP 20 PY 2006 VL 98 IS 18 BP 1275 EP 1284 DI 10.1093/jnci/djj356 PG 10 WC Oncology SC Oncology GA 101EG UT WOS:000241721100007 PM 16985246 ER PT J AU Landgren, O Engels, EA Pfeiffer, RM Gridley, G Mellemkjaer, L Olsen, JH Kerstann, KF Wheeler, W Hemminki, K Linet, MS Goldin, LR AF Landgren, Ola Engels, Eric A. Pfeiffer, Ruth M. Gridley, Gloria Mellemkjaer, Lene Olsen, Jorgen H. Kerstann, Kimberly F. Wheeler, William Hemminki, Kari Linet, Martha S. Goldin, Lynn R. TI Autoimmunity and susceptibility to Hodgkin lymphoma: A population-based case-control study in Scandinavia SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHRONIC LYMPHOCYTIC-LEUKEMIA; INFLAMMATORY-BOWEL-DISEASE; FAMILY-CANCER DATABASE; RHEUMATOID-ARTHRITIS; 1ST-DEGREE RELATIVES; INCREASED RISK; SARCOIDOSIS; EPIDEMIOLOGY; MALIGNANCY AB Background: Personal history of autoimmune diseases is consistently associated with increased risk of non-Hodgkin lymphoma. In contrast, there are limited data on risk of Hodgkin lymphoma following autoimmune diseases and almost no data addressing whether there is a familial association between the conditions. Methods: Using population-based linked registry data from Sweden and Denmark, 32 separate autoimmune and related conditions were identified from hospital diagnoses in 7476 case subjects with Hodgkin lymphoma, 18 573 matched control subjects, and more than 86 000 first-degree relatives of case and control subjects. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) as measures of relative risks for each condition using logistic regression and also applied multivariable hierarchical regression models. All P values are two-sided. Results: We found statistically significantly increased risks of Hodgkin lymphoma associated with personal histories of several autoimmune conditions, including rheumatoid arthritis (OR = 2.7, 95% CI = 1.9 to 4.0), systemic lupus erythematosus (OR = 5.8, 95% Cl = 2.2 to 15.1), sarcoidosis (OR = 14.1, 95% CI = 5.4 to 36.8), and immune thrombocytopenic purpura (OR = infinity, P = .002). A statistically significant increase in risk of Hodgkin lymphoma was associated with family histories of sarcoidosis (OR = 1.8, 95% CI = 1.01 to 3.1) and ulcerative colitis (OR = 1.6, 95% CI = 1.02 to 2.6). Conclusions: Personal or family history of certain autoimmune conditions was strongly associated with increased risk of Hodgkin lymphoma. The association between both personal and family histories of sarcoidosis and a statistically significantly increased risk of Hodgkin lymphoma suggests shared susceptibility for these conditions. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. Informat Management Serv Inc, Rockville, MD USA. Karolinska Inst, Dept Biosci Novum, Stockholm, Sweden. German Canc Res Ctr, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany. RP Landgren, O (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Bldg EPS Room 7110, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011; OI Olsen, Jorgen Helge/0000-0001-9633-5662 FU Intramural NIH HHS NR 67 TC 108 Z9 112 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 20 PY 2006 VL 98 IS 18 BP 1321 EP 1330 DI 10.1093/jnci/djj361 PG 10 WC Oncology SC Oncology GA 101EG UT WOS:000241721100012 PM 16985251 ER PT J AU Williams, WM Chung, YW AF Williams, W. M. Chung, Y. W. TI Evidence for an age-related attenuation of cerebral microvascular antioxidant response to oxidative stress SO LIFE SCIENCES LA English DT Article DE hyperoxia; oxidative stress; microvessel; mouse; aging; brain ID MANGANESE-SUPEROXIDE-DISMUTASE; ENDOTHELIAL-CELLS; SENESCENT MOUSE; RAT-BRAIN; THIOREDOXIN; PROTEINS; DAMAGE; ENZYMES; OXYGEN; DISEASE AB Effects of aging and oxidative stress were studied in cerebral microvessels and microvessel-depleted brain from 6-, 18-, and 24-month-old C57B1/ 6J mice exposed to normoxia, 24 or 48 h hyperoxia, or 24 h hyperoxia followed by 24 h normoxia. Microvessels lacked smooth muscle and consisted predominantly of endothelium. Following exposure and isolation of microvessel and parenchymal proteins, Western blot analysis was performed for detection of cytosolic thioredoxin 1 (TRx 1) and mitochondrial thioredoxin 2 (TRx 2), protein carbonyl, and mitochondrial superoxide dismutase (MnSOD). Both microvessel and parenchymal TRx I levels were increased by hyperoxia; however, the microvascular response was limited and delayed in comparison to that of the parenchymal fraction. Whereas TRx 2 levels in microvessels were increased in older mice, irrespective of exposure condition, hyperoxia per se had little or no apparent effect. Parenchymal cells showed no age-related increase in TRx 2 level under normoxic conditions, but showed increased levels following hyperoxia. Microvessel MnSOD was lower than that in parenchymal cells, but increased with age under normoxia, and also was correlated with the duration of hyperoxia. Although hyperoxia augmented MnSOD levels in young (6 months) and middle-aged (18 months) animals, the response was less pronounced in microvessels from senescent, 24-month-old mice. Unlike microvessels, which showed a sustained age-related increase in MnSOD level under each exposure condition, parenchymal cells from normoxic mice showed no increase, and hyperoxia-induced elevations declined with prolonged 48 h exposure. These results indicate that the microvessel endothelium is (1) subjected to a more intense oxidative environment than neurons and glia and (2) is limited by aging in its ability to respond to oxidative insult. (c) 2006 Elsevier Inc. All rights reserved. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Williams, WM (reprint author), NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. EM wmw5@case.edu NR 31 TC 5 Z9 5 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 EI 1879-0631 J9 LIFE SCI JI Life Sci. PD SEP 20 PY 2006 VL 79 IS 17 BP 1638 EP 1644 DI 10.1016/j.lfs.2006.05.018 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 091JU UT WOS:000241024300007 PM 16815478 ER PT J AU Anderson, GL Chlebowski, RT Rossouw, JE Rodabough, RJ McTiernan, A Margolis, KL Aggerwal, A Curb, JD Hendrix, SL Hubbell, FA Khandekar, J Lane, DS Lasser, N Lopez, AM Potter, J Ritenbaugh, C AF Anderson, Garnet L. Chlebowski, Rowan T. Rossouw, Jacques E. Rodabough, Rebecca J. McTiernan, Anne Margolis, Karen L. Aggerwal, Anita Curb, J. David Hendrix, Susan L. Hubbell, F. Allan Khandekar, Jamardan Lane, Dorothy S. Lasser, Norman Lopez, Ana Maria Potter, JoNell Ritenbaugh, Cheryl TI Prior hormone therapy and breast cancer risk in the Women's Health initiative randomized trial of estrogen plus progestin SO MATURITAS LA English DT Article DE estrogen; progestin; breast neoplasms; subgroup analyses; randomized trials ID REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; HOT FLUSHES; CARCINOMA; DESIGN AB Objectives: To assess the extent to which prior hormone therapy modifies the breast cancer risk found with estrogen plus progestin (E+P) in the Women's Health Initiative (WHI) randomized trial. Methods: Subgroup analyses of prior hormone use on invasive breast cancer incidence in 16,608 postmenopausal women in the WHI randomized trial of E+P over an average 5.6 years of follow-up. Results: Small but statistically significant differences were found between prior HT users and non-users for most breast cancer risk factors but Gail risk scores were similar. Duration of E + P use within the trial (mean 4.4 years, S.D. 2.0) did not vary by prior use. Among 4311 prior users, the adjusted hazard ratio (HR) for E+P versus placebo was 1.96 (95% confidence interval [CI]: 1.17-3.27), significantly different (p=0.03) from that among 12,297 never users (HR 1.02; 95% CI: 0.77-1.36). The interaction between study arm and follow-up time was significant overall (p=0.01) and among never users (p=0.02) but not among prior users (p=0.10). The cumulative incidence over time for the E+P and placebo groups appeared to cross after about 3 years in prior users, and after about 5 years in women with no prior use. No interaction was found with duration (p=0.08) or recency of prior use (p=0.17). Prior hormone use significantly increased the E+P hazard ratio for larger, more advanced tumors. Conclusion: A safe interval for combined hormone use could not be reliably defined with these data. However, the significant increase in breast cancer risk in the trial overall after only 5.6 years of follow-up, initially concentrated in women with prior hormone exposure, but with increasing risk over time in women without prior exposure, suggests that durations only slightly longer than those in the WHI trial are associated with increased risk of breast cancer. Longer-term exposure and follow-up data are needed. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, WHI Clin Coordinating Ctr, Seattle, WA 98109 USA. NHLBI, WHI, Rockville, MD USA. Univ Calif Los Angeles, Ctr Med, LABiomed, Los Angeles Biomed Res Inst Harbor, Torrance, CA USA. Hennepin Cty Med Ctr, Berman Ctr Clin Res, Minneapolis, MN 55415 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, Honolulu, HI 96822 USA. Wayne State Univ, Sch Med, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI USA. Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. Northwestern Univ, Dept Med, Evanston, IL USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Univ Arizona, Tucson, AZ USA. Univ Miami, Miami, FL 33152 USA. RP Anderson, GL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, WHI Clin Coordinating Ctr, 110 Fairview Ave N,M3-A410,POB 19024, Seattle, WA 98109 USA. EM garnet@whi.org OI Anderson, Garnet/0000-0001-5087-7837; Lopez, Ana Maria/0000-0002-2759-5353 NR 20 TC 113 Z9 118 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-5122 J9 MATURITAS JI Maturitas PD SEP 20 PY 2006 VL 55 IS 2 BP 103 EP 115 DI 10.1016/j.maturitas.2006.05.004 PG 13 WC Geriatrics & Gerontology; Obstetrics & Gynecology SC Geriatrics & Gerontology; Obstetrics & Gynecology GA 093WA UT WOS:000241199800001 PM 16815651 ER PT J AU Goshorn, JC AF Goshorn, Jeanne Carriere TI New web-based resources developed by the toxicology and environmental health information program of the USA National Library of Medicine SO TOXICOLOGY LETTERS LA English DT Meeting Abstract C1 Natl Lib Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP 20 PY 2006 VL 164 SI SI BP S174 EP S175 DI 10.1016/j.toxlet.2006.07.021 PG 2 WC Toxicology SC Toxicology GA 082SJ UT WOS:000240407200354 ER PT J AU Harris, CC AF Harris, Curtis C. TI p53 is a key molecular node in the inflammatory stress response network SO TOXICOLOGY LETTERS LA English DT Meeting Abstract C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP 20 PY 2006 VL 164 SI SI BP S56 EP S56 DI 10.1016/j.toxlet.2006.06.117 PG 1 WC Toxicology SC Toxicology GA 082SJ UT WOS:000240407200110 ER PT J AU Wexler, P AF Wexler, Philip TI NLM's world library of toxicology, chemical safety, and environmental health SO TOXICOLOGY LETTERS LA English DT Meeting Abstract C1 Natl Lib Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP 20 PY 2006 VL 164 SI SI BP S305 EP S306 DI 10.1016/j.toxlet.2006.07.293 PG 2 WC Toxicology SC Toxicology GA 082SJ UT WOS:000240407200626 ER PT J AU Caughey, B Caughey, WS Kocisko, DA Lee, KS Silveira, JR Morrey, JD AF Caughey, B. Caughey, W. S. Kocisko, D. A. Lee, K. S. Silveira, J. R. Morrey, J. D. TI Prions and transmissible spongiform encephalopathy (TSE) chemotherapeutics: A common mechanism for anti-TSE compounds? SO ACCOUNTS OF CHEMICAL RESEARCH LA English DT Review ID CONGO RED; PROTEIN-FORMATION; INFECTED HAMSTERS; INCUBATION PERIOD; SCRAPIE INFECTION; SULFATED GLYCANS; PRP ACCUMULATION; CULTURED-CELLS; IN-VITRO; DISEASE AB No validated treatments exist for transmissible spongiform encephalopathies (TSEs or prion diseases) in humans or livestock. The search for TSE therapeutics is complicated by persistent uncertainties about the nature of mammalian prions and their pathogenic mechanisms. In pursuit of anti-TSE drugs, we and others have focused primarily on blocking conversion of normal prion protein, PrPC, to the TSE-associated isoform, PrPSc. Recently developed high-throughput screens have hastened the identification of new inhibitors with strong in vivo anti-TSE activities such as porphyrins, phthalocyanines, and phosphorthioated oligonucleotides. New routes of administration have enhanced beneficial effects against established brain infections. Several different classes of TSE inhibitors share structural similarities, compete for the same site(s) on PrPC, and induce the clustering and internalization of PrPC from the cell surface. These activities may represent a common mechanism of action for these anti-TSE compounds. C1 NIAID, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. Utah State Univ, Dept Anim Dairy & Vet Sci, Inst Antiviral Res, Logan, UT 84322 USA. RP Caughey, B (reprint author), NIAID, NIH, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM bcaughey@nih.gov RI Lee, Kil/D-3678-2012 NR 71 TC 43 Z9 47 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0001-4842 J9 ACCOUNTS CHEM RES JI Accounts Chem. Res. PD SEP 19 PY 2006 VL 39 IS 9 BP 646 EP 653 DI 10.1021/ar050068p PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 084ZK UT WOS:000240572700011 PM 16981681 ER PT J AU Walsh, TJ Orsega, S Banks, D AF Walsh, Thomas J. Orsega, Susan Banks, David TI Lessons from Hurricane Rita: Organizing to provide medical care during a natural disaster SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 3 TC 4 Z9 4 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 19 PY 2006 VL 145 IS 6 BP 468 EP 470 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 087OU UT WOS:000240752500011 PM 16908910 ER PT J AU Koonin, EV Senkevich, TG Dolja, VV AF Koonin, Eugene V. Senkevich, Tatiana G. Dolja, Valerian V. TI The ancient Virus World and evolution of cells SO BIOLOGY DIRECT LA English DT Review ID DEPENDENT RNA-POLYMERASES; TRANSPOSABLE ELEMENTS; BACTERIAL-VIRUSES; EUKARYOTIC CELL; RETROTRANSPOSABLE ELEMENTS; COMPARATIVE GENOMICS; DNA-BACTERIOPHAGES; COMMON ANCESTRY; VIRAL-PROTEINS; TELL US AB Background: Recent advances in genomics of viruses and cellular life forms have greatly stimulated interest in the origins and evolution of viruses and, for the first time, offer an opportunity for a data-driven exploration of the deepest roots of viruses. Here we briefly review the current views of virus evolution and propose a new, coherent scenario that appears to be best compatible with comparative-genomic data and is naturally linked to models of cellular evolution that, from independent considerations, seem to be the most parsimonious among the existing ones. Results: Several genes coding for key proteins involved in viral replication and morphogenesis as well as the major capsid protein of icosahedral virions are shared by many groups of RNA and DNA viruses but are missing in cellular life forms. On the basis of this key observation and the data on extensive genetic exchange between diverse viruses, we propose the concept of the ancient virus world. The virus world is construed as a distinct contingent of viral genes that continuously retained its identity throughout the entire history of life. Under this concept, the principal lineages of viruses and related selfish agents emerged from the primordial pool of primitive genetic elements, the ancestors of both cellular and viral genes. Thus, notwithstanding the numerous gene exchanges and acquisitions attributed to later stages of evolution, most, if not all, modern viruses and other selfish agents are inferred to descend from elements that belonged to the primordial genetic pool. In this pool, RNA viruses would evolve first, followed by retroid elements, and DNA viruses. The Virus World concept is predicated on a model of early evolution whereby emergence of substantial genetic diversity antedates the advent of full-fledged cells, allowing for extensive gene mixing at this early stage of evolution. We outline a scenario of the origin of the main classes of viruses in conjunction with a specific model of precellular evolution under which the primordial gene pool dwelled in a network of inorganic compartments. Somewhat paradoxically, under this scenario, we surmise that selfish genetic elements ancestral to viruses evolved prior to typical cells, to become intracellular parasites once bacteria and archaea arrived at the scene. Selection against excessively aggressive parasites that would kill off the host ensembles of genetic elements would lead to early evolution of temperate virus-like agents and primitive defense mechanisms, possibly, based on the RNA interference principle. The emergence of the eukaryotic cell is construed as the second melting pot of virus evolution from which the major groups of eukaryotic viruses originated as a result of extensive recombination of genes from various bacteriophages, archaeal viruses, plasmids, and the evolving eukaryotic genomes. Again, this vision is predicated on a specific model of the emergence of eukaryotic cell under which archaeo-bacterial symbiosis was the starting point of eukaryogenesis, a scenario that appears to be best compatible with the data. Conclusion: The existence of several genes that are central to virus replication and structure, are shared by a broad variety of viruses but are missing from cellular genomes (virus hallmark genes) suggests the model of an ancient virus world, a flow of virus-specific genes that went uninterrupted from the precellular stage of life's evolution to this day. This concept is tightly linked to two key conjectures on evolution of cells: existence of a complex, precellular, compartmentalized but extensively mixing and recombining pool of genes, and origin of the eukaryotic cell by archaeo-bacterial fusion. The virus world concept and these models of major transitions in the evolution of cells provide complementary pieces of an emerging coherent picture of life's history. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20894 USA. Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA. Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov; tkoonina@nih.gov; doljav@cgrb.oregonstate.edu FU NIGMS NIH HHS [R01 GM053190] NR 116 TC 231 Z9 236 U1 7 U2 105 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 SEP 19 PY 2006 VL 1 AR 29 DI 10.1186/1745-6150-1-29 PG 27 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 133TM UT WOS:000244036400001 PM 16984643 ER PT J AU Putney, JW Thomas, AP AF Putney, James W., Jr. Thomas, Andrew P. TI Calcium signaling: Double duty for calcium at the mitochondrial uniporter SO CURRENT BIOLOGY LA English DT Editorial Material ID CA2+ UPTAKE; TRANSPORT; STORE; CA-2 AB Uptake of Ca2+ by mitochondria serves as a regulator of a number of important cellular functions, including energy metabolism, cytoplasmic Ca2+ signals, and apoptosis. Recent findings reveal that the process of Ca2+ uptake by the mitochondrial uniporter is itself regulated by Call in a temporally complex manner. C1 Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Univ Med & Dent New Jersey, Dept Pharmacol & Physiol, New Jersey Med Sch, Newark, NJ 07103 USA. RP Putney, JW (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. EM putney@niehs.nih.gov; thomasap@umdnj.edu FU Intramural NIH HHS [Z01 ES090087-09, 001-0123-548, Z99 ES999999] NR 20 TC 24 Z9 28 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD SEP 19 PY 2006 VL 16 IS 18 BP R812 EP R815 DI 10.1016/j.cub.2006.08.040 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 087CK UT WOS:000240719800020 PM 16979553 ER PT J AU Hiroi, Y Kim, HH Ying, H Furuya, F Huang, ZH Simoncini, T Noma, K Ulek, K Nguyen, NH Scanlan, TS Moskowitz, MA Cheng, SY Liao, JK AF Hiroi, Yukio Kim, Hyung-Hwan Ying, Hao Furuya, Fumihiko Huang, Zhihong Simoncini, Tommaso Noma, Kensuke Ulek, Kojiro Nguyen, Ngoc-Ha Scanlan, Thomas S. Moskowitz, Michael A. Cheng, Sheue-Yann Liao, James K. TI Rapid nongenomic actions of thyroid hormone SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nitric oxide; phosphatidylinositol 3-kinase; protein kinase Akt; stroke ID NITRIC-OXIDE SYNTHASE; CEREBRAL BLOOD-FLOW; B C-AKT; VENTRICULAR MYOCYTES; PHOSPHATIDYLINOSITOL 3-KINASE; IN-VIVO; ACTIVATION; RECEPTOR; MICE; KINASE AB The binding of thyroid hormone to the thyroid hormone receptor (TR) mediates important physiological effects. However, the transcriptional effects of TR mediated by the thyroid response element (TRE) cannot explain many actions of thyroid hormone. We postulate that TR can initiate rapid, non-TRE-mediated effects in the cardiovascular system through cross-coupling to the phosphatidylinositol 3-kinase (P13-kinase)/protein kinase Akt pathway. In vascular endothelial cells, the predominant TR isoform is TR alpha(1). Treatment of endothelial cells with L-3,5,3'-triiodothyronine T-3 increased the association of TR alpha(1), with the p85 alpha subunit of P13-kinase, leading to the phosphorylation and activation of Akt and endothelial nitric oxide synthase (eNOS). The activation of Akt and eNOS by T-3 was abolished by the P13-kinase inhibitors, LY294002 and wortmannin, but not by the transcriptional inhibitor, actinomycin D. To determine the physiological relevance of this P13-kinase/Akt pathway, we administered T-3 to mice undergoing transient focal cerebral ischemia. Compared with vehicle, a single bolus infusion of T-3 rapidly increased Akt activity in the brain, decreased mean blood pressure, reduced cerebral infarct volume, and improved neurological deficit score. These neuroprotective effects of T-3 were greatly attenuated or absent in eNOS(-/-) and TR alpha(-/-)(1)beta(-/-) mice and were completely abolished in WT mice pretreated with LY294002 or a T-3 antagonist, NH-3. These findings indicate that the activation of P13-kinase/Akt pathways can mediate some of the rapid, non-TRE effects of TR and suggest that the activation of Akt and eNOS contributes to some of the acute vasodilatory and neuroprotective effects of thyroid hormone. C1 Brigham & Womens Hosp, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Cambridge, MA 02139 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Lab Stroke & Neurovasc Regulat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Tokyo, Grad Sch Med, Dept Metab Dis, Tokyo 1130033, Japan. Univ Pisa, Dept Reprod Med & Child Dev, I-56126 Pisa, Italy. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA. RP Liao, JK (reprint author), Brigham & Womens Hosp, Cambridge, MA 02139 USA. EM jliao@rics.bwh.harvard.edu RI Moskowitz, Michael/D-9916-2011; OI Simoncini, Tommaso/0000-0002-2971-0079 FU NHLBI NIH HHS [HL070274, HL080187, R01 HL052233, R01 HL052233-11, R01 HL052233-12, R01 HL070274, R01 HL070274-03, R01 HL070274-04, R01 HL070274-05, R01 HL080187, R01 HL080187-03, R01 HL080187-04]; NIDDK NIH HHS [DK062729, R01 DK062729, R01 DK062729-04, R01 DK062729-05]; NINDS NIH HHS [F32 NS010828, NS010828, P01 NS010828, P50 NS010828] NR 36 TC 173 Z9 185 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 19 PY 2006 VL 103 IS 38 BP 14104 EP 14109 DI 10.1073/pnas.0601600103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 087MN UT WOS:000240746600037 PM 16966610 ER PT J AU Adams, B Holmes, EC Zhang, C Mammen, MP Nimmannitya, S Kalayanarooj, S Boots, M AF Adams, B. Holmes, E. C. Zhang, C. Mammen, M. P., Jr. Nimmannitya, S. Kalayanarooj, S. Boots, M. TI Cross-protective immunity can account for the alternating epidemic pattern of dengue virus serotypes circulating in Bangkok SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cross-immunity; mathematical model; phylogenetics; rsv; phase pattern ID ANTIBODY-DEPENDENT ENHANCEMENT; TRANSMISSION DYNAMICS; HEMORRHAGIC-FEVER; THAILAND; PREVALENCE; EVOLUTION; SELECTION; DISEASE; MODEL; PATHOGENS AB Dengue virus, the causative agent of dengue fever and its more serious manifestation dengue hemorrhagic fever, is widespread throughout tropical and subtropical regions. The virus exists as four distinct serotypes, all of which have cocirculated in Bangkok for several decades with epidemic outbreaks occurring every 8-10 years. We analyze time-series data of monthly infection incidence, revealing a distinctive pattern with epidemics of serotypes 1, 2, and 3 occurring at approximately the same time and an isolated epidemic of serotype 4 occurring in the intervening years. Phylogenetic analysis of virus samples collected over the same period shows that clade replacement events are linked to the epidemic cycle and indicates that there is an interserotypic immune reaction. Using an epidemic model with stochastic seasonal forcing showing 8- to 10-year epidemic oscillations, we demonstrate that moderate cross-protective immunity gives rise to persistent out-of-phase oscillations similar to those observed in the data, but that strong or weak cross-protection or cross-enhancement only produces in-phase patterns. This behavior suggests that the epidemic pattern observed in Bangkok is the result of cross-protective immunity and may be significantly altered by changes in the interserotypic immune reaction. C1 Univ Sheffield, Dept Anim & Plant Sci, Sheffield S10 2TN, S Yorkshire, England. Kyushu Univ, Fac Sci, Dept Biol, Fukuoka 8128581, Japan. Penn State Univ, Mueller Lab, Dept Biol, Ctr Infect Dynam, University Pk, PA 16802 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Armed Forces Res Inst Med Sci, USA Med Component, Dept Virol, Bangkok 10400, Thailand. Queen Sirikit Natl Inst Child Hlth, Bangkok 10400, Thailand. RP Adams, B (reprint author), Univ Sheffield, Dept Anim & Plant Sci, Sheffield S10 2TN, S Yorkshire, England. EM ben@bio-math10.biology.kyushu-u.ac.jp RI U-ID, Kyushu/C-5291-2016; OI Adams, Ben/0000-0001-9955-5361; Holmes, Edward/0000-0001-9596-3552 FU Wellcome Trust NR 43 TC 123 Z9 125 U1 0 U2 27 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 SEP 19 PY 2006 VL 103 IS 38 BP 14234 EP 14239 DI 10.1073/pnas.0602768103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 087MN UT WOS:000240746600059 PM 16966609 ER EF