FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Chen, KG Mallon, BS Johnson, KR Hamilton, RS Mckay, RDG Robey, PG AF Chen, Kevin G. Mallon, Barbara S. Johnson, Kory R. Hamilton, Rebecca S. McKay, Ronald D. G. Robey, Pamela G. TI Developmental insights from early mammalian embryos and core signaling pathways that influence human pluripotent cell growth and differentiation SO STEM CELL RESEARCH LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; FEEDER-FREE CONDITIONS; STEM-CELLS; SELF-RENEWAL; IN-VITRO; GSK-3-SPECIFIC INHIBITOR; CULTURE; MAINTENANCE; SUSPENSION; MOUSE AB Human pluripotent stem cells (hPSCs) have two potentially attractive applications: cell replacement-based therapies and drug discovery. Both require the efficient generation of large quantities of clinical-grade stem cells that are free from harmful genomic alterations. The currently employed colony-type culture methods often result in low cell yields, unavoidably heterogeneous cell populations, and substantial chromosomal abnormalities. Here, we shed light on the structural relationship between hPSC colonies/embryoid bodies and early-stage embryos in order to optimize current culture methods based on the insights from developmental biology. We further highlight core signaling pathways that underlie multiple epithelial-to-mesenchymal transitions (EMTs), cellular heterogeneity, and chromosomal instability in hPSCs. We also analyze emerging methods such as non-colony type monolayer (NCM) and suspension culture, which provide alternative growth models for hPSC expansion and differentiation. Furthermore, based on the influence of cell-cell interactions and signaling pathways, we propose concepts, strategies, and solutions for production of clinical-grade hPSCs, stem cell precursors, and miniorganoids, which are pivotal steps needed for future clinical applications. Published by Elsevier B.V. C1 [Chen, Kevin G.; Mallon, Barbara S.; Hamilton, Rebecca S.] NINDS, NIH Stem Cell Unit, NIH, Bethesda, MD 20892 USA. [Johnson, Kory R.] NINDS, Informat Technol & Bioinformat Program, NIH, Bethesda, MD 20892 USA. [McKay, Ronald D. G.] Lieber Inst Brain Dev, Baltimore, MD 21205 USA. [Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Chen, KG (reprint author), NINDS, NIH Stem Cell Unit, NIH, 37 Convent Dr,Room 1000, Bethesda, MD 20892 USA. EM cheng@mail.nih.gov RI Chen, Kevin/D-6769-2011; Robey, Pamela/H-1429-2011 OI Chen, Kevin/0000-0003-2983-6330; Robey, Pamela/0000-0002-5316-5576 FU National Institutes of Health (NIH) at the National Institute of Neurological Disorders and Stroke FX This work was supported by the Intramural Research Program of the National Institutes of Health (NIH) at the National Institute of Neurological Disorders and Stroke. We would like to thank Dr. Peter Zandstra for his comments and suggestions. NR 66 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-5061 EI 1876-7753 J9 STEM CELL RES JI Stem Cell Res. PD MAY PY 2014 VL 12 IS 3 BP 610 EP 621 DI 10.1016/j.scr.2014.02.002 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA AP7VX UT WOS:000342286900002 PM 24603366 ER PT J AU Vogel, J Gottesman, S Belasco, J Narberhaus, F AF Vogel, Joerg Gottesman, Susan Belasco, Joel Narberhaus, Franz TI Regulating with RNA in Bacteria 2013 SO RNA BIOLOGY LA English DT Article DE small RNA; Hfq; RNA stability; RNA-seq CRISPR; Cascade; ribonucleoprotein complex; bioinformatics ID SP PCC 6803; MESSENGER-RNA; BACILLUS-SUBTILIS; ESCHERICHIA-COLI; TRANSLATION INITIATION; CHAPERONE HFQ; HELICOBACTER-PYLORI; BIOFILM FORMATION; SOLUBLE-RNA; PROTEIN AB On June 4-8, 2013, the 3rd Conference on Regulation with RNA in Bacteria took place in Wurzburg, Germany. Following two earlier meetings in Berlin and San Juan, this conference has established itself as the primary bi-annual meeting for everyone interested in RNA-based regulations in prokaryotes. The 2013 meeting was organized by Joel Belasco, Susan Gottesman, Franz Narberhaus, and Jorg Vogel. Close to 300 participants from more than 27 countries in Europe, North America, and Asia enjoyed four days of talks and posters on many experimental and biocomputational aspects of prokaryotic RNA biology. C1 [Vogel, Joerg] Univ Wurzburg, RNA Biol Grp, IMIB, D-97070 Wurzburg, Germany. [Gottesman, Susan] NCI, Mol Biol Lab, Bethesda, MD 20892 USA. [Belasco, Joel] NYU, Sch Med, Kimmel Ctr Biol & Med, Skirball Inst, New York, NY USA. [Belasco, Joel] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA. [Narberhaus, Franz] Ruhr Univ Bochum, Bochum, Germany. RP Vogel, J (reprint author), Univ Wurzburg, RNA Biol Grp, IMIB, D-97070 Wurzburg, Germany. EM joerg.vogel@uni-wuerzburg.de; gottesms@helix.nih.gov; Joel.Belasco@med.nyu.edu; Franz.Narberhaus@ruhr-uni-bochum.de RI Vogel, Jorg/D-5574-2011 OI Vogel, Jorg/0000-0003-2220-1404 FU German Research Foundation (DFG) [NA 240/6-2] FX This conference was supported by the German Research Foundation (DFG, grant NA 240/6-2). NR 81 TC 1 Z9 1 U1 2 U2 14 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1547-6286 EI 1555-8584 J9 RNA BIOL JI RNA Biol. PD MAY PY 2014 VL 11 IS 5 BP 403 EP 412 DI 10.4161/rna.29533 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AO7FI UT WOS:000341517200001 PM 24922515 ER PT J AU Leroy, G Chen, HC Rindflesch, TC AF Leroy, Gondy Chen, Hsinchun Rindflesch, Thomas C. TI Smart and Connected Health INTRODUCTION SO IEEE INTELLIGENT SYSTEMS LA English DT Editorial Material C1 [Leroy, Gondy] Univ Arizona, Dept Management Informat Syst MIS, Tucson, AZ 85721 USA. [Chen, Hsinchun] Univ Arizona, Tucson, AZ 85721 USA. [Rindflesch, Thomas C.] Natl Lib Med, Lister Hill Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Leroy, G (reprint author), Univ Arizona, Dept Management Informat Syst MIS, Tucson, AZ 85721 USA. EM gondyleroy@email.arizona.edu; hchen@eller.arizona.edu; tcr@nlm.nih.gov NR 6 TC 1 Z9 1 U1 0 U2 2 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 1541-1672 EI 1941-1294 J9 IEEE INTELL SYST JI IEEE Intell. Syst. PD MAY-JUN PY 2014 VL 29 IS 3 BP 2 EP 5 PG 4 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA AO8AX UT WOS:000341575700001 ER PT J AU Bowman, EA Kelly, WG AF Bowman, Elizabeth A. Kelly, William G. TI RNA Polymerase II transcription elongation and Pol II CTD Ser2 phosphorylation A tail of two kinases SO NUCLEUS LA English DT Review DE transcription; RNA Polymerase II; Serine 2; Bur1; Ctk1; Cdk9; Cdk12; P-TEFb; elongation; C. elegans ID CYCLIN-DEPENDENT KINASE; CARBOXY-TERMINAL DOMAIN; EMBRYONIC STEM-CELLS; TEFB-MEDIATED PHOSPHORYLATION; BROMODOMAIN PROTEIN BRD4; P-TEFB; IN-VIVO; GENE-EXPRESSION; CAENORHABDITIS-ELEGANS; REPEAT DOMAIN AB The transition between initiation and productive elongation during RNA Polymerase II (Pol II) transcription is a well-appreciated point of regulation across many eukaryotes. Elongating Pol II is modified by phosphorylation of serine 2 (Ser2) on its carboxy terminal domain (CTD) by two kinases, Bur1/Ctk1 in yeast and Cdk9/Cdk12 in metazoans. Here, we discuss the roles and regulation of these kinases and their relationship to Pol II elongation control, and focus on recent data from work in C. elegans that point out gaps in our current understand of transcription elongation. C1 [Bowman, Elizabeth A.] NIEHS, Res Triangle Pk, NC 27709 USA. [Kelly, William G.] Emory Univ, Dept Biol, Atlanta, GA 30322 USA. RP Bowman, EA (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM bowmanea@niehs.nih.gov FU NIGMS NIH HHS [R01 GM101040] NR 169 TC 14 Z9 14 U1 1 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1949-1034 EI 1949-1042 J9 NUCLEUS-PHILA JI Nucleus PD MAY-JUN PY 2014 VL 5 IS 3 BP 224 EP 236 DI 10.4161/nucl.29347 PG 13 WC Cell Biology SC Cell Biology GA AO8YK UT WOS:000341641600005 PM 24879308 ER PT J AU Kouzine, F Levens, D Baranello, L AF Kouzine, Fedor Levens, David Baranello, Laura TI DNA topology and transcription SO NUCLEUS-AUSTIN LA English DT Article DE DNA topoisomerases; DNA topological domain; DNA topology; torsional stress; transcription ID RNA-POLYMERASE-II; NUCLEOSOME REPEAT LENGTH; C-MYC EXPRESSION; GENE-EXPRESSION; HISTONE ACETYLATION; CHROMATIN-STRUCTURE; IN-VIVO; REGULATED TRANSCRIPTION; DIVERGENT TRANSCRIPTION; ANTISENSE TRANSCRIPTION AB Chromatin is a complex assembly that compacts DNA inside the nucleus while providing the necessary level of accessibility to regulatory factors conscripted by cellular signaling systems. In this superstructure, DNA is the subject of mechanical forces applied by variety of molecular motors. Rather than being a rigid stick, DNA possesses dynamic structural variability that could be harnessed during critical steps of genome functioning. The strong relationship between DNA structure and key genomic processes necessitates the study of physical constrains acting on the double helix. Here we provide insight into the source, dynamics, and biology of DNA topological domains in the eukaryotic cells and summarize their possible involvement in gene transcription. We emphasize recent studies that might inspire and impact future experiments on the involvement of DNA topology in cellular functions. C1 [Kouzine, Fedor; Levens, David; Baranello, Laura] NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Baranello, L (reprint author), NCI, Pathol Lab, Bldg 10, Bethesda, MD 20892 USA. EM baranellolf@mail.nih.gov RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 93 TC 7 Z9 7 U1 2 U2 13 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1949-1034 EI 1949-1042 J9 NUCLEUS-AUSTIN JI Nucleus-Austin PD MAY-JUN PY 2014 VL 5 IS 3 BP 195 EP 202 DI 10.4161/nucl.28909 PG 8 WC Cell Biology SC Cell Biology GA AO8YK UT WOS:000341641600001 PM 24755522 ER PT J AU Sugiyama, H Misumi, M Kishikawa, M Iseki, M Yonehara, S Hayashi, T Soda, M Tokuoka, S Shimizu, Y Sakata, R Grant, EJ Kasagi, F Mabuchi, K Suyama, A Ozasa, K AF Sugiyama, Hiromi Misumi, Munechika Kishikawa, Masao Iseki, Masachika Yonehara, Shuji Hayashi, Tomayoshi Soda, Midori Tokuoka, Shoji Shimizu, Yukiko Sakata, Ritsu Grant, Eric J. Kasagi, Fumiyoshi Mabuchi, Kiyohiko Suyama, Akihiko Ozasa, Kotaro TI Skin Cancer Incidence among Atomic Bomb Survivors from 1958 to 1996 SO RADIATION RESEARCH LA English DT Article ID BASAL-CELL CARCINOMA; RADIATION-THERAPY; SQUAMOUS-CELL; SOLID CANCER; RISK; MORTALITY; IRRADIATION; RINGWORM; EXPOSURE; SCALP AB The radiation risk of skin cancer by histological types has been evaluated in the atomic bomb survivors. We examined 80,158 of the 120,321 cohort members who had their radiation dose estimated by the latest dosimetry system (DS02). Potential skin tumors diagnosed from 1958 to 1996 were reviewed by a panel of pathologists, and radiation risk of the first primary skin cancer was analyzed by histological types using a Poisson regression model. A significant excess relative risk (ERR) of basal cell carcinoma (BCC) (n = 123) was estimated at 1 Gy (0.74, 95% confidence interval (CI): 0.26, 1.6) for those age 30 at exposure and age 70 at observation based on a linear-threshold model with a threshold dose of 0.63 Gy (95% CI: 0.32, 0.89) and a slope of 2.0 (95% CI: 0.69, 4.3). The estimated risks were 15, 5.7, 1.3 and 0.9 for age at exposure of 0-9, 10-19, 20-39, over 40 years, respectively, and the risk increased 11% with each one-year decrease in age at exposure. The ERR for squamous cell carcinoma (SCC) in situ (n 64) using a linear model was estimated as 0.71 (95% CI: 0.063, 1.9). However, there were no significant dose responses for malignant melanoma (n = 10), SCC (n = 114), Paget disease (n = 10) or other skin cancers (n = 15). The significant linear radiation risk for BCC with a threshold at 0.63 Gy suggested that the basal cells of the epidermis had a threshold sensitivity to ionizing radiation, especially for young persons at the time of exposure. (C) 2014 by Radiation Research Society C1 [Sugiyama, Hiromi; Soda, Midori; Tokuoka, Shoji; Shimizu, Yukiko; Sakata, Ritsu; Grant, Eric J.; Ozasa, Kotaro] Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima, Japan. [Sugiyama, Hiromi; Soda, Midori; Tokuoka, Shoji; Shimizu, Yukiko; Sakata, Ritsu; Grant, Eric J.; Ozasa, Kotaro] Radiat Effects Res Fdn, Dept Epidemiol, Nagasaki, Japan. [Misumi, Munechika] Radiat Effects Res Fdn, Dept Stat, Hiroshima, Japan. [Kishikawa, Masao] Nagasaki Diagnost Pathol Clin, Nagasaki, Japan. [Iseki, Masachika] Sasebo Kyosai Hosp, Dept Pathol & Lab Med, Nagasaki, Japan. [Yonehara, Shuji] Welf Assoc Onomichi Gen Hosp, Dept Pathol, Hiroshima, Japan. [Yonehara, Shuji] Welf Assoc Onomichi Gen Hosp, Res Lab, Hiroshima, Japan. [Hayashi, Tomayoshi] Nagasaki Univ Hosp, Dept Pathol, Nagasaki, Japan. [Kasagi, Fumiyoshi] Radiat Effects Assoc, Inst Radiat Epidemiol, Tokyo, Japan. [Mabuchi, Kiyohiko] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Suyama, Akihiko] Prefecture Osaka Saiseikai Izuo Hosp, Dept Gen Internal Med, Osaka, Japan. RP Sugiyama, H (reprint author), Radiat Effects Res Fdn, Dept Epidemiol, Minami Ku, 5-2 Hijiyama Pk, Hiroshima, Japan. EM sugi@rerf.or.jp FU Japanese Ministry of Health, Labour and Welfare (MHLW); U.S. Department of Energy (DOE); DOE [DE-HS0000031]; RERF Research Protocol(s) RP [2-91, 2-02]; U.S. National Cancer Institute (NCI) [N01-CP-31012] FX We would like to thank the Hiroshima City Cancer Registry, the Hiroshima Prefecture Tumor Registry and the Nagasaki Prefecture Cancer Registry for approval to use the data, and also thank the staff of the registries for their efforts. The assistance of Ms. Sachiyo Funamoto and staff of the pathology laboratory are gratefully acknowledged. Special thanks are expressed to the late Dr. Elaine Ron for her advice. This paper is dedicated to Dr. Shoji Tokuoka, a key leader and pathologist of the site-specific cancer study program in A-bomb survivors for 25 years at RERF. His untimely death during final preparation of this paper, took from us a dedicated researcher. The Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan is a private, nonprofit foundation funded by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the U.S. Department of Energy (DOE), the latter in part through DOE Award DE-HS0000031 to the National Academy of Sciences that supported EJG. This publication was supported by RERF Research Protocol(s) RP 2-91 and 2-02, and with additional support from U.S. National Cancer Institute (NCI) contract number N01-CP-31012. The views of the authors do not necessarily reflect those of the two governments. NR 32 TC 9 Z9 10 U1 1 U2 5 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 MAY PY 2014 VL 181 IS 5 BP 531 EP 539 DI 10.1667/RR13494.1 PG 9 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA AO4KZ UT WOS:000341308100010 PM 24754560 ER PT J AU Jha, A Brailoiu, E Muallem, S AF Jha, Archana Brailoiu, Eugen Muallem, Shmuel TI How does NAADP release lysosomal Ca2+? SO CHANNELS LA English DT Editorial Material ID 2-PORE CHANNELS; ION CHANNELS C1 [Jha, Archana; Muallem, Shmuel] NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. [Brailoiu, Eugen] Temple Univ, Dept Pharmacol, Sch Med, Philadelphia, PA 19122 USA. RP Brailoiu, E (reprint author), Temple Univ, Dept Pharmacol, Sch Med, Philadelphia, PA 19122 USA. EM ebrailoiu@temple.edu; shmuel.muallem@nih.gov NR 8 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6950 EI 1933-6969 J9 CHANNELS JI Channels PD MAY-JUN PY 2014 VL 8 IS 3 DI 10.4161/chan.28995 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN6QU UT WOS:000340722000005 ER PT J AU Park, JC Citrin, DE Agarwal, PK Apolo, AB AF Park, Jong Chul Citrin, Deborah E. Agarwal, Piyush K. Apolo, Andrea B. TI Multimodal management of muscle-invasive bladder cancer SO CURRENT PROBLEMS IN CANCER LA English DT Article ID TRANSITIONAL-CELL-CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; RANDOMIZED PHASE-III; EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY; METASTATIC UROTHELIAL CANCER; SELECTIVE ORGAN PRESERVATION; CHEMOTHERAPY FOLLOWING CYSTECTOMY; UNSUSPECTED PULMONARY-EMBOLISM; GEMCITABINE PLUS CISPLATIN; COMBINED-MODALITY THERAPY C1 [Park, Jong Chul] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. [Citrin, Deborah E.] NCI, Radiat Oncol Branch, Sect Translat Radiat Oncol, Bethesda, MD 20892 USA. [Agarwal, Piyush K.] NCI, Urol Oncol Branch, Bladder Canc Sect, Bethesda, MD 20892 USA. [Apolo, Andrea B.] NCI, Bladder Canc Sect, Genitourinary Malignancies Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Park, JC (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. FU Intramural NIH HHS [ZIA BC011351-04] NR 196 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-0272 EI 1535-6345 J9 CURR PROB CANCER JI Curr. Probl. Cancer PD MAY-JUN PY 2014 VL 38 IS 3 BP 80 EP 108 DI 10.1016/j.currproblcancer.2014.06.001 PG 29 WC Oncology SC Oncology GA AN6UR UT WOS:000340734400001 PM 25087173 ER PT J AU Putluri, N Maity, S Kommangani, R Creighton, CJ Putluri, V Chen, FJ Nanda, S Bhowmik, SK Terunuma, A Dorsey, T Nardone, A Fu, XY Shaw, C Sarkar, TR Schiff, R Lydon, JP O'Malley, BW Ambs, S Das, GM Michailidis, G Sreekumar, A AF Putluri, Nagireddy Maity, Suman Kommangani, Ramakrishna Creighton, Chad J. Putluri, Vasanta Chen, Fengju Nanda, Sarmishta Bhowmik, Salil Kumar Terunuma, Atsushi Dorsey, Tiffany Nardone, Agostina Fu, Xiaoyong Shaw, Chad Sarkar, Tapasree Roy Schiff, Rachel Lydon, John P. O'Malley, Bert W. Ambs, Stefan Das, Gokul M. Michailidis, George Sreekumar, Arun TI Pathway-Centric Integrative Analysis Identifies RRM2 as a Prognostic Marker in Breast Cancer Associated with Poor Survival and Tamoxifen Resistance SO NEOPLASIA LA English DT Article ID SET ENRICHMENT ANALYSIS; LYMPH-NODE METASTASIS; PROFILING PREDICTS; MOLECULAR SUBTYPES; MASS-SPECTROMETRY; CELL-LINES; ESTROGEN; METABOLOMICS; MUTATIONS; THERAPY AB Breast cancer (BCa) molecular subtypes include luminal A, luminal B, normal-like, HER-2-enriched, and basal-like tumors, among which luminal B and basal-like cancers are highly aggressive. Biochemical pathways associated with patient survival or treatment response in these more aggressive subtypes are not well understood. With the limited availability of pathologically verified clinical specimens, cell line models are routinely used for pathway-centric studies. We measured the metabolome of luminal and basal-like BCa cell lines using mass spectrometry, linked metabolites to biochemical pathways using Gene Set Analysis, and developed a novel rank-based method to select pathways on the basis of their enrichment in patient-derived omics data sets and prognostic relevance. Key mediators of the pathway were then characterized for their role in disease progression. Pyrimidine metabolism was altered in luminal versus basal BCa, whereas the combined expression of its associated genes or expression of one key gene, ribonucleotide reductase subunit M2 (RRM2) alone, associated significantly with decreased survival across all BCa subtypes, as well as in luminal patients resistant to tamoxifen. Increased RRM2 expression in tamoxifen-resistant patients was verified using tissue microarrays, whereas the metabolic products of RRM2 were higher in tamoxifen-resistant cells and in xenograft tumors. Both genetic and pharmacological inhibition of this key enzyme in tamoxifen-resistant cells significantly decreased proliferation, reduced expression of cell cycle genes, and sensitized the cells to tamoxifen treatment. Our study suggests for evaluating RRM2-associated metabolites as noninvasive markers for tamoxifen resistance and its pharmacological inhibition as a novel approach to overcome tamoxifen resistance in BCa. C1 [Putluri, Nagireddy; Maity, Suman; Kommangani, Ramakrishna; Putluri, Vasanta; Bhowmik, Salil Kumar; Schiff, Rachel; Lydon, John P.; O'Malley, Bert W.; Sreekumar, Arun] Baylor Coll Med, Dept Mol & Cell Biol, Houston, TX 77030 USA. [Putluri, Nagireddy; Maity, Suman; Putluri, Vasanta; Bhowmik, Salil Kumar; Sreekumar, Arun] Baylor Coll Med, Verna & Marrs Mclean Dept Biochem, Houston, TX 77030 USA. [Putluri, Nagireddy; Maity, Suman; Putluri, Vasanta; Bhowmik, Salil Kumar; O'Malley, Bert W.; Sreekumar, Arun] Baylor Coll Med, Alkek Ctr Mol Discovery, Houston, TX 77030 USA. [Creighton, Chad J.; Chen, Fengju; Shaw, Chad; Schiff, Rachel] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Creighton, Chad J.; Chen, Fengju; Shaw, Chad; Schiff, Rachel; O'Malley, Bert W.; Sreekumar, Arun] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Nardone, Agostina; Fu, Xiaoyong; Schiff, Rachel] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. [Terunuma, Atsushi; Dorsey, Tiffany; Ambs, Stefan] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Sarkar, Tapasree Roy] Univ Texas MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA. [Das, Gokul M.] Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA. [Michailidis, George] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA. RP Sreekumar, A (reprint author), Baylor Coll Med, Verna & Marrs Mclean Dept Biochem, Dept Mol & Cell Biol, Houston, TX 77030 USA. EM gmichail@umich.edu; arun.sreekumar@bcm.edu FU Susan Komen Foundation [PG 1221410]; National Institute of Health (NIH) [U01 CA167234, HD-07857, NSFDMS-1161759]; National Science Foundation (NSF) [DMS-12-28164, DMS-11617838]; Cancer Prevention Research Institute of Texas [RP120092]; Alkek Center for Molecular Discovery; Breast Cancer Research Foundation; Dan L Duncan Cancer Center [NCI-P30CA016056-32]; Roswell Park Cancer Institute [PG 1221410]; NCI [RP120092, P30 CA125123]; [NCI P30 CA125123] FX This research was supported by the following grant support: Susan Komen Foundation (to A.S., N.P., R.S., and B.W.O.), PG 1221410 (to R.S.), National Institute of Health (NIH) U01 CA167234 (to A.S., N.P., and G.M.), NSFDMS-1161759 (to A.S.and G.M.), National Science Foundation (NSF) DMS-12-28164 (to G.M.) and National Science Foundation (NSF) DMS-11617838 (to G.M.), NCI P30 CA125123 (to C.J.C. and F.C.), RP120092 (to A.S. and N.P.), National Institute of Health (NIH) HD-07857 (to B.W.O.), RP120092 from Cancer Prevention Research Institute of Texas (to A.S.and N.P.), funds from the Alkek Center for Molecular Discovery (to A.S.), Breast Cancer Research Foundation (to R.S.), Dan L Duncan Cancer Center, NCI-P30CA016056-32 for Pathology Resource Network (PRN), and PG 1221410 (to R.S and B.W.O), Roswell Park Cancer Institute. NR 73 TC 11 Z9 11 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1522-8002 EI 1476-5586 J9 NEOPLASIA JI Neoplasia PD MAY PY 2014 VL 16 IS 5 BP 390 EP 402 DI 10.1016/j.neo.2014.05.007 PG 13 WC Oncology SC Oncology GA AN4JD UT WOS:000340552900002 PM 25016594 ER PT J AU Cimms, TA Howard, K Portalupi, S Saretsky, TL Hoffmann, S Crawley, JA Lorens, L Powers, JH AF Cimms, T. A. Howard, K. Portalupi, S. Saretsky, T. L. Hoffmann, S. Crawley, J. A. Lorens, L. Powers, J. H. CA FNIH Biomarkers Consortium CABP TI SIGNS, SYMPTOMS, AND EXISTING PATIENT REPORTED OUTCOME (PRO) MEASURES IN COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA (CABP): A COMPREHENSIVE LITERATURE REVIEW SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Cimms, T. A.; Crawley, J. A.] AstraZeneca, Gaithersburg, MD USA. [Howard, K.; Portalupi, S.; Saretsky, T. L.] Oxford Outcomes, San Francisco, CA USA. [Hoffmann, S.] Fdn Natl Inst Hlth, Bethesda, MD USA. [Lorens, L.] Cerexa Inc, Oakland, CA USA. [Powers, J. H.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2014 VL 17 IS 3 MA PIN84 BP A279 EP A279 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA AO1OG UT WOS:000341082001665 ER PT J AU Howard, K Portalupi, S Hoffmann, S Crawley, JA Lorens, L Cimms, TA Powers, JH AF Howard, K. Portalupi, S. Hoffmann, S. Crawley, J. A. Lorens, L. Cimms, T. A. Powers, J. H. CA FNIH Biomarkers Consortium CABP TI DEVELOPMENT OF A NEW PATIENT REPORTED OUTCOME (PRO) MEASURE FOR COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA (CABP) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Howard, K.; Portalupi, S.] Oxford Outcomes, San Francisco, CA USA. [Hoffmann, S.] Fdn Natl Inst Hlth, Bethesda, MD USA. [Crawley, J. A.; Cimms, T. A.] AstraZeneca, Gaithersburg, MD USA. [Lorens, L.] Cerexa Inc, Oakland, CA USA. [Powers, J. H.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2014 VL 17 IS 3 MA PIN85 BP A280 EP A280 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA AO1OG UT WOS:000341082001666 ER PT J AU Majercak, K Nghiem, E Byrne, C Muti, P Barba, M Lavigne, J Faupel-Badger, J Teter, B Fuhrman, B AF Majercak, K. Nghiem, E. Byrne, C. Muti, P. Barba, M. Lavigne, J. Faupel-Badger, J. Teter, B. Fuhrman, B. TI MAMMOGRAPHIC DENSITY IN ASSOCIATION WITH SMOKING STATUS AND SMOKING HISTORIES IN A SAMPLE OF POSTMENOPAUSAL WOMEN: RESULTS FROM A CROSS-SECTIONAL STUDY SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Majercak, K.; Fuhrman, B.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Nghiem, E.] Univ Maryland, College Pk, MD 20742 USA. [Byrne, C.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Muti, P.] McMaster Univ, Hamilton, ON, Canada. [Barba, M.] Italian Natl Canc Inst, Rome, Italy. [Lavigne, J.; Faupel-Badger, J.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Teter, B.] SUNY Buffalo, Buffalo, NY 14260 USA. RI Byrne, Celia/K-2964-2015 OI Byrne, Celia/0000-0001-8289-4252 NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2014 VL 17 IS 3 MA PCN26 BP A72 EP A72 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA AO1OG UT WOS:000341082000391 ER PT J AU Powers, JH Portalupi, S Devine, J Saretsky, TL Hoffmann, S Crawley, J Lorens, L Cimms, TA Howard, K AF Powers, J. H. Portalupi, S. Devine, J. Saretsky, T. L. Hoffmann, S. Crawley, J. Lorens, L. Cimms, T. A. Howard, K. CA FNIH Biomarkers Consortium CABP TI ACUTE BACTERIAL SKIN AND SKIN STRUCTURE INFECTION (ABSSI): DEVELOPMENT OF A NEW PATIENT REPORTED OUTCOME (PRO) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Powers, J. H.] NIAID, NIH, Bethesda, MD 20892 USA. [Portalupi, S.; Devine, J.; Saretsky, T. L.; Howard, K.] Oxford Outcomes, San Francisco, CA USA. [Hoffmann, S.] Fdn Natl Inst Hlth, Bethesda, MD USA. [Crawley, J.; Cimms, T. A.] AstraZeneca, Gaithersburg, MD USA. [Lorens, L.] Cerexa Inc, Oakland, CA 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 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2014 VL 17 IS 3 MA PSS31 BP A288 EP A288 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA AO1OG UT WOS:000341082001714 ER PT J AU Shi, W Greco, G Gelijns, A Blackstone, E Moskowitz, A O'Gara, Jeffries, N Bagiella, E AF Shi, W. Greco, G. Gelijns, A. Blackstone, E. Moskowitz, A. O'Gara Jeffries, N. Bagiella, E. TI ESTIMATING THE COST OF HEALTH CARE ASSOCIATED INFECTIONS CONTROLLING FOR BOTH PATIENT VARIABILITY AND TIME-DEPENDENT BIAS SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Shi, W.; Greco, G.; Gelijns, A.; Moskowitz, A.; Bagiella, E.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Blackstone, E.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [O'Gara] Brigham & Womens Hosp, Boston, MA 02115 USA. [Jeffries, N.] NHLBI, 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 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAY PY 2014 VL 17 IS 3 MA PRM30 BP A186 EP A186 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA AO1OG UT WOS:000341082001147 ER PT J AU McAuley, PA Chen, HY Lee, DC Artero, EG Bluemke, DA Burke, GL AF McAuley, Paul A. Chen, Haiying Lee, Duck-chul Artero, Enrique Garcia Bluemke, David A. Burke, Gregory L. TI Physical Activity, Measures of Obesity, and Cardiometabolic Risk: The Multi-Ethnic Study of Atherosclerosis (MESA) SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE cardiovascular disease; diabetes; ethnicity; obesity ID CARDIOVASCULAR-DISEASE RISK; BODY-MASS INDEX; LOW CARDIORESPIRATORY FITNESS; ALL-CAUSE MORTALITY; WEIGHT-LOSS; INSULIN-RESISTANCE; METABOLIC SYNDROME; MEN; HEALTH; WOMEN AB Background: The influence of higher physical activity on the relationship between adiposity and cardiometabolic risk is not completely understood. Methods: Between 2000-2002, data were collected on 6795 Multi-Ethnic Study of Atherosclerosis (MESA) participants. Self-reported intentional physical activity in the lowest quartile (0-105 MET-minutes/week) was categorized as inactive and the upper three quartiles (123-37,260 MET-minutes/week) as active. Associations of body mass index (BMI) and waist circumference categories, stratified by physical activity status (inactive or active) with cardiometabolic risk factors (dyslipidemia, hypertension, upper quartile of homeostasis model assessment of insulin resistance [HOMA-IR] for population, and impaired fasting glucose or diabetes) were assessed using logistic regression analysis adjusting for age, gender, race/ethnicity, and current smoking. Results: Among obese participants, those who were physically active had reduced odds of insulin resistance (47% lower; P < .001) and impaired fasting glucose/diabetes (23% lower; P = .04). These associations were weaker for central obesity. However, among participants with a normal waist circumference, those who were inactive were 63% more likely to have insulin resistance (OR [95% CI] 1.63 [1.24-2.15]) compared with the active reference group. Conclusions: Physical activity was inversely related to the cardiometabolic risk associated with obesity and central obesity. C1 [McAuley, Paul A.] Winston Salem State Univ, Dept Hlth Phys Educ & Sport Sci, Winston Salem, NC 27110 USA. [Chen, Haiying] Wake Forest Univ, Dept Biostat Sci, Winston Salem, NC 27109 USA. [Lee, Duck-chul] Iowa State Univ, Dept Kinesiol, Ames, IA USA. [Artero, Enrique Garcia] Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA. [Bluemke, David A.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Burke, Gregory L.] Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC USA. RP McAuley, PA (reprint author), Winston Salem State Univ, Dept Hlth Phys Educ & Sport Sci, Winston Salem, NC 27110 USA. RI Artero, Enrique G./L-8628-2014; OI Artero, Enrique G./0000-0002-2618-6128; Bluemke, David/0000-0002-8323-8086 FU NCRR NIH HHS [M01-RR07122, M01 RR007122]; NHLBI NIH HHS [N01 HC095165, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95169, N01HC95159, N01HC95166, N01HC95169] NR 31 TC 4 Z9 4 U1 1 U2 9 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 EI 1543-5474 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD MAY PY 2014 VL 11 IS 4 BP 831 EP 837 DI 10.1123/jpah.2012-0326 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AM6OM UT WOS:000339984500021 PM 23676525 ER PT J AU Rosentul, DC Plantinga, TS Farcas, M Oosting, M Hamza, OJM Scott, WK Alexander, BD Yang, JC Laird, GM Joosten, LAB van der Meer, JWM Perfect, JR Kullberg, BJ van der Ven, AJAM Johnson, MD Netea, MG AF Rosentul, Diana C. Plantinga, Theo S. Farcas, Marius Oosting, Marije Hamza, Omar J. M. Scott, William K. Alexander, Barbara D. Yang, John C. Laird, Gregory M. Joosten, Leo A. B. van der Meer, Jos W. M. Perfect, John R. Kullberg, Bart-Jan van der Ven, Andre J. A. M. Johnson, Melissa D. Netea, Mihai G. TI Role of autophagy genetic variants for the risk of Candida infections SO MEDICAL MYCOLOGY LA English DT Article DE HIV; Candida albicans; candidemia; autophagy; oropharyngeal candidiasis; genetic association study ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; GENOME-WIDE ASSOCIATION; CROHNS-DISEASE; FUNGAL-INFECTIONS; HUMAN DECTIN-1; SUSCEPTIBILITY; POLYMORPHISM; PREVALENCE; LOCI; IRGM AB Candida albicans can cause candidemia in neutropenic and critically ill patients and oropharyngeal candidiasis in human immunodeficiency virus (HIV)-positive patients with low CD4(+) counts. Because all patients at risk do not develop Candida infections, it is possible that a patient's genetic background might play a role in his or her susceptibility to infection. Autophagy mediates pathogen clearance and modulation of inflammation. Our aim was to assess the effect of genetic variations in the ATG16L1 and IRGM autophagy genes on the susceptibility of patients with candidemia and oropharyngeal candidiasis. We assessed genetic variations in the ATG16L1 and IRGM genes in a cohort of candidemia patients of both African and European origin. In addition, we evaluated the effect of these polymorphisms on the susceptibility to oropharyngeal candidiasis of an HIV-positive cohort from Tanzania. Functional studies have been performed to assess the effect of the ATG16L1 and IRGM genetic variants on both in vitro and in vivo cytokine production. The results indicate that ATG16L1 variants modulate production of tumor necrosis factor-alpha, but not other cytokines, while no effects were seen in the presence of IRGM polymorphisms. In addition, no significant associations between the single-nucleotide polymorphisms in the ATG16L1 and IRGM genetic variants and the incidence of candidemia or oropharyngeal candidiasis were identified. Despite moderate effects on the modulation of proinflammatory cytokine production, genetic variation in the autophagy genes ATG16L1 and IRGM has a minor impact on the susceptibility to both mucosal and systemic Candida infections. C1 [Rosentul, Diana C.; Plantinga, Theo S.; Farcas, Marius; Oosting, Marije; Joosten, Leo A. B.; van der Meer, Jos W. M.; Kullberg, Bart-Jan; van der Ven, Andre J. A. M.; Netea, Mihai G.] Radboud Univ Nijmegen Med Ctr, Dept Med, Nijmegen, Netherlands. [Rosentul, Diana C.; Plantinga, Theo S.; Farcas, Marius; Oosting, Marije; Joosten, Leo A. B.; van der Meer, Jos W. M.; Kullberg, Bart-Jan; van der Ven, Andre J. A. M.; Netea, Mihai G.] Radboud Univ Nijmegen Med Ctr, Nijmegen Inst Infect Inflammat & Immun, Nijmegen, Netherlands. [Farcas, Marius] Iuliu Hatieganu Univ Med & Pharm, Dept Med Genet, Cluj Napoca, Romania. [Hamza, Omar J. M.] Muhimbili Univ Coll Hlth & Allied Sci, Dar Es Salaam, Tanzania. [Scott, William K.] Univ Miami, Miller Sch Med, Dept Human Genet, Dr John T Macdonald Fdn, Miami, FL 33136 USA. [Scott, William K.] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA. [Alexander, Barbara D.; Laird, Gregory M.; Perfect, John R.; Johnson, Melissa D.] Duke Univ Med Ctr, Div Infect Dis & Int Hlth, Durham, NC USA. [Yang, John C.] Natl Jewish Hlth, Denver, CO USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Johnson, Melissa D.] Campbell Univ Sch Pharm, Dept Clin Res, Buies Creek, NC USA. RP Netea, MG (reprint author), Radboud Univ Nijmegen Med Ctr, Dept Med 463, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM mihai.netea@radboudumc.nl RI Andrade, Hugo/M-6631-2013; Plantinga, Theo/A-6895-2015; Joosten, Leo/H-3138-2015; Ven, A.J.A.M./H-8102-2014; Kullberg, Bart Jan/C-8520-2013; Netea, Mihai/N-5155-2014; van der Meer, Jos/C-8521-2013; Oosting, Marije/H-7437-2015; OI Andrade, Hugo/0000-0001-6781-6125; van der Meer, Jos/0000-0001-5120-3690; Johnson, Melissa/0000-0002-6606-9460 FU European Commission through the FINSysB Marie Curie Initial Training Network [PITN-GA-2008-214004]; Veni grant from the Netherlands Organization for Scientific Research; European Research Council from the European Research Council [310372]; National Institutes of Health [AI-51537, AI-73896] FX D.C.R. received funding from the European Commission through the FINSysB Marie Curie Initial Training Network (PITN-GA-2008-214004). T. S. P. was supported by a Veni grant from the Netherlands Organization for Scientific Research. This study was partially supported by an European Research Council Consolidator Grant (nr. 310372) from the European Research Council to M.G.N. and by National Institutes of Health grants AI-51537 to M.D.J. and AI-73896 to J.R.P. All authors had full access to all study data and take responsibility for data integrity data and accuracy of data analysis. NR 37 TC 7 Z9 7 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1369-3786 EI 1460-2709 J9 MED MYCOL JI Med. Mycol. PD MAY PY 2014 VL 52 IS 4 BP 333 EP 341 DI 10.1093/mmy/myt035 PG 9 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA AM5PX UT WOS:000339913600001 PM 24713404 ER PT J AU Bartlett, EK Kammula, US AF Bartlett, Edmund K. Kammula, Udai S. TI Location, location, location The relationship of anatomic site, antigen expression, and T-cell infiltration in human melanoma metastases SO ONCOIMMUNOLOGY LA English DT Editorial Material DE melanoma; metastases; site-specific expression; differentiation antigen; immunoediting ID HETEROGENEITY AB Metastatic cell heterogeneity presents a significant obstacle to the development of targeted molecular and immunotherapeutics. Profiling of melanocyte differentiation antigens has revealed a nonstochastic, site-specific pattern of expression in metastases that was highest in brain, intermediate in soft tissues/lymph nodes, and lowest in visceral sites. Site-specific antigen heterogeneity, thus, is an important confounding factor to consider when assessing the potential efficacy of antigen-specific therapies. C1 [Bartlett, Edmund K.; Kammula, Udai S.] NCI, Ctr Canc Res, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Kammula, US (reprint author), NCI, Ctr Canc Res, Surg Branch, NIH, Bethesda, MD 20892 USA. EM udai_kammula@nih.gov OI Bartlett, Edmund/0000-0002-0923-153X NR 10 TC 0 Z9 0 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD MAY PY 2014 VL 3 IS 5 AR e28963 DI 10.4161/onci.28963 PG 2 WC Oncology; Immunology SC Oncology; Immunology GA AM6EP UT WOS:000339956200016 ER PT J AU Ohnuki, H Tosato, G AF Ohnuki, Hidetaka Tosato, Giovanna TI Notch and TGF beta Functional partners facilitating tumor progression SO ONCOIMMUNOLOGY LA English DT Editorial Material DE Notch; Tgf beta; tumor-infiltrating myeloid cells; head and neck tumors; tumor microenvironment; tumor progression ID SIGNALING PATHWAYS; CANCER; CELLS AB Cell signals integral to the tumor microenvironment influence cancer progression. Tumor-associated myeloid cells secrete pro-tumorigenic agents including, but not limited to, the potent cytokine transforming growth factor beta (TGF beta). We have discovered a network of extrinsic signals including delta-like 4 (Dll4), Notch and TGF beta, linking malignant cells and tumor-infiltrating myeloid cells, a nexus portending a clinically-relevant anticancer treatment. C1 [Ohnuki, Hidetaka; Tosato, Giovanna] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Tosato, G (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM tosatog@mail.nih.gov RI Ohnuki, Hidetaka/E-1877-2012 OI Ohnuki, Hidetaka/0000-0001-8951-3264 NR 10 TC 1 Z9 1 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD MAY PY 2014 VL 3 IS 5 AR e29029 DI 10.4161/onci.29029 PG 2 WC Oncology; Immunology SC Oncology; Immunology GA AM6EP UT WOS:000339956200020 ER PT J AU Flegel, WA Roseff, SD Tholpady, A AF Flegel, Willy A. Roseff, Susan D. Tholpady, Ashok TI Phasing-In RHD Genotyping SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Editorial Material ID WEAK-D; PHENOTYPES; ALLELES; POPULATION; VARIANTS; ANTIGENS; DONORS C1 [Flegel, Willy A.; Tholpady, Ashok] NIH, Lab Serv Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Roseff, Susan D.] Virginia Commonwealth Univ Hlth Syst, Dept Pathol, Richmond, VA USA. RP Flegel, WA (reprint author), NIH, Lab Serv Sect, Dept Transfus Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. EM bill.flegel@nih.gov OI Tholpady, Ashok/0000-0003-3978-9574 FU Intramural NIH HHS [Z99 CL999999] NR 22 TC 2 Z9 2 U1 0 U2 0 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 2014 VL 138 IS 5 BP 585 EP 588 DI 10.5858/2013-0509-ED PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA AM0TX UT WOS:000339560900005 PM 24786114 ER PT J AU Wakaba, K Katayama, Y Sasai, H Nagao, Y Kozawa, T Tanaka, K AF Wakaba, Kyohsuke Katayama, Yasutomi Sasai, Hiroyuki Nagao, Yoko Kozawa, Takako Tanaka, Kiyoji TI Common Preferences For Weight Loss Programs In Japanese Adults: An Internet-based Survey SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 61st Annual Meeting of the American-College-of-Sports-Medicine CY APR 01-04, 2014 CL Atlanta, GA SP Amer Coll Sports Med C1 [Wakaba, Kyohsuke; Katayama, Yasutomi; Nagao, Yoko] Kogakkan Univ, Ise, Japan. [Sasai, Hiroyuki] NIA, NIH, Bethesda, MD 20892 USA. [Kozawa, Takako; Tanaka, Kiyoji] Univ Tsukuba, Tsukuba, Ibaraki, Japan. 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 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2014 VL 46 IS 5 SU 1 MA 1436 BP 383 EP 383 PG 1 WC Sport Sciences SC Sport Sciences GA AL4PW UT WOS:000339115902279 ER PT J AU Christensen, EJ Chan, L Keyser, RE AF Christensen, Eric J. Chan, Leighton Keyser, Randall E. TI Six-Minute Walk Distance and Fatigability in Patients with Interstitial Lung Disease SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 61st Annual Meeting of the American-College-of-Sports-Medicine CY APR 01-04, 2014 CL Atlanta, GA SP Amer Coll Sports Med C1 [Christensen, Eric J.; Chan, Leighton] NIH, Bethesda, MD 20892 USA. [Keyser, Randall E.] George Mason Univ, Fairfax, VA 22030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2014 VL 46 IS 5 SU 1 MA 1974 BP 541 EP 541 PG 1 WC Sport Sciences SC Sport Sciences GA AL4PW UT WOS:000339115903333 ER PT J AU Woolstenhulme, JG Chan, L Keyser, RE AF Woolstenhulme, Joshua G. Chan, Leighton Keyser, Randall E. TI Adaptations To Aerobic Exercise In Interstitial Lung Disease SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 61st Annual Meeting of the American-College-of-Sports-Medicine CY APR 01-04, 2014 CL Atlanta, GA SP Amer Coll Sports Med C1 [Woolstenhulme, Joshua G.; Chan, Leighton] NIH, Bethesda, MD 20892 USA. [Keyser, Randall E.] George Mason Univ, Fairfax, VA 22030 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2014 VL 46 IS 5 SU 1 MA 1979 BP 543 EP 543 PG 1 WC Sport Sciences SC Sport Sciences GA AL4PW UT WOS:000339115903338 ER PT J AU Chin, LMK Chan, L Keyser, RE AF Chin, Lisa M. K. Chan, Leighton Keyser, Randall E. TI Cardiorespiratory Function and Aerobic Exercise Training in Patients with Traumatic Brain Injury SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 61st Annual Meeting of the American-College-of-Sports-Medicine CY APR 01-04, 2014 CL Atlanta, GA SP Amer Coll Sports Med C1 [Chin, Lisa M. K.; Keyser, Randall E.] George Mason Univ, Fairfax, VA 22030 USA. [Chan, Leighton] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2014 VL 46 IS 5 SU 1 MA 2014 BP 554 EP 554 PG 1 WC Sport Sciences SC Sport Sciences GA AL4PW UT WOS:000339115903373 ER PT J AU Schrager, MA Schrack, JA Simonsick, EM Ferrucci, L AF Schrager, Matthew A. Schrack, Jennifer A. Simonsick, Eleanor M. Ferrucci, Luigi TI The Association between Energy Availability and Physical Activity in Older Adults SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 61st Annual Meeting of the American-College-of-Sports-Medicine CY APR 01-04, 2014 CL Atlanta, GA SP Amer Coll Sports Med C1 [Schrager, Matthew A.] Stetson Univ, Deland, FL USA. [Schrack, Jennifer A.] Johns Hopkins Sch Med, Baltimore, MD USA. [Simonsick, Eleanor M.; Ferrucci, Luigi] NIA, Baltimore, MD 21224 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 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2014 VL 46 IS 5 SU 1 MA 2420 BP 652 EP 652 PG 1 WC Sport Sciences SC Sport Sciences GA AL4PW UT WOS:000339115904225 ER PT J AU Kim, M Kim, H Sasai, H Kojima, N Varadhan, R AF Kim, Miji Kim, Hunkyung Sasai, Hiroyuki Kojima, Narumi Varadhan, Ravi TI Association Between Objectively Measured Sleep Quality and Physical Function in the Oldest Old SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 61st Annual Meeting of the American-College-of-Sports-Medicine CY APR 01-04, 2014 CL Atlanta, GA SP Amer Coll Sports Med C1 [Kim, Miji; Kim, Hunkyung; Kojima, Narumi] Tokyo Metropolitan Inst Gerontol, Tokyo, Japan. [Sasai, Hiroyuki] NIA, NIH, Bethesda, MD 20892 USA. [Varadhan, Ravi] Johns Hopkins Univ, Baltimore, MD 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 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2014 VL 46 IS 5 SU 1 MA 2671 BP 716 EP 716 PG 1 WC Sport Sciences SC Sport Sciences GA AL4PW UT WOS:000339115905008 ER PT J AU Keadle, SK Shiroma, EJ Freedson, PS Lee, IM AF Keadle, Sarah Kozey Shiroma, Eric J. Freedson, Patty S. Lee, I-Min TI Impact Of Accelerometer Data Processing Decisions On Data From Large Cohort Studies SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 61st Annual Meeting of the American-College-of-Sports-Medicine CY APR 01-04, 2014 CL Atlanta, GA SP Amer Coll Sports Med C1 [Keadle, Sarah Kozey] NCI, Bethesda, MD 20892 USA. [Shiroma, Eric J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Freedson, Patty S.] Univ Massachusetts, Amherst, MA 01003 USA. [Lee, I-Min] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2014 VL 46 IS 5 SU 1 MA 2679 BP 718 EP 718 PG 1 WC Sport Sciences SC Sport Sciences GA AL4PW UT WOS:000339115905015 ER PT J AU Arem, H Moore, SC Patel, AV Visvanathan, K Freedman, M Linet, MS Lee, IM Matthews, CE AF Arem, Hannah Moore, Steven C. Patel, Alpa V. Visvanathan, Kala Freedman, Michal Linet, Martha S. Lee, I-min Matthews, Charles E. TI Leisure Time Physical Activity And Mortality: Is More Better? SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT 61st Annual Meeting of the American-College-of-Sports-Medicine CY APR 01-04, 2014 CL Atlanta, GA SP Amer Coll Sports Med C1 [Arem, Hannah; Moore, Steven C.; Freedman, Michal; Linet, Martha S.; Matthews, Charles E.] NCI, Bethesda, MD 20892 USA. [Patel, Alpa V.] Amer Canc Soc, Atlanta, GA 30329 USA. [Visvanathan, Kala] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. [Lee, I-min] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2014 VL 46 IS 5 SU 1 MA 2866 BP 775 EP 776 PG 2 WC Sport Sciences SC Sport Sciences GA AL4PW UT WOS:000339115905197 ER PT J AU Liu, LH Gritz, D Parent, CA AF Liu, Lunhua Gritz, Derek Parent, Carole A. TI PKC beta II acts downstream of chemoattractant receptors and mTORC2 to regulate cAMP production and myosin II activity in neutrophils SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID PROTEIN-KINASE-C; CYCLASE TYPE-II; ADENYLYL-CYCLASE; CELL-MIGRATION; MYELOID-LEUKEMIA; MAMMALIAN TARGET; SIGNAL RELAY; TURN MOTIF; PHOSPHORYLATION; CHEMOTAXIS AB Chemotaxis is a process by which cells polarize and move up a chemical gradient through the spatiotemporal regulation of actin assembly and actomyosin contractility, which ultimately control front protrusions and back retractions. We previously demonstrated that in neutrophils, mammalian target of rapamycin complex 2 (mTORC2) is required for chemoatntractant- mediated activation of adenylyl cyclase 9 (AC9), which converts ATP into cAMP and regulates back contraction through MyoII phosphorylation. Here we study the mechanism by which mTORC2 regulates neutrophil chemotaxis and AC9 activity. We show that inhibition of protein kinase C beta II (PKC beta II) by CPG53353 or short hairpin RNA knockdown severely inhibits chemoattractant-induced cAMP synthesis and chemotaxis in neutrophils. Remarkably, PKC beta II-inhibited cells exhibit specific and severe tail retraction defects. In response to chemoattractant stimulation, phosphorylated PKC beta II, but not PKC alpha, is transiently translocated to the plasma membrane, where it phosphorylates and activates AC9. mTORC2-mediated PKC beta II phosphorylation on its turn motif, but not its hydrophobic motif, is required for membrane translocation of PKC beta II. Inhibition of mTORC2 activity by Rictor knockdown not only dramatically decreases PKC beta II activity, but it also strongly inhibits membrane translocation of PKC beta II. Together our findings show that PKC beta II is specifically required for mTORC2-dependent AC9 activation and back retraction during neutrophil chemotaxis. C1 [Liu, Lunhua; Gritz, Derek; Parent, Carole A.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Parent, CA (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM parentc@mail.nih.gov FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health FX We thank Amy Melpolder and the National Institutes of Health Blood Bank for providing human blood from healthy volunteers. We also thank the Parent laboratory members for excellent discussions and suggestions. This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 64 TC 11 Z9 11 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 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY 1 PY 2014 VL 25 IS 9 BP 1446 EP 1457 DI 10.1091/mbc.E14-01-0037 PG 12 WC Cell Biology SC Cell Biology GA AM2AJ UT WOS:000339650200004 PM 24600048 ER PT J AU Ma, XM Miller, MB Vishwanatha, KS Gross, MJ Wang, YP Abbott, T Lam, TT Mains, RE Eipper, BA AF Ma, Xin-Ming Miller, Megan B. Vishwanatha, K. S. Gross, Maegan J. Wang, Yanping Abbott, Thomas Lam, TuKiet T. Mains, Richard E. Eipper, Betty A. TI Nonenzymatic domains of Kalirin7 contribute to spine morphogenesis through interactions with phosphoinositides and Abl SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID NUCLEOTIDE EXCHANGE-FACTOR; DENDRITIC SPINES; HIPPOCAMPAL-NEURONS; TYROSINE PHOSPHORYLATION; EXCITATORY SYNAPSES; SYNAPTIC PLASTICITY; RECEPTOR ACTIVATION; GEF KALIRIN; FACTOR TRIO; PROTEIN AB Like several Rho GDP/GTP exchange factors (GEFs), Kalirin7 (Kal7) contains an N-terminal Sec14 domain and multiple spectrin repeats. A natural splice variant of Kalrn lacking the Sec14 domain and four spectrin repeats is unable to increase spine formation; our goal was to understand the function of the Sec14 and spectrin repeat domains. Kal7 lacking its Sec14 domain still increased spine formation, but the spines were short. Strikingly, Kal7 truncation mutants containing only the Sec14 domain and several spectrin repeats increased spine formation. The Sec14 domain bound phosphoinositides, a minor but crucial component of cellular membranes, and binding was increased by a phosphomimetic mutation. Expression of KalSec14-GFP in nonneuronal cells impaired receptor-mediated endocytosis, linking Kal7 to membrane trafficking. Consistent with genetic studies placing Abl, a non-receptor tyrosine kinase, and the Drosophila orthologue of Kalrn into the same signaling pathway, Abl1 phosphorylated two sites in the fourth spectrin repeat of Kalirin, increasing its sensitivity to calpain-mediated degradation. Treating cortical neurons of the wild-type mouse, but not the Kal7(KO) mouse, with an Abl inhibitor caused an increase in linear spine density. Phosphorylation of multiple sites in the N-terminal Sec14/spectrin region of Kal7 may allow coordination of the many signaling pathways contributing to spine morphogenesis. C1 [Ma, Xin-Ming; Miller, Megan B.; Vishwanatha, K. S.; Gross, Maegan J.; Wang, Yanping; Mains, Richard E.; Eipper, Betty A.] Univ Connecticut, Ctr Hlth, Dept Neurosci, Farmington, CT 06030 USA. [Abbott, Thomas; Lam, TuKiet T.] Yale Univ, WM Keck Fdn, Biotechnol Resource Lab, Yale NIDA Neuroprote Ctr, New Haven, CT 06511 USA. RP Eipper, BA (reprint author), Univ Connecticut, Ctr Hlth, Dept Neurosci, Farmington, CT 06030 USA. EM ma@uchc.edu; eipper@uchc.edu FU National Institutes of Health [DK-32948, DA-15464, DA-23082, P30 DA018343]; Scoville Endowment; Janice and Rodney Reynolds Endowment FX This work was supported by grants from the National Institutes of Health (DK-32948, DA-15464, DA-23082, and P30 DA018343) and by support from the Scoville Endowment and the Janice and Rodney Reynolds Endowment. We thank Darlene D'Amato for incomparable technical assistance, Laura Urbanski for assistance with the calpain studies, Kathrin Wilczak and Mary LoPresti for assistance with sample preparation, Lisa Chung for help with pTyr quantitation, and Prashant Mandela for assistance with the KalSRKO mice. NR 84 TC 6 Z9 6 U1 1 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY 1 PY 2014 VL 25 IS 9 BP 1458 EP 1471 DI 10.1091/mbc.E13-04-0215 PG 14 WC Cell Biology SC Cell Biology GA AM2AJ UT WOS:000339650200005 PM 24600045 ER PT J AU Dittmer, TA Sahni, N Kubben, N Hill, DE Vidal, M Burgess, RC Roukos, V Misteli, T AF Dittmer, Travis A. Sahni, Nidhi Kubben, Nard Hill, David E. Vidal, Marc Burgess, Rebecca C. Roukos, Vassilis Misteli, Tom TI Systematic identification of pathological lamin A interactors SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID DREIFUSS MUSCULAR-DYSTROPHY; GILFORD-PROGERIA-SYNDROME; PROTEIN-PROTEIN INTERACTIONS; NUCLEAR LAMIN; AUTOSOMAL-DOMINANT; LMNA GENE; COMPOUND HETEROZYGOSITY; DILATED CARDIOMYOPATHY; PARTIAL LIPODYSTROPHY; MUTATION ANALYSIS AB Laminopathies are a collection of phenotypically diverse diseases that include muscular dystrophies, cardiomyopathies, lipodystrophies, and premature aging syndromes. Laminopathies are caused by > 300 distinct mutations in the LMNA gene, which encodes the nuclear intermediate filament proteins lamin A and C, two major architectural elements of the mammalian cell nucleus. The genotype-phenotype relationship and the basis for the pronounced tissue specificity of laminopathies are poorly understood. Here we seek to identify on a global scale lamin A-binding partners whose interaction is affected by disease-relevant LMNA mutations. In a screen of a human genome-wide ORFeome library, we identified and validated 337 lamin A-binding proteins. Testing them against 89 known lamin A disease mutations identified 50 disease-associated interactors. Association of progerin, the lamin A isoform responsible for the premature aging disorder Hutchinson-Gilford progeria syndrome, with its partners was largely mediated by farnesylation. Mapping of the interaction sites on lamin A identified the immunoglobulin G (IgG)-like domain as an interaction hotspot and demonstrated that lamin A variants, which destabilize the Ig-like domain, affect protein-protein interactions more globally than mutations of surface residues. Analysis of a set of LMNA mutations in a single residue, which result in three phenotypically distinct diseases, identified disease-specific interactors. The results represent a systematic map of disease-relevant lamin A interactors and suggest loss of tissue-specific lamin A interactions as a mechanism for the tissue-specific appearance of laminopathic phenotypes. C1 [Dittmer, Travis A.; Kubben, Nard; Burgess, Rebecca C.; Roukos, Vassilis; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA. [Sahni, Nidhi; Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA. [Sahni, Nidhi; Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Sahni, Nidhi; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov RI Roukos, Vassilis/K-6248-2012 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; Progeria Research Foundation; National Institutes of Health [HG001715, HG006066] FX We thank Song Yi, Sam Pevzner, Ty Voss, and Orna Cohen-Fix for technical expertise. Imaging was performed in the National Cancer Institute High-Throughput Imaging Facility. This work was in part supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, the Progeria Research Foundation, and National Institutes of Health grants HG001715 and HG006066. NR 69 TC 11 Z9 11 U1 0 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY 1 PY 2014 VL 25 IS 9 BP 1493 EP 1510 DI 10.1091/mbc.E14-02-0733 PG 18 WC Cell Biology SC Cell Biology GA AM2AJ UT WOS:000339650200008 PM 24623722 ER PT J AU Johnson, JPS Kumar, P Koulnis, M Patel, M Simin, K AF Johnson, Jacob P. S. Kumar, Prashant Koulnis, Miroslav Patel, Milan Simin, Karl TI Crucial and Novel Cancer Drivers in a Mouse Model of Triple-negative Breast Cancer SO CANCER GENOMICS & PROTEOMICS LA English DT Article DE Breast cancer; CGH; integrative analysis; tumor suppressor; oncogene; mouse model; triple-negative; Wnt; Myc; Arid; Mapk; LCE ID EPITHELIAL-MESENCHYMAL TRANSITION; STEM-CELLS; MOLECULAR CHARACTERIZATION; ARRAY CGH; PATHWAYS; TUMORS; RECEPTOR; INDUCE; DEATH; IDENTIFICATION AB Background: We previously developed a mouse model of breast cancer that mimics human triple-negative breast cancer (TNBC) by inactivating the Retinoblastoma (Rb), Transformation related protein 53 (p53), and Breast cancer 1 (Brca1) pathways in the mammary gland. Despite inactivation of all three tumor suppressors throughout the epithelium, low tumor multiplicity indicated that malignant carcinoma progression requires additional oncogenic stimuli. Materials and Methods: In order to identify collaborating genetic events, we performed integrated analysis of 18 tumors (eight tumors with inactivation of pRbf/Brca1/p53 and ten tumors with inactivation of pRbf/p53) using comparative genomic hybridization and global gene expression. We then conducted flow cytometric analysis, immunostaining, tumorsphere, and cell viability assays. Results: Copy number aberrations were correlated with the transcript levels of 7.55% of genes spanned by the altered genomic regions. Recurrent genomic losses spanning large regions of chromosomes 4 and 10 included several cell death genes. Among the amplified genes were well-known drivers of tumorigenesis including Wingless-related MMTV integration site 2 (Wnt2), as well as potentially novel driver mutations including the Late cornified envelope (LCE) gene family. These tumors have a stem/luminal progenitor phenotype and active beta-catenin signaling. Tumorsphere formation and cell survival are suppressed by Wnt pathway inhibitors. Conclusion: Our novel mouse model mimics human TNBC and provides a platform to triage the pathways that underlie malignant tumor progression. C1 [Johnson, Jacob P. S.; Simin, Karl] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA. [Kumar, Prashant] ASTAR, Inst Mol & Cell Biol, Singapore, Singapore. [Koulnis, Miroslav] NIAMSD, NIH, Bethesda, MD 20892 USA. [Patel, Milan] Wright Ctr Grad Med Educ, Scranton, PA USA. RP Simin, K (reprint author), Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA. EM karl.simin@umassmed.edu FU ACS [IRG-93-033-15]; Simeon J. Fortin Charitable Foundation; Pink Revolution Breast Cancer Alliance FX This work was supported by funding from grant ACS IRG-93-033-15, the Simeon J. Fortin Charitable Foundation, and the Pink Revolution Breast Cancer Alliance to KS. NR 45 TC 3 Z9 3 U1 0 U2 3 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 1109-6535 EI 1790-6245 J9 CANCER GENOM PROTEOM JI Cancer Genomics Proteomics PD MAY-JUN PY 2014 VL 11 IS 3 BP 115 EP 126 PG 12 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA AL8MZ UT WOS:000339394600001 PM 24969692 ER PT J AU Kovalchuk, I Zhumagulova, Z Turdiev, T Reed, BM AF Kovalchuk, Irina Zhumagulova, Zhangul Turdiev, Timur Reed, Barbara M. TI GROWTH MEDIUM ALTERATIONS IMPROVE IN VITRO COLD STORAGE OF PEAR GERMPLASM SO CRYOLETTERS LA English DT Article DE germplasm storage; in vitro cold storage; mannitol; micropropagation; nitrogen; Pyrus ID INVITRO AB BACKGROUND: Development of new fruit cultivars is dependent on genetic resource collections such as those at the Pomological Garden of the Institute of Horticulture and Viticulture near Almaty, Kazakhstan. The pear germplasm collection of the Pomological Garden contains 615 cultivars and three species. In vitro cold storage of the collection would provide additional security to the field collection. OBJECTIVE: This study was designed to improve medium-term in vitro storage of pear germplasm. METHODS: Shoots of seven pear cultivars (Pyrus communis L.) were stored in plastic five-section bags at 4 degrees C and a 10-h photoperiod (7 mu mol m(-2) s(-1)). Treatments included medium with four carbohydrate sources (3% sucrose, 2% or 3% mannitol, or 2% sucrose + 2% mannitol) with 0.5 mg l(-1) BAP and 0.1 mg l(-1) IBA or without plant growth regulators (PGRs) and at three Murashige and Skoog (MS) nitrogen concentrations (100%, 50% or 25%). RESULTS: Pear shoots remained viable for 9 to 15 months without repropagation on the control MS medium with 3% sucrose without PGRs. There were significant impacts of cultivar and treatment on the duration of cold storage. Shoots of 'Mramornaya' remained viable (rating of >= 2) for 27 months with PGRs and 2% sucrose + 2% mannitol compared to 12 months for the PGR + 3% sucrose treatment. Talgarskaya Krasaviza' stored for 18 months on 2% sucrose + 2% mannitol while all other treatments lasted only 6 to 9 months. Treatments with 0.5 or 1 mg l(-1) abscisic acid (ABA) with 3% sucrose increased storage duration as did reducing the concentration of nitrogen in the medium to 25% without PGRs and with 3% sucrose. C1 [Kovalchuk, Irina; Zhumagulova, Zhangul; Turdiev, Timur] Inst Plant Biol & Biotechnol, Natl Biotechnol Ctr, Alma Ata 050040, Kazakhstan. [Reed, Barbara M.] USDA ARS, Natl Clonal Germplasm Repository, Corvallis, OR 97333 USA. RP Reed, BM (reprint author), USDA ARS, Natl Clonal Germplasm Repository, 33447 Peoria Rd, Corvallis, OR 97333 USA. EM kovalchuk_i_u@mail.ru; Barbara.Reed@ars.usda.gov FU International Science and Technology Center [K428]; USDA Agricultural Research Service CRIS [5358-21000-033D] FX The project was supported by funds from the International Science and Technology Center Grant K428 and the USDA Agricultural Research Service CRIS project 5358-21000-033D. NR 19 TC 1 Z9 1 U1 0 U2 3 PU CRYO LETTERS PI LONDON PA C/O ROYAL VETERINARY COLLEGE, ROYAL COLLEGE ST, LONDON NW1 0TU, ENGLAND SN 0143-2044 EI 1742-0644 J9 CRYOLETTERS JI CryoLetters PD MAY-JUN PY 2014 VL 35 IS 3 BP 197 EP 203 PG 7 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA AL1VA UT WOS:000338913200005 PM 24997837 ER PT J AU Rodriguez, HP Glenn, BA Olmos, TT Krist, AH Shimada, SL Kessler, R Heurtin-Roberts, S Bastani, R AF Rodriguez, Hector P. Glenn, Beth A. Olmos, Tanya T. Krist, Alex H. Shimada, Stephanie L. Kessler, Rodger Heurtin-Roberts, Suzanne Bastani, Roshan TI Real-World Implementation and Outcomes of Health Behavior and Mental Health Assessment SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Article DE Communication; Mental Health; Practice-based Research; Prevention; Screening ID PRIMARY-CARE; SCREENING-TEST; VALIDATION; DEPRESSION; RECORDS AB Background: Assessing patient-reported health behaviors is a critical first step in prioritizing prevention in primary care. We assessed the feasibility of point-of-care behavioral health assessment in 9 diverse primary care practices, including 4 federally qualified health centers (FQHCs), 4 practice-based research network practices, and a Department of Veterans Affairs practice. Methods: In this prospective mixed-methods study, practices were asked to integrate a standardized paper-based health behavior and mental health assessment into their workflow for >= 50 patients. We used 3 data sources to examine the implementation process: (1) patient responses to the health assessment, (2) patient feedback surveys about how assessments were used during encounters, and (3) post-implementation interviews. Results: Most nonurgent patients (71%) visiting the participating practices during the implementation period completed the health assessment, but reach varied by practice (range, 59% to 88%). Unhealthy diet, sedentary lifestyle, and stress were the most common patient problems, with similar frequencies observed across practices. The median number of "positive screens" per patient was similar among FQHCs (3.7 positives; standard deviation [SD], 1.8), practice-based research network practices (3.8 positives; SD, 1.9), and the Veterans Affairs clinic (4.1 positives; SD, 2.0). Primary care clinicians discussed assessment results with patients about half of the time (54%), with considerable variation between practices (range, 13% to 66%; lowest use among FQHC clinicians). Although clinicians were interested in routinely implementing assessments, many reported not feeling confident of having resources or support to address all patients' behavioral health needs. Conclusions: Primary care practices will need to revamp their patient-reported data collection processes to integrate routine health behavior assessments. Implementation support will be required if health assessments are to be actively used as part of routine primary care. C1 [Rodriguez, Hector P.; Glenn, Beth A.; Olmos, Tanya T.; Bastani, Roshan] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Glenn, Beth A.; Bastani, Roshan] Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control, Los Angeles, CA 90034 USA. [Krist, Alex H.] Virginia Commonwealth Univ, Dept Family Med & Populat Hlth, Richmond, VA 23284 USA. [Shimada, Stephanie L.] VA Healthcare Syst, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Kessler, Rodger] Univ Vermont, Dept Family Med, Burlington, VT 05405 USA. [Heurtin-Roberts, Suzanne] Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA. RP Rodriguez, HP (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Hlth Policy & Management, 50 Univ Hall,Room 245, Berkeley, CA 94720 USA. EM hrod@berkeley.edu FU National Institutes of Health/National Cancer Institute [U48DP001946]; National Institutes of Health/National Center for Advancing Translational Science UCLA Clinical and Translational Science Institute [UL1TR000124] FX This research was supported by the National Institutes of Health/National Cancer Institute (grant no. U48DP001946) and the National Institutes of Health/National Center for Advancing Translational Science UCLA Clinical and Translational Science Institute Grant no. UL1TR000124. NR 21 TC 6 Z9 7 U1 2 U2 9 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 EI 1558-7118 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD MAY-JUN PY 2014 VL 27 IS 3 BP 356 EP 366 DI 10.3122/jabfm.2014.03.130264 PG 11 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA AL5IL UT WOS:000339167000010 PM 24808114 ER PT J AU Baek, JH Rajagopala, SV Chattoraj, DK AF Baek, Jong Hwan Rajagopala, Seesandra V. Chattoraj, Dhruba K. TI Chromosome Segregation Proteins of Vibrio cholerae as Transcription Regulators SO MBIO LA English DT Article ID BACILLUS-SUBTILIS CHROMOSOME; P1 PLASMID CENTROMERE; REPLICATION INITIATION; PSEUDOMONAS-AERUGINOSA; ESCHERICHIA-COLI; ORIGIN REGION; SPO0J PARB; GENE; SPORULATION; PARTITION AB Bacterial ParA and ParB proteins are best known for their contribution to plasmid and chromosome segregation, but they may also contribute to other cell functions. In segregation, ParA interacts with ParB, which binds to parS centromere-analogous sites. In transcription, plasmid Par proteins can serve as repressors by specifically binding to their own promoters and, additionally, in the case of ParB, by spreading from a parS site to nearby promoters. Here, we have asked whether chromosomal Par proteins can likewise control transcription. Analysis of genome-wide ParB1 binding in Vibrio cholerae revealed preferential binding to the three known parS1 sites and limited spreading of ParB1 beyond the parS1 sites. Comparison of wild-type transcriptomes with those of Delta parA1, Delta parB1, and Delta parAB1 mutants revealed that two out of 20 genes (VC0067 and VC0069) covered by ParB1 spreading are repressed by both ParB1 and ParA1. A third gene (VC0076) at the outskirts of the spreading area and a few genes further away were also repressed, particularly the gene for an outer membrane protein, ompU (VC0633). Since ParA1 or ParB1 binding was not evident near VC0076 and ompU genes, the repression may require participation of additional factors. Indeed, both ParA1 and ParB1 proteins were found to interact with several V. cholerae proteins in bacterial and yeast two-hybrid screens. These studies demonstrate that chromosomal Par proteins can repress genes unlinked to parS and can do so without direct binding to the cognate promoter DNA. IMPORTANCE Directed segregation of chromosomes is essential for their maintenance in dividing cells. Many bacteria have genes (par) that were thought to be dedicated to segregation based on analogy to their roles in plasmid maintenance. It is becoming clear that chromosomal par genes are pleiotropic and that they contribute to diverse processes such as DNA replication, cell division, cell growth, and motility. One way to explain the pleiotropy is to suggest that Par proteins serve as or control other transcription factors. We tested this model by determining how Par proteins affect genome-wide transcription activity. We found that genes implicated in drug resistance, stress response, and pathogenesis were repressed by Par. Unexpectedly, the repression did not involve direct Par binding to cognate promoter DNA, indicating that the repression may involve Par interactions with other regulators. This pleiotropy highlights the degree of integration of chromosomal Par proteins into cellular control circuitries. C1 [Baek, Jong Hwan; Chattoraj, Dhruba K.] NCI, Lab Biochem & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Rajagopala, Seesandra V.] J Craig Venter Inst, Rockville, MD USA. RP Chattoraj, DK (reprint author), NCI, Lab Biochem & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM chattoraj@nih.gov FU Intramural Research Program, Center for Cancer Research; National Cancer Institute; National Institutes of Health [GM079710] FX This work was supported by the Intramural Research Program, Center for Cancer Research, the National Cancer Institute, and National Institutes of Health grant GM079710 to S.V.R. NR 40 TC 4 Z9 4 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAY-JUN PY 2014 VL 5 IS 3 AR e01061-14 DI 10.1128/mBio.01061-14 PG 8 WC Microbiology SC Microbiology GA AL1HH UT WOS:000338875900004 PM 24803519 ER PT J AU Bantysh, O Serebryakova, M Makarova, KS Dubiley, S Datsenko, KA Severinov, K AF Bantysh, Olga Serebryakova, Marina Makarova, Kira S. Dubiley, Svetlana Datsenko, Kirill A. Severinov, Konstantin TI Enzymatic Synthesis of Bioinformatically Predicted Microcin C-Like Compounds Encoded by Diverse Bacteria SO MBIO LA English DT Article ID BIOSYNTHETIC GENE-CLUSTER; ESCHERICHIA-COLI; PLASMID GENES; PANTOCIN-A; DATABASE; AMINOPEPTIDASE; SPECIFICITY; MATURATION; RESISTANCE; PEPTIDASE AB The Trojan horse Escherichia coli antibiotic microcin C (McC) consists of a heptapeptide attached to adenosine through a phosphoramidate linkage. McC is synthesized by the MccB enzyme, which terminally adenylates the ribosomally synthesized heptapeptide precursor MccA. The peptide part is responsible for McC uptake; it is degraded inside the cell to release a toxic nonhydrolyzable aspartyl-adenylate. Bionformatic analysis reveals that diverse bacterial genomes encoding mccB homologues also contain adjacent short open reading frames that may encode MccA-like adenylation substrates. Using chemically synthesized predicted peptide substrates and recombinant cognate MccB protein homologs, adenylated products were obtained in vitro for predicted MccA peptide-MccB enzyme pairs from Helicobacter pylori, Streptococcus thermophilus, Lactococcus johnsonii, Bartonella washoensis, Yersinia pseudotuberculosis, and Synechococcus sp. Some adenylated products were shown to inhibit the growth of E. coli by targeting aspartyl-tRNA synthetase, the target of McC. IMPORTANCE Our results prove that McC-like adenylated peptides are widespread and are encoded by both Gram-negative and Gram-positive bacteria and by cyanobacteria, opening ways for analyses of physiological functions of these compounds and for creation of microcin C-like antibiotics targeting various bacteria. C1 [Bantysh, Olga; Serebryakova, Marina; Dubiley, Svetlana; Severinov, Konstantin] Russian Acad Sci, Inst Gene Biol, Moscow, Russia. [Bantysh, Olga; Severinov, Konstantin] St Petersburg State Polytech Univ, St Petersburg, Russia. [Serebryakova, Marina] Moscow MV Lomonosov State Univ, Moscow, Russia. [Makarova, Kira S.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Datsenko, Kirill A.] Purdue Univ, W Lafayette, IN 47907 USA. [Severinov, Konstantin] Skolkovo Inst Sci & Technol, Skolkovo, Russia. RP Severinov, K (reprint author), Russian Acad Sci, Inst Gene Biol, Moscow, Russia. EM severik@waksman.rutgers.edu RI Serebryakova, Marina/E-2986-2012; Severinov, Konstantin/C-8545-2016 FU Russian Academy of Sciences; Ministry of Education and Science of the Russian Federation [14.B25.31.0004]; U.S. Department of Health and Human Services FX Work in K.S.'s laboratories is supported by Russian Academy of Sciences Presidium Nanotechnology and Molecular and Cellular Biology program grants and by the Ministry of Education and Science of the Russian Federation project 14.B25.31.0004 grant. The MALDI MS facility became available to us in the framework of the Moscow State University Development Program (PNG 5.13). K. M. is supported by intramural funds of the U.S. Department of Health and Human Services (allocated to the National Library of Medicine). NR 34 TC 6 Z9 6 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAY-JUN PY 2014 VL 5 IS 3 AR e01059-14 DI 10.1128/mBio.01059-14 PG 11 WC Microbiology SC Microbiology GA AL1HH UT WOS:000338875900005 PM 24803518 ER PT J AU Chen, L Mathema, B Pitout, JDD DeLeo, FR Kreiswirth, BN AF Chen, Liang Mathema, Barun Pitout, Johann D. D. DeLeo, Frank R. Kreiswirth, Barry N. TI Epidemic Klebsiella pneumoniae ST258 Is a Hybrid Strain SO MBIO LA English DT Article ID SEQUENCE TYPE 258; MOLECULAR EPIDEMIOLOGY; HISTORICAL-PERSPECTIVE; EVOLUTIONARY GENETICS; ST11 CLONE; CARBAPENEMASES; IDENTIFICATION; ENTEROBACTERIACEAE; SURVEILLANCE; EXPANSION AB Carbapenem-resistant Enterobacteriaceae (CRE), especially Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae, pose an urgent threat in health facilities in the United States and worldwide. K. pneumoniae isolates classified as sequence type 258 (ST258) by multilocus sequence typing are largely responsible for the global spread of KPC. A recent comparative genome study revealed that ST258 K. pneumoniae strains are two distinct genetic clades; however, the molecular origin of ST258 largely remains unknown, and our understanding of the evolution of the two genetic clades is incomplete. Here we compared the genetic structures and single-nucleotide polymorphism (SNP) distributions in the core genomes of strains from two ST258 clades and other STs (ST11, ST442, and ST42). We identified an similar to 1.1-Mbp region on ST258 genomes that is homogeneous to that of ST442, while the rest of the ST258 genome resembles that of ST11. Our results suggest ST258 is a hybrid clone-80% of the genome originated from ST11-like strains and 20% from ST442-like strains. Meanwhile, we sequenced an ST42 strain that carries the same K-antigen-encoding capsule polysaccharide biosynthesis gene (cps) region as ST258 clade I strains. Comparison of the cps-harboring regions between the ST42 and ST258 strains (clades I and II) suggests the ST258 clade I strains evolved from a clade II strain as a result of cps region replacement. Our findings unravel the molecular evolution history of ST258 strains, an important first step toward the development of diagnostic, therapeutic, and vaccine strategies to combat infections caused by multidrug-resistant K. pneumoniae. IMPORTANCE Recombination events and replacement of chromosomal regions have been documented in various bacteria, and these events have given rise to successful pathogenic clones. Here we used comparative genomic analyses to discover that the ST258 K. pneumoniae genome is a hybrid-80% of the chromosome is homologous to ST11 strains, while the remaining 20% is homologous to that of ST442. Meanwhile, a recent study indicated that ST258 strains can be segregated into two ST258 clades, with distinct capsule polysaccharide gene (cps) regions. Our analysis suggests ST258 clade I strains evolved from clade II through homologous recombination of cps region. Horizontal transfer of the cps region appears to be a key element driving the molecular diversification in K. pneumoniae strains. These findings not only extend our understanding of the molecular evolution of ST258 but are an important step toward the development of effective control and treatment strategies for multidrug-resistant K. pneumoniae. C1 [Chen, Liang; Mathema, Barun; Kreiswirth, Barry N.] Rutgers State Univ, New Jersey Med Sch, Publ Hlth Res Inst Ctr, Newark, NJ 07102 USA. [Mathema, Barun] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Pitout, Johann D. D.] Calgary Lab Serv, Div Microbiol, Calgary, AB, Canada. [Pitout, Johann D. D.] Univ Calgary, Dept Pathol, Calgary, AB, Canada. [Pitout, Johann D. D.] Univ Calgary, Dept Lab Med, Calgary, AB, Canada. [Pitout, Johann D. D.] Univ Calgary, Dept Microbiol Immunol & Infect Dis, Calgary, AB, Canada. [DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Kreiswirth, BN (reprint author), Rutgers State Univ, New Jersey Med Sch, Publ Hlth Res Inst Ctr, Newark, NJ 07102 USA. EM kreiswba@njms.rutgers.edu OI DeLeo, Frank/0000-0003-3150-2516 FU National Institutes of Health [1R01AI090155]; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported in part by a grant (to B.N.K.) from the National Institutes of Health (1R01AI090155) and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 36 TC 34 Z9 34 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAY-JUN PY 2014 VL 5 IS 3 AR e01355-14 DI 10.1128/mBio.01355-14 PG 8 WC Microbiology SC Microbiology GA AL1HH UT WOS:000338875900012 PM 24961694 ER PT J AU Hryckowian, AJ Battesti, A Lemke, JJ Meyer, ZC Welch, RA AF Hryckowian, Andrew J. Battesti, Aurelia Lemke, Justin J. Meyer, Zachary C. Welch, Rodney A. TI IraL Is an RssB Anti-adaptor That Stabilizes RpoS during Logarithmic Phase Growth in Escherichia coli and Shigella SO MBIO LA English DT Article ID GENERAL STRESS-RESPONSE; GRAM-NEGATIVE BACTERIA; STRAINS; SYSTEM; VIRULENCE; PROTEIN; TRANSCRIPTION; EXPRESSION; NETWORK; ROLES AB RpoS (sigma(S)), the general stress response sigma factor, directs the expression of genes under a variety of stressful conditions. Control of the cellular sigma(S) concentration is critical for appropriately scaled sigma(S)-dependent gene expression. One way to maintain appropriate levels of sigma(S) is to regulate its stability. Indeed, sigma(S) degradation is catalyzed by the ClpXP protease and the recognition of sigma(S) by ClpXP depends on the adaptor protein RssB. Three anti-adaptors (IraD, IraM, and IraP) exist in Escherichia coli K-12; each interacts with RssB and inhibits RssB activity under different stress conditions, thereby stabilizing sigma(S). Unlike K-12, some E. coli isolates, including uropathogenic E. coli strain CFT073, show comparable cellular levels of sigma(S) during the logarithmic and stationary growth phases, suggesting that there are differences in the regulation of sigma(S) levels among E. coli strains. Here, we describe IraL, an RssB anti-adaptor that stabilizes sigma(S) during logarithmic phase growth in CFT073 and other E. coli and Shigella strains. By immunoblot analyses, we show that IraL affects the levels and stability of sigma(S) during logarithmic phase growth. By computational and PCR-based analyses, we reveal that iraL is found in many E. coli pathotypes but not in laboratory-adapted strains. Finally, by bacterial two-hybrid and copurification analyses, we demonstrate that IraL interacts with RssB by a mechanism distinct from that used by other characterized anti-adaptors. We introduce a fourth RssB anti-adaptor found in E. coli species and suggest that differences in the regulation of sigma(S) levels may contribute to host and niche specificity in pathogenic and nonpathogenic E. coli strains. IMPORTANCE Bacteria must cope with a variety of environmental conditions in order to survive. RpoS (sigma(S)), the general stress response sigma factor, directs the expression of many genes under stressful conditions in both pathogenic and nonpathogenic Escherichia coli strains. The regulation of sigma(S) levels and activity allows appropriately scaled sigma(S)-dependent gene expression. Here, we describe IraL, an RssB anti-adaptor that, unlike previously described anti-adaptors, stabilizes sigma(S) during the logarithmic growth phase in the absence of additional stress. We also demonstrate that iraL is found in a large number of E. coli and Shigella isolates. These data suggest that strains containing iraL are able to initiate sigma(S)-dependent gene expression under conditions under which strains without iraL cannot. Therefore, IraL-mediated sigma(S) stabilization may contribute to host and niche specificity in E. coli. C1 [Hryckowian, Andrew J.; Lemke, Justin J.; Meyer, Zachary C.; Welch, Rodney A.] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. [Battesti, Aurelia] NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Welch, RA (reprint author), Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. EM rawelch@wisc.edu FU National Institutes of Health (NIH) [R01-DK063250-07]; NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by National Institutes of Health (NIH) grant R01-DK063250-07, and A.B. was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 32 TC 3 Z9 3 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAY-JUN PY 2014 VL 5 IS 3 AR e01043-14 DI 10.1128/mBio.01043-14 PG 8 WC Microbiology SC Microbiology GA AL1HH UT WOS:000338875900031 PM 24865554 ER PT J AU Ladner, JT Beitzel, B Chain, PSG Davenport, MG Donaldson, EF Frieman, M Kugelman, JR Kuhn, JH O'Rear, J Sabeti, PC Wentworth, DE Wiley, MR Yu, GY Sozhamannan, S Bradburne, C Palacios, G AF Ladner, Jason T. Beitzel, Brett Chain, Patrick S. G. Davenport, Matthew G. Donaldson, Eric F. Frieman, Matthew Kugelman, Jeffrey R. Kuhn, Jens H. O'Rear, Jules Sabeti, Pardis C. Wentworth, David E. Wiley, Michael R. Yu, Guo-Yun Sozhamannan, Shanmuga Bradburne, Christopher Palacios, Gustavo CA Threat Characterization Consortium TI Standards for Sequencing Viral Genomes in the Era of High-Throughput Sequencing SO MBIO LA English DT Editorial Material ID DISCOVERY; VIRUSES; CORONAVIRUS; POPULATION; DIVERSITY; CHINA AB Thanks to high-throughput sequencing technologies, genome sequencing has become a common component in nearly all aspects of viral research; thus, we are experiencing an explosion in both the number of available genome sequences and the number of institutions producing such data. However, there are currently no common standards used to convey the quality, and therefore utility, of these various genome sequences. Here, we propose five "standard" categories that encompass all stages of viral genome finishing, and we define them using simple criteria that are agnostic to the technology used for sequencing. We also provide genome finishing recommendations for various downstream applications, keeping in mind the cost-benefit trade-offs associated with different levels of finishing. Our goal is to define a common vocabulary that will allow comparison of genome quality across different research groups, sequencing platforms, and assembly techniques. C1 [Ladner, Jason T.; Beitzel, Brett; Kugelman, Jeffrey R.; Wiley, Michael R.; Yu, Guo-Yun; Palacios, Gustavo] US Army, Med Res Inst Infect Dis, Ctr Genome Sci, Ft Detrick, MD 21702 USA. [Chain, Patrick S. G.] Los Alamos Natl Lab, Bioinformat & Analyt Team, Biosci Div, Los Alamos, NM USA. [Davenport, Matthew G.; Bradburne, Christopher] Johns Hopkins Univ, Appl Phys Lab, Natl Secur Syst Biol Ctr, Asymmetr Operat Sect, Laurel, MD USA. [Donaldson, Eric F.; O'Rear, Jules] US FDA, Silver Spring, MD USA. [Frieman, Matthew] Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD USA. [Sabeti, Pardis C.] Harvard Univ, Dept Organism & Evolutionary Biol, FAS Ctr Syst Biol, Cambridge, MA 02138 USA. [Sabeti, Pardis C.] Broad Inst, Cambridge, MA USA. [Wentworth, David E.] J Craig Venter Inst, Rockville, MD USA. [Threat Characterization Consortium] Def Threat Reduct Agcy, Threat Characterizat Consortium, Ft Belvoir, VA USA. [Sozhamannan, Shanmuga] GoldBelt Raven LLC, Frederick, MD USA. [Sozhamannan, Shanmuga] Joint Program Execut Off, Crit Reagents Program, Ft Detrick, MD USA. RP Ladner, JT (reprint author), US Army, Med Res Inst Infect Dis, Ctr Genome Sci, Ft Detrick, MD 21702 USA. EM jason.t.ladner.ctr@mail.mil; gustavo.f.palacios.ctr@mail.mil RI Kuhn, Jens H./B-7615-2011; Palacios, Gustavo/I-7773-2015; OI Kuhn, Jens H./0000-0002-7800-6045; Palacios, Gustavo/0000-0001-5062-1938; Wentworth, David/0000-0002-5190-980X; Chain, Patrick/0000-0003-3949-3634 FU NIAID NIH HHS [HHSN272200700016I]; PHS HHS [HHSN272200700016I] NR 23 TC 20 Z9 20 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAY-JUN PY 2014 VL 5 IS 3 AR e01360-14 DI 10.1128/mBio.01360-14 PG 5 WC Microbiology SC Microbiology GA AL1HH UT WOS:000338875900037 PM 24939889 ER PT J AU Thompson, SJ Millecamps, M Aliaga, A Seminowicz, DA Low, LA Bedell, BJ Stone, LS Schweinhardt, P Bushnell, MC AF Thompson, Scott J. Millecamps, Magali Aliaga, Antonio Seminowicz, David A. Low, Lucie A. Bedell, Barry J. Stone, Laura S. Schweinhardt, Petra Bushnell, M. Catherine TI Metabolic brain activity suggestive of persistent pain in a rat model of neuropathic pain SO NEUROIMAGE LA English DT Article DE MicroPET; FDG; Neuropathic pain; Spared nerve injury; Formalin model ID NERVE INJURY; PERIPHERAL MONONEUROPATHY; SOMATOSENSORY CORTEX; SCIATIC-NERVE; FORMALIN TEST; ONGOING PAIN; STIMULATION; ALLODYNIA; DISORDERS; FMRI AB Persistent pain is a central characteristic of neuropathic pain conditions in humans. Knowing whether rodent models of neuropathic pain produce persistent pain is therefore crucial to their translational applicability. We investigated the spared nerve injury (SNI) model of neuropathic pain and the formalin pain model in rats using positron emission tomography (PET) with the metabolic tracer [18F]fluorodeoxyglucose (FDG) to determine if there is ongoing brain activity suggestive of persistent pain. For the formalin model, under brief anesthesia we injected one hindpaw with 5% formalin and the FDG tracer into a tail vein. We then allowed the animals to awaken and observed pain behavior for 30 min during the FDG uptake period. The rat was then anesthetized and placed in the scanner for static image acquisition, which took place between minutes 45 and 75 post-tracer injection. A single reference rat brain magnetic resonance image (MRI) was used to align the PET images with the Paxinos and Watson rat brain atlas. Increased glucose metabolism was observed in the somatosensory region associated with the injection site (S1 hindlimb contralateral), Si jaw/upper lip and cingulate cortex. Decreases were observed in the prelimbic cortex and hippocampus. Second, SNI rats were scanned 3 weeks post-surgery using the same scanning paradigm, and region-of-interest analyses revealed increased metabolic activity in the contralateral 51 hindlimb. Finally, a second cohort of SNI rats was scanned while anesthetized during the tracer uptake period, and the Si hindlimb increase was not observed. Increased brain activity in the somatosensory cortex of SNI rats resembled the activity produced with the injection of formalin, suggesting that the SNI model may produce persistent pain. The lack of increased activity in Si hindlimb with general anesthetic demonstrates that this effect can be blocked, as well as highlights the importance of investigating brain activity in awake and behaving rodents. (C) 2014 Elsevier Inc. All rights reserved. C1 [Thompson, Scott J.; Millecamps, Magali; Stone, Laura S.; Schweinhardt, Petra] McGill Univ, Alan Edwards Ctr Res Pain, Montreal, PQ H3G 0G1, Canada. [Low, Lucie A.; Bushnell, M. Catherine] NIH, Div Intramural Res, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Aliaga, Antonio; Bedell, Barry J.] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Small Anim Imaging Lab, Montreal, PQ H3A 2B4, Canada. [Millecamps, Magali; Stone, Laura S.; Schweinhardt, Petra] McGill Univ, Fac Dent, Montreal, PQ H3A 2T5, Canada. [Seminowicz, David A.] Univ Maryland, Sch Dent, Dept Neural & Pain Sci, Baltimore, MD 21201 USA. [Bedell, Barry J.; Stone, Laura S.; Schweinhardt, Petra] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada. [Thompson, Scott J.] McGill Univ, Integrated Program Neurosci, Montreal, PQ H3A 2T5, Canada. RP Thompson, SJ (reprint author), 3640 Univ St, Montreal, PQ H3A 2B3, Canada. EM scott.thompson4@mail.mcgill.ca RI Seminowicz, David/F-8732-2015; OI Seminowicz, David/0000-0003-3111-3756; Low, Lucie/0000-0001-6082-8625 FU AstraZeneca; Pfizer Canada; Intramural Research Program of the National Center for Complementary and Alternative Medicine, National Institutes of Health; Louise and Alan Edwards Foundation FX This work was partially funded by grants to Dr. Bushnell from AstraZeneca & Pfizer Canada. This research was also partially funded by the Intramural Research Program of the National Center for Complementary and Alternative Medicine, National Institutes of Health. Scott J Thompson is supported by The Louise and Alan Edwards Foundation's Edwards PhD. Studentship in Pain Research. NR 51 TC 5 Z9 5 U1 0 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD MAY 1 PY 2014 VL 91 BP 344 EP 352 DI 10.1016/j.neuroimage.2014.01.020 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AL1VJ UT WOS:000338914100035 PM 24462776 ER PT J AU Miller, RK Darrah, TH Friedman, A Li, A Stodgell, CJ Landrigan, P Walker, C Clark, EB Dole, N Thiex, N Swanson, J Culhane, J Szabo, S Moye, J AF Miller, R. K. Darrah, T. H. Friedman, A. Li, A. Stodgell, C. J. Landrigan, P. Walker, C. Clark, E. B. Dole, N. Thiex, N. Swanson, J. Culhane, J. Szabo, S. Moye, J. TI Enviromnental exposures during pregnancy: US National Children's Study formative research investigation SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the Neurobehavioral-Teratology-Society CY JUN 28-JUL 02, 2014 CL Bellevue, WA SP Neurobehavioral Teratol Soc C1 [Miller, R. K.; Darrah, T. H.; Friedman, A.; Li, A.; Stodgell, C. J.; Landrigan, P.; Walker, C.; Clark, E. B.; Dole, N.; Thiex, N.; Swanson, J.; Culhane, J.; Szabo, S.; Moye, J.] Natl Childrens Study Placental Consortium, Bethesda, MD USA. [Miller, R. K.; Friedman, A.; Stodgell, C. J.] Univ Rochester, Rochester, NY USA. [Darrah, T. H.] Ohio State Univ, Columbus, OH 43210 USA. [Li, A.] Univ Illinois, Chicago, IL USA. [Landrigan, P.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Szabo, S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Walker, C.] Univ Calif Davis, Davis, CA 95616 USA. Univ Calif Irvine, Irvine, CA USA. [Clark, E. B.] Univ Utah, Salt Lake City, UT USA. [Thiex, N.] S Dakota State Univ, Brookings, SD 57007 USA. [Dole, N.] Univ N Carolina, Chapel Hill, NC USA. [Culhane, J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Moye, J.] NIH, Bethesda, MD 20892 USA. RI Li, An/A-3395-2008 OI Li, An/0000-0002-8476-8783 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 EI 1872-9738 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2014 VL 43 MA NBTS 10 BP 79 EP 79 DI 10.1016/j.ntt.2014.04.013 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA AK7QC UT WOS:000338621800020 ER PT J AU Moghe, GD Hufnagel, DE Tang, HB Xiao, YL Dworkin, I Town, CD Conner, JK Shiu, SH AF Moghe, Gaurav D. Hufnagel, David E. Tang, Haibao Xiao, Yongli Dworkin, Ian Town, Christopher D. Conner, Jeffrey K. Shiu, Shin-Han TI Consequences of Whole-Genome Triplication as Revealed by Comparative Genomic Analyses of the Wild Radish Raphanus raphanistrum and Three Other Brassicaceae Species SO PLANT CELL LA English DT Article ID DUPLICATED GENES; ARABIDOPSIS-THALIANA; FLOWERING PLANTS; PREFERENTIAL RETENTION; POLYPLOID FORMATION; PROVIDES INSIGHT; EVOLUTION; SEQUENCE; RAPA; MODEL AB Polyploidization events are frequent among flowering plants, and the duplicate genes produced via such events contribute significantly to plant evolution. We sequenced the genome of wild radish (Raphanus raphanistrum), a Brassicaceae species that experienced a whole-genome triplication event prior to diverging from Brassica rapa. Despite substantial gene gains in these two species compared with Arabidopsis thaliana and Arabidopsis lyrata, similar to 70% of the orthologous groups experienced gene losses in R. raphanistrum and B. rapa, with most of the losses occurring prior to their divergence. The retained duplicates show substantial divergence in sequence and expression. Based on comparison of A. thaliana and R. raphanistrum ortholog floral expression levels, retained radish duplicates diverged primarily via maintenance of ancestral expression level in one copy and reduction of expression level in others. In addition, retained duplicates differed significantly from genes that reverted to singleton state in function, sequence composition, expression patterns, network connectivity, and rates of evolution. Using these properties, we established a statistical learning model for predicting whether a duplicate would be retained postpolyploidization. Overall, our study provides new insights into the processes of plant duplicate loss, retention, and functional divergence and highlights the need for further understanding factors controlling duplicate gene fate. C1 [Moghe, Gaurav D.; Shiu, Shin-Han] Michigan State Univ, Genet Program, E Lansing, MI 48824 USA. [Moghe, Gaurav D.; Shiu, Shin-Han] Michigan State Univ, Program Quantitat Biol, E Lansing, MI 48824 USA. [Hufnagel, David E.; Conner, Jeffrey K.; Shiu, Shin-Han] Michigan State Univ, Dept Plant Biol, E Lansing, MI 48824 USA. [Tang, Haibao; Town, Christopher D.] J Craig Venter Inst, Rockville, MD 20850 USA. [Xiao, Yongli] NIAID, NIH, Bethesda, MD 20892 USA. [Dworkin, Ian] Michigan State Univ, Dept Zool, E Lansing, MI 48824 USA. [Conner, Jeffrey K.] Michigan State Univ, Kellogg Biol Stn, E Lansing, MI 48824 USA. RP Shiu, SH (reprint author), Michigan State Univ, Genet Program, E Lansing, MI 48824 USA. EM shius@msu.edu OI Moghe, Gaurav/0000-0002-8761-064X; Conner, Jeffrey/0000-0003-1613-5826; Shiu, Shin-Han/0000-0001-6470-235X FU National Science Foundation [DBI-0638591, DEB-0919452, IOS-1126998] FX We thank Cindy Mills and Melissa Lehti-Shiu for maintaining the radish plants, Melissa for reading the article, Barry Williams for discussion, Alicia Massa for helping isolate genomic DNA samples, Robin Buell for discussion on sequencing strategies, John Johnston for computational support, Guangxi Wu for assistance with orthology prediction, Alex Seddon for assistance with SVM analyses, and James Birchler and the reviewers for providing valuable comments allowing further improvement of the article. This work was partially supported by National Science Foundation Grants DBI-0638591 to J.K.C., C.D.T., S.-H.S., and Y.X., DEB-0919452 to J.K.C., ID., and S.H.S., and IOS-1126998 to S.H.S. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. This is KBS contribution #1776. NR 74 TC 26 Z9 27 U1 3 U2 42 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 EI 1532-298X J9 PLANT CELL JI Plant Cell PD MAY PY 2014 VL 26 IS 5 BP 1925 EP 1937 DI 10.1105/tpc.114.124297 PG 13 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA AK9UA UT WOS:000338771700014 PM 24876251 ER PT J AU Van Laethem, F Saba, I Tikhonova, AN Singer, A AF Van Laethem, Francois Saba, Ingrid Tikhonova, Anastasia N. Singer, Alfred TI Crucial role of the CD4 and CD8 co-receptors in antigen recognition of lymphocytes T alpha beta SO M S-MEDECINE SCIENCES LA French DT News Item ID THYMIC SELECTION; AMINO-ACIDS; MHC; REPERTOIRE C1 [Van Laethem, Francois; Saba, Ingrid; Tikhonova, Anastasia N.; Singer, Alfred] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Van Laethem, F (reprint author), NCI, Expt Immunol Branch, Bldg 10, Bethesda, MD 20892 USA. EM vanlaetf@mail.nih.gov RI Tikhonova, Anastasia/F-1186-2015 NR 7 TC 0 Z9 0 U1 0 U2 0 PU EDP SCIENCES S A PI LES ULIS CEDEX A PA 17, AVE DU HOGGAR, PA COURTABOEUF, BP 112, F-91944 LES ULIS CEDEX A, FRANCE SN 0767-0974 J9 M S-MED SCI JI M S-Med. Sci. PD MAY PY 2014 VL 30 IS 5 BP 511 EP 513 DI 10.1051/medsci/20143005012 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AK5FM UT WOS:000338450100012 PM 24939536 ER PT J AU Negrouk, A Lacombe, D Trimble, EL Seymour, M AF Negrouk, Anastassia Lacombe, Denis Trimble, Edward L. Seymour, Matthew TI Clinical research for rare cancers: is it a reality in the global regulatory landscape? The international rare cancer initiative SO EXPERT OPINION ON ORPHAN DRUGS LA English DT Review DE clinical trials; international rare cancer initiative; rare cancers; regulatory ID EORTC AB Introduction: Rare cancers together account for about 22% of new cancer diagnoses each year, which is more than any single common cancer. They constitute a serious public health problem with distinctive challenges. Compared with common cancers, less is known about their etiology and molecular pathology, and therapeutic options are mostly poorly evidence based with outcomes that are on average inferior to those of more common cancers. There is, therefore, a pressing need for well-organized clinical research to address these deficiencies. The International rare cancer initiative (IRCI) was formed in 2011 with the aim of stimulating and facilitating the development of international clinical trials for patients with rare cancers, and so helping to establish better, more evidence-based treatments. As of October 2013, 8 clinical trials are in design, in set up or recruiting, in seven rare cancer types, giving IRCI a good understanding of the current research conditions for rare cancer. Areas covered: This paper sets the scene of clinical research in rare cancers and presents an overview of organizational, methodological, regulatory and financial challenges facing researchers in this field. It also proposes possible steps to improve the research environment for the future. Expert opinion: Based on our observations, we believe that measures should be taken to improve the integration of research across international boundaries, to improve the funding of academic research and to better integrate the research capacity of industry with the public sector for the greater benefits of patients and society. C1 [Negrouk, Anastassia] European Org Res Treatment Canc, Int Regulatory & Intergroup Off, B-1200 Brussels, Belgium. [Lacombe, Denis] European Org Res & Treatment Canc Headquarters, B-1200 Brussels, Belgium. [Trimble, Edward L.] NCI, Ctr Global Hlth, Washington, DC USA. [Seymour, Matthew] Natl Inst Hlth, Res Canc Res Network, Leeds, W Yorkshire, England. RP Negrouk, A (reprint author), European Org Res Treatment Canc, Int Regulatory & Intergroup Off, Ave E Mounier 83-11, B-1200 Brussels, Belgium. EM anastassia.negrouk@eortc.be NR 8 TC 1 Z9 1 U1 1 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8707 J9 EXPERT OPIN ORPHAN D JI Exp. Opin. Orphan Drugs PD MAY PY 2014 VL 2 IS 5 BP 433 EP 440 DI 10.1517/21678707.2014.888948 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AK2WC UT WOS:000338279400001 ER PT J AU Kliger, AS Chertow, GM Levin, NW Beck, GJ Daugirdas, JT Eggers, PW Larive, B Rocco, MV Greene, T AF Kliger, Alan S. Chertow, Glenn M. Levin, Nathan W. Beck, Gerald J. Daugirdas, John T. Eggers, Paul W. Larive, Brett Rocco, Michael V. Greene, Tom TI LONG-TERM EFFECTS OF FREQUENT IN-CENTER HEMODIALYSIS: FHN DAILY TRIAL SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Meeting Abstract CT 51st Congress of the European-Renal-Association(ERA)/European-Dialysis-and-Transplant-Associa tion (EDTA) CY MAY 31-JUN 03, 2014 CL Amsterdam, NETHERLANDS SP European Renal Assoc, European Dialysis & Transplant Assoc C1 [Kliger, Alan S.] Yale Univ, Sch Med, New Haven, CT USA. [Chertow, Glenn M.] Stanford Univ, Stanford, CA 94305 USA. [Levin, Nathan W.] Renal Res Inst, New York, NY USA. [Beck, Gerald J.; Larive, Brett] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Daugirdas, John T.] Univ Illinois, Chicago, IL USA. [Eggers, Paul W.] NIDDK, Bethesda, MD 20892 USA. [Rocco, Michael V.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Greene, Tom] Univ Utah, Salt Lake City, UT USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD MAY PY 2014 VL 29 SU 3 MA MO037 BP 37 EP 38 PG 2 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA AJ9FQ UT WOS:000338013500089 ER PT J AU Rocco, M Daugirdas, J Greene, T Lockridge, R Chan, C Pierratos, A Lindsay, R Larive, B Chertow, G Beck, G Eggers, P Kliger, A Grp, FT AF Rocco, Michael Daugirdas, John Greene, Tom Lockridge, Robert Chan, Christopher Pierratos, Andreas Lindsay, Robert Larive, Brett Chertow, Glenn Beck, Gerald Eggers, Paul Kliger, Alan Grp, F. H. N. Trial TI MORTALITY DURING EXTENDED FOLLOW-UP IN THE FREQUENT HEMODIALYSIS NETWORK NOCTURNAL TRIAL SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Meeting Abstract CT 51st Congress of the European-Renal-Association(ERA)/European-Dialysis-and-Transplant-Associa tion (EDTA) CY MAY 31-JUN 03, 2014 CL Amsterdam, NETHERLANDS SP European Renal Assoc, European Dialysis & Transplant Assoc C1 [Rocco, Michael] Wake Forest Univ, Winston Salem, NC 27109 USA. [Daugirdas, John] Univ Illinois, Chicago, IL USA. [Greene, Tom] Univ Utah, Salt Lake City, UT USA. [Lockridge, Robert] Univ Virginia, Lynchburg, VA USA. [Chan, Christopher; Pierratos, Andreas] Univ Toronto, Toronto, ON, Canada. [Lindsay, Robert] London Hlth Sci, London, ON, Canada. [Larive, Brett] Cleveland Clin, Cleveland, OH 44106 USA. [Chertow, Glenn] Stanford Univ, Stanford, CA 94305 USA. [Eggers, Paul] NIDDK, NIH, Bethesda, MD 20892 USA. [Kliger, Alan] Yale New Haven Med Ctr, New Haven, CT 06504 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD MAY PY 2014 VL 29 SU 3 MA MO035 BP 37 EP 37 PG 1 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA AJ9FQ UT WOS:000338013500087 ER PT J AU Koroshetz, WJ Landis, S AF Koroshetz, Walter J. Landis, Story TI Neurology's Stake in Foundational Neuroscience Research SO ANNALS OF NEUROLOGY LA English DT Editorial Material C1 [Koroshetz, Walter J.; Landis, Story] NINDS, NIH, Bethesda, MD 20892 USA. RP Koroshetz, WJ (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2014 VL 75 IS 5 BP 621 EP 622 DI 10.1002/ana.24161 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AJ5EV UT WOS:000337706100002 PM 24756692 ER PT J AU Wohlfarth, A Pang, SK Zhu, MS Gandhi, AS Scheidweiler, KB Huestis, MA AF Wohlfarth, Ariane Pang, Shaokun Zhu, Mingshe Gandhi, Adarsh S. Scheidweiler, Karl B. Huestis, Marilyn A. TI Metabolism of RCS-8, a synthetic cannabinoid with cyclohexyl structure, in human hepatocytes by high-resolution MS SO BIOANALYSIS LA English DT Article ID CHROMATOGRAPHY-MASS SPECTROMETRY; URINARY METABOLITES; QUANTITATIVE MEASUREMENT; LIQUID-CHROMATOGRAPHY; IDENTIFICATION; JWH-018; 1ST; MIXTURES; AM-2201; UR-144 AB Background: Since 2008, synthetic cannabinoids are major new designer drugs of abuse. They are extensively metabolized and excreted in urine, but limited human metabolism data are available. As there are no reports on the metabolism of RCS-8, a scheduled phenylacetylindole synthetic cannabinoid with an N-cyclohexylethyl moiety, we investigated metabolism of this new designer drug by human hepatocytes and high resolution MS. Methods: After human hepatocyte incubation with RCS-8, samples were analyzed on a TripleTOF 5600+ mass spectrometer with time-of-flight survey scan and information-dependent acquisition triggered product ion scans. Data mining of the accurate mass full scan and product ion spectra employed different data processing algorithms. Results & Conclusion: More than 20 RCS-8 metabolites were identified, products of oxidation, demethylation, and glucuronidation. Major metabolites and targets for analytical methods were hydroxyphenyl RCS-8 glucuronide, a variety of hydroxycyclohexyl-hydroxyphenyl RCS-8 glucuronides, hydroxyphenyl RCS-8, as well as the demethyl-hydroxycyclohexyl RCS-8 glucuronide. C1 [Wohlfarth, Ariane; Gandhi, Adarsh S.; Scheidweiler, Karl B.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. [Pang, Shaokun] AB SCIEX, Redwood City, CA 94065 USA. [Zhu, Mingshe] Bristol Myers Squibb Res Dev, Dept Biotransformat, Princeton, NJ 08543 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 200,Room 05A-721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU AB SCIEX; Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health FX This research was funded by AB SCIEX and the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health. A Wohlfarth, A Gandhi, K Scheidweiler and M Huestis are employees at the National Institute on Drug Abuse, National Institutes of Health. S Pang is employed by AB SCIEX, M Zhu is employed by Bristol-Myers Squibb. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 26 TC 11 Z9 11 U1 2 U2 13 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PD MAY PY 2014 VL 6 IS 9 BP 1187 EP 1200 DI 10.4155/bio.14.1 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA AJ8HX UT WOS:000337945200013 PM 24946920 ER PT J AU Yamaguchi, Y Hearing, VJ AF Yamaguchi, Yuji Hearing, Vincent J. TI Melanocytes and Their Diseases SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID DYSCHROMATOSIS SYMMETRICA HEREDITARIA; MESENCHYMAL-EPITHELIAL INTERACTIONS; KOYANAGI-HARADA SYNDROME; STEM-CELLS; GENERALIZED VITILIGO; EPIDERMAL MELANOCYTES; SUSCEPTIBILITY LOCI; SKIN PIGMENTATION; GENE-EXPRESSION; HAIR-FOLLICLES AB Human melanocytes are distributed not only in the epidermis and in hair follicles but also in mucosa, cochlea (ear), iris (eye), and mesencephalon (brain) among other tissues. Melanocytes, which are derived from the neural crest, are unique in that they produce eu-/pheomelanin pigments in unique membrane-bound organelles termed melanosomes, which can be divided into four stages depending on their degree of maturation. Pigmentation production is determined by three distinct elements: enzymes involved in melanin synthesis, proteins required for melanosome structure, and proteins required for their trafficking and distribution. Many genes are involved in regulating pigmentation at various levels, and mutations in many of them cause pigmentary disorders, which can be classified into three types: hyperpigmentation (including melasma), hypopigmentation (including oculocutaneous albinism [OCA]), and mixed hyper-/hypopigmentation (including dyschromatosis symmetrica hereditaria). We briefly review vitiligo as a representative of an acquired hypopigmentation disorder. C1 [Yamaguchi, Yuji] AbbVie GK, Tokyo 1086302, Japan. [Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM hearingv@nih.gov FU Intramural Research Program of the National Cancer Institute at NIH FX This research was supported by the Intramural Research Program of the National Cancer Institute at NIH. Y.Y. is an AbbVie employee and may receive AbbVie stock, stock options, and grants. NR 82 TC 11 Z9 11 U1 4 U2 13 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD MAY PY 2014 VL 4 IS 5 AR a017046 DI 10.1101/cshperspect.a017046 PG 18 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AJ9HV UT WOS:000338020100005 ER PT J AU Reiss, D Eccles, JS Nielsen, L AF Reiss, David Eccles, Jacquelynne S. Nielsen, Lisbeth TI Conscientiousness and Public Health: Synthesizing Current Research to Promote Healthy Aging SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE conscientiousness; personality; aging; life course; interventions ID 5-FACTOR MODEL; ENVIRONMENTAL-INFLUENCES; PERSONALITY; CHILDHOOD; TWIN AB In this special section, 9 studies and 6 commentaries make a unique contribution to the study of personality. They focus on the five-factor model and, in particular, one of those 5: conscientiousness. This trait has had astonishing success in the actuarial prediction of adaptive outcomes in adulthood and aging, but we have little understanding of the mechanisms that account for this actuarial success. The current studies and comments marshal current knowledge of conscientiousness to advance a mechanistic understanding of these predictions and to exploit that understanding toward interventions to enhance robust adult development and healthy aging. In this introductory article, we underscore the strategy we used to invite presentations and commentary. First, we sought a clearer definition of conscientiousness and a review of its assessment. Second, we sought a review of how the components of this complex trait develop in childhood and are assembled across development. Third, we sought an understanding of how mechanisms linking conscientiousness and health might be transformed across the life span. Fourth, we scrutinized naturally occurring factors that moderate the links between conscientiousness and health for clues to successful interventions. Finally, we sought ways to pull these analyses together to outline the framework for a program of interventions that, collectively, might be applicable at specific points across the life span. Six commentaries place this project in sharp relief. They remind us that the causal status of the associations between conscientiousness and health, reported throughout our 9 studies, are uncertain at best. Second, they remind us that the concept of conscientiousness is still too spare: It fails to embody the social skills required for conscientious behavior, the moral judgment of self or other implicit in its assessment, or the neurobiological mechanisms that might account for differences among individuals. Third, they raise a potent counterfactual: What, in a practical sense, does conceptualization or assessment of conscientiousness contribute-if anything-to the design of interventions to enhance conscientious behavior? C1 [Reiss, David] Yale Univ, Yale Child Study Ctr, New Haven, CT 06519 USA. [Eccles, Jacquelynne S.] Univ Michigan, Inst Social Res, Ann Arbor, MI 48109 USA. [Nielsen, Lisbeth] NIA, Div Behav & Social Res, Bethesda, MD 20892 USA. RP Reiss, D (reprint author), Yale Univ, Yale Child Study Ctr, 230 South Frontage Rd, New Haven, CT 06519 USA. EM david.reiss@yale.edu NR 38 TC 6 Z9 7 U1 1 U2 17 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 EI 1939-0599 J9 DEV PSYCHOL JI Dev. Psychol. PD MAY PY 2014 VL 50 IS 5 BP 1303 EP 1314 DI 10.1037/a0036473 PG 12 WC Psychology, Developmental SC Psychology GA AJ7TR UT WOS:000337901000001 PM 24773105 ER PT J AU Su, LJ Fontham, ETH AF Su, L. Joseph Fontham, Elizabeth T. H. TI Prostate cancer: an occupational hazard? SO FUTURE ONCOLOGY LA English DT Editorial Material DE aggressiveness; diet; lifestyle; occupation; prostate cancer; sitting; whole-body vibration ID EPIDEMIOLOGIC EVIDENCE; CONSTRUCTION WORKERS; PHYSICAL-ACTIVITY; BODY-SIZE; RISK; COHORT C1 [Su, L. Joseph] NCI, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. [Fontham, Elizabeth T. H.] Louisiana State Univ Hlth Sci Ctr, Sch Publ Hlth, New Orleans, LA 70112 USA. RP Su, LJ (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E212, Rockville, MD 20850 USA. EM sulj@mail.nih.gov NR 20 TC 1 Z9 1 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PD MAY PY 2014 VL 10 IS 6 BP 903 EP 906 DI 10.2217/fon.14.33 PG 4 WC Oncology SC Oncology GA AJ8FO UT WOS:000337938300001 PM 24941975 ER PT J AU Gotea, V Elnitski, L AF Gotea, Valer Elnitski, Laura TI Ascertaining regions affected by GC-biased gene conversion through weak-to-strong mutational hotspots SO GENOMICS LA English DT Article DE GC-biased gene conversion (gBGC); Positive selection; Weak-to-strong mutation bias; Mutation hotspots; Modified Tang-Lewontin test ID RECENT POSITIVE SELECTION; HUMAN GENOME; ACCELERATED EVOLUTION; NONCODING SEQUENCES; MOLECULAR EVOLUTION; PROTEIN EVOLUTION; HUMANS; SIGNATURES; FOXP2; ADAPTATION AB A major objective for evolutionary biology is to identify regions affected by positive selection. High d(N)/d(S) values for proteins and accelerated lineage-specific substitution rates for non-coding regions are considered classic signatures of positive selection. However, these could also be the result of non-adaptive phenomena, such as GC-biased gene conversion (gBGC), which favors the fixation of strong (C/G) over weak (A/T) nucleotides. Recent estimates indicate that gBGC affected up to 20% of regions with signatures of positive selection. Here we evaluate the impact of gBGC through its molecular signature of weak-to-strong mutational hotspots. We implemented specific modifications to the test proposed by Tang and Lewontin (1999) for identifying regions of differential variability and applied it to regions previously investigated for the influence of gBGC While we found significant agreement with previous reports, our results suggest a smaller influence of gBGC than previously estimated, warranting further development of methods for its detection. Published by Elsevier Inc. C1 [Gotea, Valer; Elnitski, Laura] NHGRI, NIH, Bethesda, MD 20892 USA. RP Gotea, V (reprint author), 5625 Fishers Ln,Room 5N-01S, Rockville, MD 20852 USA. EM vgotea@nih.gov OI Gotea, Valer/0000-0001-7857-3309 FU Intramural Program of the National Human Genome Research Institute, National Institutes of Health FX This work was supported by the Intramural Program of the National Human Genome Research Institute, National Institutes of Health. We thank F. Sanchez-Vega for critical review of the manuscript and of the mathematical formulae, and three anonymous reviewers for constructive suggestions. NR 44 TC 0 Z9 0 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD MAY-JUN PY 2014 VL 103 IS 5-6 BP 349 EP 356 DI 10.1016/j.ygeno.2014.04.001 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA AJ9AY UT WOS:000338000400005 PM 24727706 ER PT J AU Lavender, KJ Messer, RJ Race, B Hasenkrug, KJ AF Lavender, Kerry J. Messer, Ronald J. Race, Brent Hasenkrug, Kim J. TI Production of bone marrow, liver, thymus (BLT) humanized mice on the C57BL/6 Rag2(-/-)gamma(-/-)(c)CD47(-/-) background SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE ELT humanized mice; C57BL/6 Rag2(-/-)gamma(-/-)(c)CD47(-/-); Hematopoiesis ID RECEPTOR-GAMMA-CHAIN; HEMATOPOIETIC STEM-CELLS; IMMUNODEFICIENT MICE; RECONSTITUTION; ENGRAFTMENT; RAG2 AB C57BL/6 Rag2(-/-)gamma(-/-)(c)CD47(-/-) triple-knockout mice engrafted with fetal human bone marrow, liver, thymus (TKO-BLT) not only develop high levels of multi-lineage hematopoiesis but also organized lymphoid tissues including mesenteric lymph nodes, splenic follicles and gut-associated lymphoid tissues of human origin. A unique advantage of these mice is that they sustain human cell and tissue engraftment long-term without the development of graft versus host disease. Thus they can be used for long-term studies not previously feasible with other models. The production of TKO-BLT mice to obtain healthy mice with high level reconstitution of human cells and tissues requires specialized methods that are presented in detail. Published by Elsevier B.V. C1 [Lavender, Kerry J.; Messer, Ronald J.; Race, Brent; Hasenkrug, Kim J.] NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Hasenkrug, KJ (reprint author), NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM khasenkrug@nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, USA FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, USA. NR 14 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 EI 1872-7905 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAY PY 2014 VL 407 BP 127 EP 134 DI 10.1016/j.jim.2014.04.008 PG 8 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA AJ7GZ UT WOS:000337866500016 PM 24769067 ER PT J AU Berkman, BE Hull, SC Eckstein, L AF Berkman, Benjamin E. Hull, Sara Chandros Eckstein, Lisa TI The unintended implications of blurring the line between research and clinical care in a genomic age SO PERSONALIZED MEDICINE LA English DT Article DE ancillary care; incidental findings; legal liability; research ethics; secondary findings; whole-genome sequencing ID MANAGING INCIDENTAL FINDINGS; GENETIC RESEARCH; SECONDARY VARIANTS; WORKING GROUP; RECOMMENDATIONS; MEDICINE; FUTURE; RETURN; EXOME; PERSPECTIVES AB While the development of next-generation sequencing technology has had a paradigm-changing impact on biomedical research, there is likely to be a gap between discovery of therapeutic benefits in research and actual adoption of the new technology into clinical practice. This gap can create pressure on the research enterprise to provide individualized care more typical of the clinic setting because it is uniquely accessible in research. This blurring of the line between research and clinical care is understandable, and perhaps even inevitable. But even if the gap is only transitory, such a blurring can have lasting implications, both by expanding obligations imposed on researchers, but also by challenging long-held ethical views. We explore this idea, focusing on how the dissolving distinction between research and clinical care has influenced the vigorous debate around how researchers should manage genetic findings (sometimes separated into primary and incidental or secondary findings) resulting from research. C1 [Berkman, Benjamin E.; Hull, Sara Chandros] NHGRI, Off Clin Director, Bethesda, MD 20892 USA. [Berkman, Benjamin E.; Hull, Sara Chandros; Eckstein, Lisa] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. [Eckstein, Lisa] Univ Tasmania, Fac Law, Hobart, Tas 7001, Australia. RP Berkman, BE (reprint author), NHGRI, Off Clin Director, Bethesda, MD 20892 USA. EM berkmanbe@mail.nih.gov RI Eckstein, Lisa/J-7747-2014 OI Eckstein, Lisa/0000-0002-7161-7521 FU Intramural Research Program of the National Human Genome Research Institute; Department of Bioethics at the NIH Clinical Center FX The preparation of this manuscript was funded by the Intramural Research Program of the National Human Genome Research Institute and the Department of Bioethics at the NIH Clinical Center. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 55 TC 6 Z9 6 U1 1 U2 12 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 EI 1744-828X J9 PERS MED JI Pers. Med. PD MAY PY 2014 VL 11 IS 3 BP 285 EP 295 DI 10.2217/pme.14.3 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AJ7ZZ UT WOS:000337922800011 PM 25506378 ER PT J AU Avnir, Y Tallarico, AS Zhu, Q Bennett, AS Connelly, G Sheehan, J Sui, JH Fahmy, A Huang, CY Cadwell, G Bankston, LA McGuire, AT Stamatatos, L Wagner, G Liddington, RC Marasco, WA AF Avnir, Yuval Tallarico, Aimee S. Zhu, Quan Bennett, Andrew S. Connelly, Gene Sheehan, Jared Sui, Jianhua Fahmy, Amr Huang, Chiung-yu Cadwell, Greg Bankston, Laurie A. McGuire, Andrew T. Stamatatos, Leonidas Wagner, Gerhard Liddington, Robert C. Marasco, Wayne A. TI Molecular Signatures of Hemagglutinin Stem-Directed Heterosubtypic Human Neutralizing Antibodies against Influenza A Viruses SO PLOS PATHOGENS LA English DT Article ID MEMORY B-CELLS; SOMATIC HYPERMUTATION; STALK ANTIBODIES; GERMINAL CENTER; MARGINAL ZONE; COPY-NUMBER; IMMUNOGLOBULIN; REPERTOIRE; DESIGN; DOMAIN AB Recent studies have shown high usage of the IGHV1-69 germline immunoglobulin gene for influenza hemagglutinin stem-directed broadly-neutralizing antibodies (HV1-69-sBnAbs). Here we show that a major structural solution for these HV1-69-sBnAbs is achieved through a critical triad comprising two CDR-H2 loop anchor residues (a hydrophobic residue at position 53 (Ile or Met) and Phe54), and CDR-H3-Tyr at positions 98 +/- 1; together with distinctive V-segment CDR amino acid substitutions that occur in positions sparse in AID/polymerase-eta recognition motifs. A semi-synthetic IGHV1-69 phage-display library screen designed to investigate AID/pol eta restrictions resulted in the isolation of HV1-69-sBnAbs that featured a distinctive Ile52Ser mutation in the CDR-H2 loop, a universal CDR-H3 Tyr at position 98 or 99, and required as little as two additional substitutions for heterosubtypic neutralizing activity. The functional importance of the Ile52Ser mutation was confirmed by mutagenesis and by BCR studies. Structural modeling suggests that substitution of a small amino acid at position 52 (or 52a) facilitates the insertion of CDR-H2 Phe54 and CDR-H3-Tyr into adjacent pockets on the stem. These results support the concept that activation and expansion of a defined subset of IGHV1-69-encoded B cells to produce potent HV1-69-sBnAbs does not necessarily require a heavily diversified V-segment acquired through recycling/reentry into the germinal center; rather, the incorporation of distinctive amino acid substitutions by Phase 2 long-patch error-prone repair of AID-induced mutations or by random non-AID SHM events may be sufficient. We propose that these routes of B cell maturation should be further investigated and exploited as a pathway for HV1-69-sBnAb elicitation by vaccination. C1 [Avnir, Yuval; Tallarico, Aimee S.; Zhu, Quan; Bennett, Andrew S.; Connelly, Gene; Sheehan, Jared; Sui, Jianhua; Marasco, Wayne A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Med, Boston, MA 02115 USA. [Fahmy, Amr; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Huang, Chiung-yu] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. [Cadwell, Greg; Bankston, Laurie A.; Liddington, Robert C.] Sanford Burnham Med Res Inst, Infect & Inflammatory Dis Ctr, La Jolla, CA USA. [McGuire, Andrew T.; Stamatatos, Leonidas] Seattle Biomed Res Inst, Seattle, WA 98109 USA. RP Avnir, Y (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Med, 44 Binney St, Boston, MA 02115 USA. EM wayne_marasco@dfci.harvard.edu FU National Institutes of Health [NIAID U01-AI074518, NIAID P01 AI094419-01]; Defense Advanced Research Projects Agency [W911NF-10-1-0266] FX This work was supported by the following grants from the National Institutes of Health: NIAID U01-AI074518 to WAM and RCL and NIAID P01 AI094419-01 to LS. This work was also funded by the Defense Advanced Research Projects Agency's "7-Day Biodefense" program under contract # W911NF-10-1-0266 to WAM. The views expressed are those of the author and do not reflect the official policy or position of the Department of Defense or the U.S. Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 29 Z9 29 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2014 VL 10 IS 5 AR e1004103 DI 10.1371/journal.ppat.1004103 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AJ5NX UT WOS:000337732300021 PM 24788925 ER PT J AU Aydin, I Weber, S Snijder, B Ventayol, PS Kuhbacher, A Becker, M Day, PM Schiller, JT Kann, M Pelkmans, L Helenius, A Schelhaas, M AF Aydin, Inci Weber, Susanne Snijder, Berend Ventayol, Pilar Samperio Kuehbacher, Andreas Becker, Miriam Day, Patricia M. Schiller, John T. Kann, Michael Pelkmans, Lucas Helenius, Ari Schelhaas, Mario TI Large Scale RNAi Reveals the Requirement of Nuclear Envelope Breakdown for Nuclear Import of Human Papillomaviruses SO PLOS PATHOGENS LA English DT Article ID MINOR CAPSID PROTEIN; VIRUS-LIKE PARTICLES; SMALL-MOLECULE INHIBITOR; HEPARAN-SULFATE; MONOCLONAL-ANTIBODIES; HUMAN KERATINOCYTES; ALPHA(6) INTEGRIN; CELLULAR ENTRY; VIRAL-DNA; INFECTION AB A two-step, high-throughput RNAi silencing screen was used to identify host cell factors required during human papillomavirus type 16 (HPV16) infection. Analysis of validated hits implicated a cluster of mitotic genes and revealed a previously undetermined mechanism for import of the viral DNA (vDNA) into the nucleus. In interphase cells, viruses were endocytosed, routed to the perinuclear area, and uncoated, but the vDNA failed to be imported into the nucleus. Upon nuclear envelope perforation in interphase cells HPV16 infection occured. During mitosis, the vDNA and L2 associated with host cell chromatin on the metaphase plate. Hence, we propose that HPV16 requires nuclear envelope breakdown during mitosis for access of the vDNA to the nucleoplasm. The results accentuate the value of genes found by RNAi screens for investigation of viral infections. The list of cell functions required during HPV16 infection will, moreover, provide a resource for future virus-host cell interaction studies. C1 [Aydin, Inci; Weber, Susanne; Ventayol, Pilar Samperio; Becker, Miriam; Schelhaas, Mario] Univ Munster, ZMBE, Inst Mol Virol & Med Biochem, Emmy Noether Grp Virus Endocytosis, D-48149 Munster, Germany. [Aydin, Inci; Weber, Susanne; Ventayol, Pilar Samperio; Becker, Miriam; Schelhaas, Mario] Cluster Excellence EXC1003, Munster, Germany. [Snijder, Berend; Pelkmans, Lucas] Univ Zurich, Inst Mol Life Sci, Zurich, Switzerland. [Kuehbacher, Andreas; Helenius, Ari] ETH, Inst Biochem, Zurich, Switzerland. [Day, Patricia M.; Schiller, John T.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. [Kann, Michael] Univ Bordeaux Segalen, Lab Microbiol Fondamentale & Pathogenicite, Bordeaux, France. RP Aydin, I (reprint author), Univ Munster, ZMBE, Inst Mol Virol & Med Biochem, Emmy Noether Grp Virus Endocytosis, D-48149 Munster, Germany. EM schelhaas@uni-muenster.de RI Kim, Seongman/N-6910-2014; OI Snijder, Berend/0000-0003-3386-6583 FU German Research Foundation (DFG) [SCHE 1552/2-1, GRK 1409/C2, EXC 1003]; ETH Zurich; Swiss National Science Foundation (SNF); European Research Council (ERC); University of Zurich; European Union; SystemsX.ch; Swiss Initiative in Systems Biology FX MS was supported by the German Research Foundation (DFG, grants SCHE 1552/2-1, GRK 1409/C2, EXC 1003 (partly)). AH was supported by the ETH Zurich, and by grants from the Swiss National Science Foundation (SNF) and the European Research Council (ERC). LP was supported by the ETH Zurich, the University of Zurich, the European Union, and by SystemsX.ch, the Swiss Initiative in Systems Biology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 85 TC 35 Z9 35 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2014 VL 10 IS 5 AR e1004162 DI 10.1371/journal.ppat.1004162 PG 19 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AJ5NX UT WOS:000337732300058 PM 24874089 ER PT J AU Dumas, A Amiable, N Vaccari, JPD Chae, JJ Keane, RW Lacroix, S Vallieres, L AF Dumas, Aline Amiable, Nathalie Vaccari, Juan Pablo de Rivero Chae, Jae Jin Keane, Robert W. Lacroix, Steve Vallieres, Luc TI The Inflammasome Pyrin Contributes to Pertussis Toxin-Induced IL-1 beta Synthesis, Neutrophil Intravascular Crawling and Autoimmune Encephalomyelitis SO PLOS PATHOGENS LA English DT Article ID FAMILIAL MEDITERRANEAN FEVER; CENTRAL-NERVOUS-SYSTEM; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS PATIENTS; REGULATORY T-CELLS; INFECTIOUS-MONONUCLEOSIS; IL-6-DEFICIENT MICE; BRAIN VASCULATURE; COMMON MUTATIONS AB Microbial agents can aggravate inflammatory diseases, such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). An example is pertussis toxin (PTX), a bacterial virulence factor commonly used as an adjuvant to promote EAE, but whose mechanism of action is unclear. We have reported that PTX triggers an IL-6-mediated signaling cascade that increases the number of leukocytes that patrol the vasculature by crawling on its luminal surface. In the present study, we examined this response in mice lacking either TLR4 or inflammasome components and using enzymatically active and inactive forms of PTX. Our results indicate that PTX, through its ADP-ribosyltransferase activity, induces two series of events upstream of IL-6: 1) the activation of TLR4 signaling in myeloid cells, leading to pro-IL-1 beta synthesis; and 2) the formation of a pyrin-dependent inflammasome that cleaves pro-IL-1 beta into its active form. In turn, IL-1 beta stimulates nearby stromal cells to secrete IL-6, which is known to induce vascular changes required for leukocyte adhesion. Without pyrin, PTX does not induce neutrophil adhesion to cerebral capillaries and is less effective at inducing EAE in transgenic mice with encephalitogenic T lymphocytes. This study identifies the first microbial molecule that activates pyrin, a mechanism by which infections may influence MS and a potential therapeutic target for immune disorders. C1 [Dumas, Aline; Amiable, Nathalie; Lacroix, Steve; Vallieres, Luc] Univ Hosp Ctr Quebec, Quebec City, PQ, Canada. [Vaccari, Juan Pablo de Rivero] Univ Miami, Dept Neurol Surg, Miami Project Cure Paralysis, Miami, FL USA. [Chae, Jae Jin] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. [Keane, Robert W.] Univ Miami, Dept Physiol & Biophys, Miami, FL USA. [Lacroix, Steve; Vallieres, Luc] Univ Laval, Dept Mol Med, Quebec City, PQ, Canada. RP Dumas, A (reprint author), Univ Hosp Ctr Quebec, Quebec City, PQ, Canada. EM Luc.Vallieres@crchul.ulaval.ca OI de Rivero Vaccari, Juan Pablo/0000-0002-5460-8834 FU Multiple Sclerosis Society of Canada; Natural Sciences and Engineering Research Council of Canada; Fonds de Recherche du Quebec en Sante (FRQS); FRQS FX This work was supported by grants from the Multiple Sclerosis Society of Canada and the Natural Sciences and Engineering Research Council of Canada. LV and SL received Chercheur-Boursier Senior awards from the Fonds de Recherche du Quebec en Sante (FRQS). NA received a postdoctoral fellowship from the FRQS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 95 TC 20 Z9 20 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2014 VL 10 IS 5 AR e1004150 DI 10.1371/journal.ppat.1004150 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AJ5NX UT WOS:000337732300050 PM 24875775 ER PT J AU Jang, MK Shen, K McBride, AA AF Jang, Moon Kyoo Shen, Kui McBride, Alison A. TI Papillomavirus Genomes Associate with BRD4 to Replicate at Fragile Sites in the Host Genome SO PLOS PATHOGENS LA English DT Article ID BROMODOMAIN PROTEIN BRD4; DNA-DAMAGE RESPONSE; E2 PROTEIN; MITOTIC CHROMOSOMES; S-PHASE; TRANSCRIPTION FACTORS; NUCLEOTIDE-SEQUENCE; PREFERENTIAL SITES; VIRAL INTEGRATION; SUPER-ENHANCERS AB It has long been recognized that oncogenic viruses often integrate close to common fragile sites. The papillomavirus E2 protein, in complex with BRD4, tethers the viral genome to host chromatin to ensure persistent replication. Here, we map these targets to a number of large regions of the human genome and name them Persistent E2 and BRD4-Broad Localized Enrichments of Chromatin or PEB-BLOCs. PEB-BLOCs frequently contain deletions, have increased rates of asynchronous DNA replication, and are associated with many known common fragile sites. Cell specific fragile sites were mapped in human C-33 cervical cells by FANCD2 ChIP-chip, confirming the association with PEB-BLOCs. HPV-infected cells amplify viral DNA in nuclear replication foci and we show that these form adjacent to PEB-BLOCs. We propose that HPV replication, which hijacks host DNA damage responses, occurs adjacent to highly susceptible fragile sites, greatly increasing the chances of integration here, as is found in HPV-associated cancers. C1 [Jang, Moon Kyoo; McBride, Alison A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Shen, Kui] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA. RP Jang, MK (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM amcbride@nih.gov RI Shen, Kui/E-2764-2015; OI McBride, Alison/0000-0001-5607-5157 FU Intramural Research Program of NIAID, NIH [ZIA AI000713 LVD] FX This work was funded by the Intramural Research Program of NIAID, NIH grant number ZIA AI000713 LVD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 81 TC 19 Z9 19 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2014 VL 10 IS 5 AR e1004117 DI 10.1371/journal.ppat.1004117 PG 17 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AJ5NX UT WOS:000337732300033 PM 24832099 ER PT J AU Li, QS Zhang, YY Chiu, S Hu, ZY Lan, KH Cha, H Sodroski, C Zhang, F Hsu, CS Thomas, E Liang, TJ AF Li, Qisheng Zhang, Yong-Yuan Chiu, Stephan Hu, Zongyi Lan, Keng-Hsin Cha, Helen Sodroski, Catherine Zhang, Fang Hsu, Ching-Sheng Thomas, Emmanuel Liang, T. Jake TI Integrative Functional Genomics of Hepatitis C Virus Infection Identifies Host Dependencies in Complete Viral Replication Cycle SO PLOS PATHOGENS LA English DT Article ID NONSTRUCTURAL PROTEIN 5A; CLATHRIN-MEDIATED ENDOCYTOSIS; CELLULAR COFACTORS; ANTIVIRAL PROTEIN; HUMAN HEPATOCYTES; APOLIPOPROTEIN-E; ENTRY FACTOR; ALPHA-HELIX; PARTICLES; REQUIRES AB Recent functional genomics studies including genome-wide small interfering RNA (siRNA) screens demonstrated that hepatitis C virus (HCV) exploits an extensive network of host factors for productive infection and propagation. How these co-opted host functions interact with various steps of HCV replication cycle and exert pro- or antiviral effects on HCV infection remains largely undefined. Here we present an unbiased and systematic strategy to functionally interrogate HCV host dependencies uncovered from our previous infectious HCV (HCVcc) siRNA screen. Applying functional genomics approaches and various in vitro HCV model systems, including HCV pseudoparticles (HCVpp), single-cycle infectious particles (HCVsc), subgenomic replicons, and HCV cell culture systems (HCVcc), we identified and characterized novel host factors or pathways required for each individual step of the HCV replication cycle. Particularly, we uncovered multiple HCV entry factors, including E-cadherin, choline kinase alpha, NADPH oxidase CYBA, Rho GTPase RAC1 and SMAD family member 6. We also demonstrated that guanine nucleotide binding protein GNB2L1, E2 ubiquitin-conjugating enzyme UBE2J1, and 39 other host factors are required for HCV RNA replication, while the deubiquitinating enzyme USP11 and multiple other cellular genes are specifically involved in HCV IRES-mediated translation. Families of antiviral factors that target HCV replication or translation were also identified. In addition, various virologic assays validated that 66 host factors are involved in HCV assembly or secretion. These genes included insulin-degrading enzyme (IDE), a proviral factor, and N-Myc down regulated Gene 1 (NDRG1), an antiviral factor. Bioinformatics meta-analyses of our results integrated with literature mining of previously published HCV host factors allows the construction of an extensive roadmap of cellular networks and pathways involved in the complete HCV replication cycle. This comprehensive study of HCV host dependencies yields novel insights into viral infection, pathogenesis and potential therapeutic targets. C1 [Li, Qisheng; Zhang, Yong-Yuan; Chiu, Stephan; Hu, Zongyi; Lan, Keng-Hsin; Cha, Helen; Sodroski, Catherine; Zhang, Fang; Hsu, Ching-Sheng; Thomas, Emmanuel; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Li, QS (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. EM jakel@bdg10.niddk.nih.gov RI Li, Qisheng/K-1909-2013 FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; NIH [N01-DK-7-0004/HHSN26700700004C] FX This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Primary human hepatocytes were provided by the NIH funded Liver Tissue Procurement and Cell Distribution System (N01-DK-7-0004/HHSN26700700004C, PI-S. Strom, University of Pittsburgh). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 70 TC 33 Z9 34 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2014 VL 10 IS 5 AR e1004163 DI 10.1371/journal.ppat.1004163 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AJ5NX UT WOS:000337732300059 PM 24852294 ER PT J AU Mattera, R Farias, GG Mardones, GA Bonifacino, JS AF Mattera, Rafael Farias, Ginny G. Mardones, Gonzalo A. Bonifacino, Juan S. TI Co-assembly of Viral Envelope Glycoproteins Regulates Their Polarized Sorting in Neurons SO PLOS PATHOGENS LA English DT Article ID VIRUS FUSION PROTEIN; EMERGENT DEADLY PARAMYXOVIRUS; NIPAH-VIRUS; EPITHELIAL-CELLS; HIPPOCAMPAL-NEURONS; NERVOUS-SYSTEM; N-GLYCANS; MEMBRANE-PROTEINS; TARGETING SIGNAL; HENDRA VIRUS AB Newly synthesized envelope glycoproteins of neuroinvasive viruses can be sorted in a polarized manner to the somatodendritic and/or axonal domains of neurons. Although critical for transneuronal spread of viruses, the molecular determinants and interregulation of this process are largely unknown. We studied the polarized sorting of the attachment (NiV-G) and fusion (NiV-F) glycoproteins of Nipah virus (NiV), a paramyxovirus that causes fatal human encephalitis, in rat hippocampal neurons. When expressed individually, NiV-G exhibited a non-polarized distribution, whereas NiV-F was specifically sorted to the somatodendritic domain. Polarized sorting of NiV-F was dependent on interaction of tyrosine-based signals in its cytosolic tail with the clathrin adaptor complex AP-1. Co-expression of NiV-G with NiV-F abolished somatodendritic sorting of NiV-F due to incorporation of NiV-G.NiV-F complexes into axonal transport carriers. We propose that faster biosynthetic transport of unassembled NiV-F allows for its proteolytic activation in the somatodendritic domain prior to association with NiV-G and axonal delivery of NiV-G.NiV-F complexes. Our study reveals how interactions of viral glycoproteins with the host's transport machinery and between themselves regulate their polarized sorting in neurons. C1 [Mattera, Rafael; Farias, Ginny G.; Mardones, Gonzalo A.; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. RP Mattera, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. EM juan@helix.nih.gov OI Bonifacino, Juan S./0000-0002-5673-6370 FU NICHD, NIH FX This work was funded by the Intramural Program of NICHD, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 8 Z9 8 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2014 VL 10 IS 5 AR e1004107 DI 10.1371/journal.ppat.1004107 PG 18 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AJ5NX UT WOS:000337732300024 PM 24831812 ER PT J AU Park, YD Shin, S Panepinto, J Ramos, J Qiu, J Frases, S Albuquerque, P Cordero, RJB Zhang, NN Himmelreich, U Beenhouwer, D Bennett, JE Casadevall, A Williamson, PR AF Park, Yoon-Dong Shin, Soowan Panepinto, John Ramos, Jeanie Qiu, Jin Frases, Susana Albuquerque, Patricia Cordero, Radames J. B. Zhang, Nannan Himmelreich, Uwe Beenhouwer, David Bennett, John E. Casadevall, Arturo Williamson, Peter R. TI A Role for LHC1 in Higher Order Structure and Complement Binding of the Cryptococcus neoformans Capsule SO PLOS PATHOGENS LA English DT Article ID POLYSACCHARIDE CAPSULE; MONOCLONAL-ANTIBODIES; FUSARIUM-OXYSPORUM; VIRULENCE FACTOR; LACCASE; CELL; ACTIVATION; COMPONENTS; INFECTION; STRAINS AB Polysaccharide capsules are important virulence factors for many microbial pathogens including the opportunistic fungus Cryptococcus neoformans. In the present study, we demonstrate an unusual role for a secreted lactonohydrolase of C. neoformans, LHC1 in capsular higher order structure. Analysis of extracted capsular polysaccharide from wild-type and lhc1 (Delta) over bar strains by dynamic and static light scattering suggested a role for the LHC1 locus in altering the capsular polysaccharide, both reducing dimensions and altering its branching, density and solvation. These changes in the capsular structure resulted in LHC1-dependent alterations of antibody binding patterns, reductions in human and mouse complement binding and phagocytosis by the macrophage-like cell line J774, as well as increased virulence in mice. These findings identify a unique molecular mechanism for tertiary structural changes in a microbial capsule, facilitating immune evasion and virulence of a fungal pathogen. C1 [Park, Yoon-Dong; Qiu, Jin; Zhang, Nannan; Bennett, John E.; Williamson, Peter R.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Shin, Soowan; Ramos, Jeanie; Williamson, Peter R.] Univ Illinois, Dept Med, Coll Med, Infect Dis Sect, Chicago, IL USA. [Panepinto, John] SUNY Buffalo, Dept Microbiol & Immunol, Buffalo, NY 14260 USA. [Frases, Susana; Albuquerque, Patricia; Cordero, Radames J. B.; Casadevall, Arturo] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Frases, Susana; Albuquerque, Patricia; Cordero, Radames J. B.; Casadevall, Arturo] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Infect Dis, Bronx, NY 10467 USA. [Frases, Susana] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Ultraestrutura Cellular Hertha Meyer, BR-21941 Rio De Janeiro, Brazil. [Himmelreich, Uwe] Katholieke Univ Leuven, Div Radiol, Dept Med Diagnost Sci, Biomed NMR Unit, Leuven, Belgium. [Beenhouwer, David] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. [Beenhouwer, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Park, YD (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM williamsonpr@mail.nih.gov RI Albuquerque, Patricia/H-1403-2011; OI Cordero, Radames JB/0000-0002-3026-7094 FU United States Public Health Service [NIH-AI45995, AI49371, AI007506, AI033142, AI47087, HL059842-3, A1033774, A1052733, AI033142.]; Flemish government [FWO G.0804.11]; KUL [PF10/017]; CAPES-Brazil; NIH, NIAID FX This work was supported, in part, by United States Public Health Service Grants NIH-AI45995, AI49371, AI007506, AI033142, AI47087, HL059842-3, A1033774, A1052733, and AI033142. Flemish governmental funding FWO G.0804.11 and KUL funding PF10/017 and a CAPES-Brazil/Fulbright scholarship (PA). This research was also supported, in part, by the Intramural Research Program of the NIH, NIAID. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 5 Z9 5 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2014 VL 10 IS 5 AR e1004037 DI 10.1371/journal.ppat.1004037 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AJ5NX UT WOS:000337732300003 PM 24789368 ER PT J AU Anderson, SR Esposito, D Gillette, W Zhu, JY Baxa, U McNeil, SE AF Anderson, Sarah R. Esposito, Dominic Gillette, William Zhu, J. Y. Baxa, Ulrich McNeil, Scott E. TI Enzymatic preparation of nanocrystalline and microcrystalline cellulose SO TAPPI JOURNAL LA English DT Article ID MICROFIBRILLATED CELLULOSE; FILMS; SUSPENSIONS; HYDROLYSIS; NANOFIBERS; BEHAVIOR; FIBERS; PULP AB Traditional cellulose nanocrystal (CNC) production methods use harsh chemicals, are energetically expensive, and result in a hydrophilic sulfate surface chemistry with limited utility. Enzymatic production of CNCs is a less expensive alternative production method that eliminates the need for harsh chemicals and requires much less energy for mechanical fibrillation and heating. Furthermore, enzymes that selectively degrade the amorphous regions of cellulose fibers, and do not significantly digest the crystalline areas, result in CNCs that retain a hydroxyl group surface chemistry. Retention of hydroxyl groups allows for easier chemical manipulation, and thus an expanded commercial potential. Here we show that cellulase from Aspergillus niger is capable of producing CNC and micro-fibrillated cellulose (MFC) from well-solubilized kraft pulp feedstock with minimal processing, and that a chimeric cellulase partially digests kraft pulp and live wood feedstock. Additionally, we show that as a feedstock source, milled pulp from bug-killed dead and downed trees has significantly reduced energy requirements to process the feedstock into elementary fibers and MFCs when compared to live wood feedstock sources. C1 [Anderson, Sarah R.; Baxa, Ulrich] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Elect Microscopy Lab, Frederick, MD 21702 USA. [Esposito, Dominic; Gillette, William] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Prot Express Lab, Frederick, MD USA. [McNeil, Scott E.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Nanotechnol Characterizat Lab, Canc Res Technol Program, Frederick, MD USA. RP Anderson, SR (reprint author), Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Elect Microscopy Lab, Frederick, MD 21702 USA. EM ncl@mail.nih.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX The authors are grateful to all from Leidos Biomedical Research Inc.; Vanessa Wall, Jane Jones, Shelley Perkins, and Troy Taylor for cloning and protein production assistance; Andrew Stephen for help with assay development; and Rachael M. Crist for assistance with the preparation of the manuscript. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the U. S. Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. government or TAPPI. NR 26 TC 7 Z9 7 U1 4 U2 32 PU TECH ASSOC PULP PAPER IND INC PI NORCROSS PA 15 TECHNOLOGY PARK SOUTH, NORCROSS, GA 30092 USA SN 0734-1415 J9 TAPPI J JI TAPPI J. PD MAY PY 2014 VL 13 IS 5 BP 35 EP 42 PG 8 WC Materials Science, Paper & Wood SC Materials Science GA AJ8GI UT WOS:000337940400005 ER PT J AU Anderson, NW Klein, DM Dornink, SM Jespersen, DJ Kubofcik, J Nutman, TB Merrigan, SD Couturier, MR Theel, ES AF Anderson, Neil W. Klein, Diane M. Dornink, Sarina M. Jespersen, Deborah J. Kubofcik, Joseph Nutman, Thomas B. Merrigan, Stephen D. Couturier, Marc Roger Theel, Elitza S. TI Comparison of Three Immunoassays for Detection of Antibodies to Strongyloides stercoralis SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID HYPERINFECTION SYNDROME; IMPROVED DIAGNOSIS; STOOL SPECIMENS; RISK-FACTORS; INFECTION; ASSAY AB Due to the limited sensitivities of stool-based microscopy and/or culture techniques for Strongyloides stercoralis, the detection of antibodies to this intestinal nematode is relied upon as a surrogate for determining exposure status or making a diagnosis of S. stercoralis infection. Here, we evaluated three immunoassays, including the recently released InBios Strongy Detect IgG enzyme-linked immunosorbent assay (ELISA) (InBios International, Inc., Seattle, WA), the SciMedx Strongyloides serology microwell ELISA (SciMedx Corporation, Denville, NJ), and the luciferase immunoprecipitation system (LIPS) assay performed at the National Institutes of Health (NIH), for their detection of IgG antibodies to S. stercoralis. A total of 101 retrospective serum samples, previously submitted for routine S. stercoralis antibody detection using the SciMedx assay, were also evaluated by the InBios and LIPS assays. The qualitative results from each assay were compared using a Venn diagram analysis, to the consensus result among the three assays, and each ELISA was also evaluated using the LIPS assay as the reference standard. By Venn diagram analysis, 65% (66/101) of the samples demonstrated perfect agreement by all three assays. Also, the numbers of samples considered positive or negative by a single method were similar. Compared to the consensus result, the overall percent agreement of the InBios, SciMedx, and LIPS assays were comparable at 87.1%, 84.2%, and 89.1%, respectively. Finally, the two ELISAs performed analogously but demonstrated only moderate agreement (kappa coefficient for the two assays, 0.53) with the LIPS assay. Collectively, while the two commercially available ELISAs perform equivalently, neither should be used independently of clinical evaluation to diagnose strongyloidiasis. C1 [Anderson, Neil W.; Klein, Diane M.; Dornink, Sarina M.; Jespersen, Deborah J.; Theel, Elitza S.] Mayo Clin, Div Clin Microbiol, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Kubofcik, Joseph; Nutman, Thomas B.] NIH, Clin Parasitol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA. [Merrigan, Stephen D.; Couturier, Marc Roger] Inst Clin & Expt Pathol, ARUP Labs, Salt Lake City, UT USA. [Couturier, Marc Roger] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA. RP Theel, ES (reprint author), Mayo Clin, Div Clin Microbiol, Dept Lab Med & Pathol, Rochester, MN 55905 USA. EM theel.elitza@mayo.edu NR 22 TC 10 Z9 10 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 EI 1556-679X J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2014 VL 21 IS 5 BP 732 EP 736 DI 10.1128/CVI.00041-14 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AJ0NU UT WOS:000337352300017 PM 24648484 ER PT J AU O'Donnell, CD Wright, A Vogel, L Boonnak, K Treanor, JJ Subbarao, K AF O'Donnell, Christopher D. Wright, Amber Vogel, Leatrice Boonnak, Kobporn Treanor, John J. Subbarao, Kanta TI Humans and Ferrets with Prior H1N1 Influenza Virus Infections Do Not Exhibit Evidence of Original Antigenic Sin after Infection or Vaccination with the 2009 Pandemic H1N1 Influenza Virus SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID ANTIBODY-RESPONSES; PROTECTIVE IMMUNITY; CROSS-PROTECTION; MICE; VACCINES; HEMAGGLUTININ AB The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus. C1 [O'Donnell, Christopher D.; Wright, Amber; Vogel, Leatrice; Boonnak, Kobporn; Subbarao, Kanta] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. [Treanor, John J.] Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov FU NIH, NIAID FX This research was supported in part by the Intramural Research Program of the NIH, NIAID. NR 55 TC 2 Z9 3 U1 4 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 EI 1556-679X J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2014 VL 21 IS 5 BP 737 EP 746 DI 10.1128/CVI.00790-13 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AJ0NU UT WOS:000337352300018 PM 24648486 ER PT J AU Paris, R Kuschner, RA Binn, L Thomas, SJ Colloca, S Nicosia, A Cortese, R Bailer, RT Sullivan, N Koup, RA AF Paris, Robert Kuschner, Robert A. Binn, Leonard Thomas, Stephen J. Colloca, Stefano Nicosia, Alfredo Cortese, Riccardo Bailer, Robert T. Sullivan, Nancy Koup, Richard A. TI Adenovirus Type 4 and 7 Vaccination or Adenovirus Type 4 Respiratory Infection Elicits Minimal Cross-Reactive Antibody Responses to Nonhuman Adenovirus Vaccine Vectors SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID NEUTRALIZING ANTIBODIES; HIV-1 VACCINE; PREEXISTING IMMUNITY; MILITARY TRAINEES; DOUBLE-BLIND; IMMUNOGENICITY; IMMUNIZATION; EFFICACY; SAFETY; CANDIDATE AB Antivector immunity may limit the immunogenicity of adenovirus vector vaccines. We tested sera from individuals immunized with adenovirus type 4 and 7 (Ad4 and Ad7, respectively) vaccine or naturally infected with Ad4 for their ability to neutralize a panel of E1-deleted human and chimpanzee adenoviruses (ChAd). Small statistically significant increases in titers to ChAd63, ChAd3, human Ad35, and human Ad5 were observed. Neutralizing antibodies elicited by Ad4 infection or immunization results in a small amount of adenovirus cross-reactivity. C1 [Paris, Robert] Walter Reed Army Inst Res, US Mil Malaria Res Program, Silver Spring, MD USA. [Kuschner, Robert A.; Binn, Leonard; Thomas, Stephen J.] Walter Reed Army Inst Res, Viral Dis Branch, Silver Spring, MD USA. [Colloca, Stefano; Nicosia, Alfredo; Cortese, Riccardo] Okairos, Rome, Italy. [Nicosia, Alfredo; Cortese, Riccardo] CEINGE, Naples, Italy. [Nicosia, Alfredo] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy. [Bailer, Robert T.; Sullivan, Nancy; Koup, Richard A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Koup, RA (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rkoup@mail.nih.gov FU Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This research was supported by the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 26 TC 7 Z9 7 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 EI 1556-679X J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2014 VL 21 IS 5 BP 783 EP 786 DI 10.1128/CVI.00011-14 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AJ0NU UT WOS:000337352300024 PM 24623627 ER PT J AU Remais, JV Hess, JJ Ebi, KL Markandya, A Balbus, JM Wilkinson, P Haines, A Chalabi, Z AF Remais, Justin V. Hess, Jeremy J. Ebi, Kristie L. Markandya, Anil Balbus, John M. Wilkinson, Paul Haines, Andy Chalabi, Zaid TI Estimating the Health Effects of Greenhouse Gas Mitigation Strategies: Addressing Parametric, Model, and Valuation Challenges SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review ID CLIMATE-CHANGE MITIGATION; AIR-POLLUTION; INTEGRATED ASSESSMENT; CO-BENEFITS; UNITED-STATES; MEXICO-CITY; UNCERTAINTY; ADAPTATION; IMPACTS; COSTS AB Background: Policy decisions regarding climate change mitigation are increasingly incorporating the beneficial and adverse health impacts of greenhouse gas emission reduction strategies. Studies of such co-benefits and co-harms involve modeling approaches requiring a range of analytic decisions that affect the model output. Objective: Our objective was to assess analytic decisions regarding model framework, structure, choice of parameters, and handling of uncertainty when modeling health co-benefits, and to make recommendations for improvements that could increase policy uptake. Methods: We describe the assumptions and analytic decisions underlying models of mitigation co-benefits, examining their effects on modeling outputs, and consider tools for quantifying uncertainty. Discussion: There is considerable variation in approaches to valuation metrics, discounting methods, uncertainty characterization and propagation, and assessment of low-probability/high-impact events. There is also variable inclusion of adverse impacts of mitigation policies, and limited extension of modeling domains to include implementation considerations. Going forward, co-benefits modeling efforts should be carried out in collaboration with policy makers; these efforts should include the full range of positive and negative impacts and critical uncertainties, as well as a range of discount rates, and should explicitly characterize uncertainty. We make recommendations to improve the rigor and consistency of modeling of health co-benefits. Conclusion: Modeling health co-benefits requires systematic consideration of the suitability of model assumptions, of what should be included and excluded from the model framework, and how uncertainty should be treated. Increased attention to these and other analytic decisions has the potential to increase the policy relevance and application of co-benefits modeling studies, potentially helping policy makers to maximize mitigation potential while simultaneously improving health. C1 [Remais, Justin V.; Hess, Jeremy J.] Emory Univ, Rollins Sch Publ Hlth, Dept Environm Hlth, Atlanta, GA 30322 USA. [Hess, Jeremy J.] Emory Univ, Sch Med, Dept Emergency Med, Atlanta, GA 30322 USA. [Ebi, Kristie L.] ClimAdapt LLC, Los Altos, CA USA. [Markandya, Anil] Basque Ctr Climate Change, Bilbao, Spain. [Balbus, John M.] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Wilkinson, Paul; Haines, Andy; Chalabi, Zaid] Univ London London Sch Hyg & Trop Med, Fac Publ Hlth & Policy, Dept Social & Environm Hlth Res, London WC1E 7HT, England. RP Remais, JV (reprint author), Emory Univ, Rollins Sch Publ Hlth, Dept Environm Hlth, 1518 Clifton Rd NE, Atlanta, GA 30322 USA. EM justin.remais@emory.edu RI Markandya, Anil /K-9381-2013; Azkarate, Ainhoa/K-9087-2013 OI Azkarate, Ainhoa/0000-0003-0471-3094 FU National Institute for Allergy and Infectious Disease [K01AI091864]; National Institutes of Health (NIH)/National Science Foundation Ecology of Infectious Disease Program [0622743]; Emory Global Health Institute Faculty Distinction Fund; LIFE+ programme; European Commission's FX J. V. R. was supported by the National Institute for Allergy and Infectious Disease (grant K01AI091864), the National Institutes of Health (NIH)/National Science Foundation Ecology of Infectious Disease Program (grant 0622743), and the Emory Global Health Institute Faculty Distinction Fund. A.M. was supported by the LIFE+ programme, the European Commission's funding instrument for the environment. NR 109 TC 9 Z9 9 U1 11 U2 30 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 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2014 VL 122 IS 5 BP 447 EP 455 DI 10.1289/ehp.1306744 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA AJ3ZC UT WOS:000337606300013 PM 24583270 ER PT J AU Wang, Y Rogan, WJ Chen, PC Lien, GW Chen, HY Tseng, YC Longnecker, MP Wang, SL AF Wang, Yan Rogan, Walter J. Chen, Pau-Chung Lien, Guang-Wen Chen, Hsiao-Yen Tseng, Ying-Chih Longnecker, Matthew P. Wang, Shu-Li TI Association between Maternal Serum Perfluoroalkyl Substances during Pregnancy and Maternal and Cord Thyroid Hormones: Taiwan Maternal and Infant Cohort Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID PERFLUORINATED FATTY-ACIDS; CARBON-CHAIN LENGTH; PERFLUOROOCTANE SULFONATE; POLYFLUOROALKYL CHEMICALS; PLACENTAL-TRANSFER; EXPOSURE; FETAL; RATS; HYPOTHYROIDISM; ELIMINATION AB Background: Perfluoroalkyl substances (PFASs) are synthetic compounds that are widely used in industry and are often detectable in humans. In pregnant rats and their pups, PFASs can interfere with thyroid hormone homeostasis. In humans, maternal thyroid hormones supply the fetus throughout pregnancy, and thyroid hormones play a critical role in fetal growth and neurodevelopment. Objectives: We investigated the association between maternal PFAS exposure and thyroid hormone status in pregnant women and neonates. Methods: In a study of environmental exposure and health in Taiwan, we measured serum concentrations of nine PFASs and four thyroid hormones for 285 pregnant women in their third trimester, and also measured cord serum thyroid hormones for 116 neonates. Associations between maternal PFASs and maternal and cord thyroid hormones were examined in multiple linear regression models. Results: Perfluorohexanesulfonic acid concentrations were positively associated with maternal thyroid-stimulating hormone (TSH) levels. Pregnant women with higher levels of perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) had lower free thyroxine (T-4) and total T4 levels. For example, we estimated that maternal free T-4 levels decreased 0.019 ng/dL (95% CI: -0.028, -0.009) with each nanogram per milliliter increase in maternal PFNA. Finally, maternal PFNA, PFUnDA, and PFDoDA levels were associated with lower cord total triiodothyronine (T-3) and total T-4 levels, and maternal perfluorodecanoic acid (PFDeA) was associated with lower cord total T-3. Conclusions: Our results suggest that exposure to some PFASs during pregnancy may interfere with thyroid hormone homeostasis in pregnant women and fetuses. C1 [Wang, Yan; Rogan, Walter J.; Longnecker, Matthew P.; Wang, Shu-Li] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Chen, Pau-Chung; Lien, Guang-Wen] Natl Taiwan Univ, Coll Publ Hlth, Inst Occupat Med & Ind Hyg, Taipei 10764, Taiwan. [Chen, Pau-Chung] Natl Taiwan Univ, Coll Publ Hlth, Dept Publ Hlth, Taipei 10764, Taiwan. [Chen, Pau-Chung] Natl Taiwan Univ, Coll Publ Hlth, Dept Environm & Occupat Med, Taipei 10764, Taiwan. [Chen, Pau-Chung] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Chen, Hsiao-Yen; Wang, Shu-Li] Natl Hlth Res Inst, Div Environm Hlth & Occupat Med, Miaoli, Taiwan. [Tseng, Ying-Chih] Hsinchu Cathay Gen Hosp, Dept Obstet & Gynecol, Hsinchu, Taiwan. [Wang, Shu-Li] China Med Univ, Coll Publ Hlth, Dept Publ Hlth, Taichung, Taiwan. RP Wang, SL (reprint author), Natl Hlth Res Inst, Div Environm Hlth & Occupat Med, 35 Keyan Rd, Zhunan 350, Miaoli County, Taiwan. EM slwang@nhri.org.tw RI Wang, Shu-Li/C-1367-2010; Rogan, Walter/I-6034-2012; OI Rogan, Walter/0000-0002-9302-0160; Longnecker, Matthew/0000-0001-6073-5322; Chen, Pau-Chung/0000-0002-6242-5974 NR 38 TC 24 Z9 25 U1 7 U2 35 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 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2014 VL 122 IS 5 BP 529 EP 534 DI 10.1289/ehp.1306925 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA AJ3ZC UT WOS:000337606300024 PM 24577800 ER PT J AU Golding, J Steer, CD Lowery, T Jones, R Hibbeln, JR AF Golding, Jean Steer, Colin D. Lowery, Tony Jones, Robert Hibbeln, Joseph R. TI Fish Consumption and Blood Mercury Levels: Golding et al. Respond SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter ID UK TOTAL DIET C1 [Golding, Jean; Steer, Colin D.] Univ Bristol, Ctr Child & Adolescent Hlth, Bristol, RI 02809 USA. [Lowery, Tony] Natl Ocean & Atmospher Adm, Natl Marine Fisheries Serv, Natl Seafood Inspect Lab, Pascagoula, MS USA. [Jones, Robert] Ctr Dis Control & Prevent, Inorgan & Radiat Analyt Toxicol Branch, Atlanta, GA USA. [Hibbeln, Joseph R.] NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Golding, J (reprint author), Univ Bristol, Ctr Child & Adolescent Hlth, Bristol, RI 02809 USA. EM Jean.Golding@bristol.ac.uk OI Golding, Jean/0000-0003-2826-3307 NR 3 TC 0 Z9 0 U1 0 U2 10 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 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2014 VL 122 IS 5 BP A120 EP A121 DI 10.1289/ehp.1307997R PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA AJ3ZC UT WOS:000337606300004 PM 24787643 ER PT J AU Warnke, C von Geldern, G Markwerth, P Dehmel, T Hoepner, R Gold, R Pawlita, M Kumpfel, T Maurer, M Stangel, M Wegner, F Hohlfeld, R Straeten, V Limmroth, V Weber, T Hermsen, D Kleinschnitz, C Hartung, HP Wattjes, MP Svenningson, A Major, E Olsson, T Kieseier, BC Adams, O AF Warnke, C. von Geldern, G. Markwerth, P. Dehmel, T. Hoepner, R. Gold, R. Pawlita, M. Kuempfel, T. Maeurer, M. Stangel, M. Wegner, F. Hohlfeld, R. Straeten, V. Limmroth, V. Weber, T. Hermsen, D. Kleinschnitz, C. Hartung, H. -P. Wattjes, M. P. Svenningson, A. Major, E. Olsson, T. Kieseier, B. C. Adams, O. TI The CSF JCV antibody index for diagnosis of natalizumab-associated PML SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT Joint Congress of European Neurology CY MAY 31-JUN 03, 2014 CL Istanbul, TURKEY SP European Federat Neurol Soc C1 [Warnke, C.; Markwerth, P.; Dehmel, T.; Hermsen, D.; Hartung, H. -P.; Kieseier, B. C.; Adams, O.] Univ Dusseldorf, Dusseldorf, Germany. [von Geldern, G.; Major, E.] NINDS, Bethesda, MD 20892 USA. [Hoepner, R.; Gold, R.] Ruhr Univ Bochum, St Josef Hosp, Bochum, Germany. [Pawlita, M.] German Canc Res Ctr, Heidelberg, Germany. [Kuempfel, T.; Hohlfeld, R.] Univ Munich, Munich, Germany. [Maeurer, M.] Caritas Hosp, Bad Mergentheim, Germany. [Stangel, M.; Wegner, F.] Hannover Med Sch MHH, Hannover, Germany. [Straeten, V.] Johannes Wesling Hosp Minden, Minden, Germany. [Limmroth, V.] Merheim Hosp, Cologne, Germany. [Weber, T.] Marien Hosp, Hamburg, Germany. [Kleinschnitz, C.] Univ Wurzburg, D-97070 Wurzburg, Germany. [Wattjes, M. P.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Svenningson, A.] Umea Univ Hosp, S-90185 Umea, Sweden. [Olsson, T.] Karolinska Inst, Stockholm, Sweden. RI Waterboer, Tim/G-1252-2010 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 EI 1468-1331 J9 EUR J NEUROL JI Eur. J. Neurol. PD MAY PY 2014 VL 21 SU 1 SI SI MA OS2124 BP 59 EP 59 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AJ3JX UT WOS:000337563600117 ER PT J AU Bilic, E Grkovic, L Pulanic, D Seiwerth, RS Bilic, E Nemet, D Pavletic, SZ AF Bilic, E. Grkovic, L. Pulanic, D. Seiwerth, R. Serventi Bilic, E. Nemet, D. Pavletic, S. Z. TI Small fiber neuropathy in patients with chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation - preliminary results of a prospective study SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT Joint Congress of European Neurology CY MAY 31-JUN 03, 2014 CL Istanbul, TURKEY SP European Federat Neurol Soc C1 [Bilic, E.] Univ Zagreb, Sch Med, Clin Hosp Ctr Zagreb, Dept Neurol, Zagreb 41001, Croatia. [Grkovic, L.; Pulanic, D.; Seiwerth, R. Serventi; Nemet, D.] Univ Zagreb, Sch Med, Clin Hosp Ctr Zagreb, Dept Hematol, Zagreb 41001, Croatia. [Bilic, E.] Univ Zagreb, Sch Med, Clin Hosp Ctr Zagreb, Dept Pediat Hematol & Oncol, Zagreb 41001, Croatia. [Pavletic, S. Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 EI 1468-1331 J9 EUR J NEUROL JI Eur. J. Neurol. PD MAY PY 2014 VL 21 SU 1 SI SI MA PP1251 BP 469 EP 469 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AJ3JX UT WOS:000337563601136 ER PT J AU Vural, A Johnson, J Singleton, A Temucin, CM AF Vural, A. Johnson, J. Singleton, A. Temucin, C. M. TI Adult-onset case of Brown-Vialetto-Van-Laere syndrome with SLC52A3 mutation SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT Joint Congress of European Neurology CY MAY 31-JUN 03, 2014 CL Istanbul, TURKEY SP European Federat Neurol Soc C1 [Vural, A.] Besni Govt Hosp, Dept Neurol, Adiyaman, Turkey. [Johnson, J.; Singleton, A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Temucin, C. M.] Hacettepe Univ, Fac Med, Dept Neurol, TR-06100 Ankara, Turkey. RI Singleton, Andrew/C-3010-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 EI 1468-1331 J9 EUR J NEUROL JI Eur. J. Neurol. PD MAY PY 2014 VL 21 SU 1 SI SI MA PP4091 BP 657 EP 657 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AJ3JX UT WOS:000337563601412 ER PT J AU Burkey, MD Weiser, SD Fehmie, D Alamo-Talisuna, S Sunday, P Nannyunja, J Reynolds, SJ Chang, LW AF Burkey, Matthew D. Weiser, Sheri D. Fehmie, Desiree Alamo-Talisuna, Stella Sunday, Pamella Nannyunja, Joy Reynolds, Steven J. Chang, Larry W. TI Socioeconomic Determinants of Mortality in HIV: Evidence From a Clinical Cohort in Uganda SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; socioeconomic status; lost to follow-up; mortality ID SUB-SAHARAN AFRICA; ANTIRETROVIRAL THERAPY PROGRAM; SOUTH-AFRICA; FUNDAMENTAL CAUSES; SOCIAL CONDITIONS; INFECTED PATIENTS; RISK-FACTOR; FOLLOW-UP; SURVIVAL; HEALTH AB Objective: To delineate the association between baseline socioeconomic status (SES) indicators and mortality and lost to follow-up (LTFU) in a cohort of HIV-infected individuals enrolled in antiretroviral therapy (ART) in urban Uganda. Design: Retrospective cohort study nested in an antiretroviral clinic-based cohort. Methods: SES indicators including education, employment status, and a standardized wealth index, and other demographic and clinical variables were assessed at baseline among ART-treated patients in a clinic-based cohort in Kampala, Uganda. Confirmed mortality (primary outcome) and LTFU (secondary outcome) were actively ascertained over a 4-year follow-up period from 2005 to 2009. Results: Among 1763 adults [70.5% female; mean age, 36.2 years (SD = 8.4)] enrolled in ART, 14.4% (n = 253) were confirmed dead and 19.7% (n = 346) were LTFU at 4-year follow-up. No formal education [adjusted odds ratio (AOR) 1.76; 95% confidence interval (CI): 1.19 to 2.59], having fewer than 6 dependents (AOR 1.39; 95% CI: 1.04 to 1.86), unemployment (AOR 1.98; 95% CI: 1.48 to 2.66), and housing tenure index score (a component of the wealth index) (AOR 1.11; 95% CI: 1.00 to 1.23) were significantly associated with confirmed mortality at 4 years. SES indicators were not associated with LTFU at 4 years. Conclusions: Baseline SES indicators, including education, number of dependents, employment status, and components of a standard wealth index may indicate long-term vulnerability to mortality in patients with HIV/AIDS, despite uniform access to ART. Future studies delineating the pathways through which poverty and limited assets affect clinical outcomes may lead to more effective HIV interventions in low-resource settings. C1 [Burkey, Matthew D.] Johns Hopkins Univ Hosp, Dept Psychiat & Behav Sci, Div Child & Adolescent Psychiat, Baltimore, MD 21287 USA. [Weiser, Sheri D.] Univ Calif San Francisco, Div HIV AIDS, San Francisco, CA 94143 USA. [Weiser, Sheri D.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. [Fehmie, Desiree] Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA. [Alamo-Talisuna, Stella; Sunday, Pamella; Nannyunja, Joy] Reach Out Mbuya, Kampala, Uganda. [Reynolds, Steven J.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Reynolds, Steven J.; Chang, Larry W.] Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA. [Chang, Larry W.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Burkey, MD (reprint author), Johns Hopkins Univ Hosp, 1800 Orleans St,Bloomberg 12352, Baltimore, MD 21287 USA. EM mburkey1@jhmi.edu FU Johns Hopkins Center for Global Health; National Institute of Mental Health [5K23MH086338, R01MH095683]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Burke Family Foundation FX M.D.B. was supported by a grant from the Johns Hopkins Center for Global Health to conduct this study. L. W. C. was supported by the National Institute of Mental Health (5K23MH086338). S.J.R. was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. S. D. W was supported by the National Institute of Mental Health (R01MH095683) and the Burke Family Foundation. NR 38 TC 6 Z9 6 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAY 1 PY 2014 VL 66 IS 1 BP 41 EP 47 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AJ4YF UT WOS:000337685400011 PM 24378727 ER PT J AU Abate-Daga, D Beard, RE Muranski, P Lu, YC Arons, E Alexander, TA Steinberg, S Ho, M Robbins, PF Morgan, RA Rosenberg, SA AF Abate-Daga, Daniel Beard, Rachel E. Muranski, Pawel Lu, Yong-Chen Arons, Evgeny Alexander, Theresa A. Steinberg, Seth Ho, Mitchell Robbins, Paul F. Morgan, Richard A. Rosenberg, Steven A. TI Transcriptomic Analysis of Human Melanoma Lesions Resected for TIL Production Reveals the Presence of B Cells in Association With T Lymphocytes SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Abate-Daga, Daniel; Beard, Rachel E.; Muranski, Pawel; Lu, Yong-Chen; Alexander, Theresa A.; Robbins, Paul F.; Morgan, Richard A.; Rosenberg, Steven A.] NCI, Surg Branch, Bethesda, MD 20892 USA. [Arons, Evgeny; Ho, Mitchell] NCI, Mol Biol Lab, Bethesda, MD 20892 USA. [Steinberg, Seth] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Morgan, Richard A.] BlueBird Bio, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 439 BP S168 EP S169 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300434 ER PT J AU Assadipour, Y Xu, H Black, MA Rosenberg, SA Kochenderfer, JN Feldman, SA AF Assadipour, Yasmine Xu, Hui Black, Mary A. Rosenberg, Steven A. Kochenderfer, James N. Feldman, Steven A. TI Increasing Adoptive Cell Therapy Safety Through the Use of an Inducible Caspase 9 SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Assadipour, Yasmine; Xu, Hui; Black, Mary A.; Rosenberg, Steven A.; Feldman, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Kochenderfer, James N.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 435 BP S167 EP S167 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300430 ER PT J AU Bauer, TR Tuschong, LM Russell, DW Hickstein, DD AF Bauer, Thomas R., Jr. Tuschong, Laura M. Russell, David W. Hickstein, Dennis D. TI Long-Term Correction of Canine Leukocyte Adhesion Deficiency With Foamy Viral Vector-Mediated Gene Therapy Using Reduced Intensity Busulfan Conditioning SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Bauer, Thomas R., Jr.; Tuschong, Laura M.; Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Russell, David W.] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 459 BP S176 EP S176 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300454 ER PT J AU Bolduc, V Zou, YQ Lindow, M Ko, D Obad, S Bonnemann, CG AF Bolduc, Veronique Zou, Yaqun Lindow, Morten Ko, Dayoung Obad, Susanna Boennemann, Carsten G. TI Allele-Specific Silencing of a Dominant-Negative Mutation Using siRNA or LNA Antisense Oligonucleotides Alleviates the Phenotype in a Cellular Model of Ullrich Congenital Muscular Dystrophy SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Bolduc, Veronique; Zou, Yaqun; Ko, Dayoung; Boennemann, Carsten G.] NINDS, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. [Lindow, Morten; Obad, Susanna] Santaris Pharma AS, Horsholm, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 143 BP S54 EP S54 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300143 ER PT J AU Byrd, TT Fousek, K Aviles-Padilla, K Bielamowicz, K Gottschalk, S St Croix, B Fletcher, B Hegde, M Ahmed, N AF Byrd, Tiara T. Fousek, Kristen Aviles-Padilla, Kevin Bielamowicz, Kevin Gottschalk, Stephen St Croix, Bradley Fletcher, Bradley Hegde, Meenakshi Ahmed, Nabil TI A Single Chimeric Antigen Receptor Simultaneously Targets the Tumor Endothelium as Well as the Tumor Cells in Glioblastoma SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Byrd, Tiara T.; Fousek, Kristen; Gottschalk, Stephen; Ahmed, Nabil] Baylor Coll Med, Houston, TX 77030 USA. [Byrd, Tiara T.; Fousek, Kristen; Aviles-Padilla, Kevin; Bielamowicz, Kevin; Gottschalk, Stephen; Hegde, Meenakshi; Ahmed, Nabil] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Byrd, Tiara T.; Fousek, Kristen; Aviles-Padilla, Kevin; Bielamowicz, Kevin; Gottschalk, Stephen; Hegde, Meenakshi; Ahmed, Nabil] Texas Childrens Hosp, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Fletcher, Bradley] Univ Florida, Gainesville, FL USA. [St Croix, Bradley] NCI, Ctr Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 160 BP S60 EP S60 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300160 ER PT J AU Cash, A Chang, Z Ichwan, B Metais, JY Dunbar, CE Larochelle, A AF Cash, Ayla Chang, Zanetta Ichwan, Brian Metais, Jean-Yves Dunbar, Cynthia E. Larochelle, Andre TI Culture of Mobilized Rhesus Macaque CD34+Cells in Hypoxic Conditions Does Not Improve Lentiviral Transduction Efficiency in Long-Term Repopulating Hematopoietic Stem Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Cash, Ayla; Chang, Zanetta; Ichwan, Brian; Metais, Jean-Yves; Dunbar, Cynthia E.; Larochelle, Andre] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 690 BP S267 EP S267 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300681 ER PT J AU Chandler, RJ Ashok, AA Varshney, GK Lafave, MC Wu, WW Hoffmann, V Elkahloun, AG Burgess, SM Venditti, CP AF Chandler, Randy J. Ashok, Adi A. Varshney, Gaurav K. Lafave, Matthew C. Wu, Weiwei Hoffmann, Victoria Elkahloun, Abdel G. Burgess, Shawn M. Venditti, Charles P. TI Genomic Analyses Define a Common Integration Site in Hepatocellular Carcinoma Caused By Therapeutic AAV Gene Delivery: A Mouse-Specific Phenomenon or New Safety Challenge for Human Gene Therapy? SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Chandler, Randy J.; Ashok, Adi A.; Varshney, Gaurav K.; Lafave, Matthew C.; Wu, Weiwei; Hoffmann, Victoria; Elkahloun, Abdel G.; Burgess, Shawn M.; Venditti, Charles P.] Natl Human Genome Inst, NIH, Bethesda, MD USA. RI Varshney, Gaurav/L-5261-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 242 BP S92 EP S92 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300242 ER PT J AU Cohen, CJ Rosenberg, SA Robbins, PF AF Cohen, Cyrille J. Rosenberg, Steven A. Robbins, Paul F. TI Using an MHC/Tetramer-Driven Approach To Detect and Exploit Neo-Antigen Specific T-Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Cohen, Cyrille J.] Bar Ilan Univ, Lab Tumor Immunol & Immunotherapy, Ramat Gan, Israel. [Cohen, Cyrille J.; Rosenberg, Steven A.; Robbins, Paul F.] NCI, Surg Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 633 BP S245 EP S245 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300627 ER PT J AU De Ravin, SS Moir, S Theobald, N Lee, J Wu, XL Choi, U Kang, E Gray, JT Sorrentino, BP Malech, HL AF De Ravin, Suk See Moir, Susan Theobald, Narda Lee, Janet Wu, Xiaolin Choi, Uimook Kang, Elizabeth Gray, John T. Sorrentino, Brian P. Malech, Harry L. TI Lentivector Gene Therapy with Non-Myeloablative Conditioning Restores IgG Production in Young Adults with SCID-X1 SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [De Ravin, Suk See; Moir, Susan; Theobald, Narda; Lee, Janet; Choi, Uimook; Kang, Elizabeth; Malech, Harry L.] NIAID, Bethesda, MD 20892 USA. [Wu, Xiaolin] Frederick Natl Lab Canc Res, Frederick, MD USA. [Gray, John T.; Sorrentino, Brian P.] SJCRH, Memphis, TN USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 278 BP S106 EP S107 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300278 ER PT J AU Frank, JA Tebebi, P Nguyen, B Kim, S Burks, S AF Frank, Joseph A. Tebebi, Pamela Nguyen, Ben Kim, Sage Burks, Scott TI Cyclo-Oxygenase or TNF alpha Inhibitors Interferes With the Mechanotransductive Effects of Pulsed Focused Ultrasound By Blunting Enhanced Homing of Mesenchymal Stem Cell SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Frank, Joseph A.; Tebebi, Pamela; Nguyen, Ben; Kim, Sage; Burks, Scott] NIH, Frank Lab, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 473 BP S181 EP S182 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300468 ER PT J AU Fujita, A Tisdale, J Uchida, N AF Fujita, Atsushi Tisdale, John Uchida, Naoya TI Mycoplasma Contamination Can Be Caused By Frozen Lentiviral Vectors in iPS Cell Generation SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Fujita, Atsushi; Tisdale, John; Uchida, Naoya] NHLBI NIDDK, MCHB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 218 BP S83 EP S83 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300218 ER PT J AU Glait-Santar, C Feng, XM Chen, JC Desmond, R Mizukawa, B Mulloy, JC Young, NS Dunbar, CE AF Glait-Santar, Chen Feng, Xingmin Chen, Jichun Desmond, Ronan Mizukawa, Benjamin Mulloy, James C. Young, Neal S. Dunbar, Cynthia E. TI Functional Niche Competition Between Normal and Leukemic Stem Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Glait-Santar, Chen; Feng, Xingmin; Chen, Jichun; Desmond, Ronan; Young, Neal S.; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Mizukawa, Benjamin; Mulloy, James C.] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Cincinnati, OH 45229 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 688 BP S266 EP S266 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300679 ER PT J AU Haddad, MR Choi, EY Kaler, SG AF Haddad, Marie Reine Choi, Eun-Young Kaler, Stephen G. TI AAVrh10-ATP7A Administration to the Cerebrospinal Fluid, in Combination with Subcutaneous Copper, Normalizes Neurological Outcomes in a Mouse Model of Menkes Disease SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Haddad, Marie Reine; Choi, Eun-Young; Kaler, Stephen G.] NICHD, Sect Translat Neurosci, Program Mol Med, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 261 BP S99 EP S100 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300261 ER PT J AU Hanley, PJ Nikiforow, S Heslop, HE Shpall, EJ Barrett, J Rodgers, J Bollard, C AF Hanley, Patrick J. Nikiforow, Sarah Heslop, Helen E. Shpall, E. J. Barrett, John Rodgers, John Bollard, Catherine TI CMV-Specific T Cells Derived From the Naive T Cell Population To Treat Transplant Recipients SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Hanley, Patrick J.; Bollard, Catherine] Childrens Hlth Syst, Program Cell Enhancement & Technol Immunotherapy, Washington, DC USA. [Nikiforow, Sarah] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Heslop, Helen E.; Rodgers, John] Baylor Coll Med, CAGT, Houston, TX 77030 USA. [Barrett, John] NHLBI, NIH, Bethesda, MD 20892 USA. [Shpall, E. J.] MD Anderson, Stem Cell Transplantat, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 693 BP S268 EP S268 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300684 ER PT J AU Hjelm, BE Grunseich, C Narwani, K Shelley, B Shi, YJ Avalos, P Mooney, M Gowing, G Fischbeck, KH Pierson, TM AF Hjelm, Brooke E. Grunseich, Christopher Narwani, Kavita Shelley, Brandon Shi, Yijun Avalos, Pablo Mooney, Michael Gowing, Genevieve Fischbeck, Kenneth H. Pierson, Tyler M. TI Mifepristone-Inducible Gene Expression of Target Genes in Murine and Human Neural Progenitor Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Hjelm, Brooke E.; Narwani, Kavita; Shelley, Brandon; Avalos, Pablo; Gowing, Genevieve; Pierson, Tyler M.] Cedars Sinai Med Ctr, RMI, Los Angeles, CA 90048 USA. [Grunseich, Christopher; Shi, Yijun; Mooney, Michael; Fischbeck, Kenneth H.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 719 BP S277 EP S278 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300710 ER PT J AU Jung, M Winkler, T Donaires, FS Hong, SG Hsu, AP Hickstein, DD Holland, SM Dunbar, CE AF Jung, Moonjung Winkler, Thomas Donaires, Flavia S. Hong, So Gun Hsu, Amy P. Hickstein, Dennis D. Holland, Steven M. Dunbar, Cynthia E. TI Induced Pluripotent Stem Cells from a Patient with GATA2 Deficiency Display a Block in Hematopoietic Differentiation SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Jung, Moonjung; Winkler, Thomas; Donaires, Flavia S.; Hong, So Gun; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Hsu, Amy P.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Hickstein, Dennis D.] NCI, Dept Expt Transplantat & Immunol, NIH, Bethesda, MD 20892 USA. RI Sacilotto Donaires, Flavia/R-9719-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 207 BP S79 EP S79 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300207 ER PT J AU Kochenderfer, JN Kassim, SH Somerville, R Dudley, ME Carpenter, RO Lu, L Feldman, SA Morton, KE Toomey, MA Rosenberg, SA AF Kochenderfer, James N. Kassim, Sadik H. Somerville, Robert Dudley, Mark E. Carpenter, Robert O. Lu, Lily Feldman, Steven A. Morton, Kathleen E. Toomey, Mary Ann Rosenberg, Steven A. TI Treatment of Chemotherapy-Refractory B-Cell Malignancies with Anti-CD19 Chimeric Antigen Receptor T Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Kochenderfer, James N.; Carpenter, Robert O.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Kassim, Sadik H.; Somerville, Robert; Dudley, Mark E.; Lu, Lily; Feldman, Steven A.; Morton, Kathleen E.; Toomey, Mary Ann; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 765 BP S295 EP S295 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300756 ER PT J AU Kouprina, N Larionov, V AF Kouprina, Natalay Larionov, Vladimir TI Human Artificial Chromosomes or HAC-Based Gene Delivery Vectors for Biomedicine and Biotechnology SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Kouprina, Natalay; Larionov, Vladimir] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 95 BP S36 EP S36 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300095 ER PT J AU Lynn, RC Poussin, M Low, PS Dimitrov, DS Powell, DJ AF Lynn, Rachel C. Poussin, Mathilde Low, Phillip S. Dimitrov, Dimiter S. Powell, Daniel J., Jr. TI FR beta-Directed CAR T Cell Therapy for AML Can Be Enhanced By ATRA Co-Treatment SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Lynn, Rachel C.; Poussin, Mathilde; Powell, Daniel J., Jr.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, OCRC,Abramson Canc Ctr, Philadelphia, PA USA. [Low, Phillip S.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Dimitrov, Dimiter S.] NCI, Prot Interact Grp, CCR Nanobiol Program, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 159 BP S60 EP S60 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300159 ER PT J AU Mao, L Shen, FX Choi, EJ Lawton, MT Scaria, A Colosi, P Pechan, P Wu, ZJ Su, H AF Mao, Lei Shen, Fanxia Choi, Eun-Jung Lawton, Michael T. Scaria, Abraham Colosi, Peter Pechan, Peter Wu, Zhijian Su, Hua TI AAV-sFLT Inhibits and Reverses Brain Arteriovenous Malformation Phenotype in Mice SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Mao, Lei; Shen, Fanxia; Choi, Eun-Jung; Su, Hua] Univ Calif San Francisco, Ctr Cerebrovasc Res, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [Lawton, Michael T.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Scaria, Abraham; Pechan, Peter] Sanofi Genzyme R&D Ctr, Framingham, MA USA. [Colosi, Peter; Wu, Zhijian] NEI, Ocular Gene Therapy Core, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 267 BP S102 EP S102 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300267 ER PT J AU Mattoo, AR Thorgeirsson, SS Jessup, JM AF Mattoo, Abid R. Thorgeirsson, Snorri S. Jessup, J. M. TI Lessons Learned From TALEN Knockout of NANOG in Colorectal Carcinoma (CRC) Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Mattoo, Abid R.; Thorgeirsson, Snorri S.; Jessup, J. M.] NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 561 BP S217 EP S218 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300556 ER PT J AU Mattoo, AR Korokhov, N Jessup, JM AF Mattoo, Abid R. Korokhov, Nikolay Jessup, J. M. TI Lentiviral Delivered shRNA Inhibition of NANOGP8 or NANOG Activates the Intrinsic Pathway of Apoptosis In Vivo and In Vitro SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Mattoo, Abid R.; Korokhov, Nikolay; Jessup, J. M.] NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 455 BP S174 EP S174 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300450 ER PT J AU Mookherjee, S Colosi, P Hiriyanna, S Kaneshiro, K Li, LJ Qian, HH Li, TS Khanna, H Swaroop, A Wu, ZJ AF Mookherjee, Suddhasil Colosi, Peter Hiriyanna, Suja Kaneshiro, Kayleigh Li, Linjing Qian, Haohua Li, Tiansen Khanna, Hemant Swaroop, Anand Wu, Zhijian TI A Long-Term Study of AAV Vector-Mediated Gene Therapy for X-linked Retinitis Pigmentosa (XLRP) Due to RP2 Mutation SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Mookherjee, Suddhasil; Colosi, Peter; Hiriyanna, Suja; Kaneshiro, Kayleigh; Qian, Haohua; Li, Tiansen; Swaroop, Anand; Wu, Zhijian] NEI, NIH, Bethesda, MD 20892 USA. [Li, Linjing; Khanna, Hemant] Univ Massachusetts, Sch Med, Dept Ophthalmol, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 122 BP S46 EP S46 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300122 ER PT J AU Peterson, L Burke, JD Jagadeesh, GJ Myung, S Garrett, L Pourebrahim, R Davis, BR Candotti, F AF Peterson, Lisa Burke, J. Douglas Jagadeesh, G. Jaya Myung, Sangho Garrett, Lisa Pourebrahim, Rasoul Davis, Brian R. Candotti, Fabio TI Comparison of Gene Editing Strategies for Gene Correction of Wiskott-Aldrich Syndrome in Mouse Embryonic Stem Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Peterson, Lisa] Walter Reed Natl Mil Med Ctr, Dept Neonatol, Bethesda, MD USA. [Peterson, Lisa; Burke, J. Douglas; Jagadeesh, G. Jaya; Myung, Sangho; Candotti, Fabio] NIH, Bethesda, MD 20892 USA. [Garrett, Lisa] NIH, Transgen Stem Cell Core, Bethesda, MD 20892 USA. [Pourebrahim, Rasoul; Davis, Brian R.] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 558 BP S216 EP S217 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300553 ER PT J AU Richie, CT Simons-Wires, EM Trychta, KA Harvey, BK Henderson, MJ AF Richie, Christopher T. Simons-Wires, Emily M. Trychta, Kathleen A. Harvey, Brandon K. Henderson, Mark J. TI SERCaMP: A Secreted Reporter Protein to Monitor Perturbations in Endoplasmic Reticulum Calcium Homeostasis SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Richie, Christopher T.; Simons-Wires, Emily M.; Trychta, Kathleen A.; Harvey, Brandon K.; Henderson, Mark J.] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 370 BP S141 EP S141 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300368 ER PT J AU Senac, JS Venditti, CP AF Senac, Julien S. Venditti, Charles P. TI In Vivo Interallelic Complementation Assay at the Mut Locus With Adeno-Associated (AAV) Viral Gene Delivery SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Senac, Julien S.; Venditti, Charles P.] NHGRI, NIH, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 361 BP S137 EP S138 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300359 ER PT J AU Shaw, KL Sokolic, R Davila, A Silvin, C Garabedian, E de Oliveira, S Barman, P Brown, B Carbonaro, D Geiger, S Mishra, S Smogorzewska, M Jagadeesh, J Hershfield, MS Wayne, A Crooks, GM Moore, T Candotti, F Kohn, DB AF Shaw, Kit L. Sokolic, Robert Davila, Alejandra Silvin, Christopher Garabedian, Elizabeth de Oliveira, Satiro Barman, Provaboti Brown, Berkley Carbonaro, Denise Geiger, Sabine Mishra, Suparna Smogorzewska, Monika Jagadeesh, Jayashree Hershfield, Michael S. Wayne, Alan Crooks, Gay M. Moore, Theodore Candotti, Fabio Kohn, Donald B. TI Phase II Clinical Trial of Gene Therapy for Adenosine Deaminase-Deficient Severe Combined Immune Deficiency (ADA-SCID) SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Shaw, Kit L.; Davila, Alejandra; de Oliveira, Satiro; Barman, Provaboti; Brown, Berkley; Carbonaro, Denise; Geiger, Sabine; Mishra, Suparna; Crooks, Gay M.; Moore, Theodore; Kohn, Donald B.] Univ Calif Los Angeles, Los Angeles, CA USA. [Sokolic, Robert; Silvin, Christopher; Garabedian, Elizabeth; Jagadeesh, Jayashree; Wayne, Alan; Candotti, Fabio] NIH, Bethesda, MD 20892 USA. [Smogorzewska, Monika] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Hershfield, Michael S.] Duke Univ, Durham, NC USA. RI De Oliveira, Satiro/D-8860-2014 OI De Oliveira, Satiro/0000-0002-8181-7316 NR 0 TC 1 Z9 1 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 279 BP S107 EP S107 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300279 ER PT J AU Sloan, JL Manoli, I Harrington, E Chandler, RJ Schneider, M Calcedo, R Wilson, JM Venditti, CP AF Sloan, Jennifer L. Manoli, Irini Harrington, Elizabeth Chandler, Randy J. Schneider, Mark Calcedo, Roberto Wilson, James M. Venditti, Charles P. TI Neutralizing Antibodies Against AAV Capsids in Patients with Mut Methylmalonic Acidemia (MMA) SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Sloan, Jennifer L.; Manoli, Irini; Harrington, Elizabeth; Chandler, Randy J.; Venditti, Charles P.] NHGRI, Organ Acid Res Sect, NIH, Bethesda, MD 20892 USA. [Schneider, Mark; Calcedo, Roberto; Wilson, James M.] Univ Penn, Dept Pathol & Lab Med, Gene Therapy Program, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 192 BP S73 EP S73 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300192 ER PT J AU Smith, JB Lanitis, E Dangaj, D Flingai, S Poussin, M Xu, SW Czerniecki, BJ Li, YF Robbins, PF Powell, DJ AF Smith, Jenessa B. Lanitis, Evripidis Dangaj, Denarda Flingai, Seleeke Poussin, Mathilde Xu, Shuwen Czerniecki, Brian J. Li, Yong F. Robbins, Paul F. Powell, Daniel J. TI A Human HER2-Specific TCR Confers Potent Anti-Tumor Effector Functions in Genetically Engineered Primary Cytotoxic Lymphocytes SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Smith, Jenessa B.; Lanitis, Evripidis; Dangaj, Denarda; Flingai, Seleeke; Poussin, Mathilde; Powell, Daniel J.] Univ Penn, Dept Obstet & Gynecol, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA. [Powell, Daniel J.] Univ Penn, Dept Pathol & Lab Med, Abramson Canc Ctr, Philadelphia, PA USA. [Xu, Shuwen; Czerniecki, Brian J.] Univ Penn, Med Ctr, Dept Surg, Philadelphia, PA 19104 USA. [Li, Yong F.; Robbins, Paul F.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 429 BP S164 EP S165 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300424 ER PT J AU Uchida, N Platner, C Weitzel, RP Bonifacino, A Price, S Krouse, A Metzger, M Donahue, R Tisdale, J AF Uchida, Naoya Platner, Charlotte Weitzel, R. Patrick Bonifacino, Aylin Price, Sandra Krouse, Allen Metzger, Mark Donahue, Robert Tisdale, John TI Evaluation of Lentiviral Transduction Between Steady State Bone Marrow CD34+Cells and Mobilized CD34+Cells in Rhesus Gene Therapy Model SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Uchida, Naoya; Platner, Charlotte; Weitzel, R. Patrick; Tisdale, John] NHLBI NIDDK, MCHB, NIH, Bethesda, MD USA. [Bonifacino, Aylin; Price, Sandra; Krouse, Allen; Metzger, Mark; Donahue, Robert] NHLBI, Hematol Branch, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 548 BP S213 EP S213 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300543 ER PT J AU Valdmanis, PN Gu, S Lisowski, L Jin, L Chu, K Zhang, FJ Huang, Y Kay, MA AF Valdmanis, Paul N. Gu, Shuo Lisowski, Leszek Jin, Lan Chu, Kirk Zhang, Feijie Huang, Yong Kay, Mark A. TI Evaluating Competition of Delivered Small Hairpin RNAs with Endogenous microRNAs for Safe Effective Gene Knockdown SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Valdmanis, Paul N.; Lisowski, Leszek; Chu, Kirk; Zhang, Feijie; Huang, Yong; Kay, Mark A.] Stanford Univ, Stanford, CA 94305 USA. [Gu, Shuo; Jin, Lan] NCI, Ctr Canc Res, Frederick, MD 21701 USA. RI Gu, Shuo/K-5404-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 534 BP S208 EP S208 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300529 ER PT J AU Wu, ZJ Hiriyanna, S Qian, HH Mookherjee, S Kaneshiro, K Campos, M Gao, C Fariss, R Li, TS Colosi, P Swaroop, A AF Wu, Zhijian Hiriyanna, Suja Qian, Haohua Mookherjee, Suddhasil Kaneshiro, Kayleigh Campos, Maria Gao, Chun Fariss, Robert Li, Tiansen Colosi, Peter Swaroop, Anand TI Gene Therapy for X-Linked Retinitis Pigmentosa: A Long-Term Efficacy Study in a Mouse Model of RPGR Deficiency SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Wu, Zhijian; Hiriyanna, Suja; Qian, Haohua; Mookherjee, Suddhasil; Kaneshiro, Kayleigh; Campos, Maria; Gao, Chun; Fariss, Robert; Li, Tiansen; Colosi, Peter; Swaroop, Anand] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 537 BP S209 EP S209 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300532 ER PT J AU Xu, WQ Blankenship, T Eiden, MV AF Xu, Wenqin Blankenship, Tiffany Eiden, Maribeth V. TI Engineering a Novel Retroviral Envelope to Retarget Retroviral Vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Xu, Wenqin; Blankenship, Tiffany; Eiden, Maribeth V.] NIH, Sect Directed Gene Transfer, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 58 BP S23 EP S23 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300058 ER PT J AU Zhou, S Tang, CL Rapp, S Bonner, MA De Ravin, SS Malech, HL Sorrentino, BP AF Zhou, Sheng Tang, Chunlao Rapp, Samuel Bonner, Melissa A. De Ravin, Suk See Malech, Harry L. Sorrentino, Brian P. TI A Novel Non-Restrictive, Semi-Quantitative Method for Vector Insertion Site Analysis Based on Random Shearing of Genomic DNA SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 21-24, 2014 CL Washington, DC SP Amer Soc Gene & Cell Therapy, Genzyme C1 [Zhou, Sheng; Tang, Chunlao; Rapp, Samuel; Bonner, Melissa A.; Sorrentino, Brian P.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [De Ravin, Suk See; Malech, Harry L.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2014 VL 22 SU 1 MA 542 BP S211 EP S211 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI9ED UT WOS:000337231300537 ER PT J AU Mann, ZF Thiede, BR Chang, W Shin, JB May-Simera, HL Lovett, M Corwin, JT Kelley, MW AF Mann, Zoe F. Thiede, Benjamin R. Chang, Weise Shin, Jung-Bum May-Simera, Helen L. Lovett, Michael Corwin, Jeffrey T. Kelley, Matthew W. TI A gradient of Bmp7 specifies the tonotopic axis in the developing inner ear SO NATURE COMMUNICATIONS LA English DT Article ID ACTIVATED POTASSIUM CHANNELS; HAIR CELL REGENERATION; SUPPORTING CELLS; ACTIN-FILAMENTS; BASILAR PAPILLA; LATERAL INHIBITION; BIRD COCHLEA; EXPRESSION; STEREOCILIA; CHICK AB The auditory systems of animals that perceive sounds in air are organized to separate sound stimuli into their component frequencies. Individual tones then stimulate mechanosensory hair cells located at different positions on an elongated frequency (tonotopic) axis. During development, immature hair cells located along the axis must determine their tonotopic position in order to generate frequency-specific characteristics. Expression profiling along the developing tonotopic axis of the chick basilar papilla (BP) identified a gradient of Bmp7. Disruption of that gradient in vitro or in ovo induces changes in hair cell morphologies consistent with a loss of tonotopic organization and the formation of an organ with uniform frequency characteristics. Further, the effects of Bmp7 in determination of positional identity are shown to be mediated through activation of the Mapk, Tak1. These results indicate that graded, Bmp7-dependent, activation of Tak1 signalling controls the determination of frequency-specific hair cell characteristics along the tonotopic axis. C1 [Mann, Zoe F.; Chang, Weise; May-Simera, Helen L.; Kelley, Matthew W.] Natl Inst Deafness & Other Commun Disorders, Lab Cochlear Dev, NIH, Bethesda, MD 20892 USA. [Thiede, Benjamin R.; Shin, Jung-Bum; Corwin, Jeffrey T.] Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA. [Lovett, Michael] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW3 6LY, England. RP Mann, ZF (reprint author), Natl Inst Deafness & Other Commun Disorders, Lab Cochlear Dev, NIH, 35A Convent Dr, Bethesda, MD 20892 USA. EM mannz@nidcd.nih.gov; kelleymt@nidcd.nih.gov FU Intramural Research Program at NIDCD [1RC1DC010677]; American Hearing Research Foundation [R01-DC000200]; NRSA [F31 DC012485] FX We thank Tom Coate and Jonathan Bird for technical assistance and Mark Warchol and Thomas Friedman for providing comments on an earlier version of the manuscript. This project was supported by funds from the Intramural Research Program at NIDCD to M.W.K., grant 1RC1DC010677 (NIDCD) to M.L., a grant from the American Hearing Research Foundation to M.L., NIDCD NIH grant R01-DC000200 to J.T.C. and NRSA F31 DC012485 to B.T. NR 58 TC 13 Z9 13 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAY PY 2014 VL 5 AR 3839 DI 10.1038/ncomms4839 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AJ0VE UT WOS:000337373500001 PM 24845721 ER PT J AU Thiede, BR Mann, ZF Chang, WS Ku, YC Son, YK Lovett, M Kelley, MW Corwin, JT AF Thiede, Benjamin R. Mann, Zoe F. Chang, Weise Ku, Yuan-Chieh Son, Yena K. Lovett, Michael Kelley, Matthew W. Corwin, Jeffrey T. TI Retinoic acid signalling regulates the development of tonotopically patterned hair cells in the chicken cochlea SO NATURE COMMUNICATIONS LA English DT Article ID DEVELOPING INNER-EAR; ACTIN CROSS-LINKER; BIRD COCHLEA; RNA-SEQ; STEREOCILIA; EXPRESSION; FILAMENTS; ORGAN; ESPIN; CORTI AB Precise frequency discrimination is a hallmark of auditory function in birds and mammals and is required for distinguishing similar sounding words, like 'bat,' 'cat' and 'hat.' In the cochlea, tuning and spectral separation result from longitudinal differences in basilar membrane stiffness and numerous individual gradations in sensory hair cell phenotypes, but it is unknown what patterns the phenotypes. Here we used RNA-seq to compare transcriptomes from proximal, middle and distal regions of the embryonic chicken cochlea, and found opposing longitudinal gradients of expression for retinoic acid (RA)-synthesizing and degrading enzymes. In vitro experiments showed that RA is necessary and sufficient to induce the development of distal-like hair cell phenotypes and promotes expression of the actin-crosslinking proteins, Espin and Fscn2. These and other findings highlight a role for RA signalling in patterning the development of a longitudinal gradient of frequency-tuned hair cell phenotypes in the cochlea. C1 [Thiede, Benjamin R.; Son, Yena K.; Corwin, Jeffrey T.] Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA. [Mann, Zoe F.; Chang, Weise; Kelley, Matthew W.] Natl Inst Deafness & Other Commun Disorders, Lab Cochlear Dev, NIH, Bethesda, MD 20892 USA. [Ku, Yuan-Chieh; Lovett, Michael] Washington Univ, Sch Med, Dept Genet, Div Human Genet, St Louis, MO 63110 USA. [Corwin, Jeffrey T.] Univ Virginia, Sch Med, Dept Cell Biol, Charlottesville, VA 22908 USA. RP Corwin, JT (reprint author), Univ Virginia, Sch Med, Dept Neurosci, 409 Lane Rd, Charlottesville, VA 22908 USA. EM jtc2k@virginia.edu FU National Institutes of Health [RO1 DC000200, RC1 DC010677, F31 DC012485]; American Hearing Research Foundation FX We thank James Pagana, Wendy Baker and Jung-Bum Shin for technical advice. This work was supported by grants from the National Institutes of Health RO1 DC000200 (J.T.C.), RC1 DC010677 (M.L.), F31 DC012485 (B.R.T.) and the American Hearing Research Foundation (M.L.). NR 64 TC 9 Z9 9 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAY PY 2014 VL 5 AR 3840 DI 10.1038/ncomms4840 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AJ0VE UT WOS:000337373500002 PM 24845860 ER PT J AU Tan, F Thiele, CJ Li, ZJ AF Tan, Fei Thiele, Carol J. Li, Zhijie TI Collapsin response mediator proteins: Potential diagnostic and prognostic biomarkers in cancers SO ONCOLOGY LETTERS LA English DT Review DE collapsin response mediator proteins; biomarker; tumor suppressor; metastasis ID TISSUE GROWTH-FACTOR; DEVELOPING RAT-BRAIN; CELL LUNG-CANCER; UNC-33-LIKE PHOSPHOPROTEIN; AXON GUIDANCE; MOLECULAR CHARACTERIZATION; NEURONAL DIFFERENTIATION; GLIOBLASTOMA-MULTIFORME; CAENORHABDITIS-ELEGANS; NEURITE OUTGROWTH AB The collapsin response mediator proteins (CRMPs) were originally identified as mediators of semaphorin 3A signaling and neuronal differentiation. The CRMP family consists of five homologous cytosolic proteins, CRMP1-5. Altered expression levels of CRMPs have been observed in several malignant tumors, including lung, breast, colorectal, prostate, pancreatic and neuroendocrine lung cancer. The aim of the current study was to review the recent progress achieved in understanding the association between the different levels of CRMP expression in tumors and their involvement in pathological functions, such as tumor metastasis, disease progression, subtype differentiation and clinical outcome, to address the potential value of CRMPs as biomarkers for the diagnosis and prognosis of cancer patients. C1 [Tan, Fei] China Med Univ, Dept Neurol, Shengjing Hosp, Shenyang 110004, Liaoning, Peoples R China. [Thiele, Carol J.] NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Li, Zhijie] China Med Univ, Med Res Ctr, Shengjing Hosp, Shenyang 110004, Liaoning, Peoples R China. RP Li, ZJ (reprint author), China Med Univ, Med Res Ctr, Shengjing Hosp, 36 Sanhao St, Shenyang 110004, Liaoning, Peoples R China. EM lizhijie68@hotmail.com FU National Natural Science Foundation of China [81272538]; Society Development Foundation of Liaoning Province [201225016] FX This study was supported by the National Natural Science Foundation of China (no. 81272538) and the Society Development Foundation of Liaoning Province (no. 201225016). NR 63 TC 4 Z9 4 U1 0 U2 6 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1792-1074 EI 1792-1082 J9 ONCOL LETT JI Oncol. Lett. PD MAY PY 2014 VL 7 IS 5 BP 1333 EP 1340 DI 10.3892/ol:2014.1909 PG 8 WC Oncology SC Oncology GA AJ3HV UT WOS:000337558000002 ER PT J AU Charles, RC Hilaire, IJ Mayo-Smith, LM Teng, JE Jerome, JG Franke, MF Saha, A Yu, YN Kovac, P Calderwood, SB Ryan, ET LaRocque, RC Almazor, CP Qadri, F Ivers, LC Harris, JB AF Charles, Richelle C. Hilaire, Isabelle J. Mayo-Smith, Leslie M. Teng, Jessica E. Jerome, J. Gregory Franke, Molly F. Saha, Amit Yu, Yanan Kovac, Paul Calderwood, Stephen B. Ryan, Edward T. LaRocque, Regina C. Almazor, Charles P. Qadri, Firdausi Ivers, Louise C. Harris, Jason B. TI Immunogenicity of a Killed Bivalent (O1 and O139) Whole Cell Oral Cholera Vaccine, Shanchol, in Haiti SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID FIELD-TRIAL; BLOOD-GROUP; BANGLADESH; RESPONSES; ANTIBODY; CHILDREN; INFECTION; EFFICACY; ANTIGEN; SPECIFICITY AB Background: Studies of the immunogenicity of the killed bivalent whole cell oral cholera vaccine, Shanchol, have been performed in historically cholera-endemic areas of Asia. There is a need to assess the immunogenicity of the vaccine in Haiti and other populations without historical exposure to Vibrio cholerae. Methodology/Principal Findings: We measured immune responses after administration of Shanchol, in 25 adults, 51 older children (6-17 years), and 47 younger children (1-5 years) in Haiti, where cholera was introduced in 2010. A >= 4-fold increase in vibriocidal antibody titer against V. cholerae O1 Ogawa was observed in 91% of adults, 74% of older children, and 73% of younger children after two doses of Shanchol; similar responses were observed against the Inaba serotype. A >= 2-fold increase in serum O-antigen specific polysaccharide IgA antibody levels against V. cholerae O1 Ogawa was observed in 59% of adults, 45% of older children, and 61% of younger children; similar responses were observed against the Inaba serotype. We compared immune responses in Haitian individuals with age-and blood group-matched individuals from Bangladesh, a historically cholera-endemic area. The geometric mean vibriocidal titers after the first dose of vaccine were lower in Haitian than in Bangladeshi vaccinees. However, the mean vibriocidal titers did not differ between the two groups after the second dose of the vaccine. Conclusions/Significance: A killed bivalent whole cell oral cholera vaccine, Shanchol, is highly immunogenic in Haitian adults and children. A two-dose regimen may be important in Haiti, and other populations lacking previous repeated exposures to V. cholerae. C1 [Charles, Richelle C.; Mayo-Smith, Leslie M.; Yu, Yanan; Calderwood, Stephen B.; Ryan, Edward T.; LaRocque, Regina C.; Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.; LaRocque, Regina C.; Ivers, Louise C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hilaire, Isabelle J.; Teng, Jessica E.; Jerome, J. Gregory; Franke, Molly F.; Almazor, Charles P.; Ivers, Louise C.] Partners Hlth, Boston, MA USA. [Teng, Jessica E.; Ivers, Louise C.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Franke, Molly F.; Ivers, Louise C.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Saha, Amit; Qadri, Firdausi] Icddr B, Dhaka, Bangladesh. [Kovac, Paul] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Charles, RC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM rccharles@mgh.harvard.edu; livers@pih.org; jbharris@mgh.harvard.edu FU National Institutes of Health, National Institute of Allergy and Infectious Diseases [R01 AI099243, AI077883, AI058935, AI106878, K08 AI089721]; Bill and Melinda Gates Foundation [OPP50419]; Massachusetts General Hospital Physician Scientist Development Award from Massachusetts General Hospital FX This work was supported by grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (R01 AI099243; JBH, LCI), (AI077883, AI058935, AI106878 ETR), and the Career Development Award (K08 AI089721; RCC); the Bill and Melinda Gates Foundation (OPP50419; FQ); and a Massachusetts General Hospital Physician Scientist Development Award from Massachusetts General Hospital (RCC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 12 Z9 12 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD MAY PY 2014 VL 8 IS 5 AR e2828 DI 10.1371/journal.pntd.0002828 PG 8 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AJ5OS UT WOS:000337735100025 PM 24786645 ER PT J AU Kamuyu, G Bottomley, C Mageto, J Lowe, B Wilkins, PP Noh, JC Nutman, TB Ngugi, AK Odhiambo, R Wagner, RG Kakooza-Mwesige, A Owusu-Agyei, S Ae-Ngibise, K Masanja, H Osier, FHA Odermatt, P Newton, CR AF Kamuyu, Gathoni Bottomley, Christian Mageto, James Lowe, Brett Wilkins, Patricia P. Noh, John C. Nutman, Thomas B. Ngugi, Anthony K. Odhiambo, Rachael Wagner, Ryan G. Kakooza-Mwesige, Angelina Owusu-Agyei, Seth Ae-Ngibise, Kenneth Masanja, Honorati Osier, Faith H. A. Odermatt, Peter Newton, Charles R. CA Epidemiology Epilepsy Demographic TI Exposure to Multiple Parasites Is Associated with the Prevalence of Active Convulsive Epilepsy in Sub-Saharan Africa SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID TOXOPLASMA-GONDII; ONCHOCERCA-VOLVULUS; CRYPTOGENIC EPILEPSY; RURAL TANZANIA; RISK-FACTORS; NEUROCYSTICERCOSIS; TOXOCARIASIS; CYSTICERCOSIS; INFECTION; RESPONSES AB Background: Epilepsy is common in developing countries, and it is often associated with parasitic infections. We investigated the relationship between exposure to parasitic infections, particularly multiple infections and active convulsive epilepsy (ACE), in five sites across sub-Saharan Africa. Methods and Findings: A case-control design that matched on age and location was used. Blood samples were collected from 986 prevalent cases and 1,313 age-matched community controls and tested for presence of antibodies to Onchocerca volvulus, Toxocara canis, Toxoplasma gondii, Plasmodium falciparum, Taenia solium and HIV. Exposure (seropositivity) to Onchocerca volvulus (OR = 1.98; 95% CI: 1.52-2.58, p<0.001), Toxocara canis (OR = 1.52; 95% CI: 1.23-1.87, p<0.001), Toxoplasma gondii (OR = 1.28; 95% CI: 1.04-1.56, p=0.018) and higher antibody levels (top tertile) to Toxocara canis (OR = 1.70; 95% CI: 1.30-2.24, p<0.001) were associated with an increased prevalence of ACE. Exposure to multiple infections was common (73.8% of cases and 65.5% of controls had been exposed to two or more infections), and for T. gondii and O. volvulus co-infection, their combined effect on the prevalence of ACE, as determined by the relative excess risk due to interaction (RERI), was more than additive (T. gondii and O. volvulus, RERI = 1.19). The prevalence of T. solium antibodies was low (2.8% of cases and 2.2% of controls) and was not associated with ACE in the study areas. Conclusion: This study investigates how the degree of exposure to parasites and multiple parasitic infections are associated with ACE and may explain conflicting results obtained when only seropositivity is considered. The findings from this study should be further validated. C1 [Kamuyu, Gathoni; Mageto, James; Lowe, Brett; Ngugi, Anthony K.; Odhiambo, Rachael; Osier, Faith H. A.; Newton, Charles R.] KEMRI Wellcome Trust Res Programme, Ctr Geog Med Res Coast, Kilifi, Kenya. [Kamuyu, Gathoni; Lowe, Brett; Ngugi, Anthony K.; Kakooza-Mwesige, Angelina; Newton, Charles R.] Studies Epidemiol Epilepsy Demog Surveillance Sys, Accra, Ghana. [Bottomley, Christian] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, Dept Infect Dis Epidemiol, London WC1, England. [Bottomley, Christian] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, MRC Trop Epidemiol Grp, London WC1, England. [Bottomley, Christian] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London WC1, England. [Mageto, James] Egerton Univ, Nakuru, Kenya. [Lowe, Brett] Univ Oxford, Nuffield Dept Clin Med, Oxford, England. [Wilkins, Patricia P.; Noh, John C.] Ctr Dis Control & Prevent CDC, Div Parasit Dis & Malaria, Atlanta, GA USA. [Nutman, Thomas B.] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. [Ngugi, Anthony K.] Aga Khan Univ East Africa, Fac Hlth Sci, Res Support Unit, Nairobi, Kenya. [Wagner, Ryan G.] Univ Witwatersrand, Fac Hlth Sci, Sch Publ Hlth, MRC Wits Rural Publ Hlth & Hlth Transit Res Unit, Johannesburg, South Africa. [Wagner, Ryan G.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Kakooza-Mwesige, Angelina] Iganga Mayuge Hlth & Demog Surveillance Syst, Iganga, Uganda. [Kakooza-Mwesige, Angelina] Makerere Univ, Coll Hlth Sci, Dept Paediat & Child Hlth, Kampala, Uganda. [Owusu-Agyei, Seth; Ae-Ngibise, Kenneth] Kintampo Hlth Res Ctr, Kintampo, Ghana. [Masanja, Honorati] Ifakara Hlth Inst, Ifakara, Tanzania. [Odermatt, Peter] Swiss Trop & Publ Hlth Inst, Basel, Switzerland. [Odermatt, Peter] Unvers Basel, Basel, Switzerland. [Newton, Charles R.] UCL Inst Child Hlth, Neurosci Unit, London, England. [Newton, Charles R.] London Sch Hyg & Trop Med, Clin Res Unit, London WC1, England. [Newton, Charles R.] Univ Oxford, Dept Psychiat, Oxford, England. RP Kamuyu, G (reprint author), KEMRI Wellcome Trust Res Programme, Ctr Geog Med Res Coast, Kilifi, Kenya. EM GKamuyu@kemri-wellcome.org RI Sander, Josemir/C-1576-2008; Odermatt, Peter/K-7727-2015; OI Sander, Josemir/0000-0001-6041-9661; Odermatt, Peter/0000-0002-0296-2508; Osier, Faith/0000-0001-7133-5375; Newton, Charles/0000-0002-6999-5507 FU Wellcome Trust through a Wellcome Trust Senior Fellowship in Clinical Tropical Medicine [083744]; Wellcome Trust through a strategic training award [084538]; Wellcome Trust Master's Training Fellowship [096392] FX The Wellcome Trust funded this research through a Wellcome Trust Senior Fellowship in Clinical Tropical Medicine (No. 083744 to CRN), and supported GK to write up this work through a strategic training award (No. 084538) and a Wellcome Trust Master's Training Fellowship (No. 096392) to KEMRI-Wellcome Trust Research Programme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 20 Z9 20 U1 0 U2 18 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD MAY PY 2014 VL 8 IS 5 AR e2908 DI 10.1371/journal.pntd.0002908 PG 10 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AJ5OS UT WOS:000337735100075 PM 24875312 ER PT J AU Rivoire, BL Groathouse, NA TerLouw, S Neupane, KD Ranjit, C Sapkota, BR Khadge, S Kunwar, CB Macdonald, M Hawksworth, R Thapa, MB Hagge, DA Tibbals, M Smith, C Dube, T She, DW Wolff, M Zhou, E Makhene, M Mason, R Sizemore, C Brennan, PJ AF Rivoire, Becky L. Groathouse, Nathan A. TerLouw, Stephen Neupane, Kapil Dev Ranjit, Chaman Sapkota, Bishwa Raj Khadge, Saraswoti Kunwar, Chatra B. Macdonald, Murdo Hawksworth, Rachel Thapa, Min B. Hagge, Deanna A. Tibbals, Melinda Smith, Carol Dube, Tina She, Dewei Wolff, Mark Zhou, Eric Makhene, Mamodikoe Mason, Robin Sizemore, Christine Brennan, Patrick J. TI Safety and Efficacy Assessment of Two New Leprosy Skin Test Antigens: Randomized Double Blind Clinical Study SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID DELAYED-TYPE HYPERSENSITIVITY; LEPRAE SOLUBLE-ANTIGENS; MYCOBACTERIUM-LEPRAE; ENVIRONMENTAL MYCOBACTERIA; ENDEMIC POPULATION; TUBERCULOSIS; CONTACTS; LIPOARABINOMANNAN; DIAGNOSIS; TRIAL AB Background: New tools are required for the diagnosis of pre-symptomatic leprosy towards further reduction of disease burden and its associated reactions. To address this need, two new skin test antigens were developed to assess safety and efficacy in human trials. Methods: A Phase I safety trial was first conducted in a non-endemic region for leprosy (U. S. A.). Healthy non-exposed subjects (n = 10) received three titrated doses (2.5 mu g, 1.0 mu g and 0.1 mu g) of MLSA-LAM (n = 5) or MLCwA (n = 5) and control antigens [Rees MLSA (1.0 mu g) and saline]. A randomized double blind Phase II safety and efficacy trial followed in an endemic region for leprosy (Nepal), but involved only the 1.0 mg (high dose) and 0.1 mu g (low dose) of each antigen; Tuberculin PPD served as a control antigen. This Phase II safety and efficacy trial consisted of three Stages: Stage A and B studies were an expansion of Phase I involving 10 and 90 subjects respectively, and Stage C was then conducted in two parts (high dose and low dose), each enrolling 80 participants: 20 borderline lepromatous/lepromatous (BL/LL) leprosy patients, 20 borderline tuberculoid/tuberculoid (BT/TT) leprosy patients, 20 household contacts of leprosy patients (HC), and 20 tuberculosis (TB) patients. The primary outcome measure for the skin test was delayed type hypersensitivity induration. Findings: In the small Phase I safety trial, reactions were primarily against the 2.5 mu g dose of both antigens and Rees control antigen, which were then excluded from subsequent studies. In the Phase II, Stage A/B ramped-up safety study, 26% of subjects (13 of 50) showed induration against the high dose of each antigen, and 4% (2 of 50) reacted to the low dose of MLSA-LAM. Phase II, Stage C safety and initial efficacy trial showed that both antigens at the low dose exhibited low sensitivity at 20% and 25% in BT/TT leprosy patients, but high specificity at 100% and 95% compared to TB patients. The high dose of both antigens showed lower specificity (70% and 60%) and sensitivity (10% and 15%). BL/LL leprosy patients were anergic to the leprosy antigens. Interpretation: MLSA-LAM and MLCwA at both high (1.0 mu g) and low (0.1 mu g) doses were found to be safe for use in humans without known exposure to leprosy and in target populations. At a sensitivity rate of 20-25% these antigens are not suitable as a skin test for the detection of the early stages of leprosy infection; however, the degree of specificity is impressive given the presence of cross-reactive antigens in these complex native M. leprae preparations. C1 [Rivoire, Becky L.; Groathouse, Nathan A.; TerLouw, Stephen; Brennan, Patrick J.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. [Neupane, Kapil Dev; Ranjit, Chaman; Sapkota, Bishwa Raj; Khadge, Saraswoti; Kunwar, Chatra B.; Macdonald, Murdo; Hawksworth, Rachel; Thapa, Min B.; Hagge, Deanna A.] Anandaban Hosp, Mycobacterial Res Lab, Kathmandu, Nepal. [Tibbals, Melinda; Smith, Carol; Dube, Tina; She, Dewei; Wolff, Mark] EMMES Corp, Rockville, MD USA. [Zhou, Eric; Makhene, Mamodikoe; Mason, Robin; Sizemore, Christine] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. RP Rivoire, BL (reprint author), Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. EM brivoire@alumni.colostate.edu RI Sapkota, Bishwa/B-6403-2012; OI Hagge, Deanna A./0000-0002-3792-2266 FU NIH, NIAID [NO1 AI-25469, AI 082575] FX This work was funded by NIH, NIAID NO1 AI-25469 and NIH, NIAID AI 082575; website address: http://www.niaid.nih.gov/. The funder provided regulatory guidance, help with study design and management, and subcontracted data handling and site monitoring, but played no role in data analysis or preparation of the manuscript. NR 52 TC 2 Z9 2 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD MAY PY 2014 VL 8 IS 5 AR e2811 DI 10.1371/journal.pntd.0002811 PG 13 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AJ5OS UT WOS:000337735100018 PM 24874401 ER PT J AU VanWormer, E Miller, MA Conrad, PA Grigg, ME Rejmanek, D Carpenter, TE Mazet, JAK AF VanWormer, Elizabeth Miller, Melissa A. Conrad, Patricia A. Grigg, Michael E. Rejmanek, Daniel Carpenter, Tim E. Mazet, Jonna A. K. TI Using Molecular Epidemiology to Track Toxoplasma gondii from Terrestrial Carnivores to Marine Hosts: Implications for Public Health and Conservation SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID ENHYDRA-LUTRIS-NEREIS; SEA OTTERS; SOUTHERN CALIFORNIA; FRENCH-GUIANA; POPULATION-GENETICS; DISEASE ECOLOGY; DRINKING-WATER; MOUNTAIN LIONS; UNITED-STATES; OOCYSTS AB Background: Environmental transmission of the zoonotic parasite Toxoplasma gondii, which is shed only by felids, poses risks to human and animal health in temperate and tropical ecosystems. Atypical T. gondii genotypes have been linked to severe disease in people and the threatened population of California sea otters. To investigate land-to-sea parasite transmission, we screened 373 carnivores (feral domestic cats, mountain lions, bobcats, foxes, and coyotes) for T. gondii infection and examined the distribution of genotypes in 85 infected animals sampled near the sea otter range. Methodology/Principal Findings: Nested PCR-RFLP analyses and direct DNA sequencing at six independent polymorphic genetic loci (B1, SAG1, SAG3, GRA6, L358, and Apico) were used to characterize T. gondii strains in infected animals. Strains consistent with Type X, a novel genotype previously identified in over 70% of infected sea otters and four terrestrial wild carnivores along the California coast, were detected in all sampled species, including domestic cats. However, odds of Type X infection were 14 times higher (95% CI: 1.3-148.6) for wild felids than feral domestic cats. Type X infection was also linked to undeveloped lands (OR = 22, 95% CI: 2.3-250.7). A spatial cluster of terrestrial Type II infection (P = 0.04) was identified in developed lands bordering an area of increased risk for sea otter Type II infection. Two spatial clusters of animals infected with strains consistent with Type X (P <= 0.01) were detected in less developed landscapes. Conclusions: Differences in T. gondii genotype prevalence among domestic and wild felids, as well as the spatial distribution of genotypes, suggest co-existing domestic and wild T. gondii transmission cycles that likely overlap at the interface of developed and undeveloped lands. Anthropogenic development driving contact between these cycles may increase atypical T. gondii genotypes in domestic cats and facilitate transmission of potentially more pathogenic genotypes to humans, domestic animals, and wildlife. C1 [VanWormer, Elizabeth; Miller, Melissa A.; Conrad, Patricia A.; Rejmanek, Daniel; Mazet, Jonna A. K.] Univ Calif Davis, Sch Vet Med, Hlth Inst 1, Wildlife Hlth Ctr, Davis, CA 95616 USA. [Miller, Melissa A.] Calif Dept Fish & Wildlife, Marine Wildlife Vet Care & Res Ctr, Santa Cruz, CA USA. [Conrad, Patricia A.; Rejmanek, Daniel] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. [Grigg, Michael E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Carpenter, Tim E.] Massey Univ, EpiCtr, Palmerston North, New Zealand. RP VanWormer, E (reprint author), Univ Calif Davis, Sch Vet Med, Hlth Inst 1, Wildlife Hlth Ctr, Davis, CA 95616 USA. EM evanwormer@ucdavis.edu FU National Science Foundation Ecology of Infectious Disease Program [0525765, 1065990]; NIH; NIAID; UC Davis Wildlife Health Center FX Grants from the National Science Foundation Ecology of Infectious Disease Program (0525765, 1065990), the Intramural Research Program of the NIH and NIAID (MEG), and the UC Davis Wildlife Health Center supported this research. MEG is a scholar of the CIFAR Integrated Microbial Biodiversity Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 77 TC 10 Z9 10 U1 2 U2 65 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD MAY PY 2014 VL 8 IS 5 AR e2852 DI 10.1371/journal.pntd.0002852 PG 14 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AJ5OS UT WOS:000337735100046 PM 24874796 ER PT J AU Canna, SW AF Canna, Scott W. TI Interferon-gamma: Friend or Foe in Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still's Disease? SO ARTHRITIS & RHEUMATOLOGY LA English DT Editorial Material ID MACROPHAGE ACTIVATION SYNDROME; MICE; HEMOPHAGOCYTOSIS; SUBSETS; ANEMIA C1 [Canna, Scott W.] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Canna, SW (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, 10 Ctr Dr,Bldg 10,Room 13C103, Bethesda, MD 20892 USA. EM scott.canna@nih.gov OI Canna, Scott/0000-0003-3837-5337 NR 17 TC 6 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD MAY PY 2014 VL 66 IS 5 BP 1072 EP 1076 DI 10.1002/art.38362 PG 5 WC Rheumatology SC Rheumatology GA AJ0RM UT WOS:000337363400003 PM 24470448 ER PT J AU Golding, A Shavach, EM Hasni, S Illei, G AF Golding, Amit Shavach, Ethan M. Hasni, Sarfaraz Illei, Gabor TI FoxP3+Helios- Treg cells may play a critical role in maintaining immune homeostasis in systemic lupus erythematosus: comment on the article by Golding et al Reply SO ARTHRITIS & RHEUMATOLOGY LA English DT Letter C1 [Golding, Amit; Shavach, Ethan M.] NIAID, NIH, Bethesda, MD 20892 USA. [Hasni, Sarfaraz] Natl Inst Musculoskeletal & Skin Dis, NIH, Bethesda, MD USA. [Illei, Gabor] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Golding, A (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD MAY PY 2014 VL 66 IS 5 BP 1403 EP 1404 DI 10.1002/art.38377 PG 3 WC Rheumatology SC Rheumatology GA AJ0RM UT WOS:000337363400046 PM 24470345 ER PT J AU Gilman, JK Wright, M Lane, HC Schoomaker, EB AF Gilman, James K. Wright, Mary Lane, H. Clifford Schoomaker, Eric B. TI A MODEL OF FEDERAL INTERAGENCY COOPERATION: THE NATIONAL INTERAGENCY CONFEDERATION FOR BIOLOGICAL RESEARCH SO BIOSECURITY AND BIOTERRORISM-BIODEFENSE STRATEGY PRACTICE AND SCIENCE LA English DT Article AB The terrorist attacks of September 11 and the anthrax mailings a month later prompted a sweeping response by the federal government to improve the preparedness of the US to meet the potential threat posed by a terrorist using a biological agent. This response transcended traditional interagency boundaries, creating new opportunities while producing unique fiscal and leadership challenges. The National Interagency Confederation for Biological Research has made significant progress over the past 12 years because of its ability to adapt to the need for interagency cooperation and overcome many of these challenges. As construction of the National Interagency Biodefense Campus at Fort Detrick nears completion, the US has the capability to pursue a unique whole-of-government approach to the development of medical measures to counter the threat of bioterrorism. In addition to the high-level support of many in the federal government, the key success factors for this effort have been (1) a critical mass of leaders with the right leadership characteristics, (2) development of a compelling vision and accompanying narrative understood and articulated by all partnering organizations, and (3) recognition of the need for a partnership office to do the important communication and collaboration work in the organization to synchronize the information available to all the partners. The major barrier to interagency cooperative efforts of this kind is the inability to comingle funds from different appropriations. C1 [Gilman, James K.] Johns Hopkins Mil & Vet Hlth Inst, Glen Burnie, MD 21060 USA. [Wright, Mary; Lane, H. Clifford] NIAID, Div Clin Res, Bethesda, MD 20892 USA. [Schoomaker, Eric B.] Uniform Serv Univ Hlth Sci, Bethesda, MD USA. RP Gilman, JK (reprint author), Johns Hopkins Mil & Vet Hlth Inst, 6704 Curtis Court, Glen Burnie, MD 21060 USA. EM jgilman5@jhu.edu NR 2 TC 2 Z9 2 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1538-7135 EI 1557-850X J9 BIOSECUR BIOTERROR JI Biosecur. Bioterror. PD MAY-JUN PY 2014 VL 12 IS 3 BP 144 EP 150 DI 10.1089/bsp.2013.0084 PG 7 WC Public, Environmental & Occupational Health; International Relations SC Public, Environmental & Occupational Health; International Relations GA AI9BP UT WOS:000337221900004 PM 24819736 ER PT J AU Kosakowska-Cholody, T Lin, J Srideshikan, SM Scheffer, L Tarasova, NI Acharya, JK AF Kosakowska-Cholody, T. Lin, J. Srideshikan, S. M. Scheffer, L. Tarasova, N. I. Acharya, J. K. TI HKH40A downregulates GRP78/BiP expression in cancer cells SO CELL DEATH & DISEASE LA English DT Article DE HKH40A; GRP78/BiP; unfolded Protein Response (UPR); chemoresistance; cancer; paraptosis ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; HUMAN LUNG-CANCER; MICROSCALE THERMOPHORESIS; CLINICAL-SIGNIFICANCE; GROWTH-INHIBITION; HEPATOCELLULAR-CARCINOMA; BREAST-CANCER; UP-REGULATION; APOPTOSIS AB HKH40A, the 8-methoxy analog of WMC79, is a synthetic agent with promising in vitro and in vivo antitumor activity, especially against solid tumors. However, molecular mechanisms underlying its antitumor effects are poorly understood. Here, we report that HKH40A markedly reduces the level of GRP78/BiP protein in cancer cell lines of various origin. In this study, we show that HKH40A not only downregulates transcription of GRP78 but also directly binds to the isolated protein and induces its proteosomal degradation. Knockdown of BiP increased the efficacy of the drug and overexpression of BiP diminished its activity. BiP is generally highly elevated in solid tumors having a pivotal role in cancer cell survival and chemoresistance, and has been suggested as a novel target for therapeutic intervention. We show that reduction of BiP level by HKH40A impairs its function and induces unfolded protein response as evidenced by the activation of IRE1 alpha, ATF6 and PERK. This leads to a series of downstream events, including sustained eIF2 alpha phosphorylation, increased abundance of spliced XBP1 mRNA and protein levels of ATF4 and CHOP. We also demonstrate that HKH40A inhibited tumor formation in an in vivo xenograft tumor model. Collectively, our data show that HKH40A reduces BiP levels and this could have an important role in the activity of HKH40A against cancer cells. C1 [Kosakowska-Cholody, T.; Lin, J.; Srideshikan, S. M.; Scheffer, L.; Acharya, J. K.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. [Tarasova, N. I.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. RP Acharya, JK (reprint author), NCI, Lab Cell & Dev Signaling, Rm 22-90B,Bldg 560,1050 Boyles St, Frederick, MD 21702 USA. EM acharyaj@mail.nih.gov NR 49 TC 9 Z9 9 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD MAY PY 2014 VL 5 SI SI AR e1240 DI 10.1038/cddis.2014.203 PG 10 WC Cell Biology SC Cell Biology GA AI9DN UT WOS:000337229300040 PM 24853418 ER PT J AU Lu, H Fang, EF Sykora, P Kulikowicz, T Zhang, Y Becker, KG Croteau, DL Bohr, VA AF Lu, H. Fang, E. F. Sykora, P. Kulikowicz, T. Zhang, Y. Becker, K. G. Croteau, D. L. Bohr, V. A. TI Senescence induced by RECQL4 dysfunction contributes to Rothmund-Thomson syndrome features in mice SO CELL DEATH & DISEASE LA English DT Article DE RecQ helicase; RECQ4; RECQL4; senescence; Rothmund-Thomson syndrome; premature aging ID CELLULAR SENESCENCE; DNA-REPLICATION; WERNER-SYNDROME; GENOMIC INSTABILITY; HELICASE DOMAIN; GENE-PRODUCT; IN-VIVO; PROTEIN; FIBROBLASTS; STRESS AB Cellular senescence refers to irreversible growth arrest of primary eukaryotic cells, a process thought to contribute to aging-related degeneration and disease. Deficiency of RecQ helicase RECQL4 leads to Rothmund-Thomson syndrome (RTS), and we have investigated whether senescence is involved using cellular approaches and a mouse model. We first systematically investigated whether depletion of RECQL4 and the other four human RecQ helicases, BLM, WRN, RECQL1 and RECQL5, impacts the proliferative potential of human primary fibroblasts. BLM-, WRN- and RECQL4-depleted cells display increased staining of senescence-associated beta-galactosidase (SA-beta-gal), higher expression of p16(INK4a) or/and p21(WAF1) and accumulated persistent DNA damage foci. These features were less frequent in RECQL1-and RECQL5-depleted cells. We have mapped the region in RECQL4 that prevents cellular senescence to its N-terminal region and helicase domain. We further investigated senescence features in an RTS mouse model, Recql4-deficient mice (Recql4(HD)). Tail fibroblasts from Recql4(HD) showed increased SA-beta-gal staining and increased DNA damage foci. We also identified sparser tail hair and fewer blood cells in Recql4(HD) mice accompanied with increased senescence in tail hair follicles and in bone marrow cells. In conclusion, dysfunction of RECQL4 increases DNA damage and triggers premature senescence in both human and mouse cells, which may contribute to symptoms in RTS patients. C1 [Lu, H.; Fang, E. F.; Sykora, P.; Kulikowicz, T.; Croteau, D. L.; Bohr, V. A.] NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA. [Zhang, Y.; Becker, K. G.] NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, Room 06B133A,251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM vbohr@nih.gov FU Intramural Research Program of the NIH; NIA FX Mice were rederived from a pair of mice from Dr. Guangbin Luo of Case Western Reserve University. We thank Dr. Elin Lehrmann from the Microarray faculty of NIA for her assistance in performing microarray. We thank Vickie Hoffmann from NIH Division of Veterinary Resources for the comprehensive gross and histopathologic analyses. We also thank Jingyan Tian, Joseph Hsu and Lale Dawut for their technical support. We also want to thank Drs. Beverly Baptiste, Raghavendra Shamanna, Mengxia Li and Takashi Tadokoro at the NIA for their critical discussions. This research was supported entirely by the Intramural Research Program of the NIH, NIA. NR 60 TC 9 Z9 9 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD MAY PY 2014 VL 5 SI SI AR e1226 DI 10.1038/cddis.2014.168 PG 12 WC Cell Biology SC Cell Biology GA AI9DN UT WOS:000337229300026 PM 24832598 ER PT J AU Ostroumova, E Gudzenko, N Brenner, A Gorokh, Y Hatch, M Prysyazhnyuk, A Mabuchi, K Bazyka, D AF Ostroumova, Evgenia Gudzenko, Nataliya Brenner, Alina Gorokh, Yevgeniy Hatch, Maureen Prysyazhnyuk, Anatoliy Mabuchi, Kiyohiko Bazyka, Dimitry TI Thyroid cancer incidence in Chornobyl liquidators in Ukraine: SIR analysis, 1986-2010 SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Thyroid cancer; Liquidators; Clean-up workers; Chornobyl; Chernobyl; Ukraine ID CLEANUP WORKERS; RISK; EXPOSURE; RADIATION; COHORT; ACCIDENT; REGISTRY AB We studied thyroid cancer incidence in a cohort of 150,813 male Chornobyl clean-up workers ("liquidators") from Ukraine by calculating standardized incidence ratio (SIR) using national cancer statistics. Follow-up began on the liquidator's registration date with the Chornobyl State Registry of Ukraine (the earliest date was 05. 05. 1986) and continued through December 31, 2010, date of thyroid cancer diagnosis, date of death, or date of last known vital status, whichever came first. There were 196 incident thyroid cancers in the study cohort with an overall SIR of 3.50 [95 % confidence interval (CI) 3.04-4.03]. A significantly elevated SIR estimate of 3.86 (95 % CI 3.26-4.57) was observed for liquidators who had their first clean-up mission in the Chornobyl zone in 1986, when levels of external and internal exposure to radiation were highest; the SIR estimates for later calendar years of first clean-up mission, while significantly elevated, were lower. The SIR estimates were elevated throughout the entire follow-up period but were especially high 10-18 years after the accident: 4.62 (95 % CI 3.47-6.15) and 4.80 (95 % CI 3.78-6.10) for the period 1995-1999 and 2000-2004, respectively. Our findings support the growing evidence of increased thyroid cancer rates among Chornobyl liquidators. Although this could be partially attributed to increased medical surveillance, the observed pattern of SIR increase warrants further investigation of a potential contribution of radiation exposure to the elevated thyroid cancer rates in this large population. C1 [Ostroumova, Evgenia; Brenner, Alina; Hatch, Maureen; Mabuchi, Kiyohiko] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Gudzenko, Nataliya; Prysyazhnyuk, Anatoliy; Bazyka, Dimitry] Natl Res Ctr Radiat Med, Kiev, Ukraine. [Gorokh, Yevgeniy] Natl Canc Inst, Kiev, Ukraine. RP Ostroumova, E (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM eostroumova@gmail.com OI Bazyka, Dimitry/0000-0001-9982-5990 FU Intramural Research Program of the NIH, National Cancer Institute (USA) FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute (USA). We acknowledge the contribution of Zoya Fedorenko (Ukrainian National Cancer Register, Ukraine), Nataliya Babkina and Nataliya Trotsiuk (National Research Center for Radiation Medicine, Ukraine) to the study execution. We thank Anatoliy Romanenko, Vadim Chumak, Yuriy Belyayev (National Research Center for Radiation Medicine, Ukraine) and Vladimir Drozdovitch (National Cancer Institute, USA) for helpful discussions of study results. NR 21 TC 1 Z9 1 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 EI 1573-7284 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD MAY PY 2014 VL 29 IS 5 BP 337 EP 342 DI 10.1007/s10654-014-9896-1 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AI8GI UT WOS:000337148200004 PM 24705729 ER PT J AU Mukhopadhyay, P Rajesh, M Cao, ZX Horvath, B Park, O Wang, H Erdelyi, K Holovac, E Wang, YP Liaudet, L Hamdaoui, N Lafdil, F Hasko, G Szabo, C Boulares, AH Gao, B Pacher, P AF Mukhopadhyay, Partha Rajesh, Mohanraj Cao, Zongxian Horvath, Bela Park, Ogyi Wang, Hua Erdelyi, Katalin Holovac, Eileen Wang, Yuping Liaudet, Lucas Hamdaoui, Nabila Lafdil, Fouad Hasko, Gyoergy Szabo, Csaba Boulares, A. Hamid Gao, Bin Pacher, Pal TI Poly (ADP-Ribose) Polymerase-1 Is a Key Mediator of Liver Inflammation and Fibrosis SO HEPATOLOGY LA English DT Article ID HEPATIC STELLATE CELLS; GROWTH-FACTOR; POLY(ADP-RIBOSE) POLYMERASE; HEPATOCELLULAR-CARCINOMA; ADIPOCYTE FUNCTION; ACTIVATION; PATHWAY; PHAGOCYTOSIS; RIBOSYLATION; FIBROGENESIS AB Poly (ADP-ribose) polymerase 1 (PARP-1) is a constitutive enzyme, the major isoform of the PARP family, which is involved in the regulation of DNA repair, cell death, metabolism, and inflammatory responses. Pharmacological inhibitors of PARP provide significant therapeutic benefits in various preclinical disease models associated with tissue injury and inflammation. However, our understanding the role of PARP activation in the pathophysiology of liver inflammation and fibrosis is limited. In this study we investigated the role of PARP-1 in liver inflammation and fibrosis using acute and chronic models of carbon tetrachloride (CCl4)-induced liver injury and fibrosis, a model of bile duct ligation (BDL)-induced hepatic fibrosis in vivo, and isolated liver-derived cells ex vivo. Pharmacological inhibition of PARP with structurally distinct inhibitors or genetic deletion of PARP-1 markedly attenuated CCl4-induced hepatocyte death, inflammation, and fibrosis. Interestingly, the chronic CCl4-induced liver injury was also characterized by mitochondrial dysfunction and dysregulation of numerous genes involved in metabolism. Most of these pathological changes were attenuated by PARP inhibitors. PARP inhibition not only prevented CCl4-induced chronic liver inflammation and fibrosis, but was also able to reverse these pathological processes. PARP inhibitors also attenuated the development of BDL-induced hepatic fibrosis in mice. In liver biopsies of subjects with alcoholic or hepatitis B-induced cirrhosis, increased nitrative stress and PARP activation was noted. Conclusion: The reactive oxygen/nitrogen species-PARP pathway plays a pathogenetic role in the development of liver inflammation, metabolism, and fibrosis. PARP inhibitors are currently in clinical trials for oncological indications, and the current results indicate that liver inflammation and liver fibrosis may be additional clinical indications where PARP inhibition may be of translational potential. (Hepatology 2014;59:1998-2009) C1 [Mukhopadhyay, Partha; Rajesh, Mohanraj; Cao, Zongxian; Horvath, Bela; Erdelyi, Katalin; Holovac, Eileen; Wang, Yuping; Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20852 USA. [Horvath, Bela] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44106 USA. [Park, Ogyi; Wang, Hua; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20852 USA. [Liaudet, Lucas] BH 08 621 Univ Hosp Med Ctr, Dept Intens Care Med, Lausanne, Switzerland. [Hamdaoui, Nabila; Lafdil, Fouad] Hop Henri Mondor, INSERM, U955, F-94010 Creteil, France. [Hamdaoui, Nabila; Lafdil, Fouad] Univ Paris Est, Fac Med, UMR S955, Creteil, France. [Hasko, Gyoergy] Rutgers New Jersey Med Sch, Dept Surg, Newark, NJ USA. [Szabo, Csaba] Univ Texas Med Branch, Dept Anesthesiol, Galveston, TX 77555 USA. [Boulares, A. Hamid] Louisiana State Univ, Hlth Sci Ctr, Stanley Scott Canc Ctr, New Orleans, LA USA. [Boulares, A. Hamid] Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol, New Orleans, LA USA. RP Pacher, P (reprint author), NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20852 USA. EM pacher@mail.nih.gov RI Horvath, Bela/A-7368-2009; Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017 OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU NIH/NIAAA; NIH [P50GM060338, HL072889] FX Supported by the Intramural Program of the NIH/NIAAA to PP and BG. CS and AHB were supported by a grant from the NIH P50GM060338 and HL072889. NR 28 TC 26 Z9 27 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD MAY PY 2014 VL 59 IS 5 BP 1998 EP + DI 10.1002/hep.26763 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AI9TA UT WOS:000337278400039 PM 24089324 ER PT J AU Niciu, MJ Luckenbaugh, DA Ionescu, DF Guevara, S Machado-Vieira, R Richards, EM Brutsche, NE Nolan, NM Zarate, CA AF Niciu, Mark J. Luckenbaugh, David A. Ionescu, Dawn F. Guevara, Sara Machado-Vieira, Rodrigo Richards, Erica M. Brutsche, Nancy E. Nolan, Neal M. Zarate, Carlos A., Jr. TI Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID RAPID ANTIDEPRESSANT RESPONSE; D-ASPARTATE ANTAGONIST; ADD-ON TRIAL; BIPOLAR DEPRESSION; ALCOHOL DEPENDENCE; MOOD DISORDERS; GLUTAMATERGIC NEUROTRANSMISSION; NMDA ANTAGONIST; FAMILY-HISTORY; EFFICACY AB Objective: The N-methyl-d-aspartate receptor antagonist ketamine has rapid antidepressant effects in treatment-resistant major depressive disorder (MDD) and bipolar depression. Clinical predictors may identify those more likely to benefit from ketamine within clinically heterogeneous populations. Method: Data were analyzed from 4 studies of treatment-resistant inpatients with DSM-IV-TR-diagnosed MDD or bipolar I or II depression. Patients who were currently experiencing a moderate-to-severe major depressive episode were enrolled between November 2004 and March 2013. All subjects received a single subanesthetic (0.5 mg/kg) ketamine infusion over 40 minutes. Patients were analyzed at the 230-minute postinfusion time point (n = 108), at day 1 (n = 82), and at day 7 (n = 71). Univariate Pearson correlations were performed for each variable with percent change from baseline in the 17-item Hamilton Depression Rating Scale (HDRS). Multivariate linear regression was then conducted for statistically significant predictors (P =.05, 2-tailed). Results: Higher body mass index correlated with greater HDRS improvement at 230 minutes (standardized beta = -0.30, P =.004) and at day 1 (standardized beta = -0.37, P =.001), but not at day 7 (standardized beta = -0.18, P =.10). Family history of an alcohol use disorder in a first-degree relative was associated with greater HDRS improvement at day 1 (standardized beta = -0.27, P =.014) and day 7 (standardized beta = -0.41, P <.001). No prior history of suicide attempt(s) was associated with greater improvement only at day 7 (standardized beta = 0.28, P =.01). The overall statistical model explained 13%, 23%, and 36% of HDRS percent change variance at 230 minutes, day 1, and day 7, respectively. Conclusions: Despite its post hoc nature, this study identified several clinical correlates of ketamine's rapid and durable antidepressant effects. Further investigation of these relationships is critical for individualized treatment of depression. (C) Copyright 2014 Physicians Postgraduate Press, Inc. C1 [Niciu, Mark J.; Luckenbaugh, David A.; Ionescu, Dawn F.; Guevara, Sara; Machado-Vieira, Rodrigo; Richards, Erica M.; Brutsche, Nancy E.; Nolan, Neal M.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, IRP, NIH, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), Bldg 10 Clin Res Ctr CRC,10 Ctr Dr,Room 7-5342, Bethesda, MD 20892 USA. EM zaratec@mail.nih.gov RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Niciu, Mark/J-1766-2014; Ionescu, Dawn/K-5675-2015 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Niciu, Mark/0000-0002-5612-3021; FU IRP-NIMH-NIH; NARSAD; Brain and Behavior Research Foundation FX Funding for this work was supported by the IRP-NIMH-NIH, by a NARSAD Independent Investigator Award to Dr Zarate, and by the Brain and Behavior Mood Disorders Research Award from the Brain and Behavior Research Foundation (formerly NARSAD) to Dr Zarate. NR 38 TC 25 Z9 26 U1 3 U2 12 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 MAY PY 2014 VL 75 IS 5 BP E417 EP E423 DI 10.4088/JCP.13m08698 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AI9LZ UT WOS:000337255400003 PM 24922494 ER PT J AU Tooley, PW Browning, M Leighty, RM AF Tooley, Paul W. Browning, Marsha Leighty, Robert M. TI The effect of temperature on germination of chlamydospores of Phytophthora ramorum SO MYCOLOGIA LA English DT Article DE overwintering; ramorum blight; resting spore; sudden oak death ID SUDDEN OAK DEATH; PATHOGEN; SOIL; MANAGEMENT; CALIFORNIA; CINNAMOMI; PALMIVORA; MEDIA AB Mycelium-free chlamydospores of 12 isolates of P. ramorum representing three clonal lineages were produced with a method involving incubation in nonsterile sand at 20 C in darkness for 30 d. Chlamydospores were incubated on selective agar medium at 5, 10, 15, 20, 25 and 30 C and germination assessed after 1, 2, 4, 6 and 8 d incubation. The optimal temperature for germination based on 8 d incubation was 20 C for all three clonal lineages tested (NA1 NA2, EU1). Mean germination rates were 2, 21, 44, 67, 32 and 0 percent at 5, 10, 15, 20, 25 and 30 C respectively for all isolates combined. The highest mean germination rate was scored by isolates of the EU1 clonal lineage at 20 C (85%) after 8 d incubation However, substantial variation was observed among isolates within each clonal lineage. Overall temperatures and days of incubation on which germination was assessed isolates of the NA1 clonal lineage had the lowest mean germination, even though one isolate had the highest germination of any isolate in any lineage. The results indicate that 20 C is the optimal germination temperature for P. ramorum chlamydospores and that a great disparity in germination percentage can exist within isolates, even within a single clonal lineage. C1 [Tooley, Paul W.; Browning, Marsha] USDA ARS, Foreign Dis Weed Sci Res Unit, Ft Detrick, MD 21702 USA. [Leighty, Robert M.] Data Management Serv Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Tooley, PW (reprint author), USDA ARS, Foreign Dis Weed Sci Res Unit, 1301 Ditto Ave, Ft Detrick, MD 21702 USA. EM paul.tooley@ars.usda.gov NR 30 TC 3 Z9 3 U1 0 U2 13 PU ALLEN PRESS INC PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 0027-5514 EI 1557-2536 J9 MYCOLOGIA JI Mycologia PD MAY-JUN PY 2014 VL 106 IS 3 BP 424 EP 430 DI 10.3852/13-313 PG 7 WC Mycology SC Mycology GA AI7LF UT WOS:000337071400006 PM 24871605 ER PT J AU Thiebaut, R Drylewicz, J Prague, M Lacabaratz, C Beq, S Jarne, A Croughs, T Sekaly, RP Lederman, MM Sereti, I Commenges, D Levy, Y AF Thiebaut, Rodolphe Drylewicz, Julia Prague, Melanie Lacabaratz, Christine Beq, Stephanie Jarne, Ana Croughs, Therese Sekaly, Rafick-Pierre Lederman, Michael M. Sereti, Irini Commenges, Daniel Levy, Yves TI Quantifying and Predicting the Effect of Exogenous Interleukin-7 on CD4(+)T Cells in HIV-1 Infection SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID RECEIVING ANTIRETROVIRAL THERAPY; NAIVE T-CELLS; IN-VIVO; HOMEOSTATIC PROLIFERATION; IMMUNE RECONSTITUTION; RHESUS MACAQUES; MEMORY CELLS; IL-7; SURVIVAL; LYMPHOCYTES AB Exogenous Interleukin-7 (IL-7), in supplement to antiretroviral therapy, leads to a substantial increase of all CD4(+) T cell subsets in HIV-1 infected patients. However, the quantitative contribution of the several potential mechanisms of action of IL-7 is unknown. We have performed a mathematical analysis of repeated measurements of total and naive CD4(+) T cells and their Ki67 expression from HIV-1 infected patients involved in three phase I/II studies (N = 53 patients). We show that, besides a transient increase of peripheral proliferation, IL-7 exerts additional effects that play a significant role in CD4(+) T cell dynamics up to 52 weeks. A decrease of the loss rate of the total CD4(+) T cell is the most probable explanation. If this effect could be maintained during repeated administration of IL-7, our simulation study shows that such a strategy may allow maintaining CD4(+) T cell counts above 500 cells/mu L with 4 cycles or fewer over a period of two years. This in-depth analysis of clinical data revealed the potential for IL-7 to achieve sustained CD4(+) T cell restoration with limited IL-7 exposure in HIV-1 infected patients with immune failure despite antiretroviral therapy. C1 [Thiebaut, Rodolphe; Prague, Melanie; Jarne, Ana; Commenges, Daniel] INSERM, ISPED, Ctr INSERM U897 Epidemiol Biostat, Bordeaux, France. [Thiebaut, Rodolphe; Prague, Melanie; Jarne, Ana; Commenges, Daniel] Univ Bordeaux, ISPED, Ctr INSERM U897 Epidemiol Biostat, Bordeaux, France. [Thiebaut, Rodolphe; Prague, Melanie; Jarne, Ana; Commenges, Daniel] INRIA, SISTM Team, Bordeaux, France. [Drylewicz, Julia] Univ Med Ctr Utrecht, Lab Translat Immunol, Utrecht, Netherlands. [Drylewicz, Julia] Univ Utrecht, Dept Biol, Utrecht, Netherlands. [Lacabaratz, Christine; Levy, Yves] Hop Henri Mondor, INSERM, Unite U955, F-94010 Creteil, France. [Lacabaratz, Christine] Univ Paris Est, Fac Med, UMR S955, Creteil, France. [Beq, Stephanie; Croughs, Therese] CYTHERIS, Issy Les Moulineaux, France. [Sekaly, Rafick-Pierre] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL USA. [Lederman, Michael M.] Case Western Reserve Univ, Univ Hosp, Case Med Ctr, Cleveland, OH 44106 USA. [Sereti, Irini] NIAID, NIH, Bethesda, MD 20892 USA. [Levy, Yves] AP HP, Grp Henri Mondor Albert Chenevier, Immunol Clin, Creteil, France. RP Thiebaut, R (reprint author), INSERM, ISPED, Ctr INSERM U897 Epidemiol Biostat, Bordeaux, France. EM rodolphe.thiebaut@isped.u-bordeaux2.fr NR 61 TC 10 Z9 10 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD MAY PY 2014 VL 10 IS 5 AR e1003630 DI 10.1371/journal.pcbi.1003630 PG 12 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA AI9VB UT WOS:000337288000038 PM 24853554 ER PT J AU Pavone, ME Hirshfeld-Cytron, J Tingen, C Thomas, C Thomas, J Lowe, MP Schink, JC Woodruff, TK AF Pavone, Mary Ellen Hirshfeld-Cytron, Jennifer Tingen, Candace Thomas, Cristina Thomas, Jessina Lowe, M. Patrick Schink, Julian C. Woodruff, Teresa K. TI Human Ovarian Tissue Cortex Surrounding Benign and Malignant Lesions SO REPRODUCTIVE SCIENCES LA English DT Article DE follicle density; ovarian cancer; endometriosis; ovarian tissue cryopreservation; ovarian tissue transplantation; fertility preservation ID MONOZYGOTIC TWINS DISCORDANT; INITIAL FOLLICLE POOL; FERTILITY PRESERVATION; CANCER-PATIENTS; BRCA1-DEFICIENT MICE; GROWING FOLLICLES; BREAST-CANCER; GERM-CELLS; TRANSPLANTATION; GROWTH AB Objective: To quantify the number of follicles in patients with ovarian pathologies, benign and malignant, in pregnant and nonpregnant states and to determine how the presence of ovarian masses and BRCA status affects follicular counts. Materials and Methods: Slides from 134 reproductive-aged women undergoing oophorectomy were examined using light microscopy by 3 independent counters blinded to the diagnosis. In all, 20 patients had cancer, 69 had benign conditions, and 35 patients were BRCA+ or had a strong family history of breast and/or ovarian cancer. In all, 10 women were either pregnant or immediately postpartum. Results: Patients undergoing risk-reducing surgery had significantly decreased follicle count compared to physiologic control. Patients with cancer had significantly decreased counts compared to all other groups. There were no differences within the benign cohort. Conclusions: When compared to benign masses, the cortex surrounding an ovarian malignancy has decreased follicle density. The stretch impact may minimize any impact on total follicle numbers. Furthermore, there may be a proliferation of ovarian stroma, with the same number of follicles spread over a larger surface area. This information is important when counseling women with ovarian masses regarding the use of ovarian tissue cryopreservation. C1 [Pavone, Mary Ellen] Northwestern Univ, Dept Obstet & Gynecol, Div Reprod Biol, Chicago, IL 60611 USA. [Pavone, Mary Ellen] Northwestern Univ, Feinberg Sch Med, Div Reprod Endocrinol & Infertil, Chicago, IL 60611 USA. [Tingen, Candace] Univ Illinois, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Chicago, IL 60612 USA. [Tingen, Candace] NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. [Thomas, Cristina; Thomas, Jessina] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Lowe, M. Patrick] Advocate Hlth Care, Gynecol Oncol, Chicago, IL USA. [Schink, Julian C.] Northwestern Univ, Feinberg Sch Med, Div Gynecol Oncol, Dept Obstet & Gynecol, Chicago, IL 60611 USA. [Woodruff, Teresa K.] Northwestern Univ, Feinberg Sch Med, Div Fertil Preservat, Dept Obstet & Gynecol, Chicago, IL 60611 USA. RP Pavone, ME (reprint author), Northwestern Univ, Feinberg Sch Med, Div Reprod Endocrinol & Infertil, Chicago, IL 60611 USA. EM mpavone@nmff.org FU ASRM career development award; [K12HD050121]; [U54 HD076188] FX The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: Supported by K12HD050121, ASRM career development award (to MEP), and U54 HD076188 (to TKW). NR 59 TC 2 Z9 2 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAY PY 2014 VL 21 IS 5 BP 582 EP 589 DI 10.1177/1933719113506498 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AI9UM UT WOS:000337285300005 PM 24096576 ER PT J AU Messer, RJ Lavender, KJ Hasenkrug, KJ AF Messer, Ronald J. Lavender, Kerry J. Hasenkrug, Kim J. TI Mice of the resistant H-2(b) haplotype mount broad CD4(+) T cell responses against 9 distinct Friend virus epitopes SO VIROLOGY LA English DT Article DE Friend virus; CD4(+) T cells ID MURINE LEUKEMIA-VIRUS; FBL-3 TUMOR-CELLS; RETROVIRUS INFECTION; ANTIGEN; IMMUNITY; MODEL; GENE; IDENTIFICATION; MECHANISMS; EXPRESSION AB To date, only a single Friend virus (FV) peptide recognized by CD4(+) T cells in FV-infected mice of the resistant H-2(b) haplotype has been described. To more thoroughly examine the repertoire of CD4(+) T cell responses in H-2(b) mice infected with this retrovirus, 18mer peptides spanning the FV gag, pol, and env coding regions with 11mer overlaps were synthesized. The peptides were then used to stimulate whole splenocytes and purified CD4(+) T cells from FV-infected mice in an IFN gamma ELISPOT assay. Nine new CD4(+) T cell epitopes were identified, 3 encoded by gag, 1 by pol, and 5 by env. The high resistance of H-2(b) mice could be related to this very broad CD4(+) T cell response against multiple peptides during FV infection. Published by Elsevier Inc. C1 [Messer, Ronald J.; Lavender, Kerry J.; Hasenkrug, Kim J.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Hasenkrug, KJ (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM khasenkrug@nih.gov FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases and National Institutes of Health, USA FX This work was funded by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases and National Institutes of Health, USA. NR 32 TC 5 Z9 5 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 MAY PY 2014 VL 456 BP 139 EP 144 DI 10.1016/j.virol.2014.03.012 PG 6 WC Virology SC Virology GA AI9NF UT WOS:000337258600014 PM 24889233 ER PT J AU Teterina, NL Liu, GP Maximova, OA Pletnev, AG AF Teterina, Natalya L. Liu, Guangping Maximova, Olga A. Pletnev, Alexander G. TI Silencing of neurotropic flavivirus replication in the central nervous system by combining multiple microRNA target insertions in two distinct viral genome regions SO VIROLOGY LA English DT Article DE Flavivirus; Micrornas; Neuropathogenesis ID ATTENUATED VIRUS-VACCINES; INFLUENZA-A VIRUS; IMMUNE-RESPONSES; VECTOR TROPISM; ENCEPHALITIS; RNA; RECOGNITION; MICE; NEUROINVASIVENESS; NEUROVIRULENCE AB In recent years, microRNA-targeting has become an effective strategy for selective control of tissue-tropism and pathogenesis of both DNA and RNA viruses. Here, using a neurotropic flavivirus as a model, we demonstrate that simultaneous miRNA targeting of the viral genome in the open reading frame and 3'-noncoding regions for brain-expressed miRNAs had an additive effect and produced a more potent attenuation of the virus compared to separate targeting of those regions. Multiple miRNA co-targeting of these two distantly located regions completely abolished the virus neurotropism as no viral replication was detected in the developing brain of neonatal mice. Furthermore, no viral antigens were detected in neurons, and neuronal integrity in the brain of mice was well preserved. This miRNA co-targeting approach can be adapted for other viruses in order to minimize their replication in a cell- or tissue-type specific manner, but most importantly, to prevent virus escape from miRNA-mediated silencing. Published by Elsevier Inc. C1 [Teterina, Natalya L.; Liu, Guangping; Maximova, Olga A.; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Pletnev, AG (reprint author), NIAID, NIH, Bldg 33,Room 3W10A,33 North Dr,MSC 3203, Bethesda, MD 20892 USA. EM apletnev@niaid.nih.gov FU Division of Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Division of Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 46 TC 8 Z9 9 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 0042-6822 J9 VIROLOGY JI Virology PD MAY PY 2014 VL 456 BP 247 EP 258 DI 10.1016/j.virol.2014.04.001 PG 12 WC Virology SC Virology GA AI9NF UT WOS:000337258600025 PM 24889244 ER PT J AU Laughlin, MR Bantle, JP Havel, PJ Parks, E Klurfeld, DM Teff, K Maruvada, P AF Laughlin, Maren R. Bantle, John P. Havel, Peter J. Parks, Elizabeth Klurfeld, David M. Teff, Karen Maruvada, Padma TI Clinical Research Strategies for Fructose Metabolism SO ADVANCES IN NUTRITION LA English DT Review ID GLUCOSE-SWEETENED BEVERAGES; DE-NOVO LIPOGENESIS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; PLASMINOGEN-ACTIVATOR INHIBITOR-1; LOW-DENSITY LIPOPROTEINS; FATTY-ACID SYNTHESIS; DIETARY FRUCTOSE; CORN SYRUP; URIC-ACID; HIGH-CARBOHYDRATE AB Fructose and simple sugars are a substantial part of the western diet, and their influence on human health remains controversial. Clinical studies in fructose nutrition have proven very difficult to conduct and interpret. NIH and USDA sponsored a workshop on 13-14 November 2012, "Research Strategies for Fructose Metabolism," to identify important scientific questions and parameters to be considered while designing clinical studies. Research is needed to ascertain whether there is an obesogenic role for fructose-containing sugars via effects on eating behavior and energy balance and whether there is a dose threshold beyond which these sugars promote progression toward diabetes and liver and cardiovascular disease, especially in susceptible populations. Studies tend to fall into 2 categories, and design criteria for each are described. Mechanistic studies are meant to validate observations made in animals or to elucidate the pathways of fructose metabolism in humans. These highly controlled studies often compare the pure monosaccharides glucose and fructose. Other studies are focused on clinically significant disease outcomes or health behaviors attributable to amounts of fructose-containing sugars typically found in the American diet. These are designed to test hypotheses generated from short-term mechanistic or epidemiologic studies and provide data for health policy. Discussion brought out the opinion that, although many mechanistic questions concerning the metabolism of monosaccharide sugars in humans remain to be addressed experimentally in small highly controlled studies, health outcomes research meant to inform health policy should use large, long-term studies using combinations of sugars found in the typical American diet rather than pure fructose or glucose. C1 [Laughlin, Maren R.; Teff, Karen; Maruvada, Padma] NIDDK, NIH, Bethesda, MD 20892 USA. [Bantle, John P.] Univ Minnesota, Dept Med, Div Endocrinol & Diabet, Minneapolis, MN 55455 USA. [Havel, Peter J.] Univ Calif Davis, Sch Vet Med, Dept Nutr, Dept Mol Biosci, Davis, CA 95616 USA. [Parks, Elizabeth] Univ Missouri, Inst Clin Translat Sci, Dept Nutr & Exercise Physiol, Columbia, MO USA. [Klurfeld, David M.] USDA ARS, Beltsville, MD USA. RP Laughlin, MR (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. OI Parks, Elizabeth/0000-0001-5681-1097 FU National Institutes of Health; USDA; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart Lung and Blood Institute; Merck FX On behalf of the organizers and participants in a 2012 National Institutes of Health and USDA-sponsored workshop, 'clinical Research Strategies for Fructose Metabolism." Funding for the workshop was from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart Lung and Blood Institute, and the USDA.; Author disclosures. E. Parks serves on the Atkins Nutritionals Scientific Advisory Board, Merck Speakers Bureau and receives funding from Merck. M. R. Laughlin, J. P Bantle, P. J. Havel, D. M. Klurfeld, K Taft, P. Maruvada, no conflicts of interest NR 76 TC 9 Z9 9 U1 3 U2 29 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 2161-8313 EI 2156-5376 J9 ADV NUTR JI Adv. Nutr. PD MAY PY 2014 VL 5 IS 3 BP 248 EP 259 DI 10.3945/an.113.005249 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AI5CV UT WOS:000336883900004 PM 24829471 ER PT J AU Ash, JA Rapp, PR AF Ash, Jessica A. Rapp, Peter R. TI A quantitative neural network approach to understanding aging phenotypes SO AGEING RESEARCH REVIEWS LA English DT Review DE Graph theory; Neural networks; Neurocognitive aging ID INTRINSIC FUNCTIONAL CONNECTIVITY; TEST-RETEST RELIABILITY; RESTING-STATE NETWORKS; GRAPH-THEORETICAL ANALYSIS; DEFAULT-MODE NETWORK; AGE-RELATED-CHANGES; ALZHEIMERS-DISEASE; HUMAN BRAIN; STRUCTURAL CONNECTIVITY; TOPOLOGICAL PATTERNS AB Basic research on neurocognitive aging has traditionally adopted a reductionist approach in the search for the basis of cognitive preservation versus decline. However, increasing evidence suggests that a network level understanding of the brain can provide additional novel insight into the structural and functional organization from which complex behavior and dysfunction emerge. Using graph theory as a mathematical framework to characterize neural networks, recent data suggest that alterations in structural and functional networks may contribute to individual differences in cognitive phenotypes in advanced aging. This paper reviews literature that defines network changes in healthy and pathological aging phenotypes, while highlighting the substantial overlap in key features and patterns observed across aging phenotypes. Consistent with current efforts in this area, here we outline one analytic strategy that attempts to quantify graph theory metrics more precisely, with the goal of improving diagnostic sensitivity and predictive accuracy for differential trajectories in neurocognitive aging. Ultimately, such an approach may yield useful measures for gauging the efficacy of potential preventative interventions and disease modifying treatments early in the course of aging. Published by Elsevier B.V. C1 [Ash, Jessica A.; Rapp, Peter R.] NIA, Lab Behav Neurosci, Neurocognit Aging Sect, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Ash, JA (reprint author), NIA, Lab Behav Neurosci, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM jessica.ash@nih.gov FU Intramural Research Program of the National Institute on Aging FX We would like to thank Dr. Yihong Yang for his invaluable comments on this manuscript. This is original work supported by the Intramural Research Program of the National Institute on Aging. NR 63 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1568-1637 EI 1872-9649 J9 AGEING RES REV JI Ageing Res. Rev. PD MAY PY 2014 VL 15 BP 44 EP 50 DI 10.1016/j.arr.2014.02.001 PG 7 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA AI4ZR UT WOS:000336875700005 PM 24548925 ER PT J AU Liu, J Sirenko, S Juhaszova, M Sollott, SJ Shukla, S Yaniv, Y Lakatta, EG AF Liu, Jie Sirenko, Syevda Juhaszova, Magdalena Sollott, Steven J. Shukla, Shweta Yaniv, Yael Lakatta, Edward G. TI Age-associated abnormalities of intrinsic automaticity of sinoatrial nodal cells are linked to deficient cAMP-PKA-Ca2+ signaling SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE aging; Ca2+ transient; intrinsic heart rate; pacemaker function; PKA signaling ID CARDIAC-PACEMAKER CELLS; LOCAL CA2+ RELEASES; RAT VENTRICULAR MYOCYTES; SPONTANEOUS BEATING RATE; SARCOPLASMIC-RETICULUM; HEART-RATE; ATRIAL-FIBRILLATION; DYNAMIC EXERCISE; SEX-DIFFERENCES; AGING RABBIT AB A reduced sinoatrial node (SAN) functional reserve underlies the age-associated decline in heart rate acceleration in response to stress. SAN cell function involves an oscillatory coupled-clock system: the sarcoplasmic reticulum (SR), a Ca2+ clock, and the electrogenic-sarcolemmal membrane clock. Ca2+ activated-calmodulin-adenylyl cyclase/CaMKII-cAMP/PKA-Ca2+ signaling regulated by phosphodiesterase activity drives SAN cells automaticity. SR-generated local calcium releases (LCRs) activate Na+/Ca2+ exchanger in the membrane clock, which initiates the action potential (AP). We hypothesize that SAN cell dysfunctions accumulate with age. We found a reduction in single SAN cell AP firing in aged (20-24 mo) vs. adult (3-4 mo) mice. The sensitivity of the SAN beating rate responses to both muscarinic and adrenergic receptor activation becomes decreased in advanced age. Additionally, age-associated coincident dysfunctions occur stemming from compromised clock functions, including a reduced SR Ca2+ load and a reduced size, number, and duration of spontaneous LCRs. Moreover, the sensitivity of SAN beating rate to a cAMP stress induced by phosphodiesterase inhibitor is reduced, as are the LCR size, amplitude, and number in SAN cells from aged vs. adult mice. These functional changes coincide with decreased expression of crucial SR Ca2+-cycling proteins, including SR Ca2+-ATPase pump, ryanodine receptors, and Na+/Ca2+ exchanger. Thus a deterioration in intrinsic Ca2+ clock kinetics in aged SAN cells, due to deficits in intrinsic SR Ca2+ cycling and its response to a cAMP-dependent pathway activation, is involved in the age-associated reduction in intrinsic resting AP firing rate, and in the reduction in the acceleration of heart rate during exercise. C1 [Liu, Jie; Sirenko, Syevda; Juhaszova, Magdalena; Sollott, Steven J.; Shukla, Shweta; Yaniv, Yael; Lakatta, Edward G.] NIA, Lab Cardiovasc Sci, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Liu, Jie] Univ Sydney, Dept Physiol, Sydney, NSW 2006, Australia. RP Lakatta, EG (reprint author), NIA, Lab Cardiovasc Sci, Gerontol Res Ctr, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM LakattaE@grc.nia.nih.gov FU National Institutes of Health, National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 62 TC 1 Z9 1 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 2014 VL 306 IS 10 DI 10.1152/ajpheart.00088.2014 PG 13 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA AI5KD UT WOS:000336904100001 ER PT J AU Dobrinskikh, E Okamura, K Kopp, JB Doctor, RB Blaine, J AF Dobrinskikh, Evgenia Okamura, Kayo Kopp, Jeffrey B. Doctor, R. Brian Blaine, Judith TI Human podocytes perform polarized, caveolae-dependent albumin endocytosis SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE albumin; caveoli; endocytosis; podocytes; trafficking ID GLOMERULAR-BASEMENT-MEMBRANE; PROXIMAL TUBULE CELLS; NEONATAL FC-RECEPTOR; ENDOTHELIAL-CELLS; MEDIATED UPTAKE; KIDNEY; IGG; RATS; DEGRADATION; FILTRATION AB The renal glomerulus forms a selective filtration barrier that allows the passage of water, ions, and small solutes into the urinary space while restricting the passage of cells and macromolecules. The three layers of the glomerular filtration barrier include the vascular endothelium, glomerular basement membrane (GBM), and podocyte epithelium. Podocytes are capable of internalizing albumin and are hypothesized to clear proteins that traverse the GBM. The present study followed the fate of FITC-labeled albumin to establish the mechanisms of albumin endocytosis and processing by podocytes. Confocal imaging and total internal reflection fluorescence microscopy of immortalized human podocytes showed FITC-albumin endocytosis occurred preferentially across the basal membrane. Inhibition of clathrin-mediated endocytosis and caveolae-mediated endocytosis demonstrated that the majority of FITC-albumin entered podocytes through caveolae. Once internalized, FITC-albumin colocalized with EEA1 and LAMP1, endocytic markers, and with the neonatal Fc receptor, a marker for transcytosis. After preloading podocytes with FITC-albumin, the majority of loaded FITC-albumin was lost over the subsequent 60 min of incubation. A portion of the loss of albumin occurred via lysosomal degradation as pretreatment with leupeptin, a lysosomal protease inhibitor, partially inhibited the loss of FITC-albumin. Consistent with transcytosis of albumin, preloaded podocytes also progressively released FITC-albumin into the extracellular media. These studies confirm the ability of podocytes to endocytose albumin and provide mechanistic insight into cellular mechanisms and fates of albumin handling in podocytes. C1 [Dobrinskikh, Evgenia; Okamura, Kayo; Doctor, R. Brian; Blaine, Judith] Univ Colorado, Aurora, CO USA. [Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. RP Blaine, J (reprint author), Div Renal Dis & Hypertens, 12700 E 19th Ave,C281, Aurora, CO 80045 USA. EM Judith.Blaine@ucdenver.edu OI Kopp, Jeffrey/0000-0001-9052-186X FU NIH [DK-080769, DK-080989]; National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program (NIH); NIH/NCRR Colorado CTSI [UL1 RR-025780] FX These studies were supported by NIH grants to R. B. Doctor (DK-080769) and J. Blaine (DK-080989). J. B. Kopp was supported by the National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program (NIH). Imaging experiments were performed in the University of Colorado Anschutz Medical Campus Advance Light Microscopy Core supported in part by NIH/NCRR Colorado CTSI Grant UL1 RR-025780. NR 47 TC 16 Z9 16 U1 0 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAY PY 2014 VL 306 IS 9 BP F941 EP F951 DI 10.1152/ajprenal.00532.2013 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AI4OO UT WOS:000336844900002 PM 24573386 ER PT J AU Bayliss, EA Bonds, DE Boyd, CM Davis, MM Finke, B Fox, MH Glasgow, RE Goodman, RA Heurtin-Roberts, S Lachenmayr, S Lind, C Madigan, EA Meyers, DS Mintz, S Nilsen, WJ Okun, S Ruiz, S Salive, ME Stange, KC AF Bayliss, Elizabeth A. Bonds, Denise E. Boyd, Cynthia M. Davis, Melinda M. Finke, Bruce Fox, Michael H. Glasgow, Russell E. Goodman, Richard A. Heurtin-Roberts, Suzanne Lachenmayr, Sue Lind, Cristin Madigan, Elizabeth A. Meyers, David S. Mintz, Suzanne Nilsen, Wendy J. Okun, Sally Ruiz, Sarah Salive, Marcel E. Stange, Kurt C. TI Understanding the Context of Health for Persons With Multiple Chronic Conditions: Moving From What Is the Matter to What Matters SO ANNALS OF FAMILY MEDICINE LA English DT Article DE multiple chronic conditions; chronic illness; health services research ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIALS; TEAM SCIENCE; PRIMARY-CARE; EXTERNAL VALIDITY; BIOPSYCHOSOCIAL MODEL; COMPLEXITY SCIENCE; PATIENT-CARE; NEED; MULTIMORBIDITY AB PURPOSE An isolated focus on 1 disease at a time is insufficient to generate the scientific evidence needed to improve the health of persons living with more than 1 chronic condition. This article explores how to bring context into research efforts to improve the health of persons living with multiple chronic conditions (MCC). METHODS Forty-five experts, including persons with MCC, family and friend caregivers, researchers, policy makers, funders, and clinicians met to critically consider 4 aspects of incorporating context into research on MCC: key contextual factors, needed research, essential research methods for understanding important contextual factors, and necessary partnerships for catalyzing collaborative action in conducting and applying research. RESULTS Key contextual factors involve complementary perspectives across multiple levels: public policy, community, health care systems, family, and person, as well as the cellular and molecular levels where most research currently is focused. Needed research involves moving from a disease focus toward a person-driven, goal-directed research agenda. Relevant research methods are participatory, flexible, multilevel, quantitative and qualitative, conducive to longitudinal dynamic measurement from diverse data sources, sufficiently detailed to consider what works for whom in which situation, and generative of ongoing communities of learning, living and practice. Important partnerships for collaborative action include cooperation among members of the research enterprise, health care providers, community-based support, persons with MCC and their family and friend caregivers, policy makers, and payers, including government, public health, philanthropic organizations, and the business community. CONCLUSION Consistent attention to contextual factors is needed to enhance health research for persons with MCC. Rigorous, integrated, participatory, multimethod approaches to generate new knowledge and diverse partnerships can be used to increase the relevance of research to make health care more sustainable, safe, equitable and effective, to reduce suffering, and to improve quality of life. C1 [Bayliss, Elizabeth A.] Kaiser Permanente, Denver, CO USA. [Bonds, Denise E.] NHLBI, Bethesda, MD 20892 USA. [Boyd, Cynthia M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Boyd, Cynthia M.] Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Davis, Melinda M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Finke, Bruce] Indian Hlth Serv, Nashville, TN USA. [Fox, Michael H.; Goodman, Richard A.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Glasgow, Russell E.; Heurtin-Roberts, Suzanne] NCI, NIH, Bethesda, MD 20892 USA. [Glasgow, Russell E.] Univ Colorado, Sch Med, Denver, CO USA. [Goodman, Richard A.] Dept Hlth & Human Serv, Off Assistant Secretary Hlth, Atlanta, GA USA. [Lachenmayr, Sue; Ruiz, Sarah] Natl Council Aging, Washington, DC USA. [Lind, Cristin] Karolinska Inst, Stockholm, Sweden. [Meyers, David S.] Agcy Healthcare Res & Qual, Rockville, MD USA. [Nilsen, Wendy J.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Okun, Sally] PatientsLikeMe, Cambridge, MA USA. [Ruiz, Sarah] Univ Chicago, Chicago, IL 60637 USA. [Salive, Marcel E.] NIA, Bethesda, MD USA. RP Stange, KC (reprint author), Case Western Reserve Univ, 11000 Cedar Ave,Suite 402, Cleveland, OH 44106 USA. EM kcs@case.edu RI Ruiz, Sarah/B-3456-2017 OI Ruiz, Sarah/0000-0002-6428-2321 FU Clinical Research Professorship from the American Cancer Society; National Cancer Society FX Dr Stange's time is supported in part by a Clinical Research Professorship from the American Cancer Society and by the National Cancer Society through the Intergovernmental Personnel Act. NR 99 TC 36 Z9 36 U1 7 U2 45 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA SN 1544-1709 EI 1544-1717 J9 ANN FAM MED JI Ann. Fam. Med. PD MAY-JUN PY 2014 VL 12 IS 3 BP 260 EP 269 DI 10.1370/afm.1643 PG 10 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA AI3YM UT WOS:000336801800011 PM 24821898 ER PT J AU Ma, N Xiao, H Marrero, B Xing, C Wang, XQ Zheng, MK Han, GC Chen, GJ Hou, CM Shen, BF Li, Y Wang, RX Jiang, ZY AF Ma, Ning Xiao, He Marrero, Bernadette Xing, Chen Wang, Xiaoqian Zheng, Mingke Han, Gencheng Chen, Guojiang Hou, Chunmei Shen, Beifen Li, Yan Wang, Renxi Jiang, Zhenyu TI Combination of TACI-IgG and anti-IL-15 treats murine lupus by reducing mature and memory B cells SO CELLULAR IMMUNOLOGY LA English DT Article DE TACI-IgG; IL-15; Lupus; Memory B cells ID AUTOIMMUNE-DISEASE; LYMPHOCYTE STIMULATOR; RHEUMATOID-ARTHRITIS; T-CELLS; INTERLEUKIN-15; ERYTHEMATOSUS; IL-15; BAFF; MICE AB Clinical trials suggest that BAFF inhibitors such as atacicept (TACI-IgG) and belimumab (anti-BAFF antibody) could not reduce memory B-cell numbers, although they reduced the numbers of CD20(+) naive B cells and activated B cells. In the present study, we explored the way to reduce memory B-cell numbers. First, we used TACI-IgG to treat murine lupus. We found that TACI-IgG was effective in reducing mature B cell numbers. Accordingly it controlled the level of the anti-dsDNA antibody in lupus-like mice. In addition, TACI-IgG up-regulated memory B cells in murine lupus. Furthermore, we found that TACI-IgG up-regulated IL-15 expression in lupus-like mice. Thus, the combination of TACI-IgG and anti-IL-15 antibodies was explored to understand their effects on the treatment of murine lupus. Compared to treatments with TACI-IgG or anti-IL-15 alone, the combination of TACI-IgG and anti-IL-15 antibodies efficiently ameliorated murine lupus phenotypes. The study provides hints for the clinical application of BAFF- and IL-15-specific therapeutic agents. (C) 2014 Elsevier Inc. All rights reserved. C1 [Ma, Ning; Jiang, Zhenyu] Jilin Univ, Hosp 1, Dept Rheumatol, Changchun 130021, Peoples R China. [Ma, Ning; Xiao, He; Xing, Chen; Wang, Xiaoqian; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Shen, Beifen; Li, Yan; Wang, Renxi] Inst Basic Med Sci, Immunol Lab, Beijing 100850, Peoples R China. [Marrero, Bernadette] NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Zheng, Mingke] Henan Univ, Coll Med, Dept Immunol, Kaifeng 475001, Peoples R China. RP Jiang, ZY (reprint author), Jilin Univ, Hosp 1, Dept Rheumatol, Changchun 130021, Peoples R China. EM jlujzy@yahoo.com.cn FU National Basic Research Program 973 Grants [2013CB530506]; Beijing Natural Science Foundation [7132139] FX This study was supported by National Basic Research Program 973 Grants (2013CB530506) and Beijing Natural Science Foundation (7132139). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 20 TC 6 Z9 6 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 EI 1090-2163 J9 CELL IMMUNOL JI Cell. Immunol. PD MAY-JUN PY 2014 VL 289 IS 1-2 BP 140 EP 144 DI 10.1016/j.cellimm.2014.03.017 PG 5 WC Cell Biology; Immunology SC Cell Biology; Immunology GA AI7ZG UT WOS:000337120900021 PM 24791699 ER PT J AU Yang, TH Shen, JB Yang, RH Redden, J Dodge-Kafka, K Grady, J Jacobson, KA Liang, BT AF Yang, Tiehong Shen, Jian-bing Yang, Ronghua Redden, John Dodge-Kafka, Kimberly Grady, James Jacobson, Kenneth A. Liang, Bruce T. TI Novel Protective Role of Endogenous Cardiac Myocyte P2X4 Receptors in Heart Failure SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; myocytes, cardiac; purines ID NITRIC-OXIDE SYNTHASE; CARDIOMYOCYTE-SPECIFIC OVEREXPRESSION; P2X(4) RECEPTORS; PRESSURE-OVERLOAD; PURINERGIC RECEPTORS; REPERFUSION INJURY; MICE; HYPERTROPHY; ATP; CLASSIFICATION AB Background-Heart failure (HF), despite continuing progress, remains a leading cause of mortality and morbidity. P2X4 receptors (P2X4R) have emerged as potentially important molecules in regulating cardiac function and as potential targets for HF therapy. Transgenic P2X4R overexpression can protect against HF, but this does not explain the role of native cardiac P2X4R. Our goal is to define the physiological role of endogenous cardiac myocyte P2X4R under basal conditions and during HF induced by myocardial infarction or pressure overload. Methods and Results-Mice established with conditional cardiac-specific P2X4R knockout were subjected to left anterior descending coronary artery ligation-induced postinfarct or transverse aorta constriction-induced pressure overload HF. Knockout cardiac myocytes did not show P2X4R by immunoblotting or by any response to the P2X4R-specific allosteric enhancer ivermectin. Knockout hearts showed normal basal cardiac function but depressed contractile performance in postinfarct and pressure overload models of HF by in vivo echocardiography and ex vivo isolated working heart parameters. P2X4R coimmunoprecipitated and colocalized with nitric oxide synthase 3 (eNOS) in wild-type cardiac myocytes. Mice with cardiac-specific P2X4R overexpression had increased S-nitrosylation, cyclic GMP, NO formation, and were protected from postinfarct and pressure overload HF. Inhibitor of eNOS, L-N-5-(1-iminoethyl) ornithine hydrochloride, blocked the salutary effect of cardiac P2X4R overexpression in postinfarct and pressure overload HF as did eNOS knockout. Conclusions-This study establishes a new protective role for endogenous cardiac myocyte P2X4R in HF and is the first to demonstrate a physical interaction between the myocyte receptor and eNOS, a mediator of HF protection. C1 [Yang, Tiehong; Shen, Jian-bing; Yang, Ronghua; Redden, John; Dodge-Kafka, Kimberly; Grady, James; Liang, Bruce T.] Univ Connecticut, Med Ctr, Pat & Jim Calhoun Cardiol Ctr, Farmington, CT 06032 USA. [Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Liang, BT (reprint author), Univ Connecticut, Med Ctr, Calhoun Cardiol Ctr, 263 Farmington Ave,MC3946, Farmington, CT 06032 USA. EM bliang@uchc.edu RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU National Institutes of Health [HL48225]; National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program FX This work was supported by National Institutes of Health grant HL48225 and the National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program. NR 33 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAY PY 2014 VL 7 IS 3 BP 510 EP U252 DI 10.1161/CIRCHEARTFAILURE.113.001023 PG 27 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI3WV UT WOS:000336796900018 PM 24622244 ER PT J AU Garvey, B Turkbey, B Truong, H Bernardo, M Periaswamy, S Choyke, PL AF Garvey, Brian Tuerkbey, Baris Truong, Hong Bernardo, Marcelino Periaswamy, Senthil Choyke, Peter L. TI Clinical value of prostate segmentation and volume determination on MRI in benign prostatic hyperplasia SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY LA English DT Review ID MAGNETIC-RESONANCE; TRANSRECTAL ULTRASOUND; TRANSITION ZONE; AUTOMATIC SEGMENTATION; TISSUE COMPOSITION; RESIDUAL URINE; MEN; FINASTERIDE; IMAGES; AGE AB Benign prostatic hyperplasia (BPH) is a nonmalignant pathological enlargement of the prostate, which occurs primarily in the transitional zone. BPH is highly prevalent and is a major cause of lower urinary tract symptoms in aging males, although there is no direct relationship between prostate volume and symptom severity. The progression of BPH can be quantified by measuring the volumes of the whole prostate and its zones, based on image segmentation on magnetic resonance imaging. Prostate volume determination via segmentation is a useful measure for patients undergoing therapy for BPH. However, prostate segmentation is not widely used due to the excessive time required for even experts to manually map the margins of the prostate. Here, we review and compare new methods of prostate volume segmentation using both manual and automated methods, including the ellipsoid formula, manual planimetry, and semiautomated and fully automated segmentation approaches. We highlight the utility of prostate segmentation in the clinical context of assessing BPH. C1 [Garvey, Brian; Tuerkbey, Baris; Bernardo, Marcelino; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Truong, Hong] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Periaswamy, Senthil] iCAD Inc, Nashua, NH USA. RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. EM bturkbey@yahoo.com NR 37 TC 2 Z9 2 U1 0 U2 1 PU AVES PI FINDIKZADE PA IBRAHIM KARA, KIZILELMA CAD 5-3, FINDIKZADE, ISTANBUL 34096, TURKEY SN 1305-3825 EI 1305-3612 J9 DIAGN INTERV RADIOL JI Diagn. Interv. Radiol. PD MAY PY 2014 VL 20 IS 3 BP 229 EP 233 DI 10.5152/dir.2014.13322 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI8OC UT WOS:000337177600005 PM 24675166 ER PT J AU Hong, CW Walton-Diaz, A Rais-Bahrami, S Hoang, AN Turkbey, B Stamatakis, L Xu, S Amalou, H Siddiqui, MM Nix, JW Vourganti, S Merino, MJ Choyke, PL Wood, BJ Pinto, PA AF Hong, Cheng William Walton-Diaz, Annerleim Rais-Bahrami, Soroush Hoang, Anthony N. Tuerkbey, Baris Stamatakis, Lambros Xu, Sheng Amalou, Hayet Siddiqui, M. Minhaj Nix, Jeffrey W. Vourganti, Srinivas Merino, Maria J. Choyke, Peter L. Wood, Bradford J. Pinto, Peter A. TI Imaging and pathology findings after an initial negative MRI-US fusion-guided and 12-core extended sextant prostate biopsy session SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY LA English DT Article ID TRANSRECTAL ULTRASOUND BIOPSY; ACTIVE SURVEILLANCE; CANCER AB PURPOSE A magnetic resonance imaging-ultrasonography (MRI-US) fusion-guided prostate biopsy increases detection rates compared to an extended sextant biopsy. The imaging characteristics and pathology outcomes of subsequent biopsies in patients with initially negative MRI-US fusion biopsies are described in this study. MATERIALS AND METHODS We reviewed 855 biopsy sessions of 751 patients (June 2007 to March 2013). The fusion biopsy consisted of two cores per lesion identified on multiparametric MRI (mpMRI) and a 12-core extended sextant transrectal US (TRUS) biopsy. Inclusion criteria were at least two fusion biopsy sessions, with a negative first biopsy and mpMRI before each. RESULTS The detection rate on the initial fusion biopsy was 55.3%; 336 patients had negative findings. Forty-one patients had follow-up fusion biopsies, but only 34 of these were preceded by a repeat mpMRI. The median interval between biopsies was 15 months. Fourteen patients (41%) were positive for cancer on the repeat MRI-US fusion biopsy. Age, prostate- specific antigen (PSA), prostate volume, PSA density, digital rectal exam findings, lesion diameter, and changes on imaging were comparable between patients with negative and positive rebiopsies. Of the patients with positive rebiopsies, 79% had a positive TRUS biopsy before referral (P = 0.004). Ten patients had Gleason 3+3 disease, three had 3+4 disease, and one had 4+4 disease. CONCLUSION In patients with a negative MRI-US fusion prostate biopsy and indications for repeat biopsy, the detection rate of the follow-up sessions was lower than the initial detection rate. Of the prostate cancers subsequently found, 93% were low grade (<= 3+4). In this low risk group of patients, increasing the follow-up time interval should be considered in the appropriate clinical setting. C1 [Hong, Cheng William; Xu, Sheng; Amalou, Hayet; Wood, Bradford J.] NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA. [Walton-Diaz, Annerleim; Rais-Bahrami, Soroush; Hoang, Anthony N.; Stamatakis, Lambros; Siddiqui, M. Minhaj; Nix, Jeffrey W.; Vourganti, Srinivas; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Tuerkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Hong, CW (reprint author), NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA. EM williamhongcheng@gmail.com OI Rais-Bahrami, Soroush/0000-0001-9466-9925 FU Intramural NIH HHS [ZIA CL040011-06] NR 23 TC 4 Z9 4 U1 0 U2 1 PU AVES PI FINDIKZADE PA IBRAHIM KARA, KIZILELMA CAD 5-3, FINDIKZADE, ISTANBUL 34096, TURKEY SN 1305-3825 EI 1305-3612 J9 DIAGN INTERV RADIOL JI Diagn. Interv. Radiol. PD MAY PY 2014 VL 20 IS 3 BP 234 EP 238 DI 10.5152/dir.2014.13345 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI8OC UT WOS:000337177600006 PM 24509182 ER PT J AU Jin, GX Wong, STC AF Jin, Guangxu Wong, Stephen T. C. TI Toward better drug repositioning: prioritizing and integrating existing methods into efficient pipelines SO DRUG DISCOVERY TODAY LA English DT Review ID OFF-LABEL USE; INTERACTION DATABASE; CONNECTIVITY MAP; ONCOLOGY DRUGS; LIGAND DATABASE; MICROARRAY DATA; DISCOVERY; TARGET; INHIBITORS; NETWORKS AB Recycling old drugs, rescuing shelved drugs and extending patents' lives make drug repositioning an attractive form of drug discovery. Drug repositioning accounts for approximately 30% of the newly US Food and Drug Administration (FDA)-approved drugs and vaccines in recent years. The prevalence of drug-repositioning studies has resulted in a variety of innovative computational methods for the identification of new opportunities for the use of old drugs. Questions often arise from customizing or optimizing these methods into efficient drug-repositioning pipelines for alternative applications. It requires a comprehensive understanding of the available methods gained by evaluating both biological and pharmaceutical knowledge and the elucidated mechanism-of-action of drugs. Here, we provide guidance for prioritizing and integrating drug-repositioning methods for specific drug-repositioning pipelines. C1 [Jin, Guangxu; Wong, Stephen T. C.] Weill Cornell Med Coll, Houston Methodist Res Inst, Dept Syst Med & Bioengn, Houston, TX 77030 USA. [Jin, Guangxu; Wong, Stephen T. C.] Houston Methodist Res Inst, NCI Ctr Modeling Canc Dev, Houston, TX 77030 USA. RP Wong, STC (reprint author), Weill Cornell Med Coll, Houston Methodist Res Inst, Dept Syst Med & Bioengn, Houston, TX 77030 USA. EM stwong@tmhs.org FU National Institutes of Health (NIH) [U54 CA149196]; National Cancer Institute (NCI) [CA121225]; John S. Dunn Research Foundation; Chao Foundation grant FX This research is funded by the National Institutes of Health (NIH) U54 CA149196, National Cancer Institute (NCI) CA121225, a John S. Dunn Research Foundation grant and a T.T. & W.F. Chao Foundation grant to S.T.C.W. The authors would like to thank Rebecca Danforth for proofreading the manuscript. NR 65 TC 64 Z9 65 U1 4 U2 35 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 EI 1878-5832 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD MAY PY 2014 VL 19 IS 5 BP 637 EP 644 DI 10.1016/j.drudis.2013.11.005 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AI5ZL UT WOS:000336949400012 PM 24239728 ER PT J AU Doimo, NTS Zarate-Blades, CR Rodrigues, RF Tefe-Silva, C Trotte, MNS Souza, PRM Soares, LS Rios, WM Floriano, EM Brandao, IT Masson, AP Coelho, V Ramos, SG Silva, CL AF Doimo, Nayara T. S. Zarate-Blades, Carlos R. Rodrigues, Rodrigo F. Tefe-Silva, Cristiane Trotte, Marcele N. S. Souza, Patricia R. M. Soares, Luana S. Rios, Wendy M. Floriano, Elaine M. Brandao, Izaira T. Masson, Ana P. Coelho, Veronica Ramos, Simone G. Silva, Celio L. TI Immunotherapy of tuberculosis with Mycobacterium leprae Hsp65 as a DNA vaccine triggers cross-reactive antibodies against mammalian Hsp60 but not pathological autoimmunity SO HUMAN VACCINES & IMMUNOTHERAPEUTICS LA English DT Article DE tuberculosis; autoimmune response; heat-shock protein; DNA vaccine; immunotherapy ID T-CELLS; MICE; PATHOGENESIS; THERAPY; LUNG; IDENTIFICATION; EXPRESSION; INFECTION; ARTHRITIS; GAMMA AB Despite substantial efforts in recent years toward the development of new vaccines and drugs against tuberculosis (TB), success has remained elusive. Immunotherapy of TB with mycobacterial Hsp65 as a DNA vaccine (DNA-hsp65) results in a reduction of systemic bacterial loads and lung tissue damage, but the high homology of Hsp65 with the mammalian protein raises concern that pathological autoimmune responses may also be triggered. We searched for autoimmune responses elicited by DNA-hsp65 immunotherapy in mice chronically infected with TB by evaluating the humoral immune response and comprehensive histopathology using stereology. Cross-reactive antibodies between mycobacterial and mammalian Hsp60/65 were detected; however, no signs of pathological autoimmunity were found up to 60 days after the end of the therapy. C1 [Doimo, Nayara T. S.; Zarate-Blades, Carlos R.; Rodrigues, Rodrigo F.; Souza, Patricia R. M.; Soares, Luana S.; Rios, Wendy M.; Brandao, Izaira T.; Masson, Ana P.; Silva, Celio L.] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Biochem & Immunol, Ctr TB Res, Sao Paulo, Brazil. [Tefe-Silva, Cristiane; Floriano, Elaine M.; Ramos, Simone G.] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Pathol, Sao Paulo, Brazil. [Trotte, Marcele N. S.] Univ Estado Rio De Janeiro, Vet Med Dept Anat Pathol, Rio De Janeiro, Brazil. [Coelho, Veronica] Univ Sao Paulo, Sch Med, Heart Inst InCor, Immunol Lab, Sao Paulo, Brazil. [Coelho, Veronica] NIST, Inst Invest Immunol 3, Sao Paulo, Brazil. RP Zarate-Blades, CR (reprint author), NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM crzblades@usp.br; clsilva@fmrp.usp.br RI Zarate-Blades, Carlos/C-9663-2015; Silva, Celio/C-4639-2012 OI Zarate-Blades, Carlos/0000-0002-7728-7869; FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, FAPESP [2009/06793-7] FX This research received support from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, FAPESP (Grant number 2009/06793-7). We thank Dr Carlos A Mandarim-de-Lacerda for excellent discussion prior initiation of the study. NR 36 TC 2 Z9 3 U1 1 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2164-5515 EI 2164-554X J9 HUM VACC IMMUNOTHER JI Human Vaccines Immunother. PD MAY PY 2014 VL 10 IS 5 BP 1238 EP 1243 DI 10.4161/hv.28249 PG 6 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA AI2AA UT WOS:000336656700022 PM 24607935 ER PT J AU Del Fiol, G Workman, TE Gorman, PN AF Del Fiol, Guilherme Workman, T. Elizabeth Gorman, Paul N. TI Clinical Questions Raised by Clinicians at the Point of Care A Systematic Review SO JAMA INTERNAL MEDICINE LA English DT Article ID INFORMATION-SEEKING BEHAVIOR; PATIENT-CARE; HEALTH-CARE; FAMILY PHYSICIANS; MEDICAL INFORMATION; ONLINE EVIDENCE; NEEDS; KNOWLEDGE; RESIDENTS; ANSWERS AB IMPORTANCE In making decisions about patient care, clinicians raise questions and are unable to pursue or find answers to most of them. Unanswered questions may lead to suboptimal patient care decisions. OBJECTIVE To systematically review studies that examined the questions clinicians raise in the context of patient care decision making. DATA SOURCES MEDLINE (from 1966), CINAHL (from 1982), and Scopus (from 1947), all through May 26, 2011. STUDY SELECTION Studies that examined questions raised and observed by clinicians (physicians, medical residents, physician assistants, nurse practitioners, nurses, dentists, and care managers) in the context of patient care were independently screened and abstracted by 2 investigators. Of 21 710 citations, 72 met the selection criteria. DATA EXTRACTION AND SYNTHESIS Question frequency was estimated by pooling data from studies with similar methods. MAIN OUTCOMES AND MEASURES Frequency of questions raised, pursued, and answered and questions by type according to a taxonomy of clinical questions. Thematic analysis of barriers to information seeking and the effects of information seeking on decision making. RESULTS In 11 studies, 7012 questions were elicited through short interviews with clinicians after each patient visit. The mean frequency of questions raised was 0.57 (95% CI, 0.38-0.77) per patient seen, and clinicians pursued 51%(36%-66%) of questions and found answers to 78%(67%-88%) of those they pursued. Overall, 34% of questions concerned drug treatment, and 24% concerned potential causes of a symptom, physical finding, or diagnostic test finding. Clinicians' lack of time and doubt that a useful answer exists were the main barriers to information seeking. CONCLUSIONS AND RELEVANCE Clinicians frequently raise questions about patient care in their practice. Although they are effective at finding answers to questions they pursue, roughly half of the questions are never pursued. This picture has been fairly stable over time despite the broad availability of online evidence resources that can answer these questions. Technology-based solutions should enable clinicians to track their questions and provide just-in-time access to high-quality evidence in the context of patient care decision making. Opportunities for improvement include the recent adoption of electronic health record systems and maintenance of certification requirements. C1 [Del Fiol, Guilherme] Univ Utah, Dept Biomed Informat, Salt Lake City, UT 84108 USA. [Workman, T. Elizabeth] Natl Lib Med, Lister Hill Ctr, Bethesda, MD USA. [Gorman, Paul N.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. RP Del Fiol, G (reprint author), Univ Utah, Dept Biomed Informat, 421 Wakara Way,Ste 140, Salt Lake City, UT 84108 USA. EM guilherme.delfiol@utah.edu OI Del Fiol, Guilherme/0000-0001-9954-6799 FU Agency for Healthcare Research and Quality [K01HS018352] FX This project was supported by the Agency for Healthcare Research and Quality (grant K01HS018352). NR 80 TC 25 Z9 28 U1 4 U2 27 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAY PY 2014 VL 174 IS 5 BP 710 EP 718 DI 10.1001/jamainternmed.2014.368 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AI4NS UT WOS:000336842700013 PM 24663331 ER PT J AU Bonds, DE Harrington, M Worrall, BB Bertoni, AG Eaton, CB Hsia, J Robinson, J Clemons, TE Fine, LJ Chew, EY AF Bonds, Denise E. Harrington, Molly Worrall, Bradford B. Bertoni, Alain G. Eaton, Charles B. Hsia, Judy Robinson, Jennifer Clemons, Traci E. Fine, Lawrence J. Chew, Emily Y. CA AREDS2 Res Grp TI Effect of Long-Chain omega-3 Fatty Acids and Lutein plus Zeaxanthin Supplements on Cardiovascular Outcomes Results of the Age-Related Eye Disease Study 2 (AREDS2) Randomized Clinical Trial SO JAMA INTERNAL MEDICINE LA English DT Article ID N-3 FATTY-ACIDS; MYOCARDIAL-INFARCTION; FISH CONSUMPTION; B-VITAMINS; RISK; DEATH; ATHEROSCLEROSIS; ASSOCIATION; DYSGLYCEMIA; CAROTENOIDS AB IMPORTANCE Dietary supplements have been proposed as a mechanism to improve health and prevent disease. OBJECTIVE To determine if supplementing diet with long-chain omega-3 polyunsaturated fatty acids or with macular xanthophylls results in a reduced rate of cardiovascular disease (CVD). DESIGN, SETTING, AND PARTICIPANTS The Cardiovascular Outcome Study (COS) was an ancillary study of the Age-Related Eye Disease Study 2 (AREDS2), a factorial-designed randomized clinical trial of 4203 participants recruited from 82 US academic and community ophthalmology clinics, who were followed up for a median of 4.8 years. Individuals were eligible to participate if they were between the ages of 50 and 85 years, had intermediate or advanced age-related macular degeneration in 1 eye, and were willing to be randomized. Participants with stable, existing CVD (>12 months since initial event) were eligible to participate. Participants, staff, and outcome assessors were masked to intervention. INTERVENTIONS Daily supplementation with long-chain omega-3 polyunsaturated fatty acids (350-mg docosahexaenoic acid [DHA] + 650-mg eicosapentaenoic acid [EPA]), macular xanthophylls (10-mg lutein + 2-mg zeaxanthin), combination of the two, or matching placebos. These treatments were added to background therapy of the AREDS vitamin and mineral formulation for macular degeneration. MAIN OUTCOMES AND MEASURES A composite outcome of myocardial infarction, stroke, and cardiovascular death with 4 prespecified secondary combinations of the primary outcome with hospitalized heart failure, revascularization, or unstable angina. RESULTS Study participants were primarily white, married, and highly educated, with a median age at baseline of 74 years. A total of 602 cardiovascular events were adjudicated, and 459 were found to meet 1 of the study definitions for a CVD outcome. In intention-to-treat analysis, no reduction in the risk of CVD or secondary CVD outcomes was seen for the DHA + EPA (primary outcome: hazard ratio [HR], 0.95; 95% CI, 0.78-1.17) or lutein + zeaxanthin (primary outcome: HR, 0.94; 95% CI, 0.77-1.15) groups. No differences in adverse events or serious adverse event were seen by treatment group. The sample size was sufficient to detect a 25% reduction in CVD events with 80% power. CONCLUSIONS AND RELEVANCE Dietary supplementation of long-chain omega-3 polyunsaturated fatty acids or macular xanthophylls in addition to daily intake of minerals and vitamins did not reduce the risk of CVD in elderly participants with age-related macular degeneration. C1 [Bonds, Denise E.; Fine, Lawrence J.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Harrington, Molly; Clemons, Traci E.] EMMES Corp, Rockville, MD USA. [Worrall, Bradford B.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. [Bertoni, Alain G.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Eaton, Charles B.] Alpert Med Sch, Div Biol & Med, Dept Family Med & Epidemiol, Providence, RI USA. [Eaton, Charles B.] Brown Univ, Sch Publ Hlth, Providence, RI 02912 USA. [Hsia, Judy] AstraZeneca LLP, Washington, DC USA. [Robinson, Jennifer] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Robinson, Jennifer] Univ Iowa, Dept Med, Iowa City, IA 52242 USA. [Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. RP Bonds, DE (reprint author), NHLBI, Rockledge Ctr 2, MSC 7936,6701 Rockledge Dr,Ste 10018, Bethesda, MD 20892 USA. EM bondsde@nhlbi.nih.gov FU National Eye Institute/National Institutes of Health, Department of Health and Human Services [HHS-N-260-2005-00007-C]; ADB [N01-EY-5-0007]; National Institutes of Health (NIH): Office of Dietary Supplements; National Center for Complementary and Alternative Medicine, National Institute on Aging, National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke FX The AREDS2 study is supported by the intramural program funds and contracts from the National Eye Institute/National Institutes of Health, Department of Health and Human Services (contract No. HHS-N-260-2005-00007-C and ADB contract No. N01-EY-5-0007). Funds were generously contributed to these contracts by the following National Institutes of Health (NIH): Office of Dietary Supplements, National Center for Complementary and Alternative Medicine, National Institute on Aging, National Heart, Lung, and Blood Institute, and National Institute of Neurological Disorders and Stroke. NR 21 TC 22 Z9 22 U1 5 U2 24 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAY PY 2014 VL 174 IS 5 BP 763 EP 771 DI 10.1001/jamainternmed.2014.328 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AI4NS UT WOS:000336842700023 ER PT J AU Dutton-Regester, K Gartner, JJ Emmanuel, R Qutob, N Davies, MA Gershenwald, JE Robinson, W Robinson, S Steven, AR Scolyer, RA Mann, GJ Thompson, JF Hayward, NK Samuels, Y AF Dutton-Regester, Ken Gartner, Jared J. Emmanuel, Rafi Qutob, Nouar Davies, Michael A. Gershenwald, Jeffrey E. Robinson, William Robinson, Steven Steven, A. Rosenberg Scolyer, Richard A. Mann, Graham J. Thompson, John F. Hayward, Nicholas K. Samuels, Yardena TI A highly recurrent RPS27 5 ' UTR mutation in melanoma SO ONCOTARGET LA English DT Article DE Melanoma; somatic mutation; RPS27; exome sequencing; 5 ' untranslated region ID TOP MESSENGER-RNAS; TRANSLATIONAL CONTROL; OLIGOPYRIMIDINE-TRACT; CANCER-THERAPY; PHASE-I; PROTEIN; GENOME; MTOR; METALLOPROTEINASE; INHIBITION AB The incidence of melanoma continues to rise globally and is increasing at a rate greater than any other cancer. To systematically search for new genes involved in melanomagenesis, we collated exome sequencing data from independent melanoma cohort datasets, including those in the public domain. We identified recurrent mutations that may drive melanoma growth, survival or metastasis, and which may hold promise for the design of novel therapies to treat melanoma. These included a frequent recurrent (i.e. hotspot) mutation in the 5' untranslated region of RPS27 in similar to 10% of samples. We show that the mutation expands the 5'TOP element, a motif known to regulate the expression of most of the ribosomal protein family, to which RPS27 belongs, and thus might sensitize the mutated transcript to growth-mediated regulation. This finding highlights not only the important role of non-protein coding genetic aberrations in cancer development but also their potential as novel therapeutic targets. C1 [Dutton-Regester, Ken; Hayward, Nicholas K.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia. [Gartner, Jared J.; Steven, A. Rosenberg] NCI, NIH, Bethesda, MD 20892 USA. [Emmanuel, Rafi; Qutob, Nouar; Samuels, Yardena] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. [Davies, Michael A.; Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Robinson, William; Robinson, Steven] Univ Colorado, Sch Med, Aurora, CO USA. [Scolyer, Richard A.; Mann, Graham J.; Thompson, John F.] Melanoma Inst Australia, Sydney, NSW, Australia. [Scolyer, Richard A.] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia. [Scolyer, Richard A.] Univ Sydney, Discipline Pathol, Sydney, NSW 2006, Australia. [Mann, Graham J.] Univ Sydney, Westmead Millenium Inst, Westmead, NSW 2145, Australia. [Thompson, John F.] Dept Melanoma, Sydney, NSW, Australia. [Thompson, John F.] Dept Surg Oncol, Sydney, NSW, Australia. [Thompson, John F.] Royal Prince Alfred Hosp, Sydney, NSW, Australia. [Thompson, John F.] Univ Sydney, Discipline Surg, Sydney Med Sch, Sydney, NSW 2006, Australia. RP Samuels, Y (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. EM Nicholas.Hayward@qimrberghofer.edu.au; Yardena.Samuels@weizmann.ac.il RI hayward, nicholas/C-1367-2015; OI hayward, nicholas/0000-0003-4760-1033; Scolyer, Richard/0000-0002-8991-0013 FU National Human Genome Research Institute; National Institutes of Health, USA; University of Texas MD Anderson Cancer Center Melanoma SPORE [P50CA093459]; National Health and Medical Research Council (NHMRC) of Australia; Israel Science Foundation [1604/13, 877/13]; ERC [StG-335377]; Dukler Fund for Cancer Research; Comisaroff Family Trust; NHRMC; Gideon Hamburger, Israel FX This work was supported by the Intramural Research Programs of the National Human Genome Research Institute, National Institutes of Health, USA, The University of Texas MD Anderson Cancer Center Melanoma SPORE (P50CA093459) and the National Health and Medical Research Council (NHMRC) of Australia. YS is supported by the Israel Science Foundation grant numbers 1604/13 and 877/13, the ERC (StG-335377), Dukler Fund for Cancer Research, Comisaroff Family Trust and Gideon Hamburger, Israel. NKH and KD-R are supported by fellowships from the NHRMC. The authors gratefully acknowledge the assistance of Gulietta Pupo, Varsha Tembe, Candace Carter and other colleagues from Melanoma Institute Australia, Royal Prince Alfred Hospital and Westmead Millennium Institute, Sydney, Australia. NR 38 TC 13 Z9 14 U1 0 U2 6 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD MAY PY 2014 VL 5 IS 10 BP 2912 EP 2917 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AI6FL UT WOS:000336967000004 PM 24913145 ER PT J AU Sequeira, G Vanzulli, SI Rojas, P Lamb, C Colombo, L May, M Molinolo, A Lanari, C AF Sequeira, Gonzalo Vanzulli, Silvia I. Rojas, Paola Lamb, Caroline Colombo, Lucas May, Maria Molinolo, Alfredo Lanari, Claudia TI The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancer SO ONCOTARGET LA English DT Article DE breast cancer; PR isoforms; doxorubicin; paclitaxel; mifepristone; mammary carcinomas; Nab-paclitaxel; pegylated doxorubicin liposomes ID PROGESTERONE-RECEPTOR ISOFORMS; ALBUMIN-BOUND PACLITAXEL; PHASE-III TRIAL; MAMMARY CARCINOMAS; TUMOR-REGRESSION; GENE-REGULATION; CREMOPHOR-FREE; DOXORUBICIN; TAXOL; CELLS AB There is clinical and experimental evidence suggesting that antiprogestins might be used for the treatment of selected breast cancer patients. Our aim was to evaluate the effect of albumin-bound paclitaxel (Nab-paclitaxel) and pegylated doxorubicin liposomes (PEG-LD) in combination with mifepristone (MFP) in experimental breast cancer models expressing different ratios of progesterone receptor (PR) isoforms A and B. We used two antiprogestin-responsive (PRA>PRB) and two resistant (PRA50% of tumor cells in a majority of ASs but only in 7% of EHEs. None of the 55 ASs studied were immunohistochemically positive for TIA-1 or Granzyme B, antigens used as more specific markers for anaplastic large-cell lymphoma. Compared with AS, normal vascular endothelia of capillaries and muscular vessels showed variable positivity. Among hemangiomas, cavernous and spindle cell hemangiomas showed most frequent endothelial CD30 positivity, whereas in most other hemangiomas, CD30 positivity was scant. In conclusion, CD30 expression occurs in a significant subset of ASs and EHEs and needs to be included in the differential diagnosis with other CD30-positive malignancies to avoid a diagnostic pitfall. It remains to be determined whether patients with strongly CD30-positive ASs could be candidates for targeted therapy using the recently introduced CD30 antibody drug conjugates. C1 [Alimchandani, Meghna; Wang, Zeng-Feng; Miettinen, Markku] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Miettinen, M (reprint author), NCI, Pathol Lab, NIH, 10 Ctr Dr,Bldg 10-2B50, Bethesda, MD 20892 USA. EM miettinenmm@mail.nih.gov FU NCI's Intramural Research Program FX Supported as a part of NCI's Intramural Research Program. NR 28 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1541-2016 EI 1533-4058 J9 APPL IMMUNOHISTO M M JI Appl. Immunohistochem. PD MAY-JUN PY 2014 VL 22 IS 5 BP 358 EP 362 DI 10.1097/PAI.0000000000000048 PG 5 WC Anatomy & Morphology; Medical Laboratory Technology; Pathology SC Anatomy & Morphology; Medical Laboratory Technology; Pathology GA AI3FI UT WOS:000336745600006 PM 24805132 ER PT J AU Wu, XS Zhang, Z Zhao, WD Wang, DS Luo, FJ Wu, LG AF Wu, Xin-Sheng Zhang, Zhen Zhao, Wei-Dong Wang, Dongsheng Luo, Fujun Wu, Ling-Gang TI Calcineurin Is Universally Involved in Vesicle Endocytosis at Neuronal and Nonneuronal Secretory Cells SO CELL REPORTS LA English DT Article ID ADRENAL CHROMAFFIN CELLS; NERVE-TERMINALS; SYNAPTIC VESICLES; SYNAPTOTAGMIN-I; SLOW ENDOCYTOSIS; CALCIUM; EXOCYTOSIS; SYNAPSES; RELEASE; CALYX AB Calcium influx triggers and accelerates endocytosis in nerve terminals and nonneuronal secretory cells. Whether calcium/calmodulin-activated calcineurin, which dephosphorylates endocytic proteins, mediates this process is highly controversial for different cell types, developmental stages, and endocytic forms. Using three preparations that previously produced discrepant results (i.e., large calyx-type synapses, conventional cerebellar synapses, and neuroendocrine chromaffin cells containing large dense-core vesicles), we found that calcineurin gene knockout consistently slowed down endocytosis, regardless of cell type, developmental stage, or endocytic form (rapid or slow). In contrast, calcineurin and calmodulin blockers slowed down endocytosis at a relatively small calcium influx, but did not inhibit endocytosis at a large calcium influx, resulting in false-negative results. These results suggest that calcineurin is universally involved in endocytosis. They may also help explain the discrepancies among previous pharmacological studies. We therefore suggest that calcineurin should be included as a key player in mediating calcium-triggered and -accelerated vesicle endocytosis. C1 [Wu, Xin-Sheng; Zhang, Zhen; Zhao, Wei-Dong; Wang, Dongsheng; Luo, Fujun; Wu, Ling-Gang] NINDS, Bethesda, MD 20892 USA. RP Wu, LG (reprint author), NINDS, Bethesda, MD 20892 USA. EM wul@ninds.nih.gov FU National Institute of Neurological Disorders; Stroke Intramural Research Program FX We thank Drs. Jonathan G. Seidman (Harvard Medical School) and Jennifer L. Gooch (Emory University School of Medicine) for providing CaN Aalpha+/- mice, and Dr. Yong-Ling Zhu (Northwestern University) for providing the SypH2X construct. We thank Dr. Edaeni Hamid for commenting on the manuscript. This work was supported by the National Institute of Neurological Disorders and Stroke Intramural Research Program. NR 33 TC 13 Z9 13 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD MAY PY 2014 VL 7 IS 4 BP 982 EP 988 DI 10.1016/j.celrep.2014.04.020 PG 7 WC Cell Biology SC Cell Biology GA AH9WL UT WOS:000336495700008 PM 24835995 ER PT J AU Kemp, CJ Moore, JM Moser, R Bernard, B Teater, M Smith, LE Rabaia, NA Gurley, KE Guinney, J Busch, SE Shaknovich, R Lobanenkov, VV Liggitt, D Shmulevich, I Melnick, A Filippova, GN AF Kemp, Christopher J. Moore, James M. Moser, Russell Bernard, Brady Teater, Matt Smith, Leslie E. Rabaia, Natalia A. Gurley, Kay E. Guinney, Justin Busch, Stephanie E. Shaknovich, Rita Lobanenkov, Victor V. Liggitt, Denny Shmulevich, Ilya Melnick, Ari Filippova, Galina N. TI CTCF Haploinsufficiency Destabilizes DNA Methylation and Predisposes to Cancer SO CELL REPORTS LA English DT Article ID PROTEIN CTCF; TRANSCRIPTION FACTOR; BINDING-SITES; GENOME-WIDE; BREAST; SPECIFICITY; MUTATIONS; GENETICS; GENES; MAP AB Epigenetic alterations, particularly in DNA methylation, are ubiquitous in cancer, yet the molecular origins and the consequences of these alterations are poorly understood. CTCF, a DNA-binding protein that regulates higher-order chromatin organization, is frequently altered by hemizygous deletion or mutation in human cancer. To date, a causal role for CTCF in cancer has not been established. Here, we show that Ctcf hemizygous knockout mice are markedly susceptible to spontaneous, radiation-, and chemically induced cancer in a broad range of tissues. Ctcf(+/-) tumors are characterized by increased aggressiveness, including invasion, metastatic dissemination, and mixed epithelial/mesenchymal differentiation. Molecular analysis of Ctcf(+/-) tumors indicates that Ctcf is haploinsufficient for tumor suppression. Tissues with hemizygous loss of CTCF exhibit increased variability in CpG methylation genome wide. These findings establish CTCF as a prominent tumor-suppressor gene and point to CTCF-mediated epigenetic stability as a major barrier to neoplastic progression. C1 [Kemp, Christopher J.; Moore, James M.; Moser, Russell; Smith, Leslie E.; Rabaia, Natalia A.; Gurley, Kay E.; Busch, Stephanie E.; Filippova, Galina N.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. [Bernard, Brady; Shmulevich, Ilya] Inst Syst Biol, Seattle, WA 98106 USA. [Teater, Matt; Shaknovich, Rita; Melnick, Ari] Weill Cornell Med Coll, Div Hematol Oncol, New York, NY 10021 USA. [Guinney, Justin] Sage Bionetworks, Seattle, WA 98109 USA. [Lobanenkov, Victor V.] NIAID, Mol Pathol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Liggitt, Denny] Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA. RP Kemp, CJ (reprint author), Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. EM cjkemp@fhcrc.org; gfilippo@fhcrc.org OI Lobanenkov, Victor/0000-0001-6665-3635 FU NIH [CA68360, ES007033, DA030326, U24CA143835, U01 CA141550, U01 CA176303]; NIGMS [PHS NRSA T32 GM007270] FX This work was supported by NIH grant numbers CA68360, ES007033, DA030326, U24CA143835, U01 CA141550, U01 CA176303, and PHS NRSA T32 GM007270 from NIGMS. We thank S. Collins, C. Grandori, S. Henikoff, S. Tapscott, and F. Yang for comments on the manuscript, and the William Guy Forbeck Research Foundation. NR 24 TC 29 Z9 29 U1 3 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD MAY PY 2014 VL 7 IS 4 BP 1020 EP 1029 DI 10.1016/j.celrep.2014.04.004 PG 10 WC Cell Biology SC Cell Biology GA AH9WL UT WOS:000336495700012 PM 24794443 ER PT J AU Portmann, T Yang, M Mao, R Panagiotakos, G Ellegood, J Dolen, G Bader, PL Grueter, BA Goold, C Fisher, E Clifford, K Rengarajan, P Kalikhman, D Loureiro, D Saw, NL Zhou, ZQ Miller, MA Lerch, JP Henkelman, RM Shamloo, M Malenka, RC Crawley, JN Dolmetsch, RE AF Portmann, Thomas Yang, Mu Mao, Rong Panagiotakos, Georgia Ellegood, Jacob Dolen, Gul Bader, Patrick L. Grueter, Brad A. Goold, Carleton Fisher, Elaine Clifford, Katherine Rengarajan, Pavitra Kalikhman, David Loureiro, Darren Saw, Nay L. Zhou Zhengqui Miller, Michael A. Lerch, Jason P. Henkelman, R. Mark Shamloo, Mehrdad Malenka, Robert C. Crawley, Jacqueline N. Dolmetsch, Ricardo E. TI Behavioral Abnormalities and Circuit Defects in the Basal Ganglia of a Mouse Model of 16p11.2 Deletion Syndrome SO CELL REPORTS LA English DT Article ID DEVELOPING CEREBRAL-CORTEX; AUTISM SPECTRUM DISORDERS; SUBTYPE-SPECIFIC GENES; PROJECTION NEURONS; MOLECULAR SPECIFICATION; NUCLEUS-ACCUMBENS; PYRAMIDAL NEURONS; TIMOTHY SYNDROME; CORPUS-CALLOSUM; PHENOTYPES AB A deletion on human chromosome 16p11.2 is associated with autism spectrum disorders. We deleted the syntenic region on mouse chromosome 7F3. MRI and high-throughput single-cell transcriptomics revealed anatomical and cellular abnormalities, particularly in cortex and striatum of juvenile mutant mice (16p11(+/-)). We found elevated numbers of striatal medium spiny neurons (MSNs) expressing the dopamine D2 receptor (Drd2(+)) and fewer dopamine-sensitive (Drd1(+)) neurons in deep layers of cortex. Electrophysiological recordings of Drd2(+) MSN revealed synaptic defects, suggesting abnormal basal ganglia circuitry function in 16p11(+/-) mice. This is further supported by behavioral experiments showing hyperactivity, circling, and deficits in movement control. Strikingly, 16p11(+/-) mice showed a complete lack of habituation reminiscent of what is observed in some autistic individuals. Our findings unveil a fundamental role of genes affected by the 16p11.2 deletion in establishing the basal ganglia circuitry and provide insights in the pathophysiology of autism. C1 [Portmann, Thomas; Mao, Rong; Panagiotakos, Georgia; Goold, Carleton; Fisher, Elaine; Clifford, Katherine; Rengarajan, Pavitra; Dolmetsch, Ricardo E.] Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA. [Portmann, Thomas; Mao, Rong; Panagiotakos, Georgia; Bader, Patrick L.; Grueter, Brad A.; Goold, Carleton; Fisher, Elaine; Clifford, Katherine; Rengarajan, Pavitra; Shamloo, Mehrdad; Malenka, Robert C.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Yang, Mu; Kalikhman, David; Loureiro, Darren; Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA. Stanford Univ, Neurosci Program, Stanford, CA 94305 USA. [Ellegood, Jacob; Lerch, Jason P.; Henkelman, R. Mark] Hosp Sick Children, Mouse Imaging Ctr MICe, Toronto, ON M5T 3H7, Canada. [Dolen, Gul] Johns Hopkins Univ, Brain Sci Inst, Dept Neurosci, Baltimore, MD 21205 USA. [Bader, Patrick L.] Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. [Grueter, Brad A.; Malenka, Robert C.] Stanford Univ, Dept Psychiat & Behav Sci, Nancy Pritzker Lab, Stanford, CA 94305 USA. [Saw, Nay L.; Zhou Zhengqui; Miller, Michael A.; Shamloo, Mehrdad] Stanford Behav & Funct Neurosci Lab, Stanford, CA 94305 USA. [Lerch, Jason P.; Henkelman, R. Mark] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada. [Shamloo, Mehrdad] Stanford Inst Neuroinnovat & Translat Neurosci, Stanford, CA 94305 USA. [Dolmetsch, Ricardo E.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. RP Dolmetsch, RE (reprint author), Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA. EM ricardo.dolmetsch@novartis.com RI Dolen, Gul/J-3073-2015; Henkelman, Mark/F-3662-2011; OI Dolen, Gul/0000-0003-1780-995X; Grueter, Brad/0000-0002-4224-3866 FU Simons foundation SFARI grant [204340]; Nina Jauw; Swiss National Science Foundation [PBSKP3-123434, PA00P3_134196]; NIMH Intramural Research Program; University of California Davis MIND Institute; NIMH [MH09064802]; NIH/NIMH [MH091160]; Institute of Neurological Disorders and Stroke P30 center core grant [NS06937501A1] FX We would like to thank Ulrich Elling and Josef Penninger (IMBA Vienna, Austria) for help and advice on mouse ESC targeting, Marty Bigos of the Stanford shared FACS facility for assistance with clone sorting, Renee Reijo-Pera for generously providing the Biomark Instruments, Kristin L. Sainani for advice in statistical analysis of mouse behavioral data, and Yishan Sun for validating and providing primer pairs for the single-cell gene expression analysis. This research was funded by the Simons foundation SFARI grant no. 204340 (R.E.D. and J.N.C.), Nina Jauw (R.E.D.), the Swiss National Science Foundation (nos. PBSKP3-123434 and PA00P3_134196, T. P.), the NIMH Intramural Research Program and the University of California Davis MIND Institute (M.Y., D.K., D.L., and J.N.C.), an F31 NRSA from the NIMH (no. MH09064802, G.P.), a K99 from the NIH/NIMH (no. MH091160, R.M.), and the Institute of Neurological Disorders and Stroke P30 center core grant no. NS06937501A1 (M.S.). NR 61 TC 31 Z9 31 U1 2 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD MAY PY 2014 VL 7 IS 4 BP 1077 EP 1092 DI 10.1016/j.celrep.2014.03.036 PG 16 WC Cell Biology SC Cell Biology GA AH9WL UT WOS:000336495700018 PM 24794428 ER PT J AU Ryu, JY Galan, AK Xin, XB Dong, F Abdul-Ghani, MA Zhou, LJ Wang, CH Li, CL Holmes, BM Sloane, LB Austad, SN Guo, SD Musi, N DeFronzo, RA Deng, CX White, MF Liu, F Dong, LQ AF Ryu, Jiyoon Galan, Amanda K. Xin, Xiaoban Dong, Feng Abdul-Ghani, Muhammad A. Zhou, Lijun Wang, Changhua Li, Cuiling Holmes, Bekke M. Sloane, Lauren B. Austad, Steven N. Guo, Shaodong Musi, Nicolas DeFronzo, Ralph A. Deng, Chuxia White, Morris F. Liu, Feng Dong, Lily Q. TI APPL1 Potentiates Insulin Sensitivity by Facilitating the Binding of IRS1/2 to the Insulin Receptor SO CELL REPORTS LA English DT Article ID ADAPTER PROTEIN APPL1; NITRIC-OXIDE; IN-VIVO; ADIPONECTIN; AKT; ACTIVATION; OBESITY; KINASE; CELLS; PHOSPHORYLATION AB Binding of insulin receptor substrate proteins 1 and 2 (IRS1/2) to the insulin receptor (IR) is essential for the regulation of insulin sensitivity and energy homeostasis. However, the mechanism of IRS1/2 recruitment to the IR remains elusive. Here, we identify adaptor protein APPL1 as a critical molecule that promotes IRS1/2-IR interaction. APPL1 forms a complex with IRS1/2 under basal conditions, and this complex is then recruited to the IR in response to insulin or adiponectin stimulation. The interaction between APPL1 and IR depends on insulin- or adiponectin-stimulated APPL1 phosphorylation, which is greatly reduced in insulin target tissues in obese mice. appl1 deletion in mice consistently leads to systemic insulin resistance and a significant reduction in insulin-stimulated IRS1/2, but not IR, tyrosine phosphorylation, indicating that APPL1 sensitizes insulin signaling by acting at a site downstream of the IR. Our study uncovers a mechanism regulating insulin signaling and crosstalk between the insulin and adiponectin pathways. C1 [Ryu, Jiyoon; Galan, Amanda K.; Xin, Xiaoban; Zhou, Lijun; Sloane, Lauren B.; Austad, Steven N.; Dong, Lily Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Dong, Feng; Abdul-Ghani, Muhammad A.; Musi, Nicolas; DeFronzo, Ralph A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Wang, Changhua; Liu, Feng] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Holmes, Bekke M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Austad, Steven N.; Liu, Feng; Dong, Lily Q.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Ctr Longev & Aging Studies, San Antonio, TX 78229 USA. [Li, Cuiling; Deng, Chuxia] NIDDK, Mammalian Genet Sect, GDDB, NIH, Bethesda, MD 20892 USA. [Guo, Shaodong] Texas A&M Univ, Div Mol Cardiol, Temple, TX 76504 USA. [White, Morris F.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Endocrinol, Boston, MA 02115 USA. RP Dong, LQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. EM dongQ@uthscsa.edu RI deng, chuxia/N-6713-2016 FU Career Development Award from the American Diabetes Association; NIH [R01 DK080344, R01 DK76902, NIA T32 AG021890] FX This work was supported in part by a Career Development Award from the American Diabetes Association (to L.Q.D.) and NIH grants (R01 DK080344 to L.Q.D., R01 DK76902 to F.L., and NIA T32 AG021890 to A.K.G.). NR 36 TC 24 Z9 25 U1 2 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD MAY PY 2014 VL 7 IS 4 BP 1227 EP 1238 DI 10.1016/j.celrep.2014.04.006 PG 12 WC Cell Biology SC Cell Biology GA AH9WL UT WOS:000336495700029 PM 24813896 ER PT J AU Hong, SG Winkler, T Wu, CF Guo, V Pittaluga, S Nicolae, A Donahue, RE Metzger, ME Price, SD Uchida, N Kuznetsov, SA Kilts, T Li, L Robey, PG Dunbar, CE AF Hong, So Gun Winkler, Thomas Wu, Chuanfeng Guo, Vicky Pittaluga, Stefania Nicolae, Alina Donahue, Robert E. Metzger, Mark E. Price, Sandra D. Uchida, Naoya Kuznetsov, Sergei A. Kilts, Tina Li, Li Robey, Pamela G. Dunbar, Cynthia E. TI Path to the Clinic: Assessment of iPSC-Based Cell Therapies In Vivo in a Nonhuman Primate Model SO CELL REPORTS LA English DT Article ID PLURIPOTENT STEM-CELLS; MESENCHYMAL STEM; HEMATOPOIETIC-CELLS; STROMAL CELLS; SELF-RENEWAL; BONE; MOUSE; TRANSPLANTATION; IMMUNOGENICITY; REGENERATION AB Induced pluripotent stem cell (iPSC)-based cell therapies have great potential for regenerative medicine but are also potentially associated with tumorigenic risks. Current rodent models are not optimal predictors of efficiency and safety for clinical application. Therefore, we developed a clinically relevant nonhuman primate model to assess the tumorigenic potential and in vivo efficacy of both undifferentiated and differentiated iPSCs in autologous settings without immunosuppression. Undifferentiated autologous iPSCs indeed form mature teratomas in a dose-dependent manner. However, tumor formation is accompanied by an inflammatory reaction. On the other hand, iPSC-derived mesodermal stromal-like cells form new bone in vivo without any evidence of teratoma formation. We therefore show in a large animal model that closely resembles human physiology that undifferentiated autologous iPSCs form teratomas, and that iPSC-derived progenitor cells can give rise to a functional tissue in vivo. C1 [Hong, So Gun; Winkler, Thomas; Wu, Chuanfeng; Guo, Vicky; Donahue, Robert E.; Metzger, Mark E.; Price, Sandra D.; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Pittaluga, Stefania; Nicolae, Alina] NCI, Lab Pathol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Uchida, Naoya] NHLBI, Mol & Clin Hematol Branch, NIDDK, NIH, Bethesda, MD 20892 USA. [Kuznetsov, Sergei A.; Kilts, Tina; Li, Li; Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov RI Wu, Chuanfeng/A-1109-2016 FU Divisions of Intramural Research at the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research; National Center for Regenerative Medicine at the NIH FX This research was supported by the Divisions of Intramural Research at the National Heart, Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, and the National Center for Regenerative Medicine at the NIH. We thank the NHLBI Pathology core for tissue processing and the NHLBI Primate Facility staff for excellent animal care. The STEMCCA vector was kindly provided by Dr. Gustavo Mostoslavsky. We also thank Dr. Shoukhrat Mitalipov for providing the rhesus ESC line (ORMES-22), Dr. Harry L. Malech for sharing the Cre-GFP-puro plasmid, and Dr. Jichun Chen and Marie Desierto for their assistance in performing the teratoma assays. We are indebted to Zimmer for its gift of HA/TCP. NR 47 TC 27 Z9 27 U1 0 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD MAY PY 2014 VL 7 IS 4 BP 1298 EP 1309 DI 10.1016/j.celrep.2014.04.019 PG 12 WC Cell Biology SC Cell Biology GA AH9WL UT WOS:000336495700035 PM 24835994 ER PT J AU Rho, J Ho, N Prasad, V AF Rho, Jason Ho, Nancy Prasad, Vinay TI Counterpoint: Were Industry-Sponsored Roflumilast Trials Appropriate? No SO CHEST LA English DT Editorial Material ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CLINICAL-TRIALS; QUALITY; COPD C1 [Rho, Jason] Northwestern Univ, Dept Med, Evanston, IL 60208 USA. [Ho, Nancy] Univ Maryland, Med Ctr, Dept Med, College Pk, MD 20742 USA. [Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr,10-12N226, Bethesda, MD 20892 USA. EM vinayak.prasad@nih.gov NR 24 TC 6 Z9 6 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2014 VL 145 IS 5 BP 939 EP 942 DI 10.1378/chest.14-0114 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AI0IZ UT WOS:000336532100006 PM 24798831 ER PT J AU Rho, J Ho, N Prasad, V AF Rho, Jason Ho, Nancy Prasad, Vinay TI Rebuttal From Dr Rho et al SO CHEST LA English DT Editorial Material ID ROFLUMILAST C1 [Rho, Jason] Northwestern Univ, Dept Med, Evanston, IL 60208 USA. [Ho, Nancy] Univ Maryland, Med Ctr, Dept Med, College Pk, MD 20742 USA. [Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr,10-12N226, Bethesda, MD 20892 USA. EM vinayak.prasad@nih.gov NR 4 TC 0 Z9 0 U1 1 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2014 VL 145 IS 5 BP 943 EP 944 DI 10.1378/chest.14-0115 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AI0IZ UT WOS:000336532100008 PM 24798833 ER PT J AU Blum, AB Egorova, NN Sosunov, EA Gelijns, AC DuPree, E Moskowitz, AJ Federman, AD Ascheim, DD Keyhani, S AF Blum, Alexander B. Egorova, Natalia N. Sosunov, Eugene A. Gelijns, Annetine C. DuPree, Erin Moskowitz, Alan J. Federman, Alex D. Ascheim, Deborah D. Keyhani, Salomeh TI Impact of Socioeconomic Status Measures on Hospital Profiling in New York City SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE heart failure; patient readmission; social class ID CONGESTIVE-HEART-FAILURE; MEDICARE BENEFICIARIES; SOCIAL DETERMINANTS; 30-DAY READMISSION; UNITED-STATES; HEALTH; QUALITY; CARE AB Background-Current 30-day readmission models used by the Center for Medicare and Medicaid Services for the purpose of hospital-level comparisons lack measures of socioeconomic status (SES). We examined whether the inclusion of an SES measure in 30-day congestive heart failure readmission models changed hospital risk-standardized readmission rates in New York City (NYC) hospitals. Methods and Results-Using a Centers for Medicare & Medicaid Services (CMS)-like model, we estimated 30-day hospital-level risk-standardized readmission rates by adjusting for age, sex, and comorbid conditions. Next, we examined how hospital risk-standardized readmission rates changed relative to the NYC mean with inclusion of the Agency for Healthcare Research and Quality (AHRQ)-validated SES index score. In a secondary analysis, we examined whether inclusion of the AHRQ SES index score in 30-day readmission models disproportionately impacted the risk-standardized readmission rates of minority-serving hospitals. Higher AHRQ SES scores, indicators of higher SES, were associated with lower odds (0.99) of 30-day readmission (P<0.019). The addition of the AHRQ SES index did not change the model's C statistic (0.63). After adjustment for the AHRQ SES index, 1 hospital changed status from worse than the NYC average to no different than the NYC average. After adjustment for the AHRQ SES index, 1 NYC minority-serving hospital was reclassified from worse to no different than average. Conclusions-Although patients with higher SES were less likely to be admitted, the impact of SES on readmission was small. In NYC, inclusion of the AHRQ SES score in a CMS-based model did not impact hospital-level profiling based on 30-day readmission. C1 [Blum, Alexander B.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Blum, Alexander B.; Egorova, Natalia N.; Gelijns, Annetine C.; DuPree, Erin; Moskowitz, Alan J.; Ascheim, Deborah D.] Mt Sinai Sch Med, Dept Hlth Evidence & Policy, New York, NY USA. [Moskowitz, Alan J.; Federman, Alex D.] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY USA. [Keyhani, Salomeh] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Keyhani, Salomeh] San Francisco VA, San Francisco, CA USA. RP Blum, AB (reprint author), Evergreen Hlth Inc, 3000 Falls Rd,Suite 1, Baltimore, MD 21211 USA. EM abb@evergreenmd.org OI Moskowitz, Alan/0000-0002-4412-9450 FU Health Resources & Administration at Mount Sinai School of Medicine [T32HP10262]; Veterans Affairs Health Services Research & Development Career Development award; National Heart, Lung, and Blood Institute [R01HL116522-01A1] FX This project was not directly supported by any external grants or funds. Dr Blum was supported through a National Research Service award from the Health Resources & Administration at Mount Sinai School of Medicine (T32HP10262). Dr Keyhani was supported by a Veterans Affairs Health Services Research & Development Career Development award and a National Heart, Lung, and Blood Institute award (R01HL116522-01A1). NR 25 TC 10 Z9 10 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2014 VL 7 IS 3 BP 391 EP 397 DI 10.1161/CIRCOUTCOMES.113.000520 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI3WQ UT WOS:000336796300008 PM 24823956 ER PT J AU McGaughey, DM Abaan, HO Miller, RM Kropp, PA Brody, LC AF McGaughey, David M. Abaan, Hatice Ozel Miller, Ryan M. Kropp, Peter A. Brody, Lawrence C. TI Genomics of CpG Methylation in Developing and Developed Zebrafish SO G3-GENES GENOMES GENETICS LA English DT Article DE methylation; epigenetics; zebrafish; development; one-carbon metabolism ID DNA-METHYLATION; EMBRYONIC-DEVELOPMENT; PLURIPOTENT; PATTERNS; SEQUENCE; REVEALS; PATHWAY; SYSTEM; CELLS AB DNA methylation is a dynamic process through which specific chromatin modifications can be stably transmitted from parent to daughter cells. A large body of work has suggested that DNA methylation influences gene expression by silencing gene promoters. However, these conclusions were drawn from data focused mostly on promoter regions. Regarding the entire genome, it is unclear how methylation and gene transcription patterns are related during vertebrate development. To identify the genome-wide distribution of CpG methylation, we created series of high-resolution methylome maps of Danio rerio embryos during development and in mature, differentiated tissues. We found that embryonic and terminal tissues have unique methylation signatures in CpG islands and repetitive sequences. Fully differentiated tissues have increased CpG and LTR methylation and decreased SINE methylation relative to embryonic tissues. Unsupervised clustering analyses reveal that the embryonic and terminal tissues can be classified solely by their methylation patterning. Novel analyses also identify a previously undescribed genome-wide exon methylation signature. We also compared whole genome methylation with genome-wide mRNA expression levels using publicly available RNA-seq datasets. These comparisons revealed previously unrecognized relationships between gene expression, alternative splicing, and exon methylation. Surprisingly, we found that exonic methylation is a better predictor of mRNA expression level than promoter methylation. We also found that transcriptionally skipped exons have significantly less methylation than retained exons. Our integrative analyses reveal highly complex interplay between gene expression, alternative splicing, development, and methylation patterning in zebrafish. C1 [McGaughey, David M.; Abaan, Hatice Ozel; Miller, Ryan M.; Kropp, Peter A.; Brody, Lawrence C.] NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Brody, LC (reprint author), Bldg 50,Room 5306,50 South Dr, Bethesda, MD 20814 USA. EM lbrody@mail.nih.gov FU National Human Genome Research Institute FX We thank Peter Chines, Narisu Narisu, and Steve Parker for advice regarding computational approaches, and Laura Elnitski, Francisco Sanchez Vega, and Steve Parker for reading and commenting on the manuscript. This work was supported by the Intramural Research Program of the National Human Genome Research Institute. NR 45 TC 9 Z9 9 U1 0 U2 22 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD MAY 1 PY 2014 VL 4 IS 5 BP 861 EP 869 DI 10.1534/g3.113.009514 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA AH9TA UT WOS:000336483900011 PM 24657902 ER PT J AU Xue, ZY Ren, MD Wu, MH Dai, JB Rong, YKS Gao, GJ AF Xue, Zhaoyu Ren, Mengda Wu, Menghua Dai, Junbiao Rong, Yikang S. Gao, Guanjun TI Efficient Gene Knock-out and Knock-in with Transgenic Cas9 in Drosophila SO G3-GENES GENOMES GENETICS LA English DT Article DE knock-out; knock-in; Cas9; gRNA; Drosophila ID GENOME; MELANOGASTER; CRISPR/CAS9; STRATEGY; SYSTEM AB Bacterial Cas9 nuclease induces site-specific DNA breaks using small gRNA as guides. Cas9 has been successfully introduced into Drosophila for genome editing. Here, we improve the versatility of this method by developing a transgenic system that expresses Cas9 in the Drosophila germline. Using this system, we induced inheritable knock-out mutations by injecting only the gRNA into embryos, achieved highly efficient mutagenesis by expressing gRNA from the promoter of a novel non-coding RNA gene, and recovered homologous recombination-based knock-in of a fluorescent marker at a rate of 4.5% by co-injecting gRNA with a circular DNA donor. C1 [Xue, Zhaoyu; Ren, Mengda; Wu, Menghua; Dai, Junbiao; Gao, Guanjun] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China. [Rong, Yikang S.] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Gao, GJ (reprint author), Tsinghua Univ, Sch Life Sci, Yuanmingyuan Rd 1, Beijing 100084, Peoples R China. EM gaogu@mail.tsinghua.edu.cn FU National Natural Science Foundation of China [31171278, 31271542]; National Cancer Institute (NCI) FX We thank Dr. Hugo J. Bellen and Dr. Johannes Bischoffor for providing the PiggyBac-9A and pM 3xP3RFP-RFPattP' plasmids. We also thank Wei Wei for technical assistance with DNA sequencing and PCR analysis. This work was supported by grants from the National Natural Science Foundation of China (31171278, 31271542). Research in the laboratory of Y.S.R. is supported by the intramural program of National Cancer Institute (NCI). NR 17 TC 15 Z9 18 U1 6 U2 47 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD MAY 1 PY 2014 VL 4 IS 5 BP 925 EP 929 DI 10.1534/g3.114.010496 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA AH9TA UT WOS:000336483900017 PM 24657904 ER PT J AU Allen, JD Leyva, B Torres, MI Ospino, H Tom, L Rustan, S Bartholomew, A AF Allen, Jennifer D. Leyva, Bryan Torres, Maria Idali Ospino, Hosffman Tom, Laura Rustan, Sarah Bartholomew, Amanda TI Religious Beliefs and Cancer Screening Behaviors among Catholic Latinos: Implications for Faith-based Interventions SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Religion; spirituality; Catholicism; Hispanic; Latino; health; cancer screening; faith-based intervention; health promotion; qualitative research ID AFRICAN-AMERICAN-WOMEN; COLORECTAL-CANCER; MEXICAN-AMERICANS; HEALTH-CARE; EXPLANATORY MODELS; PROSTATE-CANCER; HISPANIC-WOMEN; SOCIAL TIES; LOW-INCOME; CHURCH AB Although most U.S. Latinos identify as Catholic, few studies have focused on the influence of this religious tradition on health beliefs among this population. This study explores the role of Catholic religious teachings, practices, and ministry on cancer screening knowledge, attitudes, and behaviors among Latinos. Eight focus groups were conducted with 67 Catholic Latino parishioners in Massachusetts. Qualitative analysis provided evidence of strong reliance on faith, God, and parish leaders for health concerns. Parishes were described as vital sources of health and social support, playing a central role in the community's health. Participants emphasized that their religious beliefs promote positive health behaviors and health care utilization, including the use of cancer screening services. In addition, they expressed willingness to participate in cancer education programs located at their parishes and provided practical recommendations for implementing health programs in parishes. Implications for culturally appropriate health communication and faith-based interventions are discussed. C1 [Allen, Jennifer D.; Tom, Laura; Bartholomew, Amanda] Dana Farber Canc Inst, Boston, MA 02215 USA. [Allen, Jennifer D.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Leyva, Bryan] NCI, Bethesda, MD 20892 USA. [Torres, Maria Idali; Rustan, Sarah] Univ Massachusetts, Boston, MA 02125 USA. [Ospino, Hosffman] Boston Coll, Chestnut Hill, MA 02167 USA. RP Allen, JD (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Phyllis F Cantor Ctr Nursing Res & Patient Care S, 450 Brookline Ave, Boston, MA 02215 USA. EM Jennifer_allen@dfci.harvard.edu RI Allen, Jennifer/M-2113-2015 FU NCCDPHP CDC HHS [U48 DP001946, U48DP001946]; NCI NIH HHS [U54 CA156732, U54CA156732]; NIMHD NIH HHS [R21 MD005976] NR 109 TC 4 Z9 4 U1 3 U2 18 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 EI 1548-6869 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD MAY PY 2014 VL 25 IS 2 BP 503 EP 526 PG 24 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AH7VJ UT WOS:000336343100007 PM 24858865 ER PT J AU Nguyen, AB Belgrave, FZ AF Nguyen, Anh B. Belgrave, Faye Z. TI Suc Khoe La Quan Trong Hon Sac Dep! Health is Better than Beauty! A Community-based Participatory Research Intervention to Improve Cancer Screening among Vietnamese Women SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Vietnamese-American; women; breast cancer; cervical cancer; ethnic identity; collectivism; community-based participatory research ID CERVICAL-CANCER; AMERICAN WOMEN; ETHNIC-IDENTITY; AFRICAN-AMERICAN; ASIAN-AMERICANS; PAP-SMEAR; SELF-REPORTS; CHINESE; BREAST; MAMMOGRAPHY AB This paper examines community-based participatory research (CBPR) intervention approaches in promoting cancer-relevant outcomes for 102 Vietnamese women. Results indicated that the intervention was effective in promoting breast and cervical cancer knowledge, positive attitudes towards breast cancer screening, and breast cancer screening. Collectivism moderated the effect of the intervention on attitudes towards breast cancer screening. The intervention led to more favorable attitudes towards breast cancer screening for women with high levels of collectivism but not for women with low levels. Ethnic identity moderated the effect of the intervention on breast cancer screening: the intervention program led to higher probability of getting a clinical breast exam; however, this effect was more pronounced for women with low ethnic identity than for those with high ethnic identity. The study provides evidence for the effectiveness of culturally-tailored strategies in developing cancer screening interventions for the Vietnamese American population. C1 [Nguyen, Anh B.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD USA. [Belgrave, Faye Z.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. RP Nguyen, AB (reprint author), 9609 Med Ctr Dr 3E638, Rockville, MD 20850 USA. EM Anh.Nguyen3@nih.gov FU NCI NIH HHS [5F31CA136235] NR 56 TC 3 Z9 3 U1 1 U2 2 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 EI 1548-6869 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD MAY PY 2014 VL 25 IS 2 BP 605 EP 623 PG 19 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AH7VJ UT WOS:000336343100013 PM 24858871 ER PT J AU Studenski, S AF Studenski, S. TI Improving care for community dwelling frail elders through patient and provider engagement SO JOURNAL OF NUTRITION HEALTH & AGING LA English DT Editorial Material ID COMPREHENSIVE GERIATRIC ASSESSMENT; CONTROLLED-TRIAL; OLDER-ADULTS; METAANALYSIS; MANAGEMENT; INPATIENT C1 NIA, Longitudinal Studies Sect, Intramural Program, Baltimore, MD 21225 USA. RP Studenski, S (reprint author), NIA, Longitudinal Studies Sect, Intramural Program, Baltimore, MD 21225 USA. EM studenskisa@mail.nih.gov NR 17 TC 1 Z9 1 U1 1 U2 3 PU SPRINGER FRANCE PI PARIS PA 22 RUE DE PALESTRO, PARIS, 75002, FRANCE SN 1279-7707 EI 1760-4788 J9 J NUTR HEALTH AGING JI J. Nutr. Health Aging PD MAY PY 2014 VL 18 IS 5 BP 455 EP 456 DI 10.1007/s12603-014-0458-8 PG 2 WC Geriatrics & Gerontology; Nutrition & Dietetics SC Geriatrics & Gerontology; Nutrition & Dietetics GA AI1KI UT WOS:000336609400002 PM 24886727 ER PT J AU Coates, TJ Kulich, M Celentano, DD Zelaya, CE Chariyalertsak, S Chingono, A Gray, G Mbwambo, JKK Morin, SF Richter, L Sweat, M van Rooyen, H McGrath, N Fiamma, A Laeyendecker, O Piwowar-Manning, E Szekeres, G Donnell, D Eshleman, SH AF Coates, Thomas J. Kulich, Michal Celentano, David D. Zelaya, Carla E. Chariyalertsak, Suwat Chingono, Alfred Gray, Glenda Mbwambo, Jessie K. K. Morin, Stephen F. Richter, Linda Sweat, Michael van Rooyen, Heidi McGrath, Nuala Fiamma, Agnes Laeyendecker, Oliver Piwowar-Manning, Estelle Szekeres, Greg Donnell, Deborah Eshleman, Susan H. CA NIMH Project Accept HPTN 043 Study TI Effect of community-based voluntary counselling and testing on HIV incidence and social and behavioural outcomes (NIMH Project Accept; HPTN 043): a cluster-randomised trial SO LANCET GLOBAL HEALTH LA English DT Article ID SUB-SAHARAN AFRICA; MALE CIRCUMCISION; ANTIRETROVIRAL THERAPY; PREVENTION; THAILAND; INTERVENTION; TRANSMISSION; STIGMA; RISK; MEN AB Background Although several interventions have shown reduced HIV incidence in clinical trials, the community-level effect of effective interventions on the epidemic when scaled up is unknown. We investigated whether a multicomponent, multilevel social and behavioural prevention strategy could reduce HIV incidence, increase HIV testing, reduce HIV risk behaviour, and change social and behavioural norms. Methods For this phase 3 cluster-randomised controlled trial, 34 communities in four sites in Africa and 14 communities in Thailand were randomly allocated in matched pairs to receive 36 months of community-based voluntary counselling and testing for HIV (intervention group) or standard counselling and testing alone (control group) between January, 2001, and December, 2011. The intervention was designed to make testing more accessible in communities, engage communities through outreach, and provide support services after testing. Randomisation was done by a computer-generated code and was not masked. Data were collected at baseline (n=14 567) and after intervention (n=56 683) by cross-sectional random surveys of community residents aged 18-32 years. The primary outcome was HIV incidence and was estimated with a cross-sectional multi-assay algorithm and antiretroviral drug screening assay. Thailand was excluded from incidence analyses because of low HIV prevalence. This trial is registered at ClinicalTrials.gov, number NCT00203749. Findings The estimated incidence of HIV in the intervention group was 1.52% versus 1.81% in the control group with an estimated reduction in HIV incidence of 13.9% (relative risk [RR] 0.86, 95% CI 0.73-1.02; p=0.082). HIV incidence was significantly reduced in women older than 24 years (RR=0.70, 0.54-0.90; p=0.0085), but not in other age or sex subgroups. Community-based voluntary counselling and testing increased testing rates by 25% overall (12-39; p=0.0003), by 45% (25-69; p<0.0001) in men and 15% (3-28; p=0.013) in women. No overall effect on sexual risk behaviour was recorded. Social norms regarding HIV testing were improved by 6% (95% CI 3-9) in communities in the intervention group. Interpretation These results are sufficiently robust, especially when taking into consideration the combined results of modest reductions in HIV incidence combined with increases in HIV testing and reductions in HIV risk behaviour, to recommend the Project Accept approach as an integral part of all interventions (including treatment as prevention) to reduce HIV transmission at the community level. Copyright (C) Coates et al. Open Access article distributed under the terms of CC BY. C1 [Coates, Thomas J.; Fiamma, Agnes; Szekeres, Greg] Univ Calif Los Angeles, UCLA Ctr World Hlth, Los Angeles, CA 90095 USA. [Kulich, Michal] Charles Univ Prague, Fac Math & Phys, Prague, Czech Republic. [Celentano, David D.; Zelaya, Carla E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Chariyalertsak, Suwat] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand. [Chingono, Alfred] Univ Zimbabwe, Coll Hlth Sci, Harare, Zimbabwe. [Gray, Glenda] Univ Witwatersrand, Chris Hani Baragwanath Hosp, Fac Hlth Sci, Perinatal HIV Res Unit, Soweto, South Africa. [Mbwambo, Jessie K. K.] Muhimbili Univ Teaching Hosp, Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania. [Morin, Stephen F.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. [Richter, Linda] Human Sci Res Council, Dalbridge, South Africa. [Sweat, Michael] Med Univ S Carolina, Family Serv Res Ctr, Charleston, SC 29425 USA. [van Rooyen, Heidi] Human Sci Res Council, Durban, South Africa. [McGrath, Nuala] Univ Southampton, Southampton Gen Hosp, Southampton, Hants, England. [Laeyendecker, Oliver] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Piwowar-Manning, Estelle; Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Laeyendecker, Oliver] NIH, Bethesda, MD 20892 USA. [Donnell, Deborah] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Coates, TJ (reprint author), Univ Calif Los Angeles, UCLA Ctr World Hlth, Los Angeles, CA 90095 USA. EM tcoates@mednet.ucla.edu RI Kulich, Michal/B-1483-2013; Maman, Suzanne/A-3802-2016; OI Kulich, Michal/0000-0002-2812-8968; Laeyendecker, Oliver/0000-0002-6429-4760; Donnell, Deborah/0000-0002-0587-7480; Mulawa, Marta/0000-0001-9687-421X FU US National Institute of Mental Health; Division of AIDS of the US National Institute of Allergy and Infectious Diseases; Office of AIDS Research of the US National Institutes of Health FX US National Institute of Mental Health, the Division of AIDS of the US National Institute of Allergy and Infectious Diseases, and the Office of AIDS Research of the US National Institutes of Health. NR 30 TC 41 Z9 41 U1 1 U2 17 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-109X J9 LANCET GLOB HEALTH JI Lancet Glob. Health PD MAY PY 2014 VL 2 IS 5 BP E267 EP E277 DI 10.1016/S2214-109X(14)70032-4 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AH8YU UT WOS:000336424900015 PM 25103167 ER PT J AU Mehta, HM Futami, M Glaubach, T Lee, DW Andolina, JR Yang, Q Whichard, Z Quinn, M Lu, HF Kao, WM Przychodzen, B Sarkar, CA Minella, A Maciejewski, JP Corey, SJ AF Mehta, H. M. Futami, M. Glaubach, T. Lee, D. W. Andolina, J. R. Yang, Q. Whichard, Z. Quinn, M. Lu, H. F. Kao, W. M. Przychodzen, B. Sarkar, C. A. Minella, A. Maciejewski, J. P. Corey, S. J. TI Alternatively spliced, truncated GCSF receptor promotes leukemogenic properties and sensitivity to JAK inhibition SO LEUKEMIA LA English DT Article DE GCSF; GCSFR; myelodysplastic syndromes; acute myeloid leukemia: JAK2 ID COLONY-STIMULATING-FACTOR; SEVERE CONGENITAL NEUTROPENIA; G-CSF RECEPTOR; ACUTE MYELOGENOUS LEUKEMIA; ACUTE MYELOID-LEUKEMIA; HYPERPROLIFERATIVE RESPONSES; DIFFERENTIATION SIGNALS; MUTATIONS; CELLS; PROLIFERATION AB Granulocyte colony-stimulating factor (GCSF) drives the production of myeloid progenitor and precursor cells toward neutrophils via the GCSF receptor (GCSFR, gene name CSF3R). Children with severe congenital neutropenia chronically receive pharmacologic doses of GCSF, and similar to 30% will develop myelodysplasia/ acute myeloid leukemia (AML) associated with GCSFR truncation mutations. In addition to mutations, multiple isoforms of CSF3R have also been reported. We found elevated expression of the alternatively spliced isoform, class IV CSF3R in adult myelodysplastic syndrome/AML patients. Aside from its association with monosomy 7 and higher rates of relapse in pediatric AML patients, little is known about the biology of the class IV isoform. We found developmental regulation of CSF3R isoforms with the class IV expression more representative of a progenitor cell stage. Striking differences were found in phosphoprotein signaling involving Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and cell cycle gene expression. Enhanced proliferation by class IV GCSFR was associated with diminished STAT3 and STAT5 activation, yet showed sensitivity to JAK2 inhibitors. Alterations in the C-terminal domain of the GCSFR result in leukemic properties of enhanced growth, impaired differentiation and resistance to apoptosis, suggesting that they can behave as oncogenic drivers, sensitive to JAK2 inhibition. C1 [Mehta, H. M.; Futami, M.; Glaubach, T.; Andolina, J. R.; Yang, Q.; Whichard, Z.; Quinn, M.; Lu, H. F.; Corey, S. J.] Northwestern Univ, Feinberg Sch Med,Lurie Childrens Hosp Chicago, Robert H Lurie Comprehens Canc Ctr, Dept Pediat Hematol Oncol & Cell & Mol Biol, Chicago, IL 60611 USA. [Futami, M.] Univ Tokyo, Inst Med Sci, Div Mol Therapy, Tokyo, Japan. [Lee, D. W.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Andolina, J. R.] Univ Rochester, Sch Med, Dept Pediat Hematol Oncol, Rochester, NY USA. [Kao, W. M.; Przychodzen, B.; Maciejewski, J. P.] Cleveland Clin, Taussig Canc Inst Translat Hematol & Oncol Res, Cleveland, OH 44106 USA. [Sarkar, C. A.] Univ Minnesota, Dept Biomed Engn, Minneapolis, MN 55455 USA. [Minella, A.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Dept Med, Chicago, IL 60611 USA. RP Corey, SJ (reprint author), Northwestern Univ, Feinberg Sch Med,Lurie Childrens Hosp Chicago, Robert H Lurie Comprehens Canc Ctr, Dept Pediat Hematol Oncol & Cell & Mol Biol, 303 E Super St, Chicago, IL 60611 USA. EM coreylab@yahoo.com RI Mehta, Hrishikesh/K-1108-2016; OI Mehta, Hrishikesh/0000-0001-9140-9765; Minella, Alex/0000-0001-6693-3362 FU NIH Independent Scientist [KO2-HL03794, RO1-CA108992]; JP McCarthy Foundation; NIH [PO1CA55164, T32CA079447]; Leukemia SPORE [CA100632]; AA/MDS International Foundation FX We thank Dr Shigekazu Nagata for providing the cDNA for rabbit GHR and Dr John Crispino for providing the JAK2 inhibitors. Funding to SJC from NIH Independent Scientist Award KO2-HL03794, RO1-CA108992, JP McCarthy Foundation, NIH PO1CA55164, Leukemia SPORE CA100632 and AA/MDS International Foundation; to MF from a New Investigator Award from the AA/MDS International Foundation; and to TG and JRA from NIH T32CA079447. NR 45 TC 4 Z9 5 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD MAY PY 2014 VL 28 IS 5 BP 1041 EP 1051 DI 10.1038/leu.2013.321 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA AI2BJ UT WOS:000336661500008 PM 24170028 ER PT J AU Goswami, M Hensel, N Smith, BD Prince, GT Qin, L Levitsky, HI Strickland, SA Jagasia, M Savani, BN Fraser, JW Sadrzadeh, H Rajkhowa, T Ito, S Jain, NA Battiwalla, M Fathi, AT Levis, MJ Barrett, AJ Hourigan, CS AF Goswami, M. Hensel, N. Smith, B. D. Prince, G. T. Qin, L. Levitsky, H. I. Strickland, S. A. Jagasia, M. Savani, B. N. Fraser, J. W. Sadrzadeh, H. Rajkhowa, T. Ito, S. Jain, N. A. Battiwalla, M. Fathi, A. T. Levis, M. J. Barrett, A. J. Hourigan, C. S. TI Expression of putative targets of immunotherapy in acute myeloid leukemia and healthy tissues SO LEUKEMIA LA English DT Letter ID CANCER-TESTIS ANTIGEN; CELLS; RESPONSES C1 [Goswami, M.; Hourigan, C. S.] NHLBI, Myeloid Malignancies Sect, NIH, Bethesda, MD 20892 USA. [Hensel, N.; Ito, S.; Jain, N. A.; Battiwalla, M.; Barrett, A. J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Smith, B. D.; Prince, G. T.; Qin, L.; Levitsky, H. I.; Rajkhowa, T.; Levis, M. J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Levitsky, H. I.] Roche Glycart AG, Canc Immunol Expt Med Pharma Res & Early Dev, Schlieren, Switzerland. [Strickland, S. A.; Jagasia, M.; Savani, B. N.] Vanderbilt Univ, Med Ctr, Div Hematol & Oncol, Nashville, TN USA. [Fraser, J. W.; Sadrzadeh, H.; Fathi, A. T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Leukaemia, Boston, MA USA. [Fraser, J. W.; Sadrzadeh, H.; Fathi, A. T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Unit,Div Hematol Oncol, Boston, MA USA. RP Goswami, M (reprint author), NHLBI, Myeloid Malignancies Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. EM hourigan@nih.gov RI Hourigan, Christopher/S-2476-2016; OI Hourigan, Christopher/0000-0002-6189-8067; Strickland, Stephen/0000-0002-6861-2041 FU Intramural NIH HHS [ZIA HL006163-01]; NCATS NIH HHS [UL1 TR001079]; NCI NIH HHS [P01 CA015396] NR 15 TC 14 Z9 14 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD MAY PY 2014 VL 28 IS 5 BP 1167 EP 1170 DI 10.1038/leu.2014.14 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA AI2BJ UT WOS:000336661500030 PM 24472813 ER PT J AU Sato, K Watanabe, R Hanaoka, H Harada, T Nakajima, T Kim, I Paik, CH Choyke, PL Kobayashi, H AF Sato, Kazuhide Watanabe, Rira Hanaoka, Hirofumi Harada, Toshiko Nakajima, Takahito Kim, Insook Paik, Chang H. Choyke, Peter L. Kobayashi, Hisataka TI Photoimmunotherapy: Comparative effectiveness of two monoclonal antibodies targeting the epidermal growth factor receptor SO MOLECULAR ONCOLOGY LA English DT Article DE Photoimmunotherapy; Epidermal growth factor receptor; Monoclonal antibody; NIR-fluorescence; Pharmacokinetics ID SQUAMOUS-CELL CARCINOMA; TUMOR SPHEROIDS; THERAPY; IMMUNOTHERAPY; RETENTION AB Photoimmunotherapy (PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. Herein we compare two commonly available anti-EGFR monoclonal antibodies, cetuximab and panitumumab, for their effectiveness as PIT agents in EGFR positive tumor models. A photosensitizer, IR-700, conjugated to either cetuximab (cet-IR700) or panitumumab (pan-IR700), was evaluated using EGFR-expressing A431 and MDAMB468-luc cells in 2D- and 3D-culture. PIT was conducted with irradiation of NIR light after exposure of the sample or animal to each conjugate. In vivo PIT was performed with fractionated exposure of NIR light after injection of each agent into A431 xenografts or a MDAMB468-luc orthotopic tumor bearing model. Cet-IR700 and pan-IR700 bound with equal affinity to the cells in 2D-culture and penetrated equally into the 3D-spheroid, resulting in identical PIT cytotoxic effects in vitro. In contrast, in vivo anti-tumor effects of PIT with cet-IR700 were inferior to that of pan-IR700. Assessment of the biodistribution showed lower accumulation into the tumors and more rapid hepatic catabolism of cet-IR700 compared to pan-IR700 Although cet-IR700 and pan-IR700 showed identical in vitro characteristics, pan-IR700 showed better therapeutic tumor responses than cet-IR700 in in vivo mice models due to the prolonged retention of the conjugate in the circulation, suggesting that retention in the circulation is advantageous for tumor responses to PIT. These results suggest that the choice of monoclonal antibody in photosensitizer conjugates may influence the effectiveness of PIT. Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies. C1 [Sato, Kazuhide; Watanabe, Rira; Hanaoka, Hirofumi; Harada, Toshiko; Nakajima, Takahito; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA. [Kim, Insook] Leidos Biomed Res Inc, Appl Dev Res Directorate, Frederick, MD 20892 USA. [Paik, Chang H.] NIH, Warren Grant Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room B3B69,MSC1088, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. K.S. is supported with JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH. NR 33 TC 30 Z9 30 U1 1 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1574-7891 EI 1878-0261 J9 MOL ONCOL JI Mol. Oncol. PD MAY PY 2014 VL 8 IS 3 BP 620 EP 632 DI 10.1016/j.molonc.2014.01.006 PG 13 WC Oncology SC Oncology GA AH9OQ UT WOS:000336472100015 PM 24508062 ER PT J AU Grady, PA Daley, K AF Grady, Patricia A. Daley, Karen TI The 2013 National Nursing Research Roundtable: Advancing the science of chronic illness self-management SO NURSING OUTLOOK LA English DT Editorial Material ID OUTCOMES C1 [Grady, Patricia A.] NINR, NIH, Bethesda, MD 20892 USA. [Daley, Karen] Amer Nurses Assoc, Silver Spring, MD USA. RP Grady, PA (reprint author), Care of Gough L, NINR, NIH, 6701 Democracy Blvd,Suite 710, Bethesda, MD 20817 USA. EM info@ninr.nih.gov NR 8 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-6554 EI 1528-3968 J9 NURS OUTLOOK JI Nurs. Outlook PD MAY-JUN PY 2014 VL 62 IS 3 BP 201 EP 203 DI 10.1016/j.outlook.2013.12.001 PG 3 WC Nursing SC Nursing GA AH8WL UT WOS:000336418800007 PM 24602784 ER PT J AU Sung, VW Rogers, RG Bann, CM Arya, L Barber, MD Lowder, J Lukacz, ES Markland, A Siddiqui, N Wilmot, A Meikle, SF AF Sung, Vivian W. Rogers, Rebecca G. Bann, Carla M. Arya, Lily Barber, Matthew D. Lowder, Jerry Lukacz, Emily S. Markland, Alayne Siddiqui, Nazema Wilmot, Amanda Meikle, Susan F. CA Pelvic Floor Disorders Network TI Symptom Outcomes Important to Women With Anal Incontinence A Conceptual Framework SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID ACCIDENTAL BOWEL LEAKAGE; FECAL INCONTINENCE; URINARY-INCONTINENCE; HEALTH; PREVALENCE; ADULTS AB OBJECTIVE: To develop a framework that describes the most important symptom outcomes for anal incontinence treatment from the patient perspective. METHODS: A conceptual framework was developed by the Pelvic Floor Disorders Network based on four semi-structured focus groups and confirmed in two sets of 10 cognitive interviews including women with anal incontinence. We explored: 1) patient-preferred terminology for describing anal incontinence symptoms; 2) patient definitions of treatment "success"; 3) importance of symptoms and outcomes in the framework; and 4) conceptual gaps (defined as outcomes not previously identified as important). Sessions were conducted according to grounded theory transcribed, coded, and qualitatively and quantitatively analyzed to identify relevant themes. Content and face validity of the framework were further assessed using cognitive interviews. RESULTS: Thirty-four women participated in focus groups and 20 in cognitive interviews. Overall, 29 (54%) were aged 60 years or older, 42 (78%) were white, and 10 (19%) had a high school degree or less. Two overarching outcome themes were identified: "primary bowel leakage symptoms" and "ancillary bowel symptoms." Subdomains important in primary bowel leakage symptoms included leakage characteristics (symptom frequency, amount of leakage, symptom bother) and conditions when bowel leakage occurs (predictability, awareness, urgency). Subdomains important under ancillary bowel symptoms included emptying disorders (constipation, obstructed defecation, and wiping issues) and discomfort (pain, burning). New outcomes identified included predictability, awareness, wiping issues, and discomfort. CONCLUSION: Women with anal incontinence desire a wide range of symptom outcomes after treatment. These are captured in our conceptual framework, which can aid clinicians and researchers in assessing anal incontinence. C1 Brown Univ, Div Urogynecol & Reconstruct Pelv Surg, Dept Obstet & Gynecol, Alpert Med Sch, Providence, RI 02903 USA. Univ New Mexico, Dept Obstet & Gynecol, Div Urogynecol, Albuquerque, NM 87131 USA. RTI Int, Program Res Survey Methodol, Res Triangle Pk, NC USA. Univ Penn, Dept Obstet & Gynecol, Hlth Syst Dept, Div Urogynecol & Pelv Reconstruct Surg, Philadelphia, PA 19104 USA. Cleveland Clin, Obstet Gynecol & Womens Hlth Inst, Ctr Urogynecol & Reconstruct Pelv Surg, Cleveland, OH 44106 USA. Univ Pittsburgh, Med Ctr, Dept Obstet & Gynecol, Womens Ctr Bladder & Pelv Hlth, Pittsburgh, PA USA. UC San Diego Hlth Syst, Dept Reprod Med, San Diego, CA USA. Univ Alabama Birmingham, Dept Med, Birmingham & Atlanta Geriatr Res Educ & Clin Ctr, Dept Vet Affairs,Med Ctr,Div Gerontol Geriatr & P, Birmingham, AL 35294 USA. Duke Univ, Med Ctr, Dept Obstet & Gynecol, Div Urogynecol, Durham, NC 27710 USA. NICHHD, Bethesda, MD 20892 USA. RP Sung, VW (reprint author), Brown Univ, Div Urogynecol & Reconstruct Pelv Surg, Women & Infants Hosp, 695 Eddy St, Providence, RI 02903 USA. EM vsung@wihri.org FU American Medical Systems; Renew Medical, Inc; Pfizer; Boston Scientific; MedEdicus; Johnson Johnson; Ethicon; National Institutes of Health (NIH); Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; National Institute of Diabetes and Digestive and Kidney Diseases; AUGS FX Dr. Rogers is a data safety monitoring board chair for the TRANSFORM trial, sponsored by American Medical Systems. She receives royalties from UpToDate for her chapter on pelvic organ prolapse. Dr. Lukacz has been a consultant and received research grants from Renew Medical, Inc, and Pfizer. She has received a research grant from Boston Scientific, has been a consultant to AMS, and she has received a stipend for continuing medical education program development from MedEdicus. She has also received an educational grant from Johnson & Johnson and Ethicon; research grant support from the National Institutes of Health (NIH) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; research grant support, travel reimbursement, and honoraria from the NIH and the National Institute of Diabetes and Digestive and Kidney Diseases; research funding from AUGS; and medicolegal expert witness fees from various sources. The other authors did not report any potential conflicts of interest. NR 25 TC 3 Z9 3 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2014 VL 123 IS 5 BP 1023 EP 1030 DI 10.1097/AOG.0000000000000236 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AI4BD UT WOS:000336809400017 PM 24785855 ER PT J AU Reddy, UM Abuhamad, AZ Levine, D Saade, GR AF Reddy, Uma M. Abuhamad, Alfred Z. Levine, Deborah Saade, George R. CA Fetal Imaging Workshop Invited Par TI Fetal Imaging Executive Summary of a Joint Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, American Institute of Ultrasound in Medicine, American College of Obstetricians and Gynecologists, American College of Radiology, Society for Pediatric Radiology, and Society of Radiologists in Ultrasound Fetal Imaging Workshop SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID CHOROID-PLEXUS CYSTS; AMNIOTIC-FLUID VOLUME; LOW-LYING PLACENTA; NERVOUS-SYSTEM ABNORMALITIES; INTRACARDIAC ECHOGENIC FOCI; TWIN TRANSFUSION SYNDROME; BIRTH-WEIGHT DISCORDANCE; LAST MENSTRUAL PERIOD; INTERNAL OS DISTANCE; ISOLATED SHORT FEMUR AB Given that practice variation exists in the frequency and performance of ultrasound and magnetic resonance imaging (MRI) in pregnancy, the Eunice Kennedy Shriver National Institute of Child Health and Human Development hosted a workshop to address indications for ultrasound and MRI in pregnancy, to discuss when and how often these studies should be performed, to consider recommendations for optimizing yield and cost effectiveness, and to identify research opportunities. This article is the executive summary of the workshop. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Texas Med Branch, Galveston, TX 77555 USA. RP Reddy, UM (reprint author), 6100 Executive Blvd,Room 4B03F, Bethesda, MD 20892 USA. EM reddyu@mail.nih.gov NR 117 TC 29 Z9 31 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2014 VL 123 IS 5 BP 1070 EP 1082 DI 10.1097/AOG.0000000000000245 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AI4BD UT WOS:000336809400022 PM 24785860 ER PT J AU Raju, TNK Mercer, BM Burchfield, DJ Joseph, GF AF Raju, Tonse N. K. Mercer, Brian M. Burchfield, David J. Joseph, Gerald F., Jr. TI Periviable Birth Executive Summary of a Joint Workshop by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, American Academy of Pediatrics, and American College of Obstetricians and Gynecologists SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID EXTREMELY PRETERM INFANTS; EXTREMELY PREMATURE-INFANTS; WEEKS GESTATIONAL-AGE; WEIGHT INFANTS; ANTENATAL CORTICOSTEROIDS; DELIVERY ROOM; UNITED-STATES; NEURODEVELOPMENTAL OUTCOMES; DEVELOPMENTAL-DISABILITY; EMERGENCY CERCLAGE AB This is an executive summary of a workshop on the management and counseling issues of women anticipated to deliver at a periviable gestation (broadly defined as 20 0/7 through 25 6/7 weeks of gestation), and the treatment options for the newborn. Upon review of the available literature, the workshop panel noted that the rates of neonatal survival and neurodevelopmental disabilities among the survivors vary greatly across the periviable gestations and are significantly influenced by the obstetric and neonatal management practices (eg, antenatal steroid, tocolytic agents, and antibiotic administration; cesarean birth; and local protocols for perinatal care, neonatal resuscitation, and intensive care support). These are, in turn, influenced by the variations in local and regional definitions of limits of viability. Because of the complexities in making difficult management decisions, obstetric and neonatal teams should confer prior to meeting with the family, when feasible. Family counseling should be coordinated with the goal of creating mutual trust, respect, and understanding and should incorporate evidence-based counseling methods. Since clinical circumstances can change rapidly with increasing gestational age, counseling should include discussion of the benefits and risks of various maternal and neonatal interventions at the time of counseling. There should be a plan for follow-up counseling as clinical circumstances evolve. The panel proposed a research agenda and recommended developing educational curricula on the care and counseling of families facing the birth of a periviable infant. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. Soc Maternal Fetal Med, Cleveland, OH USA. Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44106 USA. Univ Florida, Amer Acad Pediat, Gainesville, FL USA. Amer Coll Obstetricians & Gynecologists, Washington, DC 20024 USA. RP Mercer, BM (reprint author), MetroHlth Med Ctr, Dept Obstet & Gynecol, Suite G267,2500 MetroHlth Dr, Cleveland, OH 44109 USA. EM bmercer@metrohealth.org NR 60 TC 27 Z9 29 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2014 VL 123 IS 5 BP 1083 EP 1096 DI 10.1097/AOG.0000000000000243 PG 14 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AI4BD UT WOS:000336809400023 PM 24785861 ER PT J AU Boyce, AM Tosi, LL Paul, SM AF Boyce, Alison M. Tosi, Laura L. Paul, Scott M. TI Bisphosphonate Treatment for Children With Disabling Conditions SO PM&R LA English DT Review ID X-RAY ABSORPTIOMETRY; BONE-MINERAL DENSITY; SEVERE OSTEOGENESIS IMPERFECTA; SPINAL-CORD-INJURY; DUCHENNE MUSCULAR-DYSTROPHY; INTRAVENOUS PAMIDRONATE TREATMENT; QUANTITATIVE COMPUTED-TOMOGRAPHY; SEVERE CEREBRAL-PALSY; FIBROUS DYSPLASIA; ZOLEDRONIC ACID AB Fractures are a frequent source of morbidity in children with disabling conditions. The assessment of bone density in this population is challenging, because densitometry is influenced by dynamic forces affecting the growing skeleton and may be further confounded by positioning difficulties and surgical hardware. First-line treatment for pediatric osteoporosis involves conservative measures, including optimizing the management of underlying conditions, maintaining appropriate calcium and vitamin D intake, encouraging weight-bearing physical activity, and monitoring measurements of bone mineral density. Bisphosphonates are a class of medications that increase bone mineral density by inhibiting bone resorption. Although bisphosphonates are commonly prescribed for treatment of adult osteoporosis, their use in pediatric patients is controversial because of the lack of long-term safety and efficacy data. C1 [Boyce, Alison M.] Childrens Natl Med Ctr, Div Endocrinol & Diabetes, Washington, DC 20010 USA. [Boyce, Alison M.; Tosi, Laura L.] Childrens Natl Med Ctr, Div Orthopaed & Sports Med, Bone Hlth Program, Washington, DC 20010 USA. [Paul, Scott M.] NIH, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. RP Boyce, AM (reprint author), Childrens Natl Med Ctr, Div Endocrinol & Diabetes, 111 Michigan Ave NW, Washington, DC 20010 USA. EM aboyce@childrensnational.org FU Bone Health Program at Children's National Medical Center; Intramural Research Program at the National Institutes of Health FX supported by the Bone Health Program at Children's National Medical Center and the Intramural Research Program at the National Institutes of Health. NR 105 TC 6 Z9 6 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD MAY PY 2014 VL 6 IS 5 BP 427 EP 436 DI 10.1016/j.pmrj.2013.10.009 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AI0SR UT WOS:000336560700009 PM 24368091 ER PT J AU Kwon, JY Romero, R Mor, G AF Kwon, Ja-Young Romero, Roberto Mor, Gil TI New Insights into the Relationship between Viral Infection and Pregnancy Complications SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE Complication; infection; pregnancy; virus ID SPONTANEOUSLY ABORTED PRODUCTS; HUMAN-PAPILLOMAVIRUS INFECTION; INDUCED PRETERM LABOR; INFLAMMATORY RESPONSE; FETAL INFLAMMATION; PREECLAMPSIA; TROPHOBLAST; ACTIVATION; DELIVERY; EXPRESSION AB A recent study by McDonnold and coinvestigators published in Am J Obstet Gynecol reports an association between human papillomavirus (HPV) infection and preeclampsia. The investigation was based on the hypothesis that HPV trophoblast infection results in failed trophoblast invasion, and placental dysfunction and hypoxia. The findings from this study along with previous data addressing the relationship between viral infection and obstetrical complications highlight the relevance of viral infection during pregnancy. A better understanding of mechanisms via which virus leads to pregnancy complications will drive us closer to finding a strategy to prevent adverse outcomes. C1 [Kwon, Ja-Young; Mor, Gil] Yale Univ, Sch Med, Reprod Immunol Unit, Dept Obstet Gynecol & Reprod Sci, New Haven, CT 06520 USA. [Kwon, Ja-Young] Yonsei Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. [Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. RP Mor, G (reprint author), Yale Univ, Sch Med, Reprod Immunol Unit, Dept Obstet Gynecol & Reprod Sci, 333 Cedar St LSOG 305A, New Haven, CT 06520 USA. EM gil.mor@yale.edu FU National Institute of Health, NICDH [P01HD054713, 3N01 HD23342] FX This study is in part funded by grants from the National Institute of Health, NICDH P01HD054713 and 3N01 HD23342. NR 47 TC 9 Z9 10 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1046-7408 EI 1600-0897 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD MAY PY 2014 VL 71 IS 5 BP 387 EP 390 DI 10.1111/aji.12243 PG 4 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA AE9AK UT WOS:000334295600001 PM 24702790 ER PT J AU Guo, L Zheng, Z Ai, JT Howatt, DA Mittelstadt, PR Thacker, S Daugherty, A Ashwell, JD Remaley, AT Li, XA AF Guo, Ling Zheng, Zhong Ai, Junting Howatt, Deborah A. Mittelstadt, Paul R. Thacker, Seth Daugherty, Alan Ashwell, Jonathan D. Remaley, Alan T. Li, Xiang-An TI Scavenger Receptor BI and High-Density Lipoprotein Regulate Thymocyte Apoptosis in Sepsis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE apolipoproteins; apoptosis; lipoproteins; scavenger receptors; class B; sepsis ID APOLIPOPROTEIN-A-I; SR-BI; GLUCOCORTICOID-RECEPTOR; CHOLESTERYL ESTER; DYSFUNCTIONAL HDL; SELECTIVE UPTAKE; FAMILIAL HYPERCHOLESTEROLEMIA; ADRENOCORTICAL-RESPONSE; REDUCES ATHEROSCLEROSIS; POLYMICROBIAL SEPSIS AB Objective Thymocyte apoptosis is a major event in sepsis; however, how this process is regulated remains poorly understood. Approach and Results Septic stress induces glucocorticoids production which triggers thymocyte apoptosis. Here, we used scavenger receptor BI (SR-BI)-null mice, which are completely deficient in inducible glucocorticoids in sepsis, to investigate the regulation of thymocyte apoptosis in sepsis. Cecal ligation and puncture induced profound thymocyte apoptosis in SR-BI+/+ mice, but no thymocyte apoptosis in SR-BI-/- mice because of lack of inducible glucocorticoids. Unexpectedly, supplementation of glucocorticoids only partly restored thymocyte apoptosis in SR-BI-/- mice. We demonstrated that high-density lipoprotein (HDL) is a critical modulator for thymocyte apoptosis. SR-BI+/+ HDL significantly enhanced glucocorticoid-induced thymocyte apoptosis, but SR-BI-/- HDL had no such activity. Further study revealed that SR-BI+/+ HDL modulates glucocorticoid-induced thymocyte apoptosis via promoting glucocorticoid receptor translocation, but SR-BI-/- HDL loses such regulatory activity. To understand why SR-BI-/- HDL loses its regulatory activity, we analyzed HDL cholesterol contents. There was 3-fold enrichment of unesterified cholesterol in SR-BI-/- HDL compared with SR-BI+/+ HDL. Normalization of unesterified cholesterol in SR-BI-/- HDL by probucol administration or lecithin cholesteryl acyltransferase expression restored glucocorticoid-induced thymocyte apoptosis, and incorporating unesterified cholesterol into SR-BI+/+ HDL rendered SR-BI+/+ HDL dysfunctional. Using lckCre-GR(fl/fl) mice in which thymocytes lack cecal ligation and puncture-induced thymocyte apoptosis, we showed that lckCre-GR(fl/fl) mice were significantly more susceptible to cecal ligation and puncture-induced septic death than GR(fl/fl) control mice, suggesting that glucocorticoid-induced thymocyte apoptosis is required for protection against sepsis. Conclusions The findings in this study reveal a novel regulatory mechanism of thymocyte apoptosis in sepsis by SR-BI and HDL. C1 [Guo, Ling; Zheng, Zhong; Ai, Junting; Li, Xiang-An] Univ Kentucky, Coll Med, Dept Pediat, Lexington, KY 40536 USA. [Zheng, Zhong; Ai, Junting; Li, Xiang-An] Univ Kentucky, Coll Med, Grad Ctr Nutr Sci, Lexington, KY 40536 USA. [Howatt, Deborah A.; Daugherty, Alan; Li, Xiang-An] Univ Kentucky, Coll Med, Saha Cardiovasc Res Ctr, Lexington, KY 40536 USA. [Mittelstadt, Paul R.; Ashwell, Jonathan D.] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. [Thacker, Seth; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, NIH, Bethesda, MD 20892 USA. RP Li, XA (reprint author), Univ Kentucky, Coll Med, Dept Pediat, BBSRB B255,741 S Limestone, Lexington, KY 40536 USA. EM xli2@email.uky.edu FU National Institute of General Medical Sciences (NIGMS)/National Institutes of Health (NIH) [R01GM085231, R01GM085231-2S1, R01GM085231-5S1]; Children's Miracle Network FX This publication was made possible by grant Nos. R01GM085231, R01GM085231-2S1, and R01GM085231-5S1 from National Institute of General Medical Sciences (NIGMS)/National Institutes of Health (NIH). The content of this article is solely the responsibility of the authors and do not necessarily represent the official views of the NIGMS or NIH. This work was also supported by a grant from the Children's Miracle Network. NR 52 TC 4 Z9 4 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2014 VL 34 IS 5 BP 966 EP 975 DI 10.1161/ATVBAHA.113.302484 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AF0AJ UT WOS:000334373500007 PM 24603680 ER PT J AU Mehta, N Qamar, A Qu, L Qasim, AN Mehta, NN Reilly, MP Rader, DJ AF Mehta, Nidhi Qamar, Arman Qu, Liming Qasim, Atif N. Mehta, Nehal N. Reilly, Muredach P. Rader, Daniel J. TI Differential Association of Plasma Angiopoietin-Like Proteins 3 and 4 With Lipid and Metabolic Traits SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE angiopoietins; cholesterol; HDL; cholesterol; LDL; diabetes mellitus; epidemiology; lipid metabolism; lipids; lipoproteins; triglycerides ID TRIGLYCERIDE-METABOLISM; ANGPTL4; OVEREXPRESSION; CHOLESTEROL; DISEASE; RISK; LOCI; HDL AB Objective Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) are secreted proteins that inhibit lipoprotein lipase in vitro. Genetic variants at the ANGPTL3 and ANGPTL4 gene loci are significantly associated with plasma lipid traits. The aim of this study was to evaluate the association of plasma ANGPTL3 and ANGPTL4 concentrations with lipid and metabolic traits in a large community-based sample. Approach and Results Plasma ANGPTL3 and ANGPTL4 levels were measured in 1770 subjects using a validated ELISA assay. A Pearson unadjusted correlation analysis and a linear regression analysis adjusting for age, sex, and race were performed. ANGPTL3 levels were significantly positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels (both P<2x10(-5)) but not triglycerides. In contrast, ANGPTL4 levels were significantly negatively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (both P<2x10(-5)) and positively associated with triglycerides (P=0.003). In addition, ANGPTL4, but not ANGPTL3, levels were significantly positively associated with fasting blood glucose and metabolic syndrome. Conclusions Despite having similar biochemical effects in vitro, plasma ANGPTL3 and ANGPTL4 concentrations have nearly opposite relationships with plasma lipids. ANGPTL4 is strongly negatively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and positively with multiple features of the metabolic syndrome including triglycerides, whereas ANGPTL3 is positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and not with metabolic syndrome traits including triglycerides. Although ANGPTL3 and ANGPTL4 both inhibit lipoprotein lipase in vitro and influence lipoprotein metabolism in vivo, the physiology of these related proteins and their effects on lipoproteins is clearly divergent and complex. C1 [Mehta, Nidhi; Qamar, Arman; Qu, Liming; Reilly, Muredach P.; Rader, Daniel J.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Mehta, Nidhi; Qamar, Arman; Qu, Liming; Reilly, Muredach P.; Rader, Daniel J.] Univ Penn, Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USA. [Qasim, Atif N.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Mehta, Nehal N.] NHLBI, Bethesda, MD 20892 USA. RP Mehta, N (reprint author), Univ Penn, Div Cardiovasc Med, 3400 Civ Ctr Blvd,9 Gates Bldg, Philadelphia, PA 19104 USA. EM nidhi.mehta@uphs.upenn.edu FU National Heart, Lung, and Blood Institute [R37 HL055323, RC2 HL101834] FX This work was supported by grants R37 HL055323 and RC2 HL101834 from the National Heart, Lung, and Blood Institute. NR 22 TC 13 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2014 VL 34 IS 5 BP 1057 EP 1063 DI 10.1161/ATVBAHA.113.302802 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AF0AJ UT WOS:000334373500016 PM 24626437 ER PT J AU Huang, J Huffman, JE Yamkauchi, M Trompet, S Asselbergs, FW Sabater-Lleal, M Tregouet, DA Chen, WM Smith, NL Kleber, ME Shin, SY Becker, DM Tang, WH Dehghan, A Johnson, AD Truong, V Folkersen, L Yang, Q Oudot-Mellkah, T Buckley, BM Moore, JH Williams, FMK Campbell, H Silbernagel, G Vitart, V Rudan, I Tofler, GH Navis, GJ DeStefano, A Wright, AF Chen, MH de Craen, AJM Worrall, BB Rudnicka, AR Rumley, A Bookman, EB Psaty, BM Chen, F Keene, KL Franco, OH Bohm, BO Uitterlinden, AG Carter, AM Jukema, JW Sattar, N Bis, JC Ikram, MA Sale, MM McKnight, B Fornage, M Ford, I Taylor, K Slagboom, PE McArdle, WL Hsu, FC Franco-Cereceda, A Goodall, AH Yanek, LR Furie, KL Cushman, M Hofman, A Witteman, JCM Folsom, AR Basu, S Matijevic, N van Gilst, WH Wilson, JF Westendorp, RGJ Kathiresan, S Reilly, MP Tracy, RP Polasek, O Winkelmann, BR Grant, PJ Hillege, HL Cambien, F Stott, DJ Lowe, GD Spector, TD Meigs, JB Marz, W Eriksson, P Becker, LC Morange, PE Soranzo, N Williams, SM Hayward, C van der Harst, P Hamsten, A Lowenstein, CJ Strachan, DP O'Donnell, CJ AF Huang, Jie Huffman, Jennifer E. Yamkauchi, Munekazu Trompet, Stella Asselbergs, Folkert W. Sabater-Lleal, Maria Tregouet, David-Alexandre Chen, Wei-Min Smith, Nicholas L. Kleber, Marcus E. Shin, So-Youn Becker, Diane M. Tang, Weihong Dehghan, Abbas Johnson, Andrew D. Vinh Truong Folkersen, Lasse Yang, Qiong Oudot-Mellkah, Tiphaine Buckley, Brendan M. Moore, Jason H. Williams, Frances M. K. Campbell, Harry Silbernagel, Guenther Vitart, Veronique Rudan, Igor Tofler, Geoffrey H. Navis, Gerjan J. DeStefano, Anita Wright, Alan F. Chen, Ming-Huei de Craen, Anton J. M. Worrall, Bradford B. Rudnicka, Alicja R. Rumley, Ann Bookman, Ebony B. Psaty, Bruce M. Chen, Fang Keene, Keith L. Franco, Oscar H. Boehm, Bernhard O. Uitterlinden, Andre G. Carter, Angela M. Jukema, J. Wouter Sattar, Naveed Bis, Joshua C. Ikram, Mohammad A. Sale, Michele M. McKnight, Barbara Fornage, Myriam Ford, Ian Taylor, Kent Slagboom, P. Eline McArdle, Wendy L. Hsu, Fang-Chi Franco-Cereceda, Anders Goodall, Alison H. Yanek, Lisa R. Furie, Karen L. Cushman, Mary Hofman, Albert Witteman, Jacqueline C. M. Folsom, Aaron R. Basu, Saonli Matijevic, Nena van Gilst, Wiek H. Wilson, James F. Westendorp, Rudi G. J. Kathiresan, Sekar Reilly, Muredach P. Tracy, Russell P. Polasek, Ozren Winkelmann, Bernhard R. Grant, Peter J. Hillege, Hans L. Cambien, Francois Stott, David J. Lowe, Gordon D. Spector, Timothy D. Meigs, James B. Marz, Winfried Eriksson, Per Becker, Lewis C. Morange, Pierre-Emmanuel Soranzo, Nicole Williams, Scott M. Hayward, Caroline van der Harst, Pim Hamsten, Anders Lowenstein, Charles J. Strachan, David P. O'Donnell, Christopher J. CA CHARGE Consortium Hemostatic TI Genome-Wide Association Study for Circulating Tissue Plasminogen Activator Levels and Functional Follow-Up Implicates Endothelial STXBP5 and STX2 SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE fibrinolysis; genome-wide association study; hemostasis; meta-analysis; tissue plasminogen activator ID VON-WILLEBRAND-FACTOR; CORONARY-ARTERY-DISEASE; ACUTE ISCHEMIC-STROKE; MYOCARDIAL-INFARCTION; PLASMA-LEVELS; GENETIC-VARIATION; RISK; HEART; POLYMORPHISMS; INHIBITOR-1 AB Objective Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases. We conducted a meta-analysis of genome-wide association studies to identify novel correlates of circulating levels of tPA. Approach and Results Fourteen cohort studies with tPA measures (N=26 929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (P<5.0x10(-8)). The first locus is on 6q24.3, with the lead single nucleotide polymorphism (SNP; rs9399599; P=2.9x10(-14)) within STXBP5. The second locus is on 8p11.21. The lead SNP (rs3136739; P=1.3x10(-9)) is intronic to POLB and <200 kb away from the tPA encoding the gene PLAT. We identified a nonsynonymous SNP (rs2020921) in modest linkage disequilibrium with rs3136739 (r(2)=0.50) within exon 5 of PLAT (P=2.0x10(-8)). The third locus is on 12q24.33, with the lead SNP (rs7301826; P=1.0x10(-9)) within intron 7 of STX2. We further found evidence for the association of lead SNPs in STXBP5 and STX2 with expression levels of the respective transcripts. In in vitro cell studies, silencing STXBP5 decreased the release of tPA from vascular endothelial cells, whereas silencing STX2 increased the tPA release. Through an in silico lookup, we found no associations of the 3 lead SNPs with coronary artery disease or stroke. Conclusions We identified 3 loci associated with circulating tPA levels, the PLAT region, STXBP5, and STX2. Our functional studies implicate a novel role for STXBP5 and STX2 in regulating tPA release. C1 [Huang, Jie; Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Huang, Jie; Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Huffman, Jennifer E.; Vitart, Veronique; Wright, Alan F.; Hayward, Caroline] Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland. [Yamkauchi, Munekazu; Lowenstein, Charles J.] Univ Rochester, Sch Med & Dent, Dept Med, Aab Cardiovasc Res Inst, Rochester, NY 14642 USA. [Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RA Leiden, Netherlands. [Trompet, Stella; de Craen, Anton J. M.; Westendorp, Rudi G. J.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2300 RA Leiden, Netherlands. [Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2300 RA Leiden, Netherlands. [Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands. [Asselbergs, Folkert W.] ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands. [Asselbergs, Folkert W.] UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England. [Sabater-Lleal, Maria; Folkersen, Lasse; Slagboom, P. Eline; Hofman, Albert] Karolinska Univ Hosp, Karolinska Inst, Cardiovasc Genet & Genom Grp, Atherosclerosis Res Unit,Dept Med, Stockholm, Sweden. [Tregouet, David-Alexandre; Vinh Truong; Oudot-Mellkah, Tiphaine; Chen, Fang] Univ Paris 06, INSERM, UMRS 937, Paris, France. [Tregouet, David-Alexandre; Vinh Truong; Chen, Fang] ICAN Inst Cardiometab & Nutr, Paris, France. [Chen, Wei-Min; Worrall, Bradford B.; Chen, Fang] Univ Virginia, Ctr Publ Hlth Genom, Dept Publ Hlth Sci, Charlottesville, VA USA. [Sale, Michele M.] Univ Virginia, Ctr Publ Hlth Genom, Dept Biochem & Mol Genet, Charlottesville, VA USA. [Smith, Nicholas L.; Psaty, Bruce M.; McKnight, Barbara] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.; Bis, Joshua C.] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA USA. [Smith, Nicholas L.; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Smith, Nicholas L.] Seattle Epidemiol Res & Informat Ctr, VA Off Res & Dev, Seattle, WA USA. [Kleber, Marcus E.] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany. [Boehm, Bernhard O.] Univ Ulm, Med Ctr, Dept Internal Med 1, D-89069 Ulm, Germany. [Kleber, Marcus E.; McArdle, Wendy L.] Heidelberg Univ, Mannheim Inst Publ Hlth, Med Fac Mannheim, Mannheim, Germany. [Shin, So-Youn; Sattar, Naveed] Wellcome Trust Sanger Inst, Hinxton, England. [Shin, So-Youn] Univ Bristol, MRC Ctr CAiTE, Sch Social & Community Med, Bristol, Avon, England. [McArdle, Wendy L.] Univ Bristol, ALSPAC Lab, Dept Social Med, Bristol, Avon, England. [Becker, Diane M.; Yanek, Lisa R.; Becker, Lewis C.] Johns Hopkins Sch Med, Div Internal Med, Baltimore, MD USA. [Tang, Weihong; Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Basu, Saonli] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Dehghan, Abbas; Franco, Oscar H.; Ikram, Mohammad A.; Goodall, Alison H.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Uitterlinden, Andre G.; Grant, Peter J.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Ikram, Mohammad A.] Erasmus MC, Dept Radiol, Rotterdam, Netherlands. [Ikram, Mohammad A.] Erasmus MC, Dept Neurol, Rotterdam, Netherlands. [Dehghan, Abbas; Franco, Oscar H.; Uitterlinden, Andre G.; Slagboom, P. Eline; Goodall, Alison H.; Witteman, Jacqueline C. M.; Westendorp, Rudi G. J.] Netherlands Genom Initiat, Netherlands Consortium Hlth Aging, Leiden, Netherlands. [Yang, Qiong; DeStefano, Anita; Chen, Ming-Huei] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Buckley, Brendan M.] Natl Univ Ireland Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland. [Moore, Jason H.; Williams, Scott M.] Gesiel Sch Med Dartmouth, Dept Genet, Lebanon, NH USA. [Moore, Jason H.] Gesiel Sch Med Dartmouth, Dept Community & Family Med, Lebanon, NH USA. [Williams, Frances M. K.; Spector, Timothy D.; Soranzo, Nicole] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Campbell, Harry; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9YL, Midlothian, Scotland. [Silbernagel, Guenther] Swiss Cardiovasc Ctr, Dept Angiol, Bern, Switzerland. [Tofler, Geoffrey H.] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. [Navis, Gerjan J.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands. [van Gilst, Wiek H.; Hillege, Hans L.; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Rudnicka, Alicja R.; Strachan, David P.] St Georges Univ London, Div Populat Hlth Sci & Educ, London, England. [Rumley, Ann; Stott, David J.; Lowe, Gordon D.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland. [Bookman, Ebony B.] NHGRI, Div Genom Med, Framingham, MA USA. [Keene, Keith L.] E Carolina Univ, Dept Biol, Greenville, NC USA. [Keene, Keith L.] E Carolina Univ, Ctr Hlth Dispar Res, Greenville, NC USA. [Boehm, Bernhard O.] Nanyang Technol Univ, LKC Sch Med, Singapore 639798, Singapore. [Carter, Angela M.] Univ Leeds, Div Cardiovasc & Diabet Res, Leeds, W Yorkshire, England. [Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands. [Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands. [Sattar, Naveed] BHF Glasgow Cardiovasc Res Ctr, Fac Med, Glasgow, Lanark, Scotland. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Brown Fdn, Inst Mol Med, Houston, TX 77030 USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Div Epidemiol, Sch Publ Hlth, Houston, TX 77030 USA. [Matijevic, Nena] Univ Texas Hlth Sci Ctr Houston, Hemostasis Lab, Houston, TX 77030 USA. [Taylor, Kent] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Hsu, Fang-Chi] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Franco-Cereceda, Anders] Karolinska Inst, Dept Mol Med & Surg, Cardiothorac Surg Unit, Stockholm, Sweden. [Goodall, Alison H.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Keene, Keith L.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT USA. [Cushman, Mary; Tracy, Russell P.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. [Kathiresan, Sekar; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Kathiresan, Sekar] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA USA. [Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Polasek, Ozren] Univ Split, Dept Publ Hlth, Fac Med, Split, Croatia. [Winkelmann, Bernhard R.] Cardiol Team Sachsenhausen, Frankfurt, Germany. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Marz, Winfried] Synlab Acad, Mannheim, Germany. [Marz, Winfried] Med Univ Graz, Inst Clin Med, Graz, Austria. [Marz, Winfried] Med Univ Graz, Chem Lab Diagnost, Graz, Austria. [Morange, Pierre-Emmanuel] Aix Marseille Univ, INSERM, UMRS 1062, Marseille, France. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte St,2nd Floor, Framingham, MA 01702 USA. EM odonnellc@nhlbi.nih.gov RI Boehm, Bernhard/F-8750-2015; Wilson, James F/A-5704-2009; Polasek, Ozren/B-6002-2011; Tregouet, David-Alexandre/E-3961-2016; Rudan, Igor/I-1467-2012; Hayward, Caroline/M-8818-2016; Johnson, Andrew/G-6520-2013; Slagboom, P. Eline/R-4790-2016; OI Soranzo, Nicole/0000-0003-1095-3852; Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; Rudan, Igor/0000-0001-6993-6884; Hayward, Caroline/0000-0002-9405-9550; Slagboom, P. Eline/0000-0002-2875-4723; Williams, Frances/0000-0002-2998-2744; Folkersen, Lasse/0000-0003-0708-9530; Kleber, Marcus/0000-0003-0663-7275; Dehghan, Abbas/0000-0001-6403-016X; Sabater Lleal, Maria/0000-0002-0128-379X FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; Swedish Research Council [12660]; Stockholm County Council [20090077]; Swedish Heart-Lung Foundation [20090541, 8691]; European Commission (FAD) [Health F2 2008 200647]; Medical Research Council [G0000934]; Wellcome Trust [068545/Z/02, 076113/B/04/Z]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Diseases (NIAID); National Human Genome Research Institute (NHGRI); National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation International (JDRF); Juvenile Diabetes Research Foundation International; Wellcome Trust; National Institute for Health Research (NIHR); Cambridge Biomedical Research Centre; Wellcome Trust Strategic Award [079895]; EU [018996, LSHM-CT-2006-037593]; French Ministry of Research; NHLBI [HHSN268201200036C, N01HC85239, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295, HL087652, HL105756, N01-HC-35129, N01 HC-15103, N01-HC-75150, N01-HC-45133]; National Institute of Neurological Disorders and Stroke NINDS; National Institute on Aging (NIA) [AG023629]; National Center for Research Resources [UL1RR033176]; National Center for Advancing Translational Sciences, Clinical & Translational Science Institute [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Disease grant [DK063491]; Medical Research Council UK; Ministry of Science, Education, and Sport of the Republic of Croatia [108-10803150302]; EU 6th Framework Programme EUROSPAN project [LSHG-CT-2006-018947]; NHLBI's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK080140]; GeneSTAR from the National Institutes of Health (NIH) [1U01 HL072518, R01 HL59684]; Johns Hopkins University School of Medicine General Clinical Research Center; NIH [M01 RR00052, LM010098, HL65234, HL67466, RR018787, P01 HL56091, R01 HL074061, R01 HL78635, P01 HL65608]; Knut and Alice Wallenberg Foundation; Swedish Heart-Lung Foundation; Torsten and Ragnar Sderberg Foundation; Strategic Cardiovascular Program of Karolinska Institutet; Stockholm County Council; Foundation for Strategic Research; Marie Curie Intra European Fellowship within the EU [PIEF-GA-2009-252361]; EU 6th Framework Programme [LSHG-CT-2006-018947, LSHM-CT-2004-503485]; EU 7th Framework Programme (Atheroremo) [201668]; EU 7th Framework Programme (RiskyCAD) [305739]; Program Hospitalier de Recherche Clinique; Fondation pour la Recherche Medicale; La Region Ile de France (CODDIM); Genomic Network of the Pierre and Marie Curie University, Paris; Chief Scientist Office of the Scottish Government; Royal Society; Wellcome Trust Clinical Research Facility in Edinburgh, United Kingdom; Dutch Kidney Foundation [E033]; Netherlands Heart Foundation [2006B140, 2006T003, 2001 D 032]; EU project grant GENECURE [2006037697]; NWO VENI [91676170]; Dutch Inter University Cardiology Institute Netherlands (ICIN); Netherlands Organization for Health Research and Development (ZonMw) [90700342]; Bristol-Myers Squibb; 7th Framework Programme of the European commission [223004]; Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging) [050-060-810]; Scottish Executive Chief Scientist Office, Health Services Research Committee [CZG/4/306]; Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for Scientific Research (NWO); Netherlands Organization for ZonMw; Research Institute for Diseases in the Elderly (RIDE); Netherlands Heart Foundation; Ministry of Education, Culture and Science; Ministry of Health Welfare and Sports; European Commission; Municipality of Rotterdam; NWO [175.010.2005.011, 911-03-012, 918-76-619, 916.12.154]; Research Institute for Diseases in the Elderly [014-93-015]; Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]; EUR Fellowship; European Community [005268]; ENGAGE project [HEALTH-F4-2007-201413]; FP-5 GenomEUtwin Project [QLG2-CT-2002-01254]; Department of Health via the NIHR comprehensive Biomedical Research Centre; Biotechnology and Biological Sciences Research Council (BBSRC) project [G20234]; National Eye Institute via an NIH/Center for Inherited Disease Research (CIDR) genotyping project; Oak Foundation; American Heart Association (AHA) [EIG 0140210N]; Paul N. Yu Professorship; AHA [0835446N]; National Human Genome Research Institute (NHGRI) [U01 HG005160]; NIH; United States Public Health Service [R01 NS34447]; NINDS/NIH; ARIC [U01 HL096917, R01-HL093029]; NIA [AG-023629, AG-15928, AG-20098, AG-027058, NS17950, AG08122, AG033193]; NINDS; [U01 DK062418] FX The Atherosclerosis Risk in Communities (ARIC) study is performed as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). Advanced Study of Aortic Pathology (ASAP) work was supported by the Swedish Research Council (12660), the Stockholm County Council (20090077), the Swedish Heart-Lung Foundation (20090541), the European Commission (FAD, Health F2 2008 200647), and a donation by Fredrik Lundberg. British 1958 Birth Cohort (B58C) was funded by the Medical Research Council (grant G0000934) and the Wellcome Trust (grant 068545/Z/02; http://www.b58cgene.sgul.ac.uk/). Genotyping for the B58C-WTCCC subset was funded by the Wellcome Trust (grant 076113/B/04/Z). The B58C-T1DGC genotyping used resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD), and Juvenile Diabetes Research Foundation International (JDRF), and supported by U01 DK062418. B58CT1DGC genome-wide association study (GWAS) data were deposited by the Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research (CIMR), University of Cambridge, which is funded by Juvenile Diabetes Research Foundation International, the Wellcome Trust, and the National Institute for Health Research (NIHR), Cambridge Biomedical Research Centre; the CIMR is in receipt of a Wellcome Trust Strategic Award (079895). The B58C-GABRIEL genotyping was supported by a contract from the EU 6th Framework Programme (018996) and grants from the French Ministry of Research. CardioGenics was funded by the EU 6th Framework Programme (LSHM-CT-2006-037593). The Cardiovascular Health Study (CHS) was supported by NHLBI contracts HHSN268201200036C, N01HC85239, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086, and NHLBI grants HL080295, HL087652, HL105756 with additional contribution from the National Institute of Neurological Disorders and Stroke NINDS). Additional support was provided through AG023629 from the National Institute on Aging (NIA). A full list of CHS investigators and institutions can be found at - http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping at Cedars-Sinai Medical Center was supported in part by the National Center for Research Resources (grant UL1RR033176) and is now at the National Center for Advancing Translational Sciences, Clinical & Translational Science Institute (grant UL1TR000124), in addition to the National Institute of Diabetes and Digestive and Kidney Disease grant (DK063491) to the Southern California Diabetes Endocrinology Research Center. The CROATIAVis study in the Croatian island of Vis was supported through the grants from the Medical Research Council UK and Ministry of Science, Education, and Sport of the Republic of Croatia (number 108-10803150302) and the EU 6th Framework Programme EUROSPAN project (contract no. LSHG-CT-2006-018947). The Framingham Heart Study was partially supported by NHLBI's Framingham Heart Study (contract no. N01-HC-25195) and its contract with Affymetrix, Inc, for genotyping services (contract no. N02-HL-6-4278).; A portion of this research used the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Partial investigator support was provided by National Institute of Diabetes and Digestive and Kidney Diseases (K24 DK080140, to J. B. M). GeneSTAR was supported by grants 1U01 HL072518 and R01 HL59684 from the National Institutes of Health (NIH) and the Johns Hopkins University School of Medicine General Clinical Research Center, and the NIH grant M01 RR00052. The Precocious Coronary Artery Disease Study (PROCARDIS) was supported by the Swedish Research Council (8691), the Knut and Alice Wallenberg Foundation, the Swedish Heart-Lung Foundation, the Torsten and Ragnar Sderberg Foundation, the Strategic Cardiovascular Program of Karolinska Institutet and Stockholm County Council, the Foundation for Strategic Research, and the Stockholm County Council. M. S.-L. is a recipient of a Marie Curie Intra European Fellowship within the EU 7th Framework Programme (PIEF-GA-2009-252361). The Ludwigshafen Risk and Cardiovascular Health (LURIC) Study has received funding from the EU 6th Framework Programme (integrated project Bloodomics; grant LSHM-CT-2004-503485) and from the EU 7th Framework Programme (Atheroremo, grant agreement no. 201668; RiskyCAD, grant agreement no. 305739). The Marseille Thrombosis Association (MARTHA) project was supported by a grant from the Program Hospitalier de Recherche Clinique. T.O.M. was supported by a grant from the Fondation pour la Recherche Medicale. Statistical analyses in MARTHA benefit from the C2BIG Computing Centre funded by the Fondation pour la Recherche Medicale, La Region Ile de France (CODDIM), and the Genomic Network of the Pierre and Marie Curie University, Paris. The Orkney Complex Disease Study (ORCADES) was supported by the Chief Scientist Office of the Scottish Government, the Royal Society, and the EU 6th Framework Programme EUROSPAN project (contract no. LSHG-CT-2006-018947). DNA extractions were performed at the Wellcome Trust Clinical Research Facility in Edinburgh, United Kingdom. Prevention of Renal and Vascular Endstage Disease (PREVEND) genetics is supported by the Dutch Kidney Foundation (grant E033), The Netherlands Heart Foundation (grant 2006B140, 2006T003), NIH (grants LM010098, HL65234, HL67466, RR018787), and the EU project grant GENECURE (FP-6 LSHM CT 2006037697). P.v.d.H. is supported by the NWO VENI grant 91676170 and the Dutch Inter University Cardiology Institute Netherlands (ICIN). F.W.A. is supported by a clinical fellowship from the Netherlands Organization for Health Research and Development (ZonMw; grant 90700342). Pravastatin in Elderly Individuals at Risk of Vascular Disease (PROSPER) was supported by an investigator-initiated grant obtained from Bristol-Myers Squibb. J.W.J. is an established clinical investigator of the Netherlands Heart Foundation (grant 2001 D 032). Support for genotyping for the PROSPER/ Pharmacogenetic Study of Statins in the Elderly at Risk (PHASE) study was provided by the 7th Framework Programme of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging; grant 050-060-810). Measurement of plasma tissue plasminogen activator was funded by the Scottish Executive Chief Scientist Office, Health Services Research Committee grant number CZG/4/306.; The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research (NWO), the Netherlands Organization for ZonMw, the Research Institute for Diseases in the Elderly (RIDE), the Netherlands Heart Foundation, the Ministry of Education, Culture and Science, the Ministry of Health Welfare and Sports, the European Commission, and the Municipality of Rotterdam. Support for genotyping was provided by NWO (no. 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) project no. 050-060-810. J.C.M.W. is supported by NWO grant (vici, 918-76-619). A.D. is supported by NWO grant (veni, 916.12.154) and the EUR Fellowship. The Twins UK study was funded by the Wellcome Trust, European Community's 6th and 7th Framework Programmes (FP-6/2005-2008, FP7/2007-2013) LIFE SCIENCES & HEALTH (Ref 005268 Genetic regulation of the end stage clotting process that leads to thrombotic stroke: the EuroClot Consortium), ENGAGE project HEALTH-F4-2007-201413 and the FP-5 GenomEUtwin Project (QLG2-CT-2002-01254). The study also received support from the Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London. T.D.S. is an NIHR Senior Investigator. The project also received support from a Biotechnology and Biological Sciences Research Council (BBSRC) project grant (G20234). The authors acknowledge the funding and support of the National Eye Institute via an NIH/Center for Inherited Disease Research (CIDR) genotyping project (PI: Terri Young). S.-Y.S. is supported by a Post-Doctoral Research Fellowship from the Oak Foundation. Research at the University of Rochester was supported by grants from the NIH (P01 HL56091, R01 HL074061, R01 HL78635, P01 HL65608), American Heart Association (AHA; EIG 0140210N), and the Paul N. Yu Professorship to C.J.L. Supported by grants from the AHA (0835446N) to M. Y. The GWAS component of the Vitamin Intervention for Stroke Prevention (VISP) study was supported by the National Human Genome Research Institute (NHGRI) grant U01 HG005160 (PIs: Michele Sale amd Bradford Worrall), as part of the Genomics and Randomized Trials Network (GARNET). Genotyping services were provided by the Johns Hopkins University's CIDR, which is fully funded through a federal contract from the NIH to the Johns Hopkins University. Assistance with data cleaning was provided by the GARNET Coordinating Center (U01 HG005157; PI: Bruce S. Weir). Study recruitment and collection of data sets for the VISP clinical trial were supported by an investigator-initiated research grant (R01 NS34447; PI: James Toole) from the United States Public Health Service, NINDS/NIH. The Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) Consortium Neurology Working Group was supported by U01 HL096917 and R01-HL093029 for ARIC; by NHLBI contracts N01-HC-35129, N01 HC-15103, N01-HC-75150, N01-HC-45133, and AG-023629, AG-15928, AG-20098, and AG-027058 from the NIA, for CHS; and by NINDS and NIA grants NS17950, AG08122, and AG033193 for Framingham Heart Study. NR 29 TC 14 Z9 14 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2014 VL 34 IS 5 BP 1093 EP 1101 DI 10.1161/ATVBAHA.113.302088 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AF0AJ UT WOS:000334373500021 PM 24578379 ER PT J AU Singh, BH Gulley, JL AF Singh, B. Harpreet Gulley, James L. TI Immunotherapy and therapeutic vaccines in prostate cancer: an update on current strategies and clinical implications SO ASIAN JOURNAL OF ANDROLOGY LA English DT Review DE androgen deprivation; immunotherapy; prostate cancer; therapeutic cancer vaccines ID CYTOTOXIC T-LYMPHOCYTES; DOSE-ESCALATION TRIAL; SIPULEUCEL-T; TUMOR-CELLS; PHASE-I; METASTATIC MELANOMA; COMBINATION IMMUNOTHERAPY; CELLULAR IMMUNOTHERAPY; CTLA-4 BLOCKADE; PROSTVAC-VF AB In recent years, immunotherapy has emerged as a viable and attractive strategy for the treatment of prostate cancer. While there are multiple ways to target the immune system, therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in late-stage clinical trials. The landmark Food and Drug Administration approval of sipuleucel-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A common feature of these immune-based therapies is the appearance of improved overall survival without short-term changes in disease progression. This class effect appears to be due to modulation of tumor growth rate kinetics, in which the activated immune system exerts constant immunologic pressure that slows net tumor growth. Emerging data suggest that the ideal population for clinical trials of cancer vaccines is patients with lower tumor volume and less aggressive disease. Combination strategies that combine immunotherapy with standard therapies have been shown to augment both immune response and clinical benefit. C1 [Singh, B. Harpreet; Gulley, James L.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 81 TC 8 Z9 10 U1 0 U2 7 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1008-682X EI 1745-7262 J9 ASIAN J ANDROL JI Asian J. Androl. PD MAY PY 2014 VL 16 IS 3 BP 364 EP 371 DI 10.4103/1008-682X.122585 PG 8 WC Andrology; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA AH4FI UT WOS:000336082200007 PM 24435055 ER PT J AU Li, CD Chen, DJ Luo, MY Ge, M Zhu, JW AF Li, Chaodong Chen, Daijie Luo, Minyu Ge, Mei Zhu, Jianwei TI Knockdown of ribosomal protein L39 by RNA interference inhibits the growth of human pancreatic cancer cells in vitro and in vivo SO BIOTECHNOLOGY JOURNAL LA English DT Article DE Cell growth; Pancreatic cancer; RNA interference; RPL39; Tumor xenograft ID CASPASE ACTIVATION; K-RAS; EXPRESSION; APOPTOSIS; THERAPY; MICE; PROGRESSION; SURVIVAL; KRAS AB Pancreatic cancer remains a major unsolved health problem lacking a potent therapeutic option. Our previous studies showed that the ribosomal protein L39 (RPL39) gene was up-regulated after long-term silencing of oncogenic KRAS in pancreatic cancer PANC-1 cells, which indicated that RPL39 may be important for pancreatic cancer development and survival. In the current study, small interfering RNA (siRNA) targeting of the RPL39 gene was performed to determine the effects of the RPL39 gene on growth of pancreatic cancer PANC-1 and BxPC-3 cells in vitro and in vivo. Results from in vitro experiments showed that knockdown of RPL39 expression with RPL39-siRNA suppressed cell proliferation and specifically enhanced cell apoptosis significantly in both PANC-1 and BxPC-3 cells. The increase of caspase-8 activities and the loss of mitochondrial membrane potential after RPL39 silencing indicated that the RPL39 gene may be involved in caspase-8-related mitochondrial apoptosis. Further, treatment with the RPL39-siRNA inhibited the growth of a human pancreatic cancer xenograft in BALB/c nude mice, accompanied by a decreased expression of RPL39. In the xenograft tumors with injection of RPL39-siRNA, the expressions of Ki-67 and CD31 were significantly down-regulated, and apoptosis was markedly induced. Our findings suggested that siRNA against the RPL39 gene may be of value for gene therapy of pancreatic cancer. C1 [Li, Chaodong; Ge, Mei; Zhu, Jianwei] Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China. [Li, Chaodong; Zhu, Jianwei] SJTU, Engn Res Ctr Cell Engn & Therapeut Antibody, Shanghai, Peoples R China. [Chen, Daijie] China Natl Inst Pharmaceut Ind, Shanghai, Peoples R China. [Luo, Minyu; Ge, Mei] Shanghai Laiyi Ctr Biopharmaceut R&D, Shanghai, Peoples R China. [Zhu, Jianwei] Frederick Natl Lab Canc Res, Frederick, MD USA. RP Zhu, JW (reprint author), Shanghai Jiao Tong Univ, Sch Pharm, 800 Dongchuan Rd, Shanghai 200240, Peoples R China. EM jianweiz@sjtu.edu.cn FU National New Drug Research and Development [2010ZX09401-403] FX We are grateful to Dr. Jianzhong Xi (Peking University, Department of Biomedical Engineering College of Engineering, Beijing, China) for assistance with the RNAi experiment and critical reading of the manuscript. Authors have been supported by National New Drug Research and Development (Grant 2010ZX09401-403) for this work. NR 41 TC 1 Z9 1 U1 3 U2 10 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1860-6768 EI 1860-7314 J9 BIOTECHNOL J JI Biotechnol. J. PD MAY PY 2014 VL 9 IS 5 SI SI BP 652 EP 663 DI 10.1002/biot.201300321 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA AG9WK UT WOS:000335770500009 PM 24799381 ER PT J AU Miller, RK Darrah, TH Friedman, A Li, A Stodgell, CJ Landrigan, P Walker, C Clark, EB Dole, N Thiex, N Swanson, J Culhane, J Szabo, S Moye, J AF Miller, R. K. Darrah, T. H. Friedman, A. Li, A. Stodgell, C. J. Landrigan, P. Walker, C. Clark, E. B. Dole, N. Thiex, N. Swanson, J. Culhane, J. Szabo, S. Moye, J. TI Environmental Exposures during Pregnancy: US National Children's Study Formative Research Investigation SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Miller, R. K.; Darrah, T. H.; Friedman, A.; Li, A.; Stodgell, C. J.; Landrigan, P.; Walker, C.; Clark, E. B.; Dole, N.; Thiex, N.; Swanson, J.; Culhane, J.; Szabo, S.; Moye, J.] Natl Childrens Study Placental Consortium, Bethesda, MD USA. [Miller, R. K.; Friedman, A.; Stodgell, C. J.] Univ Rochester, Rochester, NY USA. [Darrah, T. H.] Ohio State Univ, Columbus, OH 43210 USA. [Li, A.] Univ Illinois, Chicago, IL USA. [Landrigan, P.] Icahn Sch Med, New York, NY USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Walker, C.] Univ Calif Davis, Davis, CA 95616 USA. [Swanson, J.] Univ Calif Irvine, Irvine, CA USA. [Clark, E. B.] Univ Utah, Salt Lake City, UT USA. [Thiex, N.] S Dakota State Univ, Brookings, SD 57007 USA. [Dole, N.] Univ N Carolina, Chapel Hill, NC USA. [Culhane, J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Moye, J.] NIH, Bethesda, MD 20892 USA. OI Li, An/0000-0002-8476-8783 NR 0 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2014 VL 100 IS 5 SI SI BP 369 EP 369 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA AH7AG UT WOS:000336283800019 ER PT J AU Boyd, WA Freedman, JH AF Boyd, W. A. Freedman, J. H. TI Development of a C. elegans Assay to Characterize the Effects of Toxicants on Growth, Reproduction, and Development SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Boyd, W. A.] NIEHS, Div Natl Toxicol Program, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Freedman, J. H.] NIEHS, Lab Toxicol & Pharmacol, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2014 VL 100 IS 5 SI SI BP 377 EP 377 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA AH7AG UT WOS:000336283800035 ER PT J AU Robinson, D Fenton, S AF Robinson, D. Fenton, S. TI Assessing Early Developmental and Pubertal Effects in CD-1 Mice Following In Utero Exposure to Bisphenol (BP) Analogs SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Robinson, D.] Univ N Carolina, Chapel Hill, NC USA. [Robinson, D.; Fenton, S.] NIEHS, NTP Lab Branch, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2014 VL 100 IS 5 SI SI BP 387 EP 387 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA AH7AG UT WOS:000336283800052 ER PT J AU Rigler, S Kay, D Sicko, R Fan, R Liu, A Caggana, M Browne, M Druschel, C Romitti, P Brody, L Mills, J AF Rigler, S. Kay, D. Sicko, R. Fan, R. Liu, A. Caggana, M. Browne, M. Druschel, C. Romitti, P. Brody, L. Mills, J. TI Novel Copy Number Variants in a Population-Based Investigation of Heterotaxy-Associated Congenital Heart Disease SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Rigler, S.] Naval Med Ctr Portsmouth, Portsmouth, VA USA. [Rigler, S.; Fan, R.; Liu, A.; Mills, J.] NICHD, NIH, Bethesda, MD USA. [Kay, D.; Sicko, R.; Caggana, M.; Browne, M.; Druschel, C.] New York State Dept Hlth, Albany, NY USA. [Romitti, P.] Univ Iowa, Iowa City, IA USA. [Brody, L.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2014 VL 100 IS 5 SI SI BP 397 EP 397 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA AH7AG UT WOS:000336283800071 ER PT J AU Boghossian, N Sicko, R Kay, D Rigler, S Yeung, E Druschel, C Romitti, P Browne, M Fan, R Liu, A Brody, L Mills, J AF Boghossian, N. Sicko, R. Kay, D. Rigler, S. Yeung, E. Druschel, C. Romitti, P. Browne, M. Fan, R. Liu, A. Brody, L. Mills, J. TI Rare Copy Number Variants in Urinary System and Reproductive Genes Implicated in Posterior Urethral Valves SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Boghossian, N.; Yeung, E.; Fan, R.; Liu, A.; Mills, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Sicko, R.; Kay, D.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Rigler, S.] Naval Med Ctr Portsmouth, Portsmouth, VA USA. [Druschel, C.; Browne, M.] New York State Dept Hlth, Congenital Malformat Registry, Albany, NY USA. [Romitti, P.] Univ Iowa, Iowa City, IA USA. [Brody, L.] NHGRI, Bethesda, MD 20892 USA. RI Yeung, Edwina/F-5992-2015 OI Yeung, Edwina/0000-0002-3851-2613 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2014 VL 100 IS 5 SI SI BP 410 EP 410 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA AH7AG UT WOS:000336283800097 ER PT J AU Boghossian, N Sicko, R Kay, D Rigler, S Yeung, E Druschel, C Romitti, P Browne, M Fan, R Liu, A Brody, L Mills, J AF Boghossian, N. Sicko, R. Kay, D. Rigler, S. Yeung, E. Druschel, C. Romitti, P. Browne, M. Fan, R. Liu, A. Brody, L. Mills, J. TI Novel Copy Number Variants in a Population-Based Investigation of Prune Belly Syndrome SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Boghossian, N.; Yeung, E.; Fan, R.; Liu, A.; Mills, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Sicko, R.; Kay, D.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Rigler, S.] Naval Med Ctr Portsmouth, Portsmouth, VA USA. [Romitti, P.] Univ Iowa, Iowa City, IA USA. [Druschel, C.; Browne, M.] New York State Dept Hlth, Congenital Malformat Registry, Albany, NY USA. [Brody, L.] NHGRI, Bethesda, MD 20892 USA. RI Yeung, Edwina/F-5992-2015 OI Yeung, Edwina/0000-0002-3851-2613 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2014 VL 100 IS 5 SI SI BP 425 EP 425 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA AH7AG UT WOS:000336283800125 ER PT J AU Hansen, DK Nakamura, N Juliar, B Mcintyre, B Foster, PMD Inselman, AL AF Hansen, D. K. Nakamura, N. Juliar, B. Mcintyre, B. Foster, P. M. D. Inselman, A. L. TI Preliminary Results from Segment I Fertility Study of Oxybenzone in Rats SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Hansen, D. K.; Nakamura, N.; Juliar, B.; Inselman, A. L.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Mcintyre, B.; Foster, P. M. D.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2014 VL 100 IS 5 SI SI BP 429 EP 429 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA AH7AG UT WOS:000336283800134 ER PT J AU Inselman, AL Nakamura, N Juliar, B Mcintyre, B Foster, P Hansen, DK AF Inselman, A. L. Nakamura, N. Juliar, B. Mcintyre, B. Foster, P. Hansen, D. K. TI Preliminary Results: Effects of Oxybenzone Exposure on Pre- and Postnatal Development in Rats SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Inselman, A. L.; Nakamura, N.; Juliar, B.; Hansen, D. K.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Mcintyre, B.; Foster, P.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2014 VL 100 IS 5 SI SI BP 430 EP 430 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA AH7AG UT WOS:000336283800135 ER PT J AU Siebert, M Sidransky, E Westbroek, W AF Siebert, Marina Sidransky, Ellen Westbroek, Wendy TI Glucocerebrosidase is shaking up the synucleinopathies SO BRAIN LA English DT Review DE glucocerebrosidase; alpha-synuclein; Gaucher disease; Parkinson's disease; lysosome ID UNFOLDED PROTEIN RESPONSE; SAPOSIN-C DEFICIENCY; MULTIPLE SYSTEM ATROPHY; ENDOPLASMIC-RETICULUM STRESS; ACID BETA-GLUCOSIDASE; NEURONOPATHIC GAUCHER-DISEASE; SPORADIC PARKINSONS-DISEASE; CHAPERONE-MEDIATED AUTOPHAGY; INHERITED ENZYME DEFICIENCY; LYSOSOMAL STORAGE DISORDERS AB Mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase, underlie Gaucher disease and are a risk factor for Parkinson's disease. Siebert et al. review emerging evidence that connects glucocerebrosidase with alpha-synuclein. Therapeutic strategies for Gaucher disease may inform the treatment of Parkinson's disease and other synucleinopathies.The lysosomal enzyme glucocerebrosidase, encoded by the glucocerebrosidase gene, is involved in the breakdown of glucocerebroside into glucose and ceramide. Lysosomal build-up of the substrate glucocerebroside occurs in cells of the reticulo-endothelial system in patients with Gaucher disease, a rare lysosomal storage disorder caused by the recessively inherited deficiency of glucocerebrosidase. Gaucher disease has a broad clinical phenotypic spectrum, divided into non-neuronopathic and neuronopathic forms. Like many monogenic diseases, the correlation between clinical manifestations and molecular genotype is not straightforward. There is now a well-established clinical association between mutations in the glucocerebrosidase gene and the development of more prevalent multifactorial disorders including Parkinson's disease and other synucleinopathies. In this review we discuss recent studies advancing our understanding of the cellular relationship between glucocerebrosidase and alpha-synuclein, the potential impact of established and emerging therapeutics for Gaucher disease for the treatment of the synucleinopathies, and the role of lysosomal pathways in the pathogenesis of these neurodegenerative disorders. C1 [Siebert, Marina; Sidransky, Ellen; Westbroek, Wendy] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Siebert, Marina] Univ Fed Rio Grande do Sul, Postgrad Program Cellular & Mol Biol, BR-91501970 Porto Alegre, RS, Brazil. RP Sidransky, E (reprint author), NHGRI, Med Genet Branch, NIH, Bldg 35 Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA. EM sidranse@mail.nih.gov RI di Ronza, Alberto/H-7674-2016 OI di Ronza, Alberto/0000-0002-9813-5143 FU Intramural Research Programs of the National Human Genome Research Institute; National Institutes of Health; Brazilian Federal Agency for Support and Evaluation of Graduate Education CAPES; Fulbright Brazil FX This work was supported by the Intramural Research Programs of the National Human Genome Research Institute and the National Institutes of Health. M. S. received support by the Brazilian Federal Agency for Support and Evaluation of Graduate Education CAPES and Fulbright Brazil. NR 221 TC 54 Z9 54 U1 6 U2 25 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD MAY PY 2014 VL 137 BP 1304 EP 1322 DI 10.1093/brain/awu002 PN 5 PG 19 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AH6PK UT WOS:000336252800012 PM 24531622 ER PT J AU Johnson, TV Martin, KR Tomarev, SI AF Johnson, Thomas V. Martin, Keith R. Tomarev, Stanislav I. TI Reply: Platelet-derived growth factor-BB may be involved in mesenchymal stem cell secretome-induced neuroprotection of retinal ganglion cells SO BRAIN LA English DT Letter ID PDGF; BRAIN; CHAIN C1 [Johnson, Thomas V.] Johns Hopkins Sch Med, Baltimore, MD 21205 USA. [Martin, Keith R.] Univ Cambridge, John van Geest Ctr Brain Repair, Cambridge, England. [Tomarev, Stanislav I.] NEI, Sect Retinal Gangl Cell Biol, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Johnson, TV (reprint author), Johns Hopkins Sch Med, 1830 Monument St,Suite 2-300, Baltimore, MD 21205 USA. EM tvjohnson@jhmi.edu RI Johnson, Thomas/C-9351-2011 OI Johnson, Thomas/0000-0002-5372-5457 NR 9 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD MAY PY 2014 VL 137 BP E277 EP U9 DI 10.1093/brain/awu011 PN 5 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AH6PK UT WOS:000336252800004 PM 24531624 ER PT J AU West, ES Kingsbery, MY Mintz, EM Hsu, AP Holland, SM Rady, PL Tyring, SK Grossman, ME AF West, E. S. Kingsbery, M. Y. Mintz, E. M. Hsu, A. P. Holland, S. M. Rady, P. L. Tyring, S. K. Grossman, M. E. TI Generalized verrucosis in a patient with GATA2 deficiency SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID RECALCITRANT CUTANEOUS WARTS; CELL-MEDIATED-IMMUNITY; ACUTE MYELOID-LEUKEMIA; HUMAN-PAPILLOMAVIRUS; EPIDERMODYSPLASIA-VERRUCIFORMIS; PRIMARY LYMPHEDEMA; PRIMARY IMMUNODEFICIENCIES; SPORADIC MONOCYTOPENIA; AUTOSOMAL-DOMINANT; MONOMAC SYNDROME AB Generalized verrucosis is a characteristic of several genetic and immunodeficiency disorders including epidermodysplasia verruciformis; warts, hypogammaglobulinaemia, infections and myelokathexis (WHIM) syndrome; warts, immunodeficiency, lymphoedema and anogenital dysplasia (WILD) syndrome; severe combined immune deficiency and HIV, among others. In recent years, it has been consistently recognized in patients with GATA2 deficiency, a novel immunodeficiency syndrome characterized by monocytopenia, B-cell and natural killer-cell lymphopenia, and a tendency to develop myeloid leukaemias and disseminated mycobacterial, human papillomavirus (HPV) and opportunistic fungal infections. Mutations in GATA2 cause haploinsufficiency and track in families as an autosomal dominant immunodeficiency. GATA2 is a transcription factor involved in early haematopoietic differentiation and lymphatic and vascular development. We describe a case of generalized verrucosis with HPV type 57 presenting in a young man with GATA2 deficiency. GATA2 deficiency is a novel dominant immunodeficiency that is often recognized later in life and should be considered in the differential diagnosis of patients with generalized verrucosis. C1 [West, E. S.; Kingsbery, M. Y.; Mintz, E. M.; Grossman, M. E.] Columbia Univ, Dept Dermatol, Med Ctr, New York, NY 10032 USA. [Hsu, A. P.; Holland, S. M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Rady, P. L.; Tyring, S. K.] Univ Texas Hlth Sci Ctr Houston, Dept Dermatol, Houston, TX 77030 USA. RP West, ES (reprint author), Columbia Univ, Dept Dermatol, Med Ctr, 161 Ft Washington Ave 12th Floor, New York, NY 10032 USA. EM ew2383@columbia.edu FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work is supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 28 TC 3 Z9 3 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD MAY PY 2014 VL 170 IS 5 BP 1182 EP 1186 DI 10.1111/bjd.12794 PG 5 WC Dermatology SC Dermatology GA AH9BZ UT WOS:000336436300037 PM 24359037 ER PT J AU Bernstein, MB Garnett, CT Zhang, HG Velcich, A Wattenberg, MM Gameiro, SR Kalnicki, S Hodge, JW Guha, C AF Bernstein, Michael B. Garnett, Charlie T. Zhang, Huogang Velcich, Anna Wattenberg, Max M. Gameiro, Sofia R. Kalnicki, Shalom Hodge, James W. Guha, Chandan TI Radiation-Induced Modulation of Costimulatory and Coinhibitory T-Cell Signaling Molecules on Human Prostate Carcinoma Cells Promotes Productive Antitumor Immune Interactions SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Article DE immunomodulator; immunotherapy; irradiation; preclinical study; prostate cancer ID HUMAN CARCINOEMBRYONIC ANTIGEN; IFN-GAMMA; COMBINED IMMUNOTHERAPY; CANCER; THERAPY; VACCINE; EXPRESSION; TUMOR; TOLERANCE; PATHWAY AB We sought to determine if single-dose external beam radiation therapy (EBRT) could modulate the expression signature of T-cell costimulatory and coinhibitory molecules in human prostate cancer (PCa) cell lines in vitro. We investigated the functional impact of irradiated PCa cells with a modulated costimulatory profile on responder T-cell activity. We used three PCa cell lines (DU145, PC3, and LNCaP) and two epithelial cell lines from noncancerous prostate and lung tissue. After 72 hours of EBRT, surface expression of four immunostimulatory molecules (CD70, CD275/ICOSL, CD134L/OX40L, and CD137L/41BBL) and two immunosuppressive markers (CTLA-4/CD152 and PD-L1/CD274) were evaluated by flow cytometry. We evaluated the impact of several radiation doses and the longevity of modulated expression. We examined the functional impact of radiation-induced modulation of cancer cells by cytotoxic T cells (CTL) cytotoxicity and ELISPOT assay for interferon-gamma (IFN-gamma) production. Last, we evaluated whether IFN-gamma-induced PD-L1 expression could be reversed by EBRT. After 10 Gy EBRT, expression of OX40L and 41BBL increased in all three PCa cell lines; expression of CD70 and ICOSL increased in PC3 cells. Conversely, a decrease in PD-L1 expression in DU145 and PC3 cells was detectable up to 144 hours after EBRT. No PD-L1 was detected in LNCaP. Epithelial cells from normal prostate were not modulated by radiation. CTL cytolytic activity and IFN-gamma production were enhanced by interaction with irradiated PCa cells. Finally, EBRT failed to prevent IFN-gamma-induced upregulation of PD-L1. We demonstrate that a single dose of EBRT increased surface expression of costimulatory molecules and decreased the expression of coinhibitory molecules in human PCa cell lines. Changes in irradiated tumor cells led to functional enhancement of T-cell activity, despite EBRT failing to reduce IFN-gamma-induced expression of PD-L1. These data suggest that combining radiotherapy with T-cell stimulating immunotherapy may be an attractive strategy for cancer treatment. C1 [Bernstein, Michael B.; Zhang, Huogang; Velcich, Anna; Kalnicki, Shalom; Guha, Chandan] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Radiat Oncol, Bronx, NY 10461 USA. [Garnett, Charlie T.] Georgia State Univ, Dept Biol, Ctr Inflammat Infect & Immun, Atlanta, GA USA. [Wattenberg, Max M.; Gameiro, Sofia R.; Hodge, James W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Guha, C (reprint author), Albert Einstein Coll Med, Montefiore Med Ctr, Dept Radiat Oncol, Mazer Bldg,Room 620,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM cguhamd@gmail.com RI Hodge, James/D-5518-2015; OI Hodge, James/0000-0001-5282-3154; Garnett-Benson, Charlie/0000-0002-0238-3303 FU NIH [R01 EB009040]; Center for Cancer Research, National Cancer Institute, National Institutes of Health FX We thank Bonnie L. Casey and Debra Weingarten for editorial assistance in the preparation of this article. This research was supported by NIH Grant No. R01 EB009040 and the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 39 TC 22 Z9 23 U1 1 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1084-9785 EI 1557-8852 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD MAY PY 2014 VL 29 IS 4 BP 153 EP 161 DI 10.1089/cbr.2013.1578 PG 9 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA AI0KI UT WOS:000336535800002 PM 24693958 ER PT J AU Ueda, K Yoshimi, A Kagoya, Y Nishikawa, S Marquez, VE Nakagawa, M Kurokawa, M AF Ueda, Koki Yoshimi, Akihide Kagoya, Yuki Nishikawa, Satoshi Marquez, Victor E. Nakagawa, Masahiro Kurokawa, Mineo TI Inhibition of histone methyltransferase EZH2 depletes leukemia stem cell of mixed lineage leukemia fusion leukemia through upregulation of p16 SO CANCER SCIENCE LA English DT Article DE 3-Deazaneplanocin; histones; homeobox proteins; mixed-lineage acute leukemias; polycomb repressive complex 2 ID CHRONIC MYELOID-LEUKEMIA; MOLECULAR MARKER; POLYCOMB; GENE; BMI-1; REPRESSION; PROTEINS; METHYLATION; PROGRESSION; EXPRESSION AB Leukemia stem cells (LSC) are resistant to conventional chemotherapy and persistent LSC after chemotherapy are supposed to be a major cause of relapse. However, information on genetic or epigenetic regulation of stem cell properties is still limited and LSC-targeted drugs have scarcely been identified. Epigenetic regulators are associated with many cellular processes including maintenance of stem cells. Of note are polycomb group proteins, because they potentially control stemness, and can be pharmacologically targeted by a selective inhibitor (DZNep). Therefore, we investigated the therapeutic potential of EZH2 inhibition in mixed lineage leukemia (MLL) fusion leukemia. Intriguingly, EZH2 inhibition by DZNep or shRNA not only suppressed MLL fusion leukemia proliferation but also reduced leukemia initiating cells (LIC) frequency. Expression analysis suggested that p16 upregulation was responsible for LICs reduction. Knockdown of p16 canceled the survival advantage of mice treated with DZNep. Chromatin immunoprecipitation assays demonstrated that EZH2 was highly enriched around the transcription-start-site of p16, together with H3K27 methylation marks in MLL/ENL and Hoxa9/Meis1 transduced cells but not in E2A/HLF transduced cells. Although high expression of Hoxa9 in MLL fusion leukemia is supposed to be responsible for the recruitment of EZH2, our data also suggest that there may be some other mechanisms independent of Hoxa9 activation to suppress p16 expression, because expression levels of Hoxa9 and p16 were not inversely related between MLL/ENL and Hoxa9/Meis1 transduced cells. In summary, our findings show that EZH2 is a potential therapeutic target of MLL fusion leukemia stem cells. Leukemia stem cells (LSCs) are main cause of relapse or refractoriness to conventional chemotherapy. Although eradicating LSCs are ideal goal for anti-leukemia therapy, drugs targeting LSCs have scarcely been identified. Polycomb group proteins are associated with controlling stemness including activity of cancer stem cells, and can be pharmacologically targeted by a selective inhibitor of H3K27, DZNep. To our surprise, EZH2 inhibition by DZNep or shRNA not only suppressed MLL fusion leukemia proliferation but also reduced LSCs frequency. Dysregulation of p16 is supposed to be responsible for the effect. We also show that EZH2 are highly enriched around the transcription-start-site of p16, together with H3K27 methylation marks in MLL/ENL cells. Although high expression of Hoxa9 in MLL fusion leukemia is supposed to be responsible for the recruitment of EZH2, our data also suggests that there may be some other mechanisms independent of Hoxa9 activation to suppress p16 expression. We believe that these findings would help us to develop LICs targeted therapy for MLL fusion leukemia. C1 [Ueda, Koki; Yoshimi, Akihide; Kagoya, Yuki; Nishikawa, Satoshi; Nakagawa, Masahiro; Kurokawa, Mineo] Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Tokyo 1138655, Japan. [Yoshimi, Akihide; Kurokawa, Mineo] Tokyo Univ Hosp, Dept Cell Therapy & Transplantat Med, Tokyo 113, Japan. [Nishikawa, Satoshi] Kyowa Hakko Kirin, Biol Res Labs, Tokyo, Japan. [Marquez, Victor E.] NCI Frederick, Biol Chem Lab, Ctr Canc Res, Frederick, MD USA. RP Kurokawa, M (reprint author), Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM kurokawa-tky@umin.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology [KAKENHI 24890045, KAKENHI 24249055]; NIH, National Cancer Institute, Center for Cancer Research FX Ministry of Education, Culture, Sports, Science and Technology (KAKENHI 24890045 and 24249055). NIH, National Cancer Institute, Center for Cancer Research. NR 46 TC 13 Z9 15 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1349-7006 J9 CANCER SCI JI Cancer Sci. PD MAY PY 2014 VL 105 IS 5 BP 512 EP 519 DI 10.1111/cas.12386 PG 8 WC Oncology SC Oncology GA AH0RP UT WOS:000335828300003 PM 24612037 ER PT J AU Qian, WJ Lai, CC Kelley, JA Burke, TR AF Qian, Wen-Jian Lai, Christopher C. Kelley, James A. Burke, Terrence R., Jr. TI Design and Synthesis of Fmoc-Thr[PO(OH)(OPOM)] for the Preparation of Peptide Prodrugs Containing Phosphothreonine in Fully Protected Form SO CHEMISTRY & BIODIVERSITY LA English DT Article DE Phosphothreonine; Prodrug; Solid-phase synthesis; Peptides; Signal transduction ID POLO-BOX DOMAIN; SH2 DOMAIN; SIGNAL-TRANSDUCTION; CELLULAR UPTAKE; KINASE 1; PHOSPHOPEPTIDES; ALKYLATION; LIGANDS; TARGET; TOOLS AB The design and efficient synthesis of N-Fmoc-phosphothreonine protected by a mono-(pivaloyloxy)methyl (POM) moiety at its phosphoryl group (Fmoc-Thr[PO(OH)(OPOM)]-OH, 1, is reported. This reagent is suitable for solid-phase syntheses employing acid-labile resins and Fmoc-based protocols. It allows the preparation of phosphothreonine (pThr)-containing peptides bearing bis-POM-phosphoryl protection. The methodology allows the first reported synthesis of pThr-containing polypeptides having bioreversible prodrug protection, and as such it should be useful in a variety of biological applications. C1 [Qian, Wen-Jian; Lai, Christopher C.; Kelley, James A.; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA. RP Burke, TR (reprint author), NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH, POB B, Frederick, MD 21702 USA. EM burkete@helix.nih.gov RI Burke, Terrence/N-2601-2014 FU NIH, Center for Cancer Research, NCI-Frederick; National Cancer Institute, National Institutes of Health FX This work was supported by the Intramural Research Program of the NIH, Center for Cancer Research, NCI-Frederick and the National Cancer Institute, National Institutes of Health. NR 27 TC 1 Z9 1 U1 0 U2 6 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1612-1872 EI 1612-1880 J9 CHEM BIODIVERS JI Chem. Biodivers. PD MAY PY 2014 VL 11 IS 5 BP 784 EP 791 DI 10.1002/cbdv.201300202 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA AH8GY UT WOS:000336376200010 PM 24827688 ER PT J AU Kornides, ML Nansel, TR Quick, V Haynie, DL Lipsky, LM Laffel, LMB Mehta, SN AF Kornides, M. L. Nansel, T. R. Quick, V. Haynie, D. L. Lipsky, L. M. Laffel, L. M. B. Mehta, S. N. TI Associations of family meal frequency with family meal habits and meal preparation characteristics among families of youth with type 1 diabetes SO CHILD CARE HEALTH AND DEVELOPMENT LA English DT Article DE adolescents; diabetes; family meals; nutrition ID CHOICE COPING STRATEGIES; DIET QUALITY; EMPLOYED PARENTS; ADOLESCENTS; PATTERNS; CHILDREN; DINNER; FOOD; VALIDATION; BEHAVIORS AB BackgroundWhile benefits of family mealtimes, such as improved dietary quality and increased family communication, have been well-documented in the general population, less is known about family meal habits that contribute to more frequent family meals in youth with type 1 diabetes. MethodsThis cross-sectional study surveyed 282 youth ages 8-18 years with type 1 diabetes and their parents on measures regarding diabetes-related and dietary behaviours. T-tests determined significant differences in youth's diet quality, adherence to diabetes management and glycaemic control between those with and without regular family meals (defined as 5 meals per week). Logistic regression analyses determined unadjusted and adjusted associations of age, socio-demographics, family meal habits, and family meal preparation characteristics with regular family meals. Results57% of parents reported having regular family meals. Families with regular family meals had significantly better diet quality as measured by the Healthy Eating Index (P < 0.05) and the NRF9.3 (P < 0.01), and adherence to diabetes management (P < 0.001); the difference in glycaemic control approached statistical significance (P = 0.06). Priority placed on, pleasant atmosphere and greater structure around family meals were each associated with regular family meals (P < 0.05). Meals prepared at home were positively associated with regular family meals, while convenience and fast foods were negatively associated (P < 0.05). Families in which at least one parent worked part-time or stayed at home were significantly more likely to have regular family meals than families in which both parents worked full-time (P < 0.05). In the multivariate logistic regression model, greater parental priority given to family mealtimes (P < 0.001) and more home-prepared meals (P < 0.001) predicted occurrence of regular family meals; adjusting for parent work status and other family meal habits. ConclusionsStrategies for promoting families meals should not only highlight the benefits of family meals, but also facilitate parents' skills for and barriers to home-prepared meals. C1 [Kornides, M. L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Nansel, T. R.; Quick, V.; Haynie, D. L.; Lipsky, L. M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. [Laffel, L. M. B.; Mehta, S. N.] Harvard Univ, Pediat Adolescent & Young Adult Sect, Genet & Epidemiol Sect, Joslin Diabet Ctr,Med Sch, Boston, MA 02115 USA. RP Kornides, ML (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM melanie.kornides@mail.harvard.edu RI Kornides, Melanie/N-5862-2016; OI Kornides, Melanie/0000-0003-1900-4530; Quick, Virginia/0000-0002-4338-963X; Nansel, Tonja/0000-0002-8298-7595; Haynie, Denise/0000-0002-8270-6079; Lipsky, Leah/0000-0003-2645-4388 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Developmen [HHSN267200703434C]; National Institute of Child Health and Human Development, National Institutes of Health [T32HD060454] FX This research was supported by the intramural research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, contract number HHSN267200703434C.; Melanie Kornides was supported by Training Grant T32HD060454 in Reproductive, Perinatal and Pediatric Epidemiology from the National Institute of Child Health and Human Development, National Institutes of Health. NR 25 TC 3 Z9 3 U1 5 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0305-1862 EI 1365-2214 J9 CHILD CARE HLTH DEV JI Child Care Health Dev. PD MAY PY 2014 VL 40 IS 3 BP 405 EP 411 DI 10.1111/cch.12078 PG 7 WC Psychology, Developmental; Pediatrics SC Psychology; Pediatrics GA AE8WI UT WOS:000334283300013 PM 23731337 ER PT J AU Aronow, ME Chew, EY AF Aronow, Mary E. Chew, Emily Y. TI Age-related Eye Disease Study 2: perspectives, recommendations, and unanswered questions SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Review DE age-related macular degeneration; antioxidant vitamins; lutein; omega-3 fatty acids; zeaxanthin ID FATTY-ACID INTAKE; MACULAR DEGENERATION; BETA-CAROTENE; VISUAL IMPAIRMENT; FISH CONSUMPTION; CLINICAL-TRIAL; VITAMIN-C; ZINC; ASSOCIATIONS; MACULOPATHY AB Purpose of reviewThis review provides a perspective on the Age-related Eye Disease Study 2 (AREDS2) including a summary of the goals and rationale of the study, major findings, subsequent management recommendations, and questions that remain to be answered.Recent findingsThe primary goal of the AREDS2 was to evaluate the efficacy and safety of lutein plus zeaxanthin and/or omega-3 long-chain polyunsaturated acid supplementation in reducing the risk of developing advanced age-related macular degeneration (AMD). AREDS2 also investigated the effects of omitting -carotene and reducing the concentration of zinc from the original AREDS formulation. Although primary analysis from the AREDS2 did not reveal a benefit of daily supplementation with lutein/zeaxanthin on AMD progression, secondary exploratory analyses suggested that lutein/zeaxanthin were helpful in reducing this risk. Comparison of low-dose to higher-dose zinc showed no significant benefit.SummaryThe overall evidence on the beneficial and adverse effects from AREDS2 and other studies suggests that lutein/zeaxanthin could be more appropriate than -carotene in AREDS-type supplements. Questions remain regarding the AREDS2 study results such as: whether the findings are generalizable to the population as a whole, what is the long-term safety profile of lutein/zeaxanthin supplementation, should other carotenoids be included in AREDS-type supplements, and at what optimal doses? C1 [Aronow, Mary E.; Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. RP Chew, EY (reprint author), NEI, Div Epidemiol & Clin Applicat, NIH, Bldg 10,CRC,Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA. EM echew@nei.nih.gov FU National Eye Institute/National Institutes of Health (NEI/NIH), Department of Health and Human Services, Bethesda, Maryland [HHS-N-260-2005-00007-C]; National Eye Institute/National Institutes of Health (NEI/NIH), Department of Health and Human Services, Bethesda, Maryland (ADB) [N01-EY-5-0007] FX The authors have no commercial relationships to disclose. AREDS2 was supported by the intramural program funds and contracts from the National Eye Institute/National Institutes of Health (NEI/NIH), Department of Health and Human Services, Bethesda, Maryland (contract No. HHS-N-260-2005-00007-C and ADB contract No. N01-EY-5-0007). NR 31 TC 19 Z9 19 U1 3 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8738 EI 1531-7021 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD MAY PY 2014 VL 25 IS 3 BP 186 EP 190 DI 10.1097/ICU.0000000000000046 PG 5 WC Ophthalmology SC Ophthalmology GA AF1GC UT WOS:000334461400006 PM 24614146 ER PT J AU Cobuzzi, JL Siletti, KA Hurwitz, ZE Wetzell, B Baumann, MH Riley, AL AF Cobuzzi, Jennifer L. Siletti, Kayla A. Hurwitz, Zachary E. Wetzell, Bradley Baumann, Michael H. Riley, Anthony L. TI Age Differences in (+/-) 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Conditioned Taste Aversions and Monoaminergic Levels SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article DE adolescent; adult; sprague-dawley rats; MDMA; CTA; HPLC; monoamine ID PLACE PREFERENCE CPP; ADULT-RATS; LONG-TERM; ADOLESCENT RATS; DOPAMINE RELEASE; FRONTAL-CORTEX; D-AMPHETAMINE; ECSTASY MDMA; STRESS; DRUGS AB Preclinical work indicates that adolescent rats appear more sensitive to the rewarding effects and less sensitive to the aversive effects of abused drugs. The present investigation utilized the conditioned taste aversion (CTA) design to measure the relative aversive effects of (+/-)3,4-methylenedioxymethamphetamine (MDMA; 0, 1.0, 1.8, or 3.2mg/kg) in adolescent and adult Sprague-Dawley rats. After behavioral testing was complete, monoamine and associated metabolite levels in discrete brain regions were quantified using high-performance liquid chromatography coupled to electrochemical detection (HPLC-ECD) to determine if adolescent animals displayed a different neurochemical profile than did adult animals after being exposed to subcutaneous low doses of MDMA. Adolescent rats displayed less robust MDMA-induced taste aversions than adults during acquisition and on a final two-bottle aversion test. MDMA at these doses had no consistent effect on monoamine levels in either age group, although levels did vary with age. The relative insensitivity of adolescents to MDMA's aversive effects may engender an increased vulnerability to MDMA abuse in this specific population. (c) 2013 Wiley Periodicals, Inc. Dev Psychobiol 56: 635-646, 2014. C1 [Cobuzzi, Jennifer L.; Siletti, Kayla A.; Hurwitz, Zachary E.; Wetzell, Bradley; Riley, Anthony L.] Amer Univ, Dept Psychol, Psychopharmacol Lab, Washington, DC 20016 USA. [Baumann, Michael H.] NIDA, Clin Psychopharmacol Sect, Intramural Res Program, Baltimore, MD 21224 USA. RP Cobuzzi, JL (reprint author), Amer Univ, Dept Psychol, Psychopharmacol Lab, 4400 Massachusetts Ave NW, Washington, DC 20016 USA. EM jen.cobuzzi@american.edu FU Mellon Foundation; National Institute on Drug Abuse; National Institutes of Health; Public Health Service; US Department of Health and Human Services FX Contract grant sponsor: Mellon Foundation; Grant Sponsor: National Institute on Drug Abuse; Grant Sponsor: National Institutes of Health; Grant Sponsor: Public Health Service; Grant Sponsor: US Department of Health and Human Services. NR 82 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0012-1630 EI 1098-2302 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD MAY PY 2014 VL 56 IS 4 BP 635 EP 646 DI 10.1002/dev.21132 PG 12 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA AE1DQ UT WOS:000333707600004 PM 23775255 ER PT J AU Conradt, E Abar, B Sheinkopf, S Lester, B Lagasse, L Seifer, R Shankaran, S Bada-Ellzey, H Bauer, C Whitaker, T Hinckley, M Hammond, J Higgins, R AF Conradt, Elisabeth Abar, Beau Sheinkopf, Stephen Lester, Barry Lagasse, Linda Seifer, Ronald Shankaran, Seetha Bada-Ellzey, Henrietta Bauer, Charles Whitaker, Toni Hinckley, Matt Hammond, Jane Higgins, Rosemary TI The Role of Prenatal Substance Exposure and Early Adversity on Parasympathetic Functioning from 3 to 6 Years of Age SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article DE allostatic load; prenatal substance exposure; early adversity; respiratory sinus arrhythmia ID RESPIRATORY SINUS ARRHYTHMIA; CARDIAC VAGAL TONE; AUTONOMIC NERVOUS-SYSTEM; CHILD-BEHAVIOR PROBLEMS; STILL-FACE PARADIGM; COCAINE EXPOSURE; DIFFERENTIAL SUSCEPTIBILITY; PHYSIOLOGICAL REGULATION; STRESS REACTIVITY; YOUNG-CHILDREN AB We employed latent growth curve analysis to examine trajectories of respiratory sinus arrhythmia (RSA) from 3 to 6 years among children with varying levels of prenatal substance exposure and early adversity. Data were drawn from a prospective longitudinal study of prenatal substance exposure that included 1,121 participants. Baseline RSA and RSA reactivity to an attention-demanding task were assessed at 3, 4, 5, and 6 years. Overall, there were significant individual differences in the trajectories of RSA reactivity, but not baseline RSA, across development. Greater levels of prenatal substance exposure, and less exposure to early adversity, were associated with increased RSA reactivity at 3 years, but by 6 years, both were associated with greater RSA reactivity. Prenatal substance exposure had an indirect influence through early adversity on growth in RSA reactivity. Results are in support of and contribute to the framework of allostatic load. (c) 2013 Wiley Periodicals, Inc. Dev Psychobiol 9999: 1-15, 2013. C1 [Conradt, Elisabeth; Abar, Beau; Sheinkopf, Stephen; Lester, Barry; Lagasse, Linda; Hinckley, Matt] Women & Infants Hosp Rhode Isl, Brown Ctr Study Children Risk, Dept Pediat, Providence, RI 02905 USA. [Conradt, Elisabeth; Sheinkopf, Stephen; Lester, Barry; Seifer, Ronald] Brown Univ, Warren Alpert Med Sch, Dept Psychiat, Providence, RI 02912 USA. [Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48202 USA. [Bada-Ellzey, Henrietta] Univ Kentucky, Dept Pediat, Lexington, KY 40506 USA. [Bauer, Charles] Univ Miami, Miller Sch Med, Dept Pediat, Coral Gables, FL 33124 USA. [Whitaker, Toni] Univ Tennessee, Dept Pediat, Knoxville, TN 37996 USA. [Hammond, Jane] Res Triangle Inst, Chapel Hill, NC USA. [Higgins, Rosemary] Natl Inst Hlth, Bethesda, MD USA. RP Conradt, E (reprint author), Women & Infants Hosp Rhode Isl, Brown Ctr Study Children Risk, Dept Pediat, Providence, RI 02905 USA. EM econradt@wihri.org OI Seifer, Ronald/0000-0003-4879-2839 FU National Institute of Child Health and Human Development (NICHD) Neonatal Research Network; National Institute on Drug Abuse (NIDA) [U10-DA-024117-01, U10-HD-21385, I10-DA-024128-06, U10-HD-2786, U10-DA-024119-01, U10-HD-27904, U10-DA-024118-01, U10-HD-21397]; NICHD [N01-HD-2-3159]; National Institute on Drug Abuse [F32DA032175] FX Contract grant sponsor: National Institute of Child Health and Human Development (NICHD) Neonatal Research Network; Contract grant sponsor: National Institute on Drug Abuse (NIDA); Contract grant numbers: U10-DA-024117-01, U10-HD-21385, I10-DA-024128-06, U10-HD-2786, U10-DA-024119-01, U10-HD-27904, U10-DA-024118-01, U10-HD-21397; Contract grant sponsor: NICHD; Contract grant number: N01-HD-2-3159; Contract grant sponsor: National Institute on Drug Abuse; Contract grant number: F32DA032175 NR 96 TC 2 Z9 2 U1 6 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0012-1630 EI 1098-2302 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD MAY PY 2014 VL 56 IS 4 BP 821 EP 835 DI 10.1002/dev.21155 PG 15 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA AE1DQ UT WOS:000333707600019 PM 24002807 ER PT J AU Simpson, EA Paukner, A Suomi, SJ Ferrari, PF AF Simpson, Elizabeth A. Paukner, Annika Suomi, Stephen J. Ferrari, Pier F. TI Visual Attention during Neonatal Imitation in Newborn Macaque Monkeys SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article DE rhesus macaque; infant; visual attention; neonatal imitation; monkey; newborn; social behavior; communication; facial gestures; mother-infant interaction; mirror neuron system ID CHIMPANZEES PAN-TROGLODYTES; FACIAL GESTURES; INFANTS AB Previous studies suggest that about 50% of rhesus macaque infants engage in neonatal imitation of facial gestures. Here we measured whether individual differences in newborn macaques' (n=49) visual attention may explain why some infants imitate lipsmacking (LPS) and tongue protrusion (TP) gestures. LPS imitators, but not TP imitators, looked more to a human experimenter's face and to a control stimulus compared to nonimitators (p=.017). LPS imitation was equally accurate when infants were looking at faces and when they were looking away (p=.221); TP imitation was more accurate when infants were looking at faces (p=.001). Potentially, less attention is necessary for LPS imitation compared to TP imitation, as LPS is part of macaques' natural communicative repertoire. These findings suggest that facial gestures may differentially engage imitators and nonimitators, and infants' visual attention during neonatal assessments may uncover the conditions that support this skill. (c) 2013 Wiley Periodicals, Inc. Dev Psychobiol 56: 864-870, 2014. C1 [Simpson, Elizabeth A.; Paukner, Annika; Suomi, Stephen J.; Ferrari, Pier F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, Poolesville, MD 20873 USA. [Simpson, Elizabeth A.; Ferrari, Pier F.] Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy. RP Simpson, EA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, Poolesville, MD 20873 USA. EM elizabethannsimpson@gmail.com OI Simpson, Elizabeth/0000-0003-2715-2533 FU Division of Intramural Research, NICHD; NICHD [P01HD064653] FX This research was supported by the Division of Intramural Research, NICHD, and NICHD P01HD064653. We thank Valentina Sclafani, Seth Bower, Michelle Miller, Judy Songrady, and Angela Ruggiero for help in collecting the data. Thanks to John Richards and Nathan Fox for data analysis suggestions. NR 27 TC 7 Z9 7 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0012-1630 EI 1098-2302 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD MAY PY 2014 VL 56 IS 4 BP 864 EP 870 DI 10.1002/dev.21146 PG 7 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA AE1DQ UT WOS:000333707600023 PM 23794178 ER PT J AU Bainbridge, KE Ramachandran, V AF Bainbridge, Kathleen E. Ramachandran, Virginia TI Hearing Aid Use Among Older U. S. Adults: The National Health and Nutrition Examination Survey, 2005-2006 and 2009-2010 SO EAR AND HEARING LA English DT Article DE Hearing aids; Hearing loss; Income; Socio-economic factors ID UNITED-STATES; HELP-SEEKING; IMPAIRMENT; DETERMINANTS; PREVALENCE; DISABILITY; COMMUNITY; PEOPLE; IMPACT; TRIAL AB Objectives: The authors estimated the proportion of older adults in the United States who report hearing aid use among those likely to benefit. To more fully understand what factors underlie the low proportion of hearing aid use, the authors examined a variety of socio-demographic correlates as well as measures of health care access and insurance status in relation to hearing aid use among potential hearing aid candidates. Design: The study makes use of cross-sectional data collected during 2005-2006 and 2009-2010 as part of the National Health and Nutrition Examination Survey. The 1636 adults aged 70 years and older were selected by using a complex sampling design and comprise a nationally representative sample. In addition to self-reported hearing aid use, data on pure-tone thresholds, perceived hearing ability, place for routine health care, time since last hearing test, type of insurance coverage, and socio-demographic characteristics including age, sex, race/ethnicity, family size, and income-to-poverty ratio were collected. The analytical sample consisted of 601 adults who had a better-ear pure-tone average of 35 dB HL at 500, 1000, and 2000 Hz or who reported moderate or worse hearing ability. Results: One third of the potential hearing aid candidates reported current use of hearing aids. The authors observed a 28 to 66% greater prevalence of hearing aid use among older adults in the upper four fifths of the income-to-poverty distribution compared with those in the bottom one fifth. Compared with people who had their hearing tested 5 to 9 years ago, those with more recent hearing tests were more than two to three times as likely to be a current hearing aid user. No differences were observed by age after adjusting for pure-tone average and no differences were observed by sex after adjusting for perceived hearing ability. No differences were observed by place of routine health care or by type of insurance coverage. Conclusions: Use of hearing aids is low among older adults who might benefit. Identifying and surmounting barriers to hearing aid use, especially among low-income adults, remains an important objective for hearing health care in the United States. C1 [Bainbridge, Kathleen E.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. [Ramachandran, Virginia] Henry Ford Hosp, Dept Otolaryngol Head & Neck Surg, Detroit, MI 48202 USA. RP Bainbridge, KE (reprint author), Natl Inst Deafness & Other Commun Disorders, 6001 Execut Blvd,Room 8327,MSC 9670, Bethesda, MD 20892 USA. EM bain-bridgek@mail.nih.gov FU National Institute on Deafness and Other Communication Disorders FX The National Institute on Deafness and Other Communication Disorders provided funding support for The National Health and Nutrition Examination Survey audiometric data collection via Interagency Agreements with the National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention, and the National Institute for Occupational Safety and Health (NIOSH), Centers for Disease Control and Prevention. NR 22 TC 13 Z9 13 U1 1 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 EI 1538-4667 J9 EAR HEARING JI Ear Hear. PD MAY-JUN PY 2014 VL 35 IS 3 BP 289 EP 294 DI 10.1097/01.aud.0000441036.40169.29 PG 6 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA AG7DL UT WOS:000335578200008 PM 24521924 ER PT J AU Coltella, N Percio, S Valsecchi, R Cuttano, R Guarnerio, J Ponzoni, M Pandolfi, PP Melillo, G Pattini, L Bernardi, R AF Coltella, Nadia Percio, Stefano Valsecchi, Roberta Cuttano, Roberto Guarnerio, Jlenia Ponzoni, Maurilio Pandolfi, Pier Paolo Melillo, Giovanni Pattini, Linda Bernardi, Rosa TI HIF factors cooperate with PML-RARa to promote acute promyelocytic leukemia progression and relapse SO EMBO MOLECULAR MEDICINE LA English DT Article DE acute promyelocytic leukemia; hypoxia-inducible transcription factor; leukemia-initiating cells; mouse models; PML-RAR ID TRANS-RETINOIC ACID; CANCER STEM-CELLS; EXPRESSION PROFILES; HEMATOPOIETIC STEM; MYELOID-LEUKEMIA; GENE-TRANSFER; RECEPTOR; DIFFERENTIATION; TRANSLOCATION; HIF1-ALPHA AB Acute promyelocytic leukemia (APL) is epitomized by the chromosomal translocation t(15;17) and the resulting oncogenic fusion protein PML-RAR. Although acting primarily as a transcriptional repressor, PML-RAR can also exert functions of transcriptional co-activation. Here, we find that PML-RAR stimulates transcription driven by HIF factors, which are critical regulators of adaptive responses to hypoxia and stem cell maintenance. Consistently, HIF-related gene signatures are upregulated in leukemic promyelocytes from APL patients compared to normal promyelocytes. Through in vitro and in vivo studies, we find that PML-RAR exploits a number of HIF-1-regulated pro-leukemogenic functions that include cell migration, bone marrow (BM) neo-angiogenesis and self-renewal of APL blasts. Furthermore, HIF-1 levels increase upon treatment of APL cells with all-trans retinoic acid (ATRA). As a consequence, inhibiting HIF-1 in APL mouse models delays leukemia progression and exquisitely synergizes with ATRA to eliminate leukemia-initiating cells (LICs). C1 [Coltella, Nadia; Valsecchi, Roberta; Cuttano, Roberto; Guarnerio, Jlenia; Bernardi, Rosa] Ist Sci San Raffaele, Div Mol Oncol, Leukemia Unit, I-20132 Milan, Italy. [Percio, Stefano; Pattini, Linda] Politecn Milan, Dept Elect Informat & Bioengn, I-20133 Milan, Italy. [Ponzoni, Maurilio] Ist Sci San Raffaele, Pathol Unit, Leukemia Unit, I-20132 Milan, Italy. [Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med & Pathol,Canc Res Inst,Beth Israel Deaco, Boston, MA 02215 USA. [Melillo, Giovanni] Sci Applicat Int Corp Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD USA. RP Bernardi, R (reprint author), Ist Sci San Raffaele, Div Mol Oncol, Leukemia Unit, I-20132 Milan, Italy. EM bernardi.rosa@hsr.it RI bernardi, rosa/B-1650-2013; Cuttano, Roberto/B-5884-2017 OI Cuttano, Roberto/0000-0003-4150-2114 FU Giovanni Armenise-Harvard Foundation; Career Development Award; Fondazione Cariplo; Italian Association for Cancer Research (AIRC); EU FX The authors would like to thank all current and previous members of the laboratory for valuable discussion and support; M. Rocchi for tissue preparation and immunohistochemistry; M. F. Di Renzo for sharing reagents and helpful discussion; L. Greenberger, Y. Zhang and Belrose Pharma Inc. for providing EZN-2968 and EZN-3088; S. Minucci and P. G. Pelicci for U937-PR9 and U937-MT cell lines; F. Caligaris Cappio and P. Ghia for insightful discussion. This work was supported by the Giovanni Armenise-Harvard Foundation with a Career Development Award to R. Bernardi, and grants by Fondazione Cariplo, Italian Association for Cancer Research (AIRC, My First AIRC Grant) and the EU (Marie Curie International Reintegration Grant) to R. Bernardi. NR 35 TC 12 Z9 12 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1757-4676 EI 1757-4684 J9 EMBO MOL MED JI EMBO Mol. Med. PD MAY PY 2014 VL 6 IS 5 BP 640 EP 650 DI 10.1002/emmm.201303065 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AG4OT UT WOS:000335400500008 PM 24711541 ER PT J AU Hou, YJ Xiong, B Zheng, WJ Duan, X Cui, XS Kim, NH Wang, Q Xu, YX Sun, SC AF Hou, Yan-Jun Xiong, Bo Zheng, Wei-Jiang Duan, Xing Cui, Xiang-Shun Nam-Hyung Kim Wang, Qiang Xu, Yin-Xue Sun, Shao-Chen TI Oocyte Quality in Mice is Affected by a Mycotoxin-Contaminated Diet SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE mycotoxin; oocyte quality; actin; spindle; mitochondria ID IN-VITRO; GAMMA-TUBULIN; PIG OOCYTES; ZEARALENONE; MATURATION; FERTILIZATION; DEOXYNIVALENOL; REPRODUCTION; MITOCHONDRIA; EXPOSURE AB Mycotoxins, such as deoxynivalenol (DON), zearalenone (ZEN), and aflatoxin (AF), are commonly found in many food commodities and may impair the growth and reproductive efficiency of animals and humans. We investigated the effects of a mycotoxin-contaminated diet on mouse oocyte quality. Maize contaminated with DON (3.875 mg/kg), ZEN (1,897 g/kg), and AF (806 g/kg) was incorporated into a mouse diet at three different levels (0, 15, and 30% w/w). After 4 weeks, ovarian and germinal vesicle oocyte indices decreased in mycotoxin-fed mice. Oocytes from these mice exhibited low developmental competence with reduced germinal vesicle breakdown and polar body extrusion rates. Embryo developmental competence also showed a similar pattern, and the majority of embryos could not develop to the morula stage. Actin expression was also reduced in both the oocyte cortex and cytoplasm, which was accompanied by decreased expression of the actin nucleation factors profilin-1 and mDia1. Moreover, a large percentage of oocytes derived from mice that were fed a mycotoxin-contaminated diet exhibited aberrant spindle morphology, a loss of the cortical granule-free domain, and abnormal mitochondrial distributions, which further supported the decreased oocyte quality. Thus, our results demonstrate that mycotoxins are toxic to the mouse reproductive system by affecting oocyte quality. Environ. Mol. Mutagen. 55:354-362, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Hou, Yan-Jun; Zheng, Wei-Jiang; Duan, Xing; Xu, Yin-Xue; Sun, Shao-Chen] Nanjing Agr Univ, Coll Anim Sci & Technol, Nanjing 210095, Jiangsu, Peoples R China. [Xiong, Bo] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. [Cui, Xiang-Shun; Nam-Hyung Kim] Chungbuk Natl Univ, Dept Anim Sci, Cheongju 361763, South Korea. [Wang, Qiang] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing 211102, Jiangsu, Peoples R China. RP Sun, SC (reprint author), Nanjing Agr Univ, Coll Anim Sci & Technol, Nanjing 210095, Jiangsu, Peoples R China. EM sunsc@njau.edu.cn FU National Basic Research Program of China [2014CB138503]; National Natural Science Foundation of China [31301860]; Fundamental Research Funds for the Central Universities of China [KYRC201202]; BioGreen 21 Program [PJ009594, PJ00956302] FX Grant sponsor: National Basic Research Program of China; Grant number: 2014CB138503.; Grant sponsor: National Natural Science Foundation of China; Grant number: 31301860.; Grant sponsor: Fundamental Research Funds for the Central Universities of China; Grant number: KYRC201202.; Grant sponsor: BioGreen 21 Program; Grant number: PJ009594 and PJ00956302. NR 36 TC 7 Z9 7 U1 0 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD MAY PY 2014 VL 55 IS 4 BP 354 EP 362 DI 10.1002/em.21833 PG 9 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA AE1RA UT WOS:000333745800006 PM 24288346 ER PT J AU Rochitte, CE George, RT Chen, MY Arbab-Zadeh, A Dewey, M Miller, JM Niinuma, H Yoshioka, K Kitagawa, K Nakamori, S Laham, R Vavere, AL Cerci, RJ Mehra, VC Nomura, C Kofoed, KF Jinzaki, M Kuribayashi, S de Roos, A Laule, M Tan, SY Hoe, J Paul, N Rybicki, FJ Brinker, JA Arai, AE Cox, C Clouse, ME Di Carli, MF Lima, JAC AF Rochitte, Carlos E. George, Richard T. Chen, Marcus Y. Arbab-Zadeh, Armin Dewey, Marc Miller, Julie M. Niinuma, Hiroyuki Yoshioka, Kunihiro Kitagawa, Kakuya Nakamori, Shiro Laham, Roger Vavere, Andrea L. Cerci, Rodrigo J. Mehra, Vishal C. Nomura, Cesar Kofoed, Klaus F. Jinzaki, Masahiro Kuribayashi, Sachio de Roos, Albert Laule, Michael Tan, Swee Yaw Hoe, John Paul, Narinder Rybicki, Frank J. Brinker, Jeffery A. Arai, Andrew E. Cox, Christopher Clouse, Melvin E. Di Carli, Marcelo F. Lima, Joao A. C. TI Computed tomography angiography and perfusion to assess coronary artery stenosis causing perfusion defects by single photon emission computed tomography: the CORE320 study SO EUROPEAN HEART JOURNAL LA English DT Article DE Imaging; Atherosclerosis; Ischemia; Perfusion; Multislice computed tomography ID FRACTIONAL FLOW RESERVE; MYOCARDIAL-PERFUSION; CT ANGIOGRAPHY; DIAGNOSTIC PERFORMANCE; MAGNETIC-RESONANCE; NUCLEAR-CARDIOLOGY; AMERICAN-SOCIETY; DISEASE; MULTICENTER; STRESS AB To evaluate the diagnostic power of integrating the results of computed tomography angiography (CTA) and CT myocardial perfusion (CTP) to identify coronary artery disease (CAD) defined as a flow limiting coronary artery stenosis causing a perfusion defect by single photon emission computed tomography (SPECT). We conducted a multicentre study to evaluate the accuracy of integrated CTA-CTP for the identification of patients with flow-limiting CAD defined by a parts per thousand yen50% stenosis by invasive coronary angiography (ICA) with a corresponding perfusion deficit on stress single photon emission computed tomography (SPECT/MPI). Sixteen centres enroled 381 patients who underwent combined CTA-CTP and SPECT/MPI prior to conventional coronary angiography. All four image modalities were analysed in blinded independent core laboratories. The prevalence of obstructive CAD defined by combined ICA-SPECT/MPI and ICA alone was 38 and 59%, respectively. The patient-based diagnostic accuracy defined by the area under the receiver operating characteristic curve (AUC) of integrated CTA-CTP for detecting or excluding flow-limiting CAD was 0.87 [95% confidence interval (CI): 0.84-0.91]. In patients without prior myocardial infarction, the AUC was 0.90 (95% CI: 0.87-0.94) and in patients without prior CAD the AUC for combined CTA-CTP was 0.93 (95% CI: 0.89-0.97). For the combination of a CTA stenosis a parts per thousand yen50% stenosis and a CTP perfusion deficit, the sensitivity, specificity, positive predictive, and negative predicative values (95% CI) were 80% (72-86), 74% (68-80), 65% (58-72), and 86% (80-90), respectively. For flow-limiting disease defined by ICA-SPECT/MPI, the accuracy of CTA was significantly increased by the addition of CTP at both the patient and vessel levels. The combination of CTA and perfusion correctly identifies patients with flow limiting CAD defined as a parts per thousand yen50 stenosis by ICA causing a perfusion defect by SPECT/MPI. C1 [George, Richard T.; Arbab-Zadeh, Armin; Miller, Julie M.; Vavere, Andrea L.; Cerci, Rodrigo J.; Mehra, Vishal C.; Brinker, Jeffery A.; Lima, Joao A. C.] Johns Hopkins Univ Hosp, Div Cardiol, Dept Med, Baltimore, MD 21287 USA. [George, Richard T.; Arbab-Zadeh, Armin; Miller, Julie M.; Vavere, Andrea L.; Cerci, Rodrigo J.; Mehra, Vishal C.; Brinker, Jeffery A.; Lima, Joao A. C.] Sch Med, Baltimore, MD 21287 USA. [Cox, Christopher] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Rybicki, Frank J.; Di Carli, Marcelo F.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rochitte, Carlos E.] Univ Sao Paulo, Sch Med, InCor, Inst Heart, Sao Paulo, Brazil. [Chen, Marcus Y.; Arai, Andrew E.] NHLBI, NIH, Bethesda, MD 20892 USA. [Dewey, Marc] Charite, Berlin, Germany. [Niinuma, Hiroyuki; Yoshioka, Kunihiro] Iwate Med Univ, Morioka, Iwate 020, Japan. [Niinuma, Hiroyuki] St Lukes Int Hosp, Tokyo, Japan. [Kitagawa, Kakuya; Nakamori, Shiro] Mie Univ Hosp, Tsu, Mie, Japan. [Laham, Roger; Clouse, Melvin E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Nomura, Cesar] Albert Einstein Hosp, Sao Paulo, Brazil. [Kofoed, Klaus F.] Univ Copenhagen, DK-1168 Copenhagen, Denmark. [Jinzaki, Masahiro; Kuribayashi, Sachio] Keio Univ, Tokyo, Japan. [de Roos, Albert] Leiden Univ, Med Ctr, Leiden, Netherlands. [Tan, Swee Yaw] Natl Heart Ctr, Singapore, Singapore. [Hoe, John] Mt Elizabeth Hosp, Singapore, Singapore. [Paul, Narinder] Toronto Gen Hosp, Toronto, ON, Canada. RP Lima, JAC (reprint author), Johns Hopkins Univ Hosp, Div Cardiol, Dept Med, 600 N Wolfe St,Blalock 524, Baltimore, MD 21287 USA. EM jlima@jhmi.edu OI Dewey, Marc/0000-0002-4402-2733 FU Toshiba Medical Systems Corporation FX The study sponsor, Toshiba Medical Systems Corporation, was not involved in any stage of the study design, data acquisition, data analysis, or manuscript preparation. NR 33 TC 108 Z9 112 U1 3 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD MAY PY 2014 VL 35 IS 17 BP 1120 EP + DI 10.1093/eurheartj/eht488 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH4EO UT WOS:000336079800009 PM 24255127 ER PT J AU Haring, R Friedrich, N Volzke, H Vasan, RS Felix, SB Dorr, M Schwabedissen, HEMZ Nauck, M Wallaschofski, H AF Haring, Robin Friedrich, Nele Voelzke, Henry Vasan, Ramachandran S. Felix, Stephan B. Doerr, Marcus Schwabedissen, Henriette E. Meyer Zu Nauck, Matthias Wallaschofski, Henri TI Positive association of serum prolactin concentrations with all-cause and cardiovascular mortality SO EUROPEAN HEART JOURNAL LA English DT Article DE Prolactin; Mortality; Cardiovascular disease; Population-based cohort ID N-TERMINAL FRAGMENTS; POSTMENOPAUSAL WOMEN; TESTOSTERONE LEVELS; RISK; DISEASE; GROWTH; POMERANIA; RECEPTOR; HEALTH; HEART AB Aims Increased serum prolactin (PRL) concentrations have been associated with adverse cardiovascular risk profiles, but the relation between PRL and mortality risk is unknown. Methods and results We evaluated 3929 individuals (1946 men and 1983 women) aged 20-81 (mean 50.3 years) from the population-based Study of Health in Pomerania (SHIP). Associations of continuous [per standard deviation (SD) increase] and categorized (sex-specific tertiles) serum PRL concentrations with all-cause and cause-specific mortality were analysed separately for men and women by age- and multivariable-adjusted Cox regression models. During a median follow-up period of 10.1 years (38 231 person-years), 419 deaths (10.7%), 132 cardiovascular deaths (3.4%), and 152 cancer deaths (3.9%) were observed. After multivariable adjustment, we observed a positive association of PRL with all-cause mortality in men and women [hazard ratio (HR) per SD increase: 1.17, 95% confidence interval (CI): 1.07-1.29 and HR: 1.22, 95% CI: 1.03-1.46, respectively]. Similarly, individuals with PRL concentrations in the highest tertile (when compared with lowest PRL tertile) experienced the highest mortality risk (men: HR, 1.75; 95% CI, 1.32-2.32; women: HR, 1.66; 95% CI, 1.08-2.56), with a significant trend across PRL tertiles (P for trend <0.05). Cause-specific mortality analyses yielded similar associations for cardiovascular death in both sexes, but for cancer death only in men. Conclusion This is the first study to report an independent positive association of PRL concentrations with all-cause and cardiovascular mortality. Further studies are required to confirm our findings and to elucidate the potential role of PRL as a useful biomarker of cardiovascular risk and mortality assessment. C1 [Haring, Robin; Friedrich, Nele; Nauck, Matthias; Wallaschofski, Henri] Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17475 Greifswald, Germany. [Voelzke, Henry] Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Felix, Stephan B.; Doerr, Marcus] Univ Med Greifswald, Dept Cardiol, D-17475 Greifswald, Germany. [Schwabedissen, Henriette E. Meyer Zu] Univ Med Greifswald, Inst Pharmacol, D-17475 Greifswald, Germany. RP Haring, R (reprint author), Univ Med Greifswald, Inst Clin Chem & Lab Med, Ferdinand Sauerbruch Str, D-17475 Greifswald, Germany. EM robin.haring@uni-greifswald.de OI Ramachandran, Vasan/0000-0001-7357-5970 FU Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403]; Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg, West Pomerania; Ministry of Cultural Affairs of the Federal State of Mecklenburg-West Pomerania [03IS2061A]; Federal Ministry of Education and Research and the Ministry of Cultural Affairs of the Federal State of Mecklenburg, West Pomerania, Germany; Federal Ministry of Education and Research; German Centre for Cardiovascular Research (GCCR) - Federal Ministry of Education and Research; Ministry of Cultural Affairs of the Federal State of Mecklenburg, West Pomerania, Germany FX Study of Health in Pomerania is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg, West Pomerania. The GANI_ MED consortium is funded by the Federal Ministry of Education and Research and the Ministry of Cultural Affairs of the Federal State of Mecklenburg-West Pomerania (03IS2061A). This study was carried out in collaboration with the German Centre for Cardiovascular Research (GCCR) which is funded by the Federal Ministry of Education and Research and the Ministry of Cultural Affairs of the Federal State of Mecklenburg, West Pomerania, Germany. NR 48 TC 12 Z9 13 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD MAY PY 2014 VL 35 IS 18 BP 1215 EP U55 DI 10.1093/eurheartj/ehs233 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH9RT UT WOS:000336480300015 PM 22843444 ER PT J AU Rosso, AL Hunt, MJO Yang, M Brach, JS Harris, TB Newman, AB Satterfield, S Studenski, SA Yaffe, K Aizenstein, HJ Rosano, C AF Rosso, Andrea L. Hunt, Megan J. Olson Yang, Mei Brach, Jennifer S. Harris, Tamara B. Newman, Anne B. Satterfield, Suzanne Studenski, Stephanie A. Yaffe, Kristine Aizenstein, Howard J. Rosano, Caterina CA Hlth ABC Study TI Higher step length variability indicates lower gray matter integrity of selected regions in older adults SO GAIT & POSTURE LA English DT Article DE Gait disorders; Diffusion tensor imaging; Aging; Brain ID GAIT VARIABILITY; PARKINSONS-DISEASE; MEAN DIFFUSIVITY; WALKING SPEED; WHITE-MATTER; BRAIN; VOLUME; AGE AB Step length variability (SLV) increases with age in those without overt neurologic disease, is higher in neurologic patients, is associated with falls, and predicts dementia. Whether higher SLV in older adults without neurologic disease indicates presence of neurologic abnormalities is unknown. Our objective was to identify whether SLV in older adults without overt disease is associated with findings from multimodal neuroimaging. A well-characterized cohort of 265 adults (79-90 years) was concurrently assessed by gait mat, magnetic resonance imaging with diffusion tensor, and neurological exam. Linear regression models adjusted for gait speed, demographic, health, and functional covariates assessed associations of MRI measures (gray matter volume, white matter hyperintensity volume, mean diffusivity, fractional anisotropy) with SLV. Regional distribution of associations was assessed by sparse partial least squares analyses. Higher SLV (mean: 8.4, SD: 3.3) was significantly associated with older age, slower gait speed, and poorer executive function and also with lower graymatter integrity measured by mean diffusivity (standardized beta = 0.16; p = 0.02). Associations between SLV and gray matter integrity were strongest for the hippocampus and anterior cingulate gyrus (both b = 0.18) as compared to other regions. Associations of SLV with other neuroimaging markers were not significant. Lower integrity of normal-appearing gray matter may underlie higher SLV in older adults. Our results highlighted the hippocampus and anterior cingulate gyrus, regions involved in memory and executive function. These findings support previous research indicating a role for cognitive function in motor control. Higher SLV may indicate focal neuropathology in those without diagnosed neurologic disease. (C) 2014 Elsevier B.V. All rights reserved. C1 [Rosso, Andrea L.; Yang, Mei; Newman, Anne B.; Rosano, Caterina] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Hunt, Megan J. Olson] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Brach, Jennifer S.] Univ Pittsburgh, Dept Phys Therapy, Sch Hlth & Rehabil Sci, Pittsburgh, PA USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Satterfield, Suzanne] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Studenski, Stephanie A.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Aizenstein, Howard J.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. RP Rosso, AL (reprint author), 130 N Bellefield Ave,Suite 400, Pittsburgh, PA 15213 USA. EM alr143@pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Rosso, Andrea/0000-0001-5890-9856; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG-028050, K23-AG-028966, R01-AG-029232, T32-AG-000181]; NINR [R01-NR-012459]; University of Pittsburgh Claude D. Pepper Older Americans Independence Center [P30-AG-024827-07] FX Health ABC was supported by National Institute on Aging (NIA) Contracts (N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, NIA grant R01-AG-028050, and NINR grant R01-NR-012459). This research was supported in part by the Intramural Research Program of the NIA (K23-AG-028966, R01-AG-029232), the University of Pittsburgh Claude D. Pepper Older Americans Independence Center P30-AG-024827-07, and a training grant from the NIA (T32-AG-000181). The study sponsor had no role in the design, analysis, or writing of this manuscript. NR 30 TC 16 Z9 16 U1 1 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 EI 1879-2219 J9 GAIT POSTURE JI Gait Posture PD MAY PY 2014 VL 40 IS 1 BP 225 EP 230 DI 10.1016/j.gaitpost.2014.03.192 PG 6 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA AH8KS UT WOS:000336387300040 PM 24792638 ER PT J AU Mamessier, E Broussais-Guillaumot, F Chetaille, B Bouabdallah, R Xerri, L Jaffe, ES Nadel, B AF Mamessier, Emilie Broussais-Guillaumot, Florence Chetaille, Bruno Bouabdallah, Reda Xerri, Luc Jaffe, Elaine S. Nadel, Bertrand TI Nature and importance of follicular lymphoma precursors SO HAEMATOLOGICA LA English DT Review ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; TUMOR-ASSOCIATED MACROPHAGES; FONDAZIONE ITALIANA LINFOMI; RANDOMIZED CONTROLLED-TRIAL; IN-SITU; GERMINAL-CENTERS; T(14/18) TRANSLOCATION; RITUXIMAB MAINTENANCE; SOMATIC MUTATIONS AB It is now widely recognized that cancer development is a protracted process requiring the stepwise acquisition of multiple oncogenic events. In humans, this process can take decades, if not a lifetime, blurring the notion of `healthy' individuals. Follicular lymphoma exemplifies this multistep pathway of oncogenesis. In recent years, variants of follicular lymphoma have been recognized that appear to represent clonal B-cell expansions at an early stage of follicular lymphoma lymphomagenesis. These include follicular lymphoma in situ, duodenal follicular lymphoma, partial involvement by follicular lymphoma, and in the blood circulating follicular lymphoma-like B cells. Recent genetic studies have identified similarities and differences between the early lesions and overt follicular lymphoma, providing important information for understanding their biological evolution. The data indicate that there is already genomic instability at these early stages, even in instances with a low risk for clinical progression. The overexpression of BCL2 in t( 14; 18)-positive B cells puts them at risk for subsequent genetic aberrations when they re-enter the germinal center and are exposed to the influences of activation-induced cytidine deaminase and somatic hypermutations. The emerging data provide a rationale for clinical management and, in the future, may identify genetic risk factors that warrant early therapeutic intervention. C1 [Mamessier, Emilie; Nadel, Bertrand] INSERM, U631, F-13258 Marseille, France. [Mamessier, Emilie; Nadel, Bertrand] Univ Aix Marseille 2, Ctr Immunol Marseille Luminy, Marseille, France. [Mamessier, Emilie; Broussais-Guillaumot, Florence; Chetaille, Bruno; Bouabdallah, Reda; Xerri, Luc; Nadel, Bertrand] Inst Carnot CALYM, Marseilles Calym Cevi Grp, Lyon, France. [Broussais-Guillaumot, Florence; Bouabdallah, Reda] Inst J Paoli I Calmettes, Serv Oncohematol Adulte, F-13009 Marseille, France. [Chetaille, Bruno; Xerri, Luc] Inst J Paoli I Calmettes, Serv Biopathol, F-13009 Marseille, France. [Jaffe, Elaine S.] NIH, Pathol Lab, Bethesda, MD 20892 USA. RP Mamessier, E (reprint author), INSERM, U631, F-13258 Marseille, France. EM mamessier@ciml.univ-mrs.fr RI Nadel, Bertrand/J-2197-2014; OI Jaffe, Elaine/0000-0003-4632-0301 NR 99 TC 11 Z9 12 U1 1 U2 13 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD MAY PY 2014 VL 99 IS 5 BP 802 EP 810 DI 10.3324/haematol.2013.085548 PG 9 WC Hematology SC Hematology GA AH6RD UT WOS:000336257500007 PM 24790058 ER PT J AU Stringaris, K Sekine, T Khoder, A Alsuliman, A Razzaghi, B Sargeant, R Pavlu, J Brisley, G de Lavallade, H Sarvaria, A Marin, D Mielke, S Apperley, JF Shpall, EJ Barrett, AJ Rezvani, K AF Stringaris, Kate Sekine, Takuya Khoder, Ahmad Alsuliman, Abdullah Razzaghi, Bonnie Sargeant, Ruhena Pavlu, Jiri Brisley, Gill de Lavallade, Hugues Sarvaria, Anushruthi Marin, David Mielke, Stephan Apperley, Jane F. Shpall, Elizabeth J. Barrett, A. John Rezvani, Katayoun TI Leukemia-induced phenotypic and functional defects in natural killer cells predict failure to achieve remission in acute myeloid leukemia SO HAEMATOLOGICA LA English DT Article ID RESTING NK CELLS; ACUTE MYELOGENOUS LEUKEMIA; VIRUS-INFECTED CELLS; CYTOTOXICITY RECEPTORS; INHIBITORY RECEPTORS; LIGAND INCOMPATIBILITY; ACTIVATING RECEPTORS; MHC MOLECULES; MISSING SELF; CLASS-I AB The majority of patients with acute myeloid leukemia will relapse, and older patients often fail to achieve remission with induction chemotherapy. We explored the possibility that leukemic suppression of innate immunity might contribute to treatment failure. Natural killer cell phenotype and function was measured in 32 consecutive acute myeloid leukemia patients at presentation, including 12 achieving complete remission. Compared to 15 healthy age-matched controls, natural killer cells from acute myeloid leukemia patients were abnormal at presentation, with downregulation of the activating receptor NKp46 (P=0.007) and upregulation of the inhibitory receptor NKG2A (P=0.04). Natural killer cells from acute myeloid leukemia patients had impaired effector function against autologous blasts and K562 targets, with significantly reduced CD107a degranulation, TNF-alpha and IFN-gamma production. Failure to achieve remission was associated with NKG2A overexpression and reduced TNF-alpha production. These phenotypic and functional abnormalities were partially restored in the 12 patients achieving remission. In vitro co-incubation of acute myeloid leukemia blasts with natural killer cells from healthy donors induced significant impairment in natural killer cell TNF-alpha and IFN-gamma production (P=0.02 and P=0.01, respectively) against K562 targets and a trend to reduced CD107a degranulation (P=0.07). Under transwell conditions, the inhibitory effect of AML blasts on NK cytotoxicity and effector function was still present, and this inhibitory effect was primarily mediated by IL-10. These results suggest that acute myeloid leukemia blasts induce long-lasting changes in natural killer cells, impairing their effector function and reducing the competence of the innate immune system, favoring leukemia survival. C1 [Stringaris, Kate; Sekine, Takuya; Khoder, Ahmad; Alsuliman, Abdullah; Razzaghi, Bonnie; Sargeant, Ruhena; Pavlu, Jiri; Brisley, Gill; de Lavallade, Hugues; Marin, David; Apperley, Jane F.] Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London SW7 2AZ, England. [Sekine, Takuya; Sarvaria, Anushruthi; Shpall, Elizabeth J.; Barrett, A. John; Rezvani, Katayoun] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Mielke, Stephan] Univ Wurzburg, Wurzburg, Germany. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Rezvani, K (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM krezvani@mdanderson.org FU MD Anderson Cancer Center Leukemia SPORE Grant [CA100632]; Leuka registered charity [286231]; British Society for Haematology start-up grant FX This research is supported in part by the MD Anderson Cancer Center Leukemia SPORE Grant CA100632, Leuka registered charity (286231) and a British Society for Haematology start-up grant. The sponsors of this study are public or non-profit organizations that support science in general. They had no role in gathering, analyzing, or interpreting the data. NR 50 TC 28 Z9 28 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD MAY PY 2014 VL 99 IS 5 BP 836 EP 847 DI 10.3324/haematol.2013.087536 PG 12 WC Hematology SC Hematology GA AH6RD UT WOS:000336257500011 PM 24488563 ER PT J AU Morton, LM Gibson, TM Clarke, CA Lynch, CF Weisenburger, DD Engels, EA AF Morton, Lindsay M. Gibson, Todd M. Clarke, Christina A. Lynch, Charles F. Weisenburger, Dennis D. Engels, Eric A. TI Hepatitis B or C virus infection and risk of non-Hodgkin lymphoma among solid organ transplant recipients SO HAEMATOLOGICA LA English DT Letter DE HCV; HBV; NHL after solid organ transplantation ID LYMPHOPROLIFERATIVE DISORDERS; LIVER-TRANSPLANTATION; COHORT; CELL C1 [Morton, Lindsay M.; Gibson, Todd M.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Clarke, Christina A.] Canc Prevent Inst Calif, Fremont, CA USA. [Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Weisenburger, Dennis D.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA. RP Morton, LM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. EM mortonli@mail.nih.gov RI Morton, Lindsay/B-5234-2015 OI Morton, Lindsay/0000-0001-9767-2310 FU Intramural NIH HHS; NCCDPHP CDC HHS [U58 DP000824, 1U58 DP000807-01, 5658DP000805-04, 5U58/DP000808-05, 5U58DP000812-03, 5U58DP000817-05, 5U58DP000824-04, U58 DP000805, U58 DP000807, U58 DP000808, U58 DP000812, U58 DP000817, U58 DP000832, U58 DP000848, U58 DP000848-04, U58DP000832, U58DP0038789]; NCI NIH HHS [HHSN261201000024C, HHSN261201000026C, HHSN261201000027C, HHSN261201000034C, HHSN261201000035I, HHSN261201000036C, HHSN261201000037C, N01PC35137, N01PC35139, N01PC35142, N01PC35143, N01PC54405, P30 CA086862]; None [HHSN261201000035C] NR 15 TC 4 Z9 4 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD MAY PY 2014 VL 99 IS 5 BP E70 EP E73 DI 10.3324/haematol.2013.101600 PG 4 WC Hematology SC Hematology GA AH6RD UT WOS:000336257500003 PM 24561790 ER PT J AU Hooker, GW Peay, H Erby, L Bayless, T Biesecker, BB Roter, DL AF Hooker, Gillian W. Peay, Holly Erby, Lori Bayless, Theodore Biesecker, Barbara B. Roter, Debra L. TI Genetic Literacy and Patient Perceptions of IBD Testing Utility and Disease Control: A Randomized Vignette Study of Genetic Testing SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE genetic testing; genetic literacy; IBD ID INFLAMMATORY-BOWEL-DISEASE; NUMERACY; NUMBER; LOCI AB Background: Findings from inflammatory bowel disease (IBD) genome-wide association studies are being translated clinically into prognostic and diagnostic indicators of disease. Yet, patient perception and understanding of these tests and their applicability to providing risk information is unclear. The goal of this study was to determine, using hypothetical scenarios, whether patients with IBD perceive genetic testing to be useful for risk assessment, whether genetic test results impact perceived control, and whether low genetic literacy may be a barrier to patient understanding of these tests. Methods: Two hundred fifty seven patients with IBD from the Johns Hopkins gastroenterology clinics were randomized to receive a vignette depicting either a genetic testing scenario or a standard blood testing scenario. Participants were asked questions about the vignette and responses were compared between groups. Results: Perceptions of test utility for risk assessment were higher among participants responding to the genetic vignette (P < 0.001). There were no significant differences in perceptions of control over IBD after hypothetical testing between vignettes (P = 0.24). Participant responses were modified by genetic literacy, measured using a scale developed for this study. Participants randomized to the genetic vignette who scored higher on the genetic literacy scale perceived greater utility of testing for risk assessment (P = 0.008) and more control after testing (P = 0.02). Conclusions: Patients with IBD perceive utility in genetic testing for providing information relevant to family members, and this appreciation is promoted by genetic literacy. Low genetic literacy among patients poses a potential threat to effective translation of genetic and genomic tests. C1 [Hooker, Gillian W.; Peay, Holly; Biesecker, Barbara B.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Erby, Lori; Roter, Debra L.] Johns Hopkins Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD 21205 USA. [Erby, Lori; Roter, Debra L.] Johns Hopkins Sch Publ Hlth, Ctr Genom Literacy & Commun, Baltimore, MD 21205 USA. [Bayless, Theodore] Johns Hopkins Univ, Sch Med, Dept Med, Harvey M & Lyn P Meyerhoff Inflammatory Bowel Dis, Baltimore, MD 21205 USA. RP Roter, DL (reprint author), Johns Hopkins Sch Publ Hlth, Dept Hlth Behav & Soc, 624N Broadway, Baltimore, MD 21205 USA. EM droter@jhsph.edu RI Roter, Debra/N-8830-2014 FU Intramural Research program of the National Human Genome Research Institute, National Institutes of Health FX This research was supported by the Intramural Research program of the National Human Genome Research Institute, National Institutes of Health. The authors thank Dr. Steven Brant and Dr. Susan Hutfless for their comments on the manuscript and Cris Price of Abt Associates for data analysis support. NR 23 TC 5 Z9 5 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2014 VL 20 IS 5 BP 901 EP 908 DI 10.1097/MIB.0000000000000021 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AH0CU UT WOS:000335787500015 PM 24691112 ER PT J AU Chong, WP Horai, R Mattapallil, MJ Silver, PB Chen, J Zhou, R Sergeev, Y Villasmil, R Chan, CC Caspi, RR AF Chong, Wai Po Horai, Reiko Mattapallil, Mary J. Silver, Phyllis B. Chen, Jun Zhou, Ru Sergeev, Yuri Villasmil, Rafael Chan, Chi-Chao Caspi, Rachel R. TI IL-27p28 inhibits central nervous system autoimmunity by concurrently antagonizing Th1 and Th17 responses SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Autoimmunity; gp130; IL-27p28 ID CD4(+) T-CELLS; CYTOKINE GM-CSF; T(H)17 CELLS; INTERFERON-GAMMA; TERMINAL DIFFERENTIATION; EFFECTOR RESPONSE; HELPER-CELLS; UVEITIS; ENCEPHALOMYELITIS; RECEPTOR AB Central nervous system (CNS) autoimmunity such as uveitis and multiple sclerosis is accompanied by Th1 and Th17 responses. In their corresponding animal models, experimental autoimmune uveitis (EAU) and experimental autoimmune encephalomyelitis (EAE), both responses are induced and can drive disease independently. Because immune responses have inherent plasticity, therapeutic targeting of only one pathway could promote the other, without reducing pathology. IL-27p28 antagonizes gp130, required for signaling by IL-27 and IL-6, which respectively promote Th1 and Th17 responses. We therefore examined its ability to protect the CNS by concurrently targeting both effector responses. Overexpression of IL-27p28 in vivo ameliorated EAU as well as EAE pathology and reduced tissue infiltration by Th1 and Th17 cells in a disease prevention, as well as in a disease reversal protocol. Mechanistic studies revealed inhibition of Th1 and Th17 commitment in vitro and decreased lineage stability of pre-formed effectors in vivo, with reduction in expression of gp 130-dependent transcription factors and cytokines. Importantly, IL-27p28 inhibited polarization of human T cells to the Th1 and Th17 effector pathways. The ability of IL-27p28 to inhibit generation as well as function of pathogenic Th1 and Th17 effector cells has therapeutic implications for controlling immunologically complex autoimmune diseases. Published by Elsevier Ltd. C1 [Chong, Wai Po; Horai, Reiko; Mattapallil, Mary J.; Silver, Phyllis B.; Chen, Jun; Zhou, Ru; Chan, Chi-Chao; Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Sergeev, Yuri] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [Villasmil, Rafael] NEI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N222,10 Ctr Dr, Bethesda, MD 20892 USA. EM caspir@nei.nih.gov OI Caspi, Rachel/0000-0002-7140-7671 FU NIH/NEI Intramural funding [EY000184-29] FX The authors thank the NEI the Flow Cytometry Core and Histology facilities. We thank Dr. Wei Lai for technical advice on human T cell polarization. We thank Olivia Schneider of Shenandoah Biotechnology for the IL-27p28 plasmid. We are grateful to Dr. Christopher Hunter (University of Pennsylvania) for supplying to us the ZymoGenetics p28 TG mice. The study was supported by NIH/ NEI Intramural funding, project # EY000184-29. NR 59 TC 16 Z9 18 U1 0 U2 9 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 EI 1095-9157 J9 J AUTOIMMUN JI J. Autoimmun. PD MAY PY 2014 VL 50 BP 12 EP 22 DI 10.1016/j.jaut.2013.08.003 PG 11 WC Immunology SC Immunology GA AH4RB UT WOS:000336114600002 PM 24021664 ER PT J AU Li, B Cui, WP Tan, Y Luo, P Chen, Q Zhang, C Qu, W Miao, LN Cai, L AF Li, Bing Cui, Wenpeng Tan, Yi Luo, Ping Chen, Qiang Zhang, Chi Qu, Wei Miao, Lining Cai, Lu TI Zinc is essential for the transcription function of Nrf2 in human renal tubule cells in vitro and mouse kidney in vivo under the diabetic condition SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE Akt phosphorylation; diabetic nephropathy; Fyn; Nrf2; TPEN; zinc chelation ID OXIDATIVE STRESS; NF-E2-RELATED FACTOR-2; ENDOTHELIAL-CELLS; MELLITUS PATIENTS; PROTECTIVE ROLE; SUPPLEMENTATION; DEFICIENCY; RATS; NEPHROPATHY; METALLOTHIONEIN AB Increasing evidence from human and laboratory studies showed the effect of zinc (Zn) on diabetic complications. Nuclear factor-erythroid 2-related factor 2 (Nrf2) plays important role in the prevention of oxidative damage. This study was to define whether Zn statues (deficiency or supplement) affect the Nrf2 expression and function, and also affect the damage severity of human renal tubular (HK11) cells exposed to high glucose (HG) with palmitate (Pal) and kidney of diabetic mice induced by multiple low-dose streptozotocins. For Zn deficiency diabetic mice were treated with Zn chelator PTEN at 5mg/kg bw daily for 4months. Results showed that HG/Pal significantly increased the expression of pro-fibrotic mediators, connective tissue growth factor and PAI-1, in HK11 cells, which was exacerbated by TPEN that depleted intracellular free Zn and decreased Nrf2 expression and transcription. Zn supplement prevented the effects of TPEN and also increased Akt and GSK-3 phosphorylation with a decrease in Nrf2 nuclear exporter, Fyn. All these effects of Zn were abolished by Akt inhibitor. Therefore, Zn up-regulates Nrf2 function via activating Akt-mediated inhibition of Fyn function. Treatment of diabetic mice with TPEN decreased renal Zn level and Nrf2 expression and transcription, with an exacerbation of renal oxidative damage, inflammation and fibrosis. These results suggest the essentiality of Zn for Nrf2 expression and transcription function. C1 [Li, Bing; Cui, Wenpeng; Luo, Ping; Miao, Lining] Jilin Univ, Hosp 2, Dept Nephrol, Changchun 130041, Peoples R China. [Li, Bing; Cui, Wenpeng; Tan, Yi; Chen, Qiang; Zhang, Chi; Cai, Lu] Univ Louisville, Kosair Childrens Hosp Res Inst, Louisville, KY 40292 USA. [Li, Bing; Cui, Wenpeng; Tan, Yi; Chen, Qiang; Zhang, Chi; Cai, Lu] Univ Louisville, Dept Pediat, Louisville, KY 40292 USA. [Li, Bing; Cui, Wenpeng; Tan, Yi; Chen, Qiang; Zhang, Chi; Cai, Lu] Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. [Li, Bing] Jilin Prov Peoples Hosp, Dept Nephrol, Changchun, Peoples R China. [Tan, Yi; Zhang, Chi; Cai, Lu] Wenzhou Med Univ, Chinese Amer Res Inst Diabet Complicat, Wenzhou, Peoples R China. [Qu, Wei] NIEHS, Inorgan Toxicol Grp, Natl Toxicol Program Lab, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Cai, Lu] Univ Louisville, Dept Radiat Oncol, Louisville, KY 40292 USA. RP Miao, LN (reprint author), Jilin Univ, Hosp 2, 218 Ziqiang St, Changchun 130041, Peoples R China. EM mlnkidney@163.com; L0cai001@louisville.edu FU American Diabetes Association [1-13-JF-53]; Science and Technology Activities Start-Up Project of Returned Overseas Chinese Talents; Natural Science Foundation of China [81273509, 81200525]; Key Science and Technology Development Plan from Wenzhou City [Y20100001]; National Natural Science Foundation of China [81170669]; Director Funds of the National Natural Science Foundation of China [81241023]; China Scholarship Council FX We thank Dr. Rane J Madhavi, Department of Medicine at the University of Louisville, School of Medicine, for her providing HK11 cells to us as gift. We are grateful to Dr. Nicholas Mellen, Department of Pediatrics at the University of Louisville, and Drs. Katie Pelch and Yuanyuan Xu, National Toxicology Program Laboratory, Division at the National Toxicology Program, NIEHS, for their critical review of this manuscript. This study was supported in part by Junior Faculty Award from American Diabetes Association (1-13-JF-53, to YT), Science and Technology Activities Start-Up Project of Returned Overseas Chinese Talents in 2012 (to BL), Natural Science Foundation of China (81273509, to YT; 81200525, to WC), Key Science and Technology Development Plan from Wenzhou City (Y20100001, to YT), the National Natural Science Foundation of China (81170669, to LM), and the Director Funds of the National Natural Science Foundation of China (81241023, to PL). B. Li was a recipient of Scholarship under State Scholarship Fund from China Scholarship Council. NR 53 TC 21 Z9 21 U1 2 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1582-4934 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD MAY PY 2014 VL 18 IS 5 BP 895 EP 906 DI 10.1111/jcmm.12239 PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AH1EB UT WOS:000335861500015 PM 24597671 ER PT J AU Portnoy, DB Leach, CR Kaufman, AR Moser, RP Alfano, CM AF Portnoy, David B. Leach, Corinne R. Kaufman, Annette R. Moser, Richard P. Alfano, Catherine M. TI Reduced Fatalism and Increased Prevention Behavior After Two High-Profile Lung Cancer Events SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID NATIONAL TRENDS SURVEY; BREAST-CANCER; INFORMATION-SEEKING; HEALTH INFORMATION; NEWS COVERAGE; AFRICAN-AMERICAN; IMPACT; RISK; BELIEFS; WOMEN AB The positive impact of media coverage of high-profile cancer events on cancer prevention behaviors is well-established. However, less work has focused on potential adverse psychological reactions to such events, such as fatalism. Conducting 3 studies, the authors explored how the lung cancer death of Peter Jennings and diagnosis of Dana Reeve in 2005 related to fatalism. Analysis of a national media sample in Study 1 found that media coverage of these events often focused on reiterating the typical profile of those diagnosed with lung cancer; 38% of the media mentioned at least 1 known risk factor for lung cancer, most often smoking. Data from a nationally representative survey in Study 2 found that respondents reported lower lung cancer fatalism, after, compared with before, the events (OR=0.16, 95% CI [0.03, 0.93]). A sustained increase in call volume to the national tobacco Quitline after these events was found in Study 3. These results suggest that there is a temporal association between high-profile cancer events, the subsequent media coverage, psychological outcomes, and cancer prevention behaviors. These results suggest that high-profile cancer events could be leveraged as an opportunity for large-scale public heath communication campaigns through the dissemination of cancer prevention messages and services. C1 [Portnoy, David B.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, Rockville, MD USA. [Portnoy, David B.; Kaufman, Annette R.; Moser, Richard P.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD USA. [Leach, Corinne R.] Amer Canc Soc, Behav Res Ctr, Atlanta, GA 30329 USA. [Alfano, Catherine M.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Rockville, MD USA. RP Portnoy, DB (reprint author), US FDA, Ctr Tobacco Prod, 9200 Corp Blvd,CORP 330H, Rockville, MD 20850 USA. EM david.portnoy@fda.hhs.gov OI Portnoy, David/0000-0003-2175-9457 FU Intramural NIH HHS [Z99 CA999999] NR 42 TC 0 Z9 0 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 520 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1081-0730 EI 1087-0415 J9 J HEALTH COMMUN JI J. Health Commun. PD MAY 1 PY 2014 VL 19 IS 5 BP 577 EP 592 DI 10.1080/10810730.2013.821553 PG 16 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA AH1EC UT WOS:000335861600005 PM 24274730 ER PT J AU Salomon, DG Fermento, ME Gandini, NA Ferronato, MJ Arevalo, J Blasco, J Andres, NC Zenklusen, JC Curino, AC Facchinetti, MM AF Salomon, Debora G. Fermento, Maria E. Gandini, Norberto A. Ferronato, Maria J. Arevalo, Julian Blasco, Jorge Andres, Nancy C. Zenklusen, Jean C. Curino, Alejandro C. Facchinetti, Maria M. TI Vitamin D receptor expression is associated with improved overall survival in human glioblastoma multiforme SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Vitamin D receptor; Human GBM; Tissue microarray; Biomarker; Survival; Prognosis ID GLIOMA-CELL LINE; PROGNOSTIC-FACTOR; BREAST-CANCER; BRAIN-TUMORS; ASTROCYTIC GLIOMAS; GENE-EXPRESSION; VDR EXPRESSION; CALCITRIOL; INDUCTION; CARCINOMA AB Vitamin D and its analogs have been shown to display anti-proliferative effects in a wide variety of cancer types including glioblastoma multiforme (GBM). These anticancer effects are mediated by its active metabolite, 1 alpha, 25-dihydroxyvitamin D-3 (calcitriol) acting mainly through vitamin D receptor (VDR) signaling. In addition to its involvement in calcitriol action, VDR has also been demonstrated to be useful as a prognostic factor for some types of cancer. However, to our knowledge, there are no studies evaluating the expression of VDR protein and its association with outcome in gliomas. Therefore, we investigated VDR expression by using immunohistochemical analysis in human glioma tissue microarrays, and analyzed the association between VDR expression and clinico-pathological parameters. We further investigated the effects of genetic and pharmacologic modulation of VDR on survival and migration of glioma cell lines. Our data demonstrate that VDR is increased in tumor tissues when compared with VDR in non-malignant brains, and that VDR expression is associated with an improved outcome in patients with GBM. We also show that both genetic and pharmacologic modulation of VDR modulates GBM cellular migration and survival and that VDR is necessary for calcitriol-mediated effects on migration. Altogether these results provide some limited evidence supporting a role for VDR in glioma progression. C1 [Salomon, Debora G.; Fermento, Maria E.; Gandini, Norberto A.; Ferronato, Maria J.; Andres, Nancy C.; Curino, Alejandro C.; Facchinetti, Maria M.] Inst Invest Bioquim Bahia Blanca INIBIBB CONICET, Ctr Cient Tecnol Bahia Blanca, Lab Biol Canc, RA-8000 Bahia Blanca, Buenos Aires, Argentina. [Arevalo, Julian; Blasco, Jorge] Hosp Interzonal Gen Agudos Dr Jose Penna, Serv Patol, Bahia Blanca, Buenos Aires, Argentina. [Zenklusen, Jean C.] NCI, Off Canc Genom, NIH, Bethesda, MD 20892 USA. RP Facchinetti, MM (reprint author), Inst Invest Bioquim Bahia Blanca INIBIBB CONICET, Ctr Cient Tecnol Bahia Blanca, Lab Biol Canc, Camino La Carrindanga Km 7 C-C 857, RA-8000 Bahia Blanca, Buenos Aires, Argentina. EM facchinm@criba.edu.ar OI Andres, Nancy Carolina/0000-0002-6756-8878 FU National Council of Scientific and Technical Research (CONICET); National Agency for the Promotion of Science and Technology (ANPCyT); Technical Secretary of the Universidad Nacional del Sur FX This work was supported by grants from National Council of Scientific and Technical Research (CONICET), National Agency for the Promotion of Science and Technology (ANPCyT) and from the Technical Secretary of the Universidad Nacional del Sur. D. Salomon is a recipient of fellowship from Conicet. NR 58 TC 4 Z9 4 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2014 VL 118 IS 1 BP 49 EP 60 DI 10.1007/s11060-014-1416-3 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AH8HC UT WOS:000336376700006 PM 24584679 ER PT J AU Dowling, MM Noetzel, MJ Rodeghier, MJ Quinn, CT Hirtz, DG Ichord, RN Kwiatkowski, JL Roach, ES Kirkham, FJ Casella, JF DeBaun, MR AF Dowling, Michael M. Noetzel, Michael J. Rodeghier, Mark J. Quinn, Charles T. Hirtz, Deborah G. Ichord, Rebecca N. Kwiatkowski, Janet L. Roach, E. Steven Kirkham, Fenella J. Casella, James F. DeBaun, Michael R. TI Headache and Migraine in Children with Sickle Cell Disease Are Associated with Lower Hemoglobin and Higher Pain Event Rates But Not Silent Cerebral Infarction SO JOURNAL OF PEDIATRICS LA English DT Article ID BRAIN INFARCTS; ANEMIA; ADOLESCENTS; ABNORMALITIES; CRITERIA; PREVALENCE; MANAGEMENT; DISORDERS; DIAGNOSIS; OVERUSE AB Objective To identify risk factors for headache and migraine in children with sickle cell disease and test the hypothesis that either or both are independently associated with silent cerebral infarcts. Study design In this cross-sectional study, we evaluated the health history, laboratory values, and brain magnetic resonance imaging findings of participants with sickle cell disease (hemoglobinSS or hemoglobinS beta degrees-thalassemia) with no history of overt stroke or seizures. Participants characterized headache severity and quality. Migraine was defined by International Headache Society criteria modified for increased sensitivity in children. Neuroradiology and neurology committees adjudicated the presence of silent cerebral infarction by review of magnetic resonance imaging and standardized examination by pediatric neurologists. Results The cohort included 872 children (51.1% males), ranging in age from 5 to 15 years (mean age, 9.1 years). Of these children, 317 (36.4%) reported recurrent headaches, and 132 (15.1%) reported migraines. In multivariable logistic regression analyses, both were associated with lower steady-state hemoglobin (P = .01 for headaches; P < .01 for migraines) and higher pain rate (P < .01 for headaches; P < .01 for migraines), defined as the number of admissions requiring opioids in the previous 3 years. The presence of silent cerebral infarction was not associated with recurrent headaches or migraines. Only 1.9% (6 of 317) of children with recurrent headaches received medication for headache prophylaxis. Conclusion Recurrent headaches and migraines are common and un-dertreated in children with sickle cell disease. Low hemoglobin levels and high pain rates are associated with recurrent headaches and migraines; whereas, silent cerebral infarction is not. C1 [Dowling, Michael M.] Univ Texas SW Med Ctr Dallas, Dept Pediat & Neurol & Neurotherapeut, Dallas, TX 75390 USA. [Noetzel, Michael J.] St Louis Childrens Hosp, Div Pediat & Dev Neurol, Dept Neurol, St Louis, MO 63178 USA. [Noetzel, Michael J.] Washington Univ, Sch Med, St Louis, MO USA. [Rodeghier, Mark J.] Rodeghier Consultants, Chicago, IL USA. [Quinn, Charles T.] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Div Hematol, Cincinnati, OH 45229 USA. [Hirtz, Deborah G.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. [Ichord, Rebecca N.; Kwiatkowski, Janet L.] Univ Penn, Childrens Hosp Philadelphia, Dept Neurol & Pediat, Philadelphia, PA 19104 USA. [Ichord, Rebecca N.; Kwiatkowski, Janet L.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Roach, E. Steven] Ohio State Coll Med, Div Child Neurol, Columbus, OH USA. [Kirkham, Fenella J.] UCL, Inst Child Hlth, Inst Neurosci, London, England. [Casella, James F.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Pediat Hematol, Baltimore, MD 21205 USA. [DeBaun, Michael R.] Vanderbilt Univ, Sch Med, Vanderbilt Meharry Matthew Walker Ctr Excellence, Dept Pediat, Nashville, TN 37232 USA. RP DeBaun, MR (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Meharry Matthew Walker Ctr Excellence, 2200 Childrens Way,Room 11206 DOT, Nashville, TN 37232 USA. EM m.debaun@vanderbilt.edu RI Quinn, Charles/J-6842-2012; Kirkham, Fenella/C-2442-2009 OI Quinn, Charles/0000-0002-2372-2175; Kirkham, Fenella/0000-0002-2443-7958 FU National Institutes of Health [U01-NS042804]; North and Central Texas Clinical and Translational Science Initiative from the NIH [KL2 RR024983]; Doris Duke Charitable Foundation; First American Real Estate Information Services, Inc.; Johns Hopkins FX Supported by the National Institutes of Health (U01-NS042804). M. D. and C. Q. were supported by the North and Central Texas Clinical and Translational Science Initiative from the NIH (KL2 RR024983), and M. D. is supported by the Doris Duke Charitable Foundation and First American Real Estate Information Services, Inc. J.C. has received an honorarium and travel expenses in the past and presently receives salary support through Johns Hopkins for providing consultative advice to Adventrx Pharmaceuticals regarding a proposed clinical trial of an agent for treating vaso-occlusive crisis in sickle cell disease, and is an inventor and a named party on a patent and licensing agreement to ImmunArray for a panel of brain biomarkers for the detection of brain injury. Neither company had input into the design, analysis, interpretation, or content of this study and did not influence the decision to submit this manuscript. The contents of this article represent the personal opinion of the authors and should not be construed as the opinion or position of the National Institutes of Health or its affiliates. The other authors declare no conflicts of interest. NR 40 TC 8 Z9 8 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAY PY 2014 VL 164 IS 5 BP 1175 EP + DI 10.1016/j.jpeds.2014.01.001 PG 7 WC Pediatrics SC Pediatrics GA AG6GB UT WOS:000335516000046 PM 24529619 ER PT J AU Lansford, JE Deater-Deckard, K Bornstein, MH Putnick, DL Bradley, RH AF Lansford, Jennifer E. Deater-Deckard, Kirby Bornstein, Marc H. Putnick, Diane L. Bradley, Robert H. TI Attitudes Justifying Domestic Violence Predict Endorsement of Corporal Punishment and Physical and Psychological Aggression towards Children: A Study in 25 Low- and Middle-Income Countries SO JOURNAL OF PEDIATRICS LA English DT Article ID PARENTS AB Objective The Convention on the Rights of the Child has prompted countries to protect children from abuse and exploitation. Exposure to domestic violence and corporal punishment are risk factors in children's development. This study investigated how women's attitudes about domestic violence are related to attitudes about corporal punishment and harsh behaviors toward children, and whether country-wide norms regarding domestic violence and corporal punishment are related to psychological aggression and physical violence toward children. Study design Data were drawn from the Multiple Indicator Cluster Survey, a nationally representative and internationally comparable household survey developed by the United Nations Children's Fund. Measures of domestic violence and discipline were completed by 85 999 female caregivers of children between the ages of 2 and 14 years from families in 25 low-and middle-income countries. Results Mothers who believed that husbands were justified in hitting their wives were more likely to believe that corporal punishment is necessary to rear children. Mothers who believed that husbands were justified in hitting their wives and that corporal punishment is necessary to rear children were more likely to report that their child had experienced psychological aggression and physical violence. Countrywide norms regarding the acceptability of husbands hitting wives and advisability of corporal punishment moderated the links between mothers' attitudes and their behaviors toward children. Conclusions Pediatricians can address parents' psychological aggression and physical violence toward children by discussing parents' attitudes and behaviors within a framework that incorporates social norms regarding the acceptability of domestic violence and corporal punishment. C1 [Lansford, Jennifer E.] Duke Univ, Ctr Child & Family Policy, Durham, NC 27708 USA. [Deater-Deckard, Kirby] Virginia Tech Univ, Dept Psychol, Blacksburg, VA USA. [Bornstein, Marc H.; Putnick, Diane L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Bradley, Robert H.] Arizona State Univ, Dept Psychol, Sch Social & Family Dynam, Tempe, AZ 85287 USA. RP Lansford, JE (reprint author), Duke Univ, Ctr Child & Family Policy, Box 90545, Durham, NC 27708 USA. EM lansford@duke.edu OI Putnick, Diane/0000-0002-6323-749X FU NICHD NIH HHS [R01 HD054805] NR 16 TC 7 Z9 7 U1 0 U2 14 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAY PY 2014 VL 164 IS 5 BP 1208 EP 1213 DI 10.1016/j.jpeds.2013.11.060 PG 6 WC Pediatrics SC Pediatrics GA AG6GB UT WOS:000335516000051 PM 24412139 ER PT J AU Maltsev, VA Yaniv, Y Maltsev, AV Stern, MD Lakatta, EG AF Maltsev, Victor A. Yaniv, Yael Maltsev, Anna V. Stern, Michael D. Lakatta, Edward G. TI Modern Perspectives on Numerical Modeling of Cardiac Pacemaker Cell SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Review DE cardiac pacemaker; sinoatrial node cell; numerical modeling; calcium; ion channel ID RABBIT SINOATRIAL NODE; HODGKIN-HUXLEY EQUATIONS; SUSTAINED INWARD CURRENT; SPONTANEOUS BEATING RATE; RHYTHMIC CA2+ CLOCK; SUPPLY-AND-DEMAND; CURRENT I-F; SARCOPLASMIC-RETICULUM; MATHEMATICAL-MODEL; INTRACELLULAR CALCIUM AB Cardiac pacemaking is a complex phenomenon that is still not completely understood. Together with experimental studies, numerical modeling has been traditionally used to acquire mechanistic insights in this research area. This review summarizes the present state of numerical modeling of the cardiac pacemaker, including approaches to resolve present paradoxes and controversies. Specifically we discuss the requirement for realistic modeling to consider symmetrical importance of both intracellular and cell membrane processes (within a recent "coupled-clock" theory). Promising future developments of the complex pacemaker system models include the introduction of local calcium control, mitochondria function, and biochemical regulation of protein phosphorylation and cAMP production. Modern numerical and theoretical methods such as multi-parameter sensitivity analyses within extended populations of models and bifurcation analyses are also important for the definition of the most realistic parameters that describe a robust, yet simultaneously flexible operation of the coupled-clock pacemaker cell system. The systems approach to exploring cardiac pacemaker function will guide development of new therapies such as biological pacemakers for treating insufficient cardiac pacemaker function that becomes especially prevalent with advancing age. C1 [Maltsev, Victor A.; Yaniv, Yael; Stern, Michael D.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Maltsev, Anna V.] Univ Bristol, Dept Math, Bristol BS8 1TW, Avon, England. RP Maltsev, VA (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM MaltsevVi@mail.nih.gov RI Yaniv, Yael/B-3311-2015 OI Yaniv, Yael/0000-0002-5183-6284 FU Intramural Research Program of the National Institutes of Health, National Institute on Aging FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 140 TC 7 Z9 7 U1 0 U2 16 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 EI 1347-8648 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PD MAY PY 2014 VL 125 IS 1 BP 6 EP 38 DI 10.1254/jphs.13R04CR PG 33 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AI0RH UT WOS:000336556600002 PM 24748434 ER PT J AU Levy, G Hill, M Beall, S Pilgrim, JD Payson, M Propst, A AF Levy, Gary Hill, Micah Beall, Stephanie Pilgrim, Justin D. Payson, Mark Propst, Anthony TI Falling Estradiol Levels on Day After Human Chorionic Gonadotropin Administration in Assisted Reproductive Technology Cycles Are Not Predictive of Decreasing Oocyte Maturity or Pregnancy Rates SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE assisted reproductive technologies; estradiol; oocyte maturity; ovarian stimulation ID IN-VITRO FERTILIZATION; OVARIAN HYPERSTIMULATION SYNDROME; TRANSFER IVF-ET; EMBRYO-TRANSFER; HCG INJECTION; STIMULATION; ASSOCIATION; PATTERN AB OBJECTIVE: To determine whether a fall in serum estradiol levels the day after human chorionic gonadotropin (hCG) administration correlated with the incidence of a positive serum hCG in fresh, nondonor assisted reproductive technology (ART) cycles. STUDY DESIGN: A total of 1,969 women undergoing fresh, nondonor ART cycles at a tertiary referral fertility clinic between January 1, 2003, and January 31, 2010, were included and spectively analyzed. Primary outcome measures were oocyte maturity and positive serum beta-hCG. RESULTS: A total of 1,969 cycles met inclusion criteria, of which 1,875 had the same or increasing serum estradiol levels and 94 had decreasing estradiol levels on the morning after hCG trigger administration (6-11 hours after hCG injection). There were no statistically significant differences between the groups with respect to age, baseline FSH levels, type of pituitary downregulation, total ampules of gonadotropin administered, days of stimulation,, average number of oocytes retrieved, or oocyte maturity. Probability of pregnancy in women with declining E2 lavels after hCG trigger administration did not differ from patients with the same or rising estradiol levels (53% vs. 54%, p = 0.89). CONCLUSION: Absolute change in estradiol levels the morning after beta-hCG administration were not predictive of positive hCG. C1 Walter Reed Natl Mil Med Ctr, Dept Reprod Endocrinol & Infertil, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. Natl Inst Child Hlth & Human Dev, Program Reprod & Adult Endocrinol, Bethesda, MD 20889 USA. Bayne Jones Army Community Hosp, Ft Polk, LA USA. RP Levy, G (reprint author), Natl Inst Child Hlth & Human Dev, Program Adult & Reprod Endocrinol, Dept Reprod Endocrinol & Infertil, Combined Dept Obstet & Gynecol,Walter Reed Natl M, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM garylevy1@gmail.com FU Intramural NIH research Program in Reproductive and Adult Endocrinology FX This research is supported in part by the Intramural NIH research Program in Reproductive and Adult Endocrinology. NR 14 TC 1 Z9 1 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 EI 1943-3565 J9 J REPROD MED JI J. Reprod. Med. PD MAY-JUN PY 2014 VL 59 IS 5-6 BP 255 EP 259 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH8WS UT WOS:000336419500014 PM 24937966 ER PT J AU Xu, MJ Feng, DC Wang, H Guan, YF Yan, XQ Gao, B AF Xu, Ming-Jiang Feng, Dechun Wang, Hua Guan, Youfei Yan, Xiaoqiang Gao, Bin TI IL-22 Ameliorates Renal Ischemia-Reperfusion Injury by Targeting Proximal Tubule Epithelium SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE KIDNEY INJURY; FAILURE; CELLS; APOPTOSIS; PATHWAYS; JAK/STAT; PATHOPHYSIOLOGY; PROLIFERATION; EPIDEMIOLOGY; ACTIVATION AB The glomerular basement membrane (GBM) is a specialized extracellular matrix (ECM) compartment within the glomerulus that contains tissue-restricted isoforms of collagen IV and laminin. It is integral to the capillary wall and therefore, functionally linked to glomerular filtration. Although the composition of the GBM has been investigated with global and candidate-based approaches, the relative contributions of glomerular cell types to the production of ECM are not well understood. To characterize specific cellular contributions to the GBM, we used mass spectrometry-based proteomics to analyze ECM isolated from podocytes and glomerular endothelial cells in vitro. These analyses identified cell type-specific differences in ECM composition, indicating distinct contributions to glomerular ECM assembly. Coculture of podocytes and endothelial cells resulted in an altered composition and organization of ECM compared with monoculture ECMs, and electron microscopy revealed basement membrane-like ECM deposition between cocultured cells, suggesting the involvement of cell-cell cross-talk in the production of glomerular ECM. Notably, compared with monoculture ECM proteomes, the coculture ECM proteome better resembled a tissue-derived glomerular ECM dataset, indicating its relevance to GBM in vivo. Protein network analyses revealed a common core of 35 highly connected structural ECM proteins that may be important for glomerular ECM assembly. Overall, these findings show the complexity of the glomerular ECM and suggest that both ECM composition and organization are context-dependent. C1 [Xu, Ming-Jiang; Feng, Dechun; Wang, Hua; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA. [Xu, Ming-Jiang; Guan, Youfei] Peking Univ, Key Lab Mol Cardiovasc Sci, Dept Physiol & Pathophysiol, Sch Basic Med Sci,Hlth Sci Ctr,Minist Educ, Beijing 100871, Peoples R China. [Yan, Xiaoqiang] Generon Corp, Shanghai, Peoples R China. RP Xu, MJ (reprint author), Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Beijing 100871, Peoples R China. EM mingjiangxu@bjmu.edu.cn; bgao@mail.nih.gov RI Feng, Dechun/Q-5962-2016 FU National Institute of Alcohol Abuse and Alcoholism; National Institutes of Health; National Natural Science Foundation of China [81270370] FX This work was supported by the intramural program of the National Institute of Alcohol Abuse and Alcoholism and the National Institutes of Health (B.G.) and National Natural Science Foundation of China Grant 81270370 (to M.-J.X.). NR 28 TC 12 Z9 12 U1 0 U2 6 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2014 VL 25 IS 5 BP 967 EP 977 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA AG7FM UT WOS:000335583700016 PM 24459233 ER PT J AU Aseem, O Smith, BT Cooley, MA Wilkerson, BA Argraves, KM Remaley, AT Argraves, WS AF Aseem, Obaidullah Smith, Brian T. Cooley, Marion A. Wilkerson, Brent A. Argraves, Kelley M. Remaley, Alan T. Argraves, W. Scott TI Cubilin Maintains Blood Levels of HDL and Albumin SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; PROXIMAL TUBULE CELLS; RECEPTOR-ASSOCIATED PROTEIN; APOLIPOPROTEIN-A-I; CARDIOVASCULAR-DISEASE; BINDING PROTEIN; SERUM-ALBUMIN; THYROID-CELLS; NEONATAL RAT AB Cubilin is an endocytic receptor highly expressed in renal proximal tubules, where it mediates uptake of albumin and filtered forms of apoA-I/HDL. Cubilin deficiency leads to urinary loss of albumin and apoA-I; however, the consequences of cubilin loss on the homeostasis of blood albumin and apoA-I/HDL have not been studied. Using mice heterozygous for cubilin gene deletion (cubilin HT mice), we show that cubilin haploinsufficiency leads to reduced renal proximal tubular uptake of albumin and apoA-I and significantly increased urinary loss of albumin and apoA-I. Moreover, cubilin HT mice displayed significantly decreased blood levels of albumin, apoA-I, and HDL. The levels of albumin and apoA-I protein or mRNA expressed in the liver, kidney, or intestine of cubilin HT mice did not change significantly. The clearance rate of small HDL3 particles (density>1.13 g/ml) from the blood increased significantly in cubilin HT mice. In contrast, the rate of clearance of larger HDL2 particles from the blood did not change significantly, indicating a decreased half-life for HDL particles capable of filtering through the glomerulus. On the basis of these findings, we conclude that cubilin deficiency reduces renal salvage and delivery back to the blood of albumin and apoA-I, which decreases blood levels of albumin and apoA-I/HDL. These findings raise the possibility that therapeutic increase of renal cubilin expression might reduce proteinuria and increase blood levels of albumin and HDL. C1 [Aseem, Obaidullah; Smith, Brian T.; Cooley, Marion A.; Wilkerson, Brent A.; Argraves, Kelley M.; Argraves, W. Scott] Med Univ S Carolina, Regenerat Med & Cell Biol Dept, Charleston, SC 29425 USA. [Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Argraves, WS (reprint author), Med Univ S Carolina, Regenerat Med & Cell Biol Dept, 173 Ashley Avenue, Charleston, SC 29425 USA. EM argraves@musc.edu FU National Institutes of Health [HL061873, HL094883]; American Heart Association [10PRE3870038, 10PRE3910006] FX This work was supported by National Institutes of Health grants HL061873 (W.S.A.) and HL094883 (K.M.A.). O.A. was supported by a predoctoral fellowship from the American Heart Association (10PRE3870038). B.A.W. was supported by a predoctoral fellowship from the American Heart Association (10PRE3910006). NR 50 TC 10 Z9 10 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2014 VL 25 IS 5 BP 1028 EP 1036 DI 10.1681/ASN.2013060671 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AG7FM UT WOS:000335583700021 PM 24357674 ER PT J AU Parks, CG De Roos, AJ AF Parks, C. G. De Roos, A. J. TI Pesticides, chemical and industrial exposures in relation to systemic lupus erythematosus SO LUPUS LA English DT Article DE environmental risk factors; pesticides; occupational exposures; epidemiology; silica; Systemic lupus erythematosus ID OCCUPATIONAL RISK-FACTORS; RHEUMATOID-ARTHRITIS; ANTINUCLEAR ANTIBODIES; ORGANOCHLORINE PESTICIDES; AUTOIMMUNE-DISEASE; CRYSTALLINE SILICA; ASBESTOS EXPOSURE; KIDNEY-DISEASE; UNITED-STATES; MURINE LUPUS AB Growing evidence suggests exposure to chemicals and industrial pollutants may increase risk of systemic lupus erythematosus (SLE). Here we review research on SLE associations with occupational and industrial exposures, primarily drawing on studies in human populations and summarizing epidemiologic research published in the past decade. The association of occupational silica exposure with SLE is well established, but key questions remain, including the required dose and susceptibility factors, and SLE risk due to other silicate exposures. Research on SLE and other exposures is less well developed, though several potential associations merit further consideration because of the consistency of preliminary human findings, experimental animal research, and biologic plausibility. These include pesticides and solvents, for which experimental findings also support investigation of specific agents, including organochlorines and trichloroethylene. Experimental findings and biologic plausibility suggest research on SLE and occupational exposure to hydrocarbons (i.e. mineral oils) is warranted, especially given the widespread exposures in the population. Experimental and limited human findings support further investigation of SLE related to mercury exposure, especially in dental occupations. Research on environmental risk factors in risk-enriched cohorts (family-based) is recommended, as is further investigation of exposures in relation to intermediate markers of effect (e.g. antinuclear antibodies), clinical features (e.g. nephritis), and outcomes. C1 [Parks, C. G.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27599 USA. [De Roos, A. J.] Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Philadelphia, PA USA. RP Parks, CG (reprint author), NIEHS, Epidemiol Branch, A3-05,POB 12233, Res Triangle Pk, NC 27599 USA. EM Parks1@mail.nih.gov OI Parks, Christine/0000-0002-5734-3456 FU National Institutes of Health (NIH), National Institute of Environmental Health Sciences FX This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors, but was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences. NR 58 TC 6 Z9 6 U1 0 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0961-2033 EI 1477-0962 J9 LUPUS JI Lupus PD MAY PY 2014 VL 23 IS 6 SI SI BP 527 EP 536 DI 10.1177/0961203313511680 PG 10 WC Rheumatology SC Rheumatology GA AF6KU UT WOS:000334824800004 PM 24763537 ER PT J AU Wallace, BC Laws, MB Small, K Wilson, IB Trikalinos, TA AF Wallace, Byron C. Laws, M. Barton Small, Kevin Wilson, Ira B. Trikalinos, Thomas A. TI Automatically Annotating Topics in Transcripts of Patient-Provider Interactions via Machine Learning SO MEDICAL DECISION MAKING LA English DT Article DE machine learning; natural language processing; speech acts; patient-provider interaction; CRF; communication; informatics ID OF-THE-LITERATURE; HIV CARE; ADHERENCE; DIALOGUE; UTILITY AB Background. Annotated patient-provider encounters can provide important insights into clinical communication, ultimately suggesting how it might be improved to effect better health outcomes. But annotating outpatient transcripts with Roter or General Medical Interaction Analysis System (GMIAS) codes is expensive, limiting the scope of such analyses. We propose automatically annotating transcripts of patient-provider interactions with topic codes via machine learning. Methods. We use a conditional random field (CRF) to model utterance topic probabilities. The model accounts for the sequential structure of conversations and the words comprising utterances. We assess predictive performance via 10-fold cross-validation over GMIAS-annotated transcripts of 360 outpatient visits (>230,000 utterances). We then use automated in place of manual annotations to reproduce an analysis of 116 additional visits from a randomized trial that used GMIAS to assess the efficacy of an intervention aimed at improving communication around antiretroviral (ARV) adherence. Results. With respect to 6 topic codes, the CRF achieved a mean pairwise kappa compared with human annotators of 0.49 (range: 0.47-0.53) and a mean overall accuracy of 0.64 (range: 0.62-0.66). With respect to the RCT reanalysis, results using automated annotations agreed with those obtained using manual ones. According to the manual annotations, the median number of ARV-related utterances without and with the intervention was 49.5 versus 76, respectively (paired sign test P = 0.07). When automated annotations were used, the respective numbers were 39 versus 55 (P = 0.04). While moderately accurate, the predicted annotations are far from perfect. Conversational topics are intermediate outcomes, and their utility is still being researched. Conclusions. This foray into automated topic inference suggests that machine learning methods can classify utterances comprising patient-provider interactions into clinically relevant topics with reasonable accuracy. C1 [Wallace, Byron C.; Laws, M. Barton; Wilson, Ira B.; Trikalinos, Thomas A.] Brown Univ, Dept Hlth Serv Policy & Practice, Sch Publ Hlth, Providence, RI 02903 USA. [Small, Kevin] NIH, Bethesda, MD 20892 USA. RP Wallace, BC (reprint author), Brown Univ, Dept Hlth Serv Policy & Practice, 121 South Main St, Providence, RI 02903 USA. EM byron_wallace@brown.edu RI Wilson, Ira/F-9190-2016 OI Wilson, Ira/0000-0002-0246-738X FU National Institute of Mental Health [2 K24MH092242]; [R01MH083595] FX Received 13 March 2013 from Department of Health Services, Policy and Practice, Brown University, School of Public Health, Providence, RI (BCW, MBL, IBW, TAT) and National Institutes of Health, Bethesda, MD (KS). Financial support for this study was provided in part by the National Institute of Mental Health (2 K24MH092242). The annotation of the data used in this work was supported by grant R01MH083595. The funding agreement ensured the authors' independence in designing the study, interpreting the data, and writing and publishing the report. The authors declare no competing interests. Revision accepted for publication 4 November 2013. NR 28 TC 4 Z9 4 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X EI 1552-681X J9 MED DECIS MAKING JI Med. Decis. Mak. PD MAY PY 2014 VL 34 IS 4 BP 503 EP 512 DI 10.1177/0272989X13514777 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA AF0JA UT WOS:000334398900011 PM 24285151 ER PT J AU Cizza, G de Jonge, L Piaggi, P Mattingly, M Zhao, XC Lucassen, E Rother, KI Sumner, AE Csako, G AF Cizza, Giovanni de Jonge, Lilian Piaggi, Paolo Mattingly, Megan Zhao, Xiongce Lucassen, Eliane Rother, Kristina I. Sumner, Anne E. Csako, Gyorgy CA NIDDK Sleep Extension Study TI Neck Circumference Is a Predictor of Metabolic Syndrome and Obstructive Sleep Apnea in Short-Sleeping Obese Men and Women SO METABOLIC SYNDROME AND RELATED DISORDERS LA English DT Article ID INSULIN-RESISTANCE; CARDIOVASCULAR RISK; ADULTS; DURATION; QUALITY; DEPRIVATION; ADIPONECTIN; ADOLESCENTS; EPIDEMIC; DISEASE AB Background: The constellation of metabolic syndrome, although controversial with regard to its clinical usefulness, is epidemiologically related to increased diabetes risk and cardiovascular mortality. Our goal was to investigate the associations among neck circumference (NC), obstructive sleep apnea syndromes (OSAS), and metabolic syndrome in obese men and women sleeping less than 6.5hr per night. Methods: This was a cross-sectional study of obese men and premenopausal obese women sleeping less than 6.5hr per night. We enrolled 120 individuals (92 women), age 40.56.9 years and body mass index (BMI) 38.66.5kg/m(2). Metabolic syndrome severity was assessed by a score and OSAS was defined as a respiratory disturbance index (RDI) 5. Metabolic end endocrine parameters were measured, and sleep duration was determined by actigraphy and validated questionnaires. Results: Metabolic syndrome was found in 41% and OSAS in 58% (28% had both). Subjects with metabolic syndrome were 3 years older and more often Caucasian; they had higher RDI scores, larger NC, more visceral fat, lower serum adiponectin, higher 24-hr urinary norepinephrine (NE) excretion, and lower growth hormone concentrations. A NC of 38cm had a sensitivity of 54% and 58% and a specificity of 70% and 79% in predicting the presence of metabolic syndrome and OSAS, respectively. RDI, adiponectin, and NC accounted for approximately 30% of the variability in the metabolic syndrome score, as estimated by an age-, gender-, and race-corrected multivariate model (R-2=0.376, P<0.001). Conclusion: Greater NC is associated with OSAS and metabolic syndrome in short-sleeping obese men and premenopausal obese women. Addition of NC to the definition of metabolic syndrome should be considered and needs to be validated in future studies. C1 [Cizza, Giovanni; de Jonge, Lilian; Mattingly, Megan; Lucassen, Eliane] NIDDK, Sect Neuroendocrinol Obes, DEOB, Bethesda, MD 20892 USA. [Piaggi, Paolo] Univ Hosp Pisa, Endocrinol Unit, Obes Res Ctr, Pisa, Italy. [Piaggi, Paolo] NIDDK, Obes & Diabet Clin Res Sect, Phoenix, AZ USA. [Zhao, Xiongce] NIDDK, Intramural Res Program, Bethesda, MD 20892 USA. [Lucassen, Eliane] Leiden Univ, Med Ctr, Dept Mol Cell Biol, Neurophysiol Lab, Leiden, Netherlands. [Rother, Kristina I.] NIDDK, Sect Pediat Diabet & Metab, DEOB, Bethesda, MD 20892 USA. [Sumner, Anne E.] NIDDK, Ethn & Hlth Sect, DEOB, Bethesda, MD 20892 USA. [Csako, Gyorgy] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Cizza, G (reprint author), NIDDK, Sect Neuroendocrinol Obes, DEOB, CRC, Bldg 10,Room 6-3940, Bethesda, MD 20892 USA. EM gcizza@gmail.com OI de Jonge, Lilian/0000-0001-5900-0695; Piaggi, Paolo/0000-0003-2774-9161 FU National Institute of Diabetes and Digestive and Kidney Diseases and Clinical Center, National Institutes of Health (NIH) FX This work was supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases and Clinical Center, National Institutes of Health (NIH). We would like to thank in alphabetical order the following colleagues for their scientific advice and critical suggestions in the development and conduct of the study protocol: Karim Calis, Janet Gershengorn, Gregor Hasler, Emmanuel Mignot, Susan Redline, Terry Phillips, Nancy Sebring, Duncan Wallace, and Elizabeth Wright. We would also like to thank present and past members of the study team: Peter Bailey, Laide Bello, Meredith Coyle, Paula Marincola, Patrick Michaels, Svetlana Primma, Angela Ramer, Rebecca Romero, Megan Sabo, Tanner Slayden, Sara Torvik, Elizabeth Widen, Lydia Williams, and Sam Zuber. We would like to thank Dr. Alex Ling (NIH CC) for analysis of the computer tomography measurements. The bioinformatics support of Frank Pierce (Esprit Health) is gratefully acknowledged. Finally, we are grateful to all of our enthusiastic study participants. NR 47 TC 12 Z9 13 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-4196 EI 1557-8518 J9 METAB SYNDR RELAT D JI Metab. Syndr. Relat. Disord. PD MAY 1 PY 2014 VL 12 IS 4 BP 231 EP 241 DI 10.1089/met.2013.0093 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AF4II UT WOS:000334674800006 PM 24571423 ER PT J AU Richardson, SP Beck, S Bliem, B Hallett, M AF Richardson, Sarah Pirio Beck, Sandra Bliem, Barbara Hallett, Mark TI Abnormal Dorsal Premotor-Motor Inhibition in Writer's Cramp SO MOVEMENT DISORDERS LA English DT Article DE TMS; dystonia; motor cortex ID DYSTONIA; CORTEX; MOVEMENT AB The authors hypothesized that a deficient premotor-motor inhibitory network contributes to the unwanted involuntary movements in dystonia. The authors studied nine controls and nine patients with writer's cramp (WC). Dorsal premotor-motor cortical inhibition (dPMI) was tested by applying conditioning transcranial magnetic stimulation (TMS) to the dorsal premotor cortex and then a test pulse to the ipsilateral motor cortex at an interval of 6 ms. The authors used an H-reflex in flexor carpi radialis paired with TMS over the premotor cortex to assess for spinal cord excitability change. Finally, the authors interrupted a choice reaction time task with TMS over dorsal premotor cortex to assess performance in a nondystonic task. The results showed that WC patients exhibited dPMI at rest (88.5%, the ratio of conditioned to unconditioned test pulse), in contrast to controls, who did not show dPMI (109.6%) (P=0.0198). This difference between patients and controls persisted during contraction (100% vs. 112%) and pen-holding (95.6% vs. 111%). The H-reflex in the arm was not modulated by the premotor cortex stimulation. The WC patients made more errors, and the error rate improved with TMS over the premotor cortex. These results suggest that abnormal premotor-motor interactions may play a role in the pathophysiology of focal dystonia. The dPMI was not modulated by task in either group, but was constantly greater in the patients. The significance of the increased inhibition is likely to be compensatory. It appears to be a robust finding and, in combination with other features, could be further explored as a biomarker. (c) 2014 International Parkinson and Movement Disorder Society C1 [Richardson, Sarah Pirio] Univ New Mexico, Hlth Sci Ctr, Dept Neurol, Albuquerque, NM 87131 USA. [Beck, Sandra] Univ Freiburg, Dept Neurol & Clin Neurophysiol, D-79106 Freiburg, Germany. [Richardson, Sarah Pirio; Beck, Sandra; Bliem, Barbara; Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD USA. RP Richardson, SP (reprint author), 1 Univ New Mexico, Dept Neurol, Hlth Sci Ctr, MSC 10 5620, Albuquerque, NM 87131 USA. EM spiriorichardson@salud.unm.edu FU National Center for Research Resources; National Center for Advancing Translational Sciences of the National Institutes of Health [KL2 TR000089, UL1 TR000041]; NIH/NINDS FX This study was supported (in part or in full) by the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number KL2 TR000089 and Grant Number UL1 TR000041. The project was also supported through NIH/NINDS Intramural Funds. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 14 TC 3 Z9 3 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 2014 VL 29 IS 6 BP 797 EP 803 DI 10.1002/mds.25878 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AG4BI UT WOS:000335363300015 ER PT J AU Miyazaki, Y Shimizu, A Ichikawa, I Hosoya, T Pastan, I Matsusaka, T AF Miyazaki, Yoichi Shimizu, Akihiro Ichikawa, Iekuni Hosoya, Tatsuo Pastan, Ira Matsusaka, Taiji TI Mice are unable to endogenously regenerate podocytes during the repair of immunotoxin-induced glomerular injury SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE chronic renal failure; glomerulosclerosis; mouse model; podocyte; regeneration ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; PARIETAL EPITHELIAL-CELLS; RENAL PROGENITORS; MOUSE MODEL; CONTRIBUTE; DISEASE; EXPRESSION; SCLEROSIS; TURNOVER; BIOLOGY AB The average body size of mankind has continuously increased with improving health and nutrition since about 250 years (average height used to be about 15 cm smaller). It can be speculated that our podocyte endowment may no longer be sufficient to handle the increase in body size (especially in males).Recent studies have reported that podocytes are postnatally generated from progenitor cells localized in Bowman's capsule or in the bone marrow. In the present study, we investigated whether or not podocyte regeneration is important in the repair of injured glomeruli after mild podocyte injury in mice. Mild podocyte injury was induced in NEP25 mice (n = 8) by injecting an immunotoxin, LMB2 (0.625 ng/g body weight). Control mice, not injured by LMB2 injection (n = 7) was used as a comparison. Proliferating cells were labeled by continuous infusion of bromodeoxyuridine (BrdU). Podocytes, identified by nephrin, WT1 or podocin staining, that had incorporated BrdU were enumerated 4 weeks later. A total of 742 corpuscles were inspected in serial sections stained for BrdU and nephrin; 19% showed sclerosis. BrdU(+) cells were observed in both the glomeruli and Bowman's capsules, averaging 2.5 +/- 3.1 in non-sclerotic corpuscles and 7.0 +/- 5.8 in sclerotic corpuscles. Only one BrdU(+) cell was also positive for nephrin. Another cell, localized at a position consistent with its potential identification as a podocyte, was nephrin negative but had incorporated BrdU. WT1 staining similarly revealed that only two nuclei were doubly positive for BrdU and WT1. Additional 1676 corpuscles were inspected by double staining for BrdU and podocin; none were doubly positive. Podocytes are not replenished by proliferation of endogenous progenitor cells in mice with glomerular injury. C1 [Miyazaki, Yoichi; Shimizu, Akihiro; Hosoya, Tatsuo] Jikei Univ, Sch Med, Dept Internal Med, Div Kidney & Hypertens, Tokyo, Japan. [Shimizu, Akihiro; Matsusaka, Taiji] Tokai Univ, Sch Med, Dept Internal Med, Isehara, Kanagawa 25911, Japan. [Ichikawa, Iekuni] Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan. [Ichikawa, Iekuni] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. [Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Matsusaka, Taiji] Tokai Univ, Sch Med, Inst Med Sci, Isehara, Kanagawa 25911, Japan. RP Miyazaki, Y (reprint author), Jikei Univ, Sch Med, Dept Internal Med, Div Kidney & Hypertens, Tokyo, Japan. EM yoichimiyazaki@jikei.ac.jp FU Japan Society for the Promotion of Science, MEXT, HAITEKU; NIH, Center for Cancer Research at the National Cancer Institute FX We thank Ms Shiho Imai and Ms Chie Sakurai for technical assistance. This study was supported by a Grant-in Aid for Scientific Research from the Japan Society for the Promotion of Science, MEXT, HAITEKU and in part by the Intramural Research Program of the NIH, Center for Cancer Research at the National Cancer Institute. The results presented in this paper have not been published previously. NR 23 TC 6 Z9 6 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD MAY PY 2014 VL 29 IS 5 BP 1005 EP 1012 DI 10.1093/ndt/gft413 PG 8 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA AH4JT UT WOS:000336093900013 PM 24322577 ER PT J AU Huizing, M Carrillo-Carrasco, N Malicdan, MCV Noguchi, S Gahl, WA Mitrani-Rosenbaum, S Argov, Z Nishino, I AF Huizing, Marjan Carrillo-Carrasco, Nuria Malicdan, May Christine V. Noguchi, Satoru Gahl, William A. Mitrani-Rosenbaum, Stella Argov, Zohar Nishino, Ichizo TI GNE myopathy: New name and new mutation nomenclature SO NEUROMUSCULAR DISORDERS LA English DT Article DE Distal Myopathy with Rimmed Vacuoles (DMRV); Hereditary Inclusion Body Myopathy (HIBM); Inclusion Body Myopathy 2 (IBM2); Nonaka myopathy; Sialic acid; UDP-GlcNAc 2-epimersa/ManNAc kinase; GNE Myopathy ID INCLUSION-BODY MYOPATHY; DISTAL MYOPATHY; RIMMED VACUOLES; KINASE; MAPS; GENE C1 [Huizing, Marjan; Malicdan, May Christine V.; Gahl, William A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Carrillo-Carrasco, Nuria] Natl Ctr Adv Translat Sci, NIH, Bethesda, MD USA. [Noguchi, Satoru; Nishino, Ichizo] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Neuromuscular Res, Tokyo, Japan. [Mitrani-Rosenbaum, Stella] Hadassah Hebrew Univ, Med Ctr, Goldyne Savad Inst Gene Therapy, Jerusalem, Israel. [Argov, Zohar] Hadassah Hebrew Univ, Med Ctr, Dept Neurol, Jerusalem, Israel. RP Huizing, M (reprint author), NHGRI, NIH, 10 Ctr Dr,Bid 10,Rm 10C103, Bethesda, MD 20892 USA. EM mhuizing@mail.nih.gov RI Carrillo-Carrasco, Nuria/B-9034-2009; OI Carrillo-Carrasco, Nuria/0000-0003-0374-0808; Nishino, Ichizo/0000-0001-9452-112X FU Intramural NIH HHS [ZIA HG200322-09] NR 8 TC 14 Z9 14 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD MAY PY 2014 VL 24 IS 5 BP 387 EP 389 DI 10.1016/j.nmd.2014.03.004 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AH7XT UT WOS:000336349400003 PM 24685570 ER PT J AU Bertrand, AT Bonnemann, CG Bonne, G AF Bertrand, Anne T. Boennemann, Carsten G. Bonne, Gisele CA FHL1 Myopathy Consortium TI 199th ENMC international workshop: FHL1 related myopathies, June 7-9, 2013, Naarden, The Netherlands SO NEUROMUSCULAR DISORDERS LA English DT Article ID REDUCING-BODY MYOPATHY; RIGID SPINE SYNDROME; LIM DOMAIN MUTATION; BINDING-PROTEIN-C; HYPERTROPHIC CARDIOMYOPATHY; CYTOPLASMIC BODIES; 1 GENE; IDENTIFICATION; MYOFIBRILLAR; COMPONENTS C1 [Bertrand, Anne T.; Bonne, Gisele] INSERM, U974, F-75013 Paris, France. [Bertrand, Anne T.; Bonne, Gisele] Univ Paris 06, Sorbonne Univ, Inserm U974, Myol Ctr Rech,CNRS,Inst Myol, F-75651 Paris, France. [Boennemann, Carsten G.] NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, NIH, Bethesda, MD 20892 USA. [Bonne, Gisele] Grp Hosp Pitie Salpetriere, AP HP, UE Cardiogenet & Myogenet Mol, Serv Biochim Metabol, F-75013 Paris, France. RP Bonne, G (reprint author), Univ Paris 06, Sorbonne Univ, Inserm U974, Myol Ctr Rech,CNRS,Inst Myol, UM76,FRE3617,GH Pitie Salpetriere47, F-75651 Paris, France. EM g.bonne@institut-myologie.org RI Bonne, Gisele/G-3121-2013; OI Mitchell, Christina A/0000-0001-9372-3192 FU European Neuromuscular Centre (ENMC); Association Francaise contre les Myopathies (France); Deutsche Gesellschaft fur Muskelkranke (Germany); Muscular Dystrophy Campain (UK); Muskelvindfonden (Denmark); Prinses Beatrix Spierfonds (the Netherlands); Schweizerische Stiftung fur die Erforschung der Muskelkrankheiten (Switzerland); Telethon Foundation (Italy); Spierziekten Nederland (The Netherlands) FX This workshop was made possible thanks to the financial support of the European Neuromuscular Centre (ENMC) and ENMC main Sponsors: Association Francaise contre les Myopathies (France), Deutsche Gesellschaft fur Muskelkranke (Germany), Muscular Dystrophy Campain (UK), Muskelvindfonden (Denmark), Prinses Beatrix Spierfonds (the Netherlands), Schweizerische Stiftung fur die Erforschung der Muskelkrankheiten (Switzerland), Telethon Foundation (Italy), Spierziekten Nederland (The Netherlands), and Associated members: Finnish Neuromuscular Association (Finland). NR 32 TC 2 Z9 2 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD MAY PY 2014 VL 24 IS 5 BP 453 EP 462 DI 10.1016/j.nmd.2014.02.002 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AH7XT UT WOS:000336349400014 PM 24613424 ER PT J AU Wang, XY Chrysovergis, K Kosak, J Eling, TE AF Wang, Xingya Chrysovergis, Kali Kosak, Justin Eling, Thomas E. TI Lower NLRP3 Inflammasome Activity in NAG-1 Transgenic Mice Is Linked to a Resistance to Obesity and Increased Insulin Sensitivity SO OBESITY LA English DT Article ID MACROPHAGE INHIBITORY CYTOKINE-1; ADIPOSE-TISSUE; CASPASE-1 ACTIVATION; ADIPOCYTES; EXPRESSION; DIFFERENTIATION; INTERLEUKIN-18; ADIPONECTIN; NAG-1/GDF15; DEFICIENCY AB Objective: The NLRP3 inflammasome plays an important regulatory role in obesity-induced insulin resistance. NSAID activated gene-1 (NAG-1) is a divergent member of the TGF-beta superfamily. NAG-1 Tg mice are resistant to dietary- and genetic-induced obesity and have improved insulin sensitivity. The objective was to examine whether NLRP3 inflammasome activity is associated with this observed phenotype in NAG-1 Tg mice. Methods: Key components of the NLRP3 inflammasome were examined in NAG-1 Tg mice on both regular and high fat diet (HFD) conditions. Results: The expression of caspase-1 and ASC, key components of the NLRP3 inflammasome, is significantly reduced at mRNA and protein levels in white adipose tissue (WAT) of NAG-1 Tg mice. HFD increases the expression of caspase-1 and ASC in WT mice, but their expression is reduced in NAG-1 Tg mice. Furthermore, there is reduced IL-18, IL-1 beta, and TNF-alpha expression in the WAT of NAG-1 Tg mice. NAG-1 Tg mice have significantly lower serum leptin and insulin levels and reduced expression of macrophage infiltration markers (F4/80, CD11b, and CD11c) in WAT. Conclusions: The study suggests the lower NLRP3 inflammasome activity may play a role in the resistance of NAG-1 Tg mice to diet-induced obesity and improved insulin sensitivity. C1 [Wang, Xingya; Chrysovergis, Kali; Kosak, Justin; Eling, Thomas E.] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM eling@niehs.nih.gov FU NIH; NIEHS Intramural Research Program (Eling) [Z01-ES010016-14] FX This research was supported by NIH, NIEHS Intramural Research Program (Eling) Z01-ES010016-14. NR 34 TC 4 Z9 4 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD MAY PY 2014 VL 22 IS 5 BP 1256 EP 1263 DI 10.1002/oby.20638 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AH3OR UT WOS:000336034400034 PM 24124102 ER PT J AU Wing, MR Yang, W Teal, V Navaneethan, S Tao, KX Ojo, A Guzman, NN Reilly, M Wolman, M Rosas, SE Cuevas, M Fischer, M Lustigova, E Master, SR Xie, DW Appleby, D Joffe, M Kusek, J Feldman, HI Raj, DS AF Wing, Maria R. Yang, Wei Teal, Valerie Navaneethan, Sankar Tao, Kaixiang Ojo, Akinlolu Guzman, Nicolas N. Reilly, Muredach Wolman, Melanie Rosas, Sylvia E. Cuevas, Magda Fischer, Michael Lustigova, Eva Master, Stephen R. Xie, Dawei Appleby, Dina Joffe, Marshall Kusek, John Feldman, Harold I. Raj, Dominic S. CA Chronic Renal Insufficiency Cohort TI Race Modifies the Association Between Adiposity and Inflammation in Patients with Chronic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort Study SO OBESITY LA English DT Article ID BIOELECTRICAL-IMPEDANCE ANALYSIS; BODY-MASS INDEX; SKELETAL-MUSCLE; HEMODIALYSIS-PATIENTS; INTERLEUKIN-6; OBESITY; ADULTS; FAT; POPULATION; RELEASE AB Objective: The race-specific association of inflammation with adiposity and muscle mass in subjects with chronic kidney disease (CKD) was examined. Methods: Plasma concentration of interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1RA), IL-6, IL-10, tumor necrosis factor (TNF)-alpha, TGF-beta, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and serum albumin was measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Bioelectric impedance analysis was used to determine body fat mass (BFM) and fat-free mass (FFM). Results: Plasma levels of hs-CRP, fibrinogen, IL-1RA, IL-6, and TNF-alpha increased and serum albumin decreased across the quartiles of body mass index. In multivariable analysis, BFM and FFM were positively associated with hs-CRP, fibrinogen, IL-1 beta, IL-1RA, and IL-6. One standard deviation (SD) increase in BFM and FFM was associated with 0.36 (95% confidence interval [CI] 50.33, 0.39) and 0.26 (95% CI = 0.22, 0.30) SD increase in log-transformed hs-CRP, respectively (P < 0.001). Race stratified analysis showed that the association between biomarkers and BFM and FFM differed by race, with Caucasians, demonstrating a stronger association with markers of inflammation than African Americans. Conclusions: BFA and FFM are positively associated with markers of inflammation in patients with CKD. Race stratified analysis showed that Caucasians have a stronger association with markers of inflammation compared to African Americans. C1 [Wing, Maria R.; Guzman, Nicolas N.; Raj, Dominic S.] George Washington Univ, Div Renal Dis & Hypertens, Washington, DC 20052 USA. [Yang, Wei; Teal, Valerie; Tao, Kaixiang; Xie, Dawei; Appleby, Dina; Joffe, Marshall] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Navaneethan, Sankar] Cleveland Clin, Dept Hypertens & Nephrol, Cleveland, OH 44106 USA. [Ojo, Akinlolu] Univ Michigan Hlth Syst, Dept Internal Med, Ann Arbor, MI USA. [Cuevas, Magda] Univ Penn, Med Ctr, Dept Med, Philadelphia, PA 19104 USA. [Rosas, Sylvia E.] Univ Penn, Perelman Sch Med, Renal Elect & Hypertens Div, Philadelphia, PA 19104 USA. [Fischer, Michael] Univ Illinois, Med Ctr, Jesse Brown VA Med Ctr, Dept Med, Chicago, IL USA. [Lustigova, Eva] Tulane Univ, Dept Epidemiol, New Orleans, LA USA. [Master, Stephen R.] Univ Pennsylvania Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA USA. [Kusek, John] Natl Inst Diabet & Digest & Kidney Dis, Div Kidney Urol & Hematol Dis, Bethesda, MD USA. [Feldman, Harold I.] Univ Penn, Perelman Sch Med, Clin Epidemiol Unit, Philadelphia, PA USA. RP Raj, DS (reprint author), George Washington Univ, Div Renal Dis & Hypertens, Washington, DC 20052 USA. EM draj@mfa.gwu.edu OI Teal, Valerie/0000-0001-7116-5353 FU National Institute of Diabetes and Digestive and Kidney Diseases [5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963, 5U01DK060902]; National Institutes of Health [UL1RR024134, UL1RR025005, M01RR16500, UL1RR024989, M01RR000042, UL1RR024986, UL1RR029879, RR05096, UL1RR024131]; [R01 DK073665-01A1] FX This study was sponsored by R01 DK073665-01A1, The National Institute of Diabetes and Digestive and Kidney Diseases (5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963, 5U01DK060902), and The National Institutes of Health (UL1RR024134, UL1RR025005, M01RR16500, UL1RR024989, M01RR000042, UL1RR024986, UL1RR029879, RR05096, UL1RR024131). NR 35 TC 4 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD MAY PY 2014 VL 22 IS 5 BP 1359 EP 1366 DI 10.1002/oby.20692 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AH3OR UT WOS:000336034400047 PM 24415732 ER PT J AU Green, AK Jacques, PF Rogers, G Fox, CS Meigs, JB McKeown, NM AF Green, Angela K. Jacques, Paul F. Rogers, Gail Fox, Caroline S. Meigs, James B. McKeown, Nicola M. TI Sugar-Sweetened Beverages and Prevalence of the Metabolically Abnormal Phenotype in the Framingham Heart Study SO OBESITY LA English DT Article ID FOOD-FREQUENCY QUESTIONNAIRE; INSULIN-RESISTANCE; HEALTHY OBESE; CARDIOVASCULAR-DISEASE; NORMAL-WEIGHT; AGED ADULTS; US ADULTS; RISK; CONSUMPTION; REPRODUCIBILITY AB Objective: The purpose of this study was to examine the relationship between usual sugar-sweetened beverage (SSB) consumption and prevalence of abnormal metabolic health across body mass index (BMI) categories. Methods: The metabolic health of 6,842 non-diabetic adults was classified using cross-sectional data from the Framingham Heart Study Offspring (1998-2001) and Third Generation (2002-2005) cohorts. Adults were classified as normal weight, overweight or obese and, within these categories, metabolic health was defined based on five criteria-hypertension, elevated fasting glucose, elevated triglycerides, low HDL cholesterol, and insulin resistance. Individuals without metabolic abnormalities were considered metabolically healthy. Logistic regression was used to examine the associations between categories of SSB consumption and risk of metabolic health after stratification by BMI. Results: Comparing the highest category of SSB consumers (median of 7 SSB per week) to the lowest category (non-consumers), odds ratios (95% confidence intervals) for metabolically abnormal phenotypes, compared to the metabolically normal, were 1.9 (1.1-3.4) among the obese, 2.0 (1.4-2.9) among the overweight, and 1.9 (1.4-2.6) among the normal weight individuals. Conclusions: In this cross-sectional analysis, it is observed that, irrespective of weight status, consumers of SSB were more likely to display metabolic abnormalities compared to non-consumers in a dosedependent manner. C1 [Green, Angela K.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Jacques, Paul F.; Rogers, Gail; McKeown, Nicola M.] Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Jacques, Paul F.; McKeown, Nicola M.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Metab & Diabet, Dept Med, Boston, MA 02115 USA. [Fox, Caroline S.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. RP McKeown, NM (reprint author), Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA 02111 USA. EM nicola.mckeown@tufts.edu FU National Heart Lung and Blood Institute [NO1-HC-25195]; USDA Agricultural Research Service [58-1950-0-014] FX This study was supported by grants from the National Heart Lung and Blood Institute (contract NO1-HC-25195) and the USDA Agricultural Research Service (agreement 58-1950-0-014). The funding providers did not play a role in any aspect of this study. NR 36 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD MAY PY 2014 VL 22 IS 5 BP E157 EP E163 DI 10.1002/oby.20724 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AH3OR UT WOS:000336034400024 PM 24550031 ER PT J AU Aschebrook-Kilfoy, B Ward, MH Della Valle, CT Friesen, MC AF Aschebrook-Kilfoy, Briseis Ward, Mary H. Della Valle, Curt T. Friesen, Melissa C. TI Occupation and thyroid cancer SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Review ID SERUM THYROTROPIN CONCENTRATION; IONIZING-RADIATION EXPOSURE; BRITISH NUCLEAR-FUELS; AGRICULTURAL HEALTH; ENVIRONMENTAL CHEMICALS; PESTICIDE APPLICATORS; HUMAN CARCINOGENS; DISRUPTING CHEMICALS; INCREASING INCIDENCE; PAPILLARY CANCER AB Numerous occupational and environmental exposures have been shown to disrupt thyroid hormones, but much less is known about their relationships with thyroid cancer. Here we review the epidemiology studies of occupations and occupational exposures and thyroid cancer incidence to provide insight into preventable risk factors for thyroid cancer. The published literature was searched using the Web of Knowledge database for all articles through August 2013 that had in their text occupation' job' employment' or work' and thyroid cancer'. After excluding 10 mortality studies and 4 studies with less than 5 exposed incident cases, we summarised the findings of 30 articles that examined thyroid cancer incidence in relation to occupations or occupational exposure. The studies were grouped by exposure/occupation category, study design and exposure assessment approach. Where available, gender-stratified results are reported. The most studied (19 of 30 studies) and the most consistent associations were observed for radiation-exposed workers and healthcare occupations. Suggestive, but inconsistent, associations were observed in studies of pesticide-exposed workers and agricultural occupations. Findings for other exposures and occupation groups were largely null. The majority of studies had few exposed cases and assessed exposure based on occupation or industry category, self-report, or generic (population-based) job exposure matrices. The suggestive, but inconsistent findings for many of the occupational exposures reviewed here indicate that more studies with larger numbers of cases and better exposure assessment are necessary, particularly for exposures known to disrupt thyroid homeostasis. C1 [Aschebrook-Kilfoy, Briseis] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Ward, Mary H.; Della Valle, Curt T.; Friesen, Melissa C.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Rockville, MD USA. RP Aschebrook-Kilfoy, B (reprint author), Univ Chicago, Dept Hlth Studies, 5841 South Maryland Ave,N101B, Chicago, IL 60637 USA. EM brisa@uchicago.edu RI Friesen, Melissa/A-5362-2009 FU Intramural Research Program of the National Cancer Institute (NCI), NIH FX This research was supported by the Intramural Research Program of the National Cancer Institute (NCI), NIH. NR 98 TC 9 Z9 10 U1 2 U2 10 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 EI 1470-7926 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD MAY PY 2014 VL 71 IS 5 BP 366 EP 380 DI 10.1136/oemed-2013-101929 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AF0IM UT WOS:000334397500012 PM 24604144 ER PT J AU Kurmasheva, RT Reynolds, CP Kang, MH Allievi, C Houghton, PJ Smith, MA AF Kurmasheva, Raushan T. Reynolds, C. Patrick Kang, Min H. Allievi, Cecilia Houghton, Peter J. Smith, Malcolm A. TI Initial Testing (Stage 1) of the Topoisomerase II Inhibitor Pixantrone, by the Pediatric Preclinical Testing Program SO PEDIATRIC BLOOD & CANCER LA English DT Article DE developmental therapeutics; preclinical testing; topoisomerase 2 inhibitor ID AZA-ANTHRACENEDIONE; PHASE-I; BBR-2778; DNA; CYTOTOXICITY; MICE; MITOXANTRONE; FORMALDEHYDE; NEPHROPATHY; DOXORUBICIN AB Pixantrone, a novel aza-anthracenedione with cytotoxic activity, was tested against the PPTP in vitro panel (3.0nM to 30.0M) and against a limited panel of PPTP Wilms tumors and sarcomas (7.5mg/kg) administered intravenously using an every 4 dayx3 schedule. In vitro pixantrone showed a median relative IC50 value of 54nM (range <3nM to 1.03M). In vivo pixantrone induced significant differences in EFS distribution compared to controls in two of eight solid tumor xenografts at dose levels relevant to human drug exposure. A complete response was observed for one Wilms tumor xenograft. Pediatr Blood Cancer 2014;61:922-924. (c) 2013 Wiley Periodicals, Inc. C1 [Kurmasheva, Raushan T.; Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH 43205 USA. [Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Allievi, Cecilia] Cell Therapeut, Monza, Italy. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Kurmasheva, RT (reprint author), Nationwide Childrens Hosp, Ctr Childhood Canc, 700 Childrens Dr, Columbus, OH 43205 USA. EM raushan.kurmasheva@nationwidechildrens.org OI Reynolds, C. Patrick/0000-0002-2827-8536 FU National Cancer Institute [NO1-CM-42216, CA21765] FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216, CA21765. NR 18 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2014 VL 61 IS 5 BP 922 EP 924 DI 10.1002/pbc.24800 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AD7ZI UT WOS:000333485600028 PM 24166988 ER PT J AU Akshintala, S Dombi, E Baldwin, A Gillespie, A Goodspeed, W Goodwin, A Whitcomb, P Steinberg, S Widemann, B AF Akshintala, Srivandana Dombi, Eva Baldwin, Andrea Gillespie, Andy Goodspeed, Wendy Goodwin, Anne Whitcomb, Patricia Steinberg, Seth Widemann, Brigitte TI PREDICTORS OF PLEXIFORM NEUROFIBROMA (PN) GROWTH IN PATIENTS WITH NEUROFIBROMATOSIS 1 (NF1) SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Akshintala, Srivandana; Dombi, Eva; Baldwin, Andrea; Gillespie, Andy; Goodspeed, Wendy; Goodwin, Anne; Whitcomb, Patricia; Steinberg, Seth; Widemann, Brigitte] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2014 VL 61 SU 1 SI SI BP S32 EP S33 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AG5WT UT WOS:000335490100114 ER PT J AU Rao, VK Rosenberg, P Price, S Gill, F Pittaluga, S Fleisher, T Lenardo, M Jaffe, E AF Rao, V. Koneti Rosenberg, Philip Price, Susan Gill, Fred Pittaluga, Stefania Fleisher, Thomas Lenardo, Michael Jaffe, Elaine TI ENHANCED RISK OF LYMPHOMA IN AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME (ALPS) DUE TO FAS MUTATIONS SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Rao, V. Koneti; Rosenberg, Philip; Price, Susan; Gill, Fred; Pittaluga, Stefania; Fleisher, Thomas; Lenardo, Michael; Jaffe, Elaine] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2014 VL 61 SU 1 SI SI BP S82 EP S82 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AG5WT UT WOS:000335490100285 ER PT J AU Brown, RJ Yanovski, JA AF Brown, Rebecca J. Yanovski, Jack A. TI Estimation of insulin sensitivity in children: methods, measures and controversies SO PEDIATRIC DIABETES LA English DT Review DE FSIGT; glucose clamp technique; glucose tolerance; HOMA; insulin sensitivity; QUICKI; surrogate measures ID GLUCOSE-TOLERANCE TEST; BETA-CELL FUNCTION; DEPENDENT DIABETES-MELLITUS; OBESE ADOLESCENT BOYS; MINIMAL MODEL; INTRAVENOUS GLUCOSE; OVERWEIGHT CHILDREN; AFRICAN-AMERICAN; FATTY-ACID; IN-VIVO AB Insulin resistance is defined as a state where insulin produces a diminished biological response, primarily in its capacity as a glucose-regulating hormone. Insulin resistance is commonly diagnosed by pediatric clinicians, but is rarely measured directly in children or adolescents. This review provides an overview of the techniques that can be used to assess insulin sensitivity in children, summarizing the methods involved, the assumptions, pitfalls, and appropriate uses of each technique, as well as their validation and reproducibility in pediatric samples. C1 [Brown, Rebecca J.] NIDDK, Diabet Endocrinol & Obes Branch, Bethesda, MD 20892 USA. [Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,Hatfield Clin Res Ctr, 10 Ctr Dive,Bldg 10,Room 1-3330,MSC 1103, Bethesda, MD 20892 USA. EM jy15i@nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU NICHD, NIH; NIDDK, NIH FX The authors are supported by the Intramural Research Programs of NICHD, NIH, and NIDDK, NIH. J. A. Y. is a Commissioned Officer in the US Public Health Service, Department of Health and Human Services. The opinions and assertions expressed herein are those of the authors and are not to be construed as reflecting the views of the US Public Health Service, the National Institutes of Health, or the US Department of Health and Human Services. NR 72 TC 10 Z9 10 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1399-543X EI 1399-5448 J9 PEDIATR DIABETES JI Pediatr. Diabetes PD MAY PY 2014 VL 15 IS 3 BP 151 EP 161 DI 10.1111/pedi.12146 PG 11 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA AH0UL UT WOS:000335836000002 PM 24754463 ER PT J AU Cabana, MD Cheng, TL Bauer, AJ Bogue, CW Chien, AT Dean, JM Scheindlin, B Kelle, A Coyne-Beasley, T DiMeglio, L DeGraw, CA Dougherty, D Freed, GL Guttmacher, AE Minkovitz, C Shalowitz, M Cull, W AF Cabana, Michael D. Cheng, Tina L. Bauer, Andrew J. Bogue, Clifford W. Chien, Alyna T. Dean, J. Michael Scheindlin, Ben Kelle, Angela Coyne-Beasley, Tamera DiMeglio, Linda DeGraw, Christopher A. Dougherty, Denise Freed, Gary L. Guttmacher, Alan E. Minkovitz, Cynthia Shalowitz, Madeleine Cull, William CA Comm Pediat Res TI Promoting Education, Mentorship, and Support for Pediatric Research SO PEDIATRICS LA English DT Article DE pediatric education; training; workforce; epidemiology; health services research; community-based participatory research; translational research; basic science research; postgraduate training ID CLINICAL-RESEARCH; TRANSLATIONAL RESEARCH; PHYSICIAN-SCIENTISTS; CAREER-DEVELOPMENT; HEALTH; PROGRAM; CHALLENGES; PERSPECTIVES; INSTITUTES; MEDICINE AB Pediatricians play a key role in advancing child health research to best attain and improve the physical, mental, and social health and well-being of all infants, children, adolescents, and young adults. Child health presents unique issues that require investigators who specialize in pediatric research. In addition, the scope of the pediatric research enterprise is transdisciplinary and includes the full spectrum of basic science, translational, community-based, health services, and child health policy research. Although most pediatricians do not directly engage in research, knowledge of research methodologies and approaches promotes critical evaluation of scientific literature, the practice of evidence-based medicine, and advocacy for evidence-based child health policy. This statement includes specific recommendations to promote further research education and support at all levels of pediatric training, from premedical to continuing medical education, as well as recommendations to increase support and mentorship for research activities. Pediatric research is crucial to the American Academy of Pediatrics' goal of improving the health of all children. The American Academy of Pediatrics continues to promote and encourage efforts to facilitate the creation of new knowledge and ways to reduce barriers experienced by trainees, practitioners, and academic faculty pursuing research. C1 [DeGraw, Christopher A.] Maternal & Child Hlth Bur, Rockville, MD USA. [Dougherty, Denise] Agcy Healthcare Res & Qual, Rockville, MD USA. [Guttmacher, Alan E.] NICHHD, Rockville, MD USA. OI Kelle, Angela/0000-0002-5222-0916; DiMeglio, Linda/0000-0002-8033-6078 NR 50 TC 3 Z9 3 U1 1 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAY PY 2014 VL 133 IS 5 BP 943 EP 949 DI 10.1542/peds.2014-0448 PG 7 WC Pediatrics SC Pediatrics GA AG2HK UT WOS:000335236800026 ER PT J AU Suren, P Gunnes, N Roth, C Bresnahan, M Hornig, M Hirtz, D Lie, KK Lipkin, WI Magnus, P Reichborn-Kjennerud, T Schjolberg, S Susser, E Oyen, AS Smith, GD Stoltenberg, C AF Suren, Pal Gunnes, Nina Roth, Christine Bresnahan, Michaeline Hornig, Mady Hirtz, Deborah Lie, Kari Kveim Lipkin, W. Ian Magnus, Per Reichborn-Kjennerud, Ted Schjolberg, Synnve Susser, Ezra Oyen, Anne-Siri Smith, George Davey Stoltenberg, Camilla TI Parental Obesity and Risk of Autism Spectrum Disorder SO PEDIATRICS LA English DT Article DE autism spectrum disorder; autistic disorder; Asperger disorder; PDD-NOS; parental obesity; parental BMI; child cohort study ID BODY-MASS INDEX; BIRTH COHORT; BIAS; PREGNANCY; DELETIONS; ORIGIN; ADHD AB OBJECTIVES:The objective of the study was to investigate the associations among maternal prepregnancy BMI, paternal BMI, and the risk of autism spectrum disorders (ASDs) in children.METHODS:The study sample of 92909 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study. The age range was 4.0 through 13.1 (mean 7.4) years. Relative risks of ASDs were estimated by odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models.RESULTS:At the end of follow-up on December 31, 2012, 419 children in the study sample had been diagnosed with ASDs: 162 with autistic disorder, 103 with Asperger disorder, and 154 with pervasive developmental disorder not otherwise specified. Maternal obesity (BMI 30) was only weakly associated with ASD risk, whereas paternal obesity was associated with an increased risk of autistic disorder and Asperger disorder. The risk of autistic disorder was 0.27% (25 of 9267) in children of obese fathers and 0.14% (59 of 41603) in children of fathers with normal weight (BMI <25), generating an adjusted OR of 1.73 (95% CI: 1.07-2.82). For Asperger disorder, analyses were limited to children aged 7 years (n = 50116). The risk was 0.38% (18 of 4761) in children of obese fathers and 0.18% (42 of 22736) in children of normal-weight fathers, and the adjusted OR was 2.01 (95% CI: 1.13-3.57). No associations were found for pervasive developmental disorder not otherwise specified.CONCLUSIONS:Paternal obesity is an independent risk factor for ASDs in children. The associations should be investigated further in genetic and epigenetic studies. C1 [Suren, Pal; Gunnes, Nina; Roth, Christine; Lie, Kari Kveim; Magnus, Per; Reichborn-Kjennerud, Ted; Schjolberg, Synnve; Oyen, Anne-Siri; Stoltenberg, Camilla] Norwegian Inst Publ Hlth, N-0403 Oslo, Norway. [Suren, Pal] UCL Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England. [Gunnes, Nina; Roth, Christine; Bresnahan, Michaeline; Hornig, Mady; Lipkin, W. Ian; Susser, Ezra] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Bresnahan, Michaeline; Susser, Ezra] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Hirtz, Deborah] NINDS, Bethesda, MD 20892 USA. [Reichborn-Kjennerud, Ted] Univ Oslo, Inst Psychiat, Oslo, Norway. [Oyen, Anne-Siri] Lovisenberg Hosp, Nic Waals Inst, Oslo, Norway. [Smith, George Davey] Univ Bristol, MRC, Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England. [Stoltenberg, Camilla] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway. RP Suren, P (reprint author), Norwegian Inst Publ Hlth, POB 4404 Nydalen, N-0403 Oslo, Norway. EM pal.suren@fhi.no RI Davey Smith, George/A-7407-2013 OI Davey Smith, George/0000-0002-1407-8314 FU Medical Research Council [MC_UU_12013/1]; NIEHS NIH HHS [N0-ES-75558, N01ES75558]; NINDS NIH HHS [NS47537, U01 NS047537] NR 31 TC 26 Z9 28 U1 2 U2 25 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAY PY 2014 VL 133 IS 5 BP E1128 EP E1138 DI 10.1542/peds.2013-3664 PG 11 WC Pediatrics SC Pediatrics GA AG2HK UT WOS:000335236800031 PM 24709932 ER PT J AU Chung, CC Hsing, AW Yeboah, E Biritwum, R Tettey, Y Adjei, A Cook, MB De Marzo, A Netto, G Tay, E Boland, JF Yeager, M Chanock, SJ AF Chung, Charles C. Hsing, Ann W. Yeboah, Edward Biritwum, Richard Tettey, Yao Adjei, Andrew Cook, Michael B. De Marzo, Angelo Netto, George Tay, Evelyn Boland, Joseph F. Yeager, Meredith Chanock, Stephen J. TI A comprehensive resequence-analysis of 250 kb region of 8q24.21 in men of African ancestry SO PROSTATE LA English DT Article DE 8q24.21; genetics; prostate cancer ID GENOME-WIDE ASSOCIATION; PROSTATE-CANCER SUSCEPTIBILITY; LONG-RANGE INTERACTION; COLORECTAL-CANCER; RISK LOCI; SNP RS6983267; MYC ENHANCER; IDENTIFIES 5; IN-VIVO; VARIANTS AB BACKGROUND Genome-wide association studies (GWAS) have identified that a similar to 1 M region centromeric to the MYC oncogene on chromosome 8q24.21 harbors at least five independent loci associated with prostate cancer risk and additional loci associated with cancers of breast, colon, bladder, and chronic lymphocytic leukemia (CLL). Because GWAS identify genetic markers that may be indirectly associated with disease, fine-mapping based on sequence analysis provides important insights into patterns of linkage disequilibrium (LD) and is critical in defining the optimal variants to nominate for biological follow-up. METHODS To catalog variation in individuals of African ancestry, we resequenced a region (250 kb; chr8:128,050,768-128,300,801, hg19) containing several prostate cancer susceptibility loci as well as a locus associated with CLL. Our samples included 78 individuals from Ghana and 47 of African-Americans from Johns Hopkins University. RESULTS After quality control metrics were applied to next-generation sequence data, 1,838 SNPs were identified. Of these, 285 were novel and not yet reported in any public database. Using genotypes derived from sequencing, we refined the LD and recombination hotspots within the region and determined a set of tag SNPs to be used in future fine-mapping studies. Based on LD, we annotated putative risk loci and their surrogates using ENCODE data, which should help guide laboratory studies. CONCLUSIONS In comparison to the 1000 Genome Project data, we have identified additional variants that could be important in establishing priorities for future functional work designed to explain the biological basis of associations between SNPs and both prostate cancer and CLL. Prostate 74:579-589, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Chung, Charles C.; Hsing, Ann W.; Cook, Michael B.; Boland, Joseph F.; Yeager, Meredith; Chanock, Stephen J.] NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Chung, Charles C.; Boland, Joseph F.; Yeager, Meredith] SAIC Frederick Inc, Canc Gen Res Lab, Frederick, MD USA. [Chung, Charles C.; Boland, Joseph F.; Yeager, Meredith] Frederick Natl Lab Canc Res, Frederick, MD USA. [Yeboah, Edward] Univ Ghana, Dept Urol, Accra, Ghana. [Biritwum, Richard] Univ Ghana, Dept Epidemiol, Accra, Ghana. [Tettey, Yao; Adjei, Andrew] Univ Ghana, Dept Pathol, Accra, Ghana. [De Marzo, Angelo; Netto, George] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Tay, Evelyn] Korle BuTeaching Hosp, Accra, Ghana. [Tay, Evelyn] Univ Ghana, Sch Med, Accra, Ghana. RP Chanock, SJ (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Adv Technol Center NCI, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM chanocks@mail.nih.gov RI Cook, Michael/A-5641-2009 OI Cook, Michael/0000-0002-0533-7302 FU Intramural NIH HHS [ZIA CP010201-01, Z01 CP010178-06] NR 45 TC 4 Z9 4 U1 1 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-4137 EI 1097-0045 J9 PROSTATE JI Prostate PD MAY PY 2014 VL 74 IS 6 BP 579 EP 589 DI 10.1002/pros.22726 PG 11 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA AD7LN UT WOS:000333445500002 PM 24783269 ER PT J AU Huang, T Li, J Byrd, RA AF Huang, Tao Li, Jess Byrd, R. Andrew TI Solution structure of lysine-free (K0) ubiquitin SO PROTEIN SCIENCE LA English DT Article DE ubiquitin; K0-Ub; NMR; CS-Rosetta ID NMR CHEMICAL-SHIFTS; LIQUID-CRYSTALLINE PHASE; HYDROPHOBIC CORE; PROTEIN-STRUCTURE; DIUBIQUITIN; DYNAMICS; UBIQUITYLATION; RECOGNITION; COUPLINGS; ALIGNMENT AB Lysine-free ubiquitin (K0-Ub) is commonly used to study the ubiquitin-signaling pathway, where it is assumed to have the same structure and function as wild-type ubiquitin (wt-Ub). However, the K0-Ub N-15 heteronuclear single quantum correlation NMR spectrum differs significantly from wt-Ub and the melting temperature is depressed by 19 degrees C, raising the question of the structural integrity and equivalence to wt-Ub. The three-dimensional structure of K0-Ub was determined by solution NMR, using chemical shift and residual dipolar coupling data. K0-Ub adopts the same backbone structure as wt-Ub, and all significant chemical shifts can be related to interactions impacted by the K to R mutations. PDB Code(s): C1 [Huang, Tao; Li, Jess; Byrd, R. Andrew] NCI, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Byrd, RA (reprint author), NCI, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM byrdra@mail.nih.gov RI Byrd, R. Andrew/F-8042-2015 OI Byrd, R. Andrew/0000-0003-3625-4232 FU Intramural Research Program of the National Institutes of Health; National Cancer Institute; Center for Cancer Research FX Grant sponsor: Intramural Research Program of the National Institutes of Health; Grant sponsor: National Cancer Institute; Grant sponsor: Center for Cancer Research. NR 33 TC 1 Z9 1 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0961-8368 EI 1469-896X J9 PROTEIN SCI JI Protein Sci. PD MAY PY 2014 VL 23 IS 5 BP 662 EP 667 DI 10.1002/pro.2450 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AF3DU UT WOS:000334592500015 PM 24591328 ER PT J AU Anjos, SM Cohen, LG Sterr, A de Andrade, KNF Conforto, AB AF Anjos, Sarah M. Cohen, Leonardo G. Sterr, Annette de Andrade, Karina N. F. Conforto, Adriana B. TI Translational Neurorehabilitation Research in the Third World What Barriers to Trial Participation Can Teach Us SO STROKE LA English DT Article DE rehabilitation; stroke ID INDUCED MOVEMENT THERAPY; UPPER EXTREMITY FUNCTION; STROKE INCIDENCE; CASE-FATALITY; REHABILITATION; MANAGEMENT; MORTALITY; BRAZIL AB Background and Purpose Most stroke rehabilitation studies have been performed in high-income countries. The aim of this study was to identify the main barriers for patient inclusion in a research protocol performed in Brazil. MethodsWe evaluated reasons for exclusion of patients in a pilot, randomized, double-blinded clinical trial of stroke rehabilitation. Descriptive statistical analysis was performed. ResultsOnly 5.6% of 571 screened patients were included. Recurrent stroke was responsible for exclusion of 45.4% of potentially eligible patients. ConclusionsRecurrent stroke represented a big barrier to enroll patients in the protocol. External validity of rehabilitation trials will benefit from definition of study criteria according to regional characteristics of patients, including rates of recurrent stroke. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01333579. C1 [Anjos, Sarah M.; de Andrade, Karina N. F.; Conforto, Adriana B.] Univ Sao Paulo, Hosp Clin, Neurol Clin Div, Dept Neurol, Sao Paulo, Brazil. [Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Rehabil Sect, NIH, Bethesda, MD 20892 USA. [Sterr, Annette] Univ Surrey, Sch Psychol, Guildford GU2 5XH, Surrey, England. [Conforto, Adriana B.] Hosp Israelita Albert Einstein, Sao Paulo, Brazil. RP Anjos, SM (reprint author), Univ Sao Paulo, Hosp Clin, Neurol Clin Div, Av Dr Eneas C Aguiar,255-5084, Sao Paulo, Brazil. EM sarah.m.anjos@gmail.com RI DOS ANJOS, SARAH/G-9277-2015 OI DOS ANJOS, SARAH/0000-0002-7792-862X FU Sao Paulo State's Foundation for Research Support (FAPESP) [2006/55504-0]; National Council for Scientific and Technologic Development (CNPq) [301883/2010-6]; FAPESP [2010/15660-8]; National Institutes of Health [D71TW009132-01] FX This study was funded by grant 2006/55504-0 from Sao Paulo State's Foundation for Research Support (FAPESP). Dr Conforto received a research scholarship from the National Council for Scientific and Technologic Development (CNPq-2011-2013; 301883/2010-6). Training scholarships were granted by FAPESP (2010-2012; 2010/15660-8) and by the National Institutes of Health (2012-ongoing; grant D71TW009132-01) to S.M. Anjos. NR 15 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAY PY 2014 VL 45 IS 5 BP 1495 EP 1497 DI 10.1161/STROKEAHA.113.003572 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AG7DK UT WOS:000335578100063 PM 24643406 ER PT J AU Doarn, CR Pruitt, S Jacobs, J Harris, Y Bott, DM Riley, W Lamer, C Oliver, AL AF Doarn, Charles R. Pruitt, Sherilyn Jacobs, Jessica Harris, Yael Bott, David M. Riley, William Lamer, Christopher Oliver, Anthony L. TI Original Research Federal Efforts to Define and Advance Telehealth-A Work in Progress SO TELEMEDICINE AND E-HEALTH LA English DT Article DE telemedicine; telehealth; U; S; Government; healthcare reform ID ARMY TELEMEDICINE; MOBILE HEALTH; TECHNOLOGY; FUTURE; CARE; IMPLEMENTATION; PERSPECTIVES; MANAGEMENT; SUPPORT; HOME AB Background:The integration of telecommunications and information systems in healthcare is not new or novel; indeed, it is the current practice of medicine and has been an integral part of medicine in remote locations for several decades. The U.S. Government has made a significant investment, measured in hundreds of millions of dollars, and therefore has a strong presence in the integration of telehealth/telemedicine in healthcare. However, the terminologies and definitions in the lexicon vary across agencies and departments of the U.S. Government. The objective of our survey was to identify and evaluate the definitions of telehealth/telemedicine across the U.S. Government to provide a better understanding of what each agency or department means when it uses these terms.Methodology:The U.S. Government, under the leadership of the Health Resources and Services Administration in the U.S. Department of Health and Human Services, established the Federal Telemedicine (FedTel) Working Group, through which all members responded to a survey on each agency or department's definition and use of terms associated with telehealth.Results and Conclusions:Twenty-six agencies represented by more than 100 individuals participating in the FedTel Working Group identified seven unique definitions of telehealth in current use across the U.S. Government. Although many definitions are similar, there are nuanced differences that reflect each organization's legislative intent and the population they serve. These definitions affect how telemedicine has been or is being applied across the healthcare landscape, reflecting the U.S. Government's widespread and influential role in healthcare access and service delivery. The evidence base suggests that a common nomenclature for defining telemedicine may benefit efforts to advance the use of this technology to address the changing nature of healthcare and new demands for services expected as a result of health reform. C1 [Doarn, Charles R.] NASA Headquarters, Washington, DC USA. [Doarn, Charles R.] Univ Cincinnati, Coll Med, Dept Family & Community Med, Cincinnati, OH 45267 USA. [Pruitt, Sherilyn; Oliver, Anthony L.] US Dept HHS, Off Adv Telehlth, Rockville, MD USA. [Jacobs, Jessica] Aetna, Washington, DC USA. [Harris, Yael] US Dept HHS, Div Healthcare Qual, Off Dis Prevent & Hlth Promot, Rockville, MD USA. [Bott, David M.] US Dept HHS, Ctr Medicare & Medicaid Serv, Baltimore, MD USA. [Riley, William] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Lamer, Christopher] Indian Hlth Serv, Rockville, MD USA. RP Doarn, CR (reprint author), Univ Cincinnati, Coll Med, Dept Family & Community Med, Cincinnati, OH 45267 USA. EM charles.doarn@uc.edu NR 36 TC 9 Z9 9 U1 0 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 EI 1556-3669 J9 TELEMED E-HEALTH JI Telemed. e-Health PD MAY 1 PY 2014 VL 20 IS 5 BP 409 EP 418 DI 10.1089/tmj.2013.0336 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AG4MG UT WOS:000335393400004 PM 24502793 ER PT J AU Katritch, V Fenalti, G Abola, EE Roth, BL Cherezov, V Stevens, RC AF Katritch, Vsevolod Fenalti, Gustavo Abola, Enrique E. Roth, Bryan L. Cherezov, Vadim Stevens, Raymond C. TI Allosteric sodium in class A GPCR signaling SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review DE GPCR activation; allosteric modulation; biased signaling; conserved pocket; sodium ion; water binding ID PROTEIN-COUPLED RECEPTORS; MU-OPIOID RECEPTOR; MUSCARINIC ACETYLCHOLINE-RECEPTOR; RESOLUTION CRYSTAL-STRUCTURE; ALPHA-ADRENERGIC RECEPTORS; SITE-DIRECTED MUTAGENESIS; A(2A) ADENOSINE RECEPTOR; 2ND TRANSMEMBRANE DOMAIN; AMILORIDE ANALOGS; LIGAND-BINDING AB Despite their functional and structural diversity, G protein-coupled receptors (GPCRs) share a common mechanism of signal transduction via conformational changes in the seven-transmembrane (7TM) helical domain. New major insights into this mechanism come from the recent crystallographic discoveries of a partially hydrated sodium ion that is specifically bound in the middle of the 7TM bundle of multiple class A GPCRs. This review discusses the remarkable structural conservation and distinct features of the Na+ pocket in this most populous GPCR class, as well as the conformational collapse of the pocket upon receptor activation. New insights help to explain allosteric effects of sodium on GPCR agonist binding and activation, and sodium's role as a potential co-factor in class A GPCR function. C1 [Katritch, Vsevolod; Fenalti, Gustavo; Abola, Enrique E.; Cherezov, Vadim; Stevens, Raymond C.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. [Roth, Bryan L.] Univ N Carolina, Chapel Hill Med Sch, Dept Pharmacol, NIMH,Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Chapel Hill Med Sch, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA. RP Katritch, V (reprint author), Scripps Res Inst, Dept Integrat Struct & Computat Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA. EM katritch@scripps.edu RI Roth, Bryan/F-3928-2010; Cherezov, Vadim/L-9812-2013; Katritch, Vsevolod/Q-8357-2016; Stevens, Raymond/K-7272-2015; OI Cherezov, Vadim/0000-0002-5265-3914; Stevens, Raymond/0000-0002-4522-8725; Katritch, Vsevolod/0000-0003-3883-4505 FU National Institute of General Medical Sciences (NIGMS) [U54 GM094618, U19MH82441, R01DA017204] FX This work was supported by the National Institute of General Medical Sciences (NIGMS) PSI:Biology grants U54 GM094618 (V.K., V.C., and R.C.S.), U19MH82441 (B.L.R.), and R01DA017204 (B.L.R.). We thank K. Kadyshevskaya for assistance with figure preparation, A. Walker for assistance with manuscript preparation, C. Tate, K. Jacobson, A. IJzerman, and M. Audet for helpful discussions, and C. Tate for providing unreleased coordinates of the 4BVN structure. NR 106 TC 71 Z9 72 U1 4 U2 35 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 MAY PY 2014 VL 39 IS 5 BP 233 EP 244 DI 10.1016/j.tibs.2014.03.002 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AH8BW UT WOS:000336360100004 PM 24767681 ER PT J AU Viana, M Mancy, R Biek, R Cleaveland, S Cross, PC Lloyd-Smith, JO Haydon, DT AF Viana, Mafalda Mancy, Rebecca Biek, Roman Cleaveland, Sarah Cross, Paul C. Lloyd-Smith, James O. Haydon, Daniel T. TI Assembling evidence for identifying reservoirs of infection SO TRENDS IN ECOLOGY & EVOLUTION LA English DT Review ID CANINE-DISTEMPER VIRUS; APPROXIMATE BAYESIAN COMPUTATION; CRITICAL COMMUNITY SIZE; METAPOPULATION DYNAMICS; DOMESTIC DOGS; VISCERAL LEISHMANIASIS; TRANSMISSION RATES; RABIES ELIMINATION; POPULATION SIZES; UNITED-STATES AB Many pathogens persist in multihost systems, making the identification of infection reservoirs crucial for devising effective interventions. Here, we present a conceptual framework for classifying patterns of incidence and prevalence, and review recent scientific advances that allow us to study and manage reservoirs simultaneously. We argue that interventions can have a crucial role in enriching our mechanistic understanding of how reservoirs function and should be embedded as quasi-experimental studies in adaptive management frameworks. Single approaches to the study of reservoirs are unlikely to generate conclusive insights whereas the formal integration of data and methodologies, involving interventions, pathogen genetics, and contemporary surveillance techniques, promises to open up new opportunities to advance understanding of complex multihost systems. C1 [Viana, Mafalda; Mancy, Rebecca; Biek, Roman; Cleaveland, Sarah; Haydon, Daniel T.] Univ Glasgow, Coll Med Vet & Life Sci, Inst Biodivers Anim Hlth & Comparat Med, Boyd Orr Ctr Populat & Ecosyst Hlth, Glasgow G12 8QQ, Lanark, Scotland. [Mancy, Rebecca] Univ Glasgow, Sch Comp Sci, Glasgow G12 8QQ, Lanark, Scotland. [Biek, Roman; Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Cross, Paul C.] US Geol Survey, Northern Rocky Mt Sci Ctr, Bozeman, MT 59715 USA. [Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. RP Viana, M (reprint author), Univ Glasgow, Coll Med Vet & Life Sci, Inst Biodivers Anim Hlth & Comparat Med, Boyd Orr Ctr Populat & Ecosyst Hlth, Glasgow G12 8QQ, Lanark, Scotland. EM mafalda.viana@glasgow.ac.uk RI Lloyd-Smith, James/K-4080-2012; Cross, Paul/K-6987-2012; OI Lloyd-Smith, James/0000-0001-7941-502X; Cross, Paul/0000-0001-8045-5213; Haydon, Daniel/0000-0002-1240-1886; Biek, Roman/0000-0003-3471-5357 FU RAPIDD programme of the Science and Technology Directorate of the US Department of Homeland Security; National Institutes of Health Fogarty International Center; Newton International Fellowship from The Royal Society; EPSRC [EP/P505534/1]; NIH [RO1 AI047498]; National Science Foundation [OCE-1335657]; De Logi Chair in Biological Sciences; UK Medical Research Council [G0901135]; BBSRC [BB/H009302/1, BB/J010367/1] FX This paper has roots in discussions at a 2010 workshop sponsored by the RAPIDD programme of the Science and Technology Directorate of the US Department of Homeland Security and National Institutes of Health Fogarty International Center. We are grateful for comments contributed by Seth Blumberg and Juliet Pulliam at that workshop. We also thank Daniel Streicker and Andy Fenton for comments on this manuscript. M.V. is funded by a Newton International Fellowship from The Royal Society, R.M. is funded by EPSRC grant EP/P505534/1, R.B. is supported by NIH grant RO1 AI047498, J.L-S. is funded by National Science Foundation grant OCE-1335657 and the De Logi Chair in Biological Sciences, D.T.H. is funded by the UK Medical Research Council (grant G0901135), and S.C. is supported by the BBSRC (grant BB/H009302/1 and BB/J010367/1). Any mention of trade, product, or firm names is for descriptive purposes only and does not imply endorsement by the US Government. NR 98 TC 42 Z9 43 U1 4 U2 54 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0169-5347 J9 TRENDS ECOL EVOL JI Trends Ecol. Evol. PD MAY PY 2014 VL 29 IS 5 BP 270 EP 279 DI 10.1016/j.tree.2014.03.002 PG 10 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA AH4QR UT WOS:000336113600006 PM 24726345 ER PT J AU Nussinov, R Tsai, CJ AF Nussinov, Ruth Tsai, Chung-Jung TI Unraveling structural mechanisms of allosteric drug action SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review DE allosteric drug discovery; protocol; agonist; antagonist; driver atom; anchor atom; allostery ID PROTEIN-KINASE PDK1; RECEPTOR ACTIVATION; 2-STATE MODEL; PATHWAYS; SITES; COMMUNICATION; NETWORKS; DYNAMICS; MODULATION; INHIBITION AB Orthosteric drugs block the active site to obstruct function; allosteric drugs modify the population of the active state, to modulate function. Available data lead us to propose that allosteric drugs can constitute anchors and drivers. The anchor docks into an allosteric pocket. The conformation with which it interacts is unchanged during the transition between the inactive and active states. The anchor provides the foundation that allows the driver to exert a 'pull' and/or 'push' action that shifts the receptor population from the inactive to the active state. The presence or absence of driver atom in an allosteric drug can exert opposite agonism. We map a strategy for driver identification and expect the allosteric trigger concept to transform agonist/antagonist drug discovery. C1 [Nussinov, Ruth; Tsai, Chung-Jung] Leidos Biomed Res Inc, NCI, Frederick Natl Lab Canc Res, Canc & Inflammat Program, Frederick, MD 21702 USA. [Nussinov, Ruth] 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), Leidos Biomed Res Inc, NCI, Frederick Natl Lab Canc Res, Canc & Inflammat Program, Frederick, MD 21702 USA. EM NussinoR@helix.nih.gov FU National Cancer Institute, National Institutes of Health (NIH) [HHSN261200800001E]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health (NIH) under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 64 TC 42 Z9 42 U1 8 U2 40 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAY PY 2014 VL 35 IS 5 BP 256 EP 264 DI 10.1016/j.tips.2014.03.006 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AH5SB UT WOS:000336190300006 PM 24742712 ER PT J AU Shin, EH Caterson, EJ Jackson, WM Nesti, LJ AF Shin, Emily H. Caterson, Edward J. Jackson, Wesley M. Nesti, Leon J. TI Quality of healing: Defining, quantifying, and enhancing skeletal muscle healing SO WOUND REPAIR AND REGENERATION LA English DT Article ID MESENCHYMAL STEM-CELLS; PROGENITOR CELLS; ENDOTHELIAL-CELLS; STRETCH INJURY; MYOGENIC CELLS; SATELLITE CELL; STROMAL CELLS; DIFFERENTIATION; TISSUE; REPAIR AB Skeletal muscle injury is common in everyday physical activity and athletics, as well as in orthopedic trauma and disease. The overall functional disability resulting from muscle injury is directly related to the intrinsic healing properties of muscle and extrinsic treatment options designed to maximize repair and/or regeneration of muscle tissue all while minimizing pathologic healing pathways. It is important to understand the injury and repair pathways in order to improve the speed and quality of recovery. Recent military conflicts in Iraq and Afghanistan have highlighted the importance of successfully addressing muscular injury and showed the need for novel treatment options that will maximize functional regeneration of the damaged tissue. These severe, wartime injuries, when juxtaposed to peacetime, sports-related injuries, provide us with interesting case examples of the two extreme forms of muscular damage. Comparing and contrasting the differences in these healing pathways will likely provide helpful cues that will help physicians recapitulate the near complete repair and regeneration in less traumatic injuries in addition to more severe cases. C1 [Shin, Emily H.; Nesti, Leon J.] NIAMSD, Dept Orthopaed Surg, Walter Reed Natl Mil Med Ctr, NIH, Bethesda, MD 20892 USA. [Shin, Emily H.; Nesti, Leon J.] NIAMSD, Clin & Expt Orthopaed Grp, NIH, Bethesda, MD 20892 USA. [Jackson, Wesley M.; Nesti, Leon J.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. [Caterson, Edward J.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Nesti, LJ (reprint author), NIAMSD, NIH, Bldg 50,Room 1146,50 South Dr,MSC 8022, Bethesda, MD 20892 USA. EM leonnesti@gmail.com FU Department of Defense [DMRDP D10_1_AR_J5_920, USAMRAA W81XWH-09-2-0154] FX We would like to thank the Department of Defense for their generous support of this important work (DMRDP D10_1_AR_J5_920 and USAMRAA W81XWH-09-2-0154). NR 65 TC 4 Z9 4 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1067-1927 EI 1524-475X J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAY PY 2014 VL 22 SU 1 SI SI BP 18 EP 24 DI 10.1111/wrr.12163 PG 7 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA AG9SU UT WOS:000335760800005 PM 24813360 ER PT J AU Gangjee, A Pavana, RK Ihnat, MA Thorpe, JE Disch, BC Bastian, A Bailey-Downs, LC Hamel, E Bai, R AF Gangjee, Aleem Pavana, Roheeth Kumar Ihnat, Michael A. Thorpe, Jessica E. Disch, Bryan C. Bastian, Anja Bailey-Downs, Lora C. Hamel, Ernest Bai, Rouli TI Discovery of Antitubulin Agents with Antiangiogenic Activity as Single Entities with Multitarget Chemotherapy Potential SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Antitubulin; antimitotic; antiangiogenic; VEGFR2 inhibition; combination chemotherapy ID RECEPTOR TYROSINE KINASE; ANTI-ANGIOGENIC THERAPY; ANTITUMOR AGENTS; INHIBITORS; RESISTANCE; DESIGN AB Antiangiogenic agents (AA) are cytostatic, and their utility in cancer chemotherapy lies in their combination with cytotoxic chemotherapeutic agents. Clinical combinations of vascular endothelial growth factor receptor-2 (VEGFR2) inhibitors with antitubulin agents have been particularly successful. We have discovered a novel, potentially important analogue, that combines potent VEGFR2 inhibitory activity (comparable to that of sunitinib) with potent antitubulin activity (comparable to that of combretastatin A-4 (CA)) in a single molecule, with GI(50) values of 10(-7) M across the entire NCI 60 tumor cell panel. It potently inhibited tubulin assembly and circumvented the most clinically relevant tumor resistance mechanisms (P-glycoprotein and beta-III tubulin expression) to antimicrotubule agents. The compound is freely water-soluble as its HCl salt and afforded excellent antitumor activity in vivo, superior to docetaxel, sunitinib, or Temozolomide, without any toxicity. C1 [Gangjee, Aleem; Pavana, Roheeth Kumar] Duquesne Univ, Grad Sch Pharmaceut Sci, Div Med Chem, Pittsburgh, PA 15282 USA. [Ihnat, Michael A.; Thorpe, Jessica E.; Bastian, Anja; Bailey-Downs, Lora C.] Univ Oklahoma, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK 73117 USA. [Hamel, Ernest; Bai, Rouli] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA. RP Gangjee, A (reprint author), Duquesne Univ, Grad Sch Pharmaceut Sci, Div Med Chem, Pittsburgh, PA 15282 USA. EM gangjee@duq.edu RI Pavana, Roheeth/F-5839-2017 OI Pavana, Roheeth/0000-0001-6256-3683 FU NIH [CA136944, CA114021]; Duquesne University Adrian Van Kaam Chair in Scholarly Excellence; NSF [CHE 0614785] FX This work was supported, in part, by NIH Grants CA136944 (to A.G.), CA114021 (to A.G.), the Duquesne University Adrian Van Kaam Chair in Scholarly Excellence (to A.G.), and NSF equipment grant CHE 0614785 (for the NMR). NR 14 TC 7 Z9 7 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD MAY PY 2014 VL 5 IS 5 BP 480 EP 484 DI 10.1021/ml4004793 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AH1KP UT WOS:000335879300008 PM 24900865 ER PT J AU Liggins, C Snyder, HM Silverberg, N Petanceska, S Refolo, LM Ryan, L Carrillo, MC AF Liggins, Charlene Snyder, Heather M. Silverberg, Nina Petanceska, Suzana Refolo, Lorenzo M. Ryan, Laurie Carrillo, Maria C. TI International Alzheimer's Disease Research Portfolio (IADRP) aims to capture global Alzheimer's disease research funding SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Research classification; Biomedical research; Ontology AB Alzheimer's disease (AD) is a recognized international public health crisis. There is an urgent need for public and private funding agencies around the world to coordinate funding strategies and leverage existing resources to enhance and expand support of AD research. To capture and compare their existing investments in AD research and research-related resources, major funding organizations are starting to utilize the Common Alzheimer's Disease Research Ontology (CADRO) to categorize their funding information. This information is captured in the International Alzheimer's Disease Research Portfolio (IADRP) for further analysis. As of January, 2014, over fifteen organizations from the US, Canada, Europe and Australia have contributed their information. The goal of the IADRP project is to enable funding organizations to assess the changing landscape of AD research and coordinate strategies, leverage resources, and avoid duplication of effort. (C) 2014 The Alzheimer's Association. All rights reserved. C1 [Liggins, Charlene] NIA, Off Planning Anal & Evaluat, NIH, Bethesda, MD 20892 USA. [Snyder, Heather M.; Carrillo, Maria C.] Alzheimers Assoc, Chicago, IL 60631 USA. [Silverberg, Nina; Petanceska, Suzana; Refolo, Lorenzo M.; Ryan, Laurie] NIA, Div Neurosci, NIH, Bethesda, MD 20892 USA. RP Snyder, HM (reprint author), Alzheimers Assoc, Chicago, IL 60631 USA. EM heather.snyder@alz.org NR 1 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2014 VL 10 IS 3 BP 405 EP 408 DI 10.1016/j.jalz.2013.12.013 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AG7WG UT WOS:000335628900016 PM 24780512 ER PT J AU Ablashi, D Agut, H Alvarez-Lafuente, R Clark, DA Dewhurst, S DiLuca, D Flamand, L Frenkel, N Gallo, R Gompels, UA Hollsberg, P Jacobson, S Luppi, M Lusso, P Malnati, M Medveczky, P Mori, Y Pellett, PE Pritchett, JC Yamanishi, K Yoshikawa, T AF Ablashi, Dharam Agut, Henri Alvarez-Lafuente, Roberto Clark, Duncan A. Dewhurst, Stephen DiLuca, Dario Flamand, Louis Frenkel, Niza Gallo, Robert Gompels, Ursula A. Hollsberg, Per Jacobson, Steven Luppi, Mario Lusso, Paolo Malnati, Mauro Medveczky, Peter Mori, Yasuko Pellett, Philip E. Pritchett, Joshua C. Yamanishi, Koichi Yoshikawa, Tetsushi TI Classification of HHV-6A and HHV-6B as distinct viruses SO ARCHIVES OF VIROLOGY LA English DT Review ID HUMAN-HERPESVIRUS 6; HUMAN-HERPESVIRUS-6 VARIANT-A; MULTIPLE-SCLEROSIS PATIENTS; POLYMERASE-CHAIN-REACTION; STEM-CELL TRANSPLANTATION; HEALTHY BLOOD-DONORS; MESSENGER-RNA LEVELS; REAL-TIME PCR; GLYCOPROTEIN-H; FOLLOW-UP AB Shortly after the discovery of human herpesvirus 6 (HHV-6), two distinct variants, HHV-6A and HHV-6B, were identified. In 2012, the International Committee on Taxonomy of Viruses (ICTV) classified HHV-6A and HHV-6B as separate viruses. This review outlines several of the documented epidemiological, biological, and immunological distinctions between HHV-6A and HHV-6B, which support the ICTV classification. The utilization of virus-specific clinical and laboratory assays for distinguishing HHV-6A and HHV-6B is now required for further classification. For clarity in biological and clinical distinctions between HHV-6A and HHV-6B, scientists and physicians are herein urged, where possible, to differentiate carefully between HHV-6A and HHV-6B in all future publications. C1 [Ablashi, Dharam; Pritchett, Joshua C.] HHV 6 Fdn, Santa Barbara, CA USA. [Agut, Henri] UPMC Paris 06, Grp Hosp Pitie Salpetriere, Paris, France. [Alvarez-Lafuente, Roberto] Hosp Clin San Carlos, Madrid, Spain. [Clark, Duncan A.] Barts Hlth NHS Trust, London, England. [Dewhurst, Stephen] Univ Rochester, Med Ctr, Rochester, NY 14627 USA. [DiLuca, Dario] Univ Ferrara, I-44100 Ferrara, Italy. [Flamand, Louis] Univ Laval, Quebec City, PQ, Canada. [Frenkel, Niza] Tel Aviv Univ, Inst Mol Virol, IL-69978 Tel Aviv, Israel. [Gallo, Robert] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Gompels, Ursula A.] Univ London, London Sch Hyg & Trop Med, London, England. [Hollsberg, Per] Aarhus Univ, Aarhus, Denmark. [Jacobson, Steven] NINDS, NIH, Bethesda, MD 20892 USA. [Luppi, Mario] Univ Modena & Reggio Emilia, Dept Med & Surg Sci, Modena, Italy. [Lusso, Paolo] NIAID, NIH, Bethesda, MD 20892 USA. [Malnati, Mauro] OSR Sci Inst, Milan, Italy. [Medveczky, Peter] Univ S Florida, Tampa, FL USA. [Mori, Yasuko] Kobe Univ, Grad Sch Med, Osaka, Japan. [Pellett, Philip E.] Wayne State Univ, Sch Med, Detroit, MI USA. [Yamanishi, Koichi] Osaka Univ, Res Fdn Microbial Dis, Osaka, Japan. [Yoshikawa, Tetsushi] Fujita Hlth Univ, Sch Med, Toyoake, Aichi 47011, Japan. RP Ablashi, D (reprint author), HHV 6 Fdn, Santa Barbara, CA USA. EM Dharam_Ablashi@HHV-6Foundation.org RI Di Luca, Dario/M-9781-2014; Luppi, Mario/J-3668-2016; OI Di Luca, Dario/0000-0001-9643-9170; Luppi, Mario/0000-0002-0373-1154; Medveczky, Peter/0000-0002-1798-2595; Dewhurst, Stephen/0000-0001-7729-7920 FU Intramural NIH HHS [Z01 NS002817-18, Z01 NS002817-19, Z01 NS003040-01] NR 134 TC 51 Z9 53 U1 0 U2 14 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0304-8608 EI 1432-8798 J9 ARCH VIROL JI Arch. Virol. PD MAY PY 2014 VL 159 IS 5 BP 863 EP 870 DI 10.1007/s00705-013-1902-5 PG 8 WC Virology SC Virology GA AG9ZB UT WOS:000335777600003 PM 24193951 ER PT J AU Kuhn, JH Bao, YM Bavari, S Becker, S Bradfute, S Brauburger, K Brister, JR Bukreyev, AA Cai, YY Chandran, K Davey, RA Dolnik, O Dye, JM Enterlein, S Gonzalez, JP Formenty, P Freiberg, AN Hensley, LE Hoenen, T Honko, AN Ignatyev, GM Jahrling, PB Johnson, KM Klenk, HD Kobinger, G Lackemeyer, MG Leroy, EM Lever, MS Muhlberger, E Netesov, SV Olinger, GG Palacios, G Patterson, JL Paweska, JT Pitt, L Radoshitzky, SR Ryabchikova, EI Saphire, EO Shestopalov, AM Smither, SJ Sullivan, NJ Swanepoel, R Takada, A Towner, JS van der Groen, G Volchkov, VE Volchkova, VA Wahl-Jensen, V Warren, TK Warfield, KL Weidmann, M Nichol, ST AF Kuhn, Jens H. Bao, Yiming Bavari, Sina Becker, Stephan Bradfute, Steven Brauburger, Kristina Brister, J. Rodney Bukreyev, Alexander A. Cai, Yingyun Chandran, Kartik Davey, Robert A. Dolnik, Olga Dye, John M. Enterlein, Sven Gonzalez, Jean-Paul Formenty, Pierre Freiberg, Alexander N. Hensley, Lisa E. Hoenen, Thomas Honko, Anna N. Ignatyev, Georgy M. Jahrling, Peter B. Johnson, Karl M. Klenk, Hans-Dieter Kobinger, Gary Lackemeyer, Matthew G. Leroy, Eric M. Lever, Mark S. Muehlberger, Elke Netesov, Sergey V. Olinger, Gene G. Palacios, Gustavo Patterson, Jean L. Paweska, Janusz T. Pitt, Louise Radoshitzky, Sheli R. Ryabchikova, Elena I. Saphire, Erica Ollmann Shestopalov, Aleksandr M. Smither, Sophie J. Sullivan, Nancy J. Swanepoel, Robert Takada, Ayato Towner, Jonathan S. van der Groen, Guido Volchkov, Viktor E. Volchkova, Valentina A. Wahl-Jensen, Victoria Warren, Travis K. Warfield, Kelly L. Weidmann, Manfred Nichol, Stuart T. TI Virus nomenclature below the species level: a standardized nomenclature for filovirus strains and variants rescued from cDNA SO ARCHIVES OF VIROLOGY LA English DT Article ID RECOMBINANT MARBURG VIRUS; EBOLA-VIRUS; FAMILY FILOVIRIDAE; CELL-CULTURE; GUINEA-PIGS; IRF-3 ACTIVATION; IN-VITRO; REPLICATION; TRANSCRIPTION; DOMAINS AB Specific alterations (mutations, deletions, insertions) of virus genomes are crucial for the functional characterization of their regulatory elements and their expression products, as well as a prerequisite for the creation of attenuated viruses that could serve as vaccine candidates. Virus genome tailoring can be performed either by using traditionally cloned genomes as starting materials, followed by site-directed mutagenesis, or by de novo synthesis of modified virus genomes or parts thereof. A systematic nomenclature for such recombinant viruses is necessary to set them apart from wild-type and laboratory-adapted viruses, and to improve communication and collaborations among researchers who may want to use recombinant viruses or create novel viruses based on them. A large group of filovirus experts has recently proposed nomenclatures for natural and laboratory animal-adapted filoviruses that aim to simplify the retrieval of sequence data from electronic databases. Here, this work is extended to include nomenclature for filoviruses obtained in the laboratory via reverse genetics systems. The previously developed template for natural filovirus genetic variant naming, < virus name > (< strain >/)< isolation host-suffix >/< country of sampling >/< year of sampling >/< genetic variant designation >-< isolate designation >, is retained, but we propose to adapt the type of information added to each field for cDNA clone-derived filoviruses. For instance, the full-length designation of an Ebola virus Kikwit variant rescued from a plasmid developed at the US Centers for Disease Control and Prevention could be akin to "Ebola virus H.sapiens-rec/COD/1995/Kikwit-abc1" (with the suffix "rec" identifying the recombinant nature of the virus and "abc1" being a placeholder for any meaningful isolate designator). Such a full-length designation should be used in databases and the methods section of publications. Shortened designations (such as "EBOV H.sap/COD/95/Kik-abc1") and abbreviations (such as "EBOV/Kik-abc1") could be used in the remainder of the text, depending on how critical it is to convey information contained in the full-length name. "EBOV" would suffice if only one EBOV strain/variant/isolate is addressed. C1 [Kuhn, Jens H.; Cai, Yingyun; Hensley, Lisa E.; Jahrling, Peter B.; Lackemeyer, Matthew G.; Wahl-Jensen, Victoria] NIAID, Integrated Res Facil Ft Detrick IRF Frederick, DCR, NIH, Frederick, MD 21702 USA. [Bao, Yiming; Brister, J. Rodney] NIH, Informat Engn Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Bavari, Sina; Dye, John M.; Honko, Anna N.; Olinger, Gene G.; Palacios, Gustavo; Pitt, Louise; Radoshitzky, Sheli R.; Warren, Travis K.] United States Army Med Res Inst Infect Dis, Frederick, MD USA. [Becker, Stephan; Dolnik, Olga; Klenk, Hans-Dieter] Univ Marburg, Inst Virol, D-35032 Marburg, Germany. [Bradfute, Steven] Univ New Mexico, Albuquerque, NM 87131 USA. [Brauburger, Kristina; Muehlberger, Elke] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. [Brauburger, Kristina; Muehlberger, Elke] Boston Univ, Sch Med, Natl Emerging Infect Dis Lab, Boston, MA 02118 USA. [Bukreyev, Alexander A.; Freiberg, Alexander N.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Bukreyev, Alexander A.; Freiberg, Alexander N.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Chandran, Kartik] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Davey, Robert A.; Patterson, Jean L.] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX USA. [Enterlein, Sven; Warfield, Kelly L.] Integrated BioTherapeut Inc, Gaithersburg, MD USA. [Gonzalez, Jean-Paul] Inst Rech Dev, Dept Hlth, Marseille, France. [Gonzalez, Jean-Paul] Metabiota Inc, San Francisco, CA USA. [Formenty, Pierre] World Hlth Org, Geneva, Switzerland. [Hoenen, Thomas] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA. [Ignatyev, Georgy M.] Minist Hlth Russian Federat, Fed State Unitary Co Microgen Sci Ind Co Immunobi, Moscow, Russia. [Kobinger, Gary] Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada. [Leroy, Eric M.] Ctr Int Rech Med Franceville, Franceville, Gabon. [Lever, Mark S.; Smither, Sophie J.] Dstl, Dept Biomed Sci, Salisbury, Wilts, England. [Netesov, Sergey V.; Shestopalov, Aleksandr M.] Novosibirsk State Univ, Novosibirsk 630090, Novosibirsk Reg, Russia. [Paweska, Janusz T.] Natl Inst Communicable Dis, Ctr Emerging & Zoonot Dis, Natl Hlth Lab Serv, Sandringham Johannesburg, Gauteng, South Africa. [Ryabchikova, Elena I.] Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, Novosibirsk, Novosibirsk Reg, Russia. [Saphire, Erica Ollmann] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Saphire, Erica Ollmann] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Shestopalov, Aleksandr M.] State Res Ctr Virol & Biotechnol Vector, Koltsov, Novosibirsk Reg, Russia. [Sullivan, Nancy J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Swanepoel, Robert] Univ Pretoria, Zoonoses Res Unit, ZA-0002 Pretoria, South Africa. [Takada, Ayato] Hokkaido Univ, Res Ctr Zoonosis Control, Div Global Epidemiol, Sapporo, Hokkaido, Japan. [Towner, Jonathan S.; Nichol, Stuart T.] Ctr Dis Control & Prevent CDC, Natl Ctr Emerging & Zoonot Infect Dis NCEZID, Div High Consequence Pathogens Pathol DHCPP, Viral Special Pathogens Branch VSPB, Atlanta, GA 30333 USA. [van der Groen, Guido] Prins Leopold Inst Trop Geneeskunde, Antwerp, Belgium. [Volchkov, Viktor E.; Volchkova, Valentina A.] Univ Lyon, Lab Filovirus, INSERM, U758,UCB Lyon 1,Ecole Normale Super Lyon, Lyon, France. [Weidmann, Manfred] Univ Med Gottingen, Abt Virol, Gottingen, Germany. RP Kuhn, JH (reprint author), NIAID, Integrated Res Facil Ft Detrick IRF Frederick, DCR, NIH, B-8200 Res Plaza, Frederick, MD 21702 USA. EM kuhnjens@mail.nih.gov; stn1@cdc.gov RI LEROY, Eric/I-4347-2016; Volchkov, Viktor/M-7846-2014; Kuhn, Jens H./B-7615-2011; Ryabchikova, Elena /G-3089-2013; Netesov, Sergey/A-3751-2013; Becker, Stephan/A-1065-2010; Palacios, Gustavo/I-7773-2015; Weidmann, Manfred/G-1817-2015; OI LEROY, Eric/0000-0003-0022-0890; Hoenen, Thomas/0000-0002-5829-6305; Volchkov, Viktor/0000-0001-7896-8706; Kuhn, Jens H./0000-0002-7800-6045; Ryabchikova, Elena /0000-0003-4714-1524; Netesov, Sergey/0000-0002-7786-2464; Becker, Stephan/0000-0002-2794-5659; Palacios, Gustavo/0000-0001-5062-1938; Weidmann, Manfred/0000-0002-7063-7491; Shestopalov, Alexander/0000-0002-9734-0620; Honko, Anna/0000-0001-9165-148X FU Joint Science and Technology Office for Chem Bio Defense [TMTI0048_09_RD_T]; NIAID [HHSN272200700016I]; Intramural Research Program of the NIH, National Library of Medicine; Intramural Research Program of the NIH, NIAID FX The content of this publication does not necessarily reflect the views or policies of the US Department of the Army, the US Department of Defense or the US Department of Health and Human Services or of the institutions and companies affiliated with the authors. This work was funded in part by the Joint Science and Technology Office for Chem Bio Defense (proposal #TMTI0048_09_RD_T to SB). YC, JHK, and VWJ performed this work as employees of Tunnell Consulting, Inc., and MGL as an employee of Lovelace Respiratory Research Institute, both subcontractors to Battelle Memorial Institute under its prime contract with NIAID, under Contract No. HHSN272200700016I. This research was also supported in part by the Intramural Research Program of the NIH, National Library of Medicine (YB and JRB), and the Intramural Research Program of the NIH, NIAID (TH). NR 35 TC 26 Z9 28 U1 0 U2 21 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0304-8608 EI 1432-8798 J9 ARCH VIROL JI Arch. Virol. PD MAY PY 2014 VL 159 IS 5 BP 1229 EP 1237 DI 10.1007/s00705-013-1877-2 PG 9 WC Virology SC Virology GA AG9ZB UT WOS:000335777600048 PM 24190508 ER PT J AU Cotmore, SF Agbandje-McKenna, M Chiorini, JA Mukha, DV Pintel, DJ Qiu, JM Soderlund-Venermo, M Tattersall, P Tijssen, P Gatherer, D Davison, AJ AF Cotmore, Susan F. Agbandje-McKenna, Mavis Chiorini, John A. Mukha, Dmitry V. Pintel, David J. Qiu, Jianming Soderlund-Venermo, Maria Tattersall, Peter Tijssen, Peter Gatherer, Derek Davison, Andrew J. TI The family Parvoviridae SO ARCHIVES OF VIROLOGY LA English DT Article ID VIRUSES AB A set of proposals to rationalize and extend the taxonomy of the family Parvoviridae is currently under review by the International Committee on Taxonomy of Viruses (ICTV). Viruses in this family infect a wide range of hosts, as reflected by the longstanding division into two subfamilies: the Parvovirinae, which contains viruses that infect vertebrate hosts, and the Densovirinae, encompassing viruses that infect arthropod hosts. Using a modified definition for classification into the family that no longer demands isolation as long as the biological context is strong, but does require a near-complete DNA sequence, 134 new viruses and virus variants were identified. The proposals introduce new species and genera into both subfamilies, resolve one misclassified species, and improve taxonomic clarity by employing a series of systematic changes. These include identifying a precise level of sequence similarity required for viruses to belong to the same genus and decreasing the level of sequence similarity required for viruses to belong to the same species. These steps will facilitate recognition of the major phylogenetic branches within genera and eliminate the confusion caused by the near-identity of species and viruses. Changes to taxon nomenclature will establish numbered, non-Latinized binomial names for species, indicating genus affiliation and host range rather than recapitulating virus names. Also, affixes will be included in the names of genera to clarify subfamily affiliation and reduce the ambiguity that results from the vernacular use of "parvovirus" and "densovirus" to denote multiple taxon levels. C1 [Cotmore, Susan F.; Tattersall, Peter] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA. [Agbandje-McKenna, Mavis] Univ Florida, Coll Med, Dept Biochem & Mol Biol, Ctr Struct Biol,McKnight Brain Inst, Gainesville, FL 32610 USA. [Chiorini, John A.] NIH, Mol Physiol & Therapeut Branch, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. [Mukha, Dmitry V.] Russian Acad Sci, Vavilov Inst Gen Genet, Moscow 119991, Russia. [Pintel, David J.] Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Life Sci Ctr, Columbia, MO 65212 USA. [Qiu, Jianming] Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66103 USA. [Soderlund-Venermo, Maria] Univ Helsinki, Dept Virol, Haartman Inst, Helsinki, Finland. [Tattersall, Peter] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Tijssen, Peter] INRS Inst Armand Frappier, Laval, PQ, Canada. [Gatherer, Derek; Davison, Andrew J.] Univ Glasgow, Ctr Virus Res, MRC, Glasgow, Lanark, Scotland. RP Cotmore, SF (reprint author), Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA. EM susan.cotmore@yale.edu OI Gatherer, Derek/0000-0002-7385-5734 FU Public Health Service grants from the National Institutes of Health [CA029303, AI026109, AI046458, AI091588, AI070723, GM082946]; National Science Foundation [MCB 0718948]; UK Medical Research Council; Helsinki University Research Funds; Natural Sciences and Engineering Research Council of Canada; Juselius Foundation, Finland FX This work was supported in part by Public Health Service grants from the National Institutes of Health (CA029303 and AI026109), SFC and PTa; (AI046458 and AI091588), DJP; (AI070723), JQ; (GM082946), MAM; the National Science Foundation (MCB 0718948), MAM; the UK Medical Research Council, AD and DG; the Helsinki University Research Funds and Juselius Foundation, Finland, MSV; and the Natural Sciences and Engineering Research Council of Canada, PTi. NR 16 TC 112 Z9 119 U1 7 U2 28 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0304-8608 EI 1432-8798 J9 ARCH VIROL JI Arch. Virol. PD MAY PY 2014 VL 159 IS 5 BP 1239 EP 1247 DI 10.1007/s00705-013-1914-1 PG 9 WC Virology SC Virology GA AG9ZB UT WOS:000335777600049 PM 24212889 ER PT J AU Huber, AM Mamyrova, G Lachenbruch, PA Lee, JA Katz, JD Targoff, IN Miller, FW Rider, LG AF Huber, Adam M. Mamyrova, Gulnara Lachenbruch, Peter A. Lee, Julia A. Katz, James D. Targoff, Ira N. Miller, Frederick W. Rider, Lisa G. CA Childhood Myositis Heterogeneity TI Early Illness Features Associated With Mortality in the Juvenile Idiopathic Inflammatory Myopathies SO ARTHRITIS CARE & RESEARCH LA English DT Article ID LONG-TERM SURVIVAL; CLINICAL CHARACTERISTICS; DERMATOMYOSITIS; POLYMYOSITIS; MYOSITIS; OUTCOMES; CLASSIFICATION; AUTOANTIBODY; PHENOTYPES; CHILDHOOD AB Objective Because juvenile idiopathic inflammatory myopathies (IIMs) are potentially life-threatening systemic autoimmune diseases, we examined risk factors for juvenile IIM mortality. Methods Mortality status was available for 405 patients (329 with juvenile dermatomyositis [DM], 30 with juvenile polymyositis [PM], and 46 with juvenile connective tissue disease-associated myositis [CTM]) enrolled in nationwide protocols. Standardized mortality ratios (SMRs) were calculated using US population statistics. Cox regression analysis was used to assess univariable associations with mortality, and random survival forest (RSF) classification and Cox regression analysis were used for multivariable associations. Results Of 17 deaths (4.2% overall mortality), 8 (2.4%) were in juvenile DM patients. Death was related to the pulmonary system (primarily interstitial lung disease [ILD]) in 7 patients, gastrointestinal system in 3, and multisystem in 3, and of unknown etiology in 4 patients. The SMR for juvenile IIMs overall was 14.4 (95% confidence interval [95% CI] 12.2-16.5) and was 8.3 (95% CI 6.4-10.3) for juvenile DM. The top mortality risk factors in the univariable analysis included clinical subgroup (juvenile CTM, juvenile PM), antisynthetase autoantibodies, older age at diagnosis, ILD, and Raynaud's phenomenon at diagnosis. In multivariable analyses, clinical subgroup, illness severity at onset, age at diagnosis, weight loss, and delay to diagnosis were the most important predictors from RSF; clinical subgroup and illness severity at onset were confirmed by multivariable Cox regression analysis. Conclusion Overall mortality was higher in juvenile IIM patients, and several early illness features were identified as risk factors. Clinical subgroup, antisynthetase autoantibodies, older age at diagnosis, and ILD are also recognized as mortality risk factors in adult myositis. C1 [Huber, Adam M.] IWK Hlth Ctr, Halifax, NS, Canada. [Huber, Adam M.] Dalhousie Univ, Halifax, NS, Canada. [Mamyrova, Gulnara; Katz, James D.] George Washington Univ, Sch Med, Washington, DC USA. [Lachenbruch, Peter A.; Lee, Julia A.; Miller, Frederick W.; Rider, Lisa G.] NIEHS, NIH, Bethesda, MD USA. [Targoff, Ira N.] Univ Oklahoma, Hlth Sci Ctr, VAMC, Oklahoma City, OK USA. [Targoff, Ira N.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. RP Rider, LG (reprint author), Natl Inst Environm Sci, Environm Autoimmun Grp, NIH, Clin Res Ctr, Room 4-2352,10 Ctr Dr,MSC 1301, Bethesda, MD 20892 USA. EM riderl@mail.nih.gov FU NIH, National Institute of Environmental Health Sciences; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Center for Biologics Evaluation and Research, FDA; Cure JM Foundation; Amgen; Pfizer FX Supported in part by the Intramural Research Programs of the NIH, National Institute of Environmental Health Sciences, and National Institute of Arthritis and Musculoskeletal and Skin Diseases, and by the Center for Biologics Evaluation and Research, FDA. Dr. Mamyrova's work was supported by the Cure JM Foundation.; Dr. Lachenbruch has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Amgen and Pfizer. NR 31 TC 9 Z9 9 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD MAY PY 2014 VL 66 IS 5 BP 732 EP 740 DI 10.1002/acr.22212 PG 9 WC Rheumatology SC Rheumatology GA AF4CI UT WOS:000334658600012 PM 24151254 ER PT J AU Kraft, LJ Nguyen, TA Vogel, SS Kenworthy, AK AF Kraft, Lewis J. Nguyen, Tuan A. Vogel, Steven S. Kenworthy, Anne K. TI Size, stoichiometry, and organization of soluble LC3-associated complexes SO AUTOPHAGY LA English DT Article DE MAP1LC3B; FRAP; FPFA; fluorescence; FRET; diffusion; autophagy; FCS; hydrodynamic radius; ATG8 ID FLUORESCENCE CORRELATION SPECTROSCOPY; LASER-SCANNING MICROSCOPES; SELECTIVE AUTOPHAGY; FLUCTUATION SPECTROSCOPY; PROTEIN LIPIDATION; STRUCTURAL BASIS; CONFOCAL FRAP; CELL-DEATH; LC3; ATG8 AB MAP1LC3B, an ortholog of yeast Atg8 and a member of the family of proteins formerly also known as ATG8 in mammals (LC3B henceforth in the text), functions in autophagosome formation and autophagy substrate recruitment. LC3 exists in both a soluble (autophagosome-independent) form as well as a lipid modified form that becomes tightly incorporated into autophagosomal membranes. Although LC3 is known to associate with tens of proteins, relatively little is known about soluble LC3 aside from its interactions with the LC3 lipid conjugation machinery. In previous studies we found autophagosome-independent GFP-LC3B diffuses unusually slowly for a protein of its size, suggesting it may constitutively associate with a high molecular weight complex, form homo-oligomers or aggregates, or reversibly bind microtubules or membranes. To distinguish between these possibilities, we characterized the size, stoichiometry, and organization of autophagosome-independent LC3B in living cells and in cytoplasmic extracts using fluorescence recovery after photobleaching (FRAP) and fluorescence polarization fluctuation analysis (FPFA). We found that the diffusion of LC3B was unaffected by either mutational disruption of its lipid modification or microtubule depolymerization. Brightness and homo-FRET analysis indicate LC3B does not homo-oligomerize. However, mutation of specific residues on LC3B required for binding other proteins and mRNA altered the effective hydrodynamic radius of the protein as well as its stoichiometry. We conclude that when not bound to autophagosomes, LC3B associates with a multicomponent complex with an effective size of similar to 500 kDa in the cytoplasm. These findings provide new insights into the nature of soluble LC3B and illustrate the power of FRAP and FPFA to investigate the emergent properties of protein complexes in the autophagy pathway. C1 [Kraft, Lewis J.; Kenworthy, Anne K.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Dept Cell & Dev Biol, Chem & Phys Biol Program,Med Ctr, Nashville, TN 37232 USA. [Nguyen, Tuan A.; Vogel, Steven S.] NIAAA, Sect Cellular Biophoton, Lab Mol Physiol, NIH, Rockville, MD 20852 USA. RP Kenworthy, AK (reprint author), Vanderbilt Univ, Dept Mol Physiol & Biophys, Dept Cell & Dev Biol, Chem & Phys Biol Program,Med Ctr, Nashville, TN 37232 USA. EM Anne.kenworthy@vanderbilt.edu OI Kraft, Lewis/0000-0001-8663-0596; Vogel, Steven/0000-0002-3005-2667 FU National Science Foundation [NSF/DMS 0970008]; National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD; National Institute of Diabetes and Digestive and Kidney Disease [DK020593] FX We are grateful for the constructive criticism and advice from the other members of the Kenworthy laboratory and to Dr Christian Behrends for helpful discussions. This work was funded by grant NSF/DMS 0970008 from the National Science Foundation, by the intramural program of the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, and utilized the core(s) of the Vanderbilt Diabetes Research and Training Center funded by grant DK020593 from the National Institute of Diabetes and Digestive and Kidney Disease. The funding sources had no role in the study design, collection, analysis or interpretation of data, writing the report, or the decision to submit the paper for publication. NR 60 TC 5 Z9 5 U1 1 U2 14 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1554-8627 EI 1554-8635 J9 AUTOPHAGY JI Autophagy PD MAY 1 PY 2014 VL 10 IS 5 BP 861 EP 877 DI 10.4161/auto.28175 PG 17 WC Cell Biology SC Cell Biology GA AG5BI UT WOS:000335433700011 PM 24646892 ER PT J AU Jun, HS Weinstein, DA Lee, YM Mansfield, BC Chou, JY AF Jun, Hyun Sik Weinstein, David A. Lee, Young Mok Mansfield, Brian C. Chou, Janice Y. TI Molecular mechanisms of neutrophil dysfunction in glycogen storage disease type Ib SO BLOOD LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; COLONY-STIMULATING FACTOR; ACTIVATED RECEPTOR-GAMMA; CONGENITAL NEUTROPENIA; NADPH OXIDASE; RESPIRATORY BURST; GLUCOSE-TRANSPORT; MUTATIONS; CELLS; 1B AB Glycogen storage disease type Ib (GSD-Ib) is an autosomal-recessive syndrome characterized by neutropenia and impaired glucose homeostasis resulting from a deficiency in the glucose-6-phosphate (G6P) transporter (G6PT). The underlying cause of GSD-Ib neutropenia is an enhanced neutrophil apoptosis, but patients also manifest neutrophil dysfunction of unknown etiology. Previously, we showed G6PT interacts with the enzyme glucose-6-phosphatase-beta (G6Pase-beta) to regulate the availability of G6P/glucose in neutrophils. Adeficiency in G6Pase-beta activity in neutrophils impairs both their energy homeostasis and function. We now show that G6PT-deficient neutrophils from GSD-Ib patients are similarly impaired. Their energy impairment is characterized by decreased glucose uptake and reduced levels of intracellular G6P, lactate, adenosine triphosphate, and reduced NAD phosphate, whereas functional impairment is reflected in reduced neutrophil respiratory burst, chemotaxis, and calcium mobilization. We further show that the mechanism of neutrophil dysfunction in GSD-Ib arises from activation of the hypoxia-inducible factor-1 alpha/peroxisome-proliferators-activated receptor-gamma pathway. C1 [Jun, Hyun Sik; Lee, Young Mok; Mansfield, Brian C.; Chou, Janice Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. [Weinstein, David A.] Univ Florida, Dept Pediat, Div Pediat Endocrinol, Glycogen Storage Dis Program, Gainesville, FL USA. [Mansfield, Brian C.] Fdn Fighting Blindness, Columbia, MD USA. RP Chou, JY (reprint author), NIH, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov OI Mansfield, Brian/0000-0002-8533-2789 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH; University of Florida Foundation; Rural Development Administration, Republic of Korea [PJ008196/PJ008127] FX This research was supported by the Intramural Research Programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. Additional support was provided by the following philanthropic funds managed through the University of Florida Foundation: Jonah Pournazarian Type Ib GSD Research Fund, the Efforts for Ellie Fund, Jamie Konieczka Type Ib GSD Research Fund, Jerry Kaczur's Fund, and the Type Ib Glycogen Storage Disease Research Fund. Additional support was also provided by the next generation of BioGreen21 project (PJ008196/PJ008127) from the Rural Development Administration, Republic of Korea. NR 49 TC 9 Z9 9 U1 2 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 1 PY 2014 VL 123 IS 18 BP 2843 EP 2853 DI 10.1182/blood-2013-05-502435 PG 11 WC Hematology SC Hematology GA AH1QP UT WOS:000335896300019 PM 24565827 ER PT J AU Purdue, MP Hofmann, JN Kemp, TJ Chaturvedi, AK Lan, Q Park, JH Pfeiffer, RM Hildesheim, A Pinto, LA Rothman, N AF Purdue, Mark P. Hofmann, Jonathan N. Kemp, Troy J. Chaturvedi, Anil K. Lan, Qing Park, Ju-Hyun Pfeiffer, Ruth M. Hildesheim, Allan Pinto, Ligia A. Rothman, Nathaniel TI A prospective study of 67 serum immune and inflammation markers and risk of non-Hodgkin lymphoma (vol 122, pg 951, 2013) SO BLOOD LA English DT Correction C1 [Purdue, Mark P.; Hofmann, Jonathan N.; Chaturvedi, Anil K.; Lan, Qing; Pfeiffer, Ruth M.; Hildesheim, Allan; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Kemp, Troy J.; Pinto, Ligia A.] SAIC Frederick Inc, HPV Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA. [Park, Ju-Hyun] Dongguk Univ Seoul, Seoul, South Korea. RP Purdue, MP (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RI Hildesheim, Allan/B-9760-2015; Purdue, Mark/C-9228-2016 OI Hildesheim, Allan/0000-0003-0257-2363; Purdue, Mark/0000-0003-1177-3108 NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 1 PY 2014 VL 123 IS 18 BP 2901 EP 2901 DI 10.1182/blood-2014-03-563767 PG 1 WC Hematology SC Hematology GA AH1QP UT WOS:000335896300029 ER PT J AU Schloesser, RJ Jimenez, DV Hardy, NF Paredes, D Catlow, BJ Manji, HK McKay, RD Martinowich, K AF Schloesser, Robert J. Jimenez, Dennisse V. Hardy, Nicholas F. Paredes, Daniel Catlow, Briony J. Manji, Husseini K. McKay, Ronald D. Martinowich, Keri TI Atrophy of pyramidal neurons and increased stress-induced glutamate levels in CA3 following chronic suppression of adult neurogenesis SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Neurogenesis; Dentate gyrus; Excitotoxicity; Atrophy; Dendrite; CA3 ID ENHANCED SYNAPTIC PLASTICITY; HIPPOCAMPAL-FORMATION VOLUME; NEWLY GENERATED NEURONS; DENTATE GYRUS; CAPILLARY ELECTROPHORESIS; CHRONIC-SCHIZOPHRENIA; PSYCHOSOCIAL STRESS; ANXIETY DISORDERS; SELECTIVE LOSS; GRANULE CELLS AB Following their birth in the adult hippocampal dentate gyrus, newborn progenitor cells migrate into the granule cell layer where they differentiate, mature, and functionally integrate into existing circuitry. The hypothesis that adult hippocampal neurogenesis is physiologically important has gained traction, but the precise role of newborn neurons in hippocampal function remains unclear. We investigated whether loss of new neurons impacts dendrite morphology and glutamate levels in area CA3 of the hippocampus by utilizing a human GFAP promoter-driven thymidine kinase genetic mouse model to conditionally suppress adult neurogenesis. We found that chronic ablation of new neurons induces remodeling in CA3 pyramidal cells and increases stress-induced release of the neurotransmitter glutamate. The ability of persistent impairment of adult neurogenesis to influence hippocampal dendrite morphology and excitatory amino acid neurotransmission has important implications for elucidating newborn neuron function, and in particular, understanding the role of these cells in stress-related excitoxicity. C1 [Schloesser, Robert J.; Jimenez, Dennisse V.; Manji, Husseini K.; Martinowich, Keri] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Schloesser, Robert J.; Jimenez, Dennisse V.; Hardy, Nicholas F.; Paredes, Daniel; Catlow, Briony J.; McKay, Ronald D.; Martinowich, Keri] Lieber Inst Brain Dev, Baltimore, MD 21205 USA. [Schloesser, Robert J.] Univ Maryland, Dept Psychiat, Sch Med, Baltimore, MD 21201 USA. [Hardy, Nicholas F.; Martinowich, Keri] NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. [Paredes, Daniel; Catlow, Briony J.; McKay, Ronald D.] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Manji, Husseini K.] Janssen Res & Dev, Titusville, NJ USA. RP Martinowich, K (reprint author), Lieber Inst Brain Dev, Johns Hopkins Med Campus,855 N Wolfe St,347B, Baltimore, MD 21205 USA. EM keri.martinowich@libd.org RI Martinowich, Keri/F-9841-2012; OI Martinowich, Keri/0000-0002-5237-0789 FU National Institute of Mental Health Intramural Research Program; Lieber Institute for Brain Development; NARSAD Young Investigator Awards FX This work was funded by the National Institute of Mental Health Intramural Research Program and the Lieber Institute for Brain Development. RJS and KM were supported in part by NARSAD Young Investigator Awards. NR 62 TC 8 Z9 8 U1 2 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 EI 1863-2661 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD MAY PY 2014 VL 219 IS 3 BP 1139 EP 1148 DI 10.1007/s00429-013-0532-8 PG 10 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA AG9KK UT WOS:000335737900025 PM 23483239 ER PT J AU Gough, SM Lee, F Yang, F Walker, RL Zhu, YLJ Pineda, M Onozawa, M Chung, YJ Bilke, S Wagner, EK Denu, JM Ning, Y Xu, BW Wang, GG Meltzer, PS Aplan, PD AF Gough, Sheryl M. Lee, Fan Yang, Fan Walker, Robert L. Zhu, Yeulin J. Pineda, Marbin Onozawa, Masahiro Chung, Yang Jo Bilke, Sven Wagner, Elise K. Denu, John M. Ning, Yi Xu, Bowen Wang, Gang Greg Meltzer, Paul S. Aplan, Peter D. TI NUP98-PHF23 Is a Chromatin-Modifying Oncoprotein That Causes a Wide Array of Leukemias Sensitive to Inhibition of PHD Histone Reader Function SO CANCER DISCOVERY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE-EXPRESSION PROFILES; DOUBLE-TRANSGENIC MICE; EMBRYONIC STEM-CELLS; MLL TRANSLOCATIONS; HOMEOBOX GENES; MALIGNANCIES; ACTIVATION; TRANSCRIPTION AB In this report, we show that expression of a NUP98-PHF23 (NP23) fusion, associated with acute myeloid leukemia (AML) in humans, leads to myeloid, erythroid, T-cell, and B-cell leukemia in mice. The leukemic and preleukemic tissues display a stem cell-like expression signature, including Hoxa, Hoxb, and Meis1 genes. The PHF23 plant homeodomain (PHD) motif is known to bind to H3K4me3 residues, and chromatin immunoprecipitation experiments demonstrated that the NP23 protein binds to chromatin at a specific subset of H3K4me3 sites, including at Hoxa, Hoxb, and Meis1. Treatment of NP23 cells with disulfiram, which inhibits the binding of PHD motifs to H3K4me3, rapidly and selectively killed NP23-expressing myeloblasts; cell death was preceded by decreased expression of Hoxa, Hoxb, and Meis1. Furthermore, AML driven by a related fusion gene, NUP98-JARID1A (NJL), was also sensitive to disulfiram. Thus, the NP23 mouse provides a platform to evaluate compounds that disrupt binding of oncogenic PHD proteins to H3K4me3. SIGNIFICANCE: NP23 and NJL belong to a subset of chromatin-modifying fusion oncoproteins that cause leukemia characterized by overexpression of Hoxa and Meis1 genes. Inhibition of NP23 binding to H3K4me3 at Hoxa and Meis1 loci by disulfiram, a U.S. Food and Drug Administration-approved drug, leads to leukemic cell death, demonstrating the feasibility of targeting this subset of oncoproteins. (C) 2014 AACR. C1 [Gough, Sheryl M.; Lee, Fan; Yang, Fan; Walker, Robert L.; Zhu, Yeulin J.; Pineda, Marbin; Onozawa, Masahiro; Chung, Yang Jo; Bilke, Sven; Meltzer, Paul S.; Aplan, Peter D.] NCI, Genet Branch Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Ning, Yi] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Wagner, Elise K.; Denu, John M.] Univ Wisconsin, Dept Biomol Chem, Madison, WI USA. [Xu, Bowen; Wang, Gang Greg] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA. RP Aplan, PD (reprint author), NCI, Genet Branch Ctr Canc Res, NIH, Bldg 37,Room 6002,37 Convent Dr, Bethesda, MD 20892 USA. EM aplanp@mail.nih.gov RI Wang, G Greg/L-6666-2014; Aplan, Peter/K-9064-2016 OI Wang, G Greg/0000-0002-7210-9940; FU National Cancer Institute, National Institutes of Health [ZIA SC 010378, BC 010983] FX This work was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health (grant numbers ZIA SC 010378 and BC 010983). NR 50 TC 15 Z9 15 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD MAY PY 2014 VL 4 IS 5 BP 564 EP 577 DI 10.1158/2159-8290.CD-13-0419 PG 14 WC Oncology SC Oncology GA AH1ZA UT WOS:000335919200027 PM 24535671 ER PT J AU de Bruin, EC Cowell, C Warne, PH Jiang, M Saunders, RE Melnick, MA Gettinger, S Walther, Z Wurtz, A Heynen, GJ Heideman, DAM Gomez-Roman, J Garcia-Castano, A Gong, YX Ladanyi, M Varmus, H Bernards, R Smit, EF Politi, K Downward, J AF de Bruin, Elza C. Cowell, Catherine Warne, Patricia H. Jiang, Ming Saunders, Rebecca E. Melnick, Mary Ann Gettinger, Scott Walther, Zenta Wurtz, Anna Heynen, Guus J. Heideman, Danielle A. M. Gomez-Roman, Javier Garcia-Castano, Almudena Gong, Yixuan Ladanyi, Marc Varmus, Harold Bernards, Rene Smit, Egbert F. Politi, Katerina Downward, Julian TI Reduced NF1 Expression Confers Resistance to EGFR Inhibition in Lung Cancer SO CANCER DISCOVERY LA English DT Article ID TYROSINE KINASE INHIBITORS; ACQUIRED-RESISTANCE; ERLOTINIB RESISTANCE; TUMOR-SUPPRESSOR; RAF INHIBITION; RECEPTOR; MUTATIONS; GEFITINIB; AMPLIFICATION; ADENOCARCINOMA AB Activating mutations in the EGF receptor (EGFR) are associated with clinical responsiveness to EGFR tyrosine kinase inhibitors (TKI), such as erlotinib and gefitinib. However, resistance eventually arises, often due to a second EGFR mutation, most commonly T790M. Through a genome-wide siRNA screen in a human lung cancer cell line and analyses of murine mutant EGFR-driven lung adenocarcinomas, we found that erlotinib resistance was associated with reduced expression of neurofibromin, the RAS GTPase-activating protein encoded by the NF1 gene. Erlotinib failed to fully inhibit RAS-ERK signaling when neurofibromin levels were reduced. Treatment of neurofibromin-deficient lung cancers with a MAP-ERK kinase (MEK) inhibitor restored sensitivity to erlotinib. Low levels of NF1 expression were associated with primary and acquired resistance of lung adenocarcinomas to EGFR TKIs in patients. These findings identify a subgroup of patients with EGFR-mutant lung adenocarcinoma who might benefit from combination therapy with EGFR and MEK inhibitors. SIGNIFICANCE: The emergence of resistance to EGFR TKIs is a major clinical challenge in the treatment of lung adenocarcinomas driven by mutations in EGFR. This study suggests that, in a subset of patients, resistance is caused by reduced neurofibromin expression, and that in these cases there may be clinical benefit to combining EGFR TKIs with MEK inhibitors. (C) 2014 AACR. C1 [de Bruin, Elza C.; Cowell, Catherine; Warne, Patricia H.; Downward, Julian] Canc Res UK London Res Inst, Signal Transduct Lab, London WC2A 3LY, England. [Jiang, Ming; Saunders, Rebecca E.] Canc Res UK London Res Inst, High Throughput Screening Lab, London WC2A 3LY, England. [Downward, Julian] Inst Canc Res, London SW3 6JB, England. [Melnick, Mary Ann; Gettinger, Scott; Walther, Zenta; Wurtz, Anna; Politi, Katerina] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA. [Gettinger, Scott; Politi, Katerina] Yale Univ, Sch Med, Dept Med Med Oncol, New Haven, CT USA. [Walther, Zenta; Politi, Katerina] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Gong, Yixuan; Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Varmus, Harold] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. [Heynen, Guus J.; Bernards, Rene] Netherlands Canc Inst, Div Mol Carcinogenesis, Amsterdam, Netherlands. [Heideman, Danielle A. M.] Vrije Univ Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands. [Smit, Egbert F.] Vrije Univ Amsterdam Med Ctr, Div Pulm Dis, Amsterdam, Netherlands. [Gomez-Roman, Javier] Univ Marques Valdecilla, IFIMAV, Pathol Serv, Santander, Spain. [Garcia-Castano, Almudena] Univ Marques Valdecilla, IFIMAV, Oncol Serv Hosp, Santander, Spain. RP Downward, J (reprint author), Canc Res UK London Res Inst, 44 Lincolns Inn Fields, London WC2A 3LY, England. EM katerina.politi@yale.edu; downward@cancer.org.uk OI Gomez-Roman, Jose Javier/0000-0002-2849-9435; Bernards, Rene/0000-0001-8677-3423 FU KWF (Dutch Cancer Society) fellowship; European Commission's Seventh Framework Programme (FP7) [259770]; National Cancer Institute, NIH [R00 CA131488, R01 CA120247, P01 CA129243]; Pilot grant from the Section of Medical Oncology, Yale University School of Medicine; Cancer Research UK FX E.C. de Bruin was financially supported by a KWF (Dutch Cancer Society) fellowship and has received funding from the European Commission's Seventh Framework Programme (FP7/2007-2013) under the grant agreement Lungtarget (project 259770). This work was supported by grants R00 CA131488 (to K. Politi), R01 CA120247 (to K. Politi), and P01 CA129243 (to M. Ladanyi) from the National Cancer Institute, NIH; a Pilot grant from the Section of Medical Oncology, Yale University School of Medicine (to S. Gettinger and K. Politi); and was financially supported by Cancer Research UK. NR 46 TC 32 Z9 33 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD MAY PY 2014 VL 4 IS 5 BP 606 EP 619 DI 10.1158/2159-8290.CD-13-0741 PG 14 WC Oncology SC Oncology GA AH1ZA UT WOS:000335919200030 PM 24535670 ER PT J AU Linden, KG Leachman, SA Zager, JS Jakowatz, JG Viner, JL McLaren, CE Barr, RJ Carpenter, PM Chen, WP Elmets, CA Tangrea, JA Lim, SJ Cochran, AJ Meyskens, FL AF Linden, Kenneth G. Leachman, Sancy A. Zager, Jonathan S. Jakowatz, James G. Viner, Jaye L. McLaren, Christine E. Barr, Ronald J. Carpenter, Philip M. Chen, Wen-Pin Elmets, Craig A. Tangrea, Joseph A. Lim, Sung-Jig Cochran, Alistair J. Meyskens, Frank L., Jr. TI A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial of Lovastatin for Various Endpoints of Melanoma Pathobiology SO CANCER PREVENTION RESEARCH LA English DT Article ID PROLIFERATIVE ACTIVITY; MELANOCYTIC LESIONS; MALIGNANT-MELANOMA; STATIN THERAPY; RISK; SKIN; EXPRESSION; KI-67; NEVI; METAANALYSIS AB On the basis of large cardiovascular clinical trials of lipid-lowering agents that showed a considerable decrease in the incidence of primary melanomas in the active agent arm, we have carried out a randomized, double-blind clinical trial examining the impact of lovastatin on various biomarkers of melanoma pathogenesis. Subjects with at least two clinically atypical nevi were randomized to receive oral lovastatin or placebo for a 6-month period. Clinical, histopathologic, and molecular biomarkers were evaluated for change in the two groups. Eighty subjects were randomized, evaluable, and included in the analyses. Lovastatin showed no benefit in comparison with placebo in the primary endpoint of decreasing the level of histopathologic atypia, nor in any of the secondary endpoints of decreasing clinical atypia, impact on nevus number, nor in showing significant changes in any of the molecular biomarkers. There were no significant differences in adverse event profiles for lovastatin compared with placebo. The lovastatin arm did show a significant and considerable decrease in total serum cholesterol and serum low-density lipoprotein (LDL) levels compared with placebo, an expected result. This finding bolsters confidence in subject compliance. Given the results of this trial, it is concluded that if lovastatin were to lower the incidence of melanoma, it would appear not to be doing so by reversing atypia of precursor atypical nevi over the 6-month time frame studied. Further research into the pathogenesis of melanoma and in other potential chemopreventive agents is needed. C1 [Linden, Kenneth G.; Jakowatz, James G.; McLaren, Christine E.; Carpenter, Philip M.; Chen, Wen-Pin; Meyskens, Frank L., Jr.] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Orange, CA 92868 USA. [Linden, Kenneth G.; Barr, Ronald J.] Univ Calif Irvine, Dept Dermatol, Orange, CA 92868 USA. [McLaren, Christine E.] Univ Calif Irvine, Dept Epidemiol, Orange, CA 92868 USA. [Carpenter, Philip M.] Univ Calif Irvine, Dept Pathol, Orange, CA 92868 USA. [Cochran, Alistair J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Leachman, Sancy A.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Zager, Jonathan S.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Viner, Jaye L.] Takeda Cambridge USA, Cambridge, MA USA. [Elmets, Craig A.] Univ Alabama Birmingham, Birmingham, AL USA. [Tangrea, Joseph A.] NCI, Canc Prevent Div, Rockville, MD USA. [Lim, Sung-Jig] Kyung Hee Univ, Seoul, South Korea. RP Linden, KG (reprint author), Univ Calif Irvine, Med Ctr, Dept Dermatol, Chao Family Comprehens Canc Ctr, 101 City Dr, Orange, CA 92868 USA. EM kglinden@uci.edu FU [CN-35160]; [P30 CA-62203] FX This study was supported in part by NO-1 CN-35160 and P30 CA-62203 (to F.L. Meyskens Jr.). NR 30 TC 4 Z9 4 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD MAY PY 2014 VL 7 IS 5 BP 496 EP 504 DI 10.1158/1940-6207.CAPR-13-0189 PG 9 WC Oncology SC Oncology GA AH1YH UT WOS:000335917300003 PM 24614012 ER PT J AU Hamilton, DH Huang, B Fernando, RI Tsang, KY Palena, C AF Hamilton, Duane H. Huang, Bruce Fernando, Romaine I. Tsang, Kwong-Yok Palena, Claudia TI WEE1 Inhibition Alleviates Resistance to Immune Attack of Tumor Cells Undergoing Epithelial-Mesenchymal Transition SO CANCER RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR BRACHYURY; HUMAN CARCINOMA-CELLS; T-LYMPHOCYTE EPITOPE; NUCLEAR LAMINA; CANCER-CELLS; LUNG-CANCER; CDC2 KINASE; PHOSPHORYLATION; ANTIGEN; APOPTOSIS AB Aberrant expression of the T-box transcription factor brachyury in human carcinomas drives the phenomenon of epithelial-mesenchymal transition (EMT), a phenotypic modulation that facilitates tumor dissemination and resistance to conventional therapies, including chemotherapy and radiotherapy. By generating isogenic cancer cell lines with various levels of brachyury expression, we demonstrate that high levels of brachyury also significantly reduce the susceptibility of cancer cells to lysis by both antigen-specific T cells and natural killer cells. Our results indicated that resistance of brachyury-high tumor cells to immune-mediated attack was due to inefficient caspase-dependent apoptosis, manifested as inefficient nuclear lamin degradation in the presence of activated effector caspases. We correlated this phenomenon with loss of cell-cycle-dependent kinase 1 (CDK1), which mediates lamin phosphorylation. In support of a causal connection, pretreatment of tumor cells with a specific inhibitor of WEE1, a negative regulator kinase of CDK1, could counter the defective apoptosis of tumor cells expressing high levels of brachyury. Thus, our findings suggested that reconstituting CDK1 activity to threshold levels may be sufficient to restore immunosurveillance of mesenchymal-like cancer cells that have escaped previous immune detection or eradication. C1 [Hamilton, Duane H.; Huang, Bruce; Fernando, Romaine I.; Tsang, Kwong-Yok; Palena, Claudia] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Palena, C (reprint author), NCI, NIH, 10 Ctr Dr,Room 8B14, Bethesda, MD 20892 USA. EM palenac@mail.nih.gov FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH FX This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH. NR 38 TC 15 Z9 16 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2014 VL 74 IS 9 BP 2510 EP 2519 DI 10.1158/0008-5472.CAN-13-1894 PG 10 WC Oncology SC Oncology GA AH1ZH UT WOS:000335920000014 PM 24626094 ER PT J AU Fiskus, W Saba, N Shen, M Ghias, M Liu, JY Das Gupta, S Chauhan, L Rao, R Gunewardena, S Schorno, K Austin, CP Maddocks, K Byrd, J Melnick, A Huang, P Wiestner, A Bhalla, KN AF Fiskus, Warren Saba, Nakhle Shen, Min Ghias, Mondana Liu, Jinyun Das Gupta, Soumyasri Chauhan, Lata Rao, Rekha Gunewardena, Sumedha Schorno, Kevin Austin, Christopher P. Maddocks, Kami Byrd, John Melnick, Ari Huang, Peng Wiestner, Adrian Bhalla, Kapil N. TI Auranofin Induces Lethal Oxidative and Endoplasmic Reticulum Stress and Exerts Potent Preclinical Activity against Chronic Lymphocytic Leukemia SO CANCER RESEARCH LA English DT Article ID UNFOLDED PROTEIN RESPONSE; THIOREDOXIN REDUCTASE; TCL1 EXPRESSION; CELL-SURVIVAL; CANCER-CELLS; INHIBITION; APOPTOSIS; HSP90; HDAC6; GLUTATHIONE AB Chronic lymphocytic leukemia (CLL) exhibits high remission rates after initial chemoimmunotherapy, but with relapses with treatment, refractory disease is the most common outcome, especially in CLL with the deletion of chromosome 11q or 17p. In addressing the need of treatments for relapsed disease, we report the identification of an existing U. S. Food and Drug Administration-approved small-molecule drug to repurpose for CLL treatment. Auranofin ( Ridaura) is approved for use in treating rheumatoid arthritis, but it exhibited preclinical efficacy in CLL cells. By inhibiting thioredoxin reductase activity and increasing intracellular reactive oxygen species levels, auranofin induced a lethal endoplasmic reticulum stress response in cultured and primary CLL cells. In addition, auranofin displayed synergistic lethality with heme oxygenase-1 and glutamate-cysteine ligase inhibitors against CLL cells. Auranofin overcame apoptosis resistance mediated by protective stromal cells, and it also killed primary CLL cells with deletion of chromosome 11q or 17p. In TCL-1 transgenic mice, an in vivo model of CLL, auranofin treatment markedly reduced tumor cell burden and improved mouse survival. Our results provide a rationale to reposition the approved drug auranofin for clinical evaluation in the therapy of CLL. C1 [Fiskus, Warren; Bhalla, Kapil N.] Houston Methodist Res Inst, Houston, TX 77030 USA. [Liu, Jinyun; Huang, Peng] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Saba, Nakhle; Ghias, Mondana; Wiestner, Adrian] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Shen, Min] Natl Ctr Adv Translat Sci, NIH, Bethesda, MD USA. [Das Gupta, Soumyasri; Chauhan, Lata; Rao, Rekha; Gunewardena, Sumedha] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Schorno, Kevin] Univ Kansas, Inst Adv Med Innovat, Kansas City, KS USA. [Maddocks, Kami; Byrd, John] Ohio State Univ, Dept Internal Med, Ctr Comprehens Canc, Div Hematol, Columbus, OH 43210 USA. [Melnick, Ari] Weill Cornell Med Coll, New York, NY USA. RP Bhalla, KN (reprint author), Houston Methodist Res Inst, 6670 Bertner Ave,R9-113, Houston, TX 77030 USA. EM knbhalla@tmhs.org FU NCI NIH HHS [P01 CA081534, P30 CA016672, R01 CA085563, R01 CA100428] NR 48 TC 43 Z9 43 U1 3 U2 24 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2014 VL 74 IS 9 BP 2520 EP 2532 DI 10.1158/0008-5472.CAN-13-2033 PG 13 WC Oncology SC Oncology GA AH1ZH UT WOS:000335920000015 PM 24599128 ER PT J AU Hofmann, JN Hosgood, HD Liu, CS Chow, WH Shuch, B Cheng, WL Lin, TT Moore, LE Lan, Q Rothman, N Purdue, MP AF Hofmann, Jonathan N. Hosgood, H. Dean, III Liu, Chin-San Chow, Wong-Ho Shuch, Brian Cheng, Wen-Ling Lin, Ta-Tsung Moore, Lee E. Lan, Qing Rothman, Nathaniel Purdue, Mark P. TI A nested case-control study of leukocyte mitochondrial DNA copy number and renal cell carcinoma in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial SO CARCINOGENESIS LA English DT Article ID OXIDATIVE STRESS; RISK AB This study reports the first prospective evidence that high leukocyte mtDNA copy number is associated with increased future risk of RCC, suggesting that oxidative DNA damage and mitochondrial dysfunction may contribute to renal carcinogenesis.Mitochondrial DNA (mtDNA) is vulnerable to mutations, and the number of copies of mtDNA per cell may increase to compensate for DNA damage. Case-control studies have reported associations between altered mtDNA copy number and risk of renal cell carcinoma (RCC); however, this association has not been investigated prospectively. We conducted a nested case-control study (252 cases and 504 controls) of RCC risk in relation to pre-diagnostic leukocyte mtDNA copy number in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. mtDNA copy number was measured in triplicate using a fluorescence-based quantitative PCR assay; samples from 22 cases and 36 controls could not be assayed, leaving 230 cases and 468 controls for analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. High mtDNA copy number was associated with an increased risk of RCC, both overall (highest quartile versus lowest: OR = 2.0, 95% CI = 1.2-3.2; P (trend) = 0.002) and among cases diagnosed a parts per thousand yen6 years after blood collection (OR = 2.6, 95% CI = 1.4-5.0; P (trend) = 0.003). These findings did not differ significantly by sex, body mass index, history of hypertension or smoking status (P (interaction) a parts per thousand yen 0.3). Results of this study suggest that high pre-diagnostic leukocyte mtDNA copy number, a suspected marker of oxidative DNA damage and mitochondrial dysfunction, is associated with increased future RCC risk. C1 [Hofmann, Jonathan N.; Moore, Lee E.; Lan, Qing; Rothman, Nathaniel; Purdue, Mark P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Hosgood, H. Dean, III] Albert Einstein Coll Med, Div Epidemiol, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Liu, Chin-San; Cheng, Wen-Ling; Lin, Ta-Tsung] Changhua Christian Hosp, Vasc & Genom Res Ctr, Changhua 500, Taiwan. [Chow, Wong-Ho] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Shuch, Brian] Yale Univ, Sch Med, Dept Urol, New Haven, CT 06520 USA. RP Hofmann, JN (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E132,MSC 9771, Bethesda, MD 20892 USA. EM hofmannjn@mail.nih.gov RI Purdue, Mark/C-9228-2016 OI Purdue, Mark/0000-0003-1177-3108 FU Intramural Research Program of the National Cancer Institute; Division of Cancer Prevention; National Cancer Institute; National Institutes of Health; Department of Health and Human Services FX Intramural Research Program of the National Cancer Institute and contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services. NR 17 TC 11 Z9 12 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2014 VL 35 IS 5 BP 1028 EP 1031 DI 10.1093/carcin/bgt495 PG 4 WC Oncology SC Oncology GA AH3RW UT WOS:000336043800008 PM 24398668 ER PT J AU Bode, C Kinjo, T Alvord, WG Klinman, DM AF Bode, Christian Kinjo, Takeshi Alvord, W. Gregory Klinman, Dennis M. TI Suppressive oligodeoxynucleotides reduce lung cancer susceptibility in mice with silicosis SO CARCINOGENESIS LA English DT Article ID A/J MICE; CYCLOOXYGENASE-2 INHIBITOR; CHEMOPREVENTIVE ACTIVITY; IMMUNE ACTIVATION; INDUCED ARTHRITIS; TUMOR PROMOTION; TTAGGG MOTIFS; MOUSE SKIN; INFLAMMATION; CARCINOGENESIS AB Using a novel murine model, we demonstrate that silicotic inflammation increases susceptibility to lung cancer initiated by exposure to NNK, a potent carcinogen in cigarettes. Cancer susceptibility is reduced to background by blocking this inflammation through treatment with immunosuppressive oligonucleotides.Silicosis is an inflammatory lung disease induced by the inhalation of silica-containing dust particles. There is conflicting data on whether patients with silicosis are more susceptible to lung cancer induced by cigarette smoke. To examine this issue experimentally, a model was developed in which one of the most abundant and potent carcinogens present in cigarette smoke [4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK)] was administered to mice at the peak of silica-induced pulmonary inflammation. Results show that the incidence of lung tumors in silicotic mice treated with NNK was significantly increased compared with mice exposed to silica or NNK alone. Synthetic oligonucleotides (ODN) containing repetitive TTAGGG motifs can block pathologic inflammation. We therefore examined whether treatment with these suppressive (Sup) ODN could block silica-induced pulmonary inflammation and thereby reduce susceptibility to lung cancer. Results show that Sup (but not control) ODN inhibit pulmonary fibrosis and other inflammatory manifestations of chronic silicosis. Of greater import, Sup ODN reduced lung tumor incidence and multiplicity in silicotic mice exposed to NNK. These findings establish an experimental model for examining the role of silicotic inflammation in cancer susceptibility and demonstrate that Sup ODN represent a novel therapy for chronic silicosis. C1 [Bode, Christian; Kinjo, Takeshi; Klinman, Dennis M.] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Bode, Christian] Univ Hosp Bonn, Dept Anesthesiol & Intens Care Med, Bonn, Germany. [Kinjo, Takeshi] Univ Ryukyus, Dept Med, Nishihara, Okinawa 90301, Japan. [Alvord, W. Gregory] NCI, DMS Appl Informat & Management Sci, Frederick, MD 21702 USA. RP Klinman, DM (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. EM klinmand@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute FX Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 57 TC 3 Z9 3 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2014 VL 35 IS 5 BP 1078 EP 1083 DI 10.1093/carcin/bgu005 PG 6 WC Oncology SC Oncology GA AH3RW UT WOS:000336043800014 PM 24403310 ER PT J AU Wu, LS Jiang, H Chawsheen, HA Mishra, M Young, MR Gerard, M Toledano, MB Colburn, NH Wei, Q AF Wu, Lisha Jiang, Hong Chawsheen, Hedy A. Mishra, Murli Young, Matthew R. Gerard, Matthieu Toledano, Michel B. Colburn, Nancy H. Wei, Qiou TI Tumor promoter-induced sulfiredoxin is required for mouse skin tumorigenesis SO CARCINOGENESIS LA English DT Article ID SULFINIC ACID REDUCTASE; HUMAN LUNG-CANCER; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION FACTORS; 2-CYS PEROXIREDOXIN; CELL-PROLIFERATION; GENE-EXPRESSION; DUAL FUNCTIONS; TARGET GENE; NRF2 AB Srx induced by tumor promoter reduces hyperoxidized Prxs, increases cells' ability to survive through oxidative stress by inhibition of TPA-induced apoptosis and facilitates skin tumor development.Sulfiredoxin (Srx), the exclusive enzyme that reduces the hyperoxidized inactive form of peroxiredoxins (Prxs), has been found highly expressed in several types of human skin cancer. To determine whether Srx contributed to skin tumorigenesis in vivo, Srx null mice were generated on an FVB background. Mouse skin tumorigenesis was induced by a 7,12-dimethylbenz[alpha]anthracene/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA) protocol. We found that the number, volume and size of papillomas in Srx(-/-) mice were significantly fewer compared with either wild-type (Wt) or heterozygous (Het) siblings. Histopathological analysis revealed more apoptotic cells in tumors from Srx(-/-) mice. Mechanistic studies in cell culture revealed that Srx was stimulated by TPA in a redox-independent manner. This effect was mediated transcriptionally through the activation of mitogen-activated protein kinase and Jun-N-terminal kinase. We also demonstrated that Srx was capable of reducing hyperoxidized Prxs to facilitate cell survival under oxidative stress conditions. These findings suggested that loss of Srx protected mice, at least partially, from DMBA/TPA-induced skin tumorigenesis. Therefore, Srx has an oncogenic role in skin tumorigenesis and targeting Srx may provide novel strategies for skin cancer prevention or treatment. C1 [Wu, Lisha; Jiang, Hong; Chawsheen, Hedy A.; Mishra, Murli; Wei, Qiou] Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA. [Wu, Lisha; Jiang, Hong; Wei, Qiou] Univ Kentucky, Markey Canc Ctr, Lexington, KY 40536 USA. [Young, Matthew R.; Colburn, Nancy H.] Ctr Canc Res, Lab Canc Prevent, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Gerard, Matthieu] CEA Saclay, Epigenet Regulat & Canc Grp, Inst Biol & Technol Saclay, F-91191 Gif Sur Yvette, France. [Toledano, Michel B.] CEA Saclay, Oxidat Stress & Canc Grp, Inst Biol & Technol Saclay, F-91191 Gif Sur Yvette, France. RP Wei, Q (reprint author), Univ Kentucky, Grad Ctr Toxicol, 1095 VA Dr,140 HSRB, Lexington, KY 40513 USA. EM qiou.wei@uky.edu RI Mishra, Murli/A-8998-2013; OI Mishra, Murli/0000-0003-3477-0081; GERARD, Matthieu/0000-0001-8956-0597 FU National Cancer Institute, National Institutes of Health [R00CA149144] FX National Cancer Institute, National Institutes of Health (R00CA149144 to Q.W.). NR 44 TC 6 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2014 VL 35 IS 5 BP 1177 EP 1184 DI 10.1093/carcin/bgu035 PG 8 WC Oncology SC Oncology GA AH3RW UT WOS:000336043800025 PM 24503444 ER PT J AU Hernandez-Ramon, EE Sandoval, NA John, K Cline, JM Wood, CE Woodward, RA Poirier, MC AF Hernandez-Ramon, Elena E. Sandoval, Nicole A. John, Kaarthik Cline, J. Mark Wood, Charles E. Woodward, Ruth A. Poirier, Miriam C. TI Tamoxifen-DNA adduct formation in monkey and human reproductive organs SO CARCINOGENESIS LA English DT Article ID REVERSE-TRANSCRIPTASE INHIBITORS; BREAST-CANCER; MITOCHONDRIAL COMPROMISE; HUMAN ENDOMETRIUM; MASS-SPECTROMETRY; WOMEN; RAT; GENOTOXICITY; CARCINOGEN; EXPOSURE AB The estrogen analog tamoxifen (TAM), used for adjuvant therapy of breast cancer, induces endometrial and uterine tumors in breast cancer patients. Proliferation stimulus of the uterine endometrium is likely involved in tumor induction, but genotoxicity may also play a role. Formation of TAM-DNA adducts in human tissues has been reported but remains controversial. To address this issue, we examined TAM-DNA adducts in uteri from two species of monkeys, Erythrocebus patas (patas) and Macaca fascicularis (macaque), and in human endometrium and myometrium. Monkeys were given 3-4 months of chronic TAM dosing scaled to be equivalent to the daily human dose. In the uteri, livers and brains from the patas (n = 3), and endometrium from the macaques (n = 4), TAM-DNA adducts were measurable by TAM-DNA chemiluminescence immunoassay. Average TAM-DNA adduct values for the patas uteri (23 adducts/10(8) nucleotides) were similar to those found in endometrium of the macaques (19 adducts/10(8) nucleotides). Endometrium of macaques exposed to both TAM and low-dose estradiol (n = 5) averaged 34 adducts/10(8) nucleotides. To examine TAM-DNA persistence in the patas, females (n = 3) were exposed to TAM for 3 months and to no drug for an additional month, resulting in low or non-detectable TAM-DNA in livers and uteri. Human endometrial and myometrial samples from women receiving (n = 8) and not receiving (n = 8) TAM therapy were also evaluated. Women receiving TAM therapy averaged 10.3 TAM-DNA adducts/10(8) nucleotides, whereas unexposed women showed no detectable TAM-DNA. The data indicate that genotoxicity, in addition to estrogen agonist effects, may contribute to TAM-induced human endometrial cancer.We examined TAM-DNA adducts in two species of monkeys and in humans treated with TAM. Our data showed that adducts are formed in uterine tissue in monkeys and humans, suggesting a role of TAM genotoxicity in endometrial cancer. C1 [Hernandez-Ramon, Elena E.; Sandoval, Nicole A.; John, Kaarthik; Poirier, Miriam C.] NCI, Carcinogen DNA Interact Sect, LCBG, CCR,NIH, Bethesda, MD 20892 USA. [Cline, J. Mark; Wood, Charles E.] Wake Forest Sch Med, Dept Pathol, Winston Salem, NC 27157 USA. [Woodward, Ruth A.] NICHD, Res Anim Management Branch, Shared Anim Facil, NIH, Dickerson, MD 20837 USA. RP Hernandez-Ramon, EE (reprint author), NCI, Carcinogen DNA Interact Sect, LCBG, CCR,NIH, Bldg 37,Room 4032,NIH 37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM elena.hernandez-ramon@nih.gov FU Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health FX Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 32 TC 2 Z9 2 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2014 VL 35 IS 5 DI 10.1093/carcin/bgu029 PG 5 WC Oncology SC Oncology GA AH3RW UT WOS:000336043800024 PM 24501327 ER PT J AU Fox, D Yan, ZJ Ling, C Zhao, Y Lee, DY Fukagawa, T Yang, W Wang, WD AF Fox, David, III Yan, Zhijiang Ling, Chen Zhao, Ye Lee, Duck-Yeon Fukagawa, Tatsuo Yang, Wei Wang, Weidong TI The histone-fold complex MHF is remodeled by FANCM to recognize branched DNA and protect genome stability SO CELL RESEARCH LA English DT Article DE FANCM; Fanconi anemia; MHF; histone-fold; genome stability; branched DNA ID STALLED REPLICATION FORKS; COMPLEMENTATION GROUP-M; ANEMIA CORE COMPLEX; CROSS-LINK REPAIR; OUTER KINETOCHORE; DATA-BANK; ORTHOLOG; PATHWAY; MONOUBIQUITINATION; IDENTIFICATION AB Histone-fold proteins typically assemble in multiprotein complexes to bind duplex DNA. However, one histone-fold complex, MHF, associates with Fanconi anemia (FA) protein FANCM to form a branched DNA remodeling complex that senses and repairs stalled replication forks and activates FA DNA damage response network. How the FANCM-MHF complex recognizes branched DNA is unclear. Here, we solved the crystal structure of MHF and its complex with the MHF-interaction domain (referred to as MID) of FANCM, and performed structure-guided mutagenesis. We found that the MID-MHF complex consists of one histone H3-H4-like MHF heterotetramer wrapped by a single polypeptide of MID. We identified a zinc atom-liganding structure at the central interface between MID and MHF that is critical for stabilization of the complex. Notably, the DNA-binding surface of MHF was altered by MID in both electrostatic charges and allosteric conformation. This leads to a switch in the DNA-binding preference - from duplex DNA by MHF alone, to branched DNA by the MID-MHF complex. Mutations that disrupt either the composite DNA-binding surface or the protein-protein interface of the MID-MHF complex impaired activation of the FA network and genome stability. Our data provide the structural basis of how FANCM and MHF work together to recognize branched DNA, and suggest a novel mechanism by which histone-fold complexes can be remodeled by their partners to bind special DNA structures generated during DNA metabolism. C1 [Fox, David, III; Yan, Zhijiang; Ling, Chen; Wang, Weidong] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. [Zhao, Ye; Yang, Wei] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Lee, Duck-Yeon] NHLBI, Biochem Core Facil, NIH, Bethesda, MD 20892 USA. [Fukagawa, Tatsuo] Natl Inst Genet, Dept Mol Genet, Mishima, Shizuoka 4118540, Japan. [Fukagawa, Tatsuo] Grad Univ Adv Studies, Mishima, Shizuoka 4118540, Japan. RP Wang, WD (reprint author), NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. EM wangw@grc.nia.nih.gov RI Zhao, Ye/I-2936-2014; Yang, Wei/D-4926-2011 OI Zhao, Ye/0000-0002-5455-2586; Yang, Wei/0000-0002-3591-2195 FU Intramural Research Program of the National Institute on Aging, National Institute of Health [AG000688-07]; Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan FX This work was supported in part by the Intramural Research Program of the National Institute on Aging (AG000688-07), National Institute of Health; and by a Grant-in-Aid for Scientific Research (S) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan to TF. NR 43 TC 7 Z9 7 U1 0 U2 12 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD MAY PY 2014 VL 24 IS 5 BP 560 EP 575 DI 10.1038/cr.2014.42 PG 16 WC Cell Biology SC Cell Biology GA AH1XI UT WOS:000335914700005 PM 24699063 ER PT J AU Xu, XH Deng, CY Liu, Y He, M Peng, J Wang, T Yuan, L Zheng, ZS Blackshear, PJ Luo, ZG AF Xu, Xiao-Hui Deng, Cai-Yun Liu, Yang He, Miao Peng, Jian Wang, Tong Yuan, Lei Zheng, Zhi-Sheng Blackshear, Perry J. Luo, Zhen-Ge TI MARCKS regulates membrane targeting of Rab10 vesicles to promote axon development SO CELL RESEARCH LA English DT Article DE MARCKS; Rab10; plasmalemmal precursor vesicles; axon growth ID PROTEIN-KINASE-C; MAJOR SPECIFIC SUBSTRATE; NEURONAL POLARIZATION; PLASMA-MEMBRANE; ANTEROGRADE TRANSPORT; IN-VIVO; PHOSPHORYLATION; BRAIN; GROWTH; CELLS AB Axon development requires membrane addition from the intracellular supply, which has been shown to be mediated by Rab10-positive plasmalemmal precursor vesicles (PPVs). However, the molecular mechanisms underlying the membrane trafficking processes of PPVs remain unclear. Here, we show that myristoylated alanine-rich C-kinase substrate (MARCKS) mediates membrane targeting of Rab10-positive PPVs, and this regulation is critical for axon development. We found that the GTP-locked active form of Rab10 binds to membrane-associated MARCKS, whose affinity depends on the phosphorylation status of the MARCKS effector domain. Either genetic silencing of MARCKS or disruption of its interaction with Rab10 inhibited axon growth of cortical neurons, impaired docking and fusion of Rab10 vesicles with the plasma membrane, and consequently caused a loss of membrane insertion of axonal receptors responsive to extracellular axon growth factors. Thus, this study has identified a novel function of MARCKS in mediating membrane targeting of PPVs during axon development. C1 [Xu, Xiao-Hui; Deng, Cai-Yun; Liu, Yang; He, Miao; Peng, Jian; Wang, Tong; Yuan, Lei; Zheng, Zhi-Sheng; Luo, Zhen-Ge] Chinese Acad Sci, Inst Neurosci, Shanghai 200031, Peoples R China. [Xu, Xiao-Hui; Deng, Cai-Yun; Liu, Yang; He, Miao; Peng, Jian; Wang, Tong; Yuan, Lei; Zheng, Zhi-Sheng; Luo, Zhen-Ge] Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Neurosci, Shanghai 200031, Peoples R China. [Xu, Xiao-Hui] Shanghai Univ, Sch Life Sci, Shanghai 200444, Peoples R China. [Peng, Jian] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China. [Blackshear, Perry J.] Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. RP Luo, ZG (reprint author), Chinese Acad Sci, Inst Neurosci, Shanghai 200031, Peoples R China. EM zgluo@ion.ac.cn RI Wang, Tong/O-7351-2015 OI Wang, Tong/0000-0002-3680-8189 FU National Natural Science Foundation of China [31330032, 31321091, 61327902, 81171190]; National Key Basic Research Program of China [2014CB910203]; SA-SIBS Scholarship Program; Shanghai Postdoctoral Scientific Program; China Postdoctoral Science Foundation; KC Wong Education Foundation FX This work was supported by the National Natural Science Foundation of China (31330032, 31321091, and 61327902 to ZG L and 81171190 to XH X) and the National Key Basic Research Program of China (2014CB910203). We thank Dr Q Hu of ION Imaging Facility with microscope analysis and Dr Y Kong with EM analysis. XH X was supported by SA-SIBS Scholarship Program, Shanghai Postdoctoral Scientific Program, China Postdoctoral Science Foundation funded Project, and KC Wong Education Foundation. NR 58 TC 11 Z9 12 U1 4 U2 24 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD MAY PY 2014 VL 24 IS 5 BP 576 EP 594 DI 10.1038/cr.2014.33 PG 19 WC Cell Biology SC Cell Biology GA AH1XI UT WOS:000335914700006 PM 24662485 ER PT J AU van Schaijk, BCL Kumar, TRS Vos, MW Richman, A van Gemert, GJ Li, T Eappen, AG Williamson, KC Morahan, BJ Fishbaugher, M Kennedy, M Camargo, N Khan, SM Janse, CJ Sim, KL Hoffman, SL Kappe, SHI Sauerwein, RW Fidock, DA Vaughan, AM AF van Schaijk, Ben C. L. Kumar, T. R. Santha Vos, Martijn W. Richman, Adam van Gemert, Geert-Jan Li, Tao Eappen, Abraham G. Williamson, Kim C. Morahan, Belinda J. Fishbaugher, Matt Kennedy, Mark Camargo, Nelly Khan, Shahid M. Janse, Chris J. Sim, Kim Lee Hoffman, Stephen L. Kappe, Stefan H. I. Sauerwein, Robert W. Fidock, David A. Vaughan, Ashley M. TI Type II Fatty Acid Biosynthesis Is Essential for Plasmodium falciparum Sporozoite Development in the Midgut of Anopheles Mosquitoes SO EUKARYOTIC CELL LA English DT Article ID LIVER-STAGE DEVELOPMENT; TOXOPLASMA-GONDII; MALARIA PARASITES; GENE DELETION; IN-VITRO; APICOPLAST; GAMETOCYTES; INFECTION; RESISTANCE; PROTEIN AB The prodigious rate at which malaria parasites proliferate during asexual blood-stage replication, midgut sporozoite production, and intrahepatic development creates a substantial requirement for essential nutrients, including fatty acids that likely are necessary for parasite membrane formation. Plasmodium parasites obtain fatty acids either by scavenging from the vertebrate host and mosquito vector or by producing fatty acids de novo via the type two fatty acid biosynthesis pathway (FAS-II). Here, we study the FAS-II pathway in Plasmodium falciparum, the species responsible for the most lethal form of human malaria. Using antibodies, we find that the FAS-II enzyme FabI is expressed in mosquito midgut oocysts and sporozoites as well as liver-stage parasites but not during the blood stages. As expected, FabI colocalizes with the apicoplast-targeted acyl carrier protein, indicating that FabI functions in the apicoplast. We further analyze the FAS-II pathway in Plasmodium falciparum by assessing the functional consequences of deleting fabI and fabB/F. Targeted deletion or disruption of these genes in P. falciparum did not affect asexual blood-stage replication or the generation of midgut oocysts; however, subsequent sporozoite development was abolished. We conclude that the P. falciparum FAS-II pathway is essential for sporozoite development within the midgut oocyst. These findings reveal an important distinction from the rodent Plasmodium parasites P. berghei and P. yoelii, where the FAS-II pathway is known to be required for normal parasite progression through the liver stage but is not required for oocyst development in the Anopheles mosquito midgut. C1 [van Schaijk, Ben C. L.; Vos, Martijn W.; van Gemert, Geert-Jan; Sauerwein, Robert W.] Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, NL-6525 ED Nijmegen, Netherlands. [Kumar, T. R. Santha; Fidock, David A.] Columbia Univ, Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10027 USA. [Richman, Adam; Li, Tao; Eappen, Abraham G.; Sim, Kim Lee; Hoffman, Stephen L.] Sanaria Inc, Rockville, MD USA. [Williamson, Kim C.] Loyola Univ, Dept Biol, Chicago, IL 60626 USA. [Williamson, Kim C.; Morahan, Belinda J.] NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. [Fishbaugher, Matt; Kennedy, Mark; Camargo, Nelly; Kappe, Stefan H. I.; Vaughan, Ashley M.] Seattle Biomed Res Inst, Seattle, WA 98109 USA. [Khan, Shahid M.; Janse, Chris J.] Leiden Univ, Leiden Malaria Res Grp, Leiden, Netherlands. [Kappe, Stefan H. I.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. [Fidock, David A.] Columbia Univ, Coll Phys & Surg, Dept Infect Dis, New York, NY USA. RP Fidock, DA (reprint author), Columbia Univ, Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10027 USA. EM df2260@columbia.edu; ashley.vaughan@seattlebiomed.org RI Sauerwein, Robert/C-8519-2013 FU NIH [R56 AI080685, R01 AI085584]; Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative [1481]; Intramural Research Program of the National Institute of Allergy and Infectious Diseases; National Institutes of Health; Top Institute Pharma (Netherlands) [T4-102] FX The NIH (R56 AI080685 to S.H.I.K. and A.M.V. and R01 AI085584 to D.A.F.), the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative (grant no. 1481; to S.H.I.K.), the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Top Institute Pharma (Netherlands) project T4-102 all provided partial funding for this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 22 Z9 22 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 EI 1535-9786 J9 EUKARYOT CELL JI Eukaryot. Cell PD MAY PY 2014 VL 13 IS 5 BP 550 EP 559 DI 10.1128/EC.00264-13 PG 10 WC Microbiology; Mycology SC Microbiology; Mycology GA AH1UY UT WOS:000335907900001 PM 24297444 ER PT J AU Park, YN Zhao, XH Yim, YI Todor, H Ellerbrock, R Reidy, M Eisenberg, E Masison, DC Greene, LE AF Park, Yang-Nim Zhao, Xiaohong Yim, Yang-In Todor, Horia Ellerbrock, Robyn Reidy, Michael Eisenberg, Evan Masison, Daniel C. Greene, Lois E. TI Hsp104 Overexpression Cures Saccharomyces cerevisiae [PSI+] by Causing Dissolution of the Prion Seeds SO EUKARYOTIC CELL LA English DT Article ID GUANIDINE-HYDROCHLORIDE; YEAST PRION; PROTEIN DISAGGREGATION; GENE-EXPRESSION; IN-VIVO; PROPAGATION; CHAPERONE; HSP70; ELIMINATION; PSI(+) AB The [PSI+] yeast prion is formed when Sup35 misfolds into amyloid aggregates. [PSI+], like other yeast prions, is dependent on the molecular chaperone Hsp104, which severs the prion seeds so that they pass on as the yeast cells divide. Surprisingly, however, overexpression of Hsp104 also cures [PSI+]. Several models have been proposed to explain this effect: inhibition of severing, asymmetric segregation of the seeds between mother and daughter cells, and dissolution of the prion seeds. First, we found that neither the kinetics of curing nor the heterogeneity in the distribution of the green fluorescent protein (GFP)-labeled Sup35 foci in partially cured yeast cells is compatible with Hsp104 overexpression curing [PSI+] by inhibiting severing. Second, we ruled out the asymmetric segregation model by showing that the extent of curing was essentially the same in mother and daughter cells and that the fluorescent foci did not distribute asymmetrically, but rather, there was marked loss of foci in both mother and daughter cells. These results suggest that Hsp104 overexpression cures [PSI+] by dissolution of the prion seeds in a two-step process. First, trimming of the prion seeds by Hsp104 reduces their size, and second, their amyloid core is eliminated, most likely by proteolysis. C1 [Park, Yang-Nim; Zhao, Xiaohong; Yim, Yang-In; Todor, Horia; Ellerbrock, Robyn; Eisenberg, Evan; Greene, Lois E.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Reidy, Michael; Masison, Daniel C.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Greene, LE (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM greenel@helix.nih.gov OI Reidy, Michael/0000-0002-9290-7595 FU Intramural Research Program of the National Institutes of Health (NIH); National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases FX This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), the National Heart, Lung, and Blood Institute, and the National Institute of Diabetes and Digestive and Kidney Diseases. NR 44 TC 14 Z9 14 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 EI 1535-9786 J9 EUKARYOT CELL JI Eukaryot. Cell PD MAY PY 2014 VL 13 IS 5 BP 635 EP 647 DI 10.1128/EC.00300-13 PG 13 WC Microbiology; Mycology SC Microbiology; Mycology GA AH1UY UT WOS:000335907900008 PM 24632242 ER PT J AU Olafsdottir, LB Erlendsdottir, H Melo-Cristino, J Weinberger, DM Ramirez, M Kristinsson, KG Gottfredsson, M AF Olafsdottir, L. B. Erlendsdottir, H. Melo-Cristino, J. Weinberger, D. M. Ramirez, M. Kristinsson, K. G. Gottfredsson, M. TI Invasive infections due to Streptococcus pyogenes: seasonal variation of severity and clinical characteristics, Iceland, 1975 to 2012 SO EUROSURVEILLANCE LA English DT Article ID GROUP-A STREPTOCOCCI; UNITED-STATES; VITAMIN-D; DISEASE; INFLUENZA; EUROPE; SUSCEPTIBILITY; EPIDEMIOLOGY; CANDIDEMIA; NATIONWIDE AB Epidemiology and clinical characteristics of invasive Group A streptococcal infections (IGASI) are highly variable. Long-term studies are needed to understand the interplay between epidemiology and virulence. In a population-based study of IGASI in Iceland from 1975 to 2012, 288 cases were identified by positive cultures from normally sterile body sites. Charts were reviewed retrospectively and emm-types of viable Streptococcus pyogenes isolates (n=226) determined. Comparing the first and last decade of the study period, IGASI incidence increased from 1.09 to 3.96 cases per 100,000 inhabitants per year. The most common were emm types 1 (25%), 28 (11%) and 89 (11%); emm1 strains were most likely to cause severe infections. Infections in adults were significantly more likely to be severe during the seasonal peak from January to April (risk ratio: 2.36, 95% confidence interval: 1.34-4.15). Significant seasonal variability in severity was noted among patients with diagnosis of sepsis, respiratory infection and cellulitis, with 38% of severe infections in January to April compared with 16% in other months (p < 0.01). A seasonal increase in severity of IGASI suggested that generalised seasonal increase in host susceptibility, rather than introduction of more virulent strains may play a role in the pathogenesis of these potentially fatal infections. C1 [Olafsdottir, L. B.; Gottfredsson, M.] Landspitali Univ Hosp, Dept Med, Reykjavik, Iceland. [Erlendsdottir, H.; Kristinsson, K. G.] Landspitali Univ Hosp, Reykjavik, Iceland. [Erlendsdottir, H.; Kristinsson, K. G.; Gottfredsson, M.] Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland. [Melo-Cristino, J.; Ramirez, M.] Univ Lisbon, Fac Med, Inst Mol Med, Inst Microbiol, P-1699 Lisbon, Portugal. [Weinberger, D. M.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Weinberger, D. M.] Yale Univ, Dept Epidemiol Microbial Dis, Sch Publ Hlth, New Haven, CT USA. RP Olafsdottir, LB (reprint author), Landspitali Univ Hosp, Dept Med, Reykjavik, Iceland. RI Ramirez, Mario/B-4993-2008; Melo-Cristino, Jose/H-3726-2013; OI Ramirez, Mario/0000-0002-4084-6233; Melo-Cristino, Jose/0000-0001-8643-1722; Gottfredsson, Magnus/0000-0003-2465-0422 FU Icelandic Center for Research, Rannis [100436021]; Landspitali University Hospital Science Fund FX This work was supported in part by grants from the Icelandic Center for Research, Rannis [grant number 100436021]; and the Landspitali University Hospital Science Fund (http://rannis.is/english/home/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study was presented in part at ID week, San Diego, 17-21 October 2012. NR 34 TC 6 Z9 6 U1 0 U2 1 PU EUR CENTRE DIS PREVENTION & CONTROL PI STOCKHOLM PA TOMTEBODAVAGEN 11A, STOCKHOLM, 171 83, SWEDEN SN 1560-7917 J9 EUROSURVEILLANCE JI Eurosurveillance PD MAY 1 PY 2014 VL 19 IS 17 BP 5 EP 14 AR 20784 PG 10 WC Infectious Diseases SC Infectious Diseases GA AH1WX UT WOS:000335913600002 PM 24821122 ER PT J AU James, P Berrigan, D Hart, JE Hipp, JA Hoehner, CM Kerr, J Major, JM Oka, M Laden, F AF James, Peter Berrigan, David Hart, Jaime E. Hipp, J. Aaron Hoehner, Christine M. Kerr, Jacqueline Major, Jacqueline M. Oka, Masayoshi Laden, Francine TI Effects of buffer size and shape on associations between the built environment and energy balance SO HEALTH & PLACE LA English DT Article DE Built environment; Walking; Body mass index; Geographic information systems; Spatial uncertainty ID AREAL UNIT PROBLEM; BODY-MASS INDEX; PHYSICAL-ACTIVITY; URBAN FORM; NEIGHBORHOOD BOUNDARIES; FOOD ENVIRONMENT; WOMENS HEALTH; RISK-FACTORS; ZONE DESIGN; OBESITY AB Uncertainty in the relevant spatial context may drive heterogeneity in findings on the built environment and energy balance. To estimate the effect of this uncertainty, we conducted a sensitivity analysis defining intersection and business densities and counts within different buffer sizes and shapes on associations with self-reported walking and body mass index. Linear regression results indicated that the scale and shape of buffers influenced study results and may partly explain the inconsistent findings in the built environment and energy balance literature. (C) 2014 Elsevier Ltd. All rights reserved. C1 [James, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Berrigan, David] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Hart, Jaime E.] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02215 USA. [Hart, Jaime E.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Hipp, J. Aaron] Washington Univ, George Warren Brown Sch Social Work, St Louis, MO 63130 USA. [Hoehner, Christine M.] Washington Univ, George Warren Brown Sch Social Work, St Louis, MO 63110 USA. [Kerr, Jacqueline] UCSD, Dept Psychol, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Kerr, Jacqueline] SDSU, Grad Sch Publ Hlth, La Jolla, CA 92093 USA. [Major, Jacqueline M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Oka, Masayoshi] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA. [Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. RP James, P (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 401 Pk Dr,3rd Floor West, Boston, MA 02215 USA. EM pjames@hsph.harvard.edu; berrigad@mail.nih.gov; rejch@channing.harvard.edu; ahipp@brownschool.wustl.edu; hoehnerc@wudosis.wustl.edu; jkerr@ucsd.edu; jqmajor@yahoo.com; moka@wudosis.wustl.edu; francine.laden@channing.harvard.edu FU NCI Centers for Transdisciplinary Research on Energetics and Cancer (TREC) [U54 CA155626, U54 CA155435, U54 CA155850, U54 CA155796, U01 CA116850]; NCI as part of the TREC initiative; Harvard NHLBI Cardiovascular Epidemiology Training Grant [T32 HL 098048]; NIH [UM1 CA176726, R01 ES017017] FX This work was supported by the NCI Centers for Transdisciplinary Research on Energetics and Cancer (TREC) (U54 CA155626, U54 CA155435, U54 CA155850, U54 CA155796, U01 CA116850). All authors were funded by NCI as part of the TREC initiative (except Berrigan and Major). The opinions or assertions contained herein are the private ones of the authors and are not considered as official or reflecting the views of the National Institutes of Health. Work was also supported by the Harvard NHLBI Cardiovascular Epidemiology Training Grant T32 HL 098048 and NIH Grants UM1 CA176726 and R01 ES017017. We thank the TREC Spatial and Contextual Measures and Modeling Working Group who contributed greatly to this analysis. NR 59 TC 21 Z9 21 U1 3 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8292 EI 1873-2054 J9 HEALTH PLACE JI Health Place PD MAY PY 2014 VL 27 BP 162 EP 170 DI 10.1016/j.healthplace.2014.02.003 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AG9TX UT WOS:000335763800021 PM 24607875 ER PT J AU Cruse, G Metcalfe, DD Olivera, A AF Cruse, Glenn Metcalfe, Dean D. Olivera, Ana TI Functional Deregulation of KIT Link to Mast Cell Proliferative Diseases and Other Neoplasms SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article DE Mastocytosis; KIT mutations; KIT signaling; KIT trafficking; KIT inhibitors ID RECEPTOR TYROSINE KINASE; GROWTH-FACTOR-RECEPTOR; CHRONIC MYELOID-LEUKEMIA; MUTANT C-KIT; GENE-EXPRESSION PROFILE; STEM-CELL; SYSTEMIC MASTOCYTOSIS; SIGNAL-TRANSDUCTION; HEMATOPOIETIC-CELLS; CATALYTIC DOMAIN AB In-this review, the authors discuss common gain-of-function mutations in the stem cell factor receptor KIT found in mast cell proliferation disorders and summarize the current understanding of the molecular mechanisms by which these transforming mutations may affect KIT structure and function leading to altered downstream signaling and cellular transformation. Drugs targeting KIT have shown mixed success in the treatment of mastocytosis and other hyperproliferative diseases. A brief overview of the most common KIT inhibitors currently used, the reasons for the varied clinical results of such inhibitors and a discussion of potential new strategies are provided. C1 [Cruse, Glenn; Metcalfe, Dean D.; Olivera, Ana] NIAID, Mast Cell Biol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Olivera, A (reprint author), NIAID, Mast Cell Biol Sect, Lab Allerg Dis, NIH, 10 Ctr Dr,Bldg 10,Room 11C207,MSC 1881, Bethesda, MD 20892 USA. EM Ana.Olivera@nih.gov FU Division of Intramural Research of NIAID within the National Institutes of Health FX Financial support was provided by the Division of Intramural Research of NIAID within the National Institutes of Health. NR 125 TC 13 Z9 14 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 0889-8561 EI 1557-8607 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 2014 VL 34 IS 2 BP 219 EP + DI 10.1016/j.iac.2014.01.002 PG 20 WC Allergy; Immunology SC Allergy; Immunology GA AH5RI UT WOS:000336188300005 PM 24745671 ER PT J AU Richardson, BS Anderson, WF Barnholtz-Sloan, JS Tucker, MA Gerstenblith, MR AF Richardson, Blakely S. Anderson, William F. Barnholtz-Sloan, Jill S. Tucker, Margaret A. Gerstenblith, Meg R. TI The Age-Specific Effect Modification of Male Sex for Ulcerated Cutaneous Melanoma SO JAMA DERMATOLOGY LA English DT Article ID AMERICAN JOINT COMMITTEE; CANCER STAGING SYSTEM; GENDER; EXPOSURE AB IMPORTANCE Tumor ulceration is an important prognostic factor for cutaneous melanoma (CM). Previous studies demonstrated that the proportion of ulcerated to nonulcerated CM rose with increasing tumor depth. These frequency-based studies, however, were not adjusted for the population at risk. OBJECTIVE To determine the absolute incidence of ulcerated CM by tumor depth, stratified by sex and age at diagnosis. DESIGN, SETTING, AND PARTICIPANTS We compared ulcerated CM by tumor thicknesses (<= 1.00, 1.01-2.00, 2.01-4.00, and >= 4.01 mm), stratified by sex among younger (10-39 years) and older (40-84 years) non-Hispanic whites in the National Cancer Institute's Surveillance, Epidemiology, and End Results database from 2004 through 2008. Types of CM included superficial spreading, nodular, and unclassified in 5106 cases among 3206 men and 1900 women. MAIN OUTCOMES AND MEASURES Incidence of ulcerated CM by tumor depth for younger and older men and women. RESULTS The incidence of tumor ulceration was stable across all tumor depths among younger men and older women. Among younger women, it declined for the thickest lesions (0.08 per 100 000 for tumor depth >= 4.01 mm), although the trend was not statistically significant. In contrast, among older men, there was a statistically significant increase in ulceration for CM with a depth of approximately 1.4 per 100 000 for tumor depth of 2.00 mm or thicker. CONCLUSIONS AND RELEVANCE Male sex is an age-specific effect modifier for ulcerated CM by tumor depth. Future studies and staging guidelines should consider the interaction among CM ulceration, thickness, sex, and age at diagnosis. C1 [Richardson, Blakely S.; Gerstenblith, Meg R.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Dept Dermatol, Sch Med, Cleveland, OH 44106 USA. [Anderson, William F.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Barnholtz-Sloan, Jill S.] Case Western Reserve Univ, Case Comprehens Canc Ctr, Sch Med, Cleveland, OH 44106 USA. [Tucker, Margaret A.] NCI, Human Genet Program, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Gerstenblith, MR (reprint author), Case Western Reserve Univ, Univ Hosp Case Med Ctr, Dept Dermatol, Sch Med, 11100 Euclid Ave,Lakeside 3rd Floor Dermatol, Cleveland, OH 44106 USA. EM meg.gerstenblith@uhhospitals.org RI Tucker, Margaret/B-4297-2015 FU Char and Chuck Fowler Family Foundation; Dermatology Foundation Career Development Award in Medical Dermatology; National Cancer Institute [P30 CA043703] FX This study was supported by the Char and Chuck Fowler Family Foundation and the Dermatology Foundation Career Development Award in Medical Dermatology (Dr Gerstenblith), and in part by National Cancer Institute grant P30 CA043703 from the Case Comprehensive Cancer Center (Dr Barnholtz-Sloan). No other disclosures were reported. NR 15 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD MAY PY 2014 VL 150 IS 5 BP 522 EP 525 DI 10.1001/jamadermatol.2013.7127 PG 4 WC Dermatology SC Dermatology GA AH2NH UT WOS:000335957700009 PM 24599332 ER PT J AU Beal, MF Oakes, D Shoulson, I Henchcliffe, C Galpern, WR Haas, R Juncos, JL Nutt, JG Voss, TS Ravina, B Shults, CM Helles, K Snively, V Lew, MF Griebner, B Watts, A Gao, S Pourcher, E Bond, L Kompoliti, K Agarwal, P Sia, C Jog, M Cole, L Sultana, M Kurlan, R Richard, I Deeley, C Waters, CH Figueroa, A Arkun, A Brodsky, M Ondo, WG Hunter, CB Jimenez-Shahed, J Palao, A Miyasaki, JM Julie, SO Tetrud, J Reys, L Smith, K Singer, C Blenke, A Russell, DS Cotto, C Friedman, JH Lannon, M Zhang, L Drasby, E Kumar, R Subramanian, T Ford, DS Grimes, DA Cote, D Conway, J Siderowf, AD Evatt, ML Sommerfeld, B Lieberman, AN Okun, MS Rodriguez, RL Merritt, S Swartz, CL Martin, WRW King, P Stover, N Guthrie, S Watts, RL Ahmed, A Fernandez, HH Winters, A Mari, Z Dawson, TM Dunlop, B Feigin, AS Shannon, B Nirenberg, MJ Ogg, M Ellias, SA Thomas, CA Frei, K Bodis-Wollner, I Glazman, S Mayer, T Hauser, RA Pahwa, R Langhammer, A Ranawaya, R Derwent, L Sethi, KD Farrow, B Prakash, R Litvan, I Robinson, A Sahay, A Gartner, M Hinson, VK Markind, S Pelikan, M Perlmutter, JS Hartlein, J Molho, E Evans, S Adler, CH Duffy, A Lind, M Elmer, L Davis, K Spears, J Wilson, S Leehey, MA Hermanowicz, N Niswonger, S Shill, HA Obradov, S Rajput, A Cowper, M Lessig, S Song, D Fontaine, D Zadikoff, C Williams, K Blindauer, KA Bergholte, J Propsom, CS Stacy, MA Field, J Mihaila, D Chilton, M Uc, EY Sieren, J Simon, DK Kraics, L Silver, A Boyd, JT Hamill, RW Ingvoldstad, C Young, J Thomas, K Kostyk, SK Wojcieszek, J Pfeiffer, RF Panisset, M Beland, M Reich, SG Cines, M Zappala, N Rivest, J Zweig, R Lumina, LP Hilliard, CL Grill, S Kellermann, M Tuite, P Rolandelli, S Kang, UJ Young, J Rao, J Cook, MM Severt, L Boyar, K AF Beal, M. Flint Oakes, David Shoulson, Ira Henchcliffe, Claire Galpern, Wendy R. Haas, Richard Juncos, Jorge L. Nutt, John G. Voss, Tiffini Smith Ravina, Bernard Shults, Clifford M. Helles, Karen Snively, Victoria Lew, Mark F. Griebner, Brian Watts, Arthur Gao, Shan Pourcher, Emmanuelle Bond, Louisette Kompoliti, Katie Agarwal, Pinky Sia, Cherissa Jog, Mandar Cole, Linda Sultana, Munira Kurlan, Roger Richard, Irene Deeley, Cheryl Waters, Cheryl H. Figueroa, Angel Arkun, Ani Brodsky, Matthew Ondo, William G. Hunter, Christine B. Jimenez-Shahed, Joohi Palao, Alicia Miyasaki, Janis M. Julie, S. O. Tetrud, James Reys, Liza Smith, Katharine Singer, Carlos Blenke, Anita Russell, David S. Cotto, Candace Friedman, Joseph H. Lannon, Margaret Zhang, Lin Drasby, Edward Kumar, Rajeev Subramanian, Thyagarajan Ford, Donna Stuppy Grimes, David A. Cote, Diane Conway, Jennifer Siderowf, Andrew D. Evatt, Marian Leslie Sommerfeld, Barbara Lieberman, Abraham N. Okun, Michael S. Rodriguez, Ramon L. Merritt, Stacy Swartz, Camille Louise Martin, W. R. Wayne King, Pamela Stover, Natividad Guthrie, Stephanie Watts, Ray L. Ahmed, Anwar Fernandez, Hubert H. Winters, Adrienna Mari, Zoltan Dawson, Ted M. Dunlop, Becky Feigin, Andrew S. Shannon, Barbara Nirenberg, Melissa Jill Ogg, Mattson Ellias, Samuel A. Thomas, Cathi-Ann Frei, Karen Bodis-Wollner, Ivan Glazman, Sofya Mayer, Thomas Hauser, Robert A. Pahwa, Rajesh Langhammer, April Ranawaya, Ranjit Derwent, Lorelei Sethi, Kapil D. Farrow, Buff Prakash, Rajan Litvan, Irene Robinson, Annette Sahay, Alok Gartner, Maureen Hinson, Vanessa K. Markind, Samuel Pelikan, Melisa Perlmutter, Joel S. Hartlein, Johanna Molho, Eric Evans, Sharon Adler, Charles H. Duffy, Amy Lind, Marlene Elmer, Lawrence Davis, Kathy Spears, Julia Wilson, Stephanie Leehey, Maureen A. Hermanowicz, Neal Niswonger, Shari Shill, Holly A. Obradov, Sanja Rajput, Alex Cowper, Marilyn Lessig, Stephanie Song, David Fontaine, Deborah Zadikoff, Cindy Williams, Karen Blindauer, Karen A. Bergholte, Jo Propsom, Clara Schindler Stacy, Mark A. Field, Joanne Mihaila, Dragos Chilton, Mark Uc, Ergun Y. Sieren, Jeri Simon, David K. Kraics, Lauren Silver, Althea Boyd, James T. Hamill, Robert W. Ingvoldstad, Christopher Young, Jennifer Thomas, Karen Kostyk, Sandra K. Wojcieszek, Joanne Pfeiffer, Ronald F. Panisset, Michel Beland, Monica Reich, Stephen G. Cines, Michelle Zappala, Nancy Rivest, Jean Zweig, Richard Lumina, L. Pepper Hilliard, Colette Lynn Grill, Stephen Kellermann, Marye Tuite, Paul Rolandelli, Susan Kang, Un Jung Young, Joan Rao, Jayaraman Cook, Maureen M. Severt, Lawrence Boyar, Karyn TI A Randomized Clinical Trial of High-Dosage Coenzyme Q10 in Early Parkinson Disease No Evidence of Benefit SO JAMA NEUROLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; NEURODEGENERATIVE DISEASE; HUNTINGTONS-DISEASE; DOUBLE-BLIND; VITAMIN-E; Q(10); MITOCHONDRIA; THERAPY AB IMPORTANCE Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit. OBJECTIVE To examine whether CoQ10 could slow disease progression in early PD. DESIGN, SETTING, AND PARTICIPANTS A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation. INTERVENTIONS The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E. MAIN OUTCOMES AND MEASURES Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo. RESULTS The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P =.49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P =.21 relative to placebo). CONCLUSIONS AND RELEVANCE Coenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit. C1 [Beal, M. Flint; Henchcliffe, Claire; Arkun, Ani; Ogg, Mattson] New York Hosp, Weill Cornell Med Coll, Dept Neurol, New York, NY 10065 USA. [Oakes, David; Helles, Karen; Snively, Victoria; Griebner, Brian; Watts, Arthur; Gao, Shan] Univ Rochester, Med Ctr, Dept Biostat, Rochester, NY 14642 USA. [Shoulson, Ira] Georgetown Univ, Dept Neurol, Washington, DC USA. [Galpern, Wendy R.] Natl Inst Hlth, Bethesda, MD USA. [Haas, Richard; Shults, Clifford M.; Litvan, Irene] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Juncos, Jorge L.; Evatt, Marian Leslie; Sommerfeld, Barbara] Emory Univ, Sch Med, Dept Neurol, WesleyWoods Ctr, Atlanta, GA 30322 USA. [Nutt, John G.; Brodsky, Matthew] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Voss, Tiffini Smith] Merck, Rahway, NJ 07065 USA. [Ravina, Bernard] Biogen Idec Inc, Cambridge, MA USA. [Shults, Clifford M.] VA Med Ctr, San Diego, CA USA. [Lew, Mark F.] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. [Watts, Arthur; Richard, Irene; Deeley, Cheryl] Univ Rochester, Dept Neurol, Rochester, NY USA. [Pourcher, Emmanuelle; Bond, Louisette] Quebec Memory & Motor Skills Disorders Res Ctr, Clin Sainte Anne, Quebec City, PQ, Canada. [Kompoliti, Katie] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Agarwal, Pinky; Sia, Cherissa] Booth Gardner Parkinsons Care Ctr, Washington, DC USA. [Jog, Mandar; Cole, Linda; Sultana, Munira] London Hlth Sci Ctr, London, ON, Canada. [Kurlan, Roger] Overlook Med Ctr, Atlantic Neurosci Inst, Summit, NJ USA. [Waters, Cheryl H.; Figueroa, Angel] Columbia Univ, Med Ctr, Neurol Inst, New York, NY USA. [Ondo, William G.] Univ Texas Hlth Sci Ctr Houston, Dept Neurol, Houston, TX 77030 USA. [Hunter, Christine B.; Jimenez-Shahed, Joohi; Palao, Alicia] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Miyasaki, Janis M.; Julie, S. O.] Univ Toronto, Toronto Western Hosp, Morton & Gloria Shulman Movement Disorders Ctr, Toronto, ON M5T 2S8, Canada. [Tetrud, James; Reys, Liza; Smith, Katharine] Parkinsons Inst & Clin Ctr, Sunnyvale, CA USA. [Singer, Carlos; Blenke, Anita] Univ Miami, Sch Med, Dept Neurol, Miami, FL USA. [Russell, David S.; Cotto, Candace] Inst Neurodegenerat Disorders, New Haven, CT USA. [Friedman, Joseph H.; Lannon, Margaret] Butler Hosp, Dept Neurol, Providence, RI 02906 USA. [Friedman, Joseph H.] Butler Hosp, Alpert Med Sch, Providence, RI 02906 USA. [Lannon, Margaret; Drasby, Edward] Port City Neurology Inc, Scarborough, ME USA. [Zhang, Lin] Univ Calif Davis, Sch Med, Dept Neurol, Sacramento, CA 95817 USA. [Zhang, Lin] Sacramento VA Med Ctr, Sacramento, CA USA. [Subramanian, Thyagarajan; Ford, Donna Stuppy] Penn State Hershey Coll Med, Dept Neurol, Milton S Hershey Med Ctr, Hershey, PA USA. [Grimes, David A.; Cote, Diane; Conway, Jennifer] Ottawa Civic Hosp, Ottawa, ON K1Y 4E9, Canada. [Siderowf, Andrew D.] Avid Radiopharmaceut, Philadelphia, PA USA. [Evatt, Marian Leslie] Atlanta VA Med Ctr, Atlanta, GA USA. [Lieberman, Abraham N.] St Josephs Hosp, Barrow Neurol Inst, Muhammad Ali Parkinson Ctr, Phoenix, AZ USA. [Okun, Michael S.; Rodriguez, Ramon L.; Merritt, Stacy; Swartz, Camille Louise] Univ Florida, Dept Neurol, Ctr Movement Disorders & Neurorestorat, Gainesville, FL USA. [Martin, W. R. Wayne; King, Pamela] Univ Alberta, Glenrose Rehabil Hosp, Edmonton, AB, Canada. [Stover, Natividad; Guthrie, Stephanie; Watts, Ray L.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL USA. [Ahmed, Anwar; Fernandez, Hubert H.; Winters, Adrienna] Cleveland Clin, Dept Neurol, Ctr Neurol Restorat, Cleveland, OH 44106 USA. [Mari, Zoltan; Dawson, Ted M.; Dunlop, Becky; Grill, Stephen] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Feigin, Andrew S.; Shannon, Barbara] Ctr Neurosci, Feinstein Inst Med Res, Manhasset, NY USA. [Nirenberg, Melissa Jill] NYU, Dept Neurol, Langone Med Ctr, New York, NY 10016 USA. [Ellias, Samuel A.; Thomas, Cathi-Ann] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Frei, Karen] Parkinsons & Movement Disorder Inst, Fountain Valley, CA USA. [Bodis-Wollner, Ivan; Glazman, Sofya; Mayer, Thomas] State Univ New York, Downstate Med Ctr, Brooklyn, NY USA. [Hauser, Robert A.] Univ S Florida, Dept Neurol, Tampa, FL 33620 USA. [Pahwa, Rajesh; Langhammer, April] Univ Kansas Med Ctr, Dept Neurol, Kansas City, KS USA. [Ranawaya, Ranjit; Derwent, Lorelei] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Sethi, Kapil D.; Farrow, Buff; Prakash, Rajan] Georgia Hlth Sci Univ, Dept Neurol, Augusta, GA USA. [Robinson, Annette] Univ Louisville, Dept Neurol, Louisville, KY 40292 USA. [Sahay, Alok; Gartner, Maureen] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Hinson, Vanessa K.] Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. [Markind, Samuel; Pelikan, Melisa] Associated Neurol PC, Danbury, CT USA. [Perlmutter, Joel S.; Hartlein, Johanna] Washington Univ, Dept Neurol, St Louis, MO USA. [Molho, Eric; Evans, Sharon] Albany Med Ctr, Movement Disorders Ctr, Albany, NY USA. [Adler, Charles H.; Duffy, Amy; Lind, Marlene] Mayo Clin, Dept Neurol, Parkinsons Dis & Movement Disorders Ctr, Scottsdale, AZ USA. [Elmer, Lawrence] Univ Toledo, Ctr Neurol Hlth, Toledo, OH 43606 USA. [Davis, Kathy; Spears, Julia; Wilson, Stephanie] Med Univ Ohio Toledo, Dept Neurol, Toledo, OH USA. [Leehey, Maureen A.] Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. [Hermanowicz, Neal; Niswonger, Shari] Univ Calif Irvine, Dept Neurol, Irvine Med Ctr, Irvine, CA 92717 USA. [Shill, Holly A.; Obradov, Sanja] Banner Sun Hlth Res Inst, Sun City, AZ USA. [Rajput, Alex; Cowper, Marilyn] Univ Saskatchewan, Royal Univ Hosp, Dept Neurol, Saskatoon, SK S7N 0W0, Canada. [Lessig, Stephanie; Song, David; Fontaine, Deborah] Univ Calif San Diego, Dept Neurol, San Diego, CA 92103 USA. [Zadikoff, Cindy; Williams, Karen] Northwestern Univ, Dept Neurol, Feinberg Sch Med, Chicago, IL 60611 USA. [Blindauer, Karen A.; Bergholte, Jo; Propsom, Clara Schindler] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA. [Stacy, Mark A.; Field, Joanne] Duke Univ, Dept Neurol, Durham, NC USA. [Mihaila, Dragos; Chilton, Mark] State Univ New York Upstate Med Ctr, Syracuse, NY USA. [Mihaila, Dragos; Chilton, Mark] Syracuse VA Med Ctr, Syracuse, NY USA. [Uc, Ergun Y.; Sieren, Jeri] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA. [Simon, David K.; Kraics, Lauren; Silver, Althea] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Simon, David K.; Kraics, Lauren; Silver, Althea] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Boyd, James T.; Hamill, Robert W.; Ingvoldstad, Christopher; Young, Jennifer] Univ Vermont, Coll Med, Dept Neurol, Burlington, VT 05405 USA. [Thomas, Karen; Kostyk, Sandra K.] Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA. [Wojcieszek, Joanne] Indiana Univ, Sch Med, Dept Neurol, Indianapolis, IN 46202 USA. [Pfeiffer, Ronald F.] Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA. [Panisset, Michel; Beland, Monica] CHUM Hop Notre Dame, Dept Neurol, Montreal, PQ, Canada. [Reich, Stephen G.; Cines, Michelle; Zappala, Nancy] Univ Maryland, Maryland Sch Sci, Dept Neurol, Baltimore, MD 21201 USA. [Rivest, Jean] Univ Sherbrooke, Dept Neurol, Sherbrooke, PQ J1K 2R1, Canada. [Zweig, Richard; Lumina, L. Pepper] Louisiana State Univ, Hlth Sci Ctr, Dept Neurol, Shreveport, LA 71105 USA. [Hilliard, Colette Lynn] Lewis Hall Singletary Oncol Ctr, Thomasville, GA USA. [Kellermann, Marye] Parkinson & Movement Disorders Ctr Maryland, Elkridge, MD USA. [Tuite, Paul; Rolandelli, Susan] Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. [Kang, Un Jung; Young, Joan] Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. [Rao, Jayaraman; Cook, Maureen M.] Ochsner Clin Fdn, Dept Neurol, New Orleans, LA USA. [Severt, Lawrence; Boyar, Karyn] Beth Israel Deaconess Med Ctr, Dept Neurol, New York, NY 10003 USA. RP Beal, MF (reprint author), New York Hosp, Weill Cornell Med Coll, Dept Neurol, 525 E 68th St, New York, NY 10065 USA. EM fbeal@med.cornell.edu OI Miyasaki, Janis/0000-0002-6372-6007 FU National Institute of Neurological Disorders and Stroke to the Cornell University [U01 NS 050324]; [U01 NS050573] FX The study was funded by grants from the National Institute of Neurological Disorders and Stroke to the Cornell University (U01 NS 050324; Dr Beal, PI) and to the University of Rochester (U01 NS050573; Dr Oakes, PI). We were also supported by the Parkinson's Disease Foundation with regard to facilitating minority enrollment. NR 28 TC 59 Z9 59 U1 4 U2 21 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD MAY PY 2014 VL 71 IS 5 BP 543 EP 552 DI 10.1001/jamaneurol.2014.131 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA AH2MX UT WOS:000335956700005 ER PT J AU Frohman, EM Monaco, MC Remington, G Ryschkewitsch, C Jensen, PN Johnson, K Perkins, M Liebner, J Greenberg, B Monson, N Frohman, TC Douek, D Major, EO AF Frohman, Elliot M. Monaco, Maria Chiara Remington, Gina Ryschkewitsch, Caroline Jensen, Peter N. Johnson, Kory Perkins, Molly Liebner, Julia Greenberg, Benjamin Monson, Nancy Frohman, Teresa C. Douek, Daniel Major, Eugene O. TI JC Virus in CD34(+) and CD19(+) Cells in Patients With Multiple Sclerosis Treated With Natalizumab SO JAMA NEUROLOGY LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; HEMATOPOIETIC PROGENITOR CELLS; TONSILLAR STROMAL CELLS; HUMAN CYTOMEGALOVIRUS; ANTIBODY NATALIZUMAB; RISK STRATIFICATION; VIRAL LATENCY; B-LYMPHOCYTES; BONE-MARROW; GLIAL-CELLS AB IMPORTANCE Infection with JC virus (JCV) may lead to development of demyelinating progressive multifocal leukoencephalopathy in patients with multiple sclerosis (MS) who are treated with natalizumab. OBJECTIVE To determine whether mononuclear cells in circulation from MS patients treated with natalizumab harbor JCV DNA. DESIGN, SETTING, AND PARTICIPANTS In this prospective investigation, we enrolled 49 MS patients from the Clinical Center for Multiple Sclerosis at The University of Texas Southwestern Medical Center and 18 healthy volunteers. We drew 120-mL blood samples from 26 MS patients at baseline and at approximately 3-month intervals to 10 months during the course of natalizumab infusions. One blood sample was drawn from 23 MS patients receiving natalizumab for more than 24 months and from 18 healthy volunteers. INTERVENTIONS Natalizumab treatment of MS. MAIN OUTCOMES AND MEASURES The blood sampleswere separated using flow cytometry into CD34(+), CD19(+), and CD3(+) cell subsets; DNA templates were prepared using quantitative polymerase chain reaction for JCV DNA identification. Plasma samples were tested for anti-JCV antibodies by enzyme-linked A1AQ immunosorbent assays performed at the Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological and Communicative Diseases and Stroke. RESULTS Thirteen of the 26 patients (50%) with baseline and follow-up blood samples had detectable viral DNA in at least 1 cell compartment at 1 or more points. Ten of the 23 patients (44%) receiving treatment for more than 24 months and 3 of the 18 healthy volunteers (17%) also had detectable viral DNA in 1 or more cell compartment. Fifteen of the 49 MS patients (31%) were confirmed to harbor JCV in CD34(+) cells and 12 of 49 (24%) in CD19(+) cells. Only 1 of 18 healthy volunteers were viremic in CD34(+) cells and none in CD19(+) cells. Nine patients and 1 healthy volunteer were viremic but had seronegative test results for JCV antibodies. CONCLUSIONS AND RELEVANCE JC virus DNA was detectable within cell compartments of natalizumab-treated MS patients after treatment inception and longer. JC virus DNA may harbor in CD34(+) cells in bone marrow that mobilize into the peripheral circulation at high concentrations. Latently infected cells initiate differentiation to CD19(+) cells that favors growth of JCV. These data link the mechanism of natalizumab treatment with progressive multifocal leukoencephalopathy. C1 [Frohman, Elliot M.; Remington, Gina; Greenberg, Benjamin; Monson, Nancy; Frohman, Teresa C.] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA. [Frohman, Elliot M.] Univ Texas SW Med Ctr Dallas, Dept Ophthalmol, Dallas, TX 75390 USA. [Monaco, Maria Chiara; Remington, Gina; Jensen, Peter N.; Major, Eugene O.] NIH, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. [Johnson, Kory] Natl Inst Neurol & Communicat Dis & Stroke, Bioinformat Sect, NIH, Bethesda, MD USA. [Perkins, Molly; Liebner, Julia; Douek, Daniel] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Frohman, EM (reprint author), Univ Texas SW Med Ctr Dallas, Dept Neurol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM elliot.frohman@utsouthwestern.edu; majorg@ninds.nih.gov FU Division of Intramural Research; National Institute of Neurological and Communicative Diseases [NINDS]; National Institute of Allergy and Infectious Disease [NIAID]; National Multiple Sclerosis Society [RG 3780A3/3] FX This study was supported by Division of Intramural Research funds (National Institute of Neurological and Communicative Diseases [NINDS] and National Institute of Allergy and Infectious Disease [NIAID] laboratories), by contract HHSN 271200900268P (LMMN, The University of Texas Southwestern Medical Center LMMN, and NINDS), and by grant RG 3780A3/3 from the National Multiple Sclerosis Society (Dr Frohman). NR 35 TC 37 Z9 37 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD MAY PY 2014 VL 71 IS 5 BP 596 EP 602 DI 10.1001/jamaneurol.2014.63 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AH2MX UT WOS:000335956700012 PM 24664166 ER PT J AU Spira, AP An, Y Resnick, SM AF Spira, Adam P. An, Yang Resnick, Susan M. TI Self-Reported Sleep and beta-Amyloid Deposition in Older Adults Reply SO JAMA NEUROLOGY LA English DT Letter C1 [Spira, Adam P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA. [An, Yang; Resnick, Susan M.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Spira, AP (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, 624 N Broadway,Hampton House,Room 794, Baltimore, MD 21205 USA. EM aspira@jhsph.edu FU Intramural NIH HHS; NIA NIH HHS [1K01AG033195, K01 AG033195] NR 1 TC 1 Z9 1 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD MAY PY 2014 VL 71 IS 5 BP 651 EP 652 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA AH2MX UT WOS:000335956700024 PM 24818679 ER PT J AU McNeil, E Gunas, H Koroshetz, W AF McNeil, Elizabeth Gunas, Heather Koroshetz, Walter TI The Future of Neuroscience Clinical Trials SO JAMA NEUROLOGY LA English DT Letter C1 [McNeil, Elizabeth; Koroshetz, Walter] NINDS, NIH, Bethesda, MD 20892 USA. [Gunas, Heather] NCI, NIH, Bethesda, MD 20892 USA. RP McNeil, E (reprint author), NINDS, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM mcneilde@ninds.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD MAY PY 2014 VL 71 IS 5 BP 652 EP 652 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AH2MX UT WOS:000335956700025 PM 24818680 ER PT J AU Schoenbaum, M Kessler, RC Gilman, SE Colpe, LJ Heeringa, SG Stein, MB Ursano, RJ Cox, KL AF Schoenbaum, Michael Kessler, Ronald C. Gilman, Stephen E. Colpe, Lisa J. Heeringa, Steven G. Stein, Murray B. Ursano, Robert J. Cox, Kenneth L. CA Army STARRS Collaborators TI Predictors of Suicide and Accident Death in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) Results From the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) SO JAMA PSYCHIATRY LA English DT Article ID US MILITARY; PSYCHOPATHOLOGY; ATTRITION; PERSONNEL; SOLDIERS AB IMPORTANCE The Army Study to Assess Risk and Resilience in Servicemembers ( Army STARRS) is a multicomponent study designed to generate actionable recommendations to reduce Army suicides and increase knowledge of risk and resilience factors for suicidality. OBJECTIVES To present data on prevalence, trends, and basic sociodemographic and Army experience correlates of suicides and accident deaths among active duty Regular Army soldiers between January 1, 2004, and December 31, 2009, and thereby establish a foundation for future Army STARRS investigations. DESIGN, SETTING, AND PARTICIPANTS Analysis of trends and predictors of suicide and accident deaths using Army and Department of Defense administrative data systems. Participants were all members of the US Regular Army serving at any time between 2004 and 2009. MAIN OUTCOMES AND MEASURES Death by suicide or accident during active Army service. RESULTS The suicide rate rose between 2004 and 2009 among never deployed and currently and previously deployed Regular Army soldiers. The accident death rate fell sharply among currently deployed soldiers, remained constant among the previously deployed, and trended upward among the never deployed. Increased suicide risk was associated with being a man (or a woman during deployment), white race/ethnicity, junior enlisted rank, recent demotion, and current or previous deployment. Sociodemographic and Army experience predictors were generally similar for suicides and accident deaths. Time trends in these predictors and in the Army's increased use of accession waivers (which relaxed some qualifications for new soldiers) do not explain the rise in Army suicides. CONCLUSIONS AND RELEVANCE Predictors of Army suicides were largely similar to those reported elsewhere for civilians, although some predictors distinct to Army service emerged that deserve more in-depth analysis. The existence of a time trend in suicide risk among never-deployed soldiers argues indirectly against the view that exposure to combat-related trauma is the exclusive cause of the increase in Army suicides. C1 [Schoenbaum, Michael; Colpe, Lisa J.] NIMH, Bethesda, MD 20892 USA. [Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Heeringa, Steven G.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA. [Stein, Murray B.] Univ Calif San Diego, Dept Psychiat & Family, La Jolla, CA 92093 USA. [Stein, Murray B.] Univ Calif San Diego, Dept Prevent Med, La Jolla, CA 92093 USA. [Stein, Murray B.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Ursano, Robert J.] Uniformed Serv Univ Hlth Sci, Sch Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD USA. [Cox, Kenneth L.] US Army Publ Hlth Command, Aberdeen Proving Ground, MD USA. RP Schoenbaum, M (reprint author), NIMH, 6001 Execut Blvd,Room 6226,Mail Stop Code 9669, Bethesda, MD 20892 USA. EM schoenbaumm@mail.nih.gov RI Gilman, Stephen/E-7632-2010 OI Gilman, Stephen/0000-0002-8331-6419 FU Department of the Army; National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Service [UO1MHO87981] FX The Army STARRS was sponsored by the Department of the Army and funded under cooperative agreement UO1MHO87981 with the National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Services. NR 18 TC 62 Z9 62 U1 1 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD MAY PY 2014 VL 71 IS 5 BP 493 EP 503 DI 10.1001/jamapsychiatry.2013.4417 PG 11 WC Psychiatry SC Psychiatry GA AH2JP UT WOS:000335947600006 PM 24590048 ER PT J AU Kessler, RC Heeringa, SG Stein, MB Colpe, LJ Fullerton, CS Hwang, I Naifeh, JA Nock, MK Petukhova, M Sampson, NA Schoenbaum, M Zaslavsky, AM Ursano, RJ AF Kessler, Ronald C. Heeringa, Steven G. Stein, Murray B. Colpe, Lisa J. Fullerton, Carol S. Hwang, Irving Naifeh, James A. Nock, Matthew K. Petukhova, Maria Sampson, Nancy A. Schoenbaum, Michael Zaslavsky, Alan M. Ursano, Robert J. CA Army STARRS Collaborators TI Thirty-Day Prevalence of DSM-IV Mental Disorders Among Nondeployed Soldiers in the US Army Results From the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) SO JAMA PSYCHIATRY LA English DT Article ID COMORBIDITY SURVEY REPLICATION; SUBSTANCE USE DISORDERS; AGE-OF-ONSET; POSTTRAUMATIC-STRESS; MILITARY PERSONNEL; COMBAT EXPOSURE; HEALTH OUTCOMES; SEX-DIFFERENCES; MARITAL-STATUS; GULF-WAR AB IMPORTANCE Although high rates of current mental disorder are known to exist in the US Army, little is known about the proportions of these disorders that had onsets prior to enlistment. OBJECTIVE To estimate the proportions of 30-day DSM-IV mental disorders among nondeployed US Army personnel with first onsets prior to enlistment and the extent which role impairments associated with 30-day disorders differ depending on whether the disorders had pre-vs post-enlistment onsets. DESIGN, SETTING, AND PARTICIPANTS A representative sample of 5428 soldiers participating in the Army Study to Assess Risk and Resilience in Servicemembers completed self-administered questionnaires and consented to linkage of questionnaire responses with administrative records. MAIN OUTCOMES AND MEASURES Thirty-day DSM-IV internalizing (major depressive, bipolar, generalized anxiety, panic, and posttraumatic stress) and externalizing (attention-deficit/ hyperactivity, intermittent explosive, alcohol/drug) disorders were assessed with validated self-report scales. Age at onset was assessed retrospectively. Role impairment was assessed with a modified Sheehan Disability Scale. RESULTS A total of 25.1% of respondents met criteria for any 30-day disorder (15.0% internalizing; 18.4% externalizing) and 11.1% for multiple disorders. A total of 76.6% of cases reported pre-enlistment age at onset of at least one 30-day disorder (49.6% internalizing; 81.7% externalizing). Also, 12.8% of respondents reported severe role impairment. Controlling for sociodemographic and Army career correlates, which were broadly consistent with other studies, 30-day disorders with pre-enlistment (chi(2)(8) = 131.8, P <.001) and post-enlistment (chi(2)(7) 7 = 123.8, P <.001) ages at onset both significantly predicted severe role impairment, although pre-enlistment disorders were more consistent powerful predictors (7 of 8 disorders significant; odds ratios, 1.6-11.4) than post-enlistment disorders (5 of 7 disorders significant; odds ratios, 1.5-7.7). Population-attributable risk proportions of severe role impairment were 21.7% for pre-enlistment disorders, 24.3% for post-enlistment disorders, and 43.4% for all disorders. CONCLUSIONS AND RELEVANCE Interventions to limit accession or increase resilience of new soldiers with pre-enlistment mental disorders might reduce prevalence and impairments of mental disorders in the US Army. C1 [Kessler, Ronald C.; Hwang, Irving; Petukhova, Maria; Sampson, Nancy A.; Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Colpe, Lisa J.; Schoenbaum, Michael] NIMH, Bethesda, MD 20892 USA. [Heeringa, Steven G.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA. [Nock, Matthew K.] Harvard Univ, Dept Psychol, Cambridge, MA USA. [Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Stein, Murray B.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Stein, Murray B.] VA San Diego Healthcare Syst, San Diego, CA USA. [Fullerton, Carol S.; Naifeh, James A.; Ursano, Robert J.] Uniformed Serv Univ Hlth Sci, Sch Med, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD USA. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM ncs@hcp.med.harvard.edu FU Department of the Army; US Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health [UO1MHO87981] FX Army STARRS was sponsored by the Department of the Army and funded under cooperative agreement UO1MHO87981 with the US Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health. NR 78 TC 45 Z9 45 U1 1 U2 25 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD MAY PY 2014 VL 71 IS 5 BP 504 EP 513 DI 10.1001/jamapsychiatry.2014.28 PG 10 WC Psychiatry SC Psychiatry GA AH2JP UT WOS:000335947600007 PM 24590120 ER PT J AU Nock, MK Stein, MB Heeringa, SG Ursano, RJ Colpe, LJ Fullerton, CS Hwang, I Naifeh, JA Sampson, NA Schoenbaum, M Zaslavsky, AM Kessler, RC AF Nock, Matthew K. Stein, Murray B. Heeringa, Steven G. Ursano, Robert J. Colpe, Lisa J. Fullerton, Carol S. Hwang, Irving Naifeh, James A. Sampson, Nancy A. Schoenbaum, Michael Zaslavsky, Alan M. Kessler, Ronald C. CA Army STARRS Collaborators TI Prevalence and Correlates of Suicidal Behavior Among Soldiers Results From the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) SO JAMA PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MILITARY; VETERANS; ASSOCIATIONS; ADOLESCENTS; HISTORY; TRAUMA; ADULTS AB IMPORTANCE The suicide rate among US Army soldiers has increased substantially in recent years. OBJECTIVES To estimate the lifetime prevalence and sociodemographic, Army career, and psychiatric predictors of suicidal behaviors among nondeployed US Army soldiers. DESIGN, SETTING, AND PARTICIPANTS A representative cross-sectional survey of 5428 nondeployed soldiers participating in a group self-administered survey. MAIN OUTCOMES AND MEASURES Lifetime suicidal ideation, suicide plans, and suicide attempts. RESULTS The lifetime prevalence estimates of suicidal ideation, suicide plans, and suicide attempts are 13.9%, 5.3%, and 2.4%. Most reported cases (47.0%-58.2%) had pre-enlistment onsets. Pre-enlistment onset rates were lower than in a prior national civilian survey (with imputed/ simulated age at enlistment), whereas post-enlistment onsets of ideation and plans were higher, and post-enlistment first attempts were equivalent to civilian rates. Most reported onsets of plans and attempts among ideators (58.3%-63.3%) occur within the year of onset of ideation. Post-enlistment attempts are positively related to being a woman (with an odds ratio [OR] of 3.3 [95% CI, 1.5-7.5]), lower rank (OR = 5.8 [95% CI, 1.8-18.1]), and previously deployed (OR = 2.4-3.7) and are negatively related to being unmarried (OR = 0.1-0.8) and assigned to Special Operations Command (OR = 0.0 [95% CI, 0.0-0.0]). Five mental disorders predict post-enlistment first suicide attempts in multivariate analysis: pre-enlistment panic disorder (OR = 0.1 [95% CI, 0.0-0.8]), pre-enlistment posttraumatic stress disorder (OR = 0.1 [95% CI, 0.0-0.7]), post-enlistment depression (OR = 3.8 [95% CI, 1.2-11.6]), and both pre-and post-enlistment intermittent explosive disorder (OR = 3.7-3.8). Four of these 5 ORs (posttraumatic stress disorder is the exception) predict ideation, whereas only post-enlistment intermittent explosive disorder predicts attempts among ideators. The population-attributable risk proportions of lifetime mental disorders predicting post-enlistment suicide attempts are 31.3% for pre-enlistment onset disorders, 41.2% for post-enlistment onset disorders, and 59.9% for all disorders. CONCLUSIONS AND RELEVANCE The fact that approximately one-third of post-enlistment suicide attempts are associated with pre-enlistment mental disorders suggests that pre-enlistment mental disorders might be targets for early screening and intervention. The possibility of higher fatality rates among Army suicide attempts than among civilian suicide attempts highlights the potential importance of means control (ie, restricting access to lethal means [such as firearms]) as a suicide prevention strategy. C1 [Nock, Matthew K.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Stein, Murray B.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Stein, Murray B.] VA San Diego Healthcare Syst, San Diego, CA USA. [Heeringa, Steven G.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA. [Ursano, Robert J.; Fullerton, Carol S.; Naifeh, James A.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD 20814 USA. [Colpe, Lisa J.; Schoenbaum, Michael] NIMH, Bethesda, MD 20892 USA. [Hwang, Irving; Sampson, Nancy A.; Zaslavsky, Alan M.; Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Nock, MK (reprint author), Harvard Univ, Dept Psychol, William James Hall,1280,33 Kirkland St, Cambridge, MA 02138 USA. EM nock@wjh.harvard.edu FU Department of the Army; US Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health (NIMH) [UO1MHO87981] FX Army STARRS was sponsored by the Department of the Army and funded under cooperative agreement UO1MHO87981 with the US Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health (NIMH). NR 42 TC 81 Z9 81 U1 7 U2 24 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD MAY PY 2014 VL 71 IS 5 BP 514 EP 522 DI 10.1001/jamapsychiatry.2014.30 PG 9 WC Psychiatry SC Psychiatry GA AH2JP UT WOS:000335947600008 PM 24590178 ER PT J AU Lerman, C Gu, H Loughead, J Ruparel, K Yang, YH Stein, EA AF Lerman, Caryn Gu, Hong Loughead, James Ruparel, Kosha Yang, Yihong Stein, Elliot A. TI Large-Scale Brain Network Coupling Predicts Acute Nicotine Abstinence Effects on Craving and Cognitive Function SO JAMA PSYCHIATRY LA English DT Article ID INDEPENDENT COMPONENT ANALYSIS; RESTING-STATE NETWORKS; DEFAULT-MODE; WORKING-MEMORY; CONNECTIVITY MRI; HEAD MOTION; ATTENTION; TASK; VARENICLINE; VALIDATION AB IMPORTANCE Interactions of large-scale brain networks may underlie cognitive dysfunctions in psychiatric and addictive disorders. OBJECTIVES To test the hypothesis that the strength of coupling among 3 large-scale brain networks-salience, executive control, and default mode-will reflect the state of nicotine withdrawal (vs smoking satiety) and will predict abstinence-induced craving and cognitive deficits and to develop a resource allocation index (RAI) that reflects the combined strength of interactions among the 3 large-scale networks. DESIGN, SETTING, AND PARTICIPANTS A within-subject functional magnetic resonance imaging study in an academic medical center compared resting-state functional connectivity coherence strength after 24 hours of abstinence and after smoking satiety. We examined the relationship of abstinence-induced changes in the RAI with alterations in subjective, behavioral, and neural functions. We included 37 healthy smoking volunteers, aged 19 to 61 years, for analyses. INTERVENTIONS Twenty-four hours of abstinence vs smoking satiety. MAIN OUTCOMES AND MEASURES Inter-network connectivity strength (primary) and the relationship with subjective, behavioral, and neural measures of nicotine withdrawal during abstinence vs smoking satiety states (secondary). RESULTS The RAI was significantly lower in the abstinent compared with the smoking satiety states (left RAI, P =.002; right RAI, P =.04), suggesting weaker inhibition between the default mode and salience networks. Weaker inter-network connectivity (reduced RAI) predicted abstinence-induced cravings to smoke (r = -0.59; P =.007) and less suppression of default mode activity during performance of a subsequent working memory task (ventromedial prefrontal cortex, r = -0.66, P =.003; posterior cingulate cortex, r = -0.65, P =.001). CONCLUSIONS AND RELEVANCE Alterations in coupling of the salience and default mode networks and the inability to disengage from the default mode network may be critical in cognitive/affective alterations that underlie nicotine dependence. C1 [Lerman, Caryn; Loughead, James] Univ Penn, Dept Psychiat, Ctr Interdisciplinary Res Nicotine Addict, Philadelphia, PA 19104 USA. [Gu, Hong; Yang, Yihong; Stein, Elliot A.] NIDA, Intramural Res Program, Baltimore, MD USA. [Ruparel, Kosha] Univ Penn, Dept Psychiat, Brain Behav Lab, Philadelphia, PA 19104 USA. RP Lerman, C (reprint author), Univ Penn, Dept Psychiat, Ctr Interdisciplinary Res Nicotine Addict, 3535 Market St,Ste 4100, Philadelphia, PA 19104 USA. EM clerman@upenn.edu FU Intramural Research Program of the National Institute [P50 CA143187, R03 DA027438]; Commonwealth of Pennsylvania Department of Health FX This study was supported by grants P50 CA143187 and R03 DA027438 (Dr Lerman), the Intramural Research Program of the National Institute on Drug Abuse (Dr Stein), and the Commonwealth of Pennsylvania Department of Health. NR 51 TC 48 Z9 49 U1 2 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD MAY PY 2014 VL 71 IS 5 BP 523 EP 530 DI 10.1001/jamapsychiatry.2013.4091 PG 8 WC Psychiatry SC Psychiatry GA AH2JP UT WOS:000335947600009 PM 24622915 ER PT J AU Pradhan, I Zeldin, DC Ledent, C Mustafa, JS Falck, JR Nayeem, MA AF Pradhan, Isha Zeldin, Darryl C. Ledent, Catherine Mustafa, Jamal S. Falck, John R. Nayeem, Mohammed A. TI High Salt Diet Exacerbates Vascular Contraction in the Absence of Adenosine A(2A) Receptor SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE A1AR; HS; relaxation; contraction; cyp4a; NS; cyp2c29; A2AAR ID RAT PREGLOMERULAR MICROVESSELS; EPOXYEICOSATRIENOIC ACIDS; ARACHIDONIC-ACID; TUBULOGLOMERULAR FEEDBACK; AFFERENT ARTERIOLES; AORTIC RELAXATION; CYP EPOXYGENASES; SENSITIVE RATS; BLOOD-PRESSURE; NITRIC-OXIDE AB High salt (4% NaCl, HS) diet modulates adenosine-induced vascular response through adenosine A(2A) receptor (A(2A)AR). Evidence suggests that A(2A)AR stimulates cyp450-epoxygenases, leading to epoxyeicosatrienoic acids (EETs) generation. The aim of this study was to understand the vascular reactivity to HS and underlying signaling mechanism in the presence or absence of A(2A)AR. Therefore, we hypothesized that HS enhances adenosine-induced relaxation through EETs in A(2A)AR(+/+), but exaggerates contraction in A(2A)AR(-/-). Organ bath and Western blot experiments were conducted in HS and normal salt (NS, 0.18% NaCl)-fed A(2A)AR(+/+) and A(2A)AR(-/-) mice aorta. HS produced concentration-dependent relaxation to non-selective adenosine analog, NECA in A(2A)AR(+/+), whereas contraction was observed in A(2A)AR(-/-) mice and this was attenuated by A(1)AR antagonist (DPCPX). CGS 21680 (selective A(2A)AR agonist) enhanced relaxation in HS-A(2A)AR(+/+) versus NS-A(2A)AR(+/+), which was blocked by EETs antagonist (14,15-EEZE). Compared with NS, HS significantly upregulated the expression of vasodilators A(2A)AR and cyp2c29, whereas vasoconstrictors A(1)AR and cyp4a in A(2A)AR(+/+) were downregulated. In A(2A)AR(-/-) mice, however, HS significantly downregulated the expression of cyp2c29, whereas A(1)AR and cyp4a were upregulated compared with A(2A)AR(+/+) mice. Hence, our data suggest that in A(2A)AR(+/+), HS enhances A(2A)AR-induced relaxation through increased cyp-expoxygenases-derived EETs and decreased A(1)AR levels, whereas in A(2A)AR(-/-), HS exaggerates contraction through decreased cyp-epoxygenases and increased A(1)AR levels. C1 [Pradhan, Isha; Mustafa, Jamal S.; Nayeem, Mohammed A.] W Virginia Univ, Sch Pharm, Ctr Cardiovasc & Resp Sci,Sch Med, Dept Physiol & Pharmacol,Dept Basic Pharmaceut Sc, Morgantown, WV 26506 USA. [Zeldin, Darryl C.] NIEHS, Div Intramural Res, Dept Pulm, NIH, Res Triangle Pk, NC 27709 USA. [Ledent, Catherine] Univ Libre Bruxelles, IRIBHN, Brussels, Belgium. [Falck, John R.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. RP Nayeem, MA (reprint author), W Virginia Univ, Sch Pharm, Ctr Cardiovasc & Resp Sci,Sch Med, Dept Physiol & Pharmacol,Dept Basic Pharmaceut Sc, Biomed Res Bldg,2nd Floor,Room 220, Morgantown, WV 26506 USA. EM mnayeem@hsc.wvu.edu RI Nayeem, Mohammed/A-3949-2017 OI Nayeem, Mohammed/0000-0002-7827-4760 FU WVU; National Institutes of Health [HL-114559, HL-094447, HL 027339, GM- 31278, z01-ES025034] FX Supported by Bridge Grant funding (WVU), startup funding (WVU) and National Institutes of Health HL-114559 to M. A. Nayeem; HL-094447 and HL 027339 to S. J. Mustafa; GM- 31278 to J. R. Falck; and z01-ES025034 to D. C. Zeldin. NR 39 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0160-2446 EI 1533-4023 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD MAY PY 2014 VL 63 IS 5 BP 385 EP 394 DI 10.1097/FJC.0000000000000058 PG 10 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA AH2KZ UT WOS:000335951500001 PM 24390173 ER PT J AU Haverkamp, MH Marciano, BE Frucht, DM Jain, A van de Vosse, E Holland, SM AF Haverkamp, Margje H. Marciano, Beatriz E. Frucht, David M. Jain, Ashish van de Vosse, Esther Holland, Steven M. TI Correlating Interleukin-12 Stimulated Interferon-gamma Production and the Absence of Ectodermal Dysplasia and Anhidrosis (EDA) in Patients with Mutations in NF-kappa B Essential Modulator (NEMO) SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE NF-kappa B essential modulator (NEMO); ectodermal; dysplasia and anhidrosis (EDA); nontuberculous; mycobacteria (NTM); cytokines ID AVIUM COMPLEX INFECTION; IMMUNE-DEFICIENCY; INCONTINENTIA PIGMENTI; IMMUNODEFICIENCY; RECEPTOR; UBIQUITINATION; COSTIMULATION; SYSTEM; CELLS; CHILD AB Objective Patients with hypomorphic mutations in Nuclear Factor-kappa B Essential Modulator (NEMO) are immunodeficient (ID) and most display ectodermal dysplasia and anhidrosis (EDA). We compared cytokine production by NEMO-ID patients with and without EDA. Methods PBMCs of NEMO-ID patients, four with EDA carrying E315A, C417R, D311N and Q403X, and three without EDA carrying E315A, E311_L333del and R254G, were cultured with PHA, PHA plus IL-12p70, LPS, LPS plus IFN-gamma, TNF and IL-1 beta. The production of various cytokines was measured in the supernatants. Fifty-nine healthy individuals served as controls. Results PBMCs of NEMO-ID patients without EDA produce subnormal amounts of IFN-gamma after stimulation with PHA, but normal amounts of IFN-gamma after PHA plus IL-12p70. In contrast, IFN-gamma production by patients with EDA was low in both cases. Patients with EDA also generate lower PHA-stimulated IL-10 and IL-1 beta than controls, whereas the production of these cytokines by patients without EDA was normal. Conclusion Responses of PBMCs in NEMO-ID patients with EDA to PHA with and without IL-12p70 appear less robust than in NEMO-ID patients without EDA. This possibly indicates a better preserved NEMO function in our patients without EDA. C1 [Haverkamp, Margje H.; van de Vosse, Esther] Leiden Univ, Med Ctr, Dept Infect Dis, NL-2333 ZA Leiden, Netherlands. [Haverkamp, Margje H.; Marciano, Beatriz E.; Holland, Steven M.] NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Frucht, David M.] US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20014 USA. [Jain, Ashish] NIH, Lab Host Defenses, Bethesda, MD 20892 USA. RP Haverkamp, MH (reprint author), Leiden Univ, Med Ctr, Dept Infect Dis, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands. EM m.h.haverkamp@lumc.nl RI van de Vosse, Esther/B-7285-2009 OI van de Vosse, Esther/0000-0001-5199-3426 FU Fulbright/Netherland America Foundation, the intramural Research Program of the NIH; National Institute of Allergy and Infectious Diseases; Netherlands Organisation for Scientific Research (NWO); Stichting Fundatie Vrijvrouwe van Renswoude and the Stichting Algemeen Studiefonds FX M.H. has been supported by grants from the Fulbright/Netherland America Foundation, the intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases, the Netherlands Organisation for Scientific Research (NWO), the Stichting Doctor Catharine van Tussenbroek Fonds, the Prins Bernhard Cultuurfonds, the Leids Universiteits Fonds, the Stichting Dr Hendrik Muller's Vaderlandsch Fonds, the Stichting Fundatie Vrijvrouwe van Renswoude and the Stichting Algemeen Studiefonds. NR 29 TC 3 Z9 4 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAY PY 2014 VL 34 IS 4 BP 436 EP 443 DI 10.1007/s10875-014-9998-2 PG 8 WC Immunology SC Immunology GA AH3TP UT WOS:000336048700005 PM 24682681 ER PT J AU Sparks, SE Wassif, CA Goodwin, H Conley, SK Lanham, DC Kratz, LE Hyland, K Gropman, A Tierney, E Porter, FD AF Sparks, S. E. Wassif, C. A. Goodwin, H. Conley, S. K. Lanham, D. C. Kratz, L. E. Hyland, K. Gropman, A. Tierney, E. Porter, F. D. TI Decreased cerebral spinal fluid neurotransmitter levels in Smith-Lemli-Opitz syndrome SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID HUMAN SEROTONIN(1A) RECEPTOR; CEREBROSPINAL-FLUID; CHOLESTEROL-BIOSYNTHESIS; LIGAND-BINDING; OPTIZ-SYNDROME; MOUSE MODEL; 7-DEHYDROCHOLESTEROL; BEHAVIOR; AUTISM; METABOLITES AB Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive, multiple congenital anomaly syndrome with cognitive impairment and a distinct behavioral phenotype that includes autistic features. SLOS is caused by a defect in 3 beta-hydroxysterol Delta(7)-reductase which leads to decreased cholesterol levels and elevated cholesterol precursors, specifically 7- and 8-dehydrocholesterol. However, the pathological processes contributing to the neurological abnormalities in SLOS have not been defined. In view of prior data suggesting defects in SLOS in vesicular release and given the association of altered serotonin metabolism with autism, we were interested in measuring neurotransmitter metabolite levels in SLOS to assess their potential to be used as biomarkers in therapeutic trials. We measured cerebral spinal fluid levels of serotonin and dopamine metabolites, 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) respectively, in 21 SLOS subjects. Results were correlated with the SLOS anatomical severity score, Aberrant Behavior Checklist scores and concurrent sterol biochemistry. Cerebral spinal fluid (CSF) levels of both 5HIAA and HVA were significantly reduced in SLOS subjects. In individual patients, the levels of both 5HIAA and HVA were reduced to a similar degree. CSF neurotransmitter metabolite levels did not correlate with either CSF sterols or behavioral measures. This is the first study demonstrating decreased levels of CSF neurotransmitter metabolites in SLOS. We propose that decreased levels of neurotransmitters in SLOS are caused by a sterol-related defect in synaptic vesicle formation and that CSF 5HIAA and HVA will be useful biomarkers in development of future therapeutic trials. C1 [Sparks, S. E.] Carolinas Med Ctr, Dept Pediat, Charlotte, NC 28203 USA. [Wassif, C. A.; Goodwin, H.; Conley, S. K.; Porter, F. D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. [Lanham, D. C.; Tierney, E.] Kennedy Krieger Inst, Dept Psychiat, Baltimore, MD USA. [Kratz, L. E.] Kennedy Krieger Inst, Biochem Genet Lab, Baltimore, MD USA. [Hyland, K.] Med Neurogenet, Atlanta, GA USA. [Gropman, A.] Childrens Natl Med Ctr, Ctr Neurosci Res, Washington, DC 20010 USA. RP Porter, FD (reprint author), 10 CRC,Rm 5-2571,10 Ctr Dr, Bethesda, MD 20892 USA. EM fdporter@mail.nih.gov OI Wassif, Christopher/0000-0002-2524-1420 FU National Institute of Child Health and Human Development; Office of Rare Diseases; NIH Clinical Center; National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH) [UL1 TR 000424-06]; NIH Roadmap for Medical Research FX This work was supported by the intramural program of the National Institute of Child Health and Human Development and a Bench-to-Bedside award from the Office of Rare Diseases and the NIH Clinical Center. Autism Speaks, the Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number UL1 TR 000424-06 from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS or NIH. We would like to thank Richard Kelly for critical review of this manuscript. We would like to express our appreciation to the patients and families that participated in this study. NR 35 TC 5 Z9 5 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 EI 1573-2665 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD MAY PY 2014 VL 37 IS 3 BP 415 EP 420 DI 10.1007/s10545-013-9672-5 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA AG9NH UT WOS:000335745700011 PM 24500076 ER PT J AU Trakadis, YJ Alfares, A Bodamer, OA Buyukavci, M Christodoulou, J Connor, P Glamuzina, E Gonzalez-Fernandez, F Bibi, H Echenne, B Manoli, I Mitchell, J Nordwall, M Prasad, C Scaglia, F Schiff, M Schrewe, B Touati, G Tchan, MC Varet, B Venditti, CP Zafeiriou, D Rupar, CA Rosenblatt, DS Watkins, D Braverman, N AF Trakadis, Y. J. Alfares, A. Bodamer, O. A. Buyukavci, M. Christodoulou, J. Connor, P. Glamuzina, E. Gonzalez-Fernandez, F. Bibi, H. Echenne, B. Manoli, I. Mitchell, J. Nordwall, M. Prasad, C. Scaglia, F. Schiff, M. Schrewe, B. Touati, G. Tchan, M. C. Varet, B. Venditti, C. P. Zafeiriou, D. Rupar, C. A. Rosenblatt, D. S. Watkins, D. Braverman, N. TI Update on transcobalamin deficiency: clinical presentation, treatment and outcome SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID II DEFICIENCY; FOLLOW-UP; PATIENT; FAMILY; ANEMIA; SERUM AB Transcobalamin (TC) transports cobalamin from blood into cells. TC deficiency is a rare autosomal recessive disorder usually presenting in early infancy with failure to thrive, weakness, diarrhoea, pallor, anemia, and pancytopenia or agammaglobulinemia. It can sometimes resemble neonatal leukemia or severe combined immunodeficiency disease. Diagnosis of TC deficiency is suspected based on megaloblastic anemia, elevation of total plasma homocysteine, and blood or urine methylmalonic acid. It is confirmed by studying the synthesis of TC in cultured fibroblasts, or by molecular analysis of the TCN2 gene. TC deficiency is treatable with supplemental cobalamin, but the optimal type, route and frequency of cobalamin administration and long term patient outcomes are unknown. Here we present a series of 30 patients with TC deficiency, including an update on multiple previously published patients, in order to evaluate the different treatment strategies and provide information about long term outcome. Based on the data presented, current practice appears to favour treatment of individuals with TC deficiency by intramuscular injections of hydroxy- or cyanocobalamin. In most cases presented, at least weekly injections (1 mg IM) were necessary to ensure optimal treatment. Most centres adjusted the treatment regimen based on monitoring CBC, total plasma homocysteine, plasma and urine methylmalonic acid, as well as, clinical status. Finally, continuing IM treatment into adulthood appears to be beneficial. C1 [Trakadis, Y. J.; Alfares, A.; Mitchell, J.; Schrewe, B.; Rosenblatt, D. S.; Watkins, D.; Braverman, N.] McGill Univ Hlth Ctr, Dept Med Genet, Montreal, PQ, Canada. [Bodamer, O. A.] Univ Miami, Dept Human Genet, Miami, FL USA. [Bodamer, O. A.] Univ Miami, Dept Biochem, Miami, FL USA. [Bodamer, O. A.] Univ Miami, Dept Mol Biol, Miami, FL USA. [Buyukavci, M.] Ataturk Univ, Fac Med, Div Pediat Hematol Oncol Erzurum, Erzurum, Turkey. [Christodoulou, J.] Univ Sydney, Western Sydney Genet Program, Childrens Hosp Westmead, Sydney, NSW 2006, Australia. [Christodoulou, J.] Univ Sydney, Discipline Genet Med, Sydney, NSW 2006, Australia. [Christodoulou, J.] Univ Sydney, Discipline Paediat & Child Hlth, Sydney, NSW 2006, Australia. [Connor, P.] Childrens Hosp Wales Heath Pk, Dept Haematol, Cardiff, S Glam, Wales. [Glamuzina, E.] Starship Childrens Hosp, Adult & Paediat Natl Metab Serv, Auckland, New Zealand. [Gonzalez-Fernandez, F.] Hosp Clin San Carlos Madrid, Secc Eritropatol, Serv Hematol & Hemoterapia, Madrid, Spain. [Bibi, H.] Ben Gurion Univ Negev, Dept Pediat, Barzilai Med Ctr, IL-84105 Beer Sheva, Israel. [Echenne, B.] Hop Gui De Chauliac, Serv Neuropediat, F-34295 Montpellier, France. [Manoli, I.; Venditti, C. P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Nordwall, M.] Vrinnevi Hosp, Div Paediat, Norrkoping, County Of Oster, Sweden. [Prasad, C.] London Hlth Sci Ctr, Dept Pediat, London, ON, Canada. [Prasad, C.] Western Univ London, London, ON, Canada. [Scaglia, F.] Baylor Coll Med, Dept Mol Genet, Houston, TX 77030 USA. [Scaglia, F.] Baylor Coll Med, Dept Human Genet, Houston, TX 77030 USA. [Schiff, M.] Hop Robert Debre, Reference Ctr Metab Dis, F-75019 Paris, France. [Touati, G.] Univ Paris 05, Necker Enfants Malades Hosp, AP HP, Ctr Inherited Metab Disorders, Paris, France. [Tchan, M. C.] Westmead Hosp, Dept Med Genet, Sydney, NSW, Australia. [Tchan, M. C.] Univ Sydney, Sydney Med Sch, Discipline Genet Med, Sydney, NSW 2006, Australia. [Varet, B.] Paris Descartes Univ, Necker Hosp, Dept Hematol, Paris, France. [Zafeiriou, D.] Aristotle Univ Thessaloniki, Dept Paediat, Hippokrat Gen Hosp, GR-54006 Thessaloniki, Greece. [Rupar, C. A.] Univ Western Ontario, Dept Biochem, London, ON, Canada. [Rupar, C. A.] Univ Western Ontario, Dept Pediat, London, ON N6A 3K7, Canada. [Rupar, C. A.] Univ Western Ontario, Childrens Hlth Res Inst, London, ON, Canada. [Trakadis, Y. J.] McGill Univ Hlth Ctr, Montreal Childrens Hosp, Montreal, PQ, Canada. RP Trakadis, YJ (reprint author), McGill Univ Hlth Ctr, Montreal Childrens Hosp, Montreal, PQ, Canada. EM john.trakadis@mail.mcgill.ca RI Christodoulou, John/E-5866-2015; OI Manoli, Irini/0000-0003-1543-2941; Christodoulou, John/0000-0002-8431-0641 NR 29 TC 8 Z9 8 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 EI 1573-2665 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD MAY PY 2014 VL 37 IS 3 BP 461 EP 473 DI 10.1007/s10545-013-9664-5 PG 13 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA AG9NH UT WOS:000335745700017 PM 24305960 ER PT J AU Buxton, DB AF Buxton, Denis B. TI Noninvasive Measurement of Mouse Myocardial Glucose Uptake with F-18-FDG SO JOURNAL OF NUCLEAR MEDICINE LA English DT Letter ID NONPRIMATE ERYTHROCYTES; PERMEABILITY; METABOLISM; PET C1 NHLBI, Bethesda, MD 20892 USA. RP Buxton, DB (reprint author), NHLBI, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM db225a@nih.gov NR 10 TC 0 Z9 0 U1 0 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2014 VL 55 IS 5 BP 866 EP 866 DI 10.2967/jnumed.113.135152 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AH2RF UT WOS:000335968000037 PM 24652831 ER PT J AU Yang, JC Sherry, RM Rosenberg, SA AF Yang, James C. Sherry, Richard M. Rosenberg, Steven A. TI Why is sentinel lymph node biopsy 'standard of care' for melanoma? SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Editorial Material ID GUIDELINES AB A large definitive trial comparing the use of sentinel lymph node biopsy and elective lymph node dissection to observation in patients with intermediate thickness melanomas fails to show improved melanoma-specific survival. These results demand reconsideration of the routine use of sentinel lymph node biopsy in the treatment of primary melanoma. C1 [Yang, James C.; Sherry, Richard M.; Rosenberg, Steven A.] NCI, Ctr Canc Res, Surg Branch, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Ctr Canc Res, Surg Branch, CRC Room 3-5952,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sar@mail.nih.gov NR 9 TC 6 Z9 6 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD MAY PY 2014 VL 11 IS 5 BP 245 EP 246 DI 10.1038/nrclinonc.2014.65 PG 2 WC Oncology SC Oncology GA AH1VL UT WOS:000335909200002 PM 24732941 ER PT J AU Adewole, I Martin, DN Williams, MJ Adebamowo, C Bhatia, K Berling, C Casper, C Elshamy, K Elzawawy, A Lawlor, RT Legood, R Mbulaiteye, SM Odedina, FT Olopade, OI Olopade, CO Parkin, DM Rebbeck, TR Ross, H Santini, LA Torode, J Trimble, EL Wild, CP Young, AM Kerr, DJ AF Adewole, Isaac Martin, Damali N. Williams, Makeda J. Adebamowo, Clement Bhatia, Kishor Berling, Christine Casper, Corey Elshamy, Karima Elzawawy, Ahmed Lawlor, Rita T. Legood, Rosa Mbulaiteye, Sam M. Odedina, Folakemi T. Olopade, Olufunmilayo I. Olopade, Christopher O. Parkin, Donald M. Rebbeck, Timothy R. Ross, Hana Santini, Luiz A. Torode, Julie Trimble, Edward L. Wild, Christopher P. Young, Annie M. Kerr, David J. TI Building capacity for sustainable research programmes for cancer in Africa SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID SUB-SAHARAN AFRICA; GAMBIA HEPATITIS INTERVENTION; BURKITT-LYMPHOMA; BREAST-CANCER; DEVELOPING-COUNTRIES; CERVICAL-CANCER; CLINICAL-TRIALS; HEALTH RESEARCH; KAPOSI-SARCOMA; NIGERIAN WOMEN AB Cancer research in Africa will have a pivotal role in cancer control planning in this continent. However, environments (such as those in academic or clinical settings) with limited research infrastructure (laboratories, biorespositories, databases) coupled with inadequate funding and other resources have hampered African scientists from carrying out rigorous research. In September 2012, over 100 scientists with expertise in cancer research in Africa met in London to discuss the challenges in performing high-quality research, and to formulate the next steps for building sustainable, comprehensive and multi-disciplinary programmes relevant to Africa. This was the first meeting among five major organizations: the African Organisation for Research and Training in Africa (AORTIC), the Africa Oxford Cancer Foundation (AfrOx), and the National Cancer Institutes (NCI) of Brazil, France and the USA. This article summarizes the discussions and recommendations of this meeting, including the next steps required to create sustainable and impactful research programmes that will enable evidenced- based cancer control approaches and planning at the local, regional and national levels. C1 [Adewole, Isaac] Univ Ibadan, Coll Med, Dept Obster & Gynecol, Gynecol Oncol Unit, Ibadan, Nigeria. [Martin, Damali N.; Williams, Makeda J.; Mbulaiteye, Sam M.; Trimble, Edward L.] NIH, Bethesda, MD 20892 USA. [Adebamowo, Clement] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Bhatia, Kishor] NCI, Bethesda, MD 20892 USA. [Casper, Corey] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Elzawawy, Ahmed] Mansoura Univ, Mansoura, Egypt. [Lawlor, Rita T.] ARC NET Canc Res Ctr, Verona, Italy. [Legood, Rosa] London Sch Hyg & Trop Med, London, England. [Odedina, Folakemi T.] Univ Florida, Gainesville, FL 32611 USA. [Rebbeck, Timothy R.] Univ Penn, Philadelphia, PA 19104 USA. [Ross, Hana] Amer Canc Soc, Atlanta, GA 30329 USA. [Torode, Julie] Union Int Canc Control, Geneva, Switzerland. [Young, Annie M.] Univ Warwick, Coventry CV4 7AL, W Midlands, England. [Kerr, David J.] Univ Oxford, Oxford OX1 2JD, England. RP Adewole, I (reprint author), Univ Ibadan, Coll Med, Dept Obster & Gynecol, Gynecol Oncol Unit, PMB 5017,GPO, Ibadan, Nigeria. EM if.adewole@mail.ui.edu.ng OI lawlor, Rita/0000-0003-3160-0634 FU FIC NIH HHS [R25 TW007091]; Intramural NIH HHS [Z01 CP010150-08] NR 84 TC 14 Z9 14 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD MAY PY 2014 VL 11 IS 5 BP 251 EP 259 DI 10.1038/nrclinonc.2014.37 PG 9 WC Oncology SC Oncology GA AH1VL UT WOS:000335909200005 PM 24614139 ER PT J AU Lake, CR AF Lake, C. Ray TI This issue: Justification for Breaking the Goldwater Rule: Mass Murderers' Diagnoses SO PSYCHIATRIC ANNALS LA English DT Editorial Material C1 [Lake, C. Ray] Univ Kansas, Sch Med, Kansas City, KS 66103 USA. [Lake, C. Ray] NIMH, Clin Sci Lab, Bethesda, MD USA. [Lake, C. Ray] Uniformed Serv Univ Hlth Sci, Sch Med, Bethesda, MD 20814 USA. RP Lake, CR (reprint author), Univ Kansas, Sch Med, Kansas City, KS 66103 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD MAY PY 2014 VL 44 IS 5 BP 211 EP 212 DI 10.3928/00485713-20140502-03 PG 2 WC Psychiatry SC Psychiatry GA AH2LK UT WOS:000335952700003 ER PT J AU Merikangas, KR Zhang, J Emsellem, H Swanson, SA Vgontzas, A Belouad, F Blank, MM Chen, W Einen, M He, JP Heaton, L Nakamura, E Rooholamini, S Mignot, E AF Merikangas, K. R. Zhang, J. Emsellem, H. Swanson, S. A. Vgontzas, A. Belouad, F. Blank, M. M. Chen, W. Einen, M. He, J. P. Heaton, L. Nakamura, E. Rooholamini, S. Mignot, E. TI The structured Diagnostic Interview for Sleep Patterns and Disorders: rationale and initial evaluation SO SLEEP MEDICINE LA English DT Article DE Diagnostic Interview; Sleep disorders; Validity; International Classification of Sleep Disorders; Concordance; Area under the curve (AUC) ID RESTLESS LEGS SYNDROME; GENERAL-POPULATION; SEVERE INSOMNIA; RISK-FACTORS; PREVALENCE; EPIDEMIOLOGY; ADULTS; APNEA; COMMUNITY; HEALTH AB Objectives: We aimed to describe and report the initial validity of a newly developed structured interview for sleep disorders (Diagnostic Interview for Sleep Patterns and Disorders [DISP]) administered by trained lay interviewers. Methods: A total of 225 patients with various sleep disorders were recruited from two nationally recognized sleep centers in the United States. The International Classification of Sleep Disorders, second edition (ICSD-2) criteria, were used to classify sleep disorders (e.g., delayed sleep phase disorder, hypersomnia, narcolepsy with cataplexy [NC], restless legs syndrome [RLS], periodic limb movement disorder [PLMD], insomnia, rapid eye movement sleep behavior disorder [RBD], and obstructive sleep apnea [OSA]). Interview diagnoses were compared with final diagnoses by sleep specialists (reference diagnosis based on clinical history, examination, and polysomnography [PSG] when indicated). Results: DISP diagnoses had fair to substantial concordance with clinician diagnoses for various sleep disorders, with area under the receiver operator characteristic curves (AUC) ranging from 0.65 to 0.84. Participants classified by the clinician as having a sleep disorder were moderately well-detected (sensitivity ranging from 0.50 for RBD disorder to 0.87 for insomnia). Substantial specificity (> 0.8) also was seen for five of the eight sleep disorders (i.e., delayed sleep phase, hypersomnia, NC, PLMD, and RBD). Interviews were more likely than clinicians to detect disorders secondary to the primary sleep problem. Conclusions: The DISP provides an important tool for the detection of a wide range of sleep disorders in clinical settings and is particularly valuable in the detection of secondary disorders that were not the primary referral diagnosis. (C) 2014 Elsevier B.V. All rights reserved. C1 [Merikangas, K. R.; Zhang, J.; Belouad, F.; Blank, M. M.; He, J. P.; Heaton, L.; Nakamura, E.] NIMH, Genet Epidemiol Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Emsellem, H.] Ctr Sleep & Wake Disorders, Chevy Chase, MD USA. [Swanson, S. A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Vgontzas, A.] Penn State Coll Med, Hershey, PA USA. [Chen, W.; Einen, M.; Rooholamini, S.; Mignot, E.] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. RP Merikangas, KR (reprint author), NIMH, Intramural Res Program, Genet Epidemiol Res Branch, 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA. EM Kathleen.merikangas@nih.gov FU Intramural Research Program of the National Institute of Mental Health [Z01 MH002804] FX This work was supported by the Intramural Research Program of the National Institute of Mental Health (Z01 MH002804). The views and opinions expressed in this article are those of the authors and should not be construed to represent the views of any of the sponsoring organizations, agencies, or US Government. NR 53 TC 3 Z9 3 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 EI 1878-5506 J9 SLEEP MED JI Sleep Med. PD MAY PY 2014 VL 15 IS 5 BP 530 EP 535 DI 10.1016/j.sleep.2013.10.011 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA AH1YI UT WOS:000335917400009 PM 24780136 ER PT J AU Eitan, E Hutchison, ER Mattson, MP AF Eitan, Erez Hutchison, Emmette R. Mattson, Mark P. TI Telomere shortening in neurological disorders: an abundance of unanswered questions SO TRENDS IN NEUROSCIENCES LA English DT Review ID MILD COGNITIVE IMPAIRMENT; PARKINSONS-DISEASE PATIENTS; OXIDATIVE DNA-DAMAGE; WHITE BLOOD-CELLS; ALZHEIMERS-DISEASE; OLDER INDIVIDUALS; DOWN-SYNDROME; HUMAN T; NEURODEGENERATIVE DISEASES; LYMPHOCYTE SUBPOPULATIONS AB Telomeres, ribonucleoprotein complexes that cap eukaryotic chromosomes, typically shorten in leukocytes with aging. Aging is a primary risk factor for neurodegenerative disease (ND), and a common assumption has arisen that leukocyte telomere length (LTL) can serve as a predictor of neurological disease. However, the evidence for shorter LTL in Alzheimer's and Parkinson's patients is inconsistent. The diverse causes of telomere shortening may explain variability in LTL between studies and individuals. Additional research is needed to determine whether neuronal and glial telomeres shorten during aging and in neurodegenerative disorders, if and how LTL is related to brain cell telomere shortening, and whether telomere shortening plays a causal role in or exacerbates neurological disorders. C1 [Eitan, Erez; Hutchison, Emmette R.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Mattson, Mark P.] Johns Hopkins Univ, Dept Neurosci, Sch Med, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mark.mattson@nih.gov FU Intramural Research Program of the National Institute on Aging FX This work was supported by the Intramural Research Program of the National Institute on Aging. NR 102 TC 23 Z9 23 U1 4 U2 15 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAY PY 2014 VL 37 IS 5 BP 256 EP 263 DI 10.1016/j.tins.2014.02.010 PG 8 WC Neurosciences SC Neurosciences & Neurology GA AH4QS UT WOS:000336113700003 PM 24698125 ER PT J AU Richardson, VM Ferguson, SS Sey, YM DeVito, MJ AF Richardson, Vicki M. Ferguson, Stephen S. Sey, Yusupha M. DeVito, Michael J. TI In vitro metabolism of thyroxine by rat and human hepatocytes SO XENOBIOTICA LA English DT Article DE Deiodination; glucuronidation; PCB 153; sulfation; thyroid hormone; T-4 ID MICROSOMAL-ENZYME INDUCERS; UDP-GLUCURONOSYLTRANSFERASE INDUCERS; FOLLICULAR CELL-PROLIFERATION; THYROID-HORMONE METABOLISM; POLYCHLORINATED BIPHENYL CONGENERS; BILIARY-EXCRETION; IODOTHYRONINE SULFOTRANSFERASES; CYTOCHROME-P450 ENZYMES; TRIIODOTHYRONINE T-3; GENE-EXPRESSION AB 1. The liver metabolizes thyroxine (T-4) through two major pathways: deiodination and conjugation. Following exposure to xenobiotics, T-4 conjugation increases through the induction of hepatic uridine diphosphate glucuronosyltransferase (UGT) in rodents; however, it is uncertain to what degree different species employ deiodination and conjugation in the metabolism of T-4. The objective of this study was to compare the metabolism of T-4 in untreated and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153)-treated primary sandwich-cultured hepatocytes from rat (SCRH) and human (SCHH). 2. Basal metabolite concentrations were 13 times higher in the medium of SCRH compared to SCHH. Metabolite distribution in the medium of SCRH versus SCHH was as follows: T(4)G, (91.6 versus 5.3%); T4S, (3.6 versus 4.4%) and T-3+rT(3), (4.9 versus 90.3%). PCB 153 induced T(4)G in the medium of SCRH and SCHH; however, T4S and T-3+rT(3) were changed but to a much lesser degree. 3. The results indicate that baseline T-4 glucuronidation is greater in SCRH compared to SCHH. These data also suggest that glucuronidation may be a more important pathway for T4 metabolism in rats and deiodination may be a favored pathway in humans; however, with PCB 153 treatment these data support glucuronidation as a primary route of T-4 metabolism in both rat and humans. C1 [Richardson, Vicki M.; Sey, Yusupha M.] US EPA, Pharmacokinet Branch, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab,Off Res & De, Res Triangle Pk, NC 27709 USA. [Richardson, Vicki M.] Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC USA. [Ferguson, Stephen S.] Life Technol, Durham, NC USA. [DeVito, Michael J.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Richardson, VM (reprint author), US EPA, Pharmacokinet Branch, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab,Off Res & De, MD B105-03, Res Triangle Pk, NC 27709 USA. EM richardson.vicki@epa.gov NR 64 TC 6 Z9 7 U1 0 U2 15 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0049-8254 EI 1366-5928 J9 XENOBIOTICA JI Xenobiotica PD MAY PY 2014 VL 44 IS 5 BP 391 EP 403 DI 10.3109/00498254.2013.847990 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA AH1OW UT WOS:000335891600001 PM 24175917 ER PT J AU Kudenchuk, PJ Brown, SP Daya, M Morrison, LJ Grunau, BE Rea, T Aufderheide, T Powell, J Leroux, B Vaillancourt, C Larsen, J Wittwer, L Colella, MR Stephens, SW Gamber, M Egan, D Dorian, P AF Kudenchuk, Peter J. Brown, Siobhan P. Daya, Mohamud Morrison, Laurie J. Grunau, Brian E. Rea, Tom Aufderheide, Tom Powell, Judy Leroux, Brian Vaillancourt, Christian Larsen, Jonathan Wittwer, Lynn Colella, M. Riccardo Stephens, Shannon W. Gamber, Mark Egan, Debra Dorian, Paul TI Resuscitation Outcomes Consortium-Amiodarone, Lidocaine or Placebo Study (ROC-ALPS): Rationale and methodology behind an out-of-hospital cardiac arrest antiarrhythmic drug trial SO AMERICAN HEART JOURNAL LA English DT Article ID AMERICAN-HEART-ASSOCIATION; DEFIBRILLATION ENERGY-REQUIREMENTS; EMERGENCY CARDIOVASCULAR CARE; INTERNATIONAL LIAISON COMMITTEE; VENTRICULAR-FIBRILLATION; INTRAVENOUS AMIODARONE; CARDIOPULMONARY-RESUSCITATION; CONSENSUS STATEMENT; STROKE FOUNDATION; SOUTHERN AFRICA AB Background Despite their wide use, whether antiarrhythmic drugs improve survival after out-of-hospital cardiac arrest (OHCA) is not known. The ROC-ALPS is evaluating the effectiveness of these drugs for OHCA due to shock-refractory ventricular fibrillation or pulseless ventricular tachycardia (VF/VT). Methods ALPS will randomize 3,000 adults across North America with nontraumatic OHCA, persistent or recurring VF/VT after >= 1 shock, and established vascular access to receive up to 450 mg amiodarone, 180 mg lidocaine, or placebo in the field using a double-blind protocol, along with standard resuscitation measures. The designated target population is all eligible randomized recipients of any dose of ALPS drug whose initial OHCA rhythm was VF/VT. A safety analysis includes all randomized patients regardless of their eligibility, initial arrhythmia, or actual receipt of ALPS drug. The primary outcome of ALPS is survival to hospital discharge; a secondary outcome is functional survival at discharge assessed as a modified Rankin Scale score <= 3. Results The principal aim of ALPS is to determine if survival is improved by amiodarone compared with placebo; secondary aim is to determine if survival is improved by lidocaine vs placebo and/or by amiodarone vs lidocaine. Prioritizing comparisons in this manner acknowledges where differences in outcome are most expected based on existing knowledge. Each aim also represents a clinically relevant comparison between treatments that is worth investigating. Conclusions Results from ALPS will provide important information about the choice and value of antiarrhythmic therapies for VF/VT arrest with direct implications for resuscitation guidelines and clinical practice. C1 [Kudenchuk, Peter J.] Univ Washington, Dept Med, Div Cardiol, Seattle, WA 98195 USA. [Kudenchuk, Peter J.] Publ Hlth Seattle & King Cty, Seattle, WA USA. [Brown, Siobhan P.; Powell, Judy; Leroux, Brian] Univ Washington, Dept Biostat, Clin Trial Ctr, Seattle, WA 98195 USA. [Daya, Mohamud] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. [Morrison, Laurie J.] Univ Toronto, St Michaels Hosp, Dept Med, ERESCU,Keenan Res Ctr,Div Emergency Med, Toronto, ON M5B 1W8, Canada. [Grunau, Brian E.] Univ British Columbia, Dept Emergency Med, Vancouver, BC V5Z 1M9, Canada. [Rea, Tom] Univ Washington, Dept Med, Seattle, WA USA. [Aufderheide, Tom] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Vaillancourt, Christian] Univ Ottawa, Ottawa Hosp Res Inst, Dept Emergency Med, Ottawa, ON K1N 6N5, Canada. [Larsen, Jonathan] Seattle Fire Dept, Seattle, WA USA. [Wittwer, Lynn] Peace Hlth Southwest Med Ctr, Vancouver, WA USA. [Colella, M. Riccardo] Med Coll Wisconsin, Dept Emergency Med, Milwaukee, WI 53226 USA. [Stephens, Shannon W.] Univ Alabama Birmingham, Dept Emergency Med, Birmingham, AL USA. [Gamber, Mark] Plano Fire Rescue, Plano, TX USA. [Egan, Debra] NHLBI, NIH, Bethesda, MD 20892 USA. [Dorian, Paul] Univ Toronto, St Michaels Hosp, Dept Med, Div Cardiol, Toronto, ON M5B 1W8, Canada. RP Kudenchuk, PJ (reprint author), Univ Washington, Dept Med, Div Cardiol, Seattle, WA 98195 USA. EM kudenchuk@u.washington.edu RI Leroux, Brian/H-2254-2015; morrison, laurie/A-6325-2012; OI morrison, laurie/0000-0001-8369-9774; Stephens, Shannon/0000-0001-5898-5170; Brown, Siobhan/0000-0002-4774-3122; Welsford, Michelle/0000-0003-2682-641X; Ferguson, Niall/0000-0002-6213-5264; Guffey, Danielle/0000-0003-3721-614X FU Canadian Institutes of Health Research; NHLBI NIH HHS [U01 HL077873, 5U01 HL077863, HL077866, HL077867, HL077871, HL077872, HL077873, HL077881, HL077885, HL077887, HL077908, U01 HL077863, U01 HL077866, U01 HL077867, U01 HL077871, U01 HL077872, U01 HL077881, U01 HL077885, U01 HL077887, U01 HL077908] NR 47 TC 24 Z9 24 U1 1 U2 16 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD MAY PY 2014 VL 167 IS 5 BP 653 EP U40 DI 10.1016/j.ahj.2014.02.010 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG5GP UT WOS:000335447800004 PM 24766974 ER PT J AU Rosenberg, MA Maziarz, M Tan, AY Glazer, NL Zieman, SJ Kizer, JR Ix, JH Djousse, L Siscovick, DS Heckbert, SR Mukamal, KJ AF Rosenberg, Michael A. Maziarz, Marlena Tan, Alex Y. Glazer, Nicole L. Zieman, Susan J. Kizer, Jorge R. Ix, Joachim H. Djousse, Luc Siscovick, David S. Heckbert, Susan R. Mukamal, Kenneth J. TI Circulating fibrosis biomarkers and risk of atrial fibrillation: The Cardiovascular Health Study (CHS) SO AMERICAN HEART JOURNAL LA English DT Article ID GROWTH-FACTOR BETA-1; HEART-FAILURE; STRUCTURAL ABNORMALITIES; CARDIAC FIBROSIS; III PROCOLLAGEN; OLDER-ADULTS; MODEL; AGE; OVEREXPRESSION; CARDIOMYOPATHY AB Background Cardiac fibrosis is thought to play a central role in the pathogenesis of atrial fibrillation (AF). Retrospective studies have suggested that circulating fibrosis biomarkers are associated with AF, but prospective studies are limited. Methods We measured circulating levels of 2 fibrosis biomarkers, procollagen type III, N-terminal propeptide (PIIINP) and transforming growth factor beta 1 among participants of the CHS, a population-based study of older Americans. We used Cox proportional hazards and competing risks models to examine adjusted risk of incident AF over a median follow-up of 8.8 years. Results Levels of PIIINP were assessed in 2,935 participants, of whom 767 developed AF. Compared with the median PIIINP level (4.45 mu g/L), adjusted hazard ratios (95% CIs) were 0.85 (0.72-1.00) at the 10th percentile, 0.93 (0.88-0.99) at the 25th percentile, 1.04 (0.95-1.04) at the 75th percentile, and 1.07 (0.90-1.26) at the 90th. Transforming growth factor beta 1 levels, assessed in 1,538 participants with 408 cases of incident AF, were not associated with AF risk. Conclusion In older adults, PIIINP levels were associated with risk of incident AF in a complex manner, with an association that appeared to be positive up to median levels but with little relationship beyond that. Further studies are required to confirm and possibly delineate the mechanism for this relationship. C1 [Rosenberg, Michael A.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Div Cardiac Electrophysiol, Boston, MA USA. [Rosenberg, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Maziarz, Marlena] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Tan, Alex Y.] Virginia Commonwealth Univ, Div Electrophysiol, Richmond, VA USA. [Glazer, Nicole L.] Merck Pharmaceut, Translat & Hlth Informat, Boston, MA USA. [Zieman, Susan J.] NIA, Dept Med, Div Cardiol, Johns Hopkins Med Inst, Baltimore, MD 21224 USA. [Kizer, Jorge R.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol, San Diego, CA 92103 USA. [Djousse, Luc] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging,Dept Med, Boston, MA 02115 USA. [Djousse, Luc] Harvard Univ, Sch Med, Boston Vet Affairs Healthcare Syst, Boston, MA USA. [Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Heckbert, Susan R.] Univ Washington, Sch Publ Hlth, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Heckbert, Susan R.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Mukamal, Kenneth J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. [Mukamal, Kenneth J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Epidemiol, Boston, MA 02215 USA. RP Rosenberg, MA (reprint author), 1400 VFW Pkwy,111CA, Boston, MA 02132 USA. EM Michael.rosenberg@va.gov RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU NHLBI NIH HHS [U01 HL080295, HHSN268200800007C, HHSN268201200036C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, R01 HL080295]; NIA NIH HHS [R01 AG023629, R56 AG023629] NR 45 TC 8 Z9 9 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD MAY PY 2014 VL 167 IS 5 BP 723 EP U114 AR 723-728.e2 DI 10.1016/j.ahj.2014.01.010 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG5GP UT WOS:000335447800013 PM 24766983 ER PT J AU Ho, JE Yin, XY Levy, D Vasan, RS Magnani, JW Ellinor, PT McManus, DD Lubitz, SA Larson, MG Benjamin, EJ AF Ho, Jennifer E. Yin, Xiaoyan Levy, Daniel Vasan, Ramachandran S. Magnani, Jared W. Ellinor, Patrick T. McManus, David D. Lubitz, Steven A. Larson, Martin G. Benjamin, Emelia J. TI Galectin 3 and incident atrial fibrillation in the community SO AMERICAN HEART JOURNAL LA English DT Article ID CONGESTIVE-HEART-FAILURE; PREDICTING STROKE; FIBROSIS; FRAMINGHAM; DYSFUNCTION; MARKER; RISK; OVEREXPRESSION; EPIDEMIOLOGY; MACROPHAGES AB Background Galectin 3 (Gal-3) is a potential mediator of cardiac fibrosis, and Gal-3 concentrations predict incident heart failure. The same mechanisms that lead to cardiac fibrosis in heart failure may influence development of atrial fibrosis and atrial fibrillation (AF). We examined the association of Gal-3 and incident AF in the community. Methods Plasma Gal-3 concentrations were measured in 3,306 participants of the Framingham Offspring cohort who attended the sixth examination cycle (1995-1998, mean age 58 years, 54% women). Cox proportional hazards regression models were used to assess the association of baseline Gal-3 concentrations and incident AF. Results Over a median follow-up period of 10 years, 250 participants developed incident AF. Crude incidence rates of AF by increasing sex-specific Gal-3 quartiles were 3.7%, 5.9%, 9.1%, and 11.5% (log-rank test P < .0001). In age-and sex-adjusted analyses, each 1-SD increase in log(e)-Gal-3 was associated with a 19% increased hazard of incident AF (hazard ratio 1.19, 95% CI 1.05-1.36, P = .009). This association was not significant after adjustment for traditional clinical AF risk factors (hazard ratio 1.12, 95% CI 0.98-1.28, P = .10). Conclusion Higher circulating Gal-3 concentrations were associated with increased risk of developing AF over the subsequent 10 years in age-and sex-adjusted analyses but not after accounting for other traditional clinical AF risk factors. Our results do not support a role for Gal-3 in AF risk prediction. Further studies are needed to evaluate whether Gal-3 plays a role in the development of AF substrate similar to HF. C1 [Ho, Jennifer E.; Yin, Xiaoyan; Levy, Daniel; Vasan, Ramachandran S.; Magnani, Jared W.; McManus, David D.; Larson, Martin G.; Benjamin, Emelia J.] Boston Univ, Framingham, MA USA. [Ho, Jennifer E.; Yin, Xiaoyan; Levy, Daniel; Vasan, Ramachandran S.; Magnani, Jared W.; McManus, David D.; Larson, Martin G.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Ho, Jennifer E.; Magnani, Jared W.] Boston Univ, Dept Med, Sect Cardiovasc Med, Boston, MA 02459 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02459 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02459 USA. [Ellinor, Patrick T.; Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Ellinor, Patrick T.; Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02459 USA. RP Ho, JE (reprint author), Boston Univ, Med Ctr, 88 East Newton St,C-818, Boston, MA 02459 USA. EM jenho@bu.edu OI Ho, Jennifer/0000-0002-7987-4768; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NCRR NIH HHS [KL2 RR031981]; NHLBI NIH HHS [K23 HL116780, K24 HL105780, N01 HC025195, R01 HL092577, R01 HL102214, RC1 HL101056, U01 HL105268]; NINDS NIH HHS [R01 NS017950] NR 38 TC 27 Z9 28 U1 1 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD MAY PY 2014 VL 167 IS 5 BP 729 EP U121 AR 729-734.e1 DI 10.1016/j.ahj.2014.02.009 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG5GP UT WOS:000335447800014 PM 24766984 ER PT J AU Pavkov, ME Nelson, RG AF Pavkov, Meda E. Nelson, Robert G. TI Improved Early Risk Stratification With Cystatin C-Based Estimated GFR SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID GLOMERULAR-FILTRATION-RATE; SERUM CREATININE; COLLABORATIVE METAANALYSIS; ESTIMATING EQUATIONS; POPULATION COHORTS; MORTALITY; ALBUMINURIA; ASSOCIATION C1 [Pavkov, Meda E.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Nelson, Robert G.] NIH, Phoenix, AZ 85014 USA. RP Nelson, RG (reprint author), NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM rnelson@nih.gov NR 27 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2014 VL 63 IS 5 BP 745 EP 748 DI 10.1053/j.ajkd.2014.02.006 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA AG5JZ UT WOS:000335456600416 PM 24602780 ER PT J AU Chapman, AB Gibbs, P Rahbari-Oskoui, F Bae, T Bhutani, HS Grantham, J Harris, P Mrug, M Torres, V Yu, A Flessner, M Landsittel, D AF Chapman, Arlene B. Gibbs, Patrice Rahbari-Oskoui, Frederic Bae, Ty Bhutani, Harpreet Singh Grantham, Jared Harris, Peter Mrug, Michal Torres, Vicente Yu, Alan Flessner, Micheal Landsittel, Doug TI CHARACTERISTICS OF ADPKD PATIENTS WITH RAPID PROGRESSION TO RENAL FAILURE: LESSONS FROM CRISP. SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation (NKF) CY APR 22-26, 2014 CL Las Vegas, NV SP Natl Kidney Fdn C1 [Chapman, Arlene B.; Rahbari-Oskoui, Frederic; Bhutani, Harpreet Singh] Emory Univ, Atlanta, GA 30322 USA. [Gibbs, Patrice; Bae, Ty; Landsittel, Doug] Univ Pittsburgh, Pittsburgh, PA USA. [Grantham, Jared; Yu, Alan] Univ Kansas, Med Ctr, Lawrence, KS 66045 USA. [Mrug, Michal] Univ Alabama Birmingham, Birmingham, AL USA. [Flessner, Micheal] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2014 VL 63 IS 5 MA 74 BP A37 EP A37 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AG5JZ UT WOS:000335456600076 ER PT J AU Reddy, UM Abuhamad, AZ Levine, D Saade, GR AF Reddy, Uma M. Abuhamad, Alfred Z. Levine, Deborah Saade, George R. CA Fetal Imaging Workshop Invited Par TI Fetal imaging: Executive Summary of a Joint Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, American Institute of Ultrasound in Medicine, American College of Obstetricians and Gynecologists, American College of Radiology, Society for Pediatric Radiology, and Society of Radiologists in Ultrasound Fetal Imaging Workshop SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Review ID CHOROID-PLEXUS CYSTS; AMNIOTIC-FLUID VOLUME; LOW-LYING PLACENTA; NERVOUS-SYSTEM ABNORMALITIES; INTRACARDIAC ECHOGENIC FOCI; TWIN TRANSFUSION SYNDROME; BIRTH-WEIGHT DISCORDANCE; LAST MENSTRUAL PERIOD; INTERNAL OS DISTANCE; ISOLATED SHORT FEMUR AB Given that practice variation exists in the frequency and performance of ultrasound and magnetic resonance imaging in pregnancy, the Eunice Kennedy Shriver National Institute of Child Health and Human Development hosted a workshop to address indications for ultrasound and magnetic resonance imaging in pregnancy, to discuss when and how often these studies should be performed, to consider recommendations for optimizing yield and cost-effectiveness and to identify research opportunities. This article is the executive summary of the workshop. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Texas Med Branch, Galveston, TX 77555 USA. RP Reddy, UM (reprint author), 6100 Execut Blvd,Room 4B03F, Bethesda, MD 20892 USA. EM reddyu@mail.nih.gov NR 116 TC 23 Z9 23 U1 1 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2014 VL 210 IS 5 BP 387 EP 397 DI 10.1016/j.ajog.2014.02.028 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AG6EF UT WOS:000335510700003 PM 24793721 ER PT J AU Raju, TNK Mercer, BM Burchfield, DJ Joseph, GF AF Raju, Tonse N. K. Mercer, Brian M. Burchfield, David J. Joseph, Gerald F., Jr. TI Periviable birth: executive summary of a joint workshop by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, American Academy of Pediatrics, and American College of Obstetricians and Gynecologists SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article ID EXTREMELY PRETERM INFANTS; EXTREMELY PREMATURE-INFANTS; WEEKS GESTATIONAL-AGE; WEIGHT INFANTS; ANTENATAL CORTICOSTEROIDS; DELIVERY ROOM; UNITED-STATES; CARDIOPULMONARY-RESUSCITATION; NEURODEVELOPMENTAL OUTCOMES; EMERGENCY CERCLAGE AB This is an executive summary of a workshop on the management and counseling issues of women anticipated to deliver at a periviable gestation (broadly defined as 20 0/7 through 25 6/7 weeks of gestation) and the treatment options for the newborn infant. Upon review of the available literature, the workshop panel noted that the rates of neonatal survival and neurodevelopmental disabilities among the survivors vary greatly across the periviable gestations and are significantly influenced by the obstetric and neonatal management practices (eg, antenatal steroid, tocolytic agents, and antibiotic administration; cesarean birth; and local protocols for perinatal care, neonatal resuscitation, and intensive care support). These are, in turn, influenced by the variations in local and regional definitions of limits of viability. Because of the complexities in making difficult management decisions, obstetric and neonatal teams should confer prior to meeting with the family, when feasible. Family counseling should be coordinated with the goal of creating mutual trust, respect, and understanding and should incorporate evidence-based counseling methods. Since clinical circumstances can change rapidly with increasing gestational age, counseling should include discussion of the benefits and risks of various maternal and neonatal interventions at the time of counseling. There should be a plan for follow-up counseling as clinical circumstances evolve. The panel proposed a research agenda and recommended developing educational curricula on the care and counseling of families facing the birth of a periviable infant. C1 [Raju, Tonse N. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. Soc Maternal Fetal Med, Cleveland, OH USA. Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA. Amer Acad Pediat, Gainesville, FL USA. Univ Florida, Gainesville, FL USA. Amer Coll Obstetricians & Gynecologists, Washington, DC 20024 USA. RP Raju, TNK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. NR 60 TC 7 Z9 7 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2014 VL 210 IS 5 BP 406 EP 417 DI 10.1016/j.ajog.2014.02.027 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AG6EF UT WOS:000335510700005 PM 24725732 ER PT J AU Boghossian, NS Yeung, E Albert, PS Mendola, P Laughon, SK Hinkle, SN Zhang, CL AF Boghossian, Nansi S. Yeung, Edwina Albert, Paul S. Mendola, Pauline Laughon, S. Katherine Hinkle, Stefanie N. Zhang, Cuilin TI Changes in diabetes status between pregnancies and impact on subsequent newborn outcomes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE diabetes; large for gestational age; macrosomia; respiratory distress; shoulder dystocia ID RISK-FACTORS; PRETERM BIRTH; CARBOHYDRATE INTOLERANCE; MELLITUS; WOMEN; FETAL; POPULATION; HYPERGLYCEMIA; ASSOCIATION; SECRETION AB OBJECTIVE: Pregnancies complicated by gestational diabetes mellitus (GDM) or preexisting diabetes mellitus (DM) are at high risk for adverse newborn outcomes. Whether GDM history, recurrence, or transition to DM modifies such risks is unknown. STUDY DESIGN: Medical record data on 62,013 repeat singleton pregnancies were collected retrospectively from women who delivered at least twice in Utah (2002 through 2010). Poisson regression models with robust variance estimators were used to estimate relative risks (RR) and 95% confidence intervals (CI) associated with GDM/DM status at the previous and/or current pregnancy relative to those without GDM/DM at either. Large for gestational age (LGA), shoulder dystocia, preterm birth (< 37 weeks), respiratory distress syndrome, and other neonatal morbidities were examined adjusting for study site, maternal age, race, parity, interpregnancy interval, prepregnancy body mass index, and smoking status. RESULTS: GDM in the previous pregnancy alone increased the risk of LGA in the current pregnancy (RR, 1.20; 95% CI, 1.05-1.38). Recurrent GDM increased the risks of LGA (RR, 1.76; 95% CI, 1.56-1.98), shoulder dystocia (RR, 1.98; 95% CI, 1.46-2.70), and preterm birth (RR, 1.68; 95% CI, 1.44-1.96) beyond that observed for pregnancies with current GDM alone. Women with GDM in a previous pregnancy that transitioned to DM in the current pregnancy and women with DM prior to the previous pregnancy had increased risks of all above outcomes. CONCLUSION: GDM in a previous pregnancy alone without recurrence may still confer an increased LGA risk. Pregnancies complicated by GDM that transition to DM and those with DM prior to the previous pregnancy have the highest risks of adverse newborn outcomes. C1 [Boghossian, Nansi S.; Yeung, Edwina; Albert, Paul S.; Mendola, Pauline; Laughon, S. Katherine; Hinkle, Stefanie N.; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA. RP Boghossian, NS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA. RI Yeung, Edwina/F-5992-2015; Hinkle, Stefanie/F-8253-2013; OI Yeung, Edwina/0000-0002-3851-2613; Hinkle, Stefanie/0000-0003-4312-708X; Mendola, Pauline/0000-0001-5330-2844; Grantz, Katherine/0000-0003-0276-8534 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN2752008000021, HHSN27500004] FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, contract numbers HHSN2752008000021 and HHSN27500004. NR 31 TC 7 Z9 8 U1 0 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2014 VL 210 IS 5 AR 431.e1 DI 10.1016/j.ajog.2013.12.026 PG 14 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AG6EF UT WOS:000335510700010 PM 24361790 ER PT J AU Silver, RM Parker, CB Goldenberg, R Reddy, UM Dudley, DJ Saade, GR Hogue, CJR Coustan, D Varner, MW Koch, MA Conway, D Bukowski, R Pinar, H Stoll, B Moore, J Willinger, M AF Silver, Robert M. Parker, Corette B. Goldenberg, Robert Reddy, Uma M. Dudley, Donald J. Saade, George R. Hogue, Carol J. Rowland Coustan, Donald Varner, Michael W. Koch, Matthew A. Conway, Deborah Bukowski, Radek Pinar, Halit Stoll, Barbara Moore, Janet Willinger, Marian TI Bile acids in a multicenter, population-based case-control study of stillbirth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE bile acids; cholestasis; stillbirth ID INTRAHEPATIC CHOLESTASIS; OBSTETRIC CHOLESTASIS; FETAL-DEATH; PREGNANCY; MANAGEMENT; DIAGNOSIS; PATIENT AB OBJECTIVE: We sought to compare bile acids in women with and without stillbirth in a population-based study. STUDY DESIGN: The Stillbirth Collaborative Research Network conducted a multisite, population-based case-control study of stillbirth (fetal deaths >= 20 weeks). Maternal sera were obtained at the time of enrollment and frozen at -80 degrees C until assay for bile acids. RESULTS: Assays were performed in 581 women with stillbirth and 1546 women with live births. Bile acid levels were slightly higher in women with stillbirth (geometric mean [95% confidence interval {CI}] - 3.2 [3.0-3.5]) compared to live births (2.9 [2.7-3.1], P=.0327). However, the difference was not significant after adjustment for baseline risk factors for stillbirth. The proportion of women with elevated levels (>= 10 or >= 40 mu mol/L) was similar in stillbirths and live births. Results were similar when the analysis was limited to subsets of stillbirths and live births. In women with stillbirths not associated with fetal anomalies or obstetric complications bile acid levels were higher than in women with term live births (geometric mean [95% CI] 3.4 [3.0-3.8] vs 2.9 [2.7-3.0], P=.0152, unadjusted; P=.06, adjusted). However, a similar proportion of women in both groups had levels >= 10 mu mol/L (10.7 vs 7.2%; odds ratio [OR], 1.54; 95% CI, 0.97-2.44; adjusted OR, 1.29; 95% CI, 0.78-2.15) and >= 40 mmol/L (1.7 vs 0.7%; OR, 2.58; 95% CI, 0.85-7.84; adjusted OR, 2.28; 95% CI, 0.79-6.56). CONCLUSION: Our data do not support testing for bile acids in cases of stillbirth in the absence of clinical evidence of intrahepatic cholestasis of pregnancy. C1 [Silver, Robert M.; Varner, Michael W.] Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. [Parker, Corette B.; Koch, Matthew A.; Moore, Janet] RTI Int, Res Triangle Pk, NC USA. [Goldenberg, Robert] Columbia Univ, Dept Obstet & Gynecol, Coll Phys & Surg, New York, NY USA. [Reddy, Uma M.; Willinger, Marian] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. [Dudley, Donald J.; Conway, Deborah] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Saade, George R.; Bukowski, Radek] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA. [Hogue, Carol J. Rowland] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Stoll, Barbara] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. [Coustan, Donald] Brown Univ, Alpert Med Sch, Dept Obstet & Gynecol, Providence, RI 02912 USA. [Pinar, Halit] Brown Univ, Alpert Med Sch, Dept Pathol, Providence, RI 02912 USA. RP Silver, RM (reprint author), Univ Utah, Sch Med, Dept Obstet & Gynecol, 30 N 1900 East,Room 2B308, Salt Lake City, UT 84132 USA. EM bsilver@hsc.utah.edu RI Varner, Michael/K-9890-2013 OI Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; Brown University [U10-HD045953]; Emory University [U10-HD045925]; University of Texas Medical Branch at Galveston [U10-HD045952]; University of Texas Health Sciences Center at San Antonio [U10-HDO45955]; University of Utah Health Sciences Center, Salt Lake City [U10-HD045944]; RTI International, Research Triangle Park [U01-HD045954] FX This work, including the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript, was supported by grant funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development: U10-HD045953 Brown University; U10-HD045925 Emory University; U10-HD045952 University of Texas Medical Branch at Galveston; U10-HDO45955 University of Texas Health Sciences Center at San Antonio; U10-HD045944 University of Utah Health Sciences Center, Salt Lake City; and U01-HD045954 RTI International, Research Triangle Park. NR 25 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2014 VL 210 IS 5 AR 460.e1 DI 10.1016/j.ajog.2013.11.017 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AG6EF UT WOS:000335510700021 PM 24215860 ER PT J AU Blaisdell, C Noel, P Kiley, J AF Blaisdell, Carol Noel, Patricia Kiley, James TI Primary Prevention of Chronic Lung Disease: A Role for Basic Science SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Editorial Material C1 [Blaisdell, Carol; Noel, Patricia; Kiley, James] NHLBI, NIH, DHHS, Bethesda, MD 20892 USA. RP Blaisdell, C (reprint author), NHLBI, NIH, DHHS, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAY PY 2014 VL 50 IS 5 BP 841 EP 842 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA AG8DB UT WOS:000335647900003 PM 24783954 ER PT J AU Cho, HY Kleeberger, SR AF Cho, Hye-Youn Kleeberger, Steven R. TI Noblesse Oblige: NRF2 Functions in the Airways SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE acute lung injury; tumorigenesis; transcription factor ID ACUTE LUNG INJURY; NEONATAL MICE; INFLAMMATION; DEFICIENCY; PROTECTION; RESOLUTION; HYPEROXIA; DELETION; IMPAIRS; FAMILY AB The transcription factor, nuclear factor (NF), erythroid-derived 2-related factor 2 (NRF2), was discovered nearly 2 decades ago. Since then, over 4,000 papers have been published on NRF2 function in diverse biological systems, and it has been found to be a critical regulator of antioxidant and defense genes with antioxidant response elements in their promoters. NRF2 is particularly important in protecting cells and tissues under highly oxidative microenvironments, including the airways that interface with the external environment and are exposed to pollutants and other oxidant stressors. Using mice with targeted deletion of Nrf2, a protective role for this transcription factor has been determined in many model diseases, including acute lung injury, emphysema, allergy and asthma, pulmonary fibrosis, and respiratory syncytial virus disease. Recent studies have also found that murine Nrf2 is important in lung development and protection against neonatal lung injury. Moreover, functional polymorphisms in human NRF2 have been known to associate with disease severity, indicating a potentially important protective function. However, there is also a "dark side" to NRF2 function, as it has been found to enhance advanced stages of carcinogenesis in the lung and some other tissues. NRF2 inducers such as phytochemical isothyocyanates and synthetic triterpenoids, have been discovered and used in model systems of oxidant-induced lung diseases, and data suggest a potential for clinical interventions. Future investigations of NRF2 should yield further insight into its contribution to normal and pathophysiological conditions in the airways, and alternative treatment strategies to protect against oxidative respiratory disease. C1 [Cho, Hye-Youn; Kleeberger, Steven R.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Cho, HY (reprint author), NIEHS, Lab Resp Biol, NIH, 111 TW Alexander Dr,Bldg 101,MD D-201, Res Triangle Pk, NC 27709 USA. EM cho2@niehs.nih.gov FU Intramural Research Program of the National Institutes of Health; National Institute of Environmental Health Sciences; Department of Health and Human Services FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences, Department of Health and Human Services. NR 26 TC 5 Z9 5 U1 1 U2 12 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAY PY 2014 VL 50 IS 5 BP 844 EP 847 DI 10.1165/rcmb.2014-0116PS PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA AG8DB UT WOS:000335647900005 PM 24783956 ER PT J AU Lazrak, A Jurkuvenaite, A Ness, EC Zhang, SY Woodworth, BA Muhlebach, MS Stober, VP Lim, YP Garantziotis, S Matalon, S AF Lazrak, Ahmed Jurkuvenaite, Asta Ness, Emily C. Zhang, Shaoyan Woodworth, Bradford A. Muhlebach, Marianne S. Stober, Vandy P. Lim, Yow-Pin Garantziotis, Stavros Matalon, Sadis TI Inter-alpha-Inhibitor Blocks Epithelial Sodium Channel Activation and Decreases Nasal Potential Differences in Delta F508 Mice SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE alveolar type II cells; lung slices; human BAL; cystic fibrosis; biotinylation ID TRANSEPITHELIAL LIQUID TRANSPORT; HYALURONAN-BINDING PROTEIN; PIG ALVEOLAR EPITHELIA; CYSTIC-FIBROSIS; TRYPSIN-INHIBITOR; NA+ CHANNEL; CELL-SURFACE; IN-VITRO; RESPIRATORY EPITHELIA; LUNG-DISEASE AB Increased activity of lung epithelial sodium channels (ENaCs) contributes to the pathophysiology of cystic fibrosis (CF) by increasing the rate of epithelial lining fluid reabsorption. Inter-alpha-inhibitor (I alpha I), a serum protease inhibitor, may decrease ENaC activity by preventing its cleavage by serine proteases. High concentrations of I alpha I were detected in the bronchoalveolar lavage fluid (BALF) of children with CF and lower airway diseases. I alpha I decreased amiloride-sensitive (I-ENaC) but not cAMP-activated Cl- currents across confluent monolayers of rat ATII, and mouse nasal epithelial cells grew in primary culture by 45 and 25%, respectively. Changes in I-ENaC by I alpha I in ATII cells were accompanied by increased levels of uncleaved (immature) surface alpha-ENaC. I alpha I increased airway surface liquid depth overlying murine nasal epithelial cells to the same extent as amiloride, consistent with ENaC inhibition. Incubation of lung slices from C57BL/6, those lacking phenylalanine at position 508 (Delta F508), or CF transmembrane conductance regulator knockout mice with I alpha I for 3 hours decreased the open probability of their ENaC channels by 50%. Delta F508 mice had considerably higher levels the amiloride-sensitive fractions of ENaC nasal potential difference (ENaC-NPD) than wild-type littermates and only background levels of I alpha I in their BALF. A single intranasal instillation of I alpha I decreased their ENaC-NPD 24 hours later by 25%. In conclusion, we show that I alpha I is present in the BALF of children with CF, is an effective inhibitor of ENaC proteolysis, and decreases ENaC activity in lung epithelial cells of Delta F508 mice. C1 [Lazrak, Ahmed; Jurkuvenaite, Asta; Ness, Emily C.; Matalon, Sadis] Univ Alabama Birmingham, Dept Anesthesiol, Birmingham, AL USA. [Zhang, Shaoyan; Woodworth, Bradford A.] Univ Alabama Birmingham, Dept Surg, Div Otolaryngol, Birmingham, AL 35294 USA. [Lazrak, Ahmed; Jurkuvenaite, Asta; Ness, Emily C.; Matalon, Sadis] Univ Alabama Birmingham, Dept Pulm Injury & Repair, Birmingham, AL USA. [Zhang, Shaoyan; Woodworth, Bradford A.; Matalon, Sadis] Univ Alabama Birmingham, Gregory Fleming James Cyst Fibrosis Res Ctr, Birmingham, AL USA. [Muhlebach, Marianne S.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. [Stober, Vandy P.; Garantziotis, Stavros] NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. [Lim, Yow-Pin] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA. [Lim, Yow-Pin] ProThera Biol, East Providence, RI USA. RP Matalon, S (reprint author), BMR 2 224,901 19th St South, Birmingham, AL 35205 USA. EM sadis@uab.edu RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU CounterACT Program; National Institutes of Health Office of the Director; National Institute of Neurological Disorders and Stroke [5U01ES015676, 1R21ES02402701]; National Heart, Lung and Blood Institute [5R01HL031197]; Flight Attendant's Medical Research Institute Young Clinical Scientist Award [072218]; National Institutes of Health/National Heart, Lung and Blood Institute [1K08HL107142-02]; Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health FX This work was supported by the CounterACT Program; by National Institutes of Health Office of the Director and the National Institute of Neurological Disorders and Stroke grants 5U01ES015676 and 1R21ES02402701; by National Heart, Lung and Blood Institute grant 5R01HL031197 (S.M.); by the Flight Attendant's Medical Research Institute Young Clinical Scientist Award (072218) and National Institutes of Health/National Heart, Lung and Blood Institute grant 1K08HL107142-02 (B.A.W.); and by the Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health (S.G.). NR 62 TC 8 Z9 8 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAY PY 2014 VL 50 IS 5 BP 953 EP 962 DI 10.1165/rcmb.2013-0215OC PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA AG8DB UT WOS:000335647900018 PM 24303840 ER PT J AU Cantey, PT Coyle, CM Sorvillo, FJ Wilkins, PP Starr, MC Nash, TE AF Cantey, Paul T. Coyle, Christina M. Sorvillo, Frank J. Wilkins, Patricia P. Starr, Michelle C. Nash, Theodore E. TI Neglected Parasitic Infections in the United States: Cysticercosis SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID TAENIA-SOLIUM TAENIASIS; LOS-ANGELES-COUNTY; ORTHODOX JEWISH-COMMUNITY; EXTRAPARENCHYMAL NEUROCYSTICERCOSIS; CLINICAL-MANIFESTATIONS; DIAGNOSIS; DISEASE; SEROPREVALENCE; TAPEWORM; SEIZURES AB Cysticercosis is a potentially fatal and preventable neglected parasitic infection caused by the larval form of Taenia solium. Patients with symptomatic disease usually have signs and symptoms of neurocysticercosis, which commonly manifest as seizures or increased intracranial pressure. Although there are many persons living in the United States who emigrated from highly disease-endemic countries and there are foci of autochthonous transmission of the parasite in the United States, little is known about burden and epidemiology of the disease in this country. In addition, despite advances in the diagnosis and management of neurocysticercosis, there remain many unanswered questions. Improving our understanding and management of neurocysticercosis in the United States will require improved surveillance or focused prospective studies in appropriate areas and allocation of resources towards answering some of the key questions discussed in this report. C1 [Cantey, Paul T.; Wilkins, Patricia P.] Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Atlanta, GA 30333 USA. [Coyle, Christina M.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Starr, Michelle C.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Sorvillo, Frank J.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Nash, Theodore E.] NIAID, Gastrointestinal Parasites Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Cantey, PT (reprint author), Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, 1600 Clifton Rd NE,Mailstop A-06, Atlanta, GA 30333 USA. EM pcantey@cdc.gov; christina.coyle@einstein.yu.edu; franksorvillo@yahoo.com; pwilkins@cdc.gov; michelle.starr@seattlechildrens.org; tnash@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health FX This study was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health. NR 60 TC 18 Z9 18 U1 1 U2 10 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAY PY 2014 VL 90 IS 5 BP 805 EP 809 DI 10.4269/ajtmh.13-0724 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA AG8ZN UT WOS:000335707600007 PM 24808248 ER PT J AU Sirugo, G Predazzi, IM Bartlett, J Tacconelli, A Walther, M Williams, SM AF Sirugo, Giorgio Predazzi, Irene M. Bartlett, Jacquelaine Tacconelli, Alessandra Walther, Michael Williams, Scott M. TI Short Report: G6PD A- Deficiency and Severe Malaria in The Gambia: Heterozygote Advantage and Possible Homozygote Disadvantage SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID GLUCOSE-6-PHOSPHATE-DEHYDROGENASE DEFICIENCY; NATURAL-SELECTION; RESISTANCE; HETEROGENEITY; AFRICA; HEMIZYGOTES; POPULATION AB Glucose-6-phosphate dehydrogenase (G6PD) deficiency is frequent in Africa, because it confers resistance to Plasmodium falciparum malaria; however, the nature of the protection and the genotypes associated with it have been controversial. In 1972, Bienzle and others described protection from malaria in West African females heterozygous for G6PD A-. They determined that G6PD A- heterozygotes had lower parasite counts than A- homozygotes, hemizygous males, and normal individuals. However, other studies have reached different conclusions about the protective genotypes. DNA samples from 135 children with severe malaria and 146 children with mild malaria from The Gambia were genotyped for the G6PD A- mutation that is most frequent among Gambians (G6PD 968 T->C); there was a marked deficiency of heterozygotes and an excess of homozygotes with severe malaria, producing a strong deviation from Hardy Weinberg equilibrium. Our results support the protective effect in G6PD A- heterozygous females and suggest that homozygotes might be more susceptible to severe malaria attacks. C1 [Sirugo, Giorgio; Tacconelli, Alessandra] Osped San Pietro Fatebenefratelli, Ctr Ric, I-00189 Rome, Italy. [Predazzi, Irene M.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA. [Bartlett, Jacquelaine; Williams, Scott M.] Dartmouth Coll, Geisel Sch Med, Dept Genet, Hanover, NH 03755 USA. [Walther, Michael] NIAID, NIH, Lab Malaria Immunol & Vaccinol, Rockville, MD USA. MRC Labs, Banjul, Gambia. RP Sirugo, G (reprint author), Osped San Pietro Fatebenefratelli, Ctr Ric, Via Cassia 600, I-00189 Rome, Italy. EM sirugo.giorgio@fbfrm.it; irene.m.predazzi@vanderbilt.edu; Jacquelaine.Bartlett@dartmouth.edu; alessandra.tacconelli@gmail.com; michael.walther@nih.gov; Scott.Williams@dartmouth.edu FU NIH [GM103534] FX SMW was partially supported by NIH grant GM103534. NR 16 TC 8 Z9 8 U1 0 U2 7 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAY PY 2014 VL 90 IS 5 BP 856 EP 859 DI 10.4269/ajtmh.13-0622 PG 4 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA AG8ZN UT WOS:000335707600017 PM 24615128 ER PT J AU Uddin, T Aktar, A Xu, P Johnson, RA Rahman, MA Leung, DT Afrin, S Akter, A Alam, MM Rahman, A Chowdhury, F Khan, AI Bhuiyan, TR Bufano, MK Rashu, R Yu, YN Wu-Freeman, Y Harris, JB LaRocque, RC Charles, RC Kovac, P Calderwood, SB Ryan, ET Qadri, F AF Uddin, Taher Aktar, Amena Xu, Peng Johnson, Russell A. Rahman, M. Arifur Leung, Daniel T. Afrin, Sadia Akter, Aklima Alam, Mohammad Murshid Rahman, Atiqur Chowdhury, Fahima Khan, Ashraful I. Bhuiyan, Taufiqur Rahman Bufano, Meagan K. Rashu, Rasheduzzaman Yu, Yanan Wu-Freeman, Ying Harris, Jason B. LaRocque, Regina C. Charles, Richelle C. Kovac, Pavol Calderwood, Stephen B. Ryan, Edward T. Qadri, Firdausi TI Immune Responses to O-Specific Polysaccharide and Lipopolysaccharide of Vibrio cholerae O1 Ogawa in Adult Bangladeshi Recipients of an Oral Killed Cholera Vaccine and Comparison to Responses in Patients with Cholera SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID MEMORY B-CELL; ANTIBODY-SECRETING CELL; INFECTION-DERIVED IMMUNITY; WHOLE-CELL; STRUCTURAL-ANALYSIS; HOUSEHOLD CONTACTS; CONTROLLED-TRIAL; CORE REGION; ANTIGEN; CHILDREN AB Protective immunity to cholera is serogroup specific, and serogrouping is defined by the O-specific polysaccharide (OSP) of lipopolysaccharide (LPS). We characterized OSP-specific immune responses in adult recipients of an oral killed cholera vaccine (OCV WC-rBS) and compared these with responses in patients with cholera caused by Vibrio cholerae 01 Ogawa. Although vaccinees developed plasma immunoglobulin G (IgG), IgM, IgA antibody and antibody secreting cell (ASC, marker of mucosal response) to Ogawa OSP and LPS 7 days after vaccination, responses were significantly lower than that which occurred after cholera. Similarly, patients recovering from cholera had detectable IgA, IgM, and IgG memory B cell (MBC) responses against OSP and LPS on Day 30 and Day 90, whereas vaccinees only developed IgG responses to OSP 30 days after the second immunization. The markedly lower ASC and MBC responses to OSP and LPS observed among vaccinees might explain, in part, the lower protection of an OCV compared with natural infection. C1 Icddr B, Ctr Vaccine Sci, Dhaka, Bangladesh. [Uddin, Taher; Aktar, Amena; Johnson, Russell A.; Rahman, M. Arifur; Afrin, Sadia; Akter, Aklima; Alam, Mohammad Murshid; Chowdhury, Fahima; Khan, Ashraful I.; Rashu, Rasheduzzaman; Qadri, Firdausi] Icddr B, Immunol Lab, Dhaka, Bangladesh. [Xu, Peng; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD 20892 USA. [Harris, Jason B.; LaRocque, Regina C.; Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Leung, Daniel T.; Bufano, Meagan K.; Rashu, Rasheduzzaman; Yu, Yanan; Wu-Freeman, Ying] Massachusetts Gen Hosp, Boston, MA 02114 USA. [LaRocque, Regina C.; Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Rahman, Atiqur] Univ Dhaka, Dept Biochem & Mol Biol, Dhaka, Bangladesh. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Qadri, F (reprint author), 68 Shaheed Tajuddin Ahmed Sharani, Dhaka 1212, Bangladesh. EM taher_imm@icddrb.org; bio_amn015@yahoo.com; xup3@mail.nih.gov; russell.a.johnson@gmail.com; marifur@icddrb.org; dleung@partners.org; sadia_afrin89@yahoo.com; aklima17@gmail.com; shafiul@icddrb.org; atique303@gmail.com; fchowdhury@icddrb.org; ashrafk@icddrb.org; MBUFANO@partners.org; rashedimm@yahoo.co; YYVAUGHN@PARTNERS.ORG; YWUFREEMAN@PARTNERS.ORG; jbharris@partners.org; RCLAROCQUE@PARTNERS.ORG; RCCHARLES@PARTNERS.ORG; Kovac@maihnh.gov; SCALDERWOOD@PARTNERS.ORG; ETRYAN@PARTNERS.ORG; fqadri@icddrb.org RI Kovac, Pavol/B-8813-2008; Xu, Peng/K-7036-2012; OI Kovac, Pavol/0000-0001-5044-3449; leung, daniel/0000-0001-8401-0801 FU icddr,b; National Institutes of Health; NIDDK; National Institutes of Health [U01 AI058935, R03 AI063079, U01 AI077883, AI106878, K08 AI089721, K08A1100923]; Fogarty International Center; Training Grant in Vaccine Development and Public Health [TW005572]; Career Development Awards [K01 TW07409, K01 TW07144]; Fogarty International Clinical Research Scholars Award [R24 TW007988]; Swedish Sida [INT-ICDDR,B-HN-01-AV]; Howard Hughes Medical Institute; American Society for Tropical Medicine and Hygiene - Burroughs Wellcome Fund; Thrasher Research Fund Early Career Award FX This research was supported by the icddr,b, by the Intramural Research Program of the National Institutes of Health, NIDDK, and extramural grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (U01 AI058935 [S.B.C., E.T.R.], R03 AI063079 [F.Q.], U01 AI077883 and AI106878 [E.T.R.]), K08 AI089721 [R.C.C.], K08A1100923 [D.T.L.]) and the Fogarty International Center, Training Grant in Vaccine Development and Public Health (TW005572 [T.U., M.M.A., R.R., and F.Q.]), Career Development Awards (K01 TW07409 [J.B.H.] and K01 TW07144 [R.C.L.], and a Fogarty International Clinical Research Scholars Award (R24 TW007988 [T.U., R.A.J.]), as well as by Swedish Sida grant INT-ICDDR,B-HN-01-AV (F.Q.), a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (R.C.L.), a Postdoctoral Fellowship in Tropical Infectious Diseases from the American Society for Tropical Medicine and Hygiene - Burroughs Wellcome Fund (D.T.L.), and a Thrasher Research Fund Early Career Award (D.T.L.). NR 49 TC 7 Z9 7 U1 1 U2 5 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAY PY 2014 VL 90 IS 5 BP 873 EP 881 DI 10.4269/ajtmh.13-0498 PG 9 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA AG8ZN UT WOS:000335707600020 PM 24686738 ER PT J AU Fox, A Whitehead, S Anders, KL Hoa, LNM Mai, LQ Thai, PQ Yen, NT Duong, TN Thoang, DD Farrar, J Wertheim, H Simmons, C Hien, NT Horby, P AF Fox, Annette Whitehead, Stephen Anders, Katherine L. Le Nguyen Minh Hoa Le Quynh Mai Pham Quang Thai Nguyen Thu Yen Tran Nhu Duong Dang Dinh Thoang Farrar, Jeremy Wertheim, Heiman Simmons, Cameron Nguyen Tran Hien Horby, Peter TI Short Report: Investigation of Dengue and Japanese Encephalitis Virus Transmission in Hanam, Viet Nam SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID RISK-FACTORS; INFECTION; MOSQUITOS; EPIDEMIOLOGY; SURVEILLANCE; SEVERITY; THAILAND; VECTORS; COHORT AB This study investigated whether a large dengue epidemic that struck Hanoi in 2009 also affected a nearby semirural area. Seroconversion (dengue virus-reactive immunoglobulin G enzyme-linked immunosorbent assay) was high during 2009 compared with 2008, but neutralization assays showed that it was caused by both dengue virus and Japanese encephalitis virus infections. The findings highlight the importance of continued Japanese encephalitis virus vaccination and dengue surveillance. C1 Univ Oxford, Clin Res Unit, Oxford, England. Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam. Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England. NIAID, Bethesda, MD 20892 USA. [Nguyen Tran Hien] Natl Inst Hyg & Epidemiol, Hanoi, Vietnam. [Dang Dinh Thoang] Hanam Ctr Prevent Med, Hanam, Vietnam. [Fox, Annette] Natl Hosp Trop Dis Viet Nam, Hanoi, Vietnam. [Whitehead, Stephen] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. [Anders, Katherine L.] Univ Oxford, Clin Res Unit Viet Nam, Dengue Grp, Ho Chi Minh City, Vietnam. [Anders, Katherine L.; Farrar, Jeremy; Simmons, Cameron] Univ Oxford, Clin Res Unit, Hosp Trop Dis, Ho Chi Minh City, Vietnam. [Le Nguyen Minh Hoa; Wertheim, Heiman; Horby, Peter] Univ Oxford, Clin Res Unit Viet Nam, Natl Hosp Trop Dis, Hanoi, Vietnam. [Le Quynh Mai] Natl Inst Hyg & Epidemiol Virol, Hanoi, Vietnam. [Pham Quang Thai; Nguyen Thu Yen; Tran Nhu Duong] Natl Inst Hyg & Epidemiol Epidemiol, Hanoi, Vietnam. [Horby, Peter] Univ Oxford, Clin Res Unit Trop Med, Hanoi, Vietnam. RP Fox, A (reprint author), Natl Hosp Trop Dis Viet Nam, 78 Giai Phong Rd, Hanoi, Vietnam. EM afox@pacific.net.au; swhitehead@niaid.nih.gov; kanders@oucru.org; hoalnm@oucru.or; lom9@hotmail.com; phamquangthai@gmail.com; yentc2004@gmail.com; trannhuduong@gmail.com; trannhuduong@gmail.com; J.Farrar@wellcome.ac.uk; hwertheim@oucru.org; csimmons@oucru.org; ngtrhien@yahoo.com; peter.horby@gmail.com OI Simmons, Cameron P./0000-0002-9039-7392 FU Wellcome Trust United Kingdom [081613/Z/06/Z, 077078/Z/05/Z]; US National Institute of Allergy and Infectious Diseases; European Union [223498] FX This work was supported by Wellcome Trust United Kingdom Grants 081613/Z/06/Z and 077078/Z/05/Z and in part, the Intramural Research Program of the US National Institute of Allergy and Infectious Diseases. A.F. was supported by the European Union FP7 project European Management Platform for Emerging and Re-Emerging Infectious Disease Entities (EMPERIE; no. 223498). NR 20 TC 1 Z9 1 U1 0 U2 4 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAY PY 2014 VL 90 IS 5 BP 892 EP 896 DI 10.4269/ajtmh.13-0077 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA AG8ZN UT WOS:000335707600022 PM 24615123 ER PT J AU Cross, RW Waffa, B Freeman, A Riegel, C Moses, LM Bennett, A Safronetz, D Fischer, ER Feldmann, H Voss, TG Bausch, DG AF Cross, Robert W. Waffa, Bradley Freeman, Ashley Riegel, Claudia Moses, Lina M. Bennett, Andrew Safronetz, David Fischer, Elizabeth R. Feldmann, Heinz Voss, Thomas G. Bausch, Daniel G. TI Old World Hantaviruses in Rodents in New Orleans, Louisiana SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID UNITED-STATES; HEMORRHAGIC-FEVER; RENAL SYNDROME; HANTAAN VIRUS; SEOUL HANTAVIRUS; NORWAY RATS; BALTIMORE; INFECTION; MARYLAND; ANTIBODY AB Seoul virus, an Old World hantavirus, is maintained in brown rats and causes a mild form of hemorrhagic fever with renal syndrome (HFRS) in humans. We captured rodents in New Orleans, Louisiana and tested them for the presence of Old World hantaviruses by reverse transcription polymerase chain reaction (RT-PCR) with sequencing, cell culture, and electron microscopy; 6 (3.4%) of 178 rodents captured all brown rats were positive for a Seoul virus variant previously coined Tchoupitoulas virus, which was noted in rodents in New Orleans in the 1980s. The finding of Tchoupitoulas virus in New Orleans over 25 years since its first discovery suggests stable endemicity in the city. Although the degree to which this virus causes human infection and disease remains unknown, repeated demonstration of Seoul virus in rodent populations, recent cases of laboratory-confirmed HFRS in some US cities, and a possible link with hypertensive renal disease warrant additional investigation in both rodents and humans. C1 [Cross, Robert W.; Waffa, Bradley; Moses, Lina M.; Bennett, Andrew; Voss, Thomas G.; Bausch, Daniel G.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. [Freeman, Ashley; Riegel, Claudia] New Orleans Termite Mosquito & Rodent Control Boa, New Orleans, LA USA. [Safronetz, David; Fischer, Elizabeth R.; Feldmann, Heinz] NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Cross, RW (reprint author), Univ Texas Med Branch, Galveston Natl Lab, Dept Microbiol & Immunol, Room 5-324,301 Univ Blvd,Mail Route 10610, Galveston, TX 77555 USA. EM rwcross@utmb.edu; bjwaffa@ncsu.edu; Anfree1005@yahoo.com; criegel@cityofno.com; linammoses@gmail.com; Andrew.j.bennett@gmail.com; safronetzd@niaid.nih.gov; efischer@niaid.nih.gov; feldmannh@niaid.nih.gov; thomas.voss@sri.com; dbausch@tulane.edu FU Tulane University Research Enhancement grant FX Funding for this research was provided by a Tulane University Research Enhancement grant. NR 33 TC 2 Z9 2 U1 0 U2 4 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAY PY 2014 VL 90 IS 5 BP 897 EP 901 DI 10.4269/ajtmh.13-0683 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA AG8ZN UT WOS:000335707600023 PM 24639295 ER PT J AU Andersen, SW Trentham-Dietz, A Gangnon, RE Hampton, JM Figueroa, JD Skinner, HG Engelman, CD Klein, BE Titus, LJ Egan, KM Newcomb, PA AF Andersen, Shaneda Warren Trentham-Dietz, Amy Gangnon, Ronald E. Hampton, John M. Figueroa, Jonine D. Skinner, Halcyon G. Engelman, Corinne D. Klein, Barbara E. Titus, Linda J. Egan, Kathleen M. Newcomb, Polly A. TI Reproductive windows, genetic loci, and breast cancer risk SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Breast neoplasms; Epidemiology; Menarche; Menopause; Genetic loci; Histology ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; VARIANTS; 5P12; POLYMORPHISMS; CONSORTIUM; MENARCHE; TRENDS; COHORT; WOMEN AB Purpose: The reproductive windows between age at menarche and age at first birth (standardized age at first birth) and from menarche to menopause (reproductive lifespan) may interact with genetic variants in association with breast cancer risk. Methods: We assessed this hypothesis in 6131 breast cancer cases and 7274 controls who participated in the population-based Collaborative Breast Cancer Study. Risk factor information was collected through telephone interviews, and DNA samples were collected on a subsample (N = 1484 cases, 1307 controls) to genotype for 13 genome-wide association study-identified loci. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and P values for the interaction between reproductive windows and genotypes were obtained by adding cross-product terms to statistical models. Results: For standardized age at first birth, the OR was 1.52 (CI, 1.36-1.71) comparing the highest quintile with the lowest quintile. Carrier status for rs10941679 (5p12) and rs10483813 (RAD51B) appeared to modify this relationship (P = .04 and P = .02, respectively). For reproductive lifespan, the OR comparing the highest quintile with the lowest quintiles was 1.62 (CI, 1.35-1.95). No interactions were detected between genotype and reproductive lifespan (all P > .05). All results were similar regardless of ductal versus lobular breast cancer subtype. Conclusions: Our results suggest that the reproductive windows are associated with breast cancer risk and that associations may vary by genetic variants. (C) 2014 Elsevier Inc. All rights reserved. C1 [Andersen, Shaneda Warren; Trentham-Dietz, Amy; Hampton, John M.; Newcomb, Polly A.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53726 USA. [Andersen, Shaneda Warren; Trentham-Dietz, Amy; Gangnon, Ronald E.; Skinner, Halcyon G.; Engelman, Corinne D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53726 USA. [Figueroa, Jonine D.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Klein, Barbara E.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53726 USA. [Titus, Linda J.] Norris Cotton Canc Ctr, Geisel Sch Med Dartmouth, Lebanon, NH USA. [Egan, Kathleen M.] Univ S Florida, H Lee Moffitt Canc Ctr, Div Canc Prevent & Control, Tampa, FL 33682 USA. [Egan, Kathleen M.] Res Inst, Tampa, FL USA. [Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. RP Andersen, SW (reprint author), Univ Wisconsin, Carbone Canc Ctr, 610 Walnut St,WARF Room 307, Madison, WI 53726 USA. EM snandersen@uwalumni.com FU National Institutes of Health [R01CA47147, R01CA47305, R01CA69664, U10EY006594]; Department of Defense Breast Cancer Research Program [W81XWH-11-1-0047]; Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services FX The authors would like to thank the study staff and participants for all of their individual contributions. This work was supported by grants from the National Institutes of Health (grant numbers R01CA47147, R01CA47305, R01CA69664, and U10EY006594), the Department of Defense Breast Cancer Research Program (W81XWH-11-1-0047), and Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services. NR 27 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAY PY 2014 VL 24 IS 5 BP 376 EP 382 DI 10.1016/j.annepidem.2014.02.007 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AG9BB UT WOS:000335712500008 ER PT J AU Kaufman, SS Green, KY Korba, BE AF Kaufman, Stuart S. Green, Kim Y. Korba, Brent E. TI Treatment of norovirus infections: Moving antivirals from the bench to the bedside SO ANTIVIRAL RESEARCH LA English DT Review DE Norovirus; Transplant; Antiviral; Immunocompromised; Drug treatment; Diarrhea ID STEM-CELL TRANSPLANTATION; DEPENDENT RNA-POLYMERASE; NORWALK VIRUS-REPLICATION; UNITED-STATES; VIRAL GASTROENTERITIS; 3C-LIKE PROTEASES; MONOCLONAL-ANTIBODIES; FAVIPIRAVIR T-705; MURINE NOROVIRUS; INHIBITORS AB Noroviruses (NV) are the most common cause of acute gastrointestinal illness in the United States and worldwide. The development of specific antiviral countermeasures has lagged behind that of other viral pathogens, primarily because norovirus disease has been perceived as brief and self-limiting and robust assays suitable for drug discovery have been lacking. The increasing recognition that NV illness can be life-threatening, especially in immunocompromised patients who often require prolonged hospitalization and intensive supportive care, has stimulated new research to develop an effective antiviral therapy. Here, we propose a path forward for evaluating drug therapy in norovirus-infected immunocompromised individuals, a population at high risk for serious and prolonged illness. The clinical and laboratory features of norovirus illness in immunocompromised patients are reviewed, and potential markers of drug efficacy are defined. We discuss the potential design of clinical trials in these patients and how an antiviral therapy that proves effective in immunocompromised patients might also be used in the setting of acute outbreaks, especially in confined settings such as nursing homes, to block the spread of infection and reduce the severity of illness. We conclude by reviewing the current status of approved and experimental compounds that might be evaluated in a hospital setting. (c) 2014 Elsevier B.V. All rights reserved. C1 [Kaufman, Stuart S.] Georgetown Univ, Med Ctr, MedStar Georgetown Transplant Inst, Washington, DC 20007 USA. [Kaufman, Stuart S.] Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. [Green, Kim Y.] NIAID, Caliciviruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Korba, Brent E.] Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA. RP Korba, BE (reprint author), Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA. EM korbabe@georgetown.edu FU Intramural NIH HHS [Z99 AI999999] NR 107 TC 27 Z9 27 U1 0 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 EI 1872-9096 J9 ANTIVIR RES JI Antiviral Res. PD MAY PY 2014 VL 105 BP 80 EP 91 DI 10.1016/j.antiviral.2014.02.012 PG 12 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA AG7XC UT WOS:000335631100013 PM 24583027 ER PT J AU Giannouli, CC Chandris, P Proia, RL AF Giannouli, Christina C. Chandris, Panagiotis Proia, Richard L. TI Visualizing S1P-directed cellular egress by intravital imaging SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Review DE Sphingosine-1-phosphate; Sphingolipid; Signaling; Gradient; Receptor; Two-photon microscopy ID SPHINGOSINE 1-PHOSPHATE RECEPTOR; SPHINGOSINE-1-PHOSPHATE TRANSPORTER SPNS2; PROTEIN-COUPLED RECEPTOR; SPLENIC MARGINAL ZONE; LYMPHOCYTE EGRESS; T-CELLS; FLUORESCENT PROTEINS; 2-PHOTON MICROSCOPY; IN-VIVO; INTERACTION DYNAMICS AB Sphingosine-1-phosphate (S1P) is a bioactive lipid that provides cellular signals through plasma membrane G protein-coupled receptors. The SW receptor signaling system has a fundamental and widespread function in licensing the exit and release of hematopoietically derived cells from various tissues into the circulation. Although the outlines of the mechanism have been established through genetic and pharmacologic perturbations, the temporal and spatial dynamics of the cellular events involved have been unclear. Recently, two-photon intravital imaging has been applied to living tissues to visualize the cellular movements and interactions that occur during egress processes. Here we discuss how some of these recent findings provide a clearer picture regarding SW receptor signaling in modulating cell egress into the circulation. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology. Published by Elsevier B.V. C1 [Giannouli, Christina C.; Chandris, Panagiotis; Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Proia, RL (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. EM christina.giannouli@nih.gov; Panagiotis.Chandris@nih.gov; proia@nih.gov FU Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. NR 93 TC 1 Z9 1 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 EI 0006-3002 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD MAY PY 2014 VL 1841 IS 5 SI SI BP 738 EP 744 DI 10.1016/j.bbalip.2013.09.012 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA AG8ZC UT WOS:000335706400011 PM 24090699 ER PT J AU Outeda, P Huso, DL Fisher, SA Halushka, MK Kim, H Qian, F Germino, GG Watnick, T AF Outeda, Patricia Huso, David L. Fisher, Steven A. Halushka, Marc K. Kim, Hyunho Qian, Feng Germino, Gregory G. Watnick, Terry TI Polycystin Signaling Is Required for Directed Endothelial Cell Migration and Lymphatic Development SO CELL REPORTS LA English DT Article ID KIDNEY-DISEASE; 2-HIT MODEL; IN-VIVO; VESSELS; PKD1; MICE; CYSTOGENESIS; MUTATIONS; POLARITY; DEFECTS AB Autosomal dominant polycystic kidney disease is a common form of inherited kidney disease that is caused by mutations in two genes, PKD1 (polycystin-1) and PKD2 (polycystin-2). Mice with germline deletion of either gene die in midgestation with a vascular phenotype that includes profound edema. Although an endothelial cell defect has been suspected, the basis of this phenotype remains poorly understood. Here, we demonstrate that edema in Pkd1- and Pkd2-null mice is likely to be caused by defects in lymphatic development. Pkd1 and Pkd2 mutant embryos exhibit reduced lymphatic vessel density and vascular branching along with aberrant migration of early lymphatic endothelial cell precursors. We used cell-based assays to confirm that PKD1- and PKD2-depleted endothelial cells have an intrinsic defect in directional migration that is associated with a failure to establish front-rear polarity. Our studies reveal a role for polycystin signaling in lymphatic development. C1 [Outeda, Patricia; Kim, Hyunho; Qian, Feng; Watnick, Terry] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA. [Huso, David L.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21205 USA. [Fisher, Steven A.] Univ Maryland, Sch Med, Div Cardiol, Baltimore, MD 21201 USA. [Halushka, Marc K.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Germino, Gregory G.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Watnick, T (reprint author), Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA. EM twatnick@medicine.umaryland.edu OI Halushka, Marc/0000-0002-7112-7389 FU NIH [R01DK076017, R01DK095036, R01HL65314, R01DK062199, R37DK48006]; NIDDK Intramural Program [1ZIADK075042]; Maryland Kidney Foundation; National Kidney Foundation Postdoctoral Research Fellowship; American Heart Association [13GRNT16420015]; NIDDK [P30DK090868] FX We thank members of the Baltimore Polycystic Kidney Disease (PKD) Research and Clinical Core Center for helpful discussions. This work was supported by the NIH (R01DK076017 and R01DK095036 to T.W., R01HL65314 to S.A.F., R01DK062199 to F.Q., and R37DK48006 to G.G.G.), the NIDDK Intramural Program (1ZIADK075042 to G.G.G.), a Minigrant from the Maryland Kidney Foundation and a National Kidney Foundation Postdoctoral Research Fellowship to P.O., and the American Heart Association (13GRNT16420015 to M.K.H.). These studies utilized reagents provided by the Baltimore PKD Research and Clinical Core Center, sponsored by the NIDDK (P30DK090868). NR 32 TC 15 Z9 15 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD MAY PY 2014 VL 7 IS 3 BP 634 EP 644 DI 10.1016/j.celrep.2014.03.064 PG 11 WC Cell Biology SC Cell Biology GA AG6WZ UT WOS:000335560900005 PM 24767998 ER PT J AU Wang, L Du, Y Ward, JM Shimbo, T Lackford, B Zheng, XF Miao, YL Zhou, BY Han, L Fargo, DC Jothi, R Williams, CJ Wade, PA Hu, G AF Wang, Li Du, Ying Ward, James M. Shimbo, Takashi Lackford, Brad Zheng, Xiaofeng Miao, Yi-liang Zhou, Bingying Han, Leng Fargo, David C. Jothi, Raja Williams, Carmen J. Wade, Paul A. Hu, Guang TI INO80 Facilitates Pluripotency Gene Activation in Embryonic Stem Cell Self-Renewal, Reprogramming, and Blastocyst Development SO CELL STEM CELL LA English DT Article ID CORE TRANSCRIPTIONAL NETWORK; CHROMATIN REMODELING COMPLEX; RNAI SCREEN; GENOME; DIFFERENTIATION; EXPRESSION; IDENTITY; MEDIATOR; OCT4; MECHANISMS AB The master transcription factors play integral roles in the pluripotency transcription circuitry of embryonic stem cells (ESCs). How they selectively activate expression of the pluripotency network while simultaneously repressing genes involved in differentiation is not fully understood. Here, we define a requirement for the INO80 complex, a SWI/SNF family chromatin remodeler, in ESC self-renewal, somatic cell reprogramming, and blastocyst development. We show that Ino80, the chromatin remodeling ATPase, co-occupies pluripotency gene promoters with the master transcription factors, and its occupancy is dependent on OCT4 and WDR5. At the pluripotency genes, Ino80 maintains an open chromatin architecture and licenses recruitment of Mediator and RNA polymerase II for gene activation. Our data reveal an essential role for INO80 in the expression of the pluripotency network and illustrate the coordination among chromatin remodeler, transcription factor, and histone-modifying enzyme in the regulation of the pluripotent state. C1 [Wang, Li; Shimbo, Takashi; Lackford, Brad; Zheng, Xiaofeng; Jothi, Raja; Wade, Paul A.; Hu, Guang] NIEHS, Lab Mol Carcinogenesis, Res Triangle Pk, NC 27709 USA. [Du, Ying; Ward, James M.; Fargo, David C.] NIEHS, Res Triangle Pk, NC 27709 USA. [Miao, Yi-liang; Williams, Carmen J.] NIEHS, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC 27709 USA. [Zhou, Bingying] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Zhou, Bingying] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Han, Leng] Univ Texas Houston, Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. RP Wade, PA (reprint author), NIEHS, Lab Mol Carcinogenesis, Res Triangle Pk, NC 27709 USA. EM wadep2@niehs.nih.gov; hug4@niehs.nih.gov RI Jothi, Raja/G-3780-2015; Hu, Guang/E-7474-2016 OI Hu, Guang/0000-0003-0437-4723 FU NIH, National Institute of Environmental Health Sciences [Z01ES102745, Z01ES101965, Z01ES102985, Z01ES102625] FX We thank Drs. Trevor Archer and Karen Adelman for reading the manuscript. This study was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences Z01ES102745 (to G. H.), Z01ES101965 (to P. A. W.), Z01ES102985 (to C.J.W.), and Z01ES102625 (to R.J.). NR 55 TC 41 Z9 43 U1 3 U2 27 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD MAY 1 PY 2014 VL 14 IS 5 BP 575 EP 591 DI 10.1016/j.stem.2014.02.013 PG 17 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AG8HR UT WOS:000335659900008 PM 24792115 ER PT J AU Tate, JA Snitz, BE Alvarez, KA Nahin, RL Weissfeld, LA Lopez, O Angus, DC Shah, F Ives, DG Fitzpatrick, AL Williamson, JD Arnold, AM DeKosky, ST Yende, S AF Tate, Judith A. Snitz, Beth E. Alvarez, Karina A. Nahin, Richard L. Weissfeld, Lisa A. Lopez, Oscar Angus, Derek C. Shah, Faraaz Ives, Diane G. Fitzpatrick, Annette L. Williamson, Jeffrey D. Arnold, Alice M. DeKosky, Steven T. Yende, Sachin CA GEM Study Investigators TI Infection Hospitalization Increases Risk of Dementia in the Elderly SO CRITICAL CARE MEDICINE LA English DT Article DE older adults; dementia; pneumonia; infection ID RESPIRATORY-DISTRESS-SYNDROME; COMMUNITY-ACQUIRED PNEUMONIA; LONG-TERM MORTALITY; QUALITY-OF-LIFE; ALZHEIMERS-DISEASE; INFLAMMATORY MARKERS; COGNITIVE FUNCTION; VASCULAR DEMENTIA; CLINICAL-CRITERIA; PROPENSITY SCORE AB Objectives: Severe infections, often requiring ICU admission, have been associated with persistent cognitive dysfunction. Less severe infections are more common and whether they are associated with an increased risk of dementia is unclear. We determined the association of pneumonia hospitalization with risk of dementia in well-functioning older adults. Design: Secondary analysis of a randomized multicenter trial to determine the effect of Gingko biloba on incident dementia. Setting: Five academic medical centers in the United States. Subjects: Healthy community volunteers (n = 3,069) with a median follow-up of 6.1 years. Interventions: None. Measurement and Main Results: We identified pneumonia hospitalizations using International Classification of Diseases, 9th Edition-Coding Manual codes and validated them in a subset. Less than 3% of pneumonia cases necessitated ICU admission, mechanical ventilation, or vasopressor support. Dementia was adjudicated based on neuropsychological evaluation, neurological examination, and MRI. Two hundred twenty-one participants (7.2%) incurred at least one hospitalization with pneumonia (mean time to pneumonia = 3.5 yr). Of these, dementia was developed in 38 (17%) after pneumonia, with half of these cases occurring 2 years after the pneumonia hospitalization. Hospitalization with pneumonia was associated with increased risk of time to dementia diagnosis (unadjusted hazard ratio = 2.3; CI, 1.6-3.2; p < 0.0001). The association remained significant when adjusted for age, sex, race, study site, education, and baseline mini-mental status examination (hazard ratio = 1.9; CI, 1.4-2.8; p < 0.0001). Results were unchanged when additionally adjusted for smoking, hypertension, diabetes, heart disease, and preinfection functional status. Results were similar using propensity analysis where participants with pneumonia were matched to those without pneumonia based on age, probability of developing pneumonia, and similar trajectories of cognitive and physical function prior to pneumonia (adjusted prevalence rates, 91.7 vs 65 cases per 1,000 person-years; adjusted prevalence rate ratio = 1.6; CI, 1.06-2.7; p = 0.03). Sensitivity analyses showed that the higher risk also occurred among those hospitalized with other infections. Conclusion: Hospitalization with pneumonia is associated with increased risk of dementia. C1 [Tate, Judith A.] Univ Pittsburgh, Sch Nursing, Dept Acute & Tertiary Care, Pittsburgh, PA 15261 USA. [Snitz, Beth E.; Lopez, Oscar] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Alvarez, Karina A.; Weissfeld, Lisa A.] Univ Pittsburgh, Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15260 USA. [Nahin, Richard L.] NIH, NCCAM, Bethesda, MD 20892 USA. [Weissfeld, Lisa A.; Angus, Derek C.; Yende, Sachin] Univ Pittsburgh, Clin Res Invest & Syst Modeling Acute Illnes, Pittsburgh, PA USA. [Angus, Derek C.; Yende, Sachin] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA. [Shah, Faraaz] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Ives, Diane G.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Fitzpatrick, Annette L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Williamson, Jeffrey D.] Wake Forest Sch Med, Sec Gerontol & Geriatr Med, Winston Salem, NC USA. [Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [DeKosky, Steven T.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. RP Tate, JA (reprint author), Univ Pittsburgh, Sch Nursing, Dept Acute & Tertiary Care, Pittsburgh, PA 15261 USA. EM jta100@pitt.edu RI Tate, Judith/C-7447-2015; Angus, Derek/E-9671-2012; OI Nahin, Richard/0000-0002-3682-4816 FU National Center for Complementary and Alternative Medicine [U01 AT000162]; Office of Dietary Supplements; National Institute on Aging; National Heart, Lung, and Blood Institute; University of Pittsburgh Alzheimer's Disease Research Center [P50AG05133]; Roena Kulynych Center for Memory and Cognition Research; Wake Forest University School of Medicine; National Institute of Neurological Disorders and Stroke; National Institute of Mental Health [T32-MH19986]; National Institutes of Health (NIH) [T-32 MH19986]; National Institute on Aging [NIA 5K23AG038479]; NIH; National Center for Complementary and Alternative Medicine/NIH; Centers for Disease Control and Prevention (CDC); National Institute of General Medical Sciences [K23GM083215]; [T-32 (MH19986)]; [NIA: P50 AG05133-27] FX Gingko Effect on Memory study was supported by grant U01 AT000162 from the National Center for Complementary and Alternative Medicine and the Office of Dietary Supplements and National Institute on Aging; National Heart, Lung, and Blood Institute; University of Pittsburgh Alzheimer's Disease Research Center (P50AG05133); Roena Kulynych Center for Memory and Cognition Research; Wake Forest University School of Medicine; and National Institute of Neurological Disorders and Stroke.; Dr. Tate is funded by T-32 (MH19986-principal investigator [PI] Reynolds). Dr. Tate's institution received grant support from the National Institute of Mental Health (T32-MH19986-PI Reynolds). Dr. Tate received support for article research from the National Institutes of Health (NIH) (T-32 MH19986-PI Reynolds). Dr. Snitz is supported by National Institute on Aging (NIA 5K23AG038479). Dr. Snitz's institution received grant support from the NIH. Dr. Snitz received support for article research from the NIH. Dr. Nahin is employed by the NIH. Dr. Lopez consulted for Grifols, Lilly, and Baxter. Dr. Lopez's institution received grant support (NIA: P50 AG05133-27).; Dr. Ives' institution received grant support and support for travel from National Center for Complementary and Alternative Medicine/NIH. Dr. Ives is employed by the University of Pittsburgh and received support for article research from the NIH. Dr. Fitzpatrick and her institution received grant support from the NIH and Centers for Disease Control and Prevention (CDC). Dr. Fitzpatrick received support for article research from the NIH and CDC. Dr. Williamson's institution received grant support and support for travel from the NIH. Dr. Williamson received support for article research from the NIH. Dr. Arnold and her institution received grant support from the NIH. Dr. Arnold received support for travel and support for article research from the NIH. Dr. DeKosky's institution received grant support from the NIH, support for travel from the NIH, and the active Gingko Extract and the placebo tablets for the original Gingko Effect on Memory trial from Schwabe Pharamaceuticals. Dr. DeKosky received support for article research from the NIH. Dr. Yende's institution received grant support from the NIH. Dr. Yende received support for article research from the NIH and National Institute of General Medical Sciences (K23GM083215). The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 50 TC 6 Z9 6 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2014 VL 42 IS 5 BP 1037 EP 1046 DI 10.1097/CCM.0000000000000123 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA AG4IU UT WOS:000335383900018 PM 24368344 ER PT J AU Nydahl, P Ruhl, AP Bartoszek, G Dubb, R Filipovic, S Flohr, HJ Kaltwasser, A Mende, H Rothaug, O Schuchhardt, D Schwabbauer, N Needham, DM AF Nydahl, Peter Ruhl, A. Parker Bartoszek, Gabriele Dubb, Rolf Filipovic, Silke Flohr, Hans-Juergen Kaltwasser, Arnold Mende, Hendrik Rothaug, Oliver Schuchhardt, Danny Schwabbauer, Norbert Needham, Dale M. TI Early Mobilization of Mechanically Ventilated Patients: A 1-Day Point-Prevalence Study in Germany* SO CRITICAL CARE MEDICINE LA English DT Article DE intensive care units; prevalence; early mobilization; surveys; physical therapists; mechanical ventilation ID INTENSIVE-CARE-UNIT; QUALITY IMPROVEMENT PROJECT; ACUTE RESPIRATORY-FAILURE; PHYSICAL REHABILITATION; OCCUPATIONAL-THERAPY; FUNCTIONAL RECOVERY; INTERVENTION; FEASIBILITY; EXERCISE; SEDATION AB Objectives: There is growing evidence to support early mobilization of adult mechanically ventilated patients in ICUs. However, there is little knowledge regarding early mobilization in routine ICU practice. Hence, the interdisciplinary German ICU Network for Early Mobilization undertook a 1-day point-prevalence survey across Germany. Design: One-day point-prevalence study. Setting: One hundred sixteen ICUs in Germany in 2011. Patients: All adult mechanically ventilated patients. Interventions: None. Measurements and Main Results: For a 24-hour period, data were abstracted on hospital and ICU characteristics, the level of patient mobilization and associated barriers, and complications occurring during mobilization. One hundred sixteen participating ICUs provided data for 783 patients. Overall, 185 patients (24%) were mobilized out of bed (i.e., sitting on the edge of the bed or higher level of mobilization). Among patients with an endotracheal tube, tracheostomy, and noninvasive ventilation, 8%, 39%, and 53% were mobilized out of bed, respectively (p < 0.001 for difference between three groups). The most common perceived barriers to mobilizing patients out of bed were cardiovascular instability (17%) and deep sedation (15%). Mobilization out of bed versus remaining in bed was not associated with a higher frequency of complications, with no falls or extubations occurring in those mobilized out of bed. Conclusions: In this 1-day point-prevalence study conducted across Germany, only 24% of all mechanically ventilated patients and only 8% of patients with an endotracheal tube were mobilized out of bed as part of routine care. Addressing modifiable barriers for mobilization, such as deep sedation, will be important to increase mobilization in German ICUs. C1 [Nydahl, Peter] Univ Hosp Schleswig Holstein, Nursing Res Nursing & Patient Serv, Kiel, Germany. [Ruhl, A. Parker; Needham, Dale M.] Johns Hopkins Univ, Div Pulm & Crit Care Med, Outcomes Crit Illness & Surg OACIS Grp, Baltimore, MD USA. [Ruhl, A. Parker] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Bartoszek, Gabriele] Univ Witten Herdecke, Fac Nursing Sci, Witten, Germany. [Dubb, Rolf] Klinikum Stuttgart, Katharinenhosp, Dept Anaesthesiol & Operat Intens Care Med, Stuttgart, Germany. [Filipovic, Silke] Univ Hosp Giessen & Marburg GmbH, Dept Physiotherapy, Marburg, Germany. [Flohr, Hans-Juergen] Work & Life Educ Assoc, Gottingen, Germany. [Kaltwasser, Arnold] Dist Hosp Reutlingen, Dept Continuing Educ Crit Care Nursing, Reutlingen, Germany. [Mende, Hendrik] Klin Eichert, Alb Fils Kliniken GmbH, Dept Anaesthesiol & Intens Care Med, Goppingen, Germany. [Rothaug, Oliver] Univ Hosp Gottingen, Dept Anaesthesiol Emergency & Intens Care Med, Gottingen, Germany. [Schuchhardt, Danny] Zent Klin Bad Berka, Dept Anaesthesia & Intens Care Med, Bad Berka, Germany. [Schwabbauer, Norbert] Univ Hosp Tubingen, Dept Med, Tubingen, Germany. [Needham, Dale M.] Johns Hopkins Univ, Dept Phys Med & Rehabil, Baltimore, MD USA. RP Nydahl, P (reprint author), Univ Hosp Schleswig Holstein, Nursing Res Nursing & Patient Serv, Campus Kiel, Kiel, Germany. EM peter.nydahl@uksh.de FU German Interdisciplinary Association of Critical Care Medicine; National Institutes of Health FX Mr. Nydahl lectured for Hill-Rom and received support for article research from The German Interdisciplinary Association of Critical Care Medicine, which had no role in designing and conducting the study, data collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the article. Mr. Kaltwasser consulted for Kimberly-Clark Health Care (KCC) and Hollister; lectured for Hollister, KCC, and Smith Medical; received support for article preparation from Hollister; and received support for article research from German Interdisciplinary Association of Critical Care Medicine Mr. Schuchhardt lectured for and received support for the development of educational presentations from the company providing material for management of chronic wounds. Dr. Needham's institution received grant support (National Institutes of Health peer-reviewed grants). The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 42 TC 50 Z9 56 U1 3 U2 31 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2014 VL 42 IS 5 BP 1178 EP 1186 DI 10.1097/CCM.0000000000000149 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA AG4IU UT WOS:000335383900034 PM 24351373 ER PT J AU Pastores, SM Martin, GS Baumann, MH Curtis, JR Farmer, JC Fessler, HE Gupta, R Hill, NS Hyzy, RC Kvetan, V MacGregor, DA O'Grady, NP Ognibene, FP Rubenfeld, GD Sessler, CN Siegal, E Simpson, SQ Spevetz, A Ward, NS Zimmerman, JL AF Pastores, Stephen M. Martin, Greg S. Baumann, Michael H. Curtis, J. Randall Farmer, J. Christopher Fessler, Henry E. Gupta, Rakesh Hill, Nicholas S. Hyzy, Robert C. Kvetan, Vladimir MacGregor, Drew A. O'Grady, Naomi P. Ognibene, Frederick P. Rubenfeld, Gordon D. Sessler, Curtis N. Siegal, Eric Simpson, Steven Q. Spevetz, Antoinette Ward, Nicholas S. Zimmerman, Janice L. CA CCSC Task Force Critical Care Educ TI Training Internists to Meet Critical Care Needs in the United States: A Consensus Statement from the Critical Care Societies Collaborative (CCSC)* SO CRITICAL CARE MEDICINE LA English DT Article DE fellowship education; workforce; requirements; internal medicine; critical care medicine; training ID MEDICAL-EDUCATION; BED NUMBERS; BRONCHOSCOPY; RECOMMENDATIONS; GUIDELINES; SIMULATION; WORKFORCE; OUTCOMES; COSTS; ICU AB Objectives: Multiple training pathways are recognized by the Accreditation Council for Graduate Medical Education (ACGME) for internal medicine (IM) physicians to certify in critical care medicine (CCM) via the American Board of Internal Medicine. While each involves 1 year of clinical fellowship training in CCM, substantive differences in training requirements exist among the various pathways. The Critical Care Societies Collaborative convened a task force to review these CCM pathways and to provide recommendations for unified and coordinated training requirements for IM-based physicians. Participants: A group of CCM professionals certified in pulmonary-CCM and/or IM-CCM from ACGME-accredited training programs who have expertise in education, administration, research, and clinical practice. Data Sources and Synthesis: Relevant published literature was accessed through a MEDLINE search and references provided by all task force members. Material published by the ACGME, American Board of Internal Medicine, and other specialty organizations was also reviewed. Collaboratively and iteratively, the task force reached consensus using a roundtable meeting, electronic mail, and conference calls. Main Results: Internal medicine-CCM-based fellowships have disparate program requirements compared to other internal medicine subspecialties and adult CCM fellowships. Differences between IM-CCM and pulmonary-CCM programs include the ratio of key clinical faculty to fellows and a requirement to perform 50 therapeutic bronchoscopies. Competency-based training was considered uniformly desirable for all CCM training pathways. Conclusions: The task force concluded that requesting competency-based training and minimizing variations in the requirements for IM-based CCM fellowship programs will facilitate effective CCM training for both programs and trainees. C1 [Pastores, Stephen M.] Mem Sloan Kettering Canc Ctr, Dept Anesthesiol & Crit Care Med, New York, NY 10021 USA. [Martin, Greg S.] Emory Univ, Sch Med, Div Pulm Allergy & Crit Care, Atlanta, GA USA. [Baumann, Michael H.] Univ Mississippi, Med Ctr, Div Pulm Crit Care & Sleep Med, Jackson, MS 39216 USA. [Curtis, J. Randall] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Farmer, J. Christopher] Mayo Clin Arizona, Phoenix, AZ USA. [Fessler, Henry E.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Gupta, Rakesh] Orlando Hlth, Orlando Reg Med Ctr, Orlando, FL USA. [Hill, Nicholas S.] Tufts Med Ctr, Div Pulm Crit Care & Sleep Med, Boston, MA USA. Univ Michigan, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA. [Kvetan, Vladimir] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Crit Care,Crit Care Med Montefiore Med Ctr, Bronx, NY 10467 USA. [Kvetan, Vladimir] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Crit Care, Bronx, NY 10467 USA. [MacGregor, Drew A.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [O'Grady, Naomi P.; Ognibene, Frederick P.] NIH, Bethesda, MD 20892 USA. [Rubenfeld, Gordon D.] Sunnybrook Hlth Sci Ctr, Trauma Emergency & Crit Care Program, Toronto, ON M4N 3M5, Canada. [Sessler, Curtis N.] Virginia Commonwealth Univ Hlth Syst, Ctr Adult Crit Care, Med Coll Virginia Hosp & Phys, Richmond, VA USA. [Siegal, Eric] Aurora Hlth Care, Madison, WI USA. [Siegal, Eric] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Simpson, Steven Q.] Univ Kansas, Div Pulm & Crit Care, Kansas City, KS USA. [Spevetz, Antoinette] Rowan Univ, Cooper Univ Hosp, Cooper Med Sch, Camden, NJ USA. [Ward, Nicholas S.] Brown Univ, Alpert Med Sch, Div Pulm Crit Care & Sleep Med, Providence, RI 02912 USA. [Zimmerman, Janice L.] Weill Cornell Med Coll, Houston, TX USA. [Zimmerman, Janice L.] Houston Methodist Hosp, Houston, TX USA. RP Pastores, SM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Anesthesiol & Crit Care Med, 1275 York Ave, New York, NY 10021 USA. OI Pastores, Stephen/0000-0002-8850-7062; Martin, Greg/0000-0002-9684-7593 FU Spectral Diagnostics; Bayer Healthcare; NIH; FDA; Baxter Healthcare; Abbott Laboratories; ACCP Board of Regents; PCORI; CCM; Kansas City Area Life Sciences Foundation FX Dr. Pastores' institution received grant support from Spectral Diagnostics (Dr. Pastores is principal investigator at MSKCC for a septic shock clinical trial) and Bayer Healthcare (Dr. Pastores is principal investigator at MSKCC for a gram-negative pneumonia clinical trial). Dr. Martin served as an advisory board member for Cumberland Pharmaceuticals and Pulsion Medical Systems and his institution received grant support from NIH, FDA, Baxter Healthcare, and Abbott Laboratories. Dr. Baumann served as board member for ACCP Board of Regents, is employed by the University of Mississippi Medical Center, received support for the development of educational presentations (various post graduate courses and other products for ACCP and/or ATS), and received support for travel (paid as part of ACCP Board of Regents). Dr. Curtis' institution received grant support from NIH and PCORI. Dr. Fessler received support for development of educational presentations from Oakstone Medical Publishers (Payment for editorial services for a monthly journal review digest in CCM) and received support for travel from American Thoracic Society (Travel expenses to attend committee meetings) and the Association of Pulmonary and Critical Care Medicine Program Directors (Travel expenses to attend committee meetings or to represent the Association at professional society meetings). Dr. O'Grady served as a board member for ABIM and is a government employee. Dr. Ognibene is an employee of the U.S. government and has no copyright authority. Dr. Simpson received support for travel from the Surviving Sepsis Campaign (Planning committee for national sepsis collaborative) and other: IMPRESS Study (North American Co-Chair for the International Multicenter Prevalence Study on Sepsis; no honorarium). His institution received grant support from Kansas City Area Life Sciences Foundation (Grant for sepsis quality improvement work in Kansas City). The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 27 TC 2 Z9 2 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2014 VL 42 IS 5 BP 1272 EP 1279 DI 10.1097/CCM.0000000000000250 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA AG4IU UT WOS:000335383900044 ER PT J AU Ghosh, M Brancato, SJ Agarwal, PK Apolo, AB AF Ghosh, Monalisa Brancato, Sam J. Agarwal, Piyush K. Apolo, Andrea B. TI Targeted therapies in urothelial carcinoma SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE epidermal growth factor receptor family; targeted therapy; tyrosine kinase inhibitors; urothelial carcinoma; vascular endothelial growth factor ID INVASIVE BLADDER-CANCER; PHASE-II TRIAL; TRANSITIONAL-CELL CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; DOSE-ESCALATION; ONCOLOGY-GROUP; OPEN-LABEL; NEOADJUVANT CHEMOTHERAPY; SYSTEMIC CHEMOTHERAPY; CABOZANTINIB XL184 AB Purpose of reviewGreater understanding of the biology and genetics of urothelial carcinoma is helping to identify and define the role of molecules and pathways appropriate for novel-targeted therapies. Here, we review the targeted therapies that have been reported or are in ongoing urothelial carcinoma clinical trials, and highlight molecular targets characterized in preclinical and clinical studies.Recent findingsTrials in nonmuscle-invasive bladder cancer are evaluating the role of immunotherapy and agents targeting vascular endothelial growth factor (VEGF) or fibroblast growth factor receptor-3. In muscle-invasive bladder cancer, neoadjuvant studies have focused on combining VEGF agents with chemotherapy; adjuvant studies are testing vaccines and agents targeting the human epidermal growth factor receptor 2, p53, and Hsp27. In the first-line treatment of metastatic urothelial carcinoma, tubulin, cytotoxic T-lymphocyte antigen 4, Hsp27, and p53 are novel targets in clinical trials. The majority of targeted agents studied in urothelial carcinoma are in the second-line setting; new targets include CD105, polo-like kinase-1, phosphatidylinositide 3-kinases (PI3K), transforming growth factor receptor/activin receptor-like kinase , estrogen receptor, and the hepatocyte growth factor receptor (HGFR or MET).SummaryDevelopment of targeted therapies for urothelial carcinoma is still in early stages, consequently there have been no major therapeutic advances to date. However, greater understanding of urothelial carcinoma and solid tumor biology has resulted in a proliferation of clinical trials that could lead to significant advances in treatment strategies. C1 [Ghosh, Monalisa; Apolo, Andrea B.] NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA. [Brancato, Sam J.; Agarwal, Piyush K.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Apolo, AB (reprint author), 10 Ctr Dr,Rm 12N226,MSC 1906, Bethesda, MD 20892 USA. EM andrea.apolo@nih.gov RI Brancato, Sam/K-3266-2014; OI Brancato, Sam/0000-0002-3760-5818; Agarwal, Piyush/0000-0002-6042-6834 NR 92 TC 26 Z9 26 U1 0 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8746 EI 1531-703X J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD MAY PY 2014 VL 26 IS 3 BP 305 EP 320 DI 10.1097/CCO.0000000000000064 PG 16 WC Oncology SC Oncology GA AF9IP UT WOS:000335028900010 PM 24685646 ER PT J AU Su, D Stamatakis, L Singer, EA Srinivasan, R AF Su, Daniel Stamatakis, Lambros Singer, Eric A. Srinivasan, Ramaprasad TI Renal cell carcinoma: molecular biology and targeted therapy SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE immunotherapy; renal cell carcinoma; targeted therapy ID PHASE-III TRIAL; HIGH-DOSE INTERLEUKIN-2; INTERFERON-ALPHA; ADVANCED CANCER; SUNITINIB; EVEROLIMUS; SORAFENIB; ANTIBODY; SAFETY; TEMSIROLIMUS AB Purpose of reviewRenal cell carcinoma (RCC) continues to be the subject of vigorous clinical and translational investigation. Advances in systemic targeted therapies, new molecular pathways and immunotherapy approaches will be discussed.Recent findingsAgents targeting the vascular endothelial growth factor (VEGF) and/or the mammalian target of rapamycin (mTOR) pathways continue to be the mainstay for treating metastatic RCC (mRCC). Although enhanced target specificity has improved the toxicity profile associated with newer VEGF-pathway antagonists, durable complete responses remain the exception. Identification of novel pathways/agents, as well as the optimal sequencing and combination of existing targeted agents, remain areas of active study. In addition, emerging data from early clinical trials have reinvigorated interest in immunomodulatory agents.SummaryThe therapeutic armamentarium available to genitourinary oncologists continues to grow, but much work remains to be done to fully realize the potential of pathway-specific targeted strategies and immune-based approaches for mRCC. C1 [Su, Daniel; Stamatakis, Lambros; Srinivasan, Ramaprasad] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Singer, Eric A.] Rutgers Canc Inst New Jersey, Sect Urol Oncol, New Brunswick, NJ USA. [Singer, Eric A.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. RP Srinivasan, R (reprint author), NCI, Mol Canc Sect, Urol Oncol Branch, Ctr Canc Res, 10 Ctr Dr,CRC2-5950, Bethesda, MD 20892 USA. EM ramasrin@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, USA; National Cancer Institute [P30CA072720] FX This research was funded in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, USA.; This work was also supported by a grant from the National Cancer Institute (P30CA072720). NR 50 TC 24 Z9 25 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8746 EI 1531-703X J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD MAY PY 2014 VL 26 IS 3 BP 321 EP 327 DI 10.1097/CCO.0000000000000069 PG 7 WC Oncology SC Oncology GA AF9IP UT WOS:000335028900011 PM 24675233 ER PT J AU Sanjuan, PM Rice, SL Witkiewitz, K Mandler, RN Crandall, C Bogenschutz, MP AF Sanjuan, Pilar M. Rice, Samara L. Witkiewitz, Katie Mandler, Raul N. Crandall, Cameron Bogenschutz, Michael P. TI Alcohol, tobacco, and drug use among emergency department patients SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Emergency department; Alcohol; Substance abuse; Tobacco; Addiction; Negative binomial model ID ABUSE TREATMENT NEED; BRIEF INTERVENTION; SUBSTANCE USE; PRIMARY-CARE; UNITED-STATES; SERVICES UTILIZATION; GENERAL-POPULATION; PROBLEM DRINKING; SCREENING-TEST; USE DISORDERS AB Background: The prevalence of alcohol, tobacco, and other drug (ATOD) use among emergency department (ED) patients is high and many of these patients have unrecognized and unmet substance use treatment needs. Identification of patients in the ED with problem substance use is not routine at this time. Methods: We examined screening data, including standardized measures of ATOD use (HSI, AUDIT-C, DAST-10), from 14,866 ED patients in six hospitals across the United States. We expected younger age, male gender, higher triage acuity, and other substance use severity (ATOD) to be associated both with use versus abstinence and with severity of each substance use type. We used negative binomial hurdle models to examine the association between covariates and (1) substance use versus abstinence (logistic submodel) and with (2) severity among those who used substances (count submodel). Results: Rates of use and problem use in our sample were similar to or higher than other ED samples. Younger patients and males were more likely to use ATOD, but the association of age and gender with severity varied across substances. Triage level was a poor predictor of substance use severity. Alcohol, tobacco, and drug use were significantly associated with using other substances and severity of other substance use. Conclusion: Better understanding of the demographic correlates of ATOD use and severity and the patterns of comorbidity among classes of substance can inform the design of optimal screening and brief intervention procedures addressing ATOD use among ED patients. Tobacco may be an especially useful predictor. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Sanjuan, Pilar M.; Rice, Samara L.; Witkiewitz, Katie; Bogenschutz, Michael P.] Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM 87106 USA. [Rice, Samara L.] SUNY Buffalo, Res Inst Addict, Buffalo, NY 14203 USA. [Mandler, Raul N.] NIDA, Ctr Clin Trials Network, NIH, Bethesda, MD 20892 USA. [Crandall, Cameron] Univ New Mexico, Hlth Sci Ctr, Dept Emergency Med, Albuquerque, NM 87131 USA. [Bogenschutz, Michael P.] Univ New Mexico, Dept Psychiat, Hlth Sci Ctr, Albuquerque, NM 87131 USA. RP Sanjuan, PM (reprint author), Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, 2650 Yale Blvd,MSC11-6280, Albuquerque, NM 87106 USA. EM psanjuan@unm.edu OI Bogenschutz, Michael/0000-0003-4530-3470 FU NIAAA NIH HHS [L30 AA019906, T32 AA018108]; NIDA NIH HHS [U10 DA013732, K24 DA022412, L30 DA025498, U10 DA013035, U10 DA013714, U10 DA013720, U10 DA015831, U10 DA015833, U10 DA020024, U10 DA020036] NR 41 TC 7 Z9 7 U1 2 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAY 1 PY 2014 VL 138 BP 32 EP 38 DI 10.1016/j.drugalcdep.2014.01.025 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AG7SN UT WOS:000335618800005 PM 24594289 ER PT J AU Tomei, S Wang, E Delogu, LG Marincola, FM Bedognetti, D AF Tomei, Sara Wang, Ena Delogu, Lucia Gemma Marincola, Francesco M. Bedognetti, Davide TI Non-BRAF-targeted therapy, immunotherapy, and combination therapy for melanoma SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE adoptive T-cell transfer; combination therapy; immunotherapy; melanoma; targeted therapy ID PHASE-II TRIAL; TUMOR-INFILTRATING LYMPHOCYTES; DOSE RECOMBINANT INTERLEUKIN-2; GASTROINTESTINAL STROMAL TUMOR; UNTREATED METASTATIC MELANOMA; CANCER IMMUNE RESPONSIVENESS; CYTOLYTIC T-LYMPHOCYTES; TERT PROMOTER MUTATIONS; ADOPTIVE CELL THERAPY; STAGE IV MELANOMA AB Introduction: Melanoma is an aggressive disease characterized by a complex etiology. The discovery of key driving mutations (primarily BRAF mutations) led to the development of specific molecular inhibitors providing clinical benefit. Areas covered: Although BRAF-specific drugs have perhaps yielded the best results in melanoma-targeted therapy, there still remain several limitations, mostly due to the emergence of resistance and the lack of efficacy in patients without BRAF mutation. Novel drugs are currently being tested in clinical trials and showed encouraging results. Such drugs can specifically target molecular pathways aberrantly activated or repressed during melanoma development (targeted therapy) or act in a way to enhance the host immune system to fight cancer (immunotherapy). Here we provide a detailed overview of the current clinical strategies, which lay beyond BRAF-targeted therapy, spanning from molecular-targeted therapy to immunotherapy and to combination therapy. Expert opinion: Major advances in our understanding of the mechanisms behind melanoma development have led to the implementation of novel therapeutic drugs. Unfortunately, tools allowing prediction of responsiveness to a given treatment are not available yet. The increasing availability of high-throughput technologies will allow the elucidation of molecular mechanisms underlying responsiveness to cancer therapy and unveil an increased number of potential therapeutic targets. C1 [Tomei, Sara; Wang, Ena; Marincola, Francesco M.; Bedognetti, Davide] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Tomei, Sara; Wang, Ena; Marincola, Francesco M.; Bedognetti, Davide] Trans NIH Ctr Human Immunol CHI, Dept Transfus Med, IDIS, Bethesda, MD 20892 USA. [Tomei, Sara] Weill Cornell Med Coll Qatar, Dept Med Genet, Doha, Qatar. [Wang, Ena; Marincola, Francesco M.] Sidra Med & Res Ctr, Res Branch, Doha, Qatar. [Delogu, Lucia Gemma] Univ Sassari, Dipartimento Chim & Farm, I-07100 Sassari, Italy. RP Tomei, S (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. EM sat2024@qatar-med.cornell.edu; bedognettid@cc.nih.gov OI Bedognetti, Davide/0000-0002-5857-773X NR 216 TC 11 Z9 11 U1 0 U2 16 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 EI 1744-7682 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD MAY PY 2014 VL 14 IS 5 BP 663 EP 686 DI 10.1517/14712598.2014.890586 PG 24 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA AG5AC UT WOS:000335430500009 PM 24625306 ER PT J AU Takasawa, K Kashimada, K Pelosi, E Takagi, M Morio, T Asahara, H Schlessinger, D Mizutani, S Koopman, P AF Takasawa, Kei Kashimada, Kenichi Pelosi, Emanuele Takagi, Masatoshi Morio, Tomohiro Asahara, Hiroshi Schlessinger, David Mizutani, Shuki Koopman, Peter TI FOXL2 transcriptionally represses Sf1 expression by antagonizing WT1 during ovarian development in mice SO FASEB JOURNAL LA English DT Article DE sex determination; reproduction; LHX9 ID STEROIDOGENIC FACTOR-I; SEX DETERMINATION; NUCLEAR RECEPTOR; GONADAL DEVELOPMENT; FOLLICLE DEVELOPMENT; GENE-EXPRESSION; GRANULOSA-CELLS; MOUSE; FACTOR-1; PROMOTER AB Steroidogenic factor 1 (SF1; Ad4BP/NR5A1) plays key roles in gonadal development. Initially, the Sf1 gene is expressed in mouse fetal gonads of both sexes, but later is up-regulated in testes and down-regulated in ovaries. While Sf1 expression is activated and maintained by Wilms tumor 1 (WT1) and LIM homeobox 9 (LHX9), the mechanism of sex-specific regulation remains unclear. We hypothesized that Sf1 is repressed by the transcription factor Forkhead box L2 (FOXL2) during ovarian development. In an in vitro system (TM3 cells), up-regulation of Sf1 by the WT1 splice variant WT1-KTS was antagonized by FOXL2, as determined by quantitative RT-PCR. Using reporter assays, we localized the Sf1 proximal promoter region involved in this antagonism to a 674-bp interval. A conserved FOXL2 binding site was identified in this interval by in vitro chromatin immunoprecipitation. Introducing mutations into this site abolished negative regulation by FOXL2 in reporter assays. Finally, in Foxl2-null mice, Sf1 expression was increased 2-fold relative to wild-type XX fetal gonads. Our results support the hypothesis that FOXL2 negatively regulates Sf1 expression by antagonizing WT1-KTS during early ovarian development in mice.Takasawa, K., Kashimada, K., Pelosi, E., Takagi, M., Morio, T., Asahara, H., Schlessinger, D., Mizutani, S., Koopman, P. FOXL2 transcriptionally represses Sf1 expression by antagonizing WT1 during ovarian development in mice. C1 [Takasawa, Kei; Kashimada, Kenichi; Takagi, Masatoshi; Morio, Tomohiro; Mizutani, Shuki] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Pediat & Dev Biol, Bunkyo Ku, Tokyo 1138510, Japan. [Asahara, Hiroshi] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Syst BioMed, Bunkyo Ku, Tokyo 1138510, Japan. [Pelosi, Emanuele; Schlessinger, David] NIA, Intramural Res Program, Genet Lab, US Natl Inst Hlth Biomed Res Ctr, Baltimore, MD 21224 USA. [Koopman, Peter] Univ Queensland, Inst Mol Biosci, Div Mol Genet & Dev, Brisbane, Qld, Australia. RP Kashimada, K (reprint author), Tokyo Med & Dent Univ, Dept Pediat & Dev Biol, Bunkyo Ku, Tokyo 1138510, Japan. EM kkashimada.ped@tmd.ac.jp RI Koopman, Peter /C-9416-2009; OI Koopman, Peter /0000-0001-6939-0914; Pelosi, Emanuele/0000-0003-1890-9821; Takasawa, Kei/0000-0001-6947-4034; Kashimada, Kenichi/0000-0003-2505-5932 FU Intramural Research Program of the U.S. National Institutes of Health, National Institute on Aging; Ministry of Education, Culture, Sports, Science, and Technology (MEXT) [23249071]; Japan Society for the Promotion of Science (JSPS) KAKENHI grant [24115707]; Japan Science and Technology Agency (JST) Core Research for Evolutionary Science and Technology (CREST) [24591503] FX The authors thank Dagmar Wilhelm (Monash University, Melbourne, VIC, Australia) for critical reading of the manuscript and Atsushi Kubo (Tokyo Medical and Dental University) for technical support. This research was supported, in part, by the Intramural Research Program of the U.S. National Institutes of Health, National Institute on Aging, for E.P. and D.S.; Ministry of Education, Culture, Sports, Science, and Technology (MEXT) Grants-in-Aid for Scientific Research (KAKENHI) grant 23249071, Japan Society for the Promotion of Science (JSPS) KAKENHI grant 24115707, and Japan Science and Technology Agency (JST) Core Research for Evolutionary Science and Technology (CREST), for H.A.; and KAKENHI (C) grant 24591503, for K.K. NR 40 TC 14 Z9 15 U1 0 U2 10 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD MAY PY 2014 VL 28 IS 5 BP 2020 EP 2028 DI 10.1096/fj.13-246108 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AG3RA UT WOS:000335336000007 PM 24451388 ER PT J AU Devine, K Stillman, RJ DeCherney, AH AF Devine, Kate Stillman, Robert J. DeCherney, Alan H. TI The Affordable Care Act: early implications for fertility medicine SO FERTILITY AND STERILITY LA English DT Editorial Material C1 [Devine, Kate; DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Adult & Reprod Endocrinol, NIH, Bethesda, MD 20892 USA. [Stillman, Robert J.] Shady Grove Fertil Ctr, Rockville, MD USA. RP Devine, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Adult & Reprod Endocrinol, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 HD999999] NR 5 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2014 VL 101 IS 5 BP 1224 EP 1227 DI 10.1016/j.fertnstert.2014.01.024 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AG6BX UT WOS:000335504600011 PM 24582184 ER PT J AU Louis, GMB Sundaram, R Sweeney, AM Schisterman, EF Maisog, J Kannan, K AF Louis, Germaine M. Buck Sundaram, Rajeshwari Sweeney, Anne M. Schisterman, Enrique F. Maisog, Jose Kannan, Kurunthachalam TI Urinary bisphenol A, phthalates, and couple fecundity: the Longitudinal Investigation of Fertility and the Environment (LIFE) Study SO FERTILITY AND STERILITY LA English DT Article DE Bisphenol A; endocrine disrupting chemicals; fecundity; phthalates; reproduction ID ENDOCRINE-DISRUPTING CHEMICALS; IN-VITRO FERTILIZATION; REPRODUCTIVE FUNCTION; HUMAN SEMEN; EXPOSURE; HEALTH; WOMEN; INFERTILITY; METABOLITES; PREGNANCY AB Objective: To assess the relationship between environmental chemicals and couple fecundity or time to pregnancy (TTP). Design: Prospective cohort. Setting: Communities of targeted populations with reported exposure. Patient(s): 501 couples recruited upon discontinuing contraception to become pregnant, 2005-2009. Intervention(s): None. Main Outcome Measure(s): Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) estimated for each partner's chemical concentrations adjusted for age, body mass index, cotinine, creatinine, and research site while accounting for time off contraception. Result(s): Couples completed interviews and anthropometric assessments and provided the urine specimens for quantification of bisphenol A (BPA) and 14 phthalate metabolites, which were measured using high-performance liquid chromatography with electrospray triple-quadrupole mass spectrometer. Women recorded menstruation and pregnancy test results in daily journals. Couples were evaluated until a positive human-chorionic gonadotropin pregnancy test or 12 cycles without pregnancy. Neither female nor male BPA concentration was associated with TTP (FOR 0.98; 95% CI, 0.86, 1.13 and FOR 1.04; 95% CI, 0.91, 1.18, respectively). Men's urinary concentrations of monomethyl, mono-n-butyl, and monobenzyl phthalates were associated with a longer TTP (FOR 0.80; 95% CI, 0.70, 0.93; FOR 0.82, 95% CI, 0.70, 0.97; and FOR 0.77, 95% CI, 0.65 0.92, respectively). Conclusion(s): Select male but not female phthalate exposures were associated with an approximately 20% reduction in fecundity, underscoring the importance of assessing both partners' exposure to minimize erroneous conclusions. (C) 2014 by American Society for Reproductive Medicine. C1 [Louis, Germaine M. Buck; Sundaram, Rajeshwari; Schisterman, Enrique F.; Maisog, Jose] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD 20852 USA. [Sweeney, Anne M.] Texas A&M Rural Sch Publ Hlth, Dept Epidemiol & Biostat, College Stn, TX USA. [Kannan, Kurunthachalam] New York State Dept Hlth, Wadsworth Ctr, Div Environm Hlth Sci, Albany, NY USA. [Kannan, Kurunthachalam] SUNY Albany, Dept Environm Hlth Sci, Albany, NY 12222 USA. RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. EM louisg@mail.nih.gov OI Sundaram, Rajeshwari/0000-0002-6918-5002; Schisterman, Enrique/0000-0003-3757-641X; Buck Louis, Germaine/0000-0002-1774-4490 FU National Institutes of Health, Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development [N01-HD-3-3355, N01-HD-3-3356, NOH-HD-3-3358, HHSN27500001] FX Funded by the National Institutes of Health, Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts N01-HD-3-3355; N01-HD-3-3356; NOH-HD-3-3358; HHSN27500001). NR 63 TC 35 Z9 35 U1 4 U2 50 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2014 VL 101 IS 5 BP 1359 EP 1366 DI 10.1016/j.fertnstert.2014.01.022 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AG6BX UT WOS:000335504600038 ER PT J AU Whitcomb, BW Mumford, SL Perkins, NJ Wactawski-Wende, J Bertone-Johnson, ER Lynch, KE Schisterman, EF AF Whitcomb, Brian W. Mumford, Sunni L. Perkins, Neil J. Wactawski-Wende, Jean Bertone-Johnson, Elizabeth R. Lynch, Kristine E. Schisterman, Enrique F. TI Urinary cytokine and chemokine profiles across the menstrual cycle in healthy reproductive-aged women SO FERTILITY AND STERILITY LA English DT Article DE Chemokines; cytokines; immunology; inflammation; menstrual cycle ID COLONY-STIMULATING FACTOR; MARGINAL STRUCTURAL MODELS; HUMAN ENDOMETRIUM; MULTIPLE IMPUTATION; PERIPHERAL-BLOOD; FERTILE WOMEN; CELLS; IMPLANTATION; EXPRESSION; OVULATION AB Objective: To assess the utility of urinary cytokines for monitoring reproductive function by considering detection, variation across the menstrual cycle, and relations with hormones. Design: Longitudinal cohort study. Setting: Academic institution. Patient(s): Healthy, reproductive-aged women with self-reported regular menstrual cycles and at least one observed ovulatory cycle (n = 248). Intervention(s): None. Main Outcome Measure(s): Urinary cytokines measured by 30-plex immunoassays in 3,550 biospecimens, and nested random-effects analysis of variance (ANOVA) and marginal structural models used to evaluate variability and relations with hormones. Result(s): For 24 of 30 evaluated factors, detectable levels were observed in at least 50% of urine samples. Interleukin-6 (IL-6), IL-8, IL-10, IL-15, granulocyte colony stimulating factor (G-CSF), hepatocyte growth factor (HGF), interferon-alpha (IFN-alpha), and RANTES (regulated upon activation normal T-cell expressed and secreted) levels varied significantly across the menstrual cycle. The proinflammatory factors IL-1 beta, IL-6, IL-8, and HGF were 1.5-3 times higher during menses than the late follicular phase. In marginal structural models, IL-1 beta, IL-6, IL-8 were associated with lower estradiol and progesterone concentrations. Conclusion(s): Variability during the menstrual cycle and correlations with reproductive hormone levels support a role of cytokines in the menstrual cycle; however, because of the limited variability for most cytokines considered, the utility of urine as a matrix for assessment of inflammation in menstrual cycle function appears limited for clinical purposes. (C) 2014 by American Society for Reproductive Medicine. C1 [Whitcomb, Brian W.; Bertone-Johnson, Elizabeth R.; Lynch, Kristine E.] Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA. [Mumford, Sunni L.; Perkins, Neil J.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. RP Whitcomb, BW (reprint author), Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, 715 N Pleasant St, Amherst, MA 01003 USA. EM bwhitcomb@schoolph.umass.edu OI Perkins, Neil/0000-0002-6802-4733; Schisterman, Enrique/0000-0003-3757-641X FU National Institutes of Health, Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HHSN275200403394C] FX Funded by the National Institutes of Health, Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), contract HHSN275200403394C to the University at Buffalo. NR 48 TC 7 Z9 7 U1 4 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2014 VL 101 IS 5 BP 1383 EP U39 DI 10.1016/j.fertnstert.2014.01.027 PG 11 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AG6BX UT WOS:000335504600041 PM 24581581 ER PT J AU Valente, AJ Irimpen, AM Siebenlist, U Chandrasekar, B AF Valente, Anthony J. Irimpen, Anand M. Siebenlist, Ulrich Chandrasekar, Bysani TI OxLDL induces endothelial dysfunction and death via TRAF3IP2: Inhibition by HDL3 and AMPK activators SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Atherosclerosis; Oxidative stress; NADPH oxidases; Endothelial dysfunction; Free radicals ID LOW-DENSITY-LIPOPROTEIN; PROTEIN-KINASE; AIRWAY INFLAMMATION; CELL APOPTOSIS; UP-REGULATION; OXIDIZED LDL; CIKS ACT1; OX-LDL; OXIDATION; RECEPTOR AB Oxidized low-density lipoprotein (oxLDL) induces endothelial cell death through the activation of NF-kappa B and AP-1 pathways. TRAF3IP2 is a redox-sensitive cytoplasmic adapter protein and an upstream regulator of IKK/NF-kappa B and JNK/AP-1. Here we show that oxLDL-induced death in human primary coronary artery endothelial cells (ECs) was markedly attenuated by the knockdown of TRAF3IP2 or the lectin-like oxLDL receptor I (LOX-1). Further, oxLDL induced Nox2/superoxide-dependent TRAF3IP2 expression, IKK/p65 and JNK/c-Jun activation, and LOX-I upregulation, suggesting a reinforcing mechanism. Similarly, the lysolipids present in oxLDL (16:0-LPC and 18:0-LPC) and minimally modified LDL also upregulated TRAF3IP2 expression. Notably, whereas native HDL3 reversed oxLDL-induced TRAF3IP2 expression and cell death, 15-lipoxygenase-modified HDL3 potentiated its proapoptotic effects. The activators of the AMPK/Akt pathway, adiponectin, AICAR, and metformin, attenuated superoxide generation, TRAF3IP2 expression, and oxLDL/TRAF3IP2-mediated EC death. Further, both HDL3 and adiponectin reversed oxLDL/TRAF3IP2-dependent monocyte adhesion to endothelial cells in vitro. Importantly, TRAF3IP2 gene deletion and the AMPK activators reversed oxLDL-induced impaired vasorelaxation ex vivo. These results indicate that oxLDL-induced endothelial cell death and dysfunction are mediated via TRAF3IP2 and that native HDL3 and the AMPK activators inhibit this response. Targeting TRAF3IP2 could potentially inhibit progression of atherosclerotic vascular diseases. (c) 2014 Elsevier Inc. All rights reserved. C1 [Valente, Anthony J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Valente, Anthony J.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Irimpen, Anand M.; Chandrasekar, Bysani] Southeast Louisiana Vet Hlth Care Syst, Res Serv, New Orleans, LA 70161 USA. [Irimpen, Anand M.; Chandrasekar, Bysani] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA. [Siebenlist, Ulrich] NIAID, NIH, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Chandrasekar, B (reprint author), Tulane Univ, Sch Med, Inst Heart & Vasc, 1430 Tulane Ave,SL-48, New Orleans, LA 70112 USA. EM bchandra@tulane.edu FU Department of Veterans Affairs Research Career Scientist award; VA Office of Research and Development Biomedical Laboratory Research and Development Service Award [1I01BX000246]; NIH/NHLBI [HL-86787] FX B.C. is the recipient of a Department of Veterans Affairs Research Career Scientist award and is supported by VA Office of Research and Development Biomedical Laboratory Research and Development Service Award 1I01BX000246 and NIH/NHLBI Grant HL-86787. U.S. is supported by the Intramural Research Program of the NIH/NIAID. The contents of this report do not represent the views of the Department of Veterans Affairs or the United States government. NR 41 TC 15 Z9 18 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY PY 2014 VL 70 BP 117 EP 128 DI 10.1016/j.freeradbiomed.2014.02.014 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AG5VP UT WOS:000335487100012 PM 24561578 ER PT J AU Wang, GJ Tomasi, D Volkow, ND Wang, R Telang, F Caparelli, EC Dunayevich, E AF Wang, G-J Tomasi, D. Volkow, N. D. Wang, R. Telang, F. Caparelli, E. C. Dunayevich, E. TI Effect of combined naltrexone and bupropion therapy on the brain's reactivity to food cues SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE fMRI; naltrexone; bupropion ID NEURONAL RESPONSE; OBESE INDIVIDUALS; PREFRONTAL CORTEX; VENTRAL STRIATUM; EATING BEHAVIOR; ACTIVATION; HUMANS; HIPPOCAMPUS; CIRCUITRY; STIMULI AB OBJECTIVE: The significant weight loss observed with combination naltrexone-sustained release (SR) 32mg and bupropion SR 360mg (NB32) therapy is thought to be due, in part, to bupropion stimulation of hypothalamic pro-opiomelanocortin (POMC) neurons, and naltrexone blockade of opioid receptor-mediated POMC autoinhibition, but the neurobiological mechanisms are not fully understood. We assessed changes in brain reactivity to food cues before and after NB32 treatment. METHODS: Forty women (31.1 +/- 8.1 years; body mass index: 32.5 +/- 3.9) received 4 weeks of NB32 or placebo, and were instructed to maintain their dietary and exercise habits. Functional magnetic resonance imaging responses (analyzed using SPM2 and clusters (> 100 pixels)) to a 5-min food video (preparation of the subject's favorite food) and a 5-min neutral video (manipulation of neutral objects) under conditions of mild food deprivation (similar to 14 h) were assessed before and after treatment. RESULTS: The food cues video induced positive brain activation in visual and prefrontal cortices, insula and subcortical brain regions. The group-by-treatment interaction on regional brain activation was significant and showed that whereas NB32 attenuated the activation in the hypothalamus in response to food cues (P<0.01), it enhanced activation in regions involved in inhibitory control (anterior cingulate), internal awareness (superior frontal, insula, superior parietal) and memory (hippocampal) regions (whole-brain analysis; P<0.05). CONCLUSIONS: Blunting the hypothalamic reactivity to food cues while enhancing the activation of regions involved with self-control and internal awareness by NB32 might underlie its therapeutic benefits in obesity. C1 [Wang, G-J; Wang, R.] Brookhaven Natl Lab, Dept Biosci, Upton, NY 11973 USA. [Wang, G-J] SUNY Stony Brook, Dept Radiol, Stony Brook, NY 11794 USA. [Tomasi, D.; Volkow, N. D.; Telang, F.] NIAAA, Neuroimaging Lab, Intramural Program, Upton, NY USA. [Volkow, N. D.] NIDA, Off Director, Bethesda, MD 20892 USA. [Caparelli, E. C.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Dunayevich, E.] Amgen Inc, Newbury Pk, CA USA. RP Wang, GJ (reprint author), Brookhaven Natl Lab, Dept Biosci, POB 5000,30 Bell Ave,Bldg 490, Upton, NY 11973 USA. EM gjwang@bnl.gov RI Tomasi, Dardo/J-2127-2015 FU Orexigen Therapeutics Inc.; Intramural Research Program of the National Institute on Alcoholism and Alcohol Abuse [Z01AA000550] FX We thank Karen Apelskog-Torres for study protocol preparation, Millard Jayne for subject recruitment, Barbara Hubbard and Pauline Carter for patient care and Orexigen Therapeutics for scientific review of the manuscript. The functional MR study was carried out at Brookhaven National Laboratory with support from Orexigen Therapeutics Inc. (GJW) and in part from Intramural Research Program of the National Institute on Alcoholism and Alcohol Abuse, Z01AA000550 (NDV, FT, MJ). NR 46 TC 14 Z9 14 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD MAY PY 2014 VL 38 IS 5 BP 682 EP 688 DI 10.1038/ijo.2013.145 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AG5FQ UT WOS:000335445300010 PM 23924756 ER PT J AU Zhang, Y Yu, XM Ichikawa, M Lyons, JJ Datta, S Lamborn, IT Jing, H Kim, ES Biancalana, M Wolfe, LA DiMaggio, T Matthews, HF Kranick, SM Stone, KD Holland, SM Reich, DS Hughes, JD Mehmet, H McElwee, J Freeman, AF Freeze, HH Su, HC Milner, JD AF Zhang, Yu Yu, Xiaomin Ichikawa, Mie Lyons, Jonathan J. Datta, Shrimati Lamborn, Ian T. Jing, Huie Kim, Emily S. Biancalana, Matthew Wolfe, Lynne A. DiMaggio, Thomas Matthews, Helen F. Kranick, Sarah M. Stone, Kelly D. Holland, Steven M. Reich, Daniel S. Hughes, Jason D. Mehmet, Huseyin McElwee, Joshua Freeman, Alexandra F. Freeze, Hudson H. Su, Helen C. Milner, Joshua D. TI Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Atopy; immune deficiency; hyper-IgE; neurocognitive impairment; phosphoglucomutase 3; glycosylation; allergy; autoimmunity ID HYPER-IGE SYNDROME; CONGENITAL DISORDERS; NUCLEOTIDE SUGARS; STAT3 MUTATIONS; O-GLCNACYLATION; JOBS-SYNDROME; DOCK8; MYOCLONUS; CHILDREN; HEALTHY AB Background: Identifying genetic syndromes that lead to significant atopic disease can open new pathways for investigation and intervention in allergy. Objective: We sought to define a genetic syndrome of severe atopy, increased serum IgE levels, immune deficiency, autoimmunity, and motor and neurocognitive impairment. Methods: Eight patients from 2 families with similar syndromic features were studied. Thorough clinical evaluations, including brain magnetic resonance imaging and sensory evoked potentials, were performed. Peripheral lymphocyte flow cytometry, antibody responses, and T-cell cytokine production were measured. Whole-exome sequencing was performed to identify disease-causing mutations. Immunoblotting, quantitative RTPCR, enzymatic assays, nucleotide sugar, and sugar phosphate analyses, along with matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry of glycans, were used to determine the molecular consequences of the mutations. Results: Marked atopy and autoimmunity were associated with increased T(H)2 and T(H)17 cytokine production by CD4(+) T cells. Bacterial and viral infection susceptibility were noted along with T-cell lymphopenia, particularly of CD8(+) T cells, and reduced memory B-cell numbers. Apparent brain hypomyelination resulted in markedly delayed evoked potentials and likely contributed to neurologic abnormalities. Disease segregated with novel autosomal recessive mutations in a single gene, phosphoglucomutase 3 (PGM3). Although PGM3 protein expression was variably diminished, impaired function was demonstrated by decreased enzyme activity and reduced uridine diphosphate-N-acetyl-D-glucosamine, along with decreased O- and N-linked protein glycosylation in patients' cells. These results define a new congenital disorder of glycosylation. Conclusions: Autosomal recessive hypomorphic PGM3 mutations underlie a disorder of severe atopy, immune deficiency, autoimmunity, intellectual disability, and hypomyelination. C1 [Zhang, Yu; Lamborn, Ian T.; Jing, Huie; Kim, Emily S.; DiMaggio, Thomas; Su, Helen C.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Yu, Xiaomin; Lyons, Jonathan J.; Datta, Shrimati; Stone, Kelly D.; Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Biancalana, Matthew; Matthews, Helen F.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Holland, Steven M.; Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Ichikawa, Mie; Freeze, Hudson H.] Sanford Burnham Med Res Inst, La Jolla, CA USA. [Wolfe, Lynne A.] NHGRI, Undiagnosed Dis Program, Bethesda, MD 20892 USA. [Kranick, Sarah M.] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA. [Reich, Daniel S.] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Hughes, Jason D.; Mehmet, Huseyin; McElwee, Joshua] Merck & Co Inc, Merck Res Labs, Boston, MA USA. RP Milner, JD (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10CRC,Rm 5W-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM hsu@niaid.nih.gov; jdmilner@niaid.nih.gov RI Reich, Daniel/E-5701-2010; Su, Helen/H-9541-2015; OI Reich, Daniel/0000-0002-2628-4334; Su, Helen/0000-0002-5582-9110; Biancalana, Matthew/0000-0002-1078-1838; Freeze, Hudson/0000-0001-6316-0501; Lyons, Jonathan/0000-0002-2346-8189 FU Intramural Research Programs of the National Institutes of Allergy and Infectious Diseases; National Human Genome Research Institute; National Institute of Neurological Diseases and Stroke; National Institutes of Health; Rocket Fund; R01DK55615 FX Supported by the Intramural Research Programs of the National Institutes of Allergy and Infectious Diseases, the National Human Genome Research Institute, and the National Institute of Neurological Diseases and Stroke, all at the National Institutes of Health. H. H. F. and M. I. were supported by R01DK55615 and the Rocket Fund. NR 25 TC 44 Z9 44 U1 1 U2 14 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2014 VL 133 IS 5 BP 1400 EP U658 DI 10.1016/j.jaci.2014.02.013 PG 15 WC Allergy; Immunology SC Allergy; Immunology GA AG5HS UT WOS:000335450700023 PM 24589341 ER PT J AU Sassi, A Lazaroski, S Wu, G Haslam, SM Fliegauf, M Mellouli, F Patiroglu, T Unal, E Ozdemir, MA Jouhadi, Z Khadir, K Ben-Khemis, L Ben-Ali, M Ben-Mustapha, I Borchani, L Pfeifer, D Jakob, T Khemiri, M Asplund, AC Gustafsson, MO Lundin, KE Falk-Sorqvist, E Moens, LN Gungor, HE Engelhardt, KR Dziadzio, M Stauss, H Fleckenstein, B Meier, R Prayitno, K Maul-Pavicic, A Schaffer, S Rakhmanov, M Henneke, P Kraus, H Eibel, H Kolsch, U Nadifi, S Nilsson, M Bejaoui, M Schaffer, AA Smith, CIE Dell, A Barbouche, MR Grimbacher, B AF Sassi, Atfa Lazaroski, Sandra Wu, Gang Haslam, Stuart M. Fliegauf, Manfred Mellouli, Fethi Patiroglu, Turkan Unal, Ekrem Ozdemir, Mehmet Akif Jouhadi, Zineb Khadir, Khadija Ben-Khemis, Leila Ben-Ali, Meriem Ben-Mustapha, Imen Borchani, Lamia H. Pfeifer, Dietmar Jakob, Thilo Khemiri, Monia Asplund, A. Charlotta Gustafsson, Manuela O. Lundin, Karin E. Falk-Soerqvist, Elin Moens, Lotte N. Gungor, Hatice Eke Engelhardt, Karin R. Dziadzio, Magdalena Stauss, Hans Fleckenstein, Bernhard Meier, Rebecca Prayitno, Khairunnadiya Maul-Pavicic, Andrea Schaffer, Sandra Rakhmanov, Mirzokhid Henneke, Philipp Kraus, Helene Eibel, Hermann Koelsch, Uwe Nadifi, Sellama Nilsson, Mats Bejaoui, Mohamed Schaeffer, Alejandro A. Smith, C. I. Edvard Dell, Anne Barbouche, Mohamed-Ridha Grimbacher, Bodo TI Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Hyper-IgE syndrome; glycosylation; Staphylococcus aureus; signal transducer and activator of transcription 3; dedicator of cytokinesis 8; phosphoglucomutase 3 ID CONGENITAL DISORDERS; PRIMARY IMMUNODEFICIENCIES; LINKAGE ANALYSIS; GLYCOSYLATION; DEFICIENCY; DISEASE; MUTASE; DOCK8; IDENTIFICATION; INFECTIONS AB Background: Recurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. However, glycosylation defects have not been described in patients with HIES. One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans. Objective: We sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8. Methods: After establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. Protein expression was analyzed by means of Western blotting, and glycosylation was profiled by using mass spectrometry. Results: Mutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. The mutations predict amino acid changes in PGM3 (p. Glu340del and p. Leu83Ser). A third homozygous mutation (p. Asp502Tyr) and the p. Leu83Ser variant were identified in 2 other affected families, respectively. These hypomorphic mutations have an effect on the biosynthetic reactions involving uridine diphosphate N-acetylglucosamine. Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. T-cell proliferation and differentiation were impaired in patients. Most patients had developmental delay, and many had psychomotor retardation. Conclusion: Impairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype. C1 [Sassi, Atfa; Ben-Khemis, Leila; Ben-Ali, Meriem; Ben-Mustapha, Imen; Barbouche, Mohamed-Ridha] Pasteur Inst Tunis, Lab Immunopathol Vaccinol & Mol Genet, Tunis, Tunisia. [Sassi, Atfa; Ben-Khemis, Leila; Ben-Ali, Meriem; Ben-Mustapha, Imen; Barbouche, Mohamed-Ridha] Univ Tunis El Manar, Tunis, Tunisia. [Lazaroski, Sandra; Fliegauf, Manfred; Meier, Rebecca; Prayitno, Khairunnadiya; Maul-Pavicic, Andrea; Schaffer, Sandra; Rakhmanov, Mirzokhid; Henneke, Philipp; Kraus, Helene; Eibel, Hermann; Grimbacher, Bodo] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, D-79108 Freiburg, Germany. [Pfeifer, Dietmar; Smith, C. I. Edvard] Univ Med Ctr Freiburg, Dept Med Specialt Hematol Oncol & Stem Cell Trans, D-79108 Freiburg, Germany. [Jakob, Thilo] Univ Med Ctr Freiburg, Dept Dermatol, Allergy Res Grp, D-79108 Freiburg, Germany. [Wu, Gang; Haslam, Stuart M.; Dell, Anne] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, London SW7 2AZ, England. [Mellouli, Fethi; Bejaoui, Mohamed] Bone Marrow Transplantat Ctr, Dept Pediat, Tunis, Tunisia. [Patiroglu, Turkan; Unal, Ekrem; Ozdemir, Mehmet Akif] Erciyes Univ, Fac Med, Dept Pediat, Div Pediat Hematol & Oncol, Kayseri, Turkey. [Patiroglu, Turkan; Gungor, Hatice Eke] Erciyes Univ, Fac Med, Dept Pediat, Div Pediat Immunol, Kayseri, Turkey. [Jouhadi, Zineb; Khadir, Khadija] Hassan II Univ, CHU IBN ROCHD, Dept Pediat Infect Dis, Casablanca, Morocco. [Nadifi, Sellama] Hassan II Univ, Dept Genet, Casablanca, Morocco. [Borchani, Lamia H.] Inst Pasteur Tunis, Lab Venoms & Therapeut Mol, Tunis, Tunisia. [Khemiri, Monia] Childrens Hosp Tunis, Pediat Dept A, Tunis, Tunisia. [Asplund, A. Charlotta; Gustafsson, Manuela O.; Lundin, Karin E.] Karolinska Univ Hosp Huddinge, Karolinska Inst, Clin Res Ctr, Dept Lab Med, Huddinge, Sweden. [Falk-Soerqvist, Elin; Moens, Lotte N.; Nilsson, Mats] Uppsala Univ, Rudbeck Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden. [Engelhardt, Karin R.; Dziadzio, Magdalena; Stauss, Hans; Grimbacher, Bodo] UCL, Royal Free Hosp, Inst Immun & Transplantat, London WC1E 6BT, England. [Fleckenstein, Bernhard] Univ Erlangen Nurnberg, Inst Virol, D-91054 Erlangen, Germany. [Koelsch, Uwe] Campus Virchow Klinikum, Div Immunol, Lab Berlin, Berlin, Germany. [Koelsch, Uwe] Campus Virchow Klinikum, Charite, Inst Med Immunol, Berlin, Germany. [Schaeffer, Alejandro A.] NIH, Natl Ctr Biotechnol Informat, US Dept HHS, Bethesda, MD 20892 USA. RP Grimbacher, B (reprint author), Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Engesserstr 4, D-79108 Freiburg, Germany. EM bodo.grimbacher@uniklinik-freiburg.de OI Smith, C. I. Edvard/0000-0003-1907-3392 FU German Federal Ministry of Education and Research [BMBF 01 EO 0803]; Intramural Research Program of the National Library of Medicine-National Institutes of Health; Tunisian Ministry for Higher Education and Research; Swedish Medical Research Council; Swedish Cancer Society; Stockholm County Council [ALF]; European Community's 6th and 7th Framework Programs FP7/2007-2013 [Health-F5-2008-223292]; Biotechnology and Biological Sciences Research Council [BBF0083091, BB/K016164/1] FX Supported by the German Federal Ministry of Education and Research (BMBF 01 EO 0803). The research was supported in part by the Intramural Research Program of the National Library of Medicine-National Institutes of Health. Parts of the study were supported by the Tunisian Ministry for Higher Education and Research, the Swedish Medical Research Council, the Swedish Cancer Society and the Stockholm County Council ( research grant ALF), and the European Community's 6th and 7th Framework Programs FP7/2007-2013 under grant agreement Health-F5-2008-223292 (Euro-Gene-Scan). This work was also supported by the Biotechnology and Biological Sciences Research Council (BBF0083091 and BB/K016164/1 to A. D. and S. M. H). G. W. is grateful for a Sun Hung Kai Properties Kwoks' Foundation-Imperial College PhD Scholarship. NR 53 TC 34 Z9 34 U1 1 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2014 VL 133 IS 5 BP 1410 EP U681 DI 10.1016/j.jaci.2014.02.025 PG 23 WC Allergy; Immunology SC Allergy; Immunology GA AG5HS UT WOS:000335450700024 PM 24698316 ER PT J AU Legrand, F Tomasevic, N Simakova, O Lee, CCR Wang, ZF Raffeld, M Makiya, MA Palath, V Leung, J Baer, M Yarranton, G Maric, I Bebbington, C Klion, AD AF Legrand, Fanny Tomasevic, Nenad Simakova, Olga Lee, Chyi-Chia Richard Wang, Zengfang Raffeld, Mark Makiya, Michelle A. Palath, Varghese Leung, John Baer, Mark Yarranton, Geoffrey Maric, Irina Bebbington, Christopher Klion, Amy D. TI The eosinophil surface receptor epidermal growth factor-like module containing mucin-like hormone receptor 1 (EMR1): A novel therapeutic target for eosinophilic disorders SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Epidermal growth factor-like module containing mucin-like hormone receptor 1; eosinophil; hypereosinophilic syndrome; mAb therapy; afucosylated antibody; eosinophilia ID EGF-TM7 FAMILY; CELLS; ANTIBODY; CD34(+); F4/80; CD97; CYTOTOXICITY; INFLAMMATION; ACTIVATION; EXPRESSION AB Background: Although several novel agents are currently in clinical trials for eosinophilic disorders, none has demonstrated efficacy in reducing blood and tissue eosinophilia in all subjects. Additional approaches are clearly needed. Objective: We sought to explore the potential of the human eosinophil surface receptor epidermal growth factor- like module containing mucin- like hormone receptor 1 ( EMR1) as a therapeutic target for eosinophilic disorders. Methods: EMR1 expression was assessed in blood and bone marrow specimens from eosinophilic and healthy subjects, cell lines, CD34(+) cells differentiated in vitro, and tissue biopsy specimens by using flow cytometry, quantitative PCR, and immunostaining. Eosinophil targeting by a novel, humanized, afucosylated anti- EMR1 IgG(1) was evaluated in vitro by using a natural killer cell- mediated killing assay and in vivo in cynomolgus monkeys. Results: Analysis of blood and bone marrow cells from healthy and eosinophilic donors and in vitro- differentiated CD34(+) cells confirmed restriction of human EMR1 surface and mRNA expression to mature eosinophils. Tissue eosinophils also expressed EMR1. Although EMR1 was highly expressed on eosinophils from all subjects, surface expression was negatively correlated with absolute eosinophil counts ( r=520.46, P <.001), and soluble plasma levels correlated positively with absolute eosinophil counts ( r= 0.69, P <.001), suggesting modulation of EMR1 in vivo. Nevertheless, afucosylated anti- EMR1 mAb dramatically enhanced natural killer cell- mediated killing of eosinophils from healthy and eosinophilic donors and induced a rapid and sustained depletion of eosinophils in monkeys. Conclusion: EMR1 expression is restricted to mature blood and tissue eosinophils. Targeting of eosinophils with afucosylated anti- EMR1 antibody shows promise as a treatment for eosinophilic disorders. C1 [Legrand, Fanny; Makiya, Michelle A.; Klion, Amy D.] NIAID, Eosinophil Pathol Unit, Parasit Dis Lab, Bethesda, MD 20892 USA. [Tomasevic, Nenad; Palath, Varghese; Leung, John; Baer, Mark; Yarranton, Geoffrey; Bebbington, Christopher] KaloBios Pharmaceut, San Francisco, CA USA. [Simakova, Olga; Maric, Irina] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Lee, Chyi-Chia Richard; Wang, Zengfang; Raffeld, Mark] NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Legrand, F (reprint author), NIH, Bldg 4,Rm B1-28, Bethesda, MD 20892 USA. EM legrandfa@niaid.nih.gov OI Klion, Amy/0000-0002-4986-5326 FU Division of Intramural Research of the National Institutes of Allergy and Infectious Diseases/National Institutes of Health; KaloBios Pharmaceuticals FX Supported by the Division of Intramural Research of the National Institutes of Allergy and Infectious Diseases/National Institutes of Health and by KaloBios Pharmaceuticals. G.Y. and M.B. are employed by KaloBios Pharmaceuticals. N.T, J.L, V. and C.B were previously employed by and own stock/stock options in KaloBios Pharmaceuticals. NR 30 TC 14 Z9 15 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2014 VL 133 IS 5 BP 1439 EP U350 DI 10.1016/j.jaci.2013.11.041 PG 17 WC Allergy; Immunology SC Allergy; Immunology GA AG5HS UT WOS:000335450700027 PM 24530099 ER PT J AU Lyons, JJ Sun, GP Stone, KD Nelson, C Wisch, L O'Brien, M Jones, N Lindsley, A Komarow, HD Bai, Y Scott, LM Cantave, D Maric, I Abonia, JP Rothenberg, ME Schwartz, LB Milner, JD Wilson, TM AF Lyons, Jonathan J. Sun, Guangping Stone, Kelly D. Nelson, Celeste Wisch, Laura O'Brien, Michelle Jones, Nina Lindsley, Andrew Komarow, Hirsh D. Bai, Yun Scott, Linda M. Cantave, Daly Maric, Irina Abonia, J. Pablo Rothenberg, Marc E. Schwartz, Lawrence B. Milner, Joshua D. Wilson, Todd M. TI Mendelian inheritance of elevated serum tryptase associated with atopy and connective tissue abnormalities SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID MASTOCYTOSIS; DISORDERS; MUTATION; KIT C1 [Lyons, Jonathan J.; Sun, Guangping; Stone, Kelly D.; Nelson, Celeste; Wisch, Laura; O'Brien, Michelle; Komarow, Hirsh D.; Bai, Yun; Scott, Linda M.; Milner, Joshua D.; Wilson, Todd M.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Jones, Nina] Frederick Natl Lab Canc Res, Leidos Biomed Res SAIC Frederick, Clin Res Directorate CMRP, Frederick, MD USA. [Lindsley, Andrew; Abonia, J. Pablo; Rothenberg, Marc E.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Allergy & Immunol, Cincinnati, OH 45229 USA. [Cantave, Daly] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Maric, Irina] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Schwartz, Lawrence B.] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA USA. RP Lyons, JJ (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jdmilner@niaid.nih.gov; twilson@mail.nih.gov OI Abonia, Juan/0000-0003-3788-6485; Lyons, Jonathan/0000-0002-2346-8189 FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS [ZIA AI001183-01]; NCI NIH HHS [HHSN261200800001E]; NIAID NIH HHS [U19 AI077435, U19AI77435]; NICHD NIH HHS [K12 HD028827]; NIDDK NIH HHS [P30 DK090971]; PHS HHS [HHSN261200800001E] NR 9 TC 12 Z9 12 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2014 VL 133 IS 5 BP 1471 EP + DI 10.1016/j.jaci.2013.11.039 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA AG5HS UT WOS:000335450700034 PM 24472624 ER PT J AU Harwood, KR Hanover, JA AF Harwood, Katryn R. Hanover, John A. TI Nutrient-driven O-GlcNAc cycling - think globally but act locally SO JOURNAL OF CELL SCIENCE LA English DT Article DE O-GlcNAc; O-GlcNAcylation; Metabolism Post-translational modification; Signaling; Lipid droplets; Mitochondria; Epigenetics; Nuclear pores ID LINKED-N-ACETYLGLUCOSAMINE; NUCLEAR-PORE COMPLEXES; EMBRYONIC STEM-CELLS; CULTURED HIPPOCAMPAL-NEURONS; TRANSFERASE OGT; LIPID DROPLETS; AURORA-B; TETRATRICOPEPTIDE REPEATS; SUBSTRATE-SPECIFICITY; AXONAL-TRANSPORT AB Proper cellular functioning requires that cellular machinery behave in a spatiotemporally regulated manner in response to global changes in nutrient availability. Mounting evidence suggests that one way this is achieved is through the establishment of physically defined gradients of O-GlcNAcylation (O-linked addition of N-acetylglucosamine to serine and threonine residues) and O-GlcNAc turnover. Because O-GlcNAcylation levels are dependent on the nutrient-responsive hexosamine signaling pathway, this modification is uniquely poised to inform upon the nutritive state of an organism. The enzymes responsible for O-GlcNAc addition and removal are encoded by a single pair of genes: both the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA, also known as MGEA5) genes are alternatively spliced, producing protein variants that are targeted to discrete cellular locations where they must selectively recognize hundreds of protein substrates. Recent reports suggest that in addition to their catalytic functions, OGT and OGA use their multifunctional domains to anchor O-GlcNAc cycling to discrete intracellular sites, thus allowing them to establish gradients of deacetylase, kinase and phosphatase signaling activities. The localized signaling gradients established by targeted O-GlcNAc cycling influence many important cellular processes, including lipid droplet remodeling, mitochondrial functioning, epigenetic control of gene expression and proteostasis. As such, the tethering of the enzymes of O-GlcNAc cycling appears to play a role in ensuring proper spatiotemporal responses to global alterations in nutrient supply. C1 [Harwood, Katryn R.; Hanover, John A.] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Harwood, KR (reprint author), NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. EM Kate.Harwood@nih.gov; jah@helix.nih.gov FU National Institutes of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health FX The work of our laboratory is funded from the intramural program of the National Institutes of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health. Deposited in PMC for release after 12 months. NR 121 TC 16 Z9 17 U1 3 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD MAY 1 PY 2014 VL 127 IS 9 BP 1857 EP 1867 DI 10.1242/jcs.113233 PG 11 WC Cell Biology SC Cell Biology GA AH0MU UT WOS:000335814800001 PM 24762810 ER PT J AU Burke, GM Wang, N Blease, S Levy, D Magnani, JW AF Burke, Gordon M. Wang, Na Blease, Sue Levy, Daniel Magnani, Jared W. TI Assessment of reproducibility - automated and digital caliper ECG measurement in the Framingham Heart Study SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE Electrocardiogram; Reproducibility; P waves; QRS complex; QT interval ID LEFT-VENTRICULAR HYPERTROPHY AB Background: Digitized electrocardiography permits the rapid, automated quantification of electrocardiograms (ECGs) for analysis. Community- and population-based studies have increasingly integrated such data. Assessing the reproducibility of automated ECG measures with manual measures is a critical step in preparation for using automated measures for research purposes. We recently established an ECG repository of digitally recorded ECGs for the Framingham Heart Study and we sought to assess the reproducibility of automated and manual measures. Methods: We selected 185 digitally recorded ECGs from routine visits of Framingham Heart Study participants spanning from 1986 to 2012. We selected the following ECG measures for their relevance to clinical and epidemiologic research: P wave duration, P wave amplitude, and PR interval in lead II; QRS duration and R wave amplitude in lead V6; and QT interval in lead V5. We obtained automated values for each waveform, and used a digital caliper for manual measurements. Digital caliper measurements were repeated in a subset (n = 81) of the samples for intrarater assessment. Results: We calculated the intraclass correlation coefficient (ICC) values for the interrater and intrarater assessments. P wave duration had the lowest interrater ICC (r = 0.46) and lowest intrarater ICC (r = 0.57). R wave amplitude had the highest interrater and intrarater ICC (r = 0.98) indicating excellent reproducibility. The remaining measures had interrater and intrarater ICCs of r >= 0.81. Conclusions: The interrater reproducibility findings for P wave amplitude, PR interval, QT interval, QRS duration, and R wave amplitude were excellent. In contrast, the reproducibility of P wave duration was more modest. These findings indicate high reproducibility of most automated and manual ECG measurements. (C) 2014 Elsevier Inc. All rights reserved. C1 [Burke, Gordon M.] Boston Univ, Med Ctr, Dept Med, Boston, MA USA. [Wang, Na] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA. [Blease, Sue; Levy, Daniel; Magnani, Jared W.] NHLBI, Framingham, MA USA. [Blease, Sue; Levy, Daniel; Magnani, Jared W.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA. [Levy, Daniel] NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Magnani, Jared W.] Boston Univ, Dept Med, Sect Cardiovasc Med, Boston, MA 02215 USA. RP Magnani, JW (reprint author), Div Cardiol, 88 E Newton St,D-7, Boston, MA 02118 USA. EM jmagnani@bu.edu OI Burke, Gordon/0000-0002-4724-6548 FU American Heart Association [09FTF219028]; NIH [R21HL1060926, R01-NS17950, N01-HC25195] FX Dr. Magnani is supported by American Heart Association Award 09FTF219028. This work was supported by NIH grants R21HL1060926, R01-NS17950, and NIH contract N01-HC25195. NR 10 TC 2 Z9 2 U1 0 U2 5 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 EI 1532-8430 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD MAY-JUN PY 2014 VL 47 IS 3 BP 288 EP 293 DI 10.1016/j.jelectrocard.2014.01.004 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG9BD UT WOS:000335712700003 PM 24792985 ER PT J AU Stern, MD Maltseva, LA Juhaszova, M Sollott, SJ Lakatta, EG Maltsev, VA AF Stern, Michael D. Maltseva, Larissa A. Juhaszova, Magdalena Sollott, Steven J. Lakatta, Edward G. Maltsev, Victor A. TI Hierarchical clustering of ryanodine receptors enables emergence of a calcium clock in sinoatrial node cells SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article ID CARDIAC SARCOPLASMIC-RETICULUM; RAT VENTRICULAR MYOCYTES; CA2+ RELEASE; PACEMAKER CELLS; MATHEMATICAL-MODEL; SKELETAL-MUSCLE; SPARKS; TERMINATION; PHOSPHOLAMBAN; PROTEINS AB The sinoatrial node, whose cells (sinoatrial node cells [SANCs]) generate rhythmic action potentials, is the primary pacemaker of the heart. During diastole, calcium released from the sarcoplasmic reticulum (SR) via ryanodine receptors (RyRs) interacts with membrane currents to control the rate of the heartbeat. This "calcium clock" takes the form of stochastic, partially periodic, localized calcium release (LCR) events that propagate, wave-like, for limited distances. The detailed mechanisms controlling the calcium clock are not understood. We constructed a computational model of SANCs, including three-dimensional diffusion and buffering of calcium in the cytosol and SR; explicit, stochastic gating of individual RyRs and L-type calcium channels; and a full complement of voltageand calcium-dependent membrane currents. We did not include an anatomical submembrane space or inactivation of RyRs, the two heuristic components that have been used in prior models but are not observed experimentally. When RyRs were distributed in discrete clusters separated by > 1 mu m, only isolated sparks were produced in this model and LCR events did not form. However, immunofluorescent staining of SANCs for RyR revealed the presence of bridging RyR groups between large clusters, forming an irregular network. Incorporation of this architecture into the model led to the generation of propagating LCR events. Partial periodicity emerged from the interaction of LCR events, as observed experimentally. This calcium clock becomes entrained with membrane currents to accelerate the beating rate, which therefore was controlled by the activity of the SERCA pump, RyR sensitivity, and L-type current amplitude, all of which are targets of beta-adrenergic-mediated phosphorylation. Unexpectedly, simulations revealed the existence of a pathological mode at high RyR sensitivity to calcium, in which the calcium clock loses synchronization with the membrane, resulting in a paradoxical decrease in beating rate in response to beta-adrenergic stimulation. The model indicates that the hierarchical clustering of surface RyRs in SANCs may be a crucial adaptive mechanism. Pathological desynchronization of the clocks may explain sinus node dysfunction in heart failure and RyR mutations. C1 [Stern, Michael D.; Maltseva, Larissa A.; Juhaszova, Magdalena; Sollott, Steven J.; Lakatta, Edward G.; Maltsev, Victor A.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Stern, MD (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM SternMi@mail.nih.gov FU Intramural Research Program of the NIH; National Institute on Aging FX This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. NR 55 TC 10 Z9 10 U1 1 U2 13 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 EI 1540-7748 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD MAY PY 2014 VL 143 IS 5 BP 577 EP 604 DI 10.1085/jgp.201311123 PG 28 WC Physiology SC Physiology GA AG8FE UT WOS:000335653400005 PM 24778430 ER PT J AU Stoppe, M Thoma, E Liebert, UG Major, EO Hoffmann, KT Classen, J Bergh, FT AF Stoppe, Muriel Thoma, Eva Liebert, Uwe Gerd Major, Eugene O. Hoffmann, Karl-Titus Classen, Joseph Bergh, Florian Then TI Cerebellar manifestation of PML under fumarate and after efalizumab treatment of psoriasis SO JOURNAL OF NEUROLOGY LA English DT Letter ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; VIRUS; NATALIZUMAB C1 [Stoppe, Muriel; Thoma, Eva; Classen, Joseph; Bergh, Florian Then] Univ Leipzig, Dept Neurol, D-04103 Leipzig, Germany. [Stoppe, Muriel; Thoma, Eva; Bergh, Florian Then] Univ Leipzig, Translat Ctr Regenerat Med, D-04103 Leipzig, Germany. [Liebert, Uwe Gerd] Univ Leipzig, Dept Virol, D-04103 Leipzig, Germany. [Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. [Hoffmann, Karl-Titus] Univ Leipzig, Dept Neuroradiol, D-04103 Leipzig, Germany. RP Bergh, FT (reprint author), Univ Leipzig, Dept Neurol, Liebigstr 20, D-04103 Leipzig, Germany. EM ThenBerF@medizin.uni-leipzig.de NR 11 TC 13 Z9 14 U1 1 U2 3 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 EI 1432-1459 J9 J NEUROL JI J. Neurol. PD MAY PY 2014 VL 261 IS 5 BP 1021 EP 1024 DI 10.1007/s00415-014-7311-1 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AG9XE UT WOS:000335772500022 PM 24638202 ER PT J AU Li, F Jiang, CT Larsen, MC Bushkofsky, J Krausz, KW Wang, T Jefcoate, CR Gonzalez, FJ AF Li, Fei Jiang, Changtao Larsen, Michele C. Bushkofsky, Justin Krausz, Kristopher W. Wang, Ting Jefcoate, Colin R. Gonzalez, Frank J. TI Lipidomics Reveals a Link between CYP1B1 and SCD1 in Promoting Obesity SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE CYP1B1; SCD1; obesity; metabolomics; lipid metabolism; mass spectrometry; lysophosphatidylcholine ID SPECTROMETRY-BASED METABOLOMICS; INSULIN-RESISTANCE; CYTOCHROME P4501B1; METABOLISM; MICE; DEFICIENCY; BIOMARKERS; ACID; DESATURASE; SIGNATURE AB Cytochrome P450 1B1 (CYP1B1) is involved in the metabolism of xenobiotic compounds and endogenous metabolites. Disruption of Cyp1b1 in mice results in suppression of high-fat diet (HFD)-induced obesity and an extensive change in hepatic energy regulation despite minimal constitutive expression of CYP1B1 in hepatocytes. Lack of CYP1B1 is correlated with altered lipid metabolism, especially lysophosphatidylcholines, contributing to protection against obesity. Ultraperformance liquid chromatography coupled to electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOFMS)-based metabolomics revealed lysophosphatidylcholine 18:0 (LPC 18:0) as a biomarker positively related to HFD-induced obesity. The increased serum LPC 18:0 in wild-type mice is reduced in Cyp1b1-null mice on a HFD, which is reversed in CYP1B1-humanized mice. CYP1B1-humanized mice show higher diet-induced obesity compared with Cyp1b1-null mice, suggesting that human CYP1B1 shows a similar response to HFD as mouse Cyp1b1. In addition, hepatic stearoyl-CoA desaturase 1 (SCD1) expression was decreased in Cyp1b1-null mice, and the attenuated diet-induced obesity and lower serum LPC 18:0 in the Cyp1b1-null mice is elevated after SCD1 overexpression, suggesting that SCD1 is correlated with CYP1B1-induced obesity. These studies establish a biochemical link between cytochromes P450, lipids, and metabolic disorders and suggest that inhibition of CYP1B1 could be target for antiobesity drugs. C1 [Li, Fei; Jiang, Changtao; Krausz, Kristopher W.; Wang, Ting; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Larsen, Michele C.; Bushkofsky, Justin; Jefcoate, Colin R.] Univ Wisconsin, Dept Cell & Regenerat Biol, Mol & Environm Toxicol Ctr, Madison, WI 53705 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM gonzalef@mail.nih.gov RI Li, Fei/F-6849-2013 FU National Cancer Institute Intramural Research Program; National Institutes of Diabetes and Digestive and Kidney Diseases [5R01DK090249]; National Natural Science Foundation of China [81360509] FX This work was supported by the National Cancer Institute Intramural Research Program to F.J.G., the National Institutes of Diabetes and Digestive and Kidney Diseases (5R01DK090249) to C.R.J., and the National Natural Science Foundation of China (81360509) to F.L. NR 41 TC 13 Z9 13 U1 2 U2 32 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 EI 1535-3907 J9 J PROTEOME RES JI J. Proteome Res. PD MAY PY 2014 VL 13 IS 5 BP 2679 EP 2687 DI 10.1021/pr500145n PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA AG5WY UT WOS:000335490600037 PM 24684199 ER PT J AU Weiss, PF Colbert, RA AF Weiss, Pamela F. Colbert, Robert A. TI Radiography Versus Magnetic Resonance Imaging (MRI) in Juvenile Spondyloarthritis: Is the MR Image Everything? SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID SOCIETY CLASSIFICATION CRITERIA; SACROILIITIS; SPONDYLARTHROPATHY C1 [Weiss, Pamela F.] Childrens Hosp Philadelphia, Div Rheumatol, Philadelphia, PA 19104 USA. [Colbert, Robert A.] NIAMSD, Pediat Translat Res Branch, NIH, Bethesda, MD 20892 USA. RP Colbert, RA (reprint author), NIAMS, NIH, Hatfield Clin Res Ctr, 10 CRC,1-5142 10 Ctr Dr, Bethesda, MD 20892 USA. EM colbertr@mail.nih.gov NR 10 TC 1 Z9 1 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2014 VL 41 IS 5 BP 832 EP 833 DI 10.3899/jrheum.140212 PG 2 WC Rheumatology SC Rheumatology GA AG6FN UT WOS:000335514500003 PM 24788462 ER PT J AU Grayson, PC Amudala, NA McAlear, CA Leduc, RL Shereff, D Richesson, R Fraenkel, L Merkel, PA AF Grayson, Peter C. Amudala, Naomi A. McAlear, Carol A. Leduc, Renee L. Shereff, Denise Richesson, Rachel Fraenkel, Liana Merkel, Peter A. TI Causal Attributions about Disease Onset and Relapse in Patients with Systemic Vasculitis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE CAUSAL ATTRIBUTIONS; ILLNESS PERCEPTIONS; VASCULITIS ID QUALITY-OF-LIFE; WEGENERS-GRANULOMATOSIS; BEHCETS-DISEASE; ILLNESS; FATIGUE AB Objective. Patients vary in their beliefs related to the cause of serious illness. The effect of these beliefs among patients with systemic vasculitis is not known. Our study aimed to describe causal attributions about disease onset and relapse in systemic vasculitis and to examine whether causal beliefs differ by type of vasculitis or are associated with negative health outcomes. Methods. Patients with vasculitis were recruited to complete an online questionnaire. Categories of causal beliefs were assessed with the Revised Illness Perception Questionnaire (IPQ-R). Differences in beliefs about disease onset versus relapse were compared across different forms of vasculitis. Causal beliefs were assessed in association with several health outcomes including fatigue, functional impairments, and personal understanding of the condition. Results. The questionnaire was completed by 692 patients representing 9 forms of vasculitis. The majority (90%) of patients had beliefs about the cause of their illness. Causal attributions were highly variable, but altered immunity and stress were the most commonly agreed-upon causal beliefs. Frequencies of causal beliefs were strikingly similar across different forms of vasculitis, with a few notable exceptions primarily in Behcet disease. Beliefs differed about causes of disease onset versus relapse. Specific beliefs about disease onset and relapse were weakly associated with fatigue, functional impairments, and understanding of the condition. Conclusion. Patient beliefs related to the cause of systemic vasculitis are highly variable. Patterns of causal beliefs are associated with important negative health outcomes. Clinicians who care for patients with vasculitis should be mindful of these associations and consider asking about patients' causal beliefs. C1 Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, US Natl Inst Hlth NIH, Bethesda, MD USA. [Grayson, Peter C.; Amudala, Naomi A.] Boston Univ, Sch Med, Vasculitis Ctr, Rheumatol Sect, Boston, MA 02118 USA. [Grayson, Peter C.; Amudala, Naomi A.] Boston Univ, Sch Med, Clin Epidemiol Unit, Boston, MA 02118 USA. [McAlear, Carol A.; Merkel, Peter A.] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. [Leduc, Renee L.; Shereff, Denise] Univ S Florida, Tampa, FL USA. [Richesson, Rachel] Duke Univ, Sch Nursing, Durham, NC USA. [Fraenkel, Liana] Yale Univ, Div Rheumatol, New Haven, CT USA. RP Grayson, PC (reprint author), NIH, 10 Ctr Dr,Bldg 10,Room 13C101A, Bethesda, MD 20892 USA. EM peter.grayson@nih.gov OI Amudala, Naomi/0000-0001-7310-3594 FU Vasculitis Clinical Research Consortium - NIAMS [U54AR057319]; National Center for Research Resources [U54 RR019497]; Office of Rare Diseases Research; National Center for Advancing Translational Science; American College of Rheumatology-Rheumatology Research Foundation Scientist Development Award; NIAMS [K24 AR060231-01] FX Sponsored by the Vasculitis Clinical Research Consortium, which has received support from NIAMS (U54AR057319), the National Center for Research Resources (U54 RR019497); the Office of Rare Diseases Research, and the National Center for Advancing Translational Science. Dr. Grayson receives support from an American College of Rheumatology-Rheumatology Research Foundation Scientist Development Award. Dr. Fraenkel receives support from NIAMS (K24 AR060231-01). NR 32 TC 3 Z9 3 U1 0 U2 6 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2014 VL 41 IS 5 BP 923 EP 930 DI 10.3899/jrheum.131096 PG 8 WC Rheumatology SC Rheumatology GA AG6FN UT WOS:000335514500017 PM 24634202 ER PT J AU Kerridge, BT Saha, TD Hasin, DS AF Kerridge, Bradley T. Saha, Tulshi D. Hasin, Deborah S. TI DSM-IV Antisocial Personality Disorder and Conduct Disorder: Evidence for Taxonic Structures Among Individuals With and Without Substance Use Disorders in the General Population SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID ALCOHOL-USE DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; INTERVIEW SCHEDULE AUDADIS; TAXOMETRIC ANALYSIS; LATENT STRUCTURE; DRUG MODULES; PSYCHOPATHY CHECKLIST; BEHAVIORAL SYNDROMES; PRISON-INMATES; DISCRETE CLASS AB Objective: The categorical-dimensional status of DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) conduct disorder (CD) and antisocial personality disorder (ASPD) is a source of controversy. This study examined whether the underlying structure of DSM-IV CD and ASPD was dimensional or categorical (taxonic) among individuals with and without substance use disorders. Method: Using a national large representative survey of U.S. adults (n = 43,093), taxometric analyses of DSM-IV CD and ASPD diagnostic criteria were conducted on the total sample and among those with and without substance use disorders. Results: Results of three taxometric procedures were consistent in showing that the structures underlying DSM-IV CD and ASPD were clearly taxonic in the total sample and among individuals with and without substance use disorders. Comparison curve fit indices exceeded 0.57 for each model. Conclusions: Taxonic findings of the present study were in contrast to the dimensional results of prior taxometric research among incarcerated samples with substantial comorbidity of antisocial syndromes and substance use disorders. Results supported the categorical representation and diagnostic thresholds of ASPD and CD as defined in DSM-IV and DSM-5. That the structure of ASPD and CD may be taxonic suggests that further research on these disorders use group comparative designs in which samples with and without these disorders are compared in terms of sociodemographic and clinical correlates, comorbidity, and treatment utilization. The taxonic structure of ASPD and CD may contribute to future research on causal processes through which these antisocial syndromes develop. C1 [Kerridge, Bradley T.] Univ Maryland, Dept Epidemiol & Biostat, College Pk, MD 20742 USA. [Kerridge, Bradley T.; Hasin, Deborah S.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Saha, Tulshi D.] NIAAA, Lab Epidemiol & Biometry, Intramural Div Clin & Biol Res, NIH, Rockville, MD 20852 USA. [Hasin, Deborah S.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Hasin, Deborah S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Hasin, DS (reprint author), Columbia Univ, Coll Phys & Surg, Dept Psychiat, 1051 Riverside Dr,Box 123, New York, NY 10032 USA. EM dsh2@columbia.edu FU National Institute on Drug Abuse (NIDA) [5F31DA025377]; National Institute on Alcohol Abuse and Alcoholism (NIAAA) [U01AA018111, K05AA014223]; NIAAA; NIAAA, National Institutes of Health FX This research was supported by National Institute on Drug Abuse (NIDA) Grant 5F31DA025377 (to Bradley T. Kerridge) and National Institute on Alcohol Abuse and Alcoholism (NIAAA) Grants U01AA018111 and K05AA014223 (to Deborah S. Hasin). The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) was funded by the NIAAA with supplemental support from NIDA. Support is also acknowledged from the Intramural Program, NIAAA, National Institutes of Health. The views and opinions expressed in this report are those of the authors and should not be construed to represent the views of any of the sponsoring agencies of the government. NR 91 TC 2 Z9 2 U1 2 U2 11 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 EI 1938-4114 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD MAY PY 2014 VL 75 IS 3 BP 496 EP 509 PG 14 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA AG7WY UT WOS:000335630700015 PM 24766762 ER PT J AU Reddy, UM Abuhamad, AZ Levine, D Saade, GR AF Reddy, Uma M. Abuhamad, Alfred Z. Levine, Deborah Saade, George R. CA Fetal Imaging Workshop Invited Par TI Fetal Imaging Executive Summary of a Joint Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, American Institute of Ultrasound in Medicine, American College of Obstetricians and Gynecologists, American College of Radiology, Society for Pediatric Radiology, and Society of Radiologists in Ultrasound Fetal Imaging Workshop SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE fetal imaging; magnetic resonance imaging; obstetric ultrasound; ultrasound ID CHOROID-PLEXUS CYSTS; LOW-LYING PLACENTA; NERVOUS-SYSTEM ABNORMALITIES; INTRACARDIAC ECHOGENIC FOCI; TWIN TRANSFUSION SYNDROME; BIRTH-WEIGHT DISCORDANCE; LAST MENSTRUAL PERIOD; AMNIOTIC-FLUID VOLUME; INTERNAL OS DISTANCE; ISOLATED SHORT FEMUR AB Given that practice variation exists in the frequency and performance of ultrasound and magnetic resonance imaging (MRI) in pregnancy, the Eunice Kennedy Shriver National Institute of Child Health and Human Development hosted a workshop to address indications for ultrasound and MRI in pregnancy, to discuss when and how often these studies should be performed, to consider recommendations for optimizing yield and cost effectiveness, and to identify research opportunities. This article is the executive summary of the workshop. C1 [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Abuhamad, Alfred Z.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Levine, Deborah] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Saade, George R.] Univ Texas Med Branch, Galveston, TX 77555 USA. RP Reddy, UM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd,Room 4B03F, Bethesda, MD 20892 USA. EM reddyu@mail.nih.gov NR 116 TC 17 Z9 18 U1 1 U2 3 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 EI 1550-9613 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAY PY 2014 VL 33 IS 5 BP 745 EP 757 DI 10.7863/ultra.33.5.745 PG 13 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA AG7TD UT WOS:000335620700001 PM 24764329 ER PT J AU Yoshii, K Sunden, Y Yokozawa, K Igarashi, M Kariwa, H Holbrook, MR Takashima, I AF Yoshii, Kentaro Sunden, Yuji Yokozawa, Kana Igarashi, Manabu Kariwa, Hiroaki Holbrook, Michael R. Takashima, Ikuo TI A Critical Determinant of Neurological Disease Associated with Highly Pathogenic Tick-Borne Flavivirus in Mice SO JOURNAL OF VIROLOGY LA English DT Article ID WEST-NILE-VIRUS; OMSK HEMORRHAGIC-FEVER; INFECTIOUS CDNA-CLONE; AMINO-ACID CHANGES; ENCEPHALITIS-VIRUS; NS5 PROTEIN; MOUSE NEUROINVASIVENESS; SYNAPTIC PLASTICITY; ATTENUATION; MUTATIONS AB Tick-borne encephalitis virus (TBEV) and Omsk hemorrhagic fever virus (OHFV) are highly pathogenic tick-borne flaviviruses; TBEV causes neurological disease in humans, while OHFV causes a disease typically identified with hemorrhagic fever. Although TBEV and OHFV are closely related genetically, the viral determinants responsible for these distinct disease phenotypes have not been identified. In this study, chimeric viruses incorporating components of TBEV and OHFV were generated using infectious clone technology, and their pathological characteristics were analyzed in a mouse model to identify virus-specific determinants of disease. We found that only four amino acids near the C terminus of the NS5 protein were primarily responsible for the development of neurological disease. Mutation of these four amino acids had no effect on viral replication or histopathological features, including inflammatory responses, in mice. These findings suggest a critical role for NS5 in stimulating neuronal dysfunction and degeneration following TBEV infection and provide new insights into the molecular mechanisms underlying the pathogenesis of tick-borne flaviviruses. C1 [Yoshii, Kentaro; Yokozawa, Kana; Kariwa, Hiroaki; Takashima, Ikuo] Hokkaido Univ, Grad Sch Vet Med, Publ Hlth Lab, Sapporo, Hokkaido, Japan. [Sunden, Yuji] Hokkaido Univ, Grad Sch Vet Med, Lab Comparat Pathol, Sapporo, Hokkaido, Japan. [Igarashi, Manabu] Hokkaido Univ, Div Bioinformat, Res Ctr Zoonosis Control, Sapporo, Hokkaido, Japan. [Holbrook, Michael R.] NIAID, Integrated Res Facil, Frederick, MD USA. RP Yoshii, K (reprint author), Hokkaido Univ, Grad Sch Vet Med, Publ Hlth Lab, Sapporo, Hokkaido, Japan. EM kyoshii@vetmed.hokudai.ac.jp RI YOSHII, Kentaro/A-4808-2012 FU Ministry of Education, Culture, Sports, Sciences, and Technology of Japan; Health Sciences Grants for Research on Emerging and Reemerging Infectious Disease; Ministry of Health, Labor, and Welfare of Japan; National Institute of Allergy and Infectious Diseases [HHSN272200200016I]; [24780293]; [22780268]; [21405035] FX This study was supported by Grants-in-Aid for Scientific Research (24780293, 22780268, and 21405035) and the Global COE Program from the Ministry of Education, Culture, Sports, Sciences, and Technology of Japan and Health Sciences Grants for Research on Emerging and Reemerging Infectious Disease from the Ministry of Health, Labor, and Welfare of Japan. M.R.H. is supported as a subcontractor with Battelle Memorial Institute under its prime contract with the National Institute of Allergy and Infectious Diseases (HHSN272200200016I). NR 50 TC 4 Z9 4 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 2014 VL 88 IS 10 BP 5406 EP 5420 DI 10.1128/JVI.00421-14 PG 15 WC Virology SC Virology GA AG5GB UT WOS:000335446400020 PM 24574402 ER PT J AU Tsugawa, T Tatsumi, M Tsutsumi, H AF Tsugawa, Takeshi Tatsumi, Masatoshi Tsutsumi, Hiroyuki TI Virulence-Associated Genome Mutations of Murine Rotavirus Identified by Alternating Serial Passages in Mice and Cell Cultures SO JOURNAL OF VIROLOGY LA English DT Article ID REVERSE GENETICS; ANTIBODY-RESPONSES; SEQUENCE-ANALYSIS; NONSTRUCTURAL GLYCOPROTEIN; COST-EFFECTIVENESS; UNITED-STATES; C-TERMINUS; GROUP-A; VACCINE; NSP4 AB Serial passage of a virulent wild-type virus in vitro often results in loss of virulence of the virus in an original animal host, while serial passage of a cell culture-adapted avirulent virus in vivo often gains virulence in an animal host. Actually, live attenuated virus vaccines were originally produced by serial passage in cell cultures. Although clinical efficacy and safety of rotavirus vaccines were recently revealed, the mechanism of their attenuation is not well understood. We passaged serially a murine rotavirus by alternating switch of host (mice or cell cultures) repeatedly and sequenced the eleven genes of the passaged viruses to identify mutations associated with the emergence or disappearance of virulence. Sequence analysis revealed that changes in three genes (VP4, NSP1, and NSP4) were associated with virulence in mice. Intraperitoneal injection of recombinant NSP4 proteins confirmed its diarrheagenic activity in mice. These genome changes are likely to be correlated with rotavirus virulence. C1 [Tsugawa, Takeshi; Tatsumi, Masatoshi; Tsutsumi, Hiroyuki] Sapporo Med Univ, Sch Med, Dept Pediat, Sapporo, Hokkaido, Japan. [Tsugawa, Takeshi; Tatsumi, Masatoshi] NIAID, Rotavirus Vaccine Dev Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Tsugawa, T (reprint author), Sapporo Med Univ, Sch Med, Dept Pediat, Sapporo, Hokkaido, Japan. EM tsugawat@sapmed.ac.jp FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This study was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. There is no conflict of interest to declare. NR 48 TC 7 Z9 8 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 2014 VL 88 IS 10 BP 5543 EP 5558 DI 10.1128/JVI.00041-14 PG 16 WC Virology SC Virology GA AG5GB UT WOS:000335446400032 PM 24599996 ER PT J AU Caccuri, F Giagulli, C Reichelt, J Martorelli, D Marsico, S Bugatti, A Barone, I Rusnati, M Guzman, CA Dolcetti, R Caruso, A AF Caccuri, Francesca Giagulli, Cinzia Reichelt, Joachim Martorelli, Debora Marsico, Stefania Bugatti, Antonella Barone, Ines Rusnati, Marco Guzman, Carlos A. Dolcetti, Riccardo Caruso, Arnaldo TI Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Matrix Proteins Specify Different Capabilities To Modulate B Cell Growth SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 MATRIX; PROINFLAMMATORY CYTOKINES; INTERLEUKIN-8 RECEPTORS; INTRINSIC DISORDER; IL-8 RECEPTORS; HUMAN GENOME; P17; EVOLUTION; HOST; ANGIOGENESIS AB Exogenous HIV-1 matrix protein p17 ( p17) deregulates the function of different cells after its N-terminal loop (AT20) binding to the chemokine receptors CXCR1 and CXCR2. One site within AT20 has been recently found to be the major determinant of viral fitness following transmission of simian immunodeficiency virus (SIV) to the human host. Therefore, we sought to determine whether SIV matrix protein (MA) was already capable of interacting with CXCR1 and CXCR2 and mimic p17 biological activities rather than this being a newly acquired function during host adaptation. We show here that SIV MA binds with the same affinity of p17 to CXCR1 and CXCR2 and displays both p17 proangiogenic on human primary endothelial cells and chemotactic activity on human primary monocytes and B cells. However, SIV MA exhibited a higher degree of plasticity than p17 in the C terminus, a region known to play a role in modulating B cell growth. Indeed, in contrast to p17, SIV MA was found to activate the phosphatidylinositol 3-kinase/Akt signaling pathway and strongly promote B cell proliferation and clonogenic activity. Interestingly, we have recently highlighted the existence of a Ugandan HIV-1 strain- derived p17 variant (S75X) with the same B cell growth-promoting activity of SIV MA. Computational modeling allowed us to hypothesize an altered C terminus/core region interaction behind SIV MA and S75X activity. Our findings suggest the appearance of a structural constraint in the p17 C terminus that controls B cell growth, which may help to elucidate the evolutionary trajectory of HIV-1. C1 [Caccuri, Francesca; Giagulli, Cinzia; Bugatti, Antonella; Rusnati, Marco; Caruso, Arnaldo] Univ Brescia, Sch Med, Dept Mol & Translat Med, Brescia, Italy. [Caccuri, Francesca] NCI, Anim Models & Retroviral Vaccine Sect, NIH, Bethesda, MD 20892 USA. [Reichelt, Joachim; Guzman, Carlos A.] Helmholtz Ctr Infect Res, Braunschweig, Germany. [Martorelli, Debora; Dolcetti, Riccardo] Natl Canc Inst, Canc Bioimmunotherapy Unit, Aviano, Italy. [Marsico, Stefania; Barone, Ines] Univ Calabria, Dept Pharmacobiol, Arcavacata Di Rende, Italy. RP Caruso, A (reprint author), Univ Brescia, Sch Med, Dept Mol & Translat Med, Brescia, Italy. EM caruso@med.unibs.it RI Dolcetti, Riccardo/O-3832-2015; OI Dolcetti, Riccardo/0000-0003-1625-9853; BARONE, Ines/0000-0002-9769-1615; RUSNATI, Marco/0000-0001-9968-5908; MARSICO, Stefania/0000-0003-1598-0526 FU Istituto Superiore di Sanita (AIDS) [40G.16] FX This study was supported by the Istituto Superiore di Sanita (AIDS grant 40G.16). NR 64 TC 10 Z9 10 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 2014 VL 88 IS 10 BP 5706 EP 5717 DI 10.1128/JVI.03142-13 PG 12 WC Virology SC Virology GA AG5GB UT WOS:000335446400044 PM 24623414 ER PT J AU Matsusaka, T Niimura, F Pastan, I Shintani, A Nishiyama, A Ichikawa, I AF Matsusaka, Taiji Niimura, Fumio Pastan, Ira Shintani, Ayumi Nishiyama, Akira Ichikawa, Iekuni TI Podocyte injury enhances filtration of liver-derived -angiotensinogen and renal angiotensin II generation SO KIDNEY INTERNATIONAL LA English DT Article DE glomerular filtration barrier; nephrotic syndrome; podocyte; proteinuria; renin-angiotensin system ID MESSENGER-RNA; GLOMERULAR SCLEROSIS; ALDOSTERONE SYSTEM; CONVERTING ENZYME; KIDNEY-DISEASE; RAT-KIDNEY; RENIN; EXPRESSION; PROTEINURIA; NEPHROPATHY AB Intrarenal angiotensin II is increased in kidney diseases independently of plasma angiotensin ll and is thought to promote progressive deterioration of renal architecture. Here we investigated the mechanism of enhanced renal angiotensin It generation in kidney glomerular diseases. For this, kidney- or liver-specific angiotensinogen gene (Agt) knockout was superimposed on the mouse model of inducible podocyte injury (NEP25). Seven days after induction of podocyte injury, renal angiotensin II was increased ninefold in NEP25 mice with intact Agt, accompanied by increases in urinary albumin and angiotensinogen excretion, renal angiotensinogen protein, and its mRNA. Kidney Agt knockout attenuated renal Agt mRNA but not renal angiotensin II, renal, or urinary angiotensinogen protein. In contrast, liver Agt knockout markedly reduced renal angiotensin II to 18.7% of that of control NEP25 mice, renal and urinary angiotensinogen protein, but not renal Agt mRNA. Renal angiotensin II had no relationship with renal Agt mRNA, or with renal renin mRNA, which was elevated in liver Agt knockouts. Kidney and liver dual Agt knockout mice showed phenotypes comparable to those of liver Agt knockout mice. Thus, increased renal angiotensin II generation upon severe podocyte injury is attributed to increased filtered angiotensinogen of liver origin resulting from loss of macromolecular barrier function of the glomerular capillary wall that occurs upon severe podocyte injury. C1 [Matsusaka, Taiji] Tokai Univ, Sch Med, Dept Internal Med, Isehara, Kanagawa 2591193, Japan. [Matsusaka, Taiji] Tokai Univ, Sch Med, Inst Med Sci, Isehara, Kanagawa 2591193, Japan. [Niimura, Fumio] Tokai Univ, Sch Med, Dept Pediat, Isehara, Kanagawa 2591193, Japan. [Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Shintani, Ayumi] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA. [Shintani, Ayumi; Ichikawa, Iekuni] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. [Nishiyama, Akira] Kagawa Univ, Sch Med, Res Equipment Ctr, Dept Pharmacol, Takamatsu, Kagawa 760, Japan. [Nishiyama, Akira] Kagawa Univ, Sch Med, Dept Internal Med 2, Takamatsu, Kagawa 760, Japan. [Ichikawa, Iekuni] Tokai Univ, Sch Med, Isehara, Kanagawa 2591193, Japan. [Ichikawa, Iekuni] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. RP Matsusaka, T (reprint author), Tokai Univ, Sch Med, Dept Internal Med, 143 Shimokasuya, Isehara, Kanagawa 2591193, Japan. EM taijim@is.icc.u-tokai.ac.jp FU Japan Society for the Promotion of Science; MEXT; Project Research in Tokai University; American Heart Association [12GRANT11630000]; Intramural Research Program of the NIH; National Cancer Institute, Center for Cancer Research FX We acknowledge Ms Shiho lmai and Ms Chie Sakurai for excellent technical assistance and Ms Tanaka for administrative assistance. This study was supported by Grant-in Aid for Scientific Research of Japan Society for the Promotion of Science, MEXT, MEXT-Supported Program for the Strategic Research Foundation at Private Universities (2009-2013), Project Research (2010-2011) in Tokai University, Grant-in-Aid from the American Heart Association (12GRANT11630000), and in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 37 TC 16 Z9 16 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2014 VL 85 IS 5 BP 1068 EP 1077 DI 10.1038/ki.2013.453 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA AG9BJ UT WOS:000335713300016 PM 24284520 ER PT J AU Esserman, LJ Thompson, IM Reid, B Nelson, P Ransohoff, DF Welch, HG Hwang, S Berry, DA Kinzler, KW Black, WC Bissell, M Parnes, H Srivastava, S AF Esserman, Laura J. Thompson, Ian M. Reid, Brian Nelson, Peter Ransohoff, David F. Welch, H. Gilbert Hwang, Shelley Berry, Donald A. Kinzler, Kenneth W. Black, William C. Bissell, Mina Parnes, Howard Srivastava, Sudhir TI Addressing overdiagnosis and overtreatment in cancer: a prescription for change SO LANCET ONCOLOGY LA English DT Article ID CARCINOMA IN-SITU; LOCALIZED PROSTATE-CANCER; NONMELANOMA-SKIN-CANCER; BREAST-CANCER; LUNG-CANCER; BARRETTS-ESOPHAGUS; UNITED-STATES; FOLLOW-UP; SCREENING MAMMOGRAPHY; ESTROGEN-RECEPTOR AB A vast range of disorders-from indolent to fast-growing lesions-are labelled as cancer. Therefore, we believe that several changes should be made to the approach to cancer screening and care, such as use of new terminology for indolent and precancerous disorders. We propose the term indolent lesion of epithelial origin, or IDLE, for those lesions (currently labelled as cancers) and their precursors that are unlikely to cause harm if they are left untreated. Furthermore, precursors of cancer or high-risk disorders should not have the term cancer in them. The rationale for this change in approach is that indolent lesions with low malignant potential are common, and screening brings indolent lesions and their precursors to clinical attention, which leads to overdiagnosis and, if unrecognised, possible overtreatment. To minimise that potential, new strategies should be adopted to better define and manage IDLEs. Screening guidelines should be revised to lower the chance of detection of minimal-risk IDLEs and inconsequential cancers with the same energy traditionally used to increase the sensitivity of screening tests. Changing the terminology for some of the lesions currently referred to as cancer will allow physicians to shift medicolegal notions and perceived risk to reflect the evolving understanding of biology, be more judicious about when a biopsy should be done, and organise studies and registries that off er observation or less invasive approaches for indolent disease. Emphasis on avoidance of harm while assuring benefit will improve screening and treatment of patients and will be equally effective in the prevention of death from cancer. C1 [Esserman, Laura J.] Univ Calif San Francisco, San Francisco, CA 94115 USA. [Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Reid, Brian; Nelson, Peter] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Ransohoff, David F.] Univ N Carolina, Chapel Hill, NC USA. [Welch, H. Gilbert] Dartmouth Coll, Hanover, NH 03755 USA. [Hwang, Shelley] Duke Univ, Durham, NC USA. [Berry, Donald A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kinzler, Kenneth W.] Johns Hopkins Univ, Baltimore, MD USA. [Black, William C.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Bissell, Mina] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. [Parnes, Howard] NCI, Div Prostate, Bethesda, MD 20892 USA. [Parnes, Howard] NCI, Urol Canc Res Grp, Bethesda, MD 20892 USA. [Srivastava, Sudhir] NIH, Canc Biomarkers Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RP Esserman, LJ (reprint author), Univ Calif San Francisco, Carol Franc Buck Breast Care Ctr, San Francisco, CA 94115 USA. EM laura.esserman@ucsfmedctr.org FU National Cancer Institute/Pacific Northwest Prostate Cancer SPORE [P50CA097186]; Early Cancer Detection Research Network grant [CA U01-086402] FX PN was supported by National Cancer Institute (P50CA097186)/Pacific Northwest Prostate Cancer SPORE and by an Early Cancer Detection Research Network grant (CA U01-086402). We thank Barnett Kramer, Director of the Division of Cancer Prevention at the National Cancer Institute, for his vision and continuing encouragement, and all those who lent their expertise at the National Cancer Institute, Division of Cancer Prevention brainstorming meeting held in March, 2012, to discuss issues related to determining the molecular properties of indolent and aggressive cancers and the challenge of overdiagnosis and underdiagnosis; these discussions and conclusions about fruitful future directions in the field form the basis of this Personal View. We also thank Mitch Goldman and Robert Colten for their contributions and edits to the section on skin cancers, Art Dana for his thoughtful edits and patient advocacy, and Pamela Derish and Nilan Schnure for their excellent editing of the manuscript. Nadarajen A Vydelingum, Division of Cancer Prevention at the National Cancer Institute, provided administrative support and coordination among the authors throughout the preparation of this Personal View. All of these individuals received no additional compensation for their contributions to this Personal View. NR 81 TC 87 Z9 90 U1 3 U2 27 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2014 VL 15 IS 6 BP E234 EP E242 PG 9 WC Oncology SC Oncology GA AG6ES UT WOS:000335512100022 PM 24807866 ER PT J AU Sullivan, R Badwe, RA Rath, GK Pramesh, CS Shanta, V Digumarti, R D'Cruz, A Sharma, SC Viswanath, L Shet, A Vijayakumar, M Lewison, G Chandy, M Kulkarni, P Bardia, MR Kumar, S Sarin, R Sebastian, P Dhillon, PK Rajaraman, P Trimble, EL Aggarwal, A Vijaykumar, DK Purushotham, AD AF Sullivan, Richard Badwe, Rajendra A. Rath, Goura K. Pramesh, C. S. Shanta, V. Digumarti, Raghunadharao D'Cruz, Anil Sharma, Suresh C. Viswanath, Lokesh Shet, Arun Vijayakumar, Manavalan Lewison, Grant Chandy, Mammen Kulkarni, Priyadarshini Bardia, M. R. Kumar, Shaleen Sarin, Rajiv Sebastian, Paul Dhillon, Preet K. Rajaraman, Preetha Trimble, Edward L. Aggarwal, Ajay Vijaykumar, D. K. Purushotham, Arnie D. TI Cancer research in India: national priorities, global results SO LANCET ONCOLOGY LA English DT Article ID HIGH-INCOME COUNTRIES; CERVICAL-CANCER; HEALTH-CARE; NONCOMMUNICABLE DISEASES; CLINICAL-TRIALS; RESEARCH OUTPUT; MORTALITY; WORKFORCE; OUTCOMES; BURDEN AB Over the past 20 years, cancer research in India has grown in size and impact. Clinicians, scientists, and government and state policy makers in India have championed cancer research, from studies to achieve low- tech, large- scale health outcomes to some of the most advanced areas of fundamental cancer science. In this paper, we frame public policy discussions about cancer with use of an in-depth analysis of research publications from India. Cancer research in India is a complex environment that needs to balance public policy across many competing agendas. We identify major needs across these environments such as those for increased research capacity and training and protected time for clinical researchers; for more support from states and enhanced collaborative funding programmes from government; for development of national infrastructures across a range of domains (ie, clinical trials, tissue banking, registries, etc); and for a streamlined and rational regulatory environment. We also discuss improvements that should be made to translate research into improvements in cancer outcomes and public health. C1 [Sullivan, Richard; Lewison, Grant; Aggarwal, Ajay; Purushotham, Arnie D.] Kings Coll London, Inst Canc Policy, Kings Hlth Partners Canc Ctr, London SE1 9RT, England. [Badwe, Rajendra A.; Pramesh, C. S.; D'Cruz, Anil; Chandy, Mammen; Sarin, Rajiv] Tata Mem Hosp, Bombay, Maharashtra, India. [Rath, Goura K.] All India Inst Med Sci, New Delhi, India. [Kulkarni, Priyadarshini] Cipla Palliat Care & Training Ctr, Pune, Maharashtra, India. [Shanta, V.] Canc Inst Adayar, Madras, Tamil Nadu, India. [Digumarti, Raghunadharao] Nizams Inst Med Sci, Hyderabad, Andhra Pradesh, India. [Sharma, Suresh C.] Postgrad Inst Med Educ & Res, Chandigarh 160012, India. [Viswanath, Lokesh; Vijayakumar, Manavalan] Kidwai Mem, Bangalore, Karnataka, India. [Shet, Arun] St Johns Med Coll & Hosp, Bangalore, Karnataka, India. [Bardia, M. R.] Reg Canc Ctr, Bikaner, India. [Kumar, Shaleen] Sanjay Gandhi Postgrad Inst Med Sci, Lucknow, Uttar Pradesh, India. [Sebastian, Paul] Reg Canc Ctr, Thiruvananthapuram, Kerala, India. [Dhillon, Preet K.] Publ Hlth Fdn India, South Asia Network Chron Dis, New Delhi, India. [Rajaraman, Preetha] Natl Canc Inst, Ctr Global Hlth, New Delhi, India. [Trimble, Edward L.] NCI, Ctr Global Hlth, Bethesda, MD 20892 USA. [Vijaykumar, D. K.] Amrita Inst Med Sci, Kochi, Kerala, India. RP Sullivan, R (reprint author), Kings Coll London, Inst Canc Policy, London SE1 9RT, England. EM richard.sullivan@kcl.ac.uk OI Shet, Anita/0000-0002-7204-8164; Sarin, Rajiv/0000-0002-6405-8282; Sullivan, Richard/0000-0002-6435-1825 FU Wellcome Trust [084674] NR 53 TC 11 Z9 11 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2014 VL 15 IS 6 BP E213 EP E222 DI 10.1016/S1470-2045(14)70109-3 PG 10 WC Oncology SC Oncology GA AG6ES UT WOS:000335512100020 PM 24731887 ER PT J AU Jong, Y Chang, YC Tseng, E Kwon-Chung, KJ AF Jong, Y. Chang, Y. C. Tseng, E. Kwon-Chung, K. J. TI Hitch hiking through the blood-brain barrier SO MYCOSES LA English DT Meeting Abstract C1 [Jong, Y.] Childrens Hosp Los Angeles, USC Keck Sch Med, Los Angeles, CA 90027 USA. [Chang, Y. C.; Kwon-Chung, K. J.] NIAID, Bethesda, MD 20892 USA. [Tseng, E.] Mackay Med Coll, Taipei, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 EI 1439-0507 J9 MYCOSES JI Mycoses PD MAY PY 2014 VL 57 SU 1 SI SI BP 5 EP 5 DI 10.1111/myc.12196 PG 1 WC Dermatology; Mycology SC Dermatology; Mycology GA AG0FL UT WOS:000335090600003 ER PT J AU Sionov, E Chang, YC Lee, H Kwon-Chung, KJ AF Sionov, E. Chang, Y. C. Lee, H. Kwon-Chung, K. J. TI Mechanisms of resistance and heteroresistance in C. neoformans SO MYCOSES LA English DT Meeting Abstract C1 [Sionov, E.; Chang, Y. C.; Lee, H.; Kwon-Chung, K. J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 EI 1439-0507 J9 MYCOSES JI Mycoses PD MAY PY 2014 VL 57 SU 1 SI SI BP 9 EP 9 PG 1 WC Dermatology; Mycology SC Dermatology; Mycology GA AG0FL UT WOS:000335090600012 ER PT J AU Kwon-Chung, KJ Saijo, T Chen, J Chen, S Sionov, E Varma, A Rosen, LB Yi, J Sorrell, T Bennett, JE Holland, SM Browne, SK Chang, YC Barber, D Mayer-Barber, KD AF Kwon-Chung, K. J. Saijo, T. Chen, J. Chen, S. Sionov, E. Varma, A. Rosen, L. B. Yi, J. Sorrell, T. Bennett, J. E. Holland, S. M. Browne, S. K. Chang, Y. C. Barber, D. Mayer-Barber, K. D. TI Differences in the host's response to Cryptococcus gattii and C. neoformans are more pronounced than previously thought SO MYCOSES LA English DT Meeting Abstract C1 [Kwon-Chung, K. J.; Saijo, T.; Sionov, E.; Varma, A.; Rosen, L. B.; Bennett, J. E.; Holland, S. M.; Browne, S. K.; Chang, Y. C.; Barber, D.; Mayer-Barber, K. D.] NIH, Bethesda, MD 20892 USA. [Chen, J.; Yi, J.] Second Mil Med Univ, Changzheng Hosp, Shanghai, Peoples R China. [Chen, S.; Sorrell, T.] Univ Sydney, Westmead Hosp, Sydney, NSW 2006, Australia. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 EI 1439-0507 J9 MYCOSES JI Mycoses PD MAY PY 2014 VL 57 SU 1 SI SI BP 14 EP 14 PG 1 WC Dermatology; Mycology SC Dermatology; Mycology GA AG0FL UT WOS:000335090600023 ER PT J AU Panackal, AA Browne, SK Rosen, LB Freeman, AF Olivier, KN Hammoud, DA Williamson, PR AF Panackal, A. A. Browne, S. K. Rosen, L. B. Freeman, A. F. Olivier, K. N. Hammoud, D. A. Williamson, P. R. TI A new disease to learn: pulmonary alveolar proteinosis in C-gattii infections SO MYCOSES LA English DT Meeting Abstract C1 [Panackal, A. A.; Browne, S. K.; Rosen, L. B.; Freeman, A. F.; Olivier, K. N.; Hammoud, D. A.; Williamson, P. R.] NIH, Bethesda, MD 20892 USA. RI Hammoud, Dima/C-2286-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 EI 1439-0507 J9 MYCOSES JI Mycoses PD MAY PY 2014 VL 57 SU 1 SI SI BP 30 EP 30 PG 1 WC Dermatology; Mycology SC Dermatology; Mycology GA AG0FL UT WOS:000335090600065 ER PT J AU Williamson, PR Montezuma-Rusca, M Powers, H AF Williamson, P. R. Montezuma-Rusca, M. Powers, H. TI Prognostic indicators vs. treatment surrogates: implications for clinical studies in cryptococcosis SO MYCOSES LA English DT Meeting Abstract C1 [Williamson, P. R.; Montezuma-Rusca, M.; Powers, H.] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 EI 1439-0507 J9 MYCOSES JI Mycoses PD MAY PY 2014 VL 57 SU 1 SI SI BP 30 EP 31 PG 2 WC Dermatology; Mycology SC Dermatology; Mycology GA AG0FL UT WOS:000335090600066 ER PT J AU Najvar, LK Wiederhold, NP Alimardanov, A Cradock, J Xu, X Behnke, M Ottinger, EA Hoekstra, WJ Garvey, EP Brand, SR Schotzinger, RJ Moore, WR Bocanegra, R Kirkpatrick, WR Patterson, TF AF Najvar, L. K. Wiederhold, N. P. Alimardanov, A. Cradock, J. Xu, X. Behnke, M. Ottinger, E. A. Hoekstra, W. J. Garvey, E. P. Brand, S. R. Schotzinger, R. J. Moore, W. R. Bocanegra, R. Kirkpatrick, W. R. Patterson, T. F. TI The novel fungal Cyp51 inhibitor VT-1129 demonstrates potent in vivo activity against Cryptococcal meningitis with an improved formulation SO MYCOSES LA English DT Meeting Abstract C1 [Najvar, L. K.; Wiederhold, N. P.; Bocanegra, R.; Kirkpatrick, W. R.; Patterson, T. F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Alimardanov, A.; Cradock, J.; Xu, X.; Behnke, M.; Ottinger, E. A.] NIH Therapeut Rare & Neglected Dis, Bethesda, MD USA. [Hoekstra, W. J.; Garvey, E. P.; Brand, S. R.; Schotzinger, R. J.; Moore, W. R.] Viamet Pharmaceut Inc, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 EI 1439-0507 J9 MYCOSES JI Mycoses PD MAY PY 2014 VL 57 SU 1 SI SI BP 42 EP 43 PG 2 WC Dermatology; Mycology SC Dermatology; Mycology GA AG0FL UT WOS:000335090600093 ER PT J AU Lockhart, SR Iqbal, N Bolden, CB Grossman, NT Ottinger, EA Garvey, EP Brand, SR Hoekstra, WJ Moore, WR Schotzinger, RJ AF Lockhart, S. R. Iqbal, N. Bolden, C. B. Grossman, N. T. Ottinger, E. A. Garvey, E. P. Brand, S. R. Hoekstra, W. J. Moore, W. R. Schotzinger, R. J. TI Susceptibility testing of VT-1129, a novel fungal CYP51 inhibitor, against Cryptococcus neoformans and Cryptococcus gattii SO MYCOSES LA English DT Meeting Abstract C1 [Lockhart, S. R.; Iqbal, N.; Bolden, C. B.; Grossman, N. T.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Ottinger, E. A.] NIH, Bethesda, MD 20892 USA. [Garvey, E. P.; Brand, S. R.; Hoekstra, W. J.; Moore, W. R.; Schotzinger, R. J.] Viamet Pharmaceut Inc, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 EI 1439-0507 J9 MYCOSES JI Mycoses PD MAY PY 2014 VL 57 SU 1 SI SI BP 43 EP 43 PG 1 WC Dermatology; Mycology SC Dermatology; Mycology GA AG0FL UT WOS:000335090600094 ER PT J AU Larsen, RA Hollabaugh, K Lalloo, UG Ssemmanda, MM Momanyi, LM Lagat, DK Hakim, JG Ly, TT Hogg, E Komarow, L Aberg, JA AF Larsen, R. A. Hollabaugh, K. Lalloo, U. G. Ssemmanda, M. M. Momanyi, L. M. Lagat, D. K. Hakim, J. G. Ly, T. T. Hogg, E. Komarow, L. Aberg, J. A. TI High-dose fluconazole for the treatment of Cryptococcal meningitis in HIV-infected individuals SO MYCOSES LA English DT Meeting Abstract C1 [Larsen, R. A.] USC Med Ctr, Los Angeles, CA USA. [Hollabaugh, K.; Komarow, L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Lalloo, U. G.] Nelson R Mandela Sch Med, Durban, South Africa. [Ssemmanda, M. M.] Joint Clin Res Ctr, Kampala, Uganda. [Momanyi, L. M.] Keyna Med Res Inst, Kericho, Kenya. [Lagat, D. K.] MOI Univ Teaching Hosp, Eldoret, Kenya. [Hakim, J. G.] Univ Zimbabwe, Harare, Zimbabwe. [Ly, T. T.] NIH, Bethesda, MD 20892 USA. [Hogg, E.] ATCT Operat Ctr, Silver Spring, MD USA. [Aberg, J. A.] ICAHN Sch Med Mt Sinai, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 EI 1439-0507 J9 MYCOSES JI Mycoses PD MAY PY 2014 VL 57 SU 1 SI SI BP 51 EP 51 PG 1 WC Dermatology; Mycology SC Dermatology; Mycology GA AG0FL UT WOS:000335090600109 ER PT J AU Djordjevic, JT Lev, S Crossett, B Wilson, CF Desmarini, D Cha, SY Li, C Chayakulkeeree, M Williamson, PR Sorrell, T AF Djordjevic, J. T. Lev, S. Crossett, B. Wilson, C. F. Desmarini, D. Cha, S. Y. Li, C. Chayakulkeeree, M. Williamson, P. R. Sorrell, T. TI Identification of a role for virulence-related Sec14-1 of Cryptococcus neoformans in export of cell wall enzymes and cell separation using proteomics SO MYCOSES LA English DT Meeting Abstract C1 [Djordjevic, J. T.; Lev, S.; Wilson, C. F.; Desmarini, D.; Cha, S. Y.; Li, C.] Westmead Millennium Inst, Sydney, NSW, Australia. [Crossett, B.] Univ Sydney, Sydney, NSW 2006, Australia. [Chayakulkeeree, M.] Mahidol Univ, Siriraj Hosp, Bangkok 10700, Thailand. [Williamson, P. R.] NIH, Bethesda, MD 20892 USA. [Sorrell, T.] Marie Bashir Inst Infect Dis & Biosecur, Sydney, NSW, Australia. RI Crossett, Ben/G-2316-2011 NR 1 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 EI 1439-0507 J9 MYCOSES JI Mycoses PD MAY PY 2014 VL 57 SU 1 SI SI BP 55 EP 55 PG 1 WC Dermatology; Mycology SC Dermatology; Mycology GA AG0FL UT WOS:000335090600118 ER PT J AU Jong, Y Chang, YC Kwon-Chung, KJ Huang, S Shimada, S Fu, X AF Jong, Y. Chang, Y. C. Kwon-Chung, K. J. Huang, S. Shimada, S. Fu, X. TI Cryptococcus neoformans 14-3-3 is an essential gene for virulence SO MYCOSES LA English DT Meeting Abstract C1 [Jong, Y.; Huang, S.; Shimada, S.; Fu, X.] USC Keck Sch Med, Childrens Hosp Los Angeles, Los Angeles, CA USA. [Chang, Y. C.; Kwon-Chung, K. J.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 EI 1439-0507 J9 MYCOSES JI Mycoses PD MAY PY 2014 VL 57 SU 1 SI SI BP 58 EP 58 PG 1 WC Dermatology; Mycology SC Dermatology; Mycology GA AG0FL UT WOS:000335090600125 ER PT J AU Ormerod, KL Byrnes, EJ Wood, IA Lodge, JK Heitman, J Fraser, JA AF Ormerod, K. L. Byrnes, E. J., III Wood, I. A. Lodge, J. K. Heitman, J. Fraser, J. A. TI The H99 family tree: variation in the common laboratory reference strains of Cryptococcus neoformans var. grubii characterised through whole-genome sequencing SO MYCOSES LA English DT Meeting Abstract C1 [Ormerod, K. L.; Wood, I. A.; Fraser, J. A.] Univ Queensland, Brisbane, Qld, Australia. [Byrnes, E. J., III] NIH, Bethesda, MD 20892 USA. [Lodge, J. K.] Washington Univ, St Louis, MO USA. [Heitman, J.] Duke Univ, Med Ctr, Durham, NC USA. RI Wood, Ian/A-5243-2012 OI Wood, Ian/0000-0002-0711-8189 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 EI 1439-0507 J9 MYCOSES JI Mycoses PD MAY PY 2014 VL 57 SU 1 SI SI BP 69 EP 70 PG 2 WC Dermatology; Mycology SC Dermatology; Mycology GA AG0FL UT WOS:000335090600149 ER PT J AU Chang, YC Lamichhane, AK Bradley, JA Rodgers, LH Ngamskulrungroj, P Kwon-Chung, KJ AF Chang, Y. C. Lamichhane, A. Khanal Bradley, J. A. Rodgers, L. H. Ngamskulrungroj, P. Kwon-Chung, K. J. TI D-amino acid oxidase genes in Cryptococcus gattii and Cryptococcus neoformans SO MYCOSES LA English DT Meeting Abstract C1 [Chang, Y. C.; Lamichhane, A. Khanal; Kwon-Chung, K. J.] NIH, Bethesda, MD 20892 USA. [Bradley, J. A.] Univ Louisville, Louisville, KY 40292 USA. [Rodgers, L. H.] Univ Wisconsin, Madison, WI USA. [Ngamskulrungroj, P.] Mahidol Univ, Bangkok 10700, Thailand. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 EI 1439-0507 J9 MYCOSES JI Mycoses PD MAY PY 2014 VL 57 SU 1 SI SI BP 80 EP 80 PG 1 WC Dermatology; Mycology SC Dermatology; Mycology GA AG0FL UT WOS:000335090600170 ER PT J AU Sionov, E Barber, DL Mayer-Barber, KD Chang, YC Kwon-Chung, KJ AF Sionov, E. Barber, D. L. Mayer-Barber, K. D. Chang, Y. C. Kwon-Chung, K. J. TI Differences in host response toward C. neoformans and C. gattii SO MYCOSES LA English DT Meeting Abstract C1 [Sionov, E.; Barber, D. L.; Mayer-Barber, K. D.; Chang, Y. C.; Kwon-Chung, K. J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 EI 1439-0507 J9 MYCOSES JI Mycoses PD MAY PY 2014 VL 57 SU 1 SI SI BP 94 EP 94 PG 1 WC Dermatology; Mycology SC Dermatology; Mycology GA AG0FL UT WOS:000335090600200 ER PT J AU Robles-Espinoza, CD Harland, M Ramsay, AJ Aoude, LG Quesada, V Ding, ZH Pooley, KA Pritchard, AL Tiffen, JC Petljak, M Palmer, JM Symmons, J Johansson, P Stark, MS Gartside, MG Snowden, H Montgomery, GW Martin, NG Lite, JZ Choi, J Makowski, M Brown, KM Dunning, AM Keane, TM Lopez-Otin, C Gruis, NA Hayward, NK Bishop, DT Newton-Bishop, JA Adams, DJ AF Robles-Espinoza, Carla Daniela Harland, Mark Ramsay, Andrew J. Aoude, Lauren G. Quesada, Victor Ding, Zhihao Pooley, Karen A. Pritchard, Antonia L. Tiffen, Jessamy C. Petljak, Mia Palmer, Jane M. Symmons, Judith Johansson, Peter Stark, Mitchell S. Gartside, Michael G. Snowden, Helen Montgomery, Grant W. Martin, Nicholas G. Lite, Jimmy Z. Choi, Jiyeon Makowski, Matthew Brown, Kevin M. Dunning, Alison M. Keane, Thomas M. Lopez-Otin, Carlos Gruis, Nelleke A. Hayward, Nicholas K. Bishop, D. Timothy Newton-Bishop, Julia A. Adams, David J. TI POT1 loss-of-function variants predispose to familial melanoma SO NATURE GENETICS LA English DT Article ID SINGLE-STRANDED-DNA; GERMLINE MUTATIONS; PROTEIN; CANCER; RNA AB Deleterious germline variants in CDKN2A account for around 40% of familial melanoma cases(l), and rare variants in CDK4, BRCA2, BAP1 and the promoter of TERT have also been linked to the disease(2-5). Here we set out to identify new high-penetrance susceptibility genes by sequencing 184 melanoma cases from 105 pedigrees recruited in the UK, The Netherlands and Australia that were negative for variants in known predisposition genes. We identified families where melanoma cosegregates with loss-of-function variants in the protection of telomeres 1 gene (POT1), with a proportion of family members presenting with an early age of onset and multiple primary tumors. We show that these variants either affect POT1 mRNA splicing or alter key residues in the highly conserved oligonucleotide/oligosaccharide-binding (OB) domains of POT1, disrupting protein-telomere binding and leading to increased telomere length. These findings suggest that POT1 variants predispose to melanoma formation via a direct effect on telomeres. C1 [Robles-Espinoza, Carla Daniela; Ding, Zhihao; Tiffen, Jessamy C.; Petljak, Mia; Adams, David J.] Wellcome Trust Sanger Inst, Hinxton, England. [Harland, Mark; Snowden, Helen; Bishop, D. Timothy; Newton-Bishop, Julia A.] Univ Leeds, Leeds Inst Canc & Pathol, Epidemiol & Biostat Sect, Leeds, W Yorkshire, England. [Ramsay, Andrew J.; Quesada, Victor; Lopez-Otin, Carlos] Univ Oviedo, IUOPA, Dept Bioquim & Biol Mol, Oviedo, Spain. [Aoude, Lauren G.; Pritchard, Antonia L.; Palmer, Jane M.; Symmons, Judith; Johansson, Peter; Stark, Mitchell S.; Gartside, Michael G.; Hayward, Nicholas K.] QIMR Berghofer Med Res Inst, Oncogen Lab, Brisbane, Qld, Australia. [Pooley, Karen A.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England. [Montgomery, Grant W.] QIMR Berghofer Med Res Inst, Mol Epidemiol Lab, Brisbane, Qld, Australia. [Martin, Nicholas G.] QIMR Berghofer Med Res Inst, Genet Epidemiol Lab, Brisbane, Qld, Australia. [Lite, Jimmy Z.] Wellcome Trust Sanger Inst, Hinxton, England. [Choi, Jiyeon; Makowski, Matthew; Brown, Kevin M.] Natl Canc Inst, Lab Translat Gen, Bethesda, MD USA. [Dunning, Alison M.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England. [Hayward, Nicholas K.] Leiden Univ, Med Ctr, Dept Dermatol, Leiden, Netherlands. RP Adams, DJ (reprint author), Wellcome Trust Sanger Inst, Hinxton, England. EM dal@sanger.ac.uk RI Aoude, Lauren/C-7484-2014; Stark, Mitchell/E-3542-2010; hayward, nicholas/C-1367-2015; Pritchard, Antonia/F-4288-2010; Montgomery, Grant/B-7148-2008; Johansson, Peter/K-1053-2014; Quesada, Victor/B-6557-2014; Lopez-Otin, Carlos/C-6657-2013; OI Dunning, Alison Margaret/0000-0001-6651-7166; Bishop, Tim/0000-0002-8752-8785; Newton Bishop, Julia/0000-0001-9147-6802; Keane, Thomas/0000-0001-7532-6898; Martin, Nicholas/0000-0003-4069-8020; Aoude, Lauren/0000-0003-1448-3923; Stark, Mitchell/0000-0002-4510-2161; hayward, nicholas/0000-0003-4760-1033; Pritchard, Antonia/0000-0001-5336-0454; Montgomery, Grant/0000-0002-4140-8139; Johansson, Peter/0000-0001-7015-5452; Ding, Zhihao/0000-0003-0961-2284; Quesada, Victor/0000-0002-8398-3457; Lopez-Otin, Carlos/0000-0001-6964-1904; Gruis, Nelleke/0000-0002-5210-9150; Robles Espinoza, Carla Daniela/0000-0003-3277-7466 FU Consejo Nacional de Ciencia y Tecnologia of Mexico; Cancer Research UK [C1287/A9540, C8197/A10123, C588/A4994, C588/A10589]; Isaac Newton Trust; National Health and Medical Research Council of Australia (NHMRC); Cure Cancer Australia; NHMRC; Cancer Council Queensland; Dutch Cancer Society [UL 2012-5489]; Genomics Initiative; Spanish Ministry of Economy and Competitiveness through Instituto de Salud Carlos III (ISCIII); Consolider-Ingenio RNAREG Consortium; Wellcome Trust [WT091310]; Australia and New Zealand Banking Group Limited Trustees; Red Tematica de Investigacion del Cancer (RTICC) del ISCIII FX We thank the UK10K Consortium (funded by the Wellcome Trust; WT091310) for access to control data, D.J.A., C.D.R.-E., Z.D., J.Z.L., J.C.T., M.P. and T.M.K. were supported by Cancer Research UK and the Wellcome Trust (WT098051). C.D.R.-E. was also supported by the Consejo Nacional de Ciencia y Tecnologia of Mexico. K.A.P. and A.M.D. were supported by Cancer Research UK (grants C1287/A9540 and C8197/A10123) and by the Isaac Newton Trust. N.K.H. was supported by a fellowship from the National Health and Medical Research Council of Australia (NHMRC). L.G.A. was supported by an Australia and New Zealand Banking Group Limited Trustees PhD scholarship. ALP. is supported by Cure Cancer Australia. The work was funded in part by the NHMRC and Cancer Council Queensland. The work of N.A.G. was in part supported by the Dutch Cancer Society (UL 2012-5489). M.H., J.A.N.-B. and D.T.B. were supported by Cancer Research UK (programme awards C588/A4994 and C588/A10589 and the Genomics Initiative). C.L.-O., A.J.R. and V.Q. are funded by the Spanish Ministry of Economy and Competitiveness through the Instituto de Salud Carlos III (ISCIII), the Red Tematica de Investigacion del Cancer (RTICC) del ISCIII and the Consolider-Ingenio RNAREG Consortium. C.L.-O. is an investigator with the Botin Foundation. NR 25 TC 83 Z9 87 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD MAY PY 2014 VL 46 IS 5 BP 478 EP 481 DI 10.1038/ng.2947 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA AG4XE UT WOS:000335422900015 PM 24686849 ER PT J AU Shi, JX Yang, XHR Ballew, B Rotunno, M Calista, D Fargnoli, MC Ghiorzo, P Paillerets, BBD Nagore, E Avri, MF Caporaso, NE McMaster, ML Cullen, M Wang, ZM Zhang, XJ Bruno, W Pastorino, L Queirolo, P Banuls-Roca, J Garcia-Casado, Z Vaysse, A Mohamdi, H Riazalhosseini, Y Foglio, M Jouenne, F Hual, X Hyland, PL Yin, JH Vallabhaneni, H Chai, WH Minghetti, P Pellegrini, C Ravichandran, S Eggermont, A Lathrop, M Peris, K Scarra, GB Landi, G Savage, SA Sampson, JN He, J Yeager, M Goldin, LR Demenais, F Chanockl, SJ Tucker, MA Goldsteinl, AM Liu, Y Landi, MT AF Shi, Jianxin Yang, Xiaohong R. Ballew, Bari Rotunno, Melissa Calista, Donato Fargnoli, Maria Concetta Ghiorzo, Paola Paillerets, Brigitte Bressac-de Nagore, Eduardo Avri, Marie Francoise Caporaso, Neil E. McMaster, Mary L. Cullen, Michael Wang, Zhaoming Zhang, Xijun Bruno, William Pastorino, Lorenza Queirolo, Paola Banuls-Roca, Jose Garcia-Casado, Zaida Vaysse, Amaury Mohamdi, Hamida Riazalhosseini, Yasser Foglio, Mario Jouenne, Fanelie Hual, Xing Hyland, Paula L. Yin, Jinhu Vallabhaneni, Haritha Chai, Weihang Minghetti, Paola Pellegrini, Cristina Ravichandran, Sarangan Eggermont, Alexander Lathrop, Mark Peris, Ketty Scarra, Giovanna Bianchi Landi, Giorgio Savage, Sharon A. Sampson, Joshua N. He, Ji Yeager, Meredith Goldin, Lynn R. Demenais, Florence Chanockl, Stephen J. Tucker, Margaret A. Goldsteinl, Alisa M. Liu, Yie Landi, Maria Teresa CA NCI DCEG Canc Sequencing Working G NCI DCEG Canc Genomics Res Lab French Familial Melanoma Study Grp TI Rare missense variants in POT1 predispose to familial cutaneous malignant melanoma SO NATURE GENETICS LA English DT Article ID SINGLE-STRANDED-DNA; TELOMERE REPLICATION; MAMMALIAN TELOMERES; GERMLINE MUTATIONS; CDKN2A MUTATIONS; CANCER; TRF1; RECOGNITION; COMPLEX; DOMAIN AB Although CDKN2A is the most frequent high-risk melanoma susceptibility gene, the underlying genetic factors for most melanoma-prone families remain unknown. Using whole-exome sequencing, we identified a rare variant that arose as a founder mutation in the telomere shelterin gene POT1 (chromosome 7, g.124493086C>T; p.Ser270Asn) in five unrelated melanomaprone families from Romagna, Italy. Carriers of this variant had increased telomere lengths and numbers of fragile telomeres, suggesting that this variant perturbs telomere maintenance. Two additional rare POT1 variants were identified in all cases sequenced in two separate Italian families, one variant per family, yielding a frequency for POT1 variants comparable to that for CDKN2A mutations in this population. These variants were not found in public databases or in 2,038 genotyped Italian controls. We also identified two rare recurrent POT1 variants in US and French familial melanoma cases. Our findings suggest that POT1 is a major susceptibility gene for familial melanoma in several populations. C1 [Shi, Jianxin; Yang, Xiaohong R.; Ballew, Bari; Rotunno, Melissa; Caporaso, Neil E.; McMaster, Mary L.; Cullen, Michael; Wang, Zhaoming; Zhang, Xijun; Hual, Xing; Hyland, Paula L.; Eggermont, Alexander; Savage, Sharon A.; Sampson, Joshua N.; He, Ji; Yeager, Meredith; Goldin, Lynn R.; Chanockl, Stephen J.; Tucker, Margaret A.; Goldsteinl, Alisa M.; Liu, Yie; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, US Natl Inst Hlth, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Calista, Donato; Minghetti, Paola; Landi, Giorgio] Maurizio Bufalini Hosp, Dept Dermatol, Cesena, Italy. [Fargnoli, Maria Concetta; Peris, Ketty] Univ Aquila, Dept Dermatol, I-67100 Laquila, Italy. [Ghiorzo, Paola; Bruno, William; Pastorino, Lorenza; Scarra, Giovanna Bianchi] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy. [Ghiorzo, Paola; Bruno, William; Pastorino, Lorenza; Queirolo, Paola] San Martino IST Ist Nazl Is Ric Cancro, IRCCS, Genoa, Italy. [Paillerets, Brigitte Bressac-de; Jouenne, Fanelie; Eggermont, Alexander] Serv Genet, Villejuif, France. [Nagore, Eduardo] Inst Valenciano Oncol, Dept Dermatol, Valencia, Spain. [Nagore, Eduardo] Univ Catolica Valencia, Dept Dermatol, Valencia, Spain. [Avri, Marie Francoise] Univ Paris 05, AP HP, Hop Cochin, Paris, France. [Cullen, Michael; Wang, Zhaoming; Zhang, Xijun; He, Ji; Yeager, Meredith] SAIC Frederick Inc, NCI Frederick, Canc Genom Res Lab, Frederick, MD USA. [Banuls-Roca, Jose] Gen Hosp Univ Alicante, Dept Dermatol, E-03080 Alicante, Spain. [Garcia-Casado, Zaida] Inst Valenciano Oncol, Lab Mol Biol, Valencia, Spain. [Vaysse, Amaury; Mohamdi, Hamida; Demenais, Florence] INSERM, Genet Variat & Human Dis Unit, UMR 946, Paris, France. [Vaysse, Amaury; Mohamdi, Hamida; Demenais, Florence] Univ Paris Diderot, Sorbonne Paris Cite, Inst Univ Hematol, Paris, France. [Riazalhosseini, Yasser; Lathrop, Mark] McGill Univ, Montreal, PQ, Canada. [Riazalhosseini, Yasser; Lathrop, Mark] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Riazalhosseini, Yasser; Lathrop, Mark] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Foglio, Mario] SAS Quantome, Paris, France. [Yin, Jinhu; Vallabhaneni, Haritha] NIA, Lab Mol Gerontol, US Natl Inst Hlth, US Dept HHS, Baltimore, MD 21224 USA. [Chai, Weihang] Washington State Univ, Sch Mol Biosci, Sect Med Sci, Spokane, WA USA. [Pellegrini, Cristina] Univ Aquila, Dept Biotechnol & Appl Clin Sci, I-67100 Laquila, Italy. [Ravichandran, Sarangan] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Simulat Anal & Math Modeling Grp, Adv Biomed Comp Ctr, Frederick, MD USA. [Eggermont, Alexander] Univ Paris 11, Kremlin Bicetre France, Villejuif, France. [Lathrop, Mark] Fondat Jean Dausset Ctr Etude Polymorphisme Humai, Paris, France. RP Landi, MT (reprint author), NCI, Div Canc Epidemiol & Genet, US Natl Inst Hlth, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM landim@mail.nih.gov RI Queirolo, Paola/K-6778-2016; Bianchi Scarra, Giovanna/G-8933-2014; Demenais, Florence/G-3298-2013; Tucker, Margaret/B-4297-2015; Savage, Sharon/B-9747-2015; Bruno, William/N-7477-2013; Tobias, Geoffrey/M-4135-2016; OI Fargnoli, Maria Concetta/0000-0002-7249-2556; Queirolo, Paola/0000-0002-9917-6633; Bianchi Scarra, Giovanna/0000-0002-6127-1192; Demenais, Florence/0000-0001-8361-0936; Savage, Sharon/0000-0001-6006-0740; Bruno, William/0000-0002-0337-0168; Tobias, Geoffrey/0000-0002-2878-8253; Peris, Ketty/0000-0002-5237-0463 FU Intramural Research Program of the US National Institutes of Health (NIH); National Cancer Institute (NCI); Division of Cancer Epidemiology; National Institute on Aging (NIA); Division of Molecular Gerontology; Universita degli Studi di Genova Progetti di Ricerca di Ateneo PRA; IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro; 5 per 1000 per la Ricerca Corrente; Programme Hospitaller de Recherche Clinique [AOM-07-195]; Ligue Nationale Contre le Cancer [PRE 09/FD]; Genome Quebec, le Ministere de l'Enseignement Superieur, de la Recherche, de la Science et de la Technologie (MESRST) du Quebec; McGill University; US NIH, NCI [HHSN261200800001E] FX This work was supported by the Intramural Research Program of the US National Institutes of Health (NIH), National Cancer Institute (NCI), Division of Cancer Epidemiology and National Institute on Aging (NIA), Division of Molecular Gerontology. The samples from the Institut Valenciano de Oncologia were retrieved from the Biobanco del Instituto Valenciano de Oncologia. The Genoa collection was partly supported by Universita degli Studi di Genova Progetti di Ricerca di Ateneo PRA 2012-2013 and IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, 5 per 1000 per la Ricerca Corrente. The French MELARISK collection was partly supported by Programme Hospitaller de Recherche Clinique (AOM-07-195) and Ligue Nationale Contre le Cancer (PRE 09/FD). We acknowledge the contribution of Institut Gustave-Roussy (IGR) Biobank and Fondation Jean Dausset-CEPH Biobank in providing samples for melanoma-prone families or individual's. The exome sequencing of French samples was supported by a grant from Genome Quebec, le Ministere de l'Enseignement Superieur, de la Recherche, de la Science et de la Technologie (MESRST) du Quebec and McGill University. This project has also been funded in part with federal funds from the US NIH, NCI, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US government. NR 30 TC 74 Z9 77 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD MAY PY 2014 VL 46 IS 5 BP 482 EP 486 DI 10.1038/ng.2941 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA AG4XE UT WOS:000335422900016 PM 24686846 ER PT J AU Spolski, R Leonard, WJ AF Spolski, Rosanne Leonard, Warren J. TI Interleukin-21: a double-edged sword with therapeutic potential SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID T-CELL-LYMPHOMA; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHRONIC LYMPHOCYTIC-LEUKEMIA; HYPER-IGE SYNDROME; RECOMBINANT HUMAN INTERLEUKIN-21; FOLLICULAR-HELPER-CELLS; CHRONIC VIRAL-INFECTION; INFLAMMATORY-BOWEL-DISEASE; IL-21 RECEPTOR EXPRESSION; GENOME-WIDE ASSOCIATION AB Interleukin-21 is a cytokine with broad pleiotropic actions that affect the differentiation and function of lymphoid and myeloid cells. Since its discovery in 2000, a tremendous amount has been learned about its biological actions and the molecular mechanisms controlling IL-21-mediated cellular responses. IL-21 regulates both innate and adaptive immune responses, and it not only has key roles in antitumour and antiviral responses but also exerts major effects on inflammatory responses that promote the development of autoimmune diseases and inflammatory disorders. Numerous studies have shown that enhancing or inhibiting the action of IL-21 has therapeutic effects in animal models of a wide range of diseases, and various clinical trials are underway. The current challenge is to understand how to specifically modulate the actions of IL-21 in the context of each specific immune response or pathological situation. In this Review, we provide an overview of the basic biology of IL-21 and discuss how this information has been-and can be-exploited therapeutically. C1 [Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Spolski, R (reprint author), NHLBI, Lab Mol Immunol, US Natl Inst Hlth, Bldg 10, Bethesda, MD 20892 USA. EM spolskir@nhlbi.nih.gov; wjl@helix.nih.gov FU Division of Intramural Research at the National Heart, Lung, and Blood Institute, US National Institutes of Health (NIH) FX This work was supported by the Division of Intramural Research at the National Heart, Lung, and Blood Institute, US National Institutes of Health (NIH). We thank Drs E. E. West and J.-X. Lin for their critical comments. NR 190 TC 78 Z9 81 U1 1 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 EI 1474-1784 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD MAY PY 2014 VL 13 IS 5 BP 381 EP 393 DI 10.1038/nrd4296 PG 13 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA AG7TH UT WOS:000335621100019 PM 24751819 ER PT J AU Caglayan, M Batra, VK Sassa, A Prasad, R Wilson, SH AF Caglayan, Melike Batra, Vinod K. Sassa, Akira Prasad, Rajendra Wilson, Samuel H. TI Role of polymerase beta in complementing aprataxin deficiency during abasic-site base excision repair SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID DEOXYRIBOSE PHOSPHATE LYASE; STRAND-BREAK REPAIR; DNA; MECHANISM; DOMAIN AB DNA polymerase beta (pol beta) lyase removal of 5'-deoxyribose phosphate (5'-dRP) from base excision repair (BER) intermediates is critical in mammalian BER involving the abasic site. We found that pol beta also removes 5'-adenylated dRP from BER intermediates after abortive ligation. The crystal structure of a human pol beta-DNA complex showed the 5'-AMP-dRP group positioned in the lyase active site. Pol beta expression rescued methyl methanesulfonate sensitivity in aprataxin (hnt3)- and FEN1 (rad27)-deficient yeast. C1 [Caglayan, Melike; Batra, Vinod K.; Sassa, Akira; Prasad, Rajendra; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU Intramural Research Program of the US National Institutes of Health, National Institute of Environmental Health Sciences [Z01 ES050158, ES050159] FX We thank J.K. Horton for critical reading of the manuscript and M. Heacock and D. Shock for helpful discussions. We thank A. Tomkinson (University of New Mexico Cancer Center) for the XRCC1-DNA ligase III complex. This work was supported by the Intramural Research Program of the US National Institutes of Health, National Institute of Environmental Health Sciences (grants Z01 ES050158 and ES050159 to S.H.W.). NR 12 TC 12 Z9 12 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 EI 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAY PY 2014 VL 21 IS 5 BP 497 EP 499 DI 10.1038/nsmb.2818 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA AG9CW UT WOS:000335717300014 PM 24777061 ER PT J AU Elkhaled, A Jalbert, L Constantin, A Yoshihara, HAI Phillips, JJ Molinaro, AM Chang, SM Nelson, SJ AF Elkhaled, Adam Jalbert, Llewellyn Constantin, Alexandra Yoshihara, Hikari A. I. Phillips, Joanna J. Molinaro, Annette M. Chang, Susan M. Nelson, Sarah J. TI Characterization of metabolites in infiltrating gliomas using ex vivo H-1 high- resolution magic angle spinning spectroscopy SO NMR IN BIOMEDICINE LA English DT Article DE glioma; malignant transformation; H-1 HR-MAS spectroscopy; metabolite profiling; 2-hydroxyglutarate; image-guided biopsy ID MAGNETIC-RESONANCE-SPECTROSCOPY; INTEGRATED GENOMIC ANALYSIS; HR-MAS SPECTROSCOPY; LOW-GRADE GLIOMAS; IN-VIVO; BRAIN-TUMORS; H-1-NMR SPECTROSCOPY; IDH2 MUTATIONS; ADULT BRAIN; ASTROCYTOMAS AB Gliomas are routinely graded according to histopathological criteria established by the World Health Organization. Although this classification can be used to understand some of the variance in the clinical outcome of patients, there is still substantial heterogeneity within and between lesions of the same grade. This study evaluated image-guided tissue samples acquired from a large cohort of patients presenting with either new or recurrent gliomas of grades II-IV using ex vivo proton high-resolution magic angle spinning spectroscopy. The quantification of metabolite levels revealed several discrete profiles associated with primary glioma subtypes, as well as secondary subtypes that had undergone transformation to a higher grade at the time of recurrence. Statistical modeling further demonstrated that these metabolomic profiles could be differentially classified with respect to pathological grading and inter-grade conversions. Importantly, the myo-inositol to total choline index allowed for a separation of recurrent low-grade gliomas on different pathological trajectories, the heightened ratio of phosphocholine to glycerophosphocholine uniformly characterized several forms of glioblastoma multiforme, and the onco-metabolite D-2-hydroxyglutarate was shown to help distinguish secondary from primary grade IV glioma, as well as grade II and III from grade IV glioma. These data provide evidence that metabolite levels are of interest in the assessment of both intra-grade and intra-lesional malignancy. Such information could be used to enhance the diagnostic specificity of in vivo spectroscopy and to aid in the selection of the most appropriate therapy for individual patients. (c) 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd. C1 [Elkhaled, Adam; Jalbert, Llewellyn] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Elkhaled, Adam; Jalbert, Llewellyn] Univ Calif San Francisco, Grad Program Bioengn, San Francisco, CA 94143 USA. [Elkhaled, Adam; Jalbert, Llewellyn; Constantin, Alexandra; Yoshihara, Hikari A. I.; Nelson, Sarah J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Constantin, Alexandra] NIH, Bethesda, MD 20892 USA. [Yoshihara, Hikari A. I.] Univ Hosp Lausanne CHUV, Dept Cardiol, Lausanne, Switzerland. [Phillips, Joanna J.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Phillips, Joanna J.; Molinaro, Annette M.; Chang, Susan M.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Molinaro, Annette M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. RP Nelson, SJ (reprint author), UCSF Mission Bay, 1700 4th St, San Francisco, CA 94158 USA. EM Sarah.Nelson@ucsf.edu FU National Institutes of Health (NIH) Brain Tumor SPORE [P50 CA097257]; NIH [PO1 CA118816, RO1 CA127612]; NIH Clinical Center Intramural Program FX We would like to acknowledge support from the Brain Tumor Research Center at the University of California, San Francisco (UCSF) in collecting tissue samples, as well as from the Magnetic Resonance Laboratory at UCSF for the use of the spectrometer. Grant funding was provided by the National Institutes of Health (NIH) Brain Tumor SPORE P50 CA097257, NIH PO1 CA118816, NIH RO1 CA127612 and NIH Clinical Center Intramural Program. NR 46 TC 13 Z9 13 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0952-3480 EI 1099-1492 J9 NMR BIOMED JI NMR Biomed. PD MAY PY 2014 VL 27 IS 5 BP 578 EP 593 DI 10.1002/nbm.3097 PG 16 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA AE1TO UT WOS:000333753300010 PM 24596146 ER PT J AU Chen, HX Rubinstein, LV Shankar, LK Abrams, JS AF Chen, Helen X. Rubinstein, Larry V. Shankar, Lalitha K. Abrams, Jeffrey S. TI Are We Ready for the 10% Solution? SO ONCOLOGIST LA English DT Editorial Material ID RENAL-CELL CARCINOMA; TUMOR RESPONSE; SIZE; SUNITINIB; THRESHOLD; SURVIVAL; CT C1 [Chen, Helen X.; Abrams, Jeffrey S.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Rubinstein, Larry V.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. [Shankar, Lalitha K.] NCI, Canc Imaging Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Abrams, JS (reprint author), NCI, Canc Therapy Evaluat Program, 9609 Med Ctr Dr, Rockville, MD 20850 USA. EM jeff.abrams@nih.gov NR 8 TC 1 Z9 1 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD MAY PY 2014 VL 19 IS 5 BP 439 EP 440 DI 10.1634/theoncologist.2014-0126 PG 2 WC Oncology SC Oncology GA AG5XS UT WOS:000335492700001 PM 24755462 ER PT J AU Guttmacher, AE Maddox, YT Spong, CY AF Guttmacher, A. E. Maddox, Y. T. Spong, C. Y. TI The Human Placenta Project: Placental structure, development, and function in real time SO PLACENTA LA English DT Article DE Human placenta; Research ID CARDIOVASCULAR-DISEASE; ABNORMAL PLACENTATION; LIFE-SPAN; PREGNANCY; PREECLAMPSIA; ORIGINS; HEALTH; IMPLANTATION; WOMEN; SHAPE AB Despite its crucial role in the health of both the fetus and the pregnant woman, the placenta is the least understood human organ. Since a growing body of evidence also underscores the importance of placental development in the lifelong health of both mother and offspring, this lack of knowledge about placental structure and function is particularly concerning. Given modern approaches and technologies and the ability to develop new methods, we propose a coordinated "Human Placenta Project", with the ultimate goal of understanding human placental structure, development, and function in real time. Published by Elsevier Ltd. C1 [Guttmacher, A. E.; Maddox, Y. T.; Spong, C. Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. RP Spong, CY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. EM spongc@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 23 TC 36 Z9 37 U1 1 U2 15 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 EI 1532-3102 J9 PLACENTA JI Placenta PD MAY PY 2014 VL 35 IS 5 BP 303 EP 304 DI 10.1016/j.placenta.2014.02.012 PG 2 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA AG7RC UT WOS:000335614500003 PM 24661567 ER PT J AU Thomas, R Hubbard, AE McHale, CM Zhang, LP Rappaport, SM Lan, Q Rothman, N Vermeulen, R Guyton, KZ Jinot, J Sonawane, BR Smith, MT AF Thomas, Reuben Hubbard, Alan E. McHale, Cliona M. Zhang, Luoping Rappaport, Stephen M. Lan, Qing Rothman, Nathaniel Vermeulen, Roel Guyton, Kathryn Z. Jinot, Jennifer Sonawane, Babasaheb R. Smith, Martyn T. TI Characterization of Changes in Gene Expression and Biochemical Pathways at Low Levels of Benzene Exposure SO PLOS ONE LA English DT Article ID PRINCIPAL COMPONENT ANALYSIS; ACUTE MYELOID-LEUKEMIA; TESTING ASSOCIATION; VARIABLE IMPORTANCE; LONGITUDINAL DATA; BONE-MARROW; METABOLISM; IDENTIFICATION; PHENOL; KEGG AB Benzene, a ubiquitous environmental pollutant, causes acute myeloid leukemia (AML). Recently, through transcriptome profiling of peripheral blood mononuclear cells (PBMC), we reported dose-dependent effects of benzene exposure on gene expression and biochemical pathways in 83 workers exposed across four airborne concentration ranges (from < 1 ppm to > 10 ppm) compared with 42 subjects with non-workplace ambient exposure levels. Here, we further characterize these dose-dependent effects with continuous benzene exposure in all 125 study subjects. We estimated air benzene exposure levels in the 42 environmentally-exposed subjects from their unmetabolized urinary benzene levels. We used a novel nonparametric, data-adaptive model selection method to estimate the change with dose in the expression of each gene. We describe non-parametric approaches to model pathway responses and used these to estimate the dose responses of the AML pathway and 4 other pathways of interest. The response patterns of majority of genes as captured by mean estimates of the first and second principal components of the dose-response for the five pathways and the profiles of 6 AML pathway response-representative genes (identified by clustering) exhibited similar apparent supra-linear responses. Responses at or below 0.1 ppm benzene were observed for altered expression of AML pathway genes and CYP2E1. Together, these data show that benzene alters disease-relevant pathways and genes in a dose-dependent manner, with effects apparent at doses as low as 100 ppb in air. Studies with extensive exposure assessment of subjects exposed in the low-dose range between 10 ppb and 1 ppm are needed to confirm these findings. C1 [Thomas, Reuben; Hubbard, Alan E.; McHale, Cliona M.; Zhang, Luoping; Rappaport, Stephen M.; Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Superfund Res Program, Berkeley, CA 94704 USA. [Lan, Qing; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA. [Guyton, Kathryn Z.; Jinot, Jennifer; Sonawane, Babasaheb R.] US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA. [Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. RP Thomas, R (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Superfund Res Program, Berkeley, CA 94704 USA. EM reuben.thomas@berkeley.edu RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU National Institutes of Health, National Institute of Environmental Health Sciences [R01ES01896, P42 ES004705]; Environment Protection Agency [EP-11-001398] FX Original data generated through funding from National Institutes of Health grants R01ES01896 and P42 ES004705 from the National Institute of Environmental Health Sciences with additional statistical analyses being funded in part by Environment Protection Agency contract number EP-11-001398. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 11 Z9 11 U1 1 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 1 PY 2014 VL 9 IS 5 AR e91828 DI 10.1371/journal.pone.0091828 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG6EE UT WOS:000335510600005 PM 24786086 ER PT J AU Thomason, ME Brown, JA Dassanayake, MT Shastri, R Marusak, HA Hernandez-Andrade, E Yeo, L Mody, S Berman, S Hassan, SS Romero, R AF Thomason, Moriah E. Brown, Jesse A. Dassanayake, Maya T. Shastri, Rupal Marusak, Hilary A. Hernandez-Andrade, Edgar Yeo, Lami Mody, Swati Berman, Susan Hassan, Sonia S. Romero, Roberto TI Intrinsic Functional Brain Architecture Derived from Graph Theoretical Analysis in the Human Fetus SO PLOS ONE LA English DT Article ID RESTING-STATE NETWORKS; HUMAN CEREBRAL-CORTEX; DEFAULT MODE NETWORK; HEMODYNAMIC-RESPONSES; MODULAR ORGANIZATION; LOW-FREQUENCY; INFANT BRAIN; CONNECTIVITY; FMRI; BOLD AB The human brain undergoes dramatic maturational changes during late stages of fetal and early postnatal life. The importance of this period to the establishment of healthy neural connectivity is apparent in the high incidence of neural injury in preterm infants, in whom untimely exposure to ex-uterine factors interrupts neural connectivity. Though the relevance of this period to human neuroscience is apparent, little is known about functional neural networks in human fetal life. Here, we apply graph theoretical analysis to examine human fetal brain connectivity. Utilizing resting state functional magnetic resonance imaging (fMRI) data from 33 healthy human fetuses, 19 to 39 weeks gestational age (GA), our analyses reveal that the human fetal brain has modular organization and modules overlap functional systems observed postnatally. Age-related differences between younger (GA <31 weeks) and older (GA >= 31 weeks) fetuses demonstrate that brain modularity decreases, and connectivity of the posterior cingulate to other brain networks becomes more negative, with advancing GA. By mimicking functional principles observed postnatally, these results support early emerging capacity for information processing in the human fetal brain. Current technical limitations, as well as the potential for fetal fMRI to one day produce major discoveries about fetal origins or antecedents of neural injury or disease are discussed. C1 [Thomason, Moriah E.; Marusak, Hilary A.] Wayne State Univ, Merrill Palmer Skillman Inst Child & Family Dev, Detroit, MI 48202 USA. [Thomason, Moriah E.; Mody, Swati] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [Thomason, Moriah E.; Hernandez-Andrade, Edgar; Yeo, Lami; Hassan, Sonia S.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Brown, Jesse A.] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA USA. [Dassanayake, Maya T.; Shastri, Rupal] Wayne State Univ, Sch Med, Basic Med Sci Program, Detroit, MI USA. [Marusak, Hilary A.] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI 48207 USA. [Hernandez-Andrade, Edgar; Yeo, Lami; Berman, Susan; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Mody, Swati] Wayne State Univ, Sch Med, Dept Radiol, Detroit, MI USA. RP Thomason, ME (reprint author), Wayne State Univ, Merrill Palmer Skillman Inst Child & Family Dev, Detroit, MI 48202 USA. EM moriah@wayne.edu FU Merrill Palmer Skillman Institute for Child and Family Development; Department of Pediatrics, Wayne State University (WSU) School of Medicine; WSU Perinatal Initiative; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Department of Health and Human Services [N01-HD-2-3342]; WSU's Perinatology Virtual Discovery Grant (W.K. Kellogg Foundation) [P3018205]; WSU's Research Grant Program FX This research was supported, in part, by the Merrill Palmer Skillman Institute for Child and Family Development, by the Department of Pediatrics, Wayne State University (WSU) School of Medicine, by the WSU Perinatal Initiative, and by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Department of Health and Human Services through contract N01-HD-2-3342. This project was also supported by WSU's Perinatology Virtual Discovery Grant (made possible by W.K. Kellogg Foundation award P3018205) and WSU's Research Grant Program awards (to MET). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD or the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 59 TC 15 Z9 15 U1 1 U2 19 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 1 PY 2014 VL 9 IS 5 AR e94423 DI 10.1371/journal.pone.0094423 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG6EE UT WOS:000335510600012 PM 24788455 ER PT J AU Wang, XC Fan, Y Zhao, F Wang, ZM Ge, JQ Zhang, K Gao, ZX Gao, JH Yang, YH Fan, J Zou, QH Liu, PN AF Wang, Xingchao Fan, Yang Zhao, Fu Wang, Zhenmin Ge, Jianqiao Zhang, Kai Gao, Zhixian Gao, Jia-Hong Yang, Yihong Fan, Jin Zou, Qihong Liu, Pinan TI Altered Regional and Circuit Resting-State Activity Associated with Unilateral Hearing Loss SO PLOS ONE LA English DT Article ID CROSS-MODAL PLASTICITY; BRAINS DARK ENERGY; FUNCTIONAL CONNECTIVITY; INSULAR CORTEX; DEAF-CHILDREN; COCHLEAR IMPLANTS; VISUAL-ATTENTION; CORTICAL PLASTICITY; COGNITIVE FUNCTION; EXECUTIVE FUNCTION AB The deprivation of sensory input after hearing damage results in functional reorganization of the brain including cross-modal plasticity in the sensory cortex and changes in cognitive processing. However, it remains unclear whether partial deprivation from unilateral auditory loss (UHL) would similarly affect the neural circuitry of cognitive processes in addition to the functional organization of sensory cortex. Here, we used resting-state functional magnetic resonance imaging to investigate intrinsic activity in 34 participants with UHL from acoustic neuroma in comparison with 22 matched normal controls. In sensory regions, we found decreased regional homogeneity (ReHo) in the bilateral calcarine cortices in UHL. However, there was an increase of ReHo in the right anterior insular cortex (rAI), the key node of cognitive control network (CCN) and multimodal sensory integration, as well as in the left parahippocampal cortex (lPHC), a key node in the default mode network (DMN). Moreover, seed-based resting-state functional connectivity analysis showed an enhanced relationship between rAI and several key regions of the DMN. Meanwhile, lPHC showed more negative relationship with components in the CCN and greater positive relationship in the DMN. Such reorganizations of functional connectivity within the DMN and between the DMN and CCN were confirmed by a graph theory analysis. These results suggest that unilateral sensory input damage not only alters the activity of the sensory areas but also reshapes the regional and circuit functional organization of the cognitive control network. C1 [Wang, Xingchao; Wang, Zhenmin; Zhang, Kai; Gao, Zhixian; Liu, Pinan] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China. [Fan, Yang; Ge, Jianqiao; Gao, Jia-Hong; Zou, Qihong] Peking Univ, MRI Res Ctr, Beijing 100871, Peoples R China. [Fan, Yang; Ge, Jianqiao; Gao, Jia-Hong; Zou, Qihong] Peking Univ, Beijing City Key Lab Med Phys & Engn, Beijing 100871, Peoples R China. [Zhao, Fu; Liu, Pinan] Capital Med Univ, Dept Neural Reconstruct, Beijing Neurosurg Inst, Beijing, Peoples R China. [Gao, Jia-Hong] Peking Univ, McGovern Inst Brain Res, Beijing 100871, Peoples R China. [Yang, Yihong] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD USA. [Fan, Jin] CUNY Queens Coll, Dept Psychol, Flushing, NY 11367 USA. [Fan, Jin] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Fan, Jin] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY USA. [Fan, Jin] Mt Sinai Sch Med, Fishberg Dept Neurosci, New York, NY USA. RP Zou, QH (reprint author), Peking Univ, MRI Res Ctr, Beijing 100871, Peoples R China. EM zouqihong@pku.edu.cn; pinanliu@ccmu.edu.cn RI Fan, Jin/A-6716-2009 OI Fan, Jin/0000-0001-9630-8330 FU National Science and Technology Support Program of the 12th Five-Year of China [2012BAI12B03]; Natural Science Foundation of Beijing [7112049]; China's National Strategic Basic Research Program (973) [2012CB720700]; Natural Science Foundation of China [81201142, 31200761] FX This work was supported by National Science and Technology Support Program of the 12th Five-Year of China (grant number: 2012BAI12B03), Natural Science Foundation of Beijing (grant number: 7112049), China's National Strategic Basic Research Program (973) (grant number: 2012CB720700), and Natural Science Foundation of China (grant numbers: 81201142 and 31200761). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 95 TC 11 Z9 11 U1 2 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 1 PY 2014 VL 9 IS 5 AR e96126 DI 10.1371/journal.pone.0096126 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG6EE UT WOS:000335510600078 ER PT J AU Xiao, Q Moore, SC Boca, SM Matthews, CE Rothman, N Stolzenberg-Solomon, RZ Sinha, R Cross, AJ Sampson, JN AF Xiao, Qian Moore, Steven C. Boca, Simina M. Matthews, Charles E. Rothman, Nathaniel Stolzenberg-Solomon, Rachael Z. Sinha, Rashmi Cross, Amanda J. Sampson, Joshua N. TI Sources of Variability in Metabolite Measurements from Urinary Samples SO PLOS ONE LA English DT Article ID CHRONIC-FATIGUE-SYNDROME; CORTISOL METABOLITES; PREMENOPAUSAL WOMEN; DIURNAL EXCRETION; PROFILES; RISK; METABOLOMICS; REPRODUCIBILITY; DISEASE; SYSTEMS AB Background: The application of metabolomics in epidemiological studies would potentially allow researchers to identify biomarkers associated with exposures and diseases. However, within-individual variability of metabolite levels caused by temporal variation of metabolites, together with technical variability introduced by laboratory procedures, may reduce the study power to detect such associations. We assessed the sources of variability of metabolites from urine samples and the implications for designing epidemiologic studies. Methods: We measured 539 metabolites in urine samples from the Navy Colon Adenoma Study using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectroscopy (GC-MS). The study collected 2-3 samples per person from 17 male subjects (age 38-70) over 2-10 days. We estimated between-individual, within-individual, and technical variability and calculated expected study power with a specific focus on large case-control and nested case-control studies. Results: Overall technical reliability was high (median intraclass correlation = 0.92), and for 72% of the metabolites, the majority of total variance can be attributed to between-individual variability. Age, gender and body mass index explained only a small proportion of the total metabolite variability. For a relative risk (comparing upper and lower quartiles of "usual" levels) of 1.5, we estimated that a study with 500, 1,000, and 5,000 individuals could detect 1.0%, 4.5% and 75% of the metabolite associations. Conclusions: The use of metabolomics in urine samples from epidemiological studies would require large sample sizes to detect associations with moderate effect sizes. C1 [Xiao, Qian; Moore, Steven C.; Matthews, Charles E.; Stolzenberg-Solomon, Rachael Z.; Sinha, Rashmi] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA. [Boca, Simina M.; Sampson, Joshua N.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Rothman, Nathaniel] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Cross, Amanda J.] Univ London Imperial Coll Sci Technol & Med, London, England. RP Xiao, Q (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA. EM qian.xiao@nih.gov RI matthews, Charles/E-8073-2015; Moore, Steven/D-8760-2016 OI matthews, Charles/0000-0001-8037-3103; Moore, Steven/0000-0002-8169-1661 FU National Institutes of Health, National Cancer Institute, Department of Health and Human Services FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Department of Health and Human Services. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 5 Z9 5 U1 1 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 1 PY 2014 VL 9 IS 5 AR e95749 DI 10.1371/journal.pone.0095749 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG6EE UT WOS:000335510600051 PM 24788433 ER PT J AU Taha, AY Cheon, Y Faurot, KF Macintosh, B Majchrzalc-Hong, SF Mann, JD Hibbeln, JR Ringel, A Ramsden, CE AF Taha, Ameer Y. Cheon, Yewon Faurot, Keturah F. Macintosh, Beth Majchrzalc-Hong, Sharon F. Mann, J. Douglas Hibbeln, Joseph R. Ringel, Amit Ramsden, Christopher E. TI Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE Linoleic acid (LA) lowering; Arachidonic acid (AA); Plasma fatty acid concentrations; Omega-3 and omega-6 polyunsaturated; fatty acids (PUFAs); Fish; Chronic headache ID ALPHA-LINOLENIC ACID; HUMAN DEPOT FAT; ADIPOSE-TISSUE; RAT-BRAIN; DOCOSAHEXAENOIC ACID; N-3 PUFA; DEPRIVATION; DISEASE; BLOOD; TRIAL AB Background: Dietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations. Objective: To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, alters unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache. Design: Secondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet. Results: Compared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3-L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations. Conclusion: Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFAs for 12 weeks further increases n-3 PUFA plasma concentrations and reduces AA. Published by Elsevier Ltd. C1 [Taha, Ameer Y.; Cheon, Yewon] NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA. [Majchrzalc-Hong, Sharon F.; Hibbeln, Joseph R.; Ringel, Amit; Ramsden, Christopher E.] NIAAA, Sect Nutr Neurosci, NIH, Bethesda, MD USA. [Faurot, Keturah F.; Ramsden, Christopher E.] Univ N Carolina, Dept Phys Med & Rehabil, Program Integrat Med, Chapel Hill, NC USA. [Macintosh, Beth] Univ N Carolina, North Carolina Translat Clin Sci Inst, Nutr Res & Metab Core, Chapel Hill, NC USA. [Mann, J. Douglas] Univ N Carolina, Dept Neurol, Program Integrat Med, Chapel Hill, NC USA. RP Taha, AY (reprint author), NIA, NIH, 9000 Rockville Pike,Bldg 9,1S-126 BPMS, Bethesda, MD 20892 USA. EM ameer.taha@nih.gov RI Majchrzak, Sharon/F-1830-2013 OI Majchrzak, Sharon/0000-0001-8934-7294 FU Mayday Fund (primary source); North Carolina Clinical and Translational Sciences Institute (NCRR) [UL1RR025747]; NIH; UNC Nutrition Obesity Research Center; CHAI Core and Nutrition Epidemiology Core [DK056350]; NIDDK; UNC Research Fellowship in Complementary and Alternative Medicine [T32-AT003378]; NCCAM; Intramural Research Program of the National Institute on Aging; National Institute on Alcohol Abuse and Alcoholism FX The authors thank the patients who participated in the trial, Dr. Stanley Rapoport for reviewing the manuscript and the following individuals for their research assistance: Susan Gaylord, Marjorie Busby, Meg Mangan, Chanee Lynch, Rebecca Coble, David Barrow, Clarence Mayo, Jim Howerton, Derrick Williams, Olafur Palsson, Beth Fowler, Carol Carr, Regina McCoy and Tim McCaskill. This research was funded by the Mayday Fund (primary source), the North Carolina Clinical and Translational Sciences Institute (grant UL1RR025747, NCRR, NIH), the UNC Nutrition Obesity Research Center, CHAI Core and Nutrition Epidemiology Core (grant DK056350, NIDDK, NIH), the UNC Research Fellowship in Complementary and Alternative Medicine (grant T32-AT003378, NCCAM, NIH), and the Intramural Research Program of the National Institute on Aging and the National Institute on Alcohol Abuse and Alcoholism, NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Mayday Fund or the National Institutes of Health. NR 50 TC 17 Z9 17 U1 4 U2 23 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 MAY PY 2014 VL 90 IS 5 BP 151 EP 157 DI 10.1016/j.plefa.2014.02.003 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA AG7SM UT WOS:000335618700002 PM 24675168 ER PT J AU Ramadan, E Blanchard, H Cheon, Y Fox, MA Chang, L Chen, M Ma, K Rapoport, SI Basselin, M AF Ramadan, Epolia Blanchard, Helene Cheon, Yewon Fox, Meredith A. Chang, Lisa Chen, Mei Ma, Kaizong Rapoport, Stanley I. Basselin, Mireille TI Transient postnatal fluoxetine leads to decreased brain arachidonic acid metabolism and cytochrome P450 4A in adult mice SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE Fluoxetine; Arachidonic acid; Mouse; Neurodevelopment; Postnatal; Neuroimaging; Serotonin; SSRI; Cytochrome P450 4A; Metabolism; Brain ID CYTOSOLIC PHOSPHOLIPASE A(2); CEREBRAL-BLOOD-FLOW; SEROTONIN TRANSPORTER; DOCOSAHEXAENOIC ACID; RAT-BRAIN; ANIMAL-MODEL; ENDOGENOUS-DEPRESSION; UNANESTHETIZED RATS; SIGNAL-TRANSDUCTION; FRONTAL-CORTEX AB Fetal and perinatal exposure to selective serotonin (5-HT) reuptake inhibitors (SSRIs) has been reported to alter childhood behavior, while transient early exposure in rodents is reported to alter their behavior and decrease brain extracellular 5-HT in adulthood. Since 5-HT2A/2C receptor-mediated neurotransmission can involve G-protein coupled activation of cytosolic phospholipase A(2) (cPLA(2)), releasing arachidonic acid (ARA) from synaptic membrane phospholipid, we hypothesized that transient postnatal exposure to fluoxetine would alter brain ARA metabolism in adult mice. Brain ARA incorporation coefficients k* and rates A, were quantitatively imaged following intravenous [1-C-14]ARA infusion of unanesthetized adult mice that had been injected daily with fluoxetine (10 mg/kg i.p.) or saline during postnatal days P4-P21. Expression of brain ARA metabolic enzymes and other relevant markers also was measured. On neuroimaging, k* and J(in) was decreased widely in early fluoxetine- compared to salinetreated adult mice. Of the enzymes measured, cPLA2 activity was unchanged, while Ca2+ -independent iPLA(2) activity was increased. There was a significant 74% reduced protein level of cytochrome P450 (CYP) 4A, which can convert ARA to 20-HETE. Reduced brain ARA metabolism in adult mice transiently exposed to postnatal fluoxetine, and a 74% reduction in CYP4A protein, suggest long-term effects independent of drug presence in brain ARA metabolism, and in CYP4A metabolites. These changes might contribute to reported altered behavior following early SSRI in rodents. Published by Elsevier Ltd. C1 [Ramadan, Epolia; Blanchard, Helene; Cheon, Yewon; Chang, Lisa; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.; Basselin, Mireille] Natl Inst Aging, Brain Physiol & Metab Sect, Lab Neurosci, NIH, Bethesda, MD 20892 USA. [Fox, Meredith A.] Natl Inst Mental Hlth, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Basselin, M (reprint author), Natl Inst Aging, Brain Physiol & Metab Sect, Lab Neurosci, NIH, 9000 Rockville Pike,Bldg 9,Room 1S128 MSC 0947, Bethesda, MD 20892 USA. EM mirvasIn@mail.nih.gov FU Intramural Research Programs of the National Institute on Aging; National Institute of Mental Health at the National Institutes of Health FX This work was supported by the Intramural Research Programs of the National Institute on Aging and the National Institute of Mental Health at the National Institutes of Health. No author has a conflict of interest. NR 75 TC 2 Z9 2 U1 0 U2 2 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 MAY PY 2014 VL 90 IS 5 BP 191 EP 197 DI 10.1016/j.plefa.2014.01.003 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA AG7SM UT WOS:000335618700006 PM 24529827 ER PT J AU Okelo, SO Siberry, GK Solomon, BS Bilderback, AL Yamazaki, M Hetzler, T Ferrell, CL Dhepyasuwan, N Serwint, JR AF Okelo, Sande O. Siberry, George K. Solomon, Barry S. Bilderback, Andrew L. Yamazaki, Michiyo Hetzler, Theresa Ferrell, Cynthia L. Dhepyasuwan, Nui Serwint, Janet R. CA CORNET Investigators TI Asthma Treatment Decisions by Pediatric Residents Do Not Consistently Conform to Guidelines or Improve With Level of Training SO ACADEMIC PEDIATRICS LA English DT Article DE asthma; CORNET; decision making; pediatric resident education; survey; treatment; vignettes ID CONTINUITY RESEARCH NETWORK; PATIENT FACTORS; PRIMARY-CARE; VIGNETTES; CHILDREN; QUALITY AB OBJECTIVE: To compare asthma treatment decisions by pediatric residents to current asthma guidelines and to learn whether treatment decisions vary by postgraduate year in training. METHODS: We conducted a Web-based survey of residents from 10 training programs through the Continuity Research Network of the Academic Pediatric Association (CORNET). Surveys included 6 vignettes of patients receiving low-dose inhaled steroids with guideline- and non-guideline-based indicators of asthma status and 1 stable patient on high-intensity medication. RESULTS: There were 369 resident respondents (65% response rate), 26% postgraduate year (PGY) 1, 38% PGY2, and 36% PGY3+. Seventy-five percent of each resident group reported seeing fewer than 1 asthma patient per continuity clinic session. A majority of residents made appropriate treatment recommendations in 2 of 4 vignettes of guideline-based indicators of asthma status: first, 97% overall stepping up treatment for mild persistent asthma; and second, 52% overall stepping down treatment for a patient with well-controlled asthma on high-intensity medications. Inconsistent with guideline recommendations, 82% of residents overall did not step down treatment for a patient with well-controlled asthma receiving low-intensity therapy; 75% of residents did not step up treatment for a patient with a recent hospitalization for asthma. Of the 3 vignettes evaluating non-guideline-based indicators of asthma status, a majority of residents (60%) stepped up treatment for parental reports of worse asthma, while a minority did so for a parental report of being bothered by their child's asthma (27%) or when wheezing was reported at physical examination (43%). There were no statistically significant differences for any of the comparisons by year in training. CONCLUSIONS: Pediatric residents' management of asthma is consistent with national guidelines in some cases but not in others. There were no differences in the outpatient asthma management decisions between residents by years in training. Educational efforts should be focused on strategies to facilitate pediatric resident adherence to national asthma guideline recommendations for outpatient asthma management. C1 [Okelo, Sande O.] Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Pulmonol, Los Angeles, CA 90095 USA. [Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal AIDS PAMA Branch, NIH, Bethesda, MD USA. [Solomon, Barry S.; Serwint, Janet R.] Johns Hopkins Univ, Sch Med, Div Gen Pediat & Adolescent Med, Baltimore, MD USA. [Bilderback, Andrew L.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Yamazaki, Michiyo] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Family Populat & Reprod Hlth, Baltimore, MD USA. [Hetzler, Theresa] New York Med Coll, Dept Pediat, Valhalla, NY 10595 USA. [Ferrell, Cynthia L.] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA. [Dhepyasuwan, Nui] Acad Pediat Assoc, Mclean, VA USA. RP Okelo, SO (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Pediat Pulmonol, 10833 Le Conte Ave,MDCC 3878, Los Angeles, CA 90095 USA. EM sokelo@mednet.ucla.edu FU NHLBI [K23HL089410] FX We appreciate the efforts of our site coinvestigators: Baystate Medical Center: Matthew Sadof, MD; Children's Memorial Hospital, Northwestern University: Sandra M. Sanguino, MD, MPH; DeVos Children's Hospital: William Stratbucker, MD; College/Westchester: Theresa Hetzler, MD; North Carolina Children's Hospital: Michael Steiner, MD; University of Texas at Houston: Michelle S. Barratt, MD, MPH, and Lisa de Ybarrondo, MD; University of Texas Health Sciences at San Antonio: Pamela Wood, MD; University of Utah: Wendy Hobson, MD; and Wilmington Hospital Health Center: Shirley Klein, MD. Supported by NHLBI K23HL089410. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institutes of Health or the Department of Health and Human Services. NR 14 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 EI 1876-2867 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAY-JUN PY 2014 VL 14 IS 3 BP 287 EP 293 DI 10.1016/j.acap.2013.12.008 PG 7 WC Pediatrics SC Pediatrics GA AG4CX UT WOS:000335368000011 PM 24629404 ER PT J AU Elliott, JC Stohl, M Wall, MM Keyes, KM Goodwin, RD Skodol, AE Krueger, RF Grant, BF Hasin, DS AF Elliott, Jennifer C. Stohl, Malka Wall, Melanie M. Keyes, Katherine M. Goodwin, Renee D. Skodol, Andrew E. Krueger, Robert F. Grant, Bridget F. Hasin, Deborah S. TI The risk for persistent adult alcohol and nicotine dependence: the role of childhood maltreatment SO ADDICTION LA English DT Article DE maltreatment; persistence; nicotine; neglect; course; child; Abuse; dependence; chronic; alcohol ID NATIONAL EPIDEMIOLOGIC SURVEY; SUBSTANCE USE DISORDERS; PSYCHIATRIC DIAGNOSTIC MODULES; GENERAL-POPULATION SAMPLE; IV AUDADIS-IV; UNITED-STATES; DSM-IV; PERSONALITY-DISORDERS; FAMILY-HISTORY; SEXUAL-ABUSE AB Background and Aims Alcohol and nicotine dependence are associated with considerable morbidity and mortality, especially when cases are persistent. The risk for alcohol and nicotine dependence is increased by childhood maltreatment. However, the influence of childhood maltreatment on dependence course is unknown, and is evaluated in the current study. Design Physical, sexual and emotional abuse, and physical and emotional neglect, were evaluated as predictors of persistent alcohol and nicotine dependence over 3 years of follow-up, with and without control for other childhood adversities. Setting National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Participants NESARC participants completing baseline and follow-up who met criteria at baseline for past-year alcohol dependence (n = 1172) and nicotine dependence (n = 4017). Measurements Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS) measures of alcohol/nicotine dependence, childhood maltreatment and other adverse childhood experiences (e.g. parental divorce). Findings Controlling for demographics only, physical, sexual and emotional abuse and physical neglect predicted 3-year persistence of alcohol dependence [adjusted odds ratio (AOR) = 1.50-2.99; 95% CI = 1.04-4.68] and nicotine dependence (AOR = 1.37-1.74; 95% CI = 1.13-2.11). With other childhood adversities also controlled, maltreatment types remained predictive for alcohol persistence (AOR = 1.53-3.02; 95% CI = 1.07-4.71) and nicotine persistence (AOR = 1.35-1.72; 95% CI = 1.11-2.09). Further, a greater number of maltreatment types incrementally influenced persistence risk (AOR = 1.19-1.36; 95% CI = 1.11-1.56). Conclusions A history of childhood maltreatment predicts persistent adult alcohol and nicotine dependence. This association, robust to control for other childhood adversities, suggests that maltreatment (rather than a generally difficult childhood) affects the course of dependence. C1 [Elliott, Jennifer C.; Stohl, Malka; Keyes, Katherine M.; Goodwin, Renee D.; Hasin, Deborah S.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Wall, Melanie M.; Skodol, Andrew E.; Hasin, Deborah S.] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY USA. [Wall, Melanie M.; Hasin, Deborah S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Wall, Melanie M.] Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, New York, NY USA. [Goodwin, Renee D.] CUNY Queens Coll, Dept Psychol, Queens, NY USA. [Goodwin, Renee D.] CUNY, Grad Ctr, Queens, NY USA. [Skodol, Andrew E.] Univ Arizona, Dept Psychiat, Coll Med, Tucson, AZ USA. [Krueger, Robert F.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Rockville, MD 20852 USA. RP Hasin, DS (reprint author), Columbia Univ Coll Phys & Surg, Dept Psychiat, 1051 Riverside Dr 123, New York, NY 10032 USA. EM dsh2@columbia.edu FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [U01AA018111, K05AA014223]; National Institute on Drug Abuse (NIDA) [T32DA031099]; New York State Psychiatric Institute; NIAAA; Intramural Program, NIAAA, National Institutes of Health; NIDA FX This study was funded by grants U01AA018111 and K05AA014223 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) (Dr Hasin); T32DA031099 from the National Institute on Drug Abuse (NIDA) (Dr Elliott); and the New York State Psychiatric Institute (Drs Hasin and Wall). The National Epidemiologic Survey on Alcohol and Related Conditions was sponsored by the NIAAA and funded in part by the Intramural Program, NIAAA, National Institutes of Health, with additional support from NIDA. NR 53 TC 15 Z9 15 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 EI 1360-0443 J9 ADDICTION JI Addiction PD MAY PY 2014 VL 109 IS 5 BP 842 EP 850 DI 10.1111/add.12477 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AE4XO UT WOS:000333990500025 PM 24401044 ER PT J AU Mendola, P Laughon, SK Mannisto, TI AF Mendola, Pauline Laughon, S. Katherine Mannisto, Tuija I. TI Re: "Neonatal Bilirubin Levels and Childhood Asthma in the US Collaborative Perinatal Project, 1959-1965" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 [Mendola, Pauline; Laughon, S. Katherine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Bethesda, MD 20892 USA. [Mannisto, Tuija I.] Natl Inst Hlth & Welf, Kastelli Res Ctr, FIN-90014 Oulu, Finland. RP Mendola, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Bethesda, MD 20892 USA. EM pauline.mendola@nih.gov OI Mannisto, Tuija/0000-0002-6382-9153; Mendola, Pauline/0000-0001-5330-2844; Grantz, Katherine/0000-0003-0276-8534 NR 5 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 1 PY 2014 VL 179 IS 9 BP 1149 EP 1150 DI 10.1093/aje/kwu064 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AG3OY UT WOS:000335330300018 PM 24692431 ER PT J AU Doerr, TP Yu, YK AF Doerr, T. P. Yu, Yi-Kuo TI Electrical interactions in the cell: Asymmetric screening in a watery "antiverse" SO AMERICAN JOURNAL OF PHYSICS LA English DT Article ID EVOLUTION; PHYSICS AB The problem of electrostatics in biomolecular systems presents an excellent opportunity for cross-disciplinary science and a context in which fundamental physics is called for to answer complex questions. Due to the large density in biological cells of charged biomacromolecules such as protein factors and DNA, it is challenging to understand quantitatively the electric forces in these systems. Two questions are especially puzzling. First, how is it that such a dense system of charged molecules does not simply aggregate in random and non-functional ways? Second, since some mechanism apparently prevents such aggregation, how is it that binding of biomolecules still occurs so reliably? Recognizing the role of water as a universal solvent in living systems is key to understanding these questions. We present a simplified physical model in which water is regarded as a medium of high dielectric constant that nevertheless exhibits the key features essential for answering the two questions presented. The answer to the first question lies in the strong screening ability of water, which reduces the energy scale of the electrostatic interactions. Furthermore, our model reveals the existence of asymmetric screening, a pronounced asymmetry between the screening for a system with like charges and that for a system with opposite charges, and this provides an answer to the second question. (C) 2014 American Association of Physics Teachers. C1 [Doerr, T. P.; Yu, Yi-Kuo] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Doerr, TP (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike MSC 6075, Bethesda, MD 20894 USA. EM doerr@ncbi.nlm.nih.gov; yyu@ncbi.nlm.nih.gov FU NIH, National Library of Medicine FX This research was supported by the Intramural Research Program of the NIH, National Library of Medicine. NR 22 TC 3 Z9 3 U1 1 U2 7 PU AMER ASSOC PHYSICS TEACHERS AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0002-9505 EI 1943-2909 J9 AM J PHYS JI Am. J. Phys. PD MAY PY 2014 VL 82 IS 5 DI 10.1119/1.4869281 PG 6 WC Education, Scientific Disciplines; Physics, Multidisciplinary SC Education & Educational Research; Physics GA AG2BA UT WOS:000335218800013 PM 25125701 ER PT J AU Klee, MM AF Klee, Maurice M. TI Biology's built-in Faraday cages SO AMERICAN JOURNAL OF PHYSICS LA English DT Article ID CHARGE-DISTRIBUTIONS; SURFACE-CHARGES; ION CHANNELS; FIELDS; EQUILIBRIUM; CIRCUITS; CURRENTS; CELLS AB Biological fluids are water-based, ionic conductors. As such, they have both high relative dielectric constants and substantial conductivities, meaning they are lossy dielectrics. These fluids contain charged molecules (free charges), whose movements play roles in essentially all cellular processes from metabolism to communication with other cells. Using the problem of a point source in air above a biological fluid of semi-infinite extent, the bound charges in the fluid are shown to perform the function of a fast-acting Faraday cage, which protects the interior of the fluid from external electric fields. Free charges replace bound charges in accordance with the fluid's relaxation time, thereby providing a smooth transition between the initial protection provided by the bound charges and the steady state protection provided by the free charges. The electric fields within the biological fluid are thus small for all times just as they would be inside a classical Faraday cage. (C) 2014 American Association of Physics Teachers. C1 [Klee, Maurice M.] NIH, Bethesda, MD 20892 USA. EM mmk@mauriceklee.com NR 47 TC 0 Z9 0 U1 1 U2 7 PU AMER ASSOC PHYSICS TEACHERS AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0002-9505 EI 1943-2909 J9 AM J PHYS JI Am. J. Phys. PD MAY PY 2014 VL 82 IS 5 DI 10.1119/1.4868016 PG 9 WC Education, Scientific Disciplines; Physics, Multidisciplinary SC Education & Educational Research; Physics GA AG2BA UT WOS:000335218800012 ER PT J AU Keshavan, MS Vinogradov, S Rumsey, J Sherrill, J Wagner, A AF Keshavan, Matcheri S. Vinogradov, Sophia Rumsey, Judith Sherrill, Joel Wagner, Ann TI Cognitive Training in Mental Disorders: Update and Future Directions SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID DIRECT-CURRENT STIMULATION; REMEDIATION THERAPY CRT; PRIMARY MOTOR CORTEX; ADULT OWL MONKEYS; WORKING-MEMORY; ENHANCEMENT THERAPY; CORTICAL PLASTICITY; BIAS MODIFICATION; CONTROLLED-TRIAL; HAND REPRESENTATION AB Objective: This article reviews the conceptual basis, definitions, and evolution of cognitive training approaches for the treatment of mental disorders. Method: The authors review the current state of the knowledge on cognitive training in psychiatric illnesses, and its neural and behavioral targets, and summarize the factors that appear to relate to a successful response, including learner characteristics that influence clinical outcome. They also discuss methodological issues relevant to the development and testing of cognitive training approaches, with the goal of creating maximally efficient and effective approaches to training. Finally, they identify gaps in existing knowledge and outline key research directions for the future. Results: While much of the early research has been conducted in schizophrenia, cognitive training has more recently been applied to a widening range of neuropsychiatric illnesses, including-attention deficit hyperactivity disorder, mood disorders, and substance use disorders. Cognitive training harnesses the inherent neuroplastic capacities of the brain, targeting neural system function across psychiatric disorders, thus improving the cognitive processes that play a, role in emotion regulation, clinical symptoms, and adaptive community functioning. Conclusions: Cognitive training offers considerable promise, especially given the limited efficacy of pharmacological interventions in a-meliorating cognitive deficits. However, more research is needed to understand the mechanisms underlying cognitive training, predictors of response, generalization and real-world applicability, and approaches to dissemination in practice settings. C1 [Keshavan, Matcheri S.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. NIMH, Clin Neurosci Res Branch, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA. NIMH, Treatment & Prevent Intervent Res Branch, Div Serv & Intervent Res, Bethesda, MD 20892 USA. NIMH, Neurobehav Mechanisms Mental Disorders Branch, Div Dev Translat Res, Bethesda, MD 20892 USA. RP Keshavan, MS (reprint author), Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. EM mkeshava@bidmc.harvard.edu FU Sunovion; AmGen; Brain Plasticity Institute; EnVivo; Genentech; Hoffman La Roche; NIH [MH092440, MH060902, MH082818, MH068725, MH081051, MH081807]; Stanley Medical Research Institute; NIMH FX Dr. Keshavan has received grant funding from Sunovion. Dr. Vinogradov has received consulting fees from AmGen, Brain Plasticity Institute, EnVivo, Genentech, and Hoffman La Roche. The other authors report no financial relationships with commercial interests.; Dr. Keshavan has been supported by NIH grants MH092440 and MH060902. Dr. Vinogradov has been supported by NIH grants MH068725, MH082818, MH068725, MH081051, and MH081807 and the Stanley Medical Research Institute.; This research is based on a workshop sponsored by NIMH that was held on April 9 and 10, 2012. The workshop participants were Matcheri Keshavan, Harvard University (co-chair); Ann Wagner, NIMH (co-chair); Yair Bar-Haim, Tel Aviv University; Cameron Carter, University of California Davis; David Chambers, NIMH; Bruce Cuthbert, NIMH; Daniel Dickstein, Bradley Hospital/Brown University; Amy Dorin, FEGS Health and Human Services System, New York; Shaun Eack, University of Pittsburgh; Amit Etkin, Stanford University; Adam Gazzaley, University of California San Francisco; Russ Glasgow, National Cancer Institute; Adam Haim, NIMH; Jeffrey Halperin, Queens College; Courtenay Harding, The Coalition of Behavioral Health Agencies, New York; Robert Heinssen, NIMH; Thomas Insel, NIMH; Wendy Kates, SUNY Upstate Medical Center; Ellen Leibenluft, NIMH; Susan McGurk, Boston University; Alice Medalia, Columbia University; Sarah Morris, NIMH; Alvaro Pascual-Leone, Harvard Medical School; Daniel Pine, NIMH; Judith Rumsey, NIMH; Christopher Sarampote, NIMH; Suzy Scherf, Pennsylvania State University; Joel Sherrill, NIMH; David Sommers, NIMH; Leanne Tamm, Cincinnati Children's Hospital Medical Center; Carol Tamminga, University of Texas Southwestern Medical Center; Sophia Vinogradov, University of California San Francisco; Bruce Wexler, Yale University; Til Wykes, University of London Institute of Psychiatry. NR 99 TC 48 Z9 49 U1 8 U2 74 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2014 VL 171 IS 5 BP 510 EP 522 DI 10.1176/appi.ajp.2013.13081075 PG 13 WC Psychiatry SC Psychiatry GA AG0SI UT WOS:000335125500010 PM 24700194 ER PT J AU Leary, PJ Kaufman, JD Barr, RG Bluemke, DA Curl, CL Hough, CL Lima, JA Szpiro, AA Van Hee, VC Kawut, SM AF Leary, Peter J. Kaufman, Joel D. Barr, R. Graham Bluemke, David A. Curl, Cynthia L. Hough, Catherine L. Lima, Joao A. Szpiro, Adam A. Van Hee, Victor C. Kawut, Steven M. TI Traffic-related Air Pollution and the Right Ventricle The Multi-ethnic Study of Atherosclerosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE air pollutants; pulmonary circulation; heart ventricles; pulmonary hypertension ID RIGHT-HEART-FAILURE; MESA AIR; PULMONARY-HYPERTENSION; CARDIOVASCULAR EVENTS; MOLECULAR-MECHANISMS; SYSTOLIC FUNCTION; CARDIAC STRUCTURE; TERM EXPOSURE; IN-VIVO; RISK AB Rationale: Right heart failure is a cause of morbidity and mortality in common and rare heart and lung diseases. Exposure to traffic-related air pollution is linked to left ventricular hypertrophy, heart failure, and death. Relationships between traffic-related air pollution and right ventricular (RV) structure and function have not been studied. Objectives: To characterize the relationship between traffic-related air pollutants and RV structure and function. Methods: We included men and women with magnetic resonance imaging assessment of RV structure and function and estimated residential outdoor nitrogen dioxide (NO2) concentrations from the Multi-ethnic Study of Atherosclerosis, a study of individuals free of clinical cardiovascular disease at baseline. Multivariable linear regression estimated associations between NO2 exposure (averaged over the year prior to magnetic resonance imaging) and measures of RV structure and function after adjusting for demographics,anthropometrics, smoking status, diabetes mellitus, and hypertension. Adjustment for corresponding left ventricular parameters, traffic-related noise, markers of inflammation, and lung disease were considered in separate models. Secondary analyses considered oxides of nitrogen (NOx) as the exposure. Measurements and Main Results: The study sample included 3,896 participants. In fully adjusted models, higher NO2 was associated with greater RV mass and larger RV end-diastolic volume with or without further adjustment for corresponding left ventricular parameters, traffic-related noise, inflammatory markers, or lung disease (all P < 0.05). There was no association between NO2 and RV ejection fraction. Relationships between NO and RV morphology were similar. Conclusions: Higher levels of NO2 exposure were associated with greater RV mass and larger RV end-diastolic volume. C1 [Leary, Peter J.; Kaufman, Joel D.; Hough, Catherine L.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Kaufman, Joel D.; Curl, Cynthia L.] Univ Washington, Dept Environm, Seattle, WA 98195 USA. [Kaufman, Joel D.; Curl, Cynthia L.] Univ Washington, Occupat Hlth Serv, Seattle, WA 98195 USA. [Kaufman, Joel D.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Szpiro, Adam A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Barr, R. Graham] Columbia Univ, Dept Med, New York, NY USA. [Barr, R. Graham] Columbia Univ, Dept Epidemiol, New York, NY USA. [Bluemke, David A.] NIH Clin Ctr, Bethesda, MD USA. [Lima, Joao A.] Johns Hopkins Univ Hosp, Dept Med, Baltimore, MD 21287 USA. [Lima, Joao A.] Johns Hopkins Univ Hosp, Dept Radiol, Baltimore, MD 21287 USA. [Van Hee, Victor C.] Park Nicollet Med Ctr, St Louis Pk, MN USA. [Kawut, Steven M.] Univ Penn, Perelman Sch Med, Dept Epidemiol, Dept Med, Philadelphia, PA 19104 USA. [Kawut, Steven M.] Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA. RP Leary, PJ (reprint author), Univ Washington, Med Ctr, Div Pulm & Crit Care Med, Hlth Sci Ctr BB 1253, Box 356522, Seattle, WA 98195 USA. EM learyp@uw.edu RI Kaufman, Joel/B-5761-2008; OI Kaufman, Joel/0000-0003-4174-9037; Bluemke, David/0000-0002-8323-8086; Leary, Peter/0000-0001-5716-248X FU National Institutes of Health [R01-HL086719, K24-HL103844, K24-ES013195, P30ES07033, R01-HL077612, N01-HC95159, HC95165, N01-HC95169, KL2TR000421]; US Environmental protection Agency (EPA) FX Supported by the National Institutes of Health (R01-HL086719, K24-HL103844, K24-ES013195, P30ES07033, R01-HL077612, N01-HC95159 through HC95165, N01-HC95169, and KL2TR000421). This publication was developed under a STAR research assistance agreement, No. RD831697 (MESA Air), awarded by the US Environmental protection Agency (EPA). It has not been formally reviewed by the EPA. The views expressed in this document are solely those of the authors, and the EPA or National Institutes of Health do not endorse any products or commercial services mentioned in this publication. NR 41 TC 15 Z9 15 U1 1 U2 8 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY 1 PY 2014 VL 189 IS 9 BP 1093 EP 1100 DI 10.1164/rccm.201312-2298OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AG4CJ UT WOS:000335366500014 PM 24593877 ER PT J AU Xie, ZH Ghosh, CC Parikh, SM Druey, KM AF Xie, Zhihui Ghosh, Chandra C. Parikh, Samir M. Druey, Kirk M. TI Mechanistic Classification of the Systemic Capillary Leak Syndrome: Clarkson Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter ID CASE SERIES C1 [Xie, Zhihui; Druey, Kirk M.] NIAID, NIH, Bethesda, MD 20892 USA. [Ghosh, Chandra C.; Parikh, Samir M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Ghosh, Chandra C.; Parikh, Samir M.] Harvard Univ, Sch Med, Boston, MA USA. RP Xie, ZH (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL093234, R01-HL093234]; NIAID NIH HHS [AI001830]; NIDDK NIH HHS [R01-DK095072, R01 DK095072] NR 6 TC 8 Z9 8 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY 1 PY 2014 VL 189 IS 9 BP 1145 EP 1147 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AG4CJ UT WOS:000335366500023 PM 24787070 ER PT J AU Witschey, WRT Contijoch, F McGarvey, JR Ferrari, VA Hansen, MS Lee, ME Takebayashi, S Aoki, C Chirinos, JA Yushkevich, PA Gorman, JH Pilla, JJ Gorman, RC AF Witschey, Walter R. T. Contijoch, Francisco McGarvey, Jeremy R. Ferrari, Victor A. Hansen, Michael S. Lee, Madonna E. Takebayashi, Satoshi Aoki, Chikashi Chirinos, Julio A. Yushkevich, Paul A. Gorman, Joseph H., III Pilla, James J. Gorman, Robert C. TI Real-Time Magnetic Resonance Imaging Technique for Determining Left Ventricle Pressure-Volume Loops SO ANNALS OF THORACIC SURGERY LA English DT Article ID CANINE LEFT-VENTRICLE; VALIDATION; SENSITIVITY; HEART; RATIO; MR AB Background. Rapid determination of the left ventricular (LV) pressure-volume (PV) relationship as loading conditions are varied is the gold standard for assessment of LV function. Cine magnetic resonance imaging (MRI) does not have sufficient spatiotemporal resolution to assess beat-to-beat changes of the LV PV relationship required to measure the LV end-systolic elastance (EES) or preload-recruitable stroke work (PRSW). Our aim was to investigate real-time MRI and semiautomated LV measurement of LV volume to measure PV relations in large animals under normal and inotropically stressed physiologic conditions. Methods. We determined that PV relationships could be accurately measured using an image exposure time T-ex less than 100 ms and frame rate T-fr less than 50 ms at elevated heart rates (similar to 140 beats per minute) using a golden angle radial MRI k-space trajectory and active contour segmentation. Results. With an optimized exposure time (T-ex = 95 ms and frame rate T-fr = 2.8 ms), we found that there was no significant difference between cine and real-time MRI at rest in end-diastolic volume, end-systolic volume, ejection fraction, stroke volume, or cardiac output (n = 5, p < 0.05) at either normal or elevated heart rates. We found E-ES increased from 1.9 +/- 0.7 to 3.1 +/- 0.3 mm Hg/mL and PRSW increased from 6.2 +/- 1.2 to 9.1 +/- 0.9 mm Hg during continuous intravenous dobutamine infusion (n = 5, p < 0.05). Conclusions. Real-time MRI can assess LV volumes, E-ES, and PRSW at baseline and elevated inotropic states. (C) 2014 by The Society of Thoracic Surgeons C1 Univ Penn, Dept Surg, Perelman Sch Med, Gorman Cardiovasc Res Grp, Philadelphia, PA 19104 USA. Univ Penn, Dept Radiol, Perelman Sch Med, Gorman Cardiovasc Res Grp, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Perelman Sch Med, Gorman Cardiovasc Res Grp, Philadelphia, PA 19104 USA. NIH, Bethesda, MD 20892 USA. RP Gorman, RC (reprint author), Univ Penn, Smilow Ctr Translat Res, Perelman Sch Med, Gorman Cardiovasc Res Grp, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM robert.gorman@uphs.upenn.edu RI Hansen, Michael/J-5391-2015; OI Hansen, Michael/0000-0002-8087-8731; Contijoch, Francisco/0000-0001-9616-3274 FU National Institutes of Health [K99-HL108157, R01-HL063954] FX The authors gratefully acknowledge National Institutes of Health support K99-HL108157 and R01-HL063954. NR 22 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2014 VL 97 IS 5 BP 1597 EP 1603 DI 10.1016/j.athoracsur.2014.01.010 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AG5HX UT WOS:000335451200036 PM 24629301 ER PT J AU Blackstone, E Horvath, K Moskowitz, A AF Blackstone, Eugene Horvath, Keith Moskowitz, Alan TI Implicating Transfusions in Infections After Cardiac Operations Reply SO ANNALS OF THORACIC SURGERY LA English DT Letter ID RED-BLOOD-CELL; SURGERY; MORBIDITY C1 [Blackstone, Eugene] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Horvath, Keith] NHLBI, NIH, Bethesda, MD 20892 USA. [Moskowitz, Alan] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. RP Blackstone, E (reprint author), Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM alan.moskowitz@mssm.edu NR 6 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2014 VL 97 IS 5 BP 1852 EP 1853 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AG5HX UT WOS:000335451200104 PM 24792288 ER PT J AU Dimyan, MA Perez, MA Auh, S Tarula, E Wilson, M Cohen, LG AF Dimyan, Michael. A. Perez, Monica A. Auh, Sungyoung Tarula, Erick Wilson, Matthew Cohen, Leonardo G. TI Nonparetic Arm Force Does Not Overinhibit the Paretic Arm in Chronic Poststroke Hemiparesis SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Neurophysiology; Paresis; Rehabilitation; Stroke ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; INTERHEMISPHERIC INHIBITION; RECOVERY MECHANISMS; SUBCORTICAL STROKE; IFCN COMMITTEE; BRAIN; HAND; EXCITABILITY; FACILITATION AB Objective: To determine whether nonparetic arm force overinhibits the paretic arm in patients with chronic unilateral poststroke hemiparesis. Design: Case-control neurophysiological and behavioral study of patients with chronic stroke. Setting: Research institution. Participants: Eighty-six referred patients were screened to enroll 9 participants (N=9) with a > 6 month history of 1 unilateral ischemic infarct that resulted in arm hemiparesis with residual ability to produce 1Nm of wrist flexion torque and without contraindication to transcranial magnetic stimulation. Eight age- and handedness-matched healthy volunteers without neurologic diagnosis were studied for comparison. Interventions: Not applicable. Main Outcome Measure: Change in interhemispheric inhibition targeting the ipsilesional primary motor cortex (M1) during nonparetic arm force. We hypothesized that interhemispheric inhibition would increase more in healthy controls than in patients with hemiparesis. Results: Healthy age-matched controls had significantly greater increases in inhibition from their active to resting M1 than patients with stroke from their active contralesional to resting ipsilesional M1 in the same scenario (20% +/- 7% vs -1% +/- 4%, F (1,12)=6.61, P =.025). Patients with greater increases in contralesional to ipsilesional inhibition were better performers on the 9-hole peg test of paretic arm function. Conclusions: Our findings reveal that producing force with the nonparetic arm does not necessarily overinhibit the paretic arm. Though our study is limited in generalizability by the small sample size, we found that greater active contralesional to resting ipsilesional M1 inhibition was related with better recovery in this subset of patients with chronic poststroke. (C) 2014 by the American Congress of Rehabilitation Medicine C1 [Dimyan, Michael. A.; Perez, Monica A.; Tarula, Erick; Wilson, Matthew; Cohen, Leonardo G.] NINDS, Human Cort Physiol, NIH, Bethesda, MD 20892 USA. [Dimyan, Michael. A.; Perez, Monica A.; Tarula, Erick; Wilson, Matthew; Cohen, Leonardo G.] NINDS, Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA. [Auh, Sungyoung] NINDS, Clin Neurosci Program, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Dimyan, MA (reprint author), 2200 Keman Dr, Baltimore, MD 21207 USA. EM mdimyan@umm.edu OI Dimyan, Michael/0000-0002-9715-9741 FU National Institute of Neurological Disorders and Stroke, Division of Intramural Research [Z01NS003030]; National Institutes of Health Clinical Research Training Program FX Supported by the National Institute of Neurological Disorders and Stroke, Division of Intramural Research (grant no. Z01NS003030) a competitive intramural postdoctoral fellowship, and the National Institutes of Health Clinical Research Training Program. NR 39 TC 5 Z9 5 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 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 2014 VL 95 IS 5 BP 849 EP 856 DI 10.1016/j.apmr.2013.12.023 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AG3CW UT WOS:000335294400008 PM 24440364 ER PT J AU Ma, VY Chan, L Carruthers, KJ AF Ma, Vincent Y. Chan, Leighton Carruthers, Kadir J. TI Incidence, Prevalence, Costs, and Impact on Disability of Common Conditions Requiring Rehabilitation in the United States: Stroke, Spinal Cord Injury, Traumatic Brain Injury, Multiple Sclerosis, Osteoarthritis, Rheumatoid Arthritis, Limb Loss, and Back Pain SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Review DE Amputation; Back pain; Cost of disease; Cost of illness; Direct service costs; Disabled persons; Disease costs; Incidence; Multiple sclerosis; Osteoarthritis; Prevalence; Rehabilitation; Rheumatoid arthritis; Spinal cord injuries; Traumatic brain injury ID AMERICAN-HEART-ASSOCIATION; LONG-TERM DISABILITY; HEALTH-CARE COSTS; WORK DISABILITY; MEDICAL EXPENDITURES; PRODUCTIVE TIME; US; UPDATE; RISK; POPULATION AB Objective: To determine the relative incidence, prevalence, costs, and impact on disability of 8 common conditions treated by rehabilitation professionals. Data Sources: Comprehensive bibliographic searches using MEDLINTE, Google Scholar, and UpToDate, (June, 2013). Data Extraction: Two review authors independently screened the search results and performed data extraction. Eighty-two articles were identified that had relevant data on the following conditions: Stroke, Spinal Cord Injury, Traumatic Brain Injury, Multiple Sclerosis, Osteoarthritis, Rheumatoid Arthritis, Limb Loss, and Back Pain. Data Synthesis: Back pain and arthritis (osteoarthritis, rheumatoid arthritis) are the most common and costly conditions we analyzed, affecting more than 100 million individuals and costing greater than $200 billion per year. Traumatic brain injury, while less common than arthritis and back pain, carries enormous per capita direct and indirect costs, mostly because of the young age of those involved and the severe disability that it may cause. Finally, stroke, which is often listed as the most common cause of disability, is likely second to both arthritis and back pain in its impact on functional limitations. Conclusions: Of the common rehabilitation diagnoses we studied, musculoskeletal conditions such as back pain and arthritis likely have the most impact on the health care system because of their high prevalence and impact on disability. (C) 2014 by the American Congress of Rehabilitation Medicine C1 [Ma, Vincent Y.; Chan, Leighton; Carruthers, Kadir J.] NIH, Ctr Clin, Dept Rehabil Med, Bethesda, MD 20892 USA. [Ma, Vincent Y.; Carruthers, Kadir J.] Case Western Univ, Sch Med, Cleveland, OH USA. RP Chan, L (reprint author), NIH, Ctr Clin, Dept Rehabil Med, Bldg 10,Rm 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. EM chanle@cc.nih.gov FU National Institutes of Health Intramural Research Program FX Supported by resources from the National Institutes of Health Intramural Research Program. NR 87 TC 73 Z9 73 U1 23 U2 86 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 2014 VL 95 IS 5 BP 986 EP 995 DI 10.1016/j.apmr.2013.10.032 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AG3CW UT WOS:000335294400025 PM 24462839 ER PT J AU Allen, HF Daze, KD Shimbo, T Lai, A Musselman, CA Sims, JK Wade, PA Hof, F Kutateladze, TG AF Allen, Hillary F. Daze, Kevin D. Shimbo, Takashi Lai, Anne Musselman, Catherine A. Sims, Jennifer K. Wade, Paul A. Hof, Fraser Kutateladze, Tatiana G. TI Inhibition of histone binding by supramolecular hosts SO BIOCHEMICAL JOURNAL LA English DT Article DE calixarene; chromodomain helicase DNA-binding protein 4 (CHD4); histone; inhibitor; methylation; plant homeodomain (PHD) ID HP1 CHROMO DOMAIN; SELECTIVE RECOGNITION; METHYLATED LYSINE; H3; COMPLEX; DEACETYLASE; PROTEIN; HETEROCHROMATIN; FLUORESCENT; DISCOVERY AB The tandem PHD (plant homeodomain) fingers of the CHD4 (chromodomain helicase DNA-binding protein 4) ATPase are epigenetic readers that bind either unmodified histone H3 tails or H3K9me3 (histone H3 trimethylated at Lys(9)). This dual function is necessary for the transcriptional and chromatin remodelling activities of the NuRD (nucleosome remodelling and deacetylase) complex. In the present paper, we show that calixarene-based supramolecular hosts disrupt binding of the CHD4 PHD2 finger to H3K9me3, but do not affect the interaction of this protein with the H3K9me0 (unmodified histone H3) tail. A similar inhibitory effect, observed for the association of chromodomain of HP1 gamma (heterochromatin protein 1 gamma) with H3K9me3, points to a general mechanism of methyl-lysine caging by calixarenes and suggests a high potential for these compounds in biochemical applications Immunofluorescence analysis reveals that the supramolecular agents induce changes in chromatin organization that are consistent with their binding to and disruption of H3K9me3 sites in living cells. The results of the present study suggest that the aromatic macrocyclic hosts can be used as a powerful new tool for characterizing methylation-driven epigenetic mechanisms. C1 [Allen, Hillary F.; Musselman, Catherine A.; Kutateladze, Tatiana G.] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO 80045 USA. [Daze, Kevin D.; Hof, Fraser] Univ Victoria, Dept Chem, Victoria, BC V8W 3V6, Canada. [Shimbo, Takashi; Lai, Anne; Sims, Jennifer K.; Wade, Paul A.] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Hof, F (reprint author), Univ Victoria, Dept Chem, Victoria, BC V8W 3V6, Canada. EM fhof@uvic.ca; tatiana.kutateladze@ucdenver.edu OI Hof, Fraser/0000-0003-4658-9132 FU NIH (National Institutes for Health) [GM096863, GM101664]; WestCoast Ride to Live; Prostate Cancer Foundation of BC; Prostate Cancer Canada Pilot Grant; Intramural Research Program of the NIEHS (National Institute of Environmental Health Sciences) [Z01ES101965]; Neuroscience Graduate Training Grant [T32HD041697] FX This work was supported by the NIH (National Institutes for Health) [grant number GM096863 and GM101664 (to T.G.K)], WestCoast Ride to Live (to K.D.D. and F.H.), the Prostate Cancer Foundation of BC (to K.D.D.), a Prostate Cancer Canada Pilot Grant (to F.H.), and by the Intramural Research Program of the NIEHS (National Institute of Environmental Health Sciences) [grant number Z01ES101965 (to P.A.W.)]. H.F.A. is supported by a Neuroscience Graduate Training Grant [grant number T32HD041697]. F.H. is a Canada Research Chair. NR 37 TC 16 Z9 16 U1 2 U2 35 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD MAY 1 PY 2014 VL 459 BP 505 EP 512 DI 10.1042/BJ20140145 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AG0SJ UT WOS:000335125600007 PM 24576085 ER PT J AU Pine, DS AF Pine, Daniel S. TI Therapeutics and the Developmental Neurobiology of Anxiety SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE anxiety; attention; amygdala; fMRI C1 [Pine, Daniel S.] NIMH, Bethesda, DC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 15 BP 5S EP 6S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800017 ER PT J AU Thanos, P Ananth, M Volkow, N Dow-Edwards, D AF Thanos, Peter Ananth, Mala Volkow, Nora Dow-Edwards, Diana TI Sex Differences in Cocaine-Induced Brain Activation in Cocaine Sensitized Rats SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE animal model; functional connectivity; psychostimulants; behavior; neuroimaging C1 [Thanos, Peter] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Ananth, Mala] SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA. [Volkow, Nora] NIDA, NIH, Bethesda, MD 20892 USA. [Dow-Edwards, Diana] Suny Downstate Med Ctr, Dept Physiol & Pharmacol, Brooklyn, NY 11203 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 17 BP 6S EP 6S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800019 ER PT J AU Newcorn, J Duhoux, S Schulz, K Krone, B Bedard, AC Pedraza, J Adler, L White, S Blair, J AF Newcorn, Jeffrey Duhoux, Stephanie Schulz, Kurt Krone, Beth Bedard, Anne-Claude Pedraza, Juan Adler, Lenard White, Stuart Blair, James TI Effects of Lisdexamfetamine (Vyvanse (R)) on Reward Processing SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE ADHD; fMRI; Stimulants; Psychopharmacology; reward circuitry C1 [Newcorn, Jeffrey; Duhoux, Stephanie; Schulz, Kurt; Krone, Beth; Bedard, Anne-Claude; Pedraza, Juan] Icahn Sch Med Mt Sinai, New York, NY USA. [Adler, Lenard] NYU, Sch Med, New York, NY USA. [White, Stuart; Blair, James] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 19 BP 7S EP 7S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800021 ER PT J AU Gorelick, DA Kochunov, P Holcomb, HH Boggs, DL Yang, YH West, JT Wittenberg, GF Lee, MR Huestis, MA AF Gorelick, David A. Kochunov, Peter Holcomb, Henry H. Boggs, Douglas L. Yang, Yihong West, Jeffrey T. Wittenberg, George F. Lee, Mary R. Huestis, Marilyn A. TI Effect of Transcranial Magnetic Stimulation (TMS) on Brain White Matter Tracts in Nicotine-Dependent Adults SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE transcranial magnetic stimulation; diffusion tensor imaging; fractional anisotropy; fMRI; nicotine dependence C1 [Gorelick, David A.; Kochunov, Peter; Holcomb, Henry H.; Boggs, Douglas L.; West, Jeffrey T.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Gorelick, David A.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, Baltimore, MD USA. [Boggs, Douglas L.] Yale Univ, VA CT Healthcare Syst, New Haven, CT USA. [Boggs, Douglas L.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Yang, Yihong; Lee, Mary R.] NIDA, Magnet Resonance Imaging & Spect Sect, Intramural Res Program, Nihon Univ, Baltimore, MD USA. [Wittenberg, George F.] Univ Maryland, Sch Med, VA MD Healthcare Syst, Baltimore, MD 21201 USA. [Wittenberg, George F.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 50 BP 17S EP 17S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800052 ER PT J AU Lisanby, SH Husain, MM Knapp, RG Mueller, M McCall, WV Petriedes, G Young, RC Weiner, R McClintock, SM Greenberg, RM Sampson, S Prudic, J Rudorfer, MV Kellner, CH AF Lisanby, Sarah Hollingsworth Husain, Mustafa M. Knapp, Rebecca G. Mueller, Martina McCall, W. Vaughn Petriedes, Georgios Young, Robert C. Weiner, Richard McClintock, Shawn M. Greenberg, Robert M. Sampson, Shirlene Prudic, Joan Rudorfer, Matthew V. Kellner, Charles H. CA Prolonging Remission Depressed TI Ultrabrief Right Unilateral ECT in Geriatric Depression: Antidepressant and Cognitive Outcomes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE electroconvulsive therapy; depression; ultrabrief pulse; elderly; cognition C1 [Lisanby, Sarah Hollingsworth; Husain, Mustafa M.; Weiner, Richard; McClintock, Shawn M.] Duke Univ, Durham, NC USA. [Husain, Mustafa M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Knapp, Rebecca G.; Mueller, Martina] Med Univ S Carolina, Charleston, SC 29425 USA. [McCall, W. Vaughn] Georga Regents Univ, Augusta, GA USA. [Petriedes, Georgios] North Shore LIH Hlth Syst, New Hyde Pk, NY USA. [Young, Robert C.] Cornell, White Plains, NC USA. [Greenberg, Robert M.] Lutheran Med Ctr, Brooklyn, NY USA. [Sampson, Shirlene] Mayo, Rochester, MN USA. [Prudic, Joan] Columbia Univ, New York, NY USA. [Rudorfer, Matthew V.] NIMH, Bethesda, MD 20892 USA. [Kellner, Charles H.] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 61 BP 21S EP 21S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800063 ER PT J AU Maynard, KR Lu, B Tessarollo, L Schloesser, RJ Martinowich, K AF Maynard, Kristen R. Lu, Bai Tessarollo, Lino Schloesser, Robert J. Martinowich, Keri TI Loss of BDNF Production from Promoter I Impairs Serotonin Signaling and Increases Aggression in Male Mice SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE BDNF; transcription; aggression; serotonin; hypothalamus C1 [Maynard, Kristen R.; Schloesser, Robert J.; Martinowich, Keri] Johns Hopkins Med Campus, Lieber Inst Brain Dev, Baltimore, MD USA. [Lu, Bai] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China. [Tessarollo, Lino] NCI, Unit Mouse Genet, Frederick, MD 21701 USA. [Schloesser, Robert J.] Univ Maryland, Dept Psychiat, Baltimore, MD 21201 USA. [Martinowich, Keri] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Martinowich, Keri] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 128 BP 39S EP 39S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800121 ER PT J AU Schloesser, RJ Jimenez, DV Mou, ZY Palaguachi, GI Mikhnev, D Hill, JL Maynard, KR Gavrilova, O Tessarollo, L Lu, B Han, JC Martinowich, K AF Schloesser, Robert J. Jimenez, Dennisse V. Mou, Zongyang Palaguachi, Gladys I. Mikhnev, Dmytro Hill, Julia L. Maynard, Kristen R. Gavrilova, Oksana Tessarollo, Lino Lu, Bai Han, Joan C. Martinowich, Keri TI Disruption of Brain-Derived Neurotrophic Factor (BDNF) from Promoter I and II, but not IV or VI Leads to Hyperphagia and Obesity SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE BDNF; obesity; splice variants; transgenic; neuroplasticity C1 [Schloesser, Robert J.] Univ Maryland, Dept Psychiat, Baltimore, MD 21201 USA. [Jimenez, Dennisse V.; Maynard, Kristen R.; Martinowich, Keri] Lieber Inst Brain Dev, Grp Neural Plast, Baltimore, MD USA. [Mou, Zongyang; Palaguachi, Gladys I.; Mikhnev, Dmytro; Han, Joan C.] NICHD, Unit Metab & Neuroendocrinol, Bethesda, MD USA. [Gavrilova, Oksana] NIDDK, Bethesda, MD 20892 USA. [Tessarollo, Lino] NCI, Neural Dev Sect, Frederick, MD 21701 USA. [Lu, Bai] Tsinghua Univ, Dept Med, Beijing 100084, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 127 BP 39S EP 39S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800122 ER PT J AU Richards, EM Mathews, DC Machado-Vieira, R Luckenbaugh, DA Niciu, MJ Ionescu, DF Nolan, N Franco-Chaves, JA Hudzik, T Maciag, C Li, S Smith, MA Cross, A Zarate, CA AF Richards, Erica M. Mathews, Daniel C. Machado-Vieira, Rodrigo Luckenbaugh, David A. Niciu, Mark J. Ionescu, Dawn F. Nolan, Neil Franco-Chaves, Jose A. Hudzik, Thomas Maciag, Carla Li, Shuang Smith, Mark A. Cross, Alan Zarate, Carlos A. TI A Randomized, Placebo-Controlled, Pilot Trial of a Delta Opioid Agonist in Patients with Anxious Major Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE anxiety; VEGF; BDNF; mood; preclinical C1 [Richards, Erica M.; Mathews, Daniel C.; Machado-Vieira, Rodrigo; Luckenbaugh, David A.; Niciu, Mark J.; Ionescu, Dawn F.; Nolan, Neil; Franco-Chaves, Jose A.; Zarate, Carlos A.] NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Hudzik, Thomas; Maciag, Carla; Li, Shuang; Smith, Mark A.; Cross, Alan] AstraZeneca, Neurosci Innovat Med, Cambridge, MA USA. RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Cross, Alan/L-5456-2016 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Cross, Alan/0000-0002-2992-2258 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 146 BP 45S EP 45S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800140 ER PT J AU de Sousa, RT Zanetti, MV Gattaz, WF Machado-Vieira, R Teixeira, AL AF de Sousa, Rafael T. Zanetti, Marcus V. Gattaz, Wagner F. Machado-Vieira, Rodrigo Teixeira, Antonio L. TI Soluble Tumor Necrosis Factor Receptor 1 and 2 in Bipolar Depression and the Association with Lithium Treatment SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat C1 [de Sousa, Rafael T.; Zanetti, Marcus V.; Gattaz, Wagner F.; Machado-Vieira, Rodrigo] Univ Sao Paulo, Neurosci Lab, Sao Paulo, Brazil. [Zanetti, Marcus V.] Univ Sao Paulo, Lab Neuroimaging Psychiat, Sao Paulo, Brazil. [Machado-Vieira, Rodrigo] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, Sao Paulo, Brazil. [Machado-Vieira, Rodrigo] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. [Teixeira, Antonio L.] Univ Fed Minas Gerais, Sch Med, Interdisciplinary Lab Med Invest, Belo Horizonte, MG, Brazil. [Teixeira, Antonio L.] Univ Fed Minas Gerais, Neuropsychiat Branch, Belo Horizonte, MG, Brazil. RI Gattaz, Wagner/C-4456-2012; MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 154 BP 47S EP 48S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800148 ER PT J AU Orel, J Apud, J Berman, K Dickinson, D AF Orel, Jennifer Apud, Jose Berman, Karen Dickinson, Dwight TI Sub-grouping Schizophrenia: Cluster Analysis, PANSS Ratings, and Deficit Syndrome SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE schizophrenia; deficit syndrome; subtypes; negative symptoms; PANSS C1 [Orel, Jennifer; Apud, Jose; Berman, Karen; Dickinson, Dwight] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 206 BP 64S EP 64S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800200 ER PT J AU Lewis, EJ Geraci, M Blair, J Blair, K AF Lewis, Elizabeth J. Geraci, Marilla Blair, James Blair, Karina TI Patients with Generalized Anxiety Disorder, but not Generalized Social Phobia, Show a Lack of Optimism Related to Rostral Medial Prefrontal Cortex Dysfunction SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE generalized anxiety disorder; generalized social phobia; optimism; rostral medial prefrontal cortex; fMRI C1 [Lewis, Elizabeth J.; Blair, James; Blair, Karina] NIMH, Sect Affect Cognit Neurosci, Bethesda, MD 20892 USA. [Geraci, Marilla] NIMH, Clin Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 207 BP 65S EP 65S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800201 ER PT J AU Chen, DTW McMahon, FJ AF Chen, David T. W. McMahon, Francis J. CA BiGs TI Advanced Parental Age is Associated with Earlier Age at Onset in Bipolar Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Bipolar Disorder; Advanced Parental Age; Early Onset C1 [Chen, David T. W.; McMahon, Francis J.; BiGs] NIMH, Human Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 231 BP 72S EP 72S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800225 ER PT J AU Kim, DW Hawariat, G Anderson, N Chen, DTW McMahon, FJ AF Kim, Dong W. Hawariat, Girma Anderson, Natalie Chen, David T. W. McMahon, Francis J. TI Heritable Dimensions of Major Mood Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat C1 [Kim, Dong W.; Hawariat, Girma; Anderson, Natalie; Chen, David T. W.; McMahon, Francis J.] NIMH, Human Genet Unit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 230 BP 72S EP 72S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800224 ER PT J AU Raznahan, A Lee, NR Greenstein, D Wallace, GL Blumenthal, J Clasen, L Giedd, JN AF Raznahan, Armin Lee, Nancy R. Greenstein, Deanna Wallace, Gregory L. Blumenthal, Jonathan Clasen, Liv Giedd, Jay N. TI Globally Divergent but Locally Convergent X and Y Chromosome Influences on Brain Development SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Aneuploidy; Cortical Thickness; Surface Area; Pseudoautosomal; Allen Brain Atlas C1 [Raznahan, Armin; Lee, Nancy R.; Greenstein, Deanna; Wallace, Gregory L.; Blumenthal, Jonathan; Clasen, Liv; Giedd, Jay N.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RI Giedd, Jay/J-9644-2015; Lee, Nancy/M-7492-2016 OI Giedd, Jay/0000-0003-2002-8978; Lee, Nancy/0000-0002-6663-0713 NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 273 BP 86S EP 86S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800267 ER PT J AU Banerjee, D Nugent, AC Ionescu, DF Niciu, MJ Richards, EM Furey, ML Zarate, C AF Banerjee, Dipavo Nugent, Allison C. Ionescu, Dawn F. Niciu, Mark J. Richards, Erica M. Furey, Maura L. Zarate, Carlos TI Altered White Matter Integrity May Predict Response to Ketamine in Major Depressive Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE DTI; depression; ketamine; white matter; mood disorders C1 [Banerjee, Dipavo; Nugent, Allison C.; Ionescu, Dawn F.; Niciu, Mark J.; Richards, Erica M.; Furey, Maura L.; Zarate, Carlos] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 308 BP 97S EP 97S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800302 ER PT J AU Chen, Q Bassett, DS Rasetti, R Callicott, JH Mattay, VS Weinberger, DR AF Chen, Qiang Bassett, Danielle S. Rasetti, Roberta Callicott, Joseph H. Mattay, Venkata S. Weinberger, Daniel R. TI Altered Graph Theory Measures of Brain Networks in Patients with Schizophrenia: Potential Intermediate Phenotypes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE fMRI; Graph Theory; intermediate phenotype; schizophrenia C1 [Chen, Qiang; Mattay, Venkata S.; Weinberger, Daniel R.] Lieber Inst Brain Dev, Baltimore, MD USA. [Bassett, Danielle S.] Univ Penn, Sch Engn & Appl Sci, Philadelphia, PA 19104 USA. [Rasetti, Roberta] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Callicott, Joseph H.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 342 BP 109S EP 109S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800336 ER PT J AU Radulescu, E Chen, Q Ursini, G Zhang, FY Callicott, J Song, HJ Ming, GL Mattay, V Weinberger, DR AF Radulescu, Eugenia Chen, Qiang Ursini, Gianluca Zhang, Fengyu Callicott, Joseph Song, Hongjun Ming, Guo-Li Mattay, Venkata Weinberger, Daniel R. TI Confirmation of Schizophrenia Risk Associated Epistasis Within the Wave Complex in Cortical Function Measured with fMRI SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE WAVE complex; DLPFC; working memory; epistasis; fMRI C1 [Radulescu, Eugenia; Chen, Qiang; Ursini, Gianluca; Zhang, Fengyu; Mattay, Venkata; Weinberger, Daniel R.] Lieber Inst Brain Dev, Div Clin Sci, Baltimore, MD USA. [Callicott, Joseph] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Song, Hongjun; Ming, Guo-Li] Johns Hopkins Univ, Sch Med, Dept Neurol, Solomon H Snyder Dept Neurosci,Inst Cell Engn, Baltimore, MD 21205 USA. [Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD USA. [Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 343 BP 110S EP 110S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800337 ER PT J AU Ellis, JS Luckenbaugh, DA Zarate, CA Furey, ML AF Ellis, Jessica S. Luckenbaugh, David A. Zarate, Carlos A. Furey, Maura L. TI Effects of Ketamine v. Scopolamine on Individual Depression and Anxiety Symptoms SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE depression; anxiety; ketamine; scopolamine; antidepressant C1 [Ellis, Jessica S.; Luckenbaugh, David A.; Zarate, Carlos A.; Furey, Maura L.] NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 396 BP 127S EP 127S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800390 ER PT J AU Ionescu, DF Luckenbaugh, DA Slonena, EE Niciu, MJ Richards, EM Zarate, CA AF Ionescu, Dawn F. Luckenbaugh, David A. Slonena, Elizabeth E. Niciu, Mark J. Richards, Erica M. Zarate, Carlos A. TI A Comparison of Mood Improvements Following a Single Infusion of an N-methyl-D-aspartate (NMDA) Antagonist in Treatment-Resistant Patients with Anxious and Non-Anxious Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Anxious Depression; Ketamine; Treatment Resistant Depression C1 [Ionescu, Dawn F.; Luckenbaugh, David A.; Slonena, Elizabeth E.; Niciu, Mark J.; Richards, Erica M.; Zarate, Carlos A.] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 397 BP 127S EP 128S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800391 ER PT J AU Slonena, EE Luckenbaugh, DA Saligan, LN Ionescu, DF Lukkahatai, N Machado-Vieira, R Zarate, CA AF Slonena, Elizabeth E. Luckenbaugh, David A. Saligan, Leorey N. Ionescu, Dawn F. Lukkahatai, Nada Machado-Vieira, Rodrigo Zarate, Carlos A. TI A Single-Infusion of the N-methyl-D-aspartate Receptor Antagonist Ketamine Improves Fatigue Scores in Patients with Bipolar Disorder Compared to Placebo SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Bipolar Disorder; Ketamine; Treatment resistant depression; Fatigue C1 [Slonena, Elizabeth E.; Luckenbaugh, David A.; Ionescu, Dawn F.; Machado-Vieira, Rodrigo; Zarate, Carlos A.] NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Saligan, Leorey N.; Lukkahatai, Nada] NINR, NIH, Bethesda, MD 20892 USA. RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 395 BP 127S EP 127S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800389 ER PT J AU Lundin, NB Niciu, MJ Luckenbaugh, DA Ionescu, DF Richards, EM Zarate, CA AF Lundin, Nancy B. Niciu, Mark J. Luckenbaugh, David A. Ionescu, Dawn F. Richards, Erica M. Zarate, Carlos A. TI Do Vitamin B12 and Folate Predict Antidepressant Response to Ketamine in Bipolar Depression? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Ketamine; Vitamin B12; Bipolar Disorder; Folate; Treatment-Resistant Depression C1 [Lundin, Nancy B.; Niciu, Mark J.; Luckenbaugh, David A.; Ionescu, Dawn F.; Richards, Erica M.; Zarate, Carlos A.] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 398 BP 128S EP 128S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800392 ER PT J AU Niciu, MJ Luckenbaugh, DA Ionescu, DF Guevara, S Machado-Vieira, R Richards, EM Brutsche, NE Zarate, CA AF Niciu, Mark J. Luckenbaugh, David A. Ionescu, Dawn F. Guevara, Sara Machado-Vieira, Rodrigo Richards, Erica M. Brutsche, Nancy E. Zarate, Carlos A. TI Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE clinical predictors; moderators; mediators; major depression; ketamine C1 [Niciu, Mark J.; Luckenbaugh, David A.; Ionescu, Dawn F.; Guevara, Sara; Machado-Vieira, Rodrigo; Richards, Erica M.; Brutsche, Nancy E.; Zarate, Carlos A.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 399 BP 128S EP 128S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800393 ER PT J AU Szczepanik, J Furey, M Nugent, A Luckenbaugh, D Zarate, C AF Szczepanik, Joanna Furey, Maura Nugent, Allison Luckenbaugh, David Zarate, Carlos TI Amygdala Response to Processing Emotion at Baseline Predicts Antidepressant Effect of Ketamine SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat C1 [Szczepanik, Joanna; Furey, Maura; Nugent, Allison; Luckenbaugh, David; Zarate, Carlos] NIMH, ETPB, Bethesda, MD 20892 USA. [Szczepanik, Joanna] Univ Maryland, Neurosci & Cognit Sci Program, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 400 BP 128S EP 129S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101800394 ER PT J AU Innis, R AF Innis, Robert TI PET Imaging of Translocator Protein (TSPO) in Brain as a Marker of Localized Inflammation in Epilepsy and of Generalized Inflammation in Alzheimer's Disease SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE translocator protein; positron emission tomography; Alzheimer's disease; epilepsy; depression C1 [Innis, Robert] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 527 BP 143S EP 144S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801028 ER PT J AU Insel, TR AF Insel, Thomas R. TI Overview of the NIMH Experimental Medicine Approach SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Clinical Trials; Experimental Medicine; Mental Illness; Novel Targets; Treatment Development C1 [Insel, Thomas R.] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 533 BP 145S EP 145S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801034 ER PT J AU Dracheva, S Di Narzo, AF Kozlenkov, A Roussos, P Hao, K Hurd, Y Sibille, E Koonin, E AF Dracheva, Stella Di Narzo, Antonio Fabio Kozlenkov, Alexey Roussos, Panos Hao, Ke Hurd, Yasmin Sibille, Etienne Koonin, Eugene TI Unique Gene Expression Signature Associated with Serotonin 2C Receptor (5-HT2CR) RNA Editing in the Prefrontal Cortex and Altered in Suicide SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE serotonin 2C receptor; mRNA editing; suicide; gene expression C1 [Dracheva, Stella; Kozlenkov, Alexey; Roussos, Panos] Bronx VA Med Ctr, Bronx, NY USA. [Dracheva, Stella; Kozlenkov, Alexey; Roussos, Panos; Hurd, Yasmin] Icahn Sch Med Mt Sinai, New York, NY USA. 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TI Learning from Other People's Fear: Amygdala-based Social Reference Learning in Social Phobia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE generalized social phobia; social referencing; fMRI; amygdala; dorsomedial prefrontal cortex C1 [Lewis, Elizabeth J.; Blair, James R.; Blair, Karina S.] NIMH, Sect Affect Cognit Neurosci, Bethesda, MD 20892 USA. [Geraci, Marilla] NIMH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 671 BP 191S EP 192S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801172 ER PT J AU Ernst, M AF Ernst, Monique TI Alteration in Corticostriatal Function in Adolescent Anxiety SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE cortico-striatal function; reward; contingency; motivation; anxiety C1 [Ernst, Monique] NIMH, Bethesda, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 672 BP 192S EP 192S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801173 ER PT J AU Iadarola, ND Nugent, AC Niciu, MJ Salvadore, G Marquardt, C Holroyd, T Furey, ML Zarate, CA AF Iadarola, Nicolas D. Nugent, Allison C. Niciu, Mark J. Salvadore, Giacomo Marquardt, Craig Holroyd, Tom Furey, Maura L. Zarate, Carlos A. TI Differences During a Working Memory Task in Bipolar Depression as Detected by Magnetoencephalography SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Bipolar Disorder; MEG; N-Back; Working Memory C1 [Iadarola, Nicolas D.; Nugent, Allison C.; Niciu, Mark J.; Furey, Maura L.; Zarate, Carlos A.] NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Salvadore, Giacomo] Johnson & Johnson Pharmaceut, Neurosci Expt Med, Titusville, NJ USA. [Marquardt, Craig] Univ Minnesota Twin Cities, Dept Psychol, Minneapolis, MN USA. [Holroyd, Tom] NIMH, NIMH MEG Core Facil, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 684 BP 195S EP 196S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801185 ER PT J AU Miller, S Suppes, T Hellemann, G Frye, M McElroy, S Nolen, W Kupka, R Leverich, G Grunze, H Altshuler, L Keck, P Post, R AF Miller, Shefali Suppes, Trisha Hellemann, Gerhard Frye, Mark McElroy, Susan Nolen, Willem Kupka, Ralph Leverich, Gabriele Grunze, Heinz Altshuler, Lori Keck, Paul Post, Robert TI Mixed Depression in the Stanley Foundation Bipolar Treatment Network: Prevalence Rate and Clinical Correlates During Naturalistic Follow Up SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE bipolar disorder; mixed; depression; prevalence; phenomenology C1 [Miller, Shefali; Suppes, Trisha] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Hellemann, Gerhard; Altshuler, Lori] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Frye, Mark] Mayo Clin, Dept Psychiat, Rochester, MN USA. [McElroy, Susan; Keck, Paul] Univ Cincinnati, Dept Psychiat, Lindner Ctr HOPE, Cincinnati, OH USA. [Nolen, Willem] Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands. [Kupka, Ralph] Altrecht Ctr Mental Hlth Care, Dept Psychiat, Utrecht, Netherlands. [Kupka, Ralph] Univ Med Ctr, Utrecht, Netherlands. [Leverich, Gabriele] NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. [Grunze, Heinz] Newcastle Univ, Dept Clin Psychiat, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Post, Robert] George Washington Univ, Dept Psychiat & Behav Sci, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 736 BP 212S EP 212S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801236 ER PT J AU Healy, K Chen, Q Das, S Kolachana, B Cheng, X Berman, KF Weinberger, DR Mattay, VS AF Healy, Kaitlin Chen, Qiang Das, Saumitra Kolachana, Bhaskar Cheng, Xi Berman, Karen F. Weinberger, Daniel R. Mattay, Venkata S. TI Interactive Effects of APOE and WWC1 Genes on Hippocampal Function Across the Adult Lifespan SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Genetics; Aging; Cognition; fMRI; Hippocampus C1 [Healy, Kaitlin; Chen, Qiang; Das, Saumitra; Kolachana, Bhaskar; Cheng, Xi; Berman, Karen F.; Weinberger, Daniel R.; Mattay, Venkata S.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [Chen, Qiang; Cheng, Xi; Weinberger, Daniel R.; Mattay, Venkata S.] Lieber Inst Brain Dev, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 740 BP 213S EP 214S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801240 ER PT J AU Chuang, YF Tanaka, T Beason-Held, LL An, Y Terracciano, A Sutin, AR Kraut, M Singleton, AB Resnick, SM Thambisetty, M AF Chuang, Yi-Fang Tanaka, Toshiko Beason-Held, Lori L. An, Yang Terracciano, Antonio Sutin, Angelina R. Kraut, Michael Singleton, Andrew B. Resnick, Susan M. Thambisetty, Madhav TI FTO Genotype and Aging: Pleiotropic Longitudinal Effects on Adiposity, Brain Function, Impulsivity and Diet SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE FTO gene; adiposity; brain function; medial prefronal; impulsivity C1 [Chuang, Yi-Fang; Thambisetty, Madhav] NIA, Clin & Translat Neurosci Unit, Lab Behav Neurosci, Baltimore, MD 21224 USA. [Tanaka, Toshiko] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Beason-Held, Lori L.; An, Yang; Resnick, Susan M.] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA. [Terracciano, Antonio; Sutin, Angelina R.] Florida State Univ, Coll Med, Tallahassee, FL 32306 USA. [Kraut, Michael] Johns Hopkins Med Inst, Dept Radiol, Baltimore, MD 21205 USA. [Singleton, Andrew B.] NIA, Lab Neurogenet, Baltimore, MD 21224 USA. RI Singleton, Andrew/C-3010-2009 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 741 BP 214S EP 214S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801241 ER PT J AU McFadden, WC Ye, TZ Ortiz, JP Herman, M Hyde, TM Kleinman, JE AF McFadden, Whitney C. Ye, Tianzhang Ortiz, Jose Paltan Herman, Mary Hyde, Thomas M. Kleinman, Joel E. TI Uniform Distribution of Interstitial White Matter Neurons in Dorsolateral Prefrontal Cortex SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE schizophrenia; neuropathology; genetics; post-mortem human brain; white matter neuron C1 [McFadden, Whitney C.; Ortiz, Jose Paltan; Herman, Mary] NIMH, NIH, Bethesda, MD 20892 USA. [Ye, Tianzhang; Hyde, Thomas M.; Kleinman, Joel E.] Johns Hopkins Univ, Lieber Inst Brain Dev, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 749 BP 217S EP 217S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801249 ER PT J AU Hwang, S Nolan, ZT White, SF Sinclair, S Blair, J AF Hwang, Soonjo Nolan, Zachary T. White, Stuart F. Sinclair, Steve Blair, James TI Interaction Between Cognitive Control and Emotional Responding in ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Attention Deficit Hyperactivity Disorder; Affective Stroop; Top down attention control; Emotional processing; functional MRI C1 [Hwang, Soonjo; Nolan, Zachary T.; White, Stuart F.; Sinclair, Steve; Blair, James] NIMH, Sect Affect Cognit Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 790 BP 230S EP 230S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801290 ER PT J AU Wiggins, JL Swartz, JR Peltier, SJ Lord, C Monk, CS AF Wiggins, Jillian Lee Swartz, Johnna R. Peltier, Scott J. Lord, Catherine Monk, Christopher S. TI Context-dependent Amygdala-prefrontal Connectivity in Youth with Autism Spectrum Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE autism; amygdala; fMRI; connectivity; prefrontal C1 [Wiggins, Jillian Lee] NIH, Emot & Dev Branch, Bethesda, MD 20892 USA. [Swartz, Johnna R.] Univ N Carolina, Ctr Dev Sci, Chapel Hill, NC USA. [Swartz, Johnna R.] Duke Univ, Lab Neurogenet, Durham, NC USA. [Peltier, Scott J.] Univ Michigan, Funct MRI Lab, Ann Arbor, MI 48109 USA. [Lord, Catherine] Weill Cornell Med Coll, New York, NY USA. [Monk, Christopher S.] Univ Michigan, Ann Arbor, MI 48109 USA. RI Monk, Christopher/J-1805-2014 NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 791 BP 230S EP 230S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801291 ER PT J AU Anvari, AA Friedman, LA Greenstein, D Gochman, P Gogtay, N Rapoport, JL AF Anvari, Afsoon A. Friedman, Lisa A. Greenstein, Deanna Gochman, Peter Gogtay, Nitin Rapoport, Judith L. TI The Hippocampus and Childhood-Onset Schizophrenia: An Anatomical Approach to Understanding Clinical Outcome SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Hippocampus; Schizophrenia; Childhood-onset; longitudinal C1 [Anvari, Afsoon A.; Friedman, Lisa A.; Greenstein, Deanna; Gochman, Peter; Gogtay, Nitin; Rapoport, Judith L.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 838 BP 246S EP 246S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801338 ER PT J AU Bartholomew, ME Lau, WY Baranger, DAA Feighery, EL Mattay, VS Rypma, B Dickinson, D Berman, KF Weinberger, DR Callicott, JH AF Bartholomew, Morgan E. Lau, Wendy Y. Baranger, David A. A. Feighery, Emer L. Mattay, Venkata S. Rypma, Bart Dickinson, Dwight Berman, Karen F. Weinberger, Daniel R. Callicott, Joseph H. TI Further Evidence for Prefrontal Dysfunction Underlying Processing Speed Deficits in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Schizophrenia; Processing Speed; Dorsolateral Prefrontal Cortex; intermediate phenotype C1 [Bartholomew, Morgan E.; Lau, Wendy Y.; Baranger, David A. A.; Feighery, Emer L.; Dickinson, Dwight; Berman, Karen F.; Callicott, Joseph H.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [Mattay, Venkata S.; Weinberger, Daniel R.] Lieber Inst Brain Dev, Baltimore, MD USA. [Rypma, Bart] Univ Texas Dallas, Ctr Brain Hlth, Dallas, TX 75230 USA. [Rypma, Bart] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Weinberger, Daniel R.] Johns Hopkins Univ Med, Baltimore, MD USA. [Weinberger, Daniel R.] Johns Hopkins Univ Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 839 BP 246S EP 246S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801339 ER PT J AU Pratt, D Callicott, JH Weinberger, DR Berman, KF Dickinson, D AF Pratt, Danielle Callicott, Joseph H. Weinberger, Daniel R. Berman, Karen F. Dickinson, Dwight TI Intracranial Volume Predicts Symptomatology in a Large Schizophrenia Sample SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Schizophrenia; Brain structure; Positive and Negative Syndrome Scale; Intracranial volume C1 [Pratt, Danielle; Callicott, Joseph H.; Weinberger, Daniel R.; Berman, Karen F.; Dickinson, Dwight] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 840 BP 246S EP 246S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801340 ER PT J AU Dickinson, D Callicott, JH Orel, J Pratt, D Weinberger, DR Berman, KF AF Dickinson, Dwight Callicott, Joseph H. Orel, Jennifer Pratt, Danielle Weinberger, Daniel R. Berman, Karen F. TI Using Symptom Clusters to Reveal Differences in Cognition/Intracranial Volume Relationships in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE schizophrenia; cluster analysis; intracranial volume; cognition; PANSS C1 [Dickinson, Dwight; Callicott, Joseph H.; Orel, Jennifer; Pratt, Danielle; Berman, Karen F.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [Weinberger, Daniel R.] Lieber Inst Brain Dev, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 844 BP 247S EP 248S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801344 ER PT J AU Greenstein, D Kataria, R Dasgupta, A Malley, J Rapoport, J Gogtay, N AF Greenstein, Dede Kataria, Rachna Dasgupta, Abhijit Malley, James Rapoport, Judith Gogtay, Nitin TI Looking for Childhood Onset Schizophrenia: Diagnostic Algorithms for Classifying Children and Adolescents with Psychosis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE schizophrenia; classification; imaging C1 [Greenstein, Dede; Kataria, Rachna; Rapoport, Judith; Gogtay, Nitin] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Dasgupta, Abhijit] NIAMS, Clin Trials & Outcomes Branch, NIH, Bethesda, MD USA. [Malley, James] NIH, CIT, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 843 BP 247S EP 247S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801343 ER PT J AU Luscher, ZI AF Luscher, Zoe I. TI Diffusion Tensor Imaging in Patients with Childhood-Onset Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE DTI; COS; endophenotype; cuneus; FA C1 [Luscher, Zoe I.] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 841 BP 247S EP 247S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801341 ER PT J AU Marenco, S Kuo, S Meyer, CT van der Veen, JW Zhang, Y Barnett, AS DeJong, K Apud, JA Shen, J Weinberger, DR Berman, KF AF Marenco, Stefano Kuo, Susan Meyer, Christian T. van der Veen, Jan Willem Zhang, Yan Barnett, Alan S. DeJong, Katherine Apud, Jose A. Shen, Jun Weinberger, Daniel R. Berman, Karen F. TI g-amino-butyric-acid (GABA) and Glutamate (Glu) Levels in the Anterior Cingulate Cortex Measured with Magnetic Resonance Spectroscopy (MRS) in Non-medicated Patients with Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE GABA; Glutamate; schizophrenia; MRS; anterior cingulate C1 [Marenco, Stefano; Kuo, Susan; Meyer, Christian T.; DeJong, Katherine; Apud, Jose A.; Berman, Karen F.] NIMH, CBDB, Bethesda, MD 20892 USA. [van der Veen, Jan Willem; Zhang, Yan; Shen, Jun] NIMH, MRS Core, Bethesda, MD 20892 USA. [Barnett, Alan S.] NICHD, STBB, Bethesda, MD USA. [Weinberger, Daniel R.] Lieber Inst Brain Dev, Div Clin Sci, Baltimore, MD USA. RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 842 BP 247S EP 247S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801342 ER PT J AU Kuo, S van der Veen, JW Meyer, CT Barnett, AS DeJong, K Apud, JA Shen, J Berman, KF Weinberger, DR Marenco, S AF Kuo, Susan van der Veen, Jan Willem Meyer, Christian T. Barnett, Alan S. DeJong, Katherine Apud, Jose A. Shen, Jun Berman, Karen F. Weinberger, Daniel R. Marenco, Stefano TI Are g-amino-butyric-acid (GABA) Levels in the Anterior Cingulate Cortex Measured with Magnetic Resonance Spectroscopy (MRS) an Intermediate Phenotype for Schizophrenia? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE schizophrenia; GABA; anterior cingulate cortex; intermediate phenotype; siblings C1 [Kuo, Susan; Meyer, Christian T.; Barnett, Alan S.; DeJong, Katherine; Apud, Jose A.; Berman, Karen F.; Marenco, Stefano] NIMH, Clin Brain Disorders Branch, IRP, Bethesda, MD 20892 USA. [van der Veen, Jan Willem; Shen, Jun] NIMH, MRS Core Facil, IRP, Bethesda, MD 20892 USA. [Weinberger, Daniel R.] Lieber Inst Brain Dev, Baltimore, MD USA. RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 845 BP 248S EP 248S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801345 ER PT J AU Meyer, CT Zhang, Y Kuo, S Barnett, AS Slagle, AG Apud, JA Shen, J Berman, KF Weinberger, DR Marenco, S AF Meyer, Christian T. Zhang, Yan Kuo, Susan Barnett, Alan S. Slagle, Anna G. Apud, Jose A. Shen, Jun Berman, Karen F. Weinberger, Daniel R. Marenco, Stefano TI Are Glutamate (Glu) Levels Measured with Magnetic Resonance Spectroscopy (MRS) in the Dorsal Anterior Cingulate Cortex (DACC) an Intermediate Phenotype for Schizophrenia? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE schizophrenia; spectroscopy; glutamate; intermediate phenotype C1 [Meyer, Christian T.; Kuo, Susan; Barnett, Alan S.; Slagle, Anna G.; Apud, Jose A.; Berman, Karen F.; Marenco, Stefano] NIMH, Clin Brain Disorders Branch, IRP, Bethesda, MD 20892 USA. [Zhang, Yan; Shen, Jun] NIMH, MRS Core Facil, IRP, Bethesda, MD 20892 USA. [Weinberger, Daniel R.] Lieber Inst Brain Dev, Baltimore, MD USA. RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 846 BP 248S EP 248S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801346 ER PT J AU Hansen, G Nguyen, TV Reuter, J Lipska, BK Kleinman, J Schmidt, PJ Berman, KF AF Hansen, Grace Tuong-Vi Nguyen Reuter, John Lipska, Barbara K. Kleinman, Joel Schmidt, Peter J. Berman, Karen F. TI Developmentally-specific Interactions Between Expression of Genes Coding for Prosocial Peptides and Expression of the Dopamine D2 Receptor Gene SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Oxytocin; Dopamine receptor; Vasopressin; Gene expression; Reward C1 [Hansen, Grace; Tuong-Vi Nguyen; Lipska, Barbara K.; Berman, Karen F.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [Reuter, John] NIMH, Sect Behav Neuroendocrinol, Bethesda, MD 20892 USA. [Kleinman, Joel] Lieber Inst Brain Dev, Baltimore, MD USA. [Schmidt, Peter J.] NIMH, Sect Behav Endocrinol, Bethesda, MD 20892 USA. RI Lipska, Barbara/E-4569-2017 NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 860 BP 253S EP 253S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801360 ER PT J AU Raab, HA Nguyen, TV Lipska, B Kleinman, J Schmidt, P Berman, KF AF Raab, Hillary A. Tuong-Vi Nguyen Lipska, Barbara Kleinman, Joel Schmidt, Peter Berman, Karen F. TI Associations Between the Expression of G-Protein Coupled Estrogen Receptor and the Expression of Genes Involved in Neuronal, Synaptic and Glial Development in Postmortem Human Brain SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE GPER; Neuroplasticity; Prefrontal Cortex; Gene Expression C1 [Raab, Hillary A.; Tuong-Vi Nguyen; Lipska, Barbara; Berman, Karen F.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [Kleinman, Joel] Lieber Inst Brain Dev, Baltimore, MD USA. [Schmidt, Peter] NIMH, Sect Behav Endocrinol, Bethesda, MD 20892 USA. RI Lipska, Barbara/E-4569-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 861 BP 253S EP 253S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801361 ER PT J AU Reuter, J Nguyen, TV Hansen, G Lipska, BK Kleinman, J Schmidt, PJ Berman, KF AF Reuter, John Tuong-Vi Nguyen Hansen, Grace Lipska, Barbara K. Kleinman, Joel Schmidt, Peter J. Berman, Karen F. TI Relationship Between Oxytocin- and Vasopressin-related Gene Expression and Dopamine Receptor Gene Expression in Postmortem Human Brain SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE oxytocin; vasopressin; dopamine receptor; oxt/avp receptors; braicloud C1 [Reuter, John] Washington & Lee Univ, Dept Neurosci, Lexington, VA 24450 USA. [Reuter, John; Tuong-Vi Nguyen; Schmidt, Peter J.] NIMH, Sect Behav Endocrinol, Bethesda, MD 20892 USA. [Hansen, Grace; Berman, Karen F.] NIMH, Sect Integrated Neuroimaging, Bethesda, MD 20892 USA. [Lipska, Barbara K.; Kleinman, Joel] NIMH, Sect Neuropathol, Bethesda, MD 20892 USA. RI Lipska, Barbara/E-4569-2017 NR 0 TC 0 Z9 0 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 865 BP 254S EP 255S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801365 ER PT J AU Driver, DI Ordonez, A Orloff, M Penzak, S Overman, J Greenstein, D Dillard-Broadnax, D Rapoport, J Gogtay, N AF Driver, David I. Ordonez, Anna Orloff, Mark Penzak, Scott Overman, Jerry Greenstein, Deanna Dillard-Broadnax, Diane Rapoport, Judith Gogtay, Nitin TI The Effect of Blood Plasma Clozapine Levels on Specific Measures of Behavior in Childhood Onset Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Childhood Onset Schizophrenia; Clozapine C1 [Driver, David I.; Ordonez, Anna; Greenstein, Deanna; Dillard-Broadnax, Diane; Rapoport, Judith; Gogtay, Nitin] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Orloff, Mark; Penzak, Scott; Overman, Jerry] NIH, Clin Ctr Pharm Dept, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 895 BP 264S EP 264S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801395 ER PT J AU Ordonez, AE AF Ordonez, Anna E. TI Clozapine Treatment in Pediatric Onset Schizophrenia: Lessons From the NIMH Experience SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Childhood Onset Schizophrenia; Clozapine; Treatment Refractory; Antipsychotic Medication; Pediatric Psychosis C1 [Ordonez, Anna E.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 894 BP 264S EP 264S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101801394 ER PT J AU Austin, CP AF Austin, Christopher P. TI NCATS: Catalyzing Translational Innovation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat C1 [Austin, Christopher P.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1002 BP 275S EP 275S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802003 ER PT J AU Roberson-Nay, R Leibenluft, E Lichenstein, P Kendler, KS AF Roberson-Nay, Roxann Leibenluft, Ellen Lichenstein, Paul Kendler, Kenneth S. TI Longitudinal Stability of Genetic Influences on Irritability SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Irritability; genetic; development; sex effects; twins C1 [Roberson-Nay, Roxann; Kendler, Kenneth S.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Leibenluft, Ellen] NIMH, Bethesda, MD 20892 USA. [Lichenstein, Paul] Karolinska Inst, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1015 BP 280S EP 280S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802016 ER PT J AU Salum, GA Ernst, M Leibenluft, E Pine, D Rohde, LA Affonseca-Bressan, R Jackowski, A Manfro, GG Sato, JR AF Salum, Giovanni Abrahao Ernst, Monique Leibenluft, Ellen Pine, Daniel Rohde, Luis Augusto Affonseca-Bressan, Rodrigo Jackowski, Andrea Manfro, Gisele Gus Sato, Joao Ricardo TI Irritability and Amygdala Functional Connectivity in Fear and Distress Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Irritability; Fear; Anxiety; Resting-State; Cognition C1 [Salum, Giovanni Abrahao; Rohde, Luis Augusto; Manfro, Gisele Gus] Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil. [Ernst, Monique; Leibenluft, Ellen; Pine, Daniel] NIMH, Bethesda, MD 20892 USA. [Affonseca-Bressan, Rodrigo; Jackowski, Andrea] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Sato, Joao Ricardo] Fed Univ ABC, Santo Andre, Brazil. RI Rohde, Luis Augusto/A-6426-2008; Salum, Giovanni/A-7849-2010; Jackowski, Andrea/D-8616-2012 OI Rohde, Luis Augusto/0000-0002-4552-4188; Salum, Giovanni/0000-0002-7537-7289; Jackowski, Andrea/0000-0001-8842-5406 NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1017 BP 280S EP 280S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802018 ER PT J AU Stoddard, J Hsu, D Pine, DS Ernst, M Leibenluft, E Dickstein, DP AF Stoddard, Joel Hsu, Derek Pine, Daniel S. Ernst, Monique Leibenluft, Ellen Dickstein, Daniel P. TI Amygdala Functional Connectivity in Pediatric Bipolar Disorder and Severe Irritability SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE resting state functional connectivity; irritability; bipolar disorder C1 [Stoddard, Joel; Hsu, Derek; Pine, Daniel S.; Ernst, Monique; Leibenluft, Ellen] NIMH, Div Intramural Res Programs, Bethesda, MD 20892 USA. [Dickstein, Daniel P.] Brown Univ, Dept Psychiat & Human Behav, Alpert Med Sch, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1018 BP 281S EP 281S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802019 ER PT J AU Weinberger, DR Radulescu, E Zhang, FY Callicott, J Mattay, V Kleinman, JE Shin, JH Hyde, TM Ursini, G AF Weinberger, Daniel R. Radulescu, Eugenia Zhang, Fengyu Callicott, Joseph Mattay, Venkatta Kleinman, Joel E. Shin, Joo Hoen Hyde, Thomas M. Ursini, Gianluca TI Epistasis in Functional Imaging Genetics and Insights to Missing Heritability SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE epistasis; CYFIP1; 15q11 deletion; schizophrenia; fMRI C1 [Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Radulescu, Eugenia; Zhang, Fengyu; Mattay, Venkatta; Kleinman, Joel E.; Shin, Joo Hoen; Hyde, Thomas M.; Ursini, Gianluca] Lieber Inst Brain Dev, Baltimore, MD USA. [Callicott, Joseph] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1090 BP 302S EP 302S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802083 ER PT J AU Ariza, VL Seguin, JR Boivin, M Pine, DS Lepore, F Tremblay, RE Maheu, FS AF Ariza, Valerie La Buissonniere Seguin, Jean R. Boivin, Michel Pine, Daniel S. Lepore, Franco Tremblay, Richard E. Maheu, Francoise S. TI Neuronal Connectivity Patterns During Fear Processing in Adolescents Reared in Harsh Parenting Conditions: Can These Biomarkers Predict Risk or Resilience to Anxiety? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE fear conditioning; fear extinction; psychophysiological interactions; youth; fMRI C1 [Ariza, Valerie La Buissonniere; Seguin, Jean R.; Lepore, Franco; Maheu, Francoise S.] Univ Montreal, Montreal, PQ, Canada. [Ariza, Valerie La Buissonniere; Seguin, Jean R.; Lepore, Franco; Maheu, Francoise S.] St Justine Univ Hosp, Res Ctr, Montreal, PQ, Canada. [Boivin, Michel] Univ Laval, Quebec City, PQ, Canada. [Pine, Daniel S.] NIMH, Emot & Dev Branch, Bethesda, MD 20892 USA. [Tremblay, Richard E.] Univ Coll Dublin, Dept Psychol & Pediat, Dublin 2, Ireland. RI Seguin, Jean/B-5349-2008; Tremblay, Richard/O-1360-2014 OI Seguin, Jean/0000-0003-3359-6202; NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1099 BP 305S EP 305S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802092 ER PT J AU Soeiro-de-Souza, MG Teixeira, AL Machado-Vieira, R AF Soeiro-de-Souza, Marcio G. Teixeira, Antonio Lucio Machado-Vieira, Rodrigo TI Lower Leukocyte Telomerase Activity Associated with Antidepressant Efficacy of Lithium in Bipolar Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE bipolar; depression; telomerase; antidepressant; mood C1 [Soeiro-de-Souza, Marcio G.] Univ Sao Paulo, Sao Paulo, Brazil. [Teixeira, Antonio Lucio] Univ Minas Gerais, Sao Paulo, Brazil. [Machado-Vieira, Rodrigo] NIMH, Bethesda, DC USA. RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1151 BP 322S EP 322S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802144 ER PT J AU Brotman, MA Stoddard, J Harkins, EA Haring, CT Pine, DS Leibenluft, E AF Brotman, Melissa A. Stoddard, Joel Harkins, Elizabeth A. Haring, Catherine T. Pine, Daniel S. Leibenluft, Ellen TI Diffusion Model Differentiates Impairments in Attention Deficit Hyperactivity Disorder and Severe Mood Dysregulation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE diffusion model; attention; irritability; severe mood dysregulation; flanker C1 [Brotman, Melissa A.; Stoddard, Joel; Harkins, Elizabeth A.; Pine, Daniel S.; Leibenluft, Ellen] NIMH, Emot & Dev Branch, Bethesda, MD 20892 USA. [Haring, Catherine T.] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. RI Brotman, Melissa/H-7409-2013 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1166 BP 326S EP 327S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802159 ER PT J AU Gregory, MD Kippenhan, JS Callicott, J Kolachana, B Feng, NP Weinberger, DR Mattay, VS Berman, KF AF Gregory, Michael D. Kippenhan, J. Shane Callicott, Joseph Kolachana, Bhaskar Feng, Ningping Weinberger, Daniel R. Mattay, Venkata S. Berman, Karen F. TI Quantitative Trait Locus Analysis of the Williams Syndrome Critical Region and Right Intraparietal Sulcus Gray Matter Volume SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Williams syndrome; Genetics; Imaging; LIMK1; CLIP2 C1 [Gregory, Michael D.; Kippenhan, J. Shane; Berman, Karen F.] NIMH, Sect Integrat Neuroimaging, Intramural Res Program, Bethesda, MD 20892 USA. [Gregory, Michael D.; Kippenhan, J. Shane; Callicott, Joseph; Kolachana, Bhaskar; Feng, Ningping; Weinberger, Daniel R.; Mattay, Venkata S.; Berman, Karen F.] NIMH, Clin Brain Disorders Branch, Intramural Res Program, Bethesda, MD 20892 USA. [Weinberger, Daniel R.; Mattay, Venkata S.] Lieber Inst Brain Dev, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1227 BP 345S EP 346S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802220 ER PT J AU Sternberg, LH Tong, YX Healy, K Sambataro, F Das, S Kolachana, B Goldberg, TE Berman, KF Weinberger, DR Mattay, VSA AF Sternberg, Lauren H. Tong, Yunxia Healy, Katilin Sambataro, Fabio Das, Saumitra Kolachana, Bhaskar Goldberg, Terry E. Berman, Karen F. Weinberger, Daniel R. Mattay, Venkata S. Anand TI Interaction Between DRD2 and Dopamine Transporter Genes on Striatal Function During Working Memory Updating SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Genetics; Working Memory; Cognition; fMRI; Striatum C1 [Sternberg, Lauren H.; Tong, Yunxia; Healy, Katilin; Das, Saumitra; Kolachana, Bhaskar; Berman, Karen F.; Weinberger, Daniel R.; Mattay, Venkata S. Anand] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [Sambataro, Fabio] Brain Ctr Motor & Social Cognit, Italian Inst Technol, Parma, Italy. [Goldberg, Terry E.] Albert Einstein Coll Med, Dept Psychiat, Bethesda, MD USA. [Weinberger, Daniel R.; Mattay, Venkata S. Anand] Lieber Inst Brain Dev, Baltimore, MD USA. RI Sambataro, Fabio/E-3426-2010 OI Sambataro, Fabio/0000-0003-2102-416X NR 0 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1226 BP 345S EP 345S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802219 ER PT J AU Perez-Rodriguez, MM Rothstein, E Rimsky, L Hoque, N Lichtman, T McMaster, A Chowdhury, S Mascitelli, K Bevilacqua, L Ungar, A Ripoll, L Goldman, D Hodgkinson, C Goodman, M New, AS Siever, LJ AF Perez-Rodriguez, M. Mercedes Rothstein, Ethan Rimsky, Liza Hoque, Nabila Lichtman, Tamar McMaster, Antonia Chowdhury, Salwa Mascitelli, Katie Bevilacqua, Laura Ungar, Allison Ripoll, Luis Goldman, David Hodgkinson, Colin Goodman, Marianne New, Antonia S. Siever, Larry J. TI Arginine Vasopressin Receptor Gene Variants Associated with Aggression, Borderline and Schizotypal Personality Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Vasopressin; Borderline personality disorder; Schizotypal personality disorder; SNP; Aggression C1 [Perez-Rodriguez, M. Mercedes; Rothstein, Ethan; Rimsky, Liza; Hoque, Nabila; Lichtman, Tamar; McMaster, Antonia; Chowdhury, Salwa; Mascitelli, Katie; Ungar, Allison; Ripoll, Luis; Goodman, Marianne; New, Antonia S.; Siever, Larry J.] Icahn Sch Med Mt Sinai, New York, NY USA. [Perez-Rodriguez, M. Mercedes; Rothstein, Ethan; Rimsky, Liza; Hoque, Nabila; Lichtman, Tamar; McMaster, Antonia; Chowdhury, Salwa; Mascitelli, Katie; Goodman, Marianne; New, Antonia S.; Siever, Larry J.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Bevilacqua, Laura; Goldman, David; Hodgkinson, Colin] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. RI Perez Rodriguez, Maria/B-9410-2013 OI Perez Rodriguez, Maria/0000-0001-5137-1993 NR 0 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1239 BP 349S EP 349S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802232 ER PT J AU Karlsen, AS Hyde, TM Ursini, G Tao, R Jaffe, A Trampush, J Shin, JH Parachikova, A Dickinson, D Weinberger, D Plath, N AF Karlsen, Anna S. Hyde, Thomas M. Ursini, Gianluca Tao, Ran Jaffe, Andrew Trampush, Joey Shin, Joo Heon Parachikova, Anna Dickinson, Dwight Weinberger, Daniel Plath, Niels TI The Wnt Pathway in Schizophrenia: AXIN1 Polymorphisms are Associated with Diagnosis, Cognition, Gene Expression and DNA Methylation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Genetic polymorphisms; Wnt pathway; Schizophrenia; Cognitive function C1 [Karlsen, Anna S.] Bispebjerg Hosp, Res Lab Stereol & Neurosci, Copenhagen, Denmark. [Karlsen, Anna S.; Parachikova, Anna; Plath, Niels] H Lundbeck & Co AS, Synapt Transmiss 1, Valby, Denmark. [Hyde, Thomas M.; Ursini, Gianluca; Tao, Ran; Jaffe, Andrew; Shin, Joo Heon; Weinberger, Daniel] Johns Hopkins Univ Med Campus, Leiber Inst Brain Dev, Baltimore, MD USA. [Hyde, Thomas M.; Trampush, Joey; Dickinson, Dwight; Weinberger, Daniel] NIMH, Clin Brain Disorders Branch, NIH, IRP, Bethesda, MD 20892 USA. [Hyde, Thomas M.; Weinberger, Daniel] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Hyde, Thomas M.; Weinberger, Daniel] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1245 BP 351S EP 351S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802238 ER PT J AU Rapoport, S Primiani, C Rao, J Blanchard, H Ahn, K Ryan, V AF Rapoport, Stanley Primiani, Christopher Rao, Jagadeesh Blanchard, Helene Ahn, Kwangmi Ryan, Veronica TI Changes in Gene Expression of Arachidonic and Docosahexaenoic Acid Cascade Enzymes are Coordinated During Human Brain Development and Aging SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Gene expression; Aging; Development; Metabolism; Arachidonic C1 [Rapoport, Stanley; Primiani, Christopher; Rao, Jagadeesh; Ryan, Veronica] NIA, Neurosci Lab, Bethesda, MD 20892 USA. [Blanchard, Helene] NIH, Off Intramural Training & Educ, Bethesda, MD 20892 USA. [Ahn, Kwangmi] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1252 BP 354S EP 354S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802245 ER PT J AU Satterthwaite, TD Vandekar, L Katchmar, N Ruparel, K Elliott, MA Baldassano, C Leibenluft, E Thase, ME Gur, RC Gur, RE Kable, JW Wolf, DH AF Satterthwaite, Theodore D. Vandekar, Lillie Katchmar, Natalie Ruparel, Kosha Elliott, Mark A. Baldassano, Claudia Leibenluft, Ellen Thase, Michael E. Gur, Ruben C. Gur, Raquel E. Kable, Joseph W. Wolf, Daniel H. TI Common and Divergent Reward Responses Associated with Severity of Unipolar and Bipolar Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE Reward; Ventral striatum; Major depression; Bipolar disorder; fMRI C1 [Satterthwaite, Theodore D.; Vandekar, Lillie; Katchmar, Natalie; Ruparel, Kosha; Elliott, Mark A.; Baldassano, Claudia; Thase, Michael E.; Gur, Ruben C.; Gur, Raquel E.; Kable, Joseph W.; Wolf, Daniel H.] Univ Penn, Philadelphia, PA 19104 USA. [Leibenluft, Ellen] NIMH, Emot & Dev Branch, Mood & Anxiety Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1307 BP 371S EP 371S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802300 ER PT J AU Innis, RB AF Innis, Robert B. TI Fluoxetine Administered to Juvenile Monkeys: Effects on the Serotonin Transporter and Behavior SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry CY 2014 CL New York, NY SP Soc Biol Psychiat DE PET (positron emission tomography); serotonin transporter (SERT); serotonin-1A (5-HT1A) receptor; selective serotonin reuptake inhibitors (SSRIs); neocortex; hippocampus; raphe C1 [Innis, Robert B.] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2014 VL 75 IS 9 SU S MA 1365 BP 390S EP 390S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AE6KS UT WOS:000334101802358 ER PT J AU Guo, M Mao, HJ Li, YL Zhu, AJ He, H Yang, H Wang, YY Tian, X Ge, CC Peng, QL Wang, XY Yang, XL Chen, XY Liu, G Chen, HB AF Guo, Miao Mao, Huajian Li, Yanli Zhu, Aijun He, Hui Yang, Hong Wang, Yangyun Tian, Xin Ge, Cuicui Peng, Qiaoli Wang, Xianyong Yang, Xiangliang Chen, Xiaoyuan Liu, Gang Chen, Huabing TI Dual imaging-guided photothermal/photodynamic therapy using micelles SO BIOMATERIALS LA English DT Article DE Micelles; Photosensitizer; Near infrared fluorescent imaging; Photoacoustic imaging; Photothermal therapy; Photodynamic therapy ID RESPONSIVE GOLD NANOPARTICLES; VIVO PHOTODYNAMIC THERAPY; INDOCYANINE-GREEN; INFRARED LIGHT; CANCER-CELLS; PHOTOTHERMAL THERAPY; PHOTOSENSITIZER; NANOSPHERES; DOXORUBICIN; DELIVERY AB We report a type of photosensitizer (PS)-loaded micelles integrating cyanine dye as potential theranostic micelles for precise anatomical tumor localization via dual photoacoustic (PA)/near-infrared fluorescent (NIRF) imaging modalities, and simultaneously superior cancer therapy via sequential synergistic photothermal therapy (PTT)/photodynamic therapy (PDT). The micelles exhibit enhanced photostability, cell internalization and tumor accumulation. The dual NIRF/PA imaging modalities of the micelles cause the high imaging contrast and spatial resolution of tumors, which provide precise anatomical localization of the tumor and its inner vasculature for guiding PTT/PDT treatments. Moreover, the micelles can generate severe photothermal damage on cancer cells and destabilization of the lysosomes upon PTT photo-irradiation, which subsequently facilitate synergistic photodynamic injury via PS under PDT treatment. The sequential treatments of PTT/PDT trigger the enhanced cytoplasmic delivery of PS, which contributes to the synergistic anticancer efficacy of PS. Our strategy provides a dual-modal cancer imaging with high imaging contrast and spatial resolution, and subsequent therapeutic synergy of PTT/PDT for potential multimodal theranostic application. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Guo, Miao; Mao, Huajian; Li, Yanli; Zhu, Aijun; He, Hui; Yang, Hong; Chen, Huabing] Soochow Univ, Coll Pharmaceut Sci, Jiangsu Key Lab Translat Res & Therapy Neuropsych, Suzhou 215123, Peoples R China. [Wang, Yangyun; Tian, Xin; Ge, Cuicui; Chen, Huabing] Soochow Univ, Sch Radiol & Interdisciplinary Sci RAD X, Suzhou 215123, Peoples R China. [Wang, Yangyun; Tian, Xin; Ge, Cuicui; Chen, Huabing] Soochow Univ, Sch Radiat Med & Protect, Suzhou 215123, Peoples R China. [Peng, Qiaoli; Wang, Xianyong; Liu, Gang] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Peoples R China. [Yang, Xiangliang] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan 430074, Peoples R China. [Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. RP Chen, HB (reprint author), Soochow Univ, Coll Pharmaceut Sci, Jiangsu Key Lab Translat Res & Therapy Neuropsych, Suzhou 215123, Peoples R China. EM gangliu.cmitm@xmu.edu.cn; chenhb@suda.edu.cn RI Chen, Huabing/B-3687-2011 FU National Natural Science Foundation of China [81202472, 81101101, 51273165, 81371596]; National Basic Research Program [2012CB932500, 2013CB733802, 2014CB744503]; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD); Program for New Century Excellent Talents in University [NCET-13-0502]; Fundamental Research Funds for the Central Universities [2013121039] FX This work was supported by National Natural Science Foundation of China (81202472, 81101101, 51273165, and 81371596), National Basic Research Program (2012CB932500, 2013CB733802, and 2014CB744503), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), the Program for New Century Excellent Talents in University (NCET-13-0502), and Fundamental Research Funds for the Central Universities (2013121039). NR 49 TC 67 Z9 68 U1 23 U2 266 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 EI 1878-5905 J9 BIOMATERIALS JI Biomaterials PD MAY PY 2014 VL 35 IS 16 BP 4656 EP 4666 DI 10.1016/j.biomaterials.2014.02.018 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA AG1UJ UT WOS:000335201400006 PM 24613048 ER PT J AU Baratz-Goldstein, R Rubovitch, V Tweedie, D Schreiber, S Greig, NH Pick, CG AF Baratz-Goldstein, Renana Rubovitch, Vardit Tweedie, David Schreiber, Shaul Greig, Nigel H. Pick, Chaim G. TI The therapeutic impact of thalidomide analogue, 3,6 '-dithiothalidomide, on recovery from minimal traumatic brain injury SO BRAIN INJURY LA English DT Meeting Abstract C1 [Baratz-Goldstein, Renana; Rubovitch, Vardit; Pick, Chaim G.] Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel. [Tweedie, David; Greig, Nigel H.] NIA, Drug Design & Dev Sect, IRP, NIH, Baltimore, MD 21224 USA. [Schreiber, Shaul] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Psychiat, IL-69978 Tel Aviv, Israel. [Schreiber, Shaul] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PD MAY PY 2014 VL 28 IS 5-6 MA 0068 BP 537 EP 537 PG 1 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AF9EA UT WOS:000335017000056 ER PT J AU Tweedie, D Rachmany, L Rubovitch, V Hoffer, B Pick, C Greig, N AF Tweedie, David Rachmany, Lital Rubovitch, Vardit Hoffer, Barry Pick, Chaim Greig, Nigel TI Exendin-4, a candidate treatment for the clinical management of traumatic brain injury SO BRAIN INJURY LA English DT Meeting Abstract C1 [Tweedie, David; Greig, Nigel] NIA, NIH, Baltimore, MD 21224 USA. [Rachmany, Lital; Rubovitch, Vardit; Pick, Chaim] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Hoffer, Barry] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PD MAY PY 2014 VL 28 IS 5-6 MA 0101 BP 549 EP 550 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AF9EA UT WOS:000335017000087 ER PT J AU Lopez, K Levy, S Dsurney, J Chan, L AF Lopez, Katherine Levy, Sarah Dsurney, John Chan, Leighton TI Neuropsychological performance in individuals with mild traumatic brain injury with and without post-traumatic stress disorder SO BRAIN INJURY LA English DT Meeting Abstract C1 [Lopez, Katherine; Levy, Sarah; Dsurney, John] Ctr Neurosci & Regenerat Med, Bethesda, MD USA. [Chan, Leighton] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PD MAY PY 2014 VL 28 IS 5-6 MA 0767 BP 802 EP 802 PG 1 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AF9EA UT WOS:000335017000693 ER PT J AU Levy, S Lopez, K Dsurney, J Chan, L AF Levy, Sarah Lopez, Katherine Dsurney, John Chan, Leighton TI The utility of structural MRI as a predictor of neuropsychological outcome in TBI 1 month post injury: A pilot study SO BRAIN INJURY LA English DT Meeting Abstract C1 [Levy, Sarah; Lopez, Katherine; Dsurney, John] Ctr Neurosci & Regenerat Med, Bethesda, MD USA. [Chan, Leighton] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PD MAY PY 2014 VL 28 IS 5-6 MA 0771 BP 803 EP 804 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AF9EA UT WOS:000335017000697 ER PT J AU Shenouda, C Dsurney, J McNally, S Levy, S Lopez, K Chan, L AF Shenouda, Christian Dsurney, John McNally, Shannon Levy, Sarah Lopez, Katherine Chan, Leighton TI Evaluation of residual symptoms in subjects with single or multiple head injuries SO BRAIN INJURY LA English DT Meeting Abstract C1 [Shenouda, Christian; Dsurney, John; Levy, Sarah; Lopez, Katherine] Ctr Neurosci & Regenerat Med, Bethesda, MD USA. [McNally, Shannon; Chan, Leighton] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PD MAY PY 2014 VL 28 IS 5-6 MA 0777 BP 805 EP 806 PG 2 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AF9EA UT WOS:000335017000702 ER PT J AU Dsurney, J Lopez, K Pham, D McNally, S Levy, S Butman, J van der Merwe, A Shenouda, C Chan, L AF Dsurney, John Lopez, Katherine Dzung Pham McNally, Shannon Levy, Sarah Butman, John van der Merwe, Andre Shenouda, Christian Chan, Leighton TI A preliminary examination of the relationship between brain volume and cognitive functioning in a traumatic brain injury sample SO BRAIN INJURY LA English DT Meeting Abstract C1 [Dsurney, John; Lopez, Katherine; Dzung Pham; Levy, Sarah; van der Merwe, Andre; Shenouda, Christian] Ctr Neurosci & Regenerat Med, Bethesda, MD USA. [McNally, Shannon; Butman, John; Chan, Leighton] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PD MAY PY 2014 VL 28 IS 5-6 MA 0798 BP 815 EP 815 PG 1 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AF9EA UT WOS:000335017000723 ER PT J AU Wilson, A Rana, Z Rubenstein, L Murphy, D AF Wilson, Anne Rana, Zakar Rubenstein, Liza Murphy, Dennis TI Unexpected high incidence of traumatic brain injury and other coexisting neuropsychiatric disorders among 605 consecutive obsessive-compulsive disorder genetics clinic admissions SO BRAIN INJURY LA English DT Meeting Abstract C1 [Wilson, Anne; Rana, Zakar; Rubenstein, Liza; Murphy, Dennis] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PD MAY PY 2014 VL 28 IS 5-6 MA 0860 BP 839 EP 839 PG 1 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AF9EA UT WOS:000335017000780 ER PT J AU Edwards, BK Noone, AM Mariotto, AB Simard, EP Boscoe, FP Henley, SJ Jemal, A Cho, H Anderson, RN Kohler, BA Eheman, CR Ward, EM AF Edwards, Brenda K. Noone, Anne-Michelle Mariotto, Angela B. Simard, Edgar P. Boscoe, Francis P. Henley, S. Jane Jemal, Ahmedin Cho, Hyunsoon Anderson, Robert N. Kohler, Betsy A. Eheman, Christie R. Ward, Elizabeth M. TI Annual Report to the Nation on the status of cancer, 1975-2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer SO CANCER LA English DT Editorial Material DE survival; North American Association of Central Cancer Registries (NAACCR); Surveillance; multiple chronic conditions; comorbidity; Epidemiology; trends; mortality; incidence; multiple health conditions; National Program of Cancer Registries (NPCR); and End Results (SEER)-Medicare ID ONCOLOGY SPECIALTY CARE; ADJUSTED LIFE-YEARS; QUALITY-OF-CARE; UNITED-STATES; SURVIVORSHIP CARE; SURVEILLANCE DATA; INCIDENCE RATES; SPECIAL SECTION; GLOBAL BURDEN; MEDICARE DATA AB BACKGROUND The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updates on cancer incidence and death rates and trends in these outcomes for the United States. This year's report includes the prevalence of comorbidity at the time of first cancer diagnosis among patients with lung, colorectal, breast, or prostate cancer and survival among cancer patients based on comorbidity level. METHODS Data on cancer incidence were obtained from the NCI, the CDC, and the NAACCR; and data on mortality were obtained from the CDC. Long-term (1975/1992-2010) and short-term (2001-2010) trends in age-adjusted incidence and death rates for all cancers combined and for the leading cancers among men and women were examined by joinpoint analysis. Through linkage with Medicare claims, the prevalence of comorbidity among cancer patients who were diagnosed between 1992 through 2005 residing in 11 Surveillance, Epidemiology, and End Results (SEER) areas were estimated and compared with the prevalence in a 5% random sample of cancer-free Medicare beneficiaries. Among cancer patients, survival and the probabilities of dying of their cancer and of other causes by comorbidity level, age, and stage were calculated. RESULTS Death rates continued to decline for all cancers combined for men and women of all major racial and ethnic groups and for most major cancer sites; rates for both sexes combined decreased by 1.5% per year from 2001 through 2010. Overall incidence rates decreased in men and stabilized in women. The prevalence of comorbidity was similar among cancer-free Medicare beneficiaries (31.8%), breast cancer patients (32.2%), and prostate cancer patients (30.5%); highest among lung cancer patients (52.9%); and intermediate among colorectal cancer patients (40.7%). Among all cancer patients and especially for patients diagnosed with local and regional disease, age and comorbidity level were important influences on the probability of dying of other causes and, consequently, on overall survival. For patients diagnosed with distant disease, the probability of dying of cancer was much higher than the probability of dying of other causes, and age and comorbidity had a smaller effect on overall survival. CONCLUSIONS Cancer death rates in the United States continue to decline. Estimates of survival that include the probability of dying of cancer and other causes stratified by comorbidity level, age, and stage can provide important information to facilitate treatment decisions. Cancer 2014;120:1290-1314. (c) 2013 American Cancer Society. C1 [Edwards, Brenda K.; Noone, Anne-Michelle; Mariotto, Angela B.; Cho, Hyunsoon] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Simard, Edgar P.; Jemal, Ahmedin; Ward, Elizabeth M.] Amer Canc Soc, Surveillance Res Program, Atlanta, GA 30329 USA. [Boscoe, Francis P.; Kohler, Betsy A.] North Amer Assoc Cent Canc Registries, Springfield, IL USA. [Henley, S. Jane; Eheman, Christie R.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Anderson, Robert N.] Ctr Dis Control & Prevent, Div Vital Stat, Natl Ctr Hlth Stat, Hyattsville, MD USA. RP Edwards, BK (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E338, Bethesda, MD 20892 USA. EM edwardsb@mail.nih.gov OI Henley, S Jane/0000-0002-2420-306X FU Intramural NIH HHS [Z99 CA999999] NR 113 TC 240 Z9 251 U1 8 U2 54 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD MAY 1 PY 2014 VL 120 IS 9 BP 1290 EP 1314 DI 10.1002/cncr.28509 PG 25 WC Oncology SC Oncology GA AF4BT UT WOS:000334657100005 PM 24343171 ER PT J AU Tseng, J Citrin, DE Waldman, M White, DE Rosenberg, SA Yang, JC AF Tseng, Jennifer Citrin, Deborah E. Waldman, Meryl White, Donald E. Rosenberg, Steven A. Yang, James C. TI Thrombotic microangiopathy in metastatic melanoma patients treated with adoptive cell therapy and total body irradiation SO CANCER LA English DT Article DE adopted cell therapy; total body irradiation; thrombotic microangiopathy; autologous T cell therapy; tumor infiltrating lymphocytes; immunotherapy; metastatic melanoma ID BONE-MARROW-TRANSPLANTATION; RENAL DYSFUNCTION; RADIATION NEPHRITIS; NEPHROPATHY; FLUDARABINE; PREVENTION; TOXICITY; DISEASE AB BACKGROUND Thrombotic microangiopathy (TMA) is a complication that developed in some patients receiving 12 Gy total body irradiation (TBI) in addition to lymphodepleting preparative chemotherapy prior to infusion of autologous tumor-infiltrating lymphocytes (TIL) with high-dose aldesleukin (IL-2). This article describes the incidence, presentation, and course of radiation-associated TMA. METHODS The data for patients with metastatic melanoma who received ACT with TIL plus aldesleukin following myeloablative chemotherapy and 12-Gy TBI was examined, in order to look at patient characteristics and the natural history of TMA. RESULTS The median time to presentation was approximately 8 months after completing TBI. The estimated cumulative incidence of TMA was 31.2% (median follow-up of 24 months). Noninvasive criteria for diagnosis included newly elevated creatinine levels, new-onset hypertension, new-onset anemia, microscopic hematuria, thrombocytopenia, low haptoglobin, and elevated lactate dehydrogenase values. Once diagnosed, patients were managed with control of their hypertension with multiple agents and supportive red blood cell transfusions. TMA typically stabilized or improved and no patient progressed to dialysis. TMA was associated with a higher probability of an antitumor response. CONCLUSIONS TMA occurs in approximately a third of patients treated with a lymphodepleting preparative chemotherapy regimen with TBI prior to autologous T cell therapy. The disease has a variable natural history, however, no patient developed end-stage renal failure. Successful management with supportive care and aggressive hypertension control is vital to the safe application of a systemic therapy that has shown curative potential for patients with disseminated melanoma. Cancer 2014;120:1426-1432. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. C1 [Tseng, Jennifer; Citrin, Deborah E.; White, Donald E.; Rosenberg, Steven A.; Yang, James C.] NCI, Bethesda, MD 20892 USA. [Waldman, Meryl] NIDDK, Bethesda, MD 20892 USA. RP Yang, JC (reprint author), NCI, Ctr Canc Res, Bldg 10 CRC,Room 3-5952, Bethesda, MD 20892 USA. EM jamesyang@mail.nih.gov FU National Institutes of Health FX All financial and material support for the research and the work was provided by the National Institutes of Health. NR 26 TC 6 Z9 6 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD MAY 1 PY 2014 VL 120 IS 9 BP 1426 EP 1432 DI 10.1002/cncr.28547 PG 7 WC Oncology SC Oncology GA AF4BT UT WOS:000334657100020 PM 24474396 ER PT J AU Phillips, SM Alfano, CM Perna, FM Glasgow, RE AF Phillips, Siobhan M. Alfano, Catherine M. Perna, Frank M. Glasgow, Russell E. TI Accelerating Translation of Physical Activity and Cancer Survivorship Research into Practice: Recommendations for a More Integrated and Collaborative Approach SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIALS; BREAST-CANCER; CHILDHOOD-CANCER; UNITED-STATES; HEALTH-CARE; ACTIVITY INTERVENTIONS; EXERCISE PROGRAM; CLINICAL-TRIALS; OLDER-ADULTS; US ADULTS AB Physical activity has been deemed safe and effective in reducing many negative side effects of treatment for cancer survivors and promoting better overall health. However, most of this research has focused on highly controlled randomized trials and little of this research has been translated into care or policy for survivors. The purpose of the present article is to present a research agenda for the field to accelerate the dissemination and implementation of empirically supported physical activity interventions into care. We provide rationale for the role of basic, behavioral, clinical implementation, and population scientists in moving this science forward and call for a more coordinated effort across different phases of research. In addition, we provide key strategies and examples for ongoing and future studies using the RE-AIM (reach, efficacy/effectiveness, adoption, implementation, and maintenance) framework and pose recommendations for collaborations between researchers and stakeholders to enhance the integration of this research into policy and practice. Overall, we recommend that physical activity and cancer survivorship research use additional study designs, include relevant stakeholders, and be more collaborative, integrated, contextual, and representative in terms of both setting and participants. (C) 2014 AACR. C1 [Phillips, Siobhan M.; Alfano, Catherine M.] NCI, Off Canc Survivorship, Rockville, MD 20850 USA. [Phillips, Siobhan M.; Glasgow, Russell E.] NCI, Implementat Sci Team, Rockville, MD 20850 USA. [Perna, Frank M.] NCI, Hlth Behav Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. [Glasgow, Russell E.] Univ Colorado, Colorado Hlth Outcomes Program, Boulder, CO 80309 USA. RP Phillips, SM (reprint author), NCI, 9609 Med Ctr Dr,Off 4E516, Rockville, MD 20850 USA. EM siobhan.phillips@nih.gov FU Intramural NIH HHS [Z99 CA999999]; NIA NIH HHS [F31 AG034025] NR 96 TC 18 Z9 18 U1 3 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2014 VL 23 IS 5 BP 687 EP 699 DI 10.1158/1055-9965.EPI-13-1355 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZU UT WOS:000335145300001 PM 24599577 ER PT J AU Karimi, P Islami, F Anandasabapathy, S Freedman, ND Kamangar, F AF Karimi, Parisa Islami, Farhad Anandasabapathy, Sharmila Freedman, Neal D. Kamangar, Farin TI Gastric Cancer: Descriptive Epidemiology, Risk Factors, Screening, and Prevention SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID HELICOBACTER-PYLORI INFECTION; BODY-MASS INDEX; GASTROESOPHAGEAL-REFLUX DISEASE; INTERNATIONAL BEACON CONSORTIUM; PACIFIC CONSENSUS GUIDELINES; NUTRITION INTERVENTION TRIAL; GENOME-WIDE ASSOCIATION; SQUAMOUS-CELL CARCINOMA; 2 DISTINCT ETIOLOGIES; STOMACH-CANCER AB Less than a century ago, gastric cancer was the most common cancer in the United States and perhaps throughout the world. Despite its worldwide decline in incidence over the past century, gastric cancer remains a major killer across the globe. This article reviews the epidemiology, screening, and prevention of gastric cancer. We first discuss the descriptive epidemiology of gastric cancer, including its incidence, survival, mortality, and trends over time. Next, we characterize the risk factors for gastric cancer, both environmental and genetic. Serologic markers and histological precursor lesions of gastric cancer and early detection of gastric cancer using these markers are reviewed. Finally, we discuss prevention strategies and provide suggestions for further research. (C) 2014 AACR. C1 [Karimi, Parisa] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21251 USA. [Kamangar, Farin] Morgan State Univ, Dept Publ Hlth Anal, Sch Community Hlth & Policy, Baltimore, MD 21251 USA. [Freedman, Neal D.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Islami, Farhad] Mt Sinai Med Ctr, Mt Sinai Sch Med, Inst Transit Epidemiol, New York, NY 10029 USA. [Anandasabapathy, Sharmila] Mt Sinai Med Ctr, Dept Med, Div Gastroenterol, New York, NY 10029 USA. [Islami, Farhad; Kamangar, Farin] Univ Tehran Med Sci, Digest Dis Res Inst, Digest Oncol Res Ctr, Tehran, Iran. RP Kamangar, F (reprint author), Morgan State Univ, Dept Publ Hlth Anal, Sch Community Hlth & Policy, 4530 Portage Ave,Room 302, Baltimore, MD 21251 USA. EM farin.kamangar@morgan.edu RI Freedman, Neal/B-9741-2015 OI Freedman, Neal/0000-0003-0074-1098 FU Intramural Program of the National Cancer Institute, NIH FX The writing of this review article was supported in part by the Intramural Program of the National Cancer Institute, NIH. NR 174 TC 75 Z9 80 U1 5 U2 33 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2014 VL 23 IS 5 BP 700 EP 713 DI 10.1158/1055-9965.EPI-13-1057 PG 14 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZU UT WOS:000335145300002 PM 24618998 ER PT J AU Yu, GQ Gail, MH Shi, JX Klepac-Ceraj, V Paster, BJ Dye, BA Wang, GQ Wei, WQ Fan, JH Qiao, YL Dawsey, SM Freedman, ND Abnet, CC AF Yu, Guoqin Gail, Mitchell H. Shi, Jianxin Klepac-Ceraj, Vanja Paster, Bruce J. Dye, Bruce A. Wang, Guo-Qing Wei, Wen-Qiang Fan, Jin-Hu Qiao, You-Lin Dawsey, Sanford M. Freedman, Neal D. Abnet, Christian C. TI Association between Upper Digestive Tract Microbiota and Cancer-Predisposing States in the Esophagus and Stomach SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SQUAMOUS-CELL CARCINOMA; HELICOBACTER-PYLORI INFECTION; INFLAMMATORY BOWEL DISEASES; SERUM PEPSINOGENS; GUT MICROBIOME; GASTRIC-CANCER; PERNICIOUS-ANEMIA; HIGH-RISK; POPULATION; CHINA AB Background: The human upper digestive tract microbial community (microbiota) is not well characterized and few studies have explored how it relates to human health. We examined the relationship between upper digestive tract microbiota and two cancer-predisposing states, serum pepsinogen I/pepsinogen II ratio (PGI/II; predictor of gastric cancer risk) and esophageal squamous dysplasia (ESD; the precursor lesion of esophageal squamous cell carcinoma; ESCC) in a cross-sectional design. Methods: The Human Oral Microbe Identification Microarray was used to test for the presence of 272 bacterial species in 333 upper digestive tract samples from a Chinese cancer screening cohort. Serum PGI and PGII were determined by ELISA. ESD was determined by chromoendoscopy with biopsy. Results: Lower microbial richness (number of bacterial genera per sample) was significantly associated with lower PGI/II ratio (P = 0.034) and the presence of ESD (P = 0.018). We conducted principal component (PC) analysis on a beta-diversity matrix (pairwise difference in microbiota), and observed significant correlations between PC1, PC3, and PGI/II (P = 0.004 and 0.009, respectively), and between PC1 and ESD (P = 0.003). Conclusions: Lower microbial richness in upper digestive tract was independently associated with both cancer-predisposing states in the esophagus and stomach (presence of ESD and lower PGI/II). Impact: These novel findings suggest that the upper digestive tract microbiota may play a role in the etiology of chronic atrophic gastritis and ESD, and therefore in the development of gastric and esophageal cancers. (C) 2014 AACR. C1 [Yu, Guoqin; Gail, Mitchell H.; Shi, Jianxin; Dawsey, Sanford M.; Freedman, Neal D.; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Dye, Bruce A.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD USA. [Klepac-Ceraj, Vanja; Paster, Bruce J.] Forsyth Inst, Cambridge, MA USA. [Klepac-Ceraj, Vanja] Wellesley Coll, Wellesley, MA 02181 USA. [Paster, Bruce J.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Wang, Guo-Qing; Wei, Wen-Qiang; Fan, Jin-Hu; Qiao, You-Lin] Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. RP Yu, GQ (reprint author), NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, 9609 Med Ctr Dr,Room 6E518,MSC 9704, Bethesda, MD 20892 USA. EM yug3@mail.nih.gov RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015; OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098; Klepac-Ceraj, Vanja/0000-0001-5387-5706 FU Intramural Research Program of the NIH, National Cancer Institute FX This study was supported by the Intramural Research Program of the NIH, National Cancer Institute. NR 33 TC 14 Z9 15 U1 0 U2 25 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2014 VL 23 IS 5 BP 735 EP 741 DI 10.1158/1055-9965.EPI-13-0855 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZU UT WOS:000335145300005 PM 24700175 ER PT J AU Marks, MA Engels, EA AF Marks, Morgan A. Engels, Eric A. TI Venous Thromboembolism and Cancer Risk among Elderly Adults in the United States SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DEEP-VEIN THROMBOSIS; PULMONARY-EMBOLISM; PANCREATIC-CANCER; MULTIPLE-MYELOMA; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; COLORECTAL-CANCER; OVARIAN-CANCER; MEDICARE DATA; POPULATION AB Background: Few studies have evaluated cancer risk following venous thromboembolism (VTE). Both VTE and cancer disproportionately affect older adults. Methods: Using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we evaluated 1.2 million cancer cases and 200,000 controls (66-99 years old, 1992-2005). VTEs occurring before selection were identified using Medicare claims. Logistic regression was used to estimate ORs. Results: VTE was present in 2.5% of cases and 2.2% of controls. VTE was associated with risk of cancers of the lung [OR = 1.18; 95% confidence interval (CI), 1.12-1.23], stomach (OR = 1.19; 95% CI, 1.09-1.30), small intestine (OR = 1.42; 95% CI, 1.17-1.71), colon (OR = 1.25; 95% CI, 1.18-1.31), gallbladder (OR = 1.39; 95% CI, 1.16-1.67), pancreas (OR = 1.53; 95% CI, 1.43-1.64), soft tissue (OR = 1.43; 95% CI, 1.21-1.68), ovary (OR = 1.35; 95% CI, 1.22-1.50), and kidney/renal pelvis (OR = 1.34; 95% CI, 1.23-1.46), and melanoma (OR = 1.17; 95% CI, 1.081.27), non-Hodgkin lymphoma (OR = 1.27; 95% CI, 1.20-1.35), myeloma (OR = 1.48; 95% CI, 1.35-1.63), and acute myeloid leukemia (OR = 1.35; 95% CI, 1.19-1.54). Strongest risks were observed within 1 year of VTE diagnosis, but risks were elevated more than 6 years after VTE for colon cancer (OR = 1.24; 95% CI, 1.12-1.37), pancreatic cancer (OR = 1.33; 95% CI, 1.15-1.54), and myeloma (OR = 1.35; 95% CI, 1.10-1.66). Few differences in risk were observed by VTE subtype. Cancers of the lung, stomach, and pancreas were more likely to have distant metastases within one year after VTE. Conclusion: Among elderly adults, cancer risk is elevated following VTE diagnosis. Impact: Short-term associations with cancer are likely driven by enhanced screening following VTE and reverse causation. While obesity, other comorbidities, and smoking cannot be excluded as explanations, longer-term elevations for select cancers suggest that some VTEs may be caused by cancer precursors. (C) 2014 AACR. C1 [Marks, Morgan A.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Marks, MA (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E226 MSC 9767, Bethesda, MD 20892 USA. EM mmarksster@gmail.com FU Intramural Research Program of the National Cancer Institute at the National Institutes of Health FX This work was supported by the Intramural Research Program of the National Cancer Institute at the National Institutes of Health (M. Marks). NR 47 TC 7 Z9 7 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2014 VL 23 IS 5 BP 774 EP 783 DI 10.1158/1055-9965.EPI-13-1138 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZU UT WOS:000335145300009 PM 24608188 ER PT J AU Land, SR Liu, Q Wickerham, DL Costantino, JP Ganz, PA AF Land, Stephanie R. Liu, Qing Wickerham, D. Lawrence Costantino, Joseph P. Ganz, Patricia A. TI Cigarette Smoking, Physical Activity, and Alcohol Consumption as Predictors of Cancer Incidence among Women at High Risk of Breast Cancer in the NSABP P-1 Trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SURGICAL ADJUVANT BREAST; BOWEL PROJECT P-1; RESEARCH POLICY STATEMENT; ENDOMETRIAL CANCER; PROSPECTIVE COHORT; COLORECTAL-CANCER; POSTMENOPAUSAL WOMEN; AMERICAN ASSOCIATION; CLINICAL-TRIALS; POOLED ANALYSIS AB Background: NSABP P-1 provides an opportunity to examine the association of behavioral factors with prospectively monitored cancer incidence and interactions with tamoxifen. Methods: From 1992 to 1997, 13,388 women with estimated 5-year breast cancer risk greater than 1.66% or a history of lobular carcinoma in situ (87% younger than age 65; 67% postmenopausal) were randomly assigned to tamoxifen versus placebo. Invasive breast cancer, lung cancer, colon cancer, and endometrial cancer were analyzed with Cox regression. Predictors were baseline cigarette smoking, leisure-time physical activity, alcohol consumption, and established risk factors. Results: At median 7 years follow-up, we observed 395, 66, 35, and 74 breast cancer, lung cancer, colon cancer, and endometrial cancer, respectively. Women who had smoked were at increased risk of breast cancer (P = 0.007; HR = 1.3 for 15-35 years smoking, HR 1.6 for >= 35 years), lung cancer (P < 0.001; HR = 3.9 for 15-35 years, HR 18.4 for >= 35 years), and colon cancer (P < 0.001; HR 5.1 for >= 35 years) versus never-smokers. Low activity predicted increased breast cancer risk only among women assigned to placebo (P = 0.021 activity main effect, P = 0.013 activity-treatment interaction; HR = 1.4 for the placebo group) and endometrial cancer among all women (P = 0.026, HR = 1.7). Moderate alcohol (>0-1 drink/day) was associated with decreased risk of colon cancer (P = 0.019; HR = 0.35) versus no alcohol. There were no other significant associations between these behaviors and cancer risk. Conclusion: Among women with elevated risk of breast cancer, smoking has an even greater impact on breast cancer risk than observed in past studies in the general population. Impact: Women who smoke or are inactive should be informed of the increased risk of multiple types of cancer. (C) 2014 AACR. C1 [Land, Stephanie R.; Liu, Qing; Wickerham, D. Lawrence; Costantino, Joseph P.; Ganz, Patricia A.] Univ Pittsburgh, Grad Sch Publ Hlth, Natl Surg Adjuvant Breast & Bowel Project NSABP, Pittsburgh, PA USA. [Liu, Qing; Costantino, Joseph P.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Wickerham, D. Lawrence] Allegheny Hlth Network, Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA USA. [Land, Stephanie R.] NCI, Div Canc Control & Populat Sci, Behav Res Program, Bethesda, MD 20892 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Ganz, Patricia A.] Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90034 USA. RP Land, SR (reprint author), 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM stephanie.land@nih.gov FU National Cancer Institute, Department of Health and Human Services [U10-CA-37377, U10-CA-69974, R03CA134199-02] FX This work is supported by Public Health Service Grants U10-CA-37377 (S.R. Land, Q. Liu, D.L. Wickerham, J.P. Costantino, P.A. Ganz), U10-CA-69974 (S.R. Land, Q. Liu, D.L. Wickerham, J.P. Costantino, P.A. Ganz), and R03CA134199-02 (S.R. Land, P.A. Ganz) from the National Cancer Institute, Department of Health and Human Services. NR 55 TC 11 Z9 11 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2014 VL 23 IS 5 BP 823 EP 832 DI 10.1158/1055-9965.EPI-13-1105-T PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZU UT WOS:000335145300013 PM 24569437 ER PT J AU Gurel, B Lucia, MS Thompson, IM Goodman, PJ Tangen, CM Kristal, AR Parnes, HL Hoque, A Lippman, SM Sutcliffe, S Peskoe, SB Drake, CG Nelson, WG De Marzo, AM Platz, EA AF Gurel, Bora Lucia, M. Scott Thompson, Ian M., Jr. Goodman, Phyllis J. Tangen, Catherine M. Kristal, Alan R. Parnes, Howard L. Hoque, Ashraful Lippman, Scott M. Sutcliffe, Siobhan Peskoe, Sarah B. Drake, Charles G. Nelson, William G. De Marzo, Angelo M. Platz, Elizabeth A. TI Chronic Inflammation in Benign Prostate Tissue Is Associated with High-Grade Prostate Cancer in the Placebo Arm of the Prostate Cancer Prevention Trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RADICAL PROSTATECTOMY; RISK; MEN; PSA; HYPERPLASIA; ANTIGEN; LESIONS AB Background: Chronic inflammation is hypothesized to influence prostate cancer development, although a definitive link has not been established. Methods: Prostate cancer cases (N = 191) detected on a for-cause (clinically indicated) or end-of-study (protocol directed) biopsy, and frequency-matched controls (N 209), defined as negative for cancer on an end-of- study biopsy, were sampled from the placebo arm of the Prostate Cancer Prevention Trial. Inflammation prevalence and extent in benign areas of biopsy cores were visually assessed using digital images of hematoxylin and eosin-stained sections. Logistic regression was used to estimate associations. Results: Of note, 86.2% of cases and 78.2% of controls had at least one biopsy core (of three assessed) with inflammation in benign areas, most of which was chronic. Men who had at least one biopsy core with inflammation had 1.78 [95% confidence interval (CI), 1.04-3.06] times the odds of prostate cancer compared with men who had zero cores with inflammation. The association was stronger for high-grade disease (Gleason sum 7-10, N = 94; OR, 2.24; 95% CI, 1.06-4.71). These patterns were present when restricting to cases and controls in whom intraprostatic inflammation was the least likely to have influenced biopsy recommendation because their prostate-specific antigen (PSA) was low (<2 ng/mL at biopsy). Conclusion: Inflammation, most of which was chronic, was common in benign prostate tissue, and was positively associated with prostate cancer, especially high grade. The association did not seem to be due to detection bias. Impact: This study supports an etiologic link between inflammation and prostate carcinogenesis, and suggests an avenue for prevention by mitigating intraprostatic inflammation. (C) 2014 AACR. C1 [Gurel, Bora; Nelson, William G.; De Marzo, Angelo M.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA. [Drake, Charles G.] Johns Hopkins Sch Med, Dept Immunol, Baltimore, MD USA. [Drake, Charles G.; Nelson, William G.; De Marzo, Angelo M.; Platz, Elizabeth A.] Johns Hopkins Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD USA. [Drake, Charles G.; Nelson, William G.; De Marzo, Angelo M.; Platz, Elizabeth A.] Johns Hopkins Sch Med, Dept Urol, Baltimore, MD USA. [Peskoe, Sarah B.; Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Drake, Charles G.; Nelson, William G.; De Marzo, Angelo M.; Platz, Elizabeth A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Parnes, Howard L.] NCI, Canc Prevent Div, US Dept HHS, NIH, Bethesda, MD 20892 USA. [Lucia, M. Scott] Univ Colorado, Sch Med, Aurora, CO USA. [Thompson, Ian M., Jr.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Hoque, Ashraful] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. [Goodman, Phyllis J.; Tangen, Catherine M.] SWOG Stat Ctr, Seattle, WA USA. [Kristal, Alan R.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Program, Seattle, WA 98104 USA. [Lippman, Scott M.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Sutcliffe, Siobhan] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA. [Sutcliffe, Siobhan] Washington Univ, Sch Med, Dept Surg, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. RP Platz, EA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Room E6132,615 North Wolfe St, Baltimore, MD 21205 USA. EM ademarz@jhmi.edu; eplatz@jhsph.edu RI Gurel, Bora/A-5458-2016; OI Gurel, Bora/0000-0002-5018-8078; Sutcliffe, Siobhan/0000-0002-4613-8107 FU National Cancer Institute, NIH [P01 CA108964, U10 CA37429, P50 CA58236] FX This work was funded by the National Cancer Institute, NIH P01 CA108964 (to I. M. Thompson; project 4; to E. A. Platz), U10 CA37429 (to C. D. Blanke), and P50 CA58236 (to W. G. Nelson). NR 18 TC 40 Z9 40 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2014 VL 23 IS 5 BP 847 EP 856 DI 10.1158/1055-9965.EPI-13-1126 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZU UT WOS:000335145300015 PM 24748218 ER PT J AU Inoue-Choi, M Greenlee, H Oppeneer, SJ Robien, K AF Inoue-Choi, Maki Greenlee, Heather Oppeneer, Sarah J. Robien, Kim TI The Association between Postdiagnosis Dietary Supplement Use and Total Mortality Differs by Diet Quality among Older Female Cancer Survivors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; BREAST-CANCER; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; LIFE-STYLE; ALTERNATIVE MEDICINE; MULTIVITAMIN USE; FOLIC-ACID; COHORT; HEALTH AB Background: Dietary supplements are widely used by cancer survivors. However, health effects among older cancer survivors are unclear. Methods: We used the Iowa Women's Health Study, a prospective cohort study with 2,118 postmenopausal women with a confirmed cancer diagnosis (1986-2002), to evaluate the association between postdiagnosis dietary supplement use assessed in 2004 and subsequent all-cause mortality. Risk of death was evaluated using multivariable-adjusted Cox proportional hazards regression. We performed stratified analyses by diet quality score, dietary micronutrient intake, and perceived general health. Results: Through 2010, 608 deaths were identified. Approximately 85% of the cancer survivors used dietary supplements. Overall supplement use and multivitamin use were not associated with mortality. Iron supplement use was associated with 39% higher risk of death [95% confidence interval (CI), 1.09-1.77]. This association was stronger among survivors with deteriorating general health. Folic acid supplement use was associated with higher risk of death, only among survivors reporting low-quality diets (HR, 2.33; 95% CI, 1.334.08; P-interaction = 0.006). Multivitamin use and using a greater number of supplements was associated with a trend towards higher mortality only among those with poor diet quality. Using vitamin E supplements in combination with multivitamin was associated with lower risk of death only among survivors with higher dietary vitamin E intake (HR, 0.61; 95% CI, 0.39-0.94; P-interaction 0.02). Conclusions: Postdiagnosis supplement use was associated with higher mortality among older female cancer survivors with poor general health and/ or poor dietary intake. Impact: The association between postdiagnosis dietary supplement use and mortality may differ by diet quality and health status among older female cancer survivors. C1 [Inoue-Choi, Maki; Oppeneer, Sarah J.; Robien, Kim] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Greenlee, Heather] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Greenlee, Heather] Columbia Univ, Herbert Irving Comprehens Canc Ctr, Med Ctr, New York, NY USA. [Robien, Kim] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, Washington, DC USA. RP Inoue-Choi, M (reprint author), NCI, 9609 Med Ctr Dr 6E-640, Rockville, MD 20850 USA. EM maki.inoue-choi@nih.gov OI Robien, Kim/0000-0002-2120-2280 FU National Cancer Institute [R01 CA039742, K23 CA141052, T32 CA132670] FX This study was supported by National Cancer Institute R01 CA039742 (to M. Inoue-Choi and K. Robien), K23 CA141052 (to H. Greenlee), and T32 CA132670 (to S. J. Oppeneer). NR 48 TC 2 Z9 2 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2014 VL 23 IS 5 BP 865 EP 875 DI 10.1158/1055-9965.EPI-13-1303 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZU UT WOS:000335145300017 PM 24621441 ER PT J AU Lynch, BM Friedenreich, CM Kopciuk, KA Hollenbeck, AR Moore, SC Matthews, CE AF Lynch, Brigid M. Friedenreich, Christine M. Kopciuk, Karen A. Hollenbeck, Albert R. Moore, Steven C. Matthews, Charles E. TI Sedentary Behavior and Prostate Cancer Risk in the NIH-AARP Diet and Health Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PHYSICAL-ACTIVITY; PREVENTION; ADULTS; QUESTIONNAIRE; RELIABILITY; MORTALITY; VALIDITY; COHORT; MEN; TOO AB Sedentary behavior (sitting time) has been proposed as an independent risk factor for some cancers; however, its role in the development of prostate cancer has not been determined. Weexamined the prospective associations of self-reported daily sitting time and daily television/video viewing time with the risk of developing or dying from prostate cancer among 170,481 men in the NIH-AARP Diet and Health Study. We estimatedHRsand95% confidence intervals (CI) using Cox proportional hazards regression. Between 1996 and 2006, there were 13,751 incident (including 1,365 advanced) prostate cancer cases identified; prostate cancer mortality (through 2008) was 669. Nostrong or significant association with prostate cancer risk was seen in fully adjusted models for either daily sitting or television/video time. There were some suggestions of effect modification by body mass index (BMI; interaction for television/video time and BMI, P 0.02). For total prostate cancer risk, television/video time was associated with a slightly elevated, but nonsignificant, increase amongst obese men (HR 1.28; 95% CI, 0.98-1.69); a null association was observed amongst overweight men (HR 1.04; 0.89-1.22); and, for men with a normal BMI, television/video time was associated with a nonsignificant risk decrease (HR 0.82; 95% CI, 0.66-1.01). Similar patterns were observed for total daily sitting and television/video time in advanced prostate cancer and prostate cancer mortality. Sedentary behavior seems to play a limited role in the development of prostate cancer; however, we cannot rule out potential effect modification by BMI or the impact of measurement error on results. C1 [Lynch, Brigid M.] Baker IDI Heart & Diabet Inst, Phys Act Lab, Melbourne, Vic 3004, Australia. [Lynch, Brigid M.] Univ Melbourne, Fac Med Dent & Hlth Sci, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia. [Friedenreich, Christine M.; Kopciuk, Karen A.] Alberta Hlth Services Canc Control, Dept Populat Hlth Res, Calgary, AB, Canada. [Friedenreich, Christine M.; Kopciuk, Karen A.] Univ Calgary, Dept Oncol, Calgary, AB, Canada. [Friedenreich, Christine M.] Univ Calgary, Dept Community Hlth Sci, Calgary, AB, Canada. [Kopciuk, Karen A.] Univ Calgary, Dept Math & Stat, Calgary, AB T2N 1N4, Canada. [Hollenbeck, Albert R.] AARP, Washington, DC USA. [Moore, Steven C.; Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Lynch, BM (reprint author), Baker IDI Heart & Diabet Inst, Phys Act Lab, Level 4,99 Commercial Rd, Melbourne, Vic 3004, Australia. EM brigid.lynch@bakeridi.edu.au RI matthews, Charles/E-8073-2015; Moore, Steven/D-8760-2016 OI matthews, Charles/0000-0001-8037-3103; Moore, Steven/0000-0002-8169-1661 FU AARP and the Intramural Research Programof the NIH; National Cancer Institute; National Health and Medical Research Council [586727]; Victorian Government's Operational Infrastructure Support Program; Alberta Innovates- Health Solutions Health Senior Scholar Award FX This work was supported by the AARP and the Intramural Research Programof the NIH, National Cancer Institute. Brigid M. Lynch is funded by a Public Health Training Fellowship from the National Health and Medical Research Council (586727) and the Victorian Government's Operational Infrastructure Support Program. Christine M. Friedenreich is funded by an Alberta Innovates- Health Solutions Health Senior Scholar Award, and is the Alberta Cancer Foundation Weekend to End Women's Cancers Breast Cancer Chair. NR 24 TC 3 Z9 3 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2014 VL 23 IS 5 BP 882 EP 889 DI 10.1158/1055-9965.EPI-13-0808 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AG0ZU UT WOS:000335145300019 PM 24526287 ER PT J AU Tan, CY Wei, L Vistica, BP Shi, GP Wawrousek, EF Gery, I AF Tan, Cuiyan Wei, Lai Vistica, Barbara P. Shi, Guangpu Wawrousek, Eric F. Gery, Igal TI Phenotypes of Th lineages generated by the commonly used activation with anti-CD3/CD28 antibodies differ from those generated by the physiological activation with the specific antigen SO CELLULAR & MOLECULAR IMMUNOLOGY LA English DT Article DE Eye; Inflammation; Microarray; T-cell differentiation ID T-HELPER-2 CELLS; TGF-BETA; INFLAMMATION; COMMITMENT; INDUCTION; SUBSETS AB T-helper (Th) lineages have been generated in vitro by activating CD4 cells with anti-CD3/CD28 antibodies during polarization. Physiologically, however, the generation of Th lineages is by activation with the specific antigen presented by antigen-presenting cells (APC). Here, we used T-cell receptor (TCR)-transgenic mice to compare the phenotypes of Th1, Th9 and Th17 lineages when generated by either one of the two activation modes. Lineage Th cells specific against hen egg lysozyme (HEL), were adoptively transferred into recipient mice transgenically expressing HEL in their lens. Remarkable differences were found between lineages of Th1, Th9 or Th17, generated by either one of the two modes in their capacities to migrate to and proliferate in the recipient spleen and, importantly, to induce inflammation in the recipient mouse eyes. Substantial differences were also observed between the lineage pairs in their transcript expression profiles of certain chemokines and chemokine receptors. Surprisingly, however, close similarities were observed between the transcript expression profiles of lineages of the three phenotypes, activated by the same mode. Furthermore, Th cell lineages generated by the two activation modes differed considerably in their pattern of gene expression, as monitored by microarray analysis, but exhibited commonality with lineages of other phenotypes generated by the same activation mode. This study thus shows that (i) Th lineages generated by activation with anti-CD3/CD28 antibodies differ from lineages generated by antigen/APC; and (ii) the mode of activation determines to a large extent the expression profile of major transcripts. C1 [Tan, Cuiyan; Wei, Lai; Vistica, Barbara P.; Shi, Guangpu; Gery, Igal] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Wawrousek, Eric F.] NEI, Lab Mol & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Gery, I (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Rm 10N208, Bethesda, MD 20892 USA. EM geryi@nei.nih.gov FU National Eye Institute, NIH FX We thank Robert S Lee for tail DNA analysis, Samuel J H Hinshaw for digital microphotography, Rafael Villasmil for cell sorting and the NEI Histology Core Facility for tissue section preparations. This work was supported by the Intramural Research Program of the National Eye Institute, NIH. NR 25 TC 6 Z9 6 U1 0 U2 3 PU CHIN SOCIETY IMMUNOLOGY PI BEING PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA SN 1672-7681 EI 2042-0226 J9 CELL MOL IMMUNOL JI Cell. Mol. Immunol. PD MAY PY 2014 VL 11 IS 3 BP 305 EP 313 DI 10.1038/cmi.2014.8 PG 9 WC Immunology SC Immunology GA AG4FF UT WOS:000335374000012 PM 24583715 ER PT J AU Dagur, PK Biancotto, A Stansky, E Sen, HN Nussenblatt, RB Mccoy, JP AF Dagur, Pradeep K. Biancotto, Angelique Stansky, Elena Sen, H. Nida Nussenblatt, Robert B. McCoy, J. Philip TI Secretion of interleukin-17 by CD8+T cells expressing CD146 (MCAM) SO CLINICAL IMMUNOLOGY LA English DT Article DE CD146/MCAM; Tc17; Inflammation; Class I antigen ID T-CELLS; BIRDSHOT CHORIORETINOPATHY; AUTOIMMUNE-DISEASES; BEHCETS-DISEASE; SUSCEPTIBILITY; LYMPHOCYTES; MARKER; IL-17; DIFFERENTIATION; IDENTIFICATION AB Interleukin-17 (IL-17) has been associated with the pathogenesis of numerous autoimmune diseases. CD4+ T cells secreting IL-17 are termed Th17 cells. CD8+ T cells, designated Tc17 cells, are also capable of secreting IL-17. Here we describe a population of Tc17 cells characterized by the expression of surface CD146, an endothelial adhesion molecule. These cells display signatures of a human Tc17 genotype and phenotype. Circulating CD8+CD146+ T cells are present in tow levels in healthy adults. Elevations in CD8+CD146+ T cells are found in Behcet's disease and birdshot retinochoroidopathy, which have been reported to have HLA class I associations. Sarcoidosis does not have a class I association and displays an increase in CD4+ CD146+ T cells but not in CD8+CD146+ T cells. CD146 on these cells may facilitate their ability to bind to, and migrate through, endothelium, as has been reported for CD4+CD146+ T cells. Published by Elsevier Inc. C1 [Dagur, Pradeep K.; Stansky, Elena; McCoy, J. Philip] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Biancotto, Angelique; Nussenblatt, Robert B.; McCoy, J. Philip] NIH, Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA. [Sen, H. Nida; Nussenblatt, Robert B.] NEI, Clin Immunol Sect, NIH, Bethesda, MD 20892 USA. RP Mccoy, JP (reprint author), NHLBI, NIH, 10 Ctr Dr,MSC 1357,Bldg 10,Rm 8C103D, Bethesda, MD 20892 USA. EM mccoyjp@mail.nih.gov FU National Institutes of Health; National Heart, Lung, and Blood Institute, Division of Intramural Research FX This study was funded by the National Institutes of Health, National Heart, Lung, and Blood Institute, Division of Intramural Research. NR 30 TC 16 Z9 16 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 1521-6616 EI 1521-7035 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAY-JUN PY 2014 VL 152 IS 1-2 BP 36 EP 47 DI 10.1016/j.clim.2014.01.009 PG 12 WC Immunology SC Immunology GA AG3BS UT WOS:000335291400005 PM 24681356 ER PT J AU Tempia, S Walaza, S Viboud, C Cohen, AL Madhi, SA Venter, M McAnerney, JM Cohen, C AF Tempia, Stefano Walaza, Sibongile Viboud, Cecile Cohen, Adam L. Madhi, Shabir A. Venter, Marietjie McAnerney, Johanna M. Cohen, Cheryl TI Mortality Associated With Seasonal and Pandemic Influenza and Respiratory Syncytial Virus Among Children < 5 Years of Age in a High HIV Prevalence Setting-South Africa, 1998-2009 SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE influenza; respiratory syncytial virus; HIV; mortality; South Africa ID UNITED-STATES; EXCESS MORTALITY; TRACT INFECTIONS; BURDEN; HOSPITALIZATIONS; EPIDEMIOLOGY; PNEUMONIA; ADULTS; SEVERITY; DEATHS AB Background. There are few published data describing the mortality burden associated with influenza and respiratory syncytial virus (RSV) infection in children in low- and middle-income countries and particularly from Africa and settings with high prevalence of human immunodeficiency virus (HIV). Methods. We modeled the excess mortality attributable to influenza (seasonal and pandemic) and RSV infection by applying Poisson regression models to monthly all-respiratory and pneumonia and influenza deaths, using national influenza and RSV laboratory surveillance data as covariates. In addition, we estimated the seasonal influenza- and RSV-associated deaths among HIV-infected and -uninfected children using Poisson regression models that incorporated HIV prevalence and highly active antiretroviral therapy coverage as covariates. Results. In children <5 years of age, the mean annual numbers of seasonal influenza- and RSV-associated all-respiratory deaths were 452 (8 per 100 000 person-years [PY]) and 546 (10 per 100 000 PY), respectively. Infants <1 year of age experienced higher mortality rates compared with children 1-4 years of age for both influenza (22 vs 5 per 100 000 PY) and RSV (35 vs 4 per 100 000 PY). HIV-infected compared with HIV-uninfected children <5 years of age were at increased risk of death associated with influenza (age-adjusted relative risk [aRR], 11.5; 95% confidence interval [CI], 9.6-12.6) and RSV (aRR, 8.1; 95% CI, 6.9-9.3) infection. In 2009, we estimated 549 (11 per 100 000 PY) all-respiratory influenza A(H1N1) pdm09-associated deaths among children aged <5 years. Conclusions. Our findings support increased research efforts to guide and prioritize interventions such as influenza vaccination and HIV prevention in low- and middle-income countries with high HIV prevalence such as South Africa. C1 [Tempia, Stefano; Cohen, Adam L.] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA USA. [Tempia, Stefano; Cohen, Adam L.] Ctr Dis Control & Prevent, Influenza Div, Pretoria, South Africa. [Tempia, Stefano; Walaza, Sibongile; Madhi, Shabir A.; Venter, Marietjie; McAnerney, Johanna M.; Cohen, Cheryl] Natl Hlth Lab Serv, Natl Inst Communicable Dis, Ctr Resp Dis & Meningitis, Johannesburg, South Africa. [Viboud, Cecile] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Madhi, Shabir A.] Univ Witwatersrand, Fac Hlth Sci, Resp & Meningeal Pathogens Res Unit, Johannesburg, South Africa. [Madhi, Shabir A.] Univ Witwatersrand, Natl Res Fdn Vaccine Preventable Dis, Dept Sci & Technol, Johannesburg, South Africa. [Venter, Marietjie] Univ Pretoria, Dept Med Virol, Zoonoses Res Unit, Johannesburg, South Africa. [Cohen, Cheryl] Univ Witwatersrand, Sch Publ Hlth, Johannesburg, South Africa. RP Tempia, S (reprint author), Natl Inst Communicable Dis, Ctr Resp Dis & Meningitis, Private Bag X4, ZA-2131 Johannesburg, Gauteng, South Africa. EM stefanot@nicd.ac.za RI Venter, Marietjie/P-9604-2016 OI Venter, Marietjie/0000-0003-2696-824X NR 46 TC 22 Z9 23 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 1 PY 2014 VL 58 IS 9 BP 1241 EP 1249 DI 10.1093/cid/ciu095 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AF9AJ UT WOS:000335006900007 PM 24567249 ER PT J AU Masur, H Brooks, JT Benson, CA Holmes, KK Pau, AK Kaplan, JE AF Masur, Henry Brooks, John T. Benson, Constance A. Holmes, King K. Pau, Alice K. Kaplan, Jonathan E. TI Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents: Updated Guidelines From the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE opportunistic infections; HIV/AIDS; guideline; revision; online ID RECONSTITUTION INFLAMMATORY SYNDROME; ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; RISK-FACTORS; UNITED-STATES; TRENDS; COHORT; MORTALITY; RECOMMENDATIONS; TUBERCULOSIS AB In May 2013, a revised and updated version of the Centers for Disease Control and Prevention/National Institutes of Health/HIV Medicine Association Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents was released online. These guidelines, since their inception in 1989, have been widely accessed in the United States and abroad. These guidelines have focused on the management of HIV/AIDS-related opportunistic infections that occur in the United States. In other parts of the world, the spectrum of complications may be different and the resources available for diagnosis and management may not be identical to those in the United States. The sections that have been most extensively updated are those on immune reconstitution inflammatory syndrome, tuberculosis, hepatitis B, hepatitis C, human papillomavirus, and immunizations. The guidelines will not be published in hard copy form. This document will be revised as needed throughout each year as new data become available. C1 [Masur, Henry; Pau, Alice K.] NIH, Bethesda, MD 20892 USA. [Brooks, John T.; Kaplan, Jonathan E.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Benson, Constance A.] Univ Calif San Diego, San Diego, CA 92103 USA. [Holmes, King K.] Univ Washington, Seattle, WA 98195 USA. RP Masur, H (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr,Rm 2C145, Bethesda, MD 20892 USA. EM hmasur@nih.gov NR 37 TC 28 Z9 30 U1 0 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 1 PY 2014 VL 58 IS 9 BP 1308 EP 1311 DI 10.1093/cid/ciu094 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AF9AJ UT WOS:000335006900017 PM 24585567 ER PT J AU Holmes, KL Fontes, B Hogarth, P Konz, R Monard, S Pletcher, CH Wadley, RB Schmid, I Perfetto, SP AF Holmes, Kevin L. Fontes, Benjamin Hogarth, Philip Konz, Richard Monard, Simon Pletcher, Charles H., Jr. Wadley, Robert B. Schmid, Ingrid Perfetto, Stephen P. TI International Society for the Advancement of Cytometry Cell Sorter Biosafety Standards SO CYTOMETRY PART A LA English DT Article DE flow cytometry; occupational health; biohazards; cell sorting; biosafety; aerosol containment ID LABORATORY-ASSOCIATED INFECTIONS; HUMAN-IMMUNODEFICIENCY-VIRUS; ACQUIRED INFECTIONS; UNFIXED CELLS; TRANSMISSION; AEROSOL; CONTAINMENT; WORKER AB Flow cytometric cell sorting of biological specimens has become prevalent in basic and clinical research laboratories. These specimens may contain known or unknown infectious agents, necessitating precautions to protect instrument operators and the environment from biohazards arising from the use of sorters. To this end the International Society of Analytical Cytology (ISAC) was proactive in establishing biosafety guidelines in 1997 (Schmid et al., Cytometry 1997;28:99-117) and subsequently published revised biosafety standards for cell sorting of unfixed samples in 2007 (Schmid et al., Cytometry Part A J Int Soc Anal Cytol 2007;71A:414-437). Since their publication, these documents have become recognized worldwide as the standard of practice and safety precautions for laboratories performing cell sorting experiments. However, the field of cytometry has progressed since 2007, and the document requires an update. The new Standards provides guidance: (1) for laboratory design for cell sorter laboratories; (2) for the creation of laboratory or instrument specific Standard Operating Procedures (SOP); and (3) on procedures for the safe operation of cell sorters, including personal protective equipment (PPE) and validation of aerosol containment. Published (c) 2013 Wiley Periodicals Inc.(dagger .10). During the laboratory meal, WCA consumed less energy from snack-type foods than no-WCA (M = 245.0, SD = 156.1 vs. M = 341.6, SD = 192.3 kcal; p = .01). Conclusions: Reported WCAs are highly prevalent and are associated with greater psychopathology symptoms among adolescent girls with LOC eating. Prospective data are needed to determine whether these overlapping risk behaviors confer differential vulnerability for developing eating disorders and obesity. C1 [Vannucci, Anna; Shomaker, Lauren B.; Field, Sara E.; Sbrocco, Tracy; Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. [Vannucci, Anna; Shomaker, Lauren B.; Field, Sara E.; Yanovski, Jack A.; Tanofsky-Kraff, Marian] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. [Stephens, Mark] Uniformed Serv Univ Hlth Sci, Dept Family Med, Bethesda, MD 20814 USA. [Kozlosky, Merel] NIH, Dept Nutr, Ctr Clin, Bethesda, MD 20892 USA. [Reynolds, James C.] NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD USA. RP Tanofsky-Kraff, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM mtanofsky@usuhs.edu RI Stephens, Mark/A-2679-2015; OI Yanovski, Jack/0000-0001-8542-1637 FU NIDDK [1R01DK080906]; USUHS [R072IC]; Intramural Research Program, NIH; NICHD [1ZIAHD000641]; NIMHD FX Jack A. Yanovski and Merel Kozlosky are commissioned officers in the U.S. Public Health Service (PHS). Mark Stephens is a commissioned officer in the U.S. Navy. The opinions and assertions expressed herein are those of the authors and are not to be construed as reflecting the views of the PHS, USUHS, the Department of the Navy, or the U.S. Department of Defense. Research support was provided by NIDDK grant 1R01DK080906 and USUHS grant R072IC (to MTK) and Intramural Research Program, NIH, grant 1ZIAHD000641 from the NICHD with supplemental funding from NIMHD (to JAY). NR 32 TC 2 Z9 2 U1 0 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 EI 1930-7810 J9 HEALTH PSYCHOL JI Health Psychol. PD MAY PY 2014 VL 33 IS 5 BP 419 EP 423 DI 10.1037/a0033184 PG 5 WC Psychology, Clinical; Psychology SC Psychology GA AG1AK UT WOS:000335147000003 PM 23815764 ER PT J AU de Campos, AC Kukke, SN Hallett, M Alter, KE Damiano, DL AF de Campos, Ana Carolina Kukke, Sahana N. Hallett, Mark Alter, Katharine E. Damiano, Diane L. TI Characteristics of Bilateral Hand Function in Individuals With Unilateral Dystonia Due to Perinatal Stroke Sensory and Motor Aspects SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE motor skills; hemiplegia; sensory function; cerebral palsy; stroke; dystonia ID HEMIPLEGIC CEREBRAL-PALSY; TACTILE SPATIAL-RESOLUTION; KINEMATIC CHARACTERISTICS; GRATING ORIENTATION; SECONDARY DYSTONIA; REACHING MOVEMENTS; DIGITAL DEXTERITY; PRETERM CHILDREN; MANUAL ABILITY; DISCRIMINATION AB The authors assessed bilateral motor and sensory function in individuals with upper limb dystonia due to unilateral perinatal stroke and explored interrelationships of motor function and sensory ability. Reach kinematics and tactile sensation were measured in 7 participants with dystonia and 9 healthy volunteers. The dystonia group had poorer motor (hold time, reach time, shoulder/elbow correlation) and sensory (spatial discrimination, stereognosis) outcomes than the control group on the nondominant side. On the dominant side, only sensation (spatial discrimination, stereognosis) was poorer in the dystonia group compared with the control group. In the dystonia group, although sensory and motor outcomes were uncorrelated, dystonia severity was related to poorer stereognosis, longer hold and reach times, and decreased shoulder/elbow coordination. Findings of bilateral sensory deficits in dystonia can be explained by neural reorganization. Visual compensation for somatosensory changes in the nonstroke hemisphere may explain the lack of bilateral impairments in reaching. C1 [de Campos, Ana Carolina; Kukke, Sahana N.; Alter, Katharine E.; Damiano, Diane L.] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. [Kukke, Sahana N.; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bethesda, MD USA. [Alter, Katharine E.] Mt Washington Pediat Hosp, Baltimore, MD USA. RP Damiano, DL (reprint author), NIH, Dept Rehabil Med, Funct & Appl Biomech Sect, Clin Ctr,CRC, 10 Ctr Dr,Room 1-1469,Bldg 10,MSC 1604, Bethesda, MD 20892 USA. EM damianod@cc.nih.gov RI Damiano, Diane/B-3338-2010 OI Damiano, Diane/0000-0002-2770-5356 FU Intramural Research Program of the National Institutes of Health Clinical Center; National Institute of Neurological Disorders and Stroke; National Council for Scientific and Technological Development (CNPq), Brazil FX The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by the Intramural Research Program of the National Institutes of Health Clinical Center, the National Institute of Neurological Disorders and Stroke, and the National Council for Scientific and Technological Development (CNPq), Brazil (scholarship to ACC). NR 58 TC 4 Z9 4 U1 0 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 EI 1708-8283 J9 J CHILD NEUROL JI J. Child Neurol. PD MAY PY 2014 VL 29 IS 5 BP 623 EP 632 DI 10.1177/0883073813512523 PG 10 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA AG0FJ UT WOS:000335090400008 PM 24396131 ER PT J AU Kono, M Tucker, AE Tran, J Bergner, JB Turner, EM Proia, RL AF Kono, Mari Tucker, Ana E. Tran, Jennifer Bergner, Jennifer B. Turner, Ewa M. Proia, Richard L. TI Sphingosine-1-phosphate receptor 1 reporter mice reveal receptor activation sites in vivo SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PROTEIN-COUPLED-RECEPTOR; SPHINGOSINE 1-PHOSPHATE RECEPTOR; ENDOTHELIAL BARRIER FUNCTION; LYMPHOCYTE EGRESS; GENE-EXPRESSION; VASCULAR MATURATION; MULTIPLE-SCLEROSIS; S1P GRADIENTS; CELLS; FTY720 AB Activation of the GPCR sphingosine-l-phosphate receptor 1 (S1P1) by sphingosine-l-phosphate (S1P) regulates key physiological processes. S1P1 activation also has been implicated in pathologic processes, including autoimm.unity and inflammation; however, the in vivo sites of S1P1 activation under normal and disease conditions are unclear. Here, we describe the development of a mouse model that allows in vivo evaluation of S1P1 activation. These mice, known as S1P1 GFP signaling mice, produce a S1P1 fusion protein containing a transcription factor linked by a protease cleavage site at the C terminus as well as a beta-arrestin/protease fusion protein. Activated S1P1 recruits the beta-arrestin/protease, resulting in the release of the transcription factor, which stimulates the expression of a GFP reporter gene. Under normal conditions, S1P1 was activated in endothelial cells of lymphoid tissues and in cells in the marginal zone of the spleen, while administration of an S1P1 agonist promoted S1P1 activation in endothelial cells and hepatocytes. In S1P1 GFP signaling mice, LPS-mediated systemic inflammation activated S1P1 in endothelial cells and hepatocytes via hematopoietically derived SW. These data demonstrate that S1P1 GFP signaling mice can be used to evaluate S1P1 activation and S1P1-active compounds in vivo. Furthermore, this strategy could be potentially applied to any GPCR to identify sites of receptor activation during normal physiology and disease. C1 [Kono, Mari; Tucker, Ana E.; Tran, Jennifer; Bergner, Jennifer B.; Turner, Ewa M.; Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Proia, RL (reprint author), NIDDK, Genet Dev & Dis Branch, Bldg 10,Room 9D-06,10 Ctr DR MSC 1821, Bethesda, MD 20892 USA. EM richardp@intra.niddk.nih.gov FU Intramural Research Programs of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases; Lipidomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina [P30 CA138313]; Lipidomics Core in the SC Lipidomics and Pathobiology COBRE [P20 RR017677] FX This research was supported by the Intramural Research Programs of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases, the Lipidomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina (P30 CA138313), and the Lipidomics Core in the SC Lipidomics and Pathobiology COBRE (P20 RR017677). We thank Chuxia Deng and Cuiling Li for helping to generate the chimera mice and Galina Tuymetova for supplying the Sphk mutant mice. NR 70 TC 26 Z9 27 U1 0 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2014 VL 124 IS 5 BP 2076 EP 2086 DI 10.1172/JCI71194 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AG4XU UT WOS:000335424500023 PM 24667638 ER PT J AU Liu, QZ Tomei, S Ascierto, ML De Giorgi, V Bedognetti, D Dai, CL Uccellini, L Spivey, T Pos, Z Thomas, J Reinboth, J Murtas, D Zhang, QB Chouchane, L Weiss, GR Slingluff, CL Lee, PP Rosenberg, SA Alter, H Yao, KT Wang, E Marincola, FM AF Liu, Qiuzhen Tomei, Sara Ascierto, Maria Libera De Giorgi, Valeria Bedognetti, Davide Dai, Cuilian Uccellini, Lorenzo Spivey, Tara Pos, Zoltan Thomas, Jaime Reinboth, Jennifer Murtas, Daniela Zhang, Qianbing Chouchane, Lotfi Weiss, Geoffrey R. Slingluff, Craig L., Jr. Lee, Peter P. Rosenberg, Steven A. Alter, Harvey Yao, Kaitai Wang, Ena Marincola, Francesco M. TI Melanoma NOS1 expression promotes dysfunctional IFN signaling SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CANCER IMMUNE RESPONSIVENESS; NEGATIVE BREAST-CANCER; T-CELLS; METASTATIC MELANOMA; MALIGNANT-MELANOMA; COLORECTAL-CANCER; SUPPRESSOR-CELLS; EFFECTOR-CELLS; IN-VITRO; RESPONSES AB In multiple forms of cancer, constitutive activation of type I IFN signaling is a critical consequence of immune surveillance against cancer; however, PBMCs isolated from cancer patients exhibit depressed STAT1 phosphorylation in response to IFN-alpha, suggesting IFN signaling dysfunction. Here, we demonstrated in a coculture system that melanoma cells differentially impairs the IFN-alpha response in PBMCs and that the inhibitory potential of a particular melanoma cell correlates with NOS1 expression. Comparison of gene transcription and array comparative genomic hybridization (aCGH) between melanoma cells from different patients indicated that suppression of IFN-alpha signaling correlates with an amplification of the NOS1 locus within segment 12q22-24. Evaluation of NOS1 levels in melanomas and IFN responsiveness of purified PBMCs from patients indicated a negative correlation between NOS1 expression in melanomas and the responsiveness of PBMCs to IFN-alpha. Furthermore, in an explorative study, NOS1 expression in melanoma metastases was negatively associated with patient response to adoptive T cell therapy. This study provides a link between cancer cell phenotype and IFN signal dysfunction in circulating immune cells. C1 [Liu, Qiuzhen; Ascierto, Maria Libera; De Giorgi, Valeria; Bedognetti, Davide; Thomas, Jaime; Reinboth, Jennifer; Murtas, Daniela; Alter, Harvey; Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Clin Ctr & Trans NIH,CHI, Bethesda, MD 20892 USA. [Liu, Qiuzhen; Zhang, Qianbing; Yao, Kaitai] Southern Med Univ, Canc Res Inst, Guangzhou, Guangdong, Peoples R China. [Tomei, Sara] Weill Cornell Med Coll, Doha, Qatar. [Dai, Cuilian] Xiamen Univ, Sch Med, Zhongshan Hosp, Xiamen Heart Ctr, Xiamen, Fujian, Peoples R China. [Uccellini, Lorenzo] Columbia Univ, New York, NY USA. [Spivey, Tara] Rush Med Sch, Chicago, IL USA. [Pos, Zoltan] Expt & Translat lmmun Res Grp, MTA SE, Budapest, Hungary. [Pos, Zoltan] Semmelweis Univ, Dept Genet Cell & Immunobiol, H-1085 Budapest, Hungary. [Weiss, Geoffrey R.; Wang, Ena; Marincola, Francesco M.] Sidra Med & Res Ctr, Res Branch, Doha, Qatar. [Weiss, Geoffrey R.; Slingluff, Craig L., Jr.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Lee, Peter P.] City Hope & Beckman Res Inst, Duarte, CA USA. [Rosenberg, Steven A.] NCI, Surg Branch, Bethesda, MD 20892 USA. RP Liu, QZ (reprint author), Southern Med Univ, Canc Res Inst, Guangzhou, Guangdong, Peoples R China. EM liuqiu-zhen@126.gov; fmarincola@sidra.org RI Pos, Zoltan/C-3623-2014; De Giorgi, Valeria/D-4582-2017; OI Pos, Zoltan/0000-0002-2574-7616; Bedognetti, Davide/0000-0002-5857-773X FU Conquer Cancer Foundation of American Society of Clinical Oncology; National Basic Research Program of China [2010CB529406]; Department of Transfusion Medicine; Clinical Center and trans-NIH Center for Human Immunology (CHI); NIH FX We thank David A. Wink (Radiation Biology Branch, NCI, NIH) and Harvey Klein (Department of Transfusion Medicine, Clinical Center and trans-NIH CHI, NIH) for their useful comments. D. Bedognetes fellowship was supported by a 2011 Young Investigator Award from the Conquer Cancer Foundation of the American Society of Clinical Oncology. This work was supported by funds from the National Basic Research Program of China (973 Program 2010CB529406). The majority of this work was performed at the Infectious Disease and Immunogenetics Section (IDIS) of the Department of Transfusion Medicine, Clinical Center and trans-NIH Center for Human Immunology (CHI), NIH. NR 42 TC 10 Z9 10 U1 3 U2 17 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2014 VL 124 IS 5 BP 2147 EP 2159 DI 10.1172/JCI69611 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AG4XU UT WOS:000335424500029 PM 24691438 ER PT J AU Liesman, RM Buchholz, UJ Luongo, CL Yang, LJ Proia, AD DeVincenzo, JP Collins, PL Pickles, RJ AF Liesman, Rachael M. Buchholz, Ursula J. Luongo, Cindy L. Yang, Lijuan Proia, Alan D. DeVincenzo, John P. Collins, Peter L. Pickles, Raymond J. TI RSV-encoded NS2 promotes epithelial cell shedding and distal airway obstruction SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; NF-KAPPA-B; PARAINFLUENZA VIRUS; CILIATED CELLS; IN-VITRO; NONSTRUCTURAL PROTEINS; BRONCHIAL EPITHELIUM; PATHOLOGICAL-CHANGES; INTERFERON PATHWAYS; GENE-EXPRESSION AB Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in young children. The factors that contribute to the increased propensity of RSV-induced distal airway disease compared with other commonly encountered respiratory viruses remain unclear. Here, we identified the RSV-encoded nonstructural 2 (NS2) protein as a viral genetic determinant for initiating RSV-induced distal airway obstruction. Infection of human cartilaginous airway epithelium (HAE) and a hamster model of disease with recombinant respiratory viruses revealed that NS2 promotes shedding of infected epithelial cells, resulting in two consequences of virus infection. First, epithelial cell shedding accelerated the reduction of virus titers, presumably by clearing virus-infected cells from airway mucosa. Second, epithelial cells shedding into the narrow-diameter bronchiolar airway lumens resulted in rapid accumulation of detached, pleomorphic epithelial cells, leading to acute distal airway obstruction. Together, these data indicate that RSV infection of the airway epithelium, via the action of NS2, promotes epithelial cell shedding, which not only accelerates viral clearance but also contributes to acute obstruction of the distal airways. Our results identify RSV NS2 as a contributing factor for the enhanced propensity of RSV to cause severe airway disease in young children and suggest NS2 as a potential therapeutic target for reducing the severity of distal airway disease. C1 [Liesman, Rachael M.; Pickles, Raymond J.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. [Liesman, Rachael M.; Pickles, Raymond J.] Univ N Carolina, Cyst Fibrosis & Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA. [Buchholz, Ursula J.; Luongo, Cindy L.; Yang, Lijuan; Collins, Peter L.] NIAID, Infect Dis Lab, RNA Viruses Sect, NIH, Bethesda, MD 20892 USA. [Proia, Alan D.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [DeVincenzo, John P.] Univ Tennessee, Lebonheur Childrens Med Ctr, Memphis, TN USA. [DeVincenzo, John P.] Childrens Fdn Res Ctr, Memphis, TN USA. RP Pickles, RJ (reprint author), Univ N Carolina, Cyst Fibrosis & Pulm Res & Treatment Ctr, 7021 Thurston Bowles Bldg, Chapel Hill, NC 27599 USA. EM branston@med.unc.edu FU UNC University Research Council; NIH [R01HL103940, R01HL77844, P50HL084934, T32A1007419]; Intramural Research Program of the NIAID; NIH; HHMI through the Med-into-Grad Initiative FX The authors thank the Directors and teams of the UNC Cystic Fibrosis Center Core Facilities used during these studies: the Tissue Procurement and Cell Culture Core, the Morphology and Morphometry Core, and the Michael Hooker Microscopy Facility. We thank Kui Shen of the Computational Biology Section of the NIAID, NIH, for assistance with statistical analysis. We also thank Shirin Munir for the RSV NS1 and NS2 cDNAs, Richard Randall for providing the SVS-V plasmid, Robert Lamb for providing the PIVS-GFP virus, and Daniel Kolakofsky for providing the SeV-GFP virus. These studies were funded by grants from the UNC University Research Council and the NIH (R01HL103940, R01HL77844, P50HL084934, T32A1007419). U.J. Buchholz, C.L. Luongo, L. Yang, and P.L. Collins were supported by the Intramural Research Program of the NIAID, NIH. R.M. Liesman is a Howard Hughes Medical Institute (HHMI) Med-into-Grad Scholar supported in part by a grant to the University of North Carolina at Chapel Hill from HHMI through the Med-into-Grad Initiative. NR 70 TC 13 Z9 13 U1 1 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2014 VL 124 IS 5 BP 2219 EP 2233 DI 10.1172/JCI72948 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AG4XU UT WOS:000335424500036 PM 24713657 ER PT J AU Gros, A Robbins, PF Yao, X Li, YF Turcotte, S Tran, E Wunderlich, JR Mixon, A Farid, S Dudley, ME Hanada, K Almeida, JR Darko, S Douek, DC Yang, JC Rosenberg, SA AF Gros, Alena Robbins, Paul F. Yao, Xin Li, Yong F. Turcotte, Simon Tran, Eric Wunderlich, John R. Mixon, Arnold Farid, Shawn Dudley, Mark E. Hanada, Ken-ichi Almeida, Jorge R. Darko, Sam Douek, Daniel C. Yang, James C. Rosenberg, Steven A. TI PD-1 identifies the patient-specific CD8(+) tumor-reactive repertoire infiltrating human tumors SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID T-CELL EXHAUSTION; REVERSIBLE IMMUNE DYSFUNCTION; CHRONIC VIRAL-INFECTION; CANCER REGRESSION; MELANOMA PATIENTS; TRANSFER THERAPY; UP-REGULATION; INHIBITORY RECEPTORS; METASTATIC MELANOMA; DISEASE PROGRESSION AB Adoptive transfer of tumor-infiltrating lymphocytes (TILs) can mediate regression of metastatic melanoma; however, TILs are a heterogeneous population, and there are no effective markers to specifically identify and select the repertoire of tumor-reactive and mutation-specific CD8(+) lymphocytes. The lack of biomarkers limits the ability to study these cells and develop strategies to enhance clinical efficacy and extend this therapy to other malignancies. Here, we evaluated unique phenotypic traits of CD8(+) TILs and TCR (3 chain (TCR) clonotypic frequency in melanoma tumors to identify patient-specific repertoires of tumor-reactive CD8(+) lymphocytes. In all 6 tumors studied, expression of the inhibitory receptors programmed cell death 1 (PD-1; also known as CD279), lymphocyte-activation gene 3 (LAG-3; also known as CD223), and T cell immunoglobulin and mucin domain 3 (TIM-3) on CD8(+) TILs identified the autologous tumor-reactive repertoire, including mutated neoantigen-specific CD8(+) lymphocytes, whereas only a fraction of the tumor-reactive population expressed the costimulatory receptor 4-1BB (also known as CD137). TCR beta deep sequencing revealed oligodonal expansion of specific TCR(3 clonotypes in CD8(+)PD-1(+) compared with CD8(+)PD-1(-) TIL populations. Furthermore, the most highly expanded TCR beta clonotypes in the CD8(+) and the CD8(+)PD-1(+) populations recognized the autologous tumor and included donotypes targeting mutated antigens. Thus, in addition to the well-documented negative regulatory role of PD-1 in T cells, our findings demonstrate that PD-1 expression on CD8(+) TILs also accurately identifies the repertoire of clonally expanded tumor-reactive cells and reveal a dual importance of PD-1 expression in the tumor microenvironment. C1 [Gros, Alena; Robbins, Paul F.; Yao, Xin; Li, Yong F.; Turcotte, Simon; Tran, Eric; Wunderlich, John R.; Mixon, Arnold; Farid, Shawn; Dudley, Mark E.; Hanada, Ken-ichi; Yang, James C.; Rosenberg, Steven A.] NCI, Bethesda, MD 20892 USA. [Almeida, Jorge R.; Darko, Sam; Douek, Daniel C.] NCI, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Ctr Canc Res, Bldg 10 Hatfield CRC,Room 3-3940, Bethesda, MD 20892 USA. EM SAR@nih.gov OI Gros, Alena/0000-0002-1207-1880 FU Milstein Family Foundation FX We thank Christian Hinrichs, Sanja Stevanovic, Anna Pasetto, Mojgan Ahmadzadeh, Pawel Muranski, and Mona El-Gamil for helpful discussion, revision of the manuscript, and technical advice. This work was supported in part by a generous contribution from the Milstein Family Foundation. NR 70 TC 172 Z9 173 U1 7 U2 38 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2014 VL 124 IS 5 BP 2246 EP 2259 DI 10.1172/JC173639 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AG4XU UT WOS:000335424500038 PM 24667641 ER PT J AU Orgel, E Sposto, R Malvar, J Seibel, NL Ladas, E Gaynon, PS Freyer, DR AF Orgel, Etan Sposto, Richard Malvar, Jemily Seibel, Nita L. Ladas, Elena Gaynon, Paul S. Freyer, David R. TI Impact on Survival and Toxicity by Duration of Weight Extremes During Treatment for Pediatric Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BODY-MASS INDEX; NUTRITIONAL-STATUS; PROGNOSTIC-FACTOR; OBESITY; PHARMACOKINETICS; ADOLESCENTS; DIAGNOSIS; OVERWEIGHT; VALIDITY; THERAPY AB Purpose Previous studies regarding the influence of weight on event-free survival (EFS) and treatment-related toxicity (TRT) in childhood acute lymphoblastic leukemia (ALL) considered only weight at diagnosis. Inasmuch as weight varies substantially over treatment, we hypothesized its impact on EFS is instead determined by cumulative time spent at an extreme weight during therapy and on TRT by weight at the time of toxicity. Patients and Methods In a cohort of 2,008 children treated for high-risk ALL in Children's Oncology Group study CCG-1961, we determined the effect on EFS of cumulative time receiving therapy at an extreme weight (either obese or underweight) between end of induction and start of maintenance therapy. We also evaluated the association between weight category and incidence and patterns of TRT during 13,946 treatment courses. Results Being obese or underweight at diagnosis and for >= 50% of the time between end of induction and start of maintenance therapy resulted in inferior EFS (hazard ratios, 1.43 and 2.30, respectively; global P < .001). Normalization of weight during that period resulted in mitigation of this risk comparable to never being obese or underweight. Obese or underweight status at start of each treatment course was significantly associated with specific patterns of TRT. Conclusion Influence of weight extremes on EFS and TRT is not set at diagnosis as previously reported but is moderated by subsequent weight status during intensive postinduction treatment phases. These observations suggest that weight is a potentially addressable risk factor to improve EFS and morbidity in pediatric ALL. C1 [Orgel, Etan] Miller Childrens Hosp, Jonathan Jaques Childrens Canc Ctr, Long Beach, CA USA. [Orgel, Etan; Gaynon, Paul S.; Freyer, David R.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Orgel, Etan; Sposto, Richard; Malvar, Jemily; Gaynon, Paul S.; Freyer, David R.] Childrens Hosp Los Angeles, Childrens Ctr Canc & Blood Dis, Los Angeles, CA 90027 USA. [Sposto, Richard] Univ So Calif, Los Angeles, CA USA. [Seibel, Nita L.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Ladas, Elena] Columbia Univ, Ctr Comprehens Wellness, New York, NY USA. RP Orgel, E (reprint author), Miller Childrens Hosp Long Beach, Jonathan Jaques Childrens Canc Ctr, 2801 Atlantic Ave, Long Beach, CA 90806 USA. EM eorgel@memorialcare.org OI Orgel, Etan/0000-0002-1487-6818 FU NCI NIH HHS [U10CA98413, U10 CA095861, U10CA98543, U10 CA180899, U10 CA098543, U10 CA180886, U10 CA098413] NR 39 TC 25 Z9 25 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2014 VL 32 IS 13 BP 1331 EP + DI 10.1200/JCO.2013.52.6962 PG 9 WC Oncology SC Oncology GA AF7SP UT WOS:000334915300011 PM 24687836 ER PT J AU Brennan, CW Olds, DM Dolansky, M Estrada, CA Patrician, PA AF Brennan, Caitlin W. Olds, Danielle M. Dolansky, Mary Estrada, Carlos A. Patrician, Patricia A. TI Learning by doing: observing an interprofessional process as an interprofessional team SO JOURNAL OF INTERPROFESSIONAL CARE LA English DT Article DE Interprofessional collaboration; interprofessional education; interprofessional evaluation; teams ID EDUCATION; PROGRAM; QUALITY AB New competencies exist for interprofessional education, which are centered on the goal of improving quality of care and patient safety through improved interprofessional collaboration. Interprofessional education and effective interprofessional collaboration are cornerstones of the Veterans Affairs Quality Scholars fellowship program. The purpose of this project was to evaluate an innovative interprofessional education strategy in which teams of physicians and nurses were "learning by doing'' as they observed and analyzed the functioning of an interprofessional process, specifically, inpatient discharge. Fellows completed voluntary, anonymous surveys seeking their perspectives about the project. Fellows' feedback revealed several themes, with both positive and negative characteristics related to team functioning, interprofessional understanding, microsystem knowledge, pooled knowledge and assignment challenges. The strength of this strategy is exemplified by the fact that fellows not only learned from each other's separate professional observations, but also observed the emergence of a shared interprofessional perspective through working together. C1 [Brennan, Caitlin W.] NIH, Ctr Clin, Dept Nursing Res & Practice Dev, Bethesda, MD 20892 USA. [Olds, Danielle M.] Univ Kansas, Med Ctr, NDNQI, Kansas City, KS 66103 USA. [Dolansky, Mary] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA. [Estrada, Carlos A.] Univ Alabama Birmingham, Birmingham VA Med Ctr, Birmingham, AL USA. [Patrician, Patricia A.] Univ Alabama Birmingham, Birmingham, AL USA. RP Brennan, CW (reprint author), NIH, Ctr Clin, Dept Nursing, 10 Ctr Dr,Room 2B08, Bethesda, MD 20892 USA. EM caitlin.brennan@nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 6 TC 5 Z9 5 U1 0 U2 7 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1356-1820 EI 1469-9567 J9 J INTERPROF CARE JI J. Interprofessional Care PD MAY PY 2014 VL 28 IS 3 BP 249 EP 251 DI 10.3109/13561820.2013.838750 PG 3 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AG2DI UT WOS:000335225800012 PM 24070019 ER PT J AU Kim, S Lee, J Heo, NJ Lee, JW Han, JS AF Kim, Sejoong Lee, Jeonghwan Heo, Nam Ju Lee, Jae Wook Han, Jin Suk TI Alkali Therapy Attenuates the Progression of Kidney Injury via Na/H Exchanger Inhibition in 5/6 Nephrectomized Rats SO JOURNAL OF KOREAN MEDICAL SCIENCE LA English DT Article DE Sodium Bicarbonate; Acidosis; Kidney Failure Chronic ID GLOMERULAR-FILTRATION-RATE; CHRONIC METABOLIC-ACIDOSIS; THICK ASCENDING LIMB; ACUTE-RENAL-FAILURE; PROXIMAL TUBULE; NA+/H+ EXCHANGER; SODIUM; EXPRESSION; ENDOTHELIN; ENAC AB Metabolic acidosis is a cause of renal disease progression, and alkali therapy ameliorates its progression. However, there are few reports on the role of renal acid-base transporters during alkali therapy. We evaluated the effect of sodium bicarbonate therapy and the role of acid-base transporters on renal disease progression in rats with a remnant kidney. Sprague-Dawley rats consumed dietary sodium bicarbonate (NaHCO3) or sodium chloride (NaCl) with 20% casein after a 5/6 nephrectomy. After being provided with a casein diet, the NaHCO3-treated group had higher levels of serum bicarbonate than the control group. At week 4, the glomerular filtration rate in the NaHCO3 group was higher than that in the NaCl group, and the difference became prominent at week 10. The glomerulosclerosis and tubulointerstitial damage indices in the NaHCO3 group were less severe compared with controls at week 4 and 10. The expression of the Na/H exchanger (NHE) was decreased, and apical reactivity was decreased in the NaHCO3 group, compared with the NaCl group. Endothelin-1 levels in the kidney were also decreased in the NaHCO3 group. Dietary sodium bicarbonate has the effects of ameliorating renal disease progression, which may be related to the altered expression of NHE in the remaining kidney. C1 [Kim, Sejoong; Heo, Nam Ju; Han, Jin Suk] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Kim, Sejoong] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam, South Korea. [Lee, Jeonghwan] Hallym Univ, Hangang Sacred Heart Hosp, Dept Internal Med, Seoul, South Korea. [Heo, Nam Ju] Seoul Natl Univ Hosp, Dept Internal Med, Healthcare Syst Gangnam Ctr, Seoul 110744, South Korea. [Lee, Jae Wook] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA. RP Han, JS (reprint author), Seoul Natl Univ Hosp, Dept Internal Med, 101 Daehak Ro, Seoul 110744, South Korea. EM jshan@snu.ac.kr OI Lee, Jae Wook/0000-0003-0120-8164 NR 28 TC 1 Z9 1 U1 0 U2 3 PU KOREAN ACAD MEDICAL SCIENCES PI SEOUL PA 302 75 DONG DU ICHON, DONG YONGSAN KU, SEOUL 140 031, SOUTH KOREA SN 1011-8934 EI 1598-6357 J9 J KOREAN MED SCI JI J. Korean Med. Sci. PD MAY PY 2014 VL 29 IS 5 BP 691 EP 698 DI 10.3346/jkms.2014.29.5.691 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AG4GY UT WOS:000335378800014 PM 24851027 ER PT J AU Chen, X Oppenheim, JJ AF Chen, Xin Oppenheim, Joost J. TI Th17 cells and T-regs: unlikely allies SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE inflammation; immunosuppression; TNFR2; TNF; Foxp3; IL-17 ID VERSUS-HOST-DISEASE; TUMOR-INFILTRATING LYMPHOCYTES; HUMAN PERIPHERAL-BLOOD; HUMANIZED MOUSE MODEL; EX-VIVO EXPANSION; REGULATORY-CELLS; DENDRITIC CELLS; IN-VIVO; PROINFLAMMATORY CYTOKINES; AUTOIMMUNE-DISEASE AB Review on the reciprocal stimulatory effects of proinflammatory Th17 cells, wth immunosuppressive T-reg cells. Identification of CD4(+)Foxp3(+) T-regs and Th17 modified the historical Th1-Th2 paradigm. Currently, the Th17-T-regs dichotomy provides a dominant conceptual framework for the comprehension of immunity/inflammation and tolerance/immunosuppression in an increasing number of diseases. Targeting proinflammatory Th17 cells or immunosuppressive T-regs has been widely considered as a promising therapeutic strategy in the treatment of major human diseases, including autoimmunity and cancer. The efficacy and safety of such therapy rely on a thorough understanding of immunobiology and interaction of these two subsets of Th cells. In this article, we review recent progress concerning complicated interplay of Th17 cells and T-regs. There is compelling evidence that T-regs potently inhibit Th1 and Th2 responses; however, the inhibitory effect of T-regs on Th17 responses is a controversial subject. There is increasing evidence showing that T-regs actually promote the differentiation of Th17 cells in vitro and in vivo and consequently, enhanced the functional consequences of Th17 cells, including the protective effect in host defense, as well as detrimental effect in inflammation and in the support of tumor growth. On the other hand, Th17 cells were also the most potent Th subset in the stimulation and support of expansion and phenotypic stability of T-regs in vivo. These results indicate that these two subsets of Th cells reciprocally stimulate each other. This bidirectional crosstalk is largely dependent on the TNF-TNFR2 pathway. These mutual stimulatory effects should be considered in devising future Th17 cell- and T-reg-targeting therapy. C1 [Chen, Xin] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Basic Sci Program, Frederick, MD USA. [Chen, Xin; Oppenheim, Joost J.] NCI, Ctr Canc Res, Canc Inflammat Program, Mol Immunoregulat Lab, Frederick, MD 21702 USA. RP Chen, X (reprint author), NCI, Ctr Canc Res, Canc Inflammat Program, Mol Immunoregulat Lab, Bldg 560,Rm 31-19,1050 Boyles St,POB B, Frederick, MD 21702 USA. EM chenxin@mail.nih.gov; oppenhej@mail.nih.gov OI Chen, Xin/0000-0002-2628-4027 FU National Cancer Institute, U.S. National Institutes of Health [HHSN26120080001E]; Intramural Research Program of the U.S. National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This project has been funded, in whole or in part, with federal funds from the National Cancer Institute, U.S. National Institutes of Health, under contract HHSN26120080001E. This research was supported, in part, by the Intramural Research Program of the U.S. National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 130 TC 15 Z9 16 U1 2 U2 24 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 EI 1938-3673 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAY PY 2014 VL 95 IS 5 BP 723 EP 731 DI 10.1189/jlb.1213633 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA AG3SV UT WOS:000335340900005 PM 24563509 ER PT J AU Meilleur, KG Zukosky, K Medne, L Fequiere, P Powell-Hamilton, N Winder, TL Alsaman, A El-Hattab, AW Dastgir, J Hu, Y Donkervoort, S Golden, JA Eagle, R Finkel, R Scavina, M Hood, IC Rorke-Adams, LB Bonnemann, CG AF Meilleur, Katherine G. Zukosky, Kristen Medne, Livija Fequiere, Pierre Powell-Hamilton, Nina Winder, Thomas L. Alsaman, Abdulaziz El-Hattab, Ayman W. Dastgir, Jahannaz Hu, Ying Donkervoort, Sandra Golden, Jeffrey A. Eagle, Ralph Finkel, Richard Scavina, Mena Hood, Ian C. Rorke-Adams, Lucy B. Boennemann, Carsten G. TI Clinical, Pathologic, and Mutational Spectrum of Dystroglycanopathy Caused by LARGE Mutations SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Agyria; Congenital muscular dystrophy; Dystroglycanopathy; LARGE; Neuropathology; Polymicrogyria ID CONGENITAL MUSCULAR-DYSTROPHY; WALKER-WARBURG-SYNDROME; HUMAN LARGE GENE; ALPHA-DYSTROGLYCAN; DEFECTIVE GLYCOSYLATION; GLYCOPROTEIN COMPLEX; LAMININ-BINDING; FUKUYAMA-TYPE; INVOLVEMENT; ISPD AB Dystroglycanopathies are a subtype of congenital muscular dystrophy of varying severity that can affect the brain and eyes, ranging from Walker-Warburg syndrome with severe brain malformation to milder congenital muscular dystrophy presentations with affected or normal cognition and later onset. Mutations in dystroglycanopathy genes affect a specific glycoepitope on -dystroglycan; of the 14 genes implicated to date, LARGE encodes the glycosyltransferase that adds the final xylose and glucuronic acid, allowing -dystroglycan to bind ligands, including laminin 211 and neurexin. Only 11 patients with LARGE mutations have been reported. We report the clinical, neuroimaging, and genetic features of 4 additional patients. We confirm that gross deletions and rearrangements are important mutational mechanisms for LARGE. The brain abnormalities overshadowed the initially mild muscle phenotype in all 4 patients. We present the first comprehensive postnatal neuropathology of the brain, spinal cord, and eyes of a patient with a homozygous LARGE mutation at Cys443. In this patient, polymicrogyria was the predominant cortical malformation; densely festooned polymicrogyria were overlaid by a continuous agyric surface. In view of the severity of these abnormalities, Cys443 may be a functionally important residue in the LARGE protein, whereas the mutation p.Glu509Lys of Patient 1 in this study may confer a milder phenotype. Overall, these results expand the clinical and genetic spectrum of dystroglycanopathy. C1 [Meilleur, Katherine G.] NINR, Bethesda, MD 20892 USA. [Zukosky, Kristen; Dastgir, Jahannaz; Hu, Ying; Donkervoort, Sandra; Boennemann, Carsten G.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. [Medne, Livija; Rorke-Adams, Lucy B.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Fequiere, Pierre] Univ Alabama Birmingham, Dept Pediat, Div Pediat Neurol, Birmingham, AL USA. [Powell-Hamilton, Nina; Scavina, Mena] Nemours Alfred I duPont Hosp Children, Wilmington, DE USA. [Winder, Thomas L.] Prevent Genet, Marshfield, WI USA. [Alsaman, Abdulaziz] King Fahad Med City, Natl Neurosci Inst, Pediat Neurol Dept, Riyadh, Saudi Arabia. [El-Hattab, Ayman W.] King Fahad Med City, Childrens Hosp, Dept Pediat, Div Med Genet, Riyadh, Saudi Arabia. [Alsaman, Abdulaziz; El-Hattab, Ayman W.] King Saud bin Abdulaziz Univ Hlth Sci, Coll Med, Riyadh, Saudi Arabia. [Golden, Jeffrey A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Golden, Jeffrey A.] Harvard Univ, Sch Med, Boston, MA USA. [Eagle, Ralph] Thomas Jefferson Univ, Dept Pathol, Wills Eye Inst, Philadelphia, PA 19107 USA. [Finkel, Richard] Nemours Childrens Hosp, Orlando, FL USA. [Hood, Ian C.] Med Examiners Off, Mt Holly, NJ USA. RP Bonnemann, CG (reprint author), Natl Inst Neurol Disorders & Stroke, Porter Neurosci Res Ctr, NIH, Room 2A-116,Bldg 35,35 Convent Dr, Bethesda, MD 20892 USA. EM carsten.bonnemann@nih.gov FU Division of Intramural Research of the National Institute of Neurological Disorders and Stroke FX Katherine G. Meilleur, Kristen Zukosky, Ying Hu, Jahannaz Dastgir, Sandra Donkervoort, and Carsten G. Bonnemann received funding from the Division of Intramural Research of the National Institute of Neurological Disorders and Stroke. NR 48 TC 8 Z9 9 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 EI 1554-6578 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2014 VL 73 IS 5 BP 425 EP 441 DI 10.1097/NEN.0000000000000065 PG 17 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AF9BY UT WOS:000335011300005 PM 24709677 ER PT J AU Tanabe, S Cumming, BG AF Tanabe, Seiji Cumming, Bruce G. TI Delayed suppression shapes disparity selective responses in monkey V1 SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE vision; binocular; receptive field; striate cortex; suppression ID STEREO CORRESPONDENCE PROBLEM; CAT STRIATE CORTEX; BINOCULAR DISPARITY; VISUAL-CORTEX; RECEPTIVE-FIELDS; MACAQUE V1; DEPTH DISCRIMINATION; COMPLEX CELLS; NEURONS; MECHANISMS AB The stereo correspondence problem poses a challenge to visual neurons because localized receptive fields potentially cause false responses. Neurons in the primary visual cortex (V1) partially resolve this problem by combining excitatory and suppressive responses to encode binocular disparity. We explored the time course of this combination in awake, monkey V1 neurons using subspace mapping of receptive fields. The stimulus was a binocular noise pattern constructed from discrete spatial frequency components. We forward correlated the firing of the V1 neuron with the occurrence of binocular presentations of each spatial frequency component. The forward correlation yielded a complete set of response time courses to every combination of spatial frequency and interocular phase difference. Some combinations produced suppressive responses. Typically, if an interocular phase difference for a given spatial frequency produced strong excitation, we saw suppression in response to the opposite interocular phase difference at lower spatial frequencies. The suppression was delayed relative to the excitation, with a median difference in latency of 7 ms. We found that the suppressive mechanism explains a well-known mismatch of monocular and binocular signals. The suppressive components increased power at low spatial frequencies in disparity tuning, whereas they reduced the monocular response to low spatial frequencies. This long-recognized mismatch of binocular and monocular signals reflects a suppressive mechanism that helps reduce the response to false matches. C1 [Tanabe, Seiji; Cumming, Bruce G.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Tanabe, S (reprint author), 1410 Pelham Pkwy S,Rm 822, Bronx, NY 10461 USA. EM seiji.tanabe@gmail.com FU Intramural Program of the National Eye Institute; Long-Term Fellowship of the Human Frontier Science Program FX This work was supported by the Intramural Program of the National Eye Institute. S. Tanabe was partially supported by the Long-Term Fellowship of the Human Frontier Science Program. NR 27 TC 4 Z9 4 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2014 VL 111 IS 9 BP 1759 EP 1769 DI 10.1152/jn.00426.2013 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA AG9ZR UT WOS:000335779300005 PM 24501264 ER PT J AU Lonser, RR Butman, JA Huntoon, K Asthagiri, AR Wu, TX Bakhtian, KD Chew, EY Zhuang, ZP Linehan, WM Oldfield, EH AF Lonser, Russell R. Butman, John A. Huntoon, Kristin Asthagiri, Ashok R. Wu, Tianxia Bakhtian, Kamran D. Chew, Emily Y. Zhuang, Zhengping Linehan, W. Marston Oldfield, Edward H. TI Prospective natural history study of central nervous system hemangioblastomas in von Hippel-Lindau disease Clinical article SO JOURNAL OF NEUROSURGERY LA English DT Article DE central nervous system; hemangioblastoma; natural history; von Hippel-Lindau disease; oncology ID ENDOLYMPHATIC SAC TUMORS; MORBID HEARING-LOSS; PROTEIN; MANIFESTATIONS; PROGRESSION; MANAGEMENT; MUTATIONS; FAMILIES; FEATURES; CANCER AB Object. The tumors most frequently associated with von Hippel-Lindau (VHL) disease are hemangioblastomas. While they are associated with significant neurological impairment and mortality, their natural history and optimal management have not been fully defined. Methods. Patients with VHL were enrolled in a prospective study designed to define the natural history of CNS hemangioblastomas. In the present analysis, serial imaging, laboratory, genetic, and clinical data were evaluated in those with at least 2 years of follow-up data. Results. At study entrance 225 patients (111 males, 114 females) harbored 1921 CNS hemangioblastomas in the supratentorial compartment (21 tumors [1%]), cerebellum (865 [45%]), brainstem (129 [7%]), spinal cord (689 [36%]), cauda equina (212 [11%]), and nerve roots (5 [0.3%]; follow-up 15,819 hemangioblastoma-years). Increased tumor burden was associated with partial deletions in the VHL gene (p = 0.005) and male sex (p = 0.002). Hemangioblastoma development (median 0.3 new tumors/year) was associated with younger age (p < 0.0001) and more tumors at study entrance (p < 0.0001). While 1278 hemangioblastomas (51%) did not grow, 1227 hemangioblastomas (49%) grew in a saltatory (886 [72%]), linear (76 [6%]), or exponential (264 [22%]) pattern. Faster tumor growth was associated with male sex (p = 0.001), symptomatic tumors (p < 0.0001), and tumors associdted with cysts (p < 0.0001). Location-dependent tumor size was the primary predictor of eventual symptom formation (159 symptomatic tumors [6.3%]; area under the curve > 0.9). Conclusions. Central nervous system hemangioblastoma burden in VHL is associated with partial germline deletions and male sex. Unpredictable growth of hemangioblastomas compromises assessment of nonsurgical therapies. The judicious treatment of symptom-producing hemangioblastomas, while avoiding unnecessary treatment of asymptomatic tumors that may not progress, can provide clinical stability. Clinical trial registration no.: NCT00005902 (ClinicalTrials.gov). C1 [Lonser, Russell R.; Huntoon, Kristin; Asthagiri, Ashok R.; Bakhtian, Kamran D.; Zhuang, Zhengping; Oldfield, Edward H.] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. [Wu, Tianxia] NINDS, Off Clin Director, Bethesda, MD 20892 USA. [Butman, John A.] NIH, Neuroradiol Sect, Ctr Clin, Bethesda, MD 20892 USA. [Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. [Linehan, W. Marston] NIH, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Lonser, Russell R.] Ohio State Univ, Dept Neurol Surg, Wexner Med Ctr, Columbus, OH 43210 USA. [Oldfield, Edward H.] Univ Virginia, Dept Neurol Surg, Charlottesville, VA USA. RP Lonser, RR (reprint author), Ohio State Univ, Dept Neurol Surg, Wexner Med Ctr, 410 West 10th Ave,Doan Hall N1047, Columbus, OH 43210 USA. EM russell.lonser@osumc.edu RI Butman, John/J-2780-2013 OI Butman, John/0000-0002-1547-9195 FU Intramural Research Programs of the National Institute of Neurological Disorders and Stroke; Clinical Center; National Eye Institute; National Cancer Institute at the National Institutes of Health FX This research was supported by the Intramural Research Programs of the National Institute of Neurological Disorders and Stroke, the Clinical Center, National Eye Institute and the National Cancer Institute at the National Institutes of Health. The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. NR 34 TC 18 Z9 19 U1 0 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 2014 VL 120 IS 5 BP 1055 EP 1062 DI 10.3171/2014.1.JNS131431 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AF7OD UT WOS:000334903500006 PM 24579662 ER PT J AU Taylor, CL Patterson, KY Roseland, JM Wise, SA Merkel, JM Pehrsson, PR Yetley, EA AF Taylor, Christine L. Patterson, Kristine Y. Roseland, Janet M. Wise, Stephen A. Merkel, Joyce M. Pehrsson, Pamela R. Yetley, Elizabeth A. TI Including Food 25-Hydroxyvitamin D in Intake Estimates May Reduce the Discrepancy between Dietary and Serum Measures of Vitamin D Status SO JOURNAL OF NUTRITION LA English DT Article ID TANDEM MASS-SPECTROMETRY; BIOLOGICAL-ACTIVITY; MAJOR METABOLITES; D-3; FORTIFICATION; TRANSPORT; PRESSURE; ADULTS AB The discrepancy between the commonly used vitamin D status measures intake and serum 25-hydroxyvitamin D [25(OH)D] concentrations has been perplexing. Sun exposure increases serum 25(OH)D concentrations and is often used as an explanation for the higher population-based serum concentrations in the face of apparently low vitamin D intake. However, sun exposure may not be the total explanation. 25(OH)D, a metabolite of vitamin D, is known to be present in animal-based foods. It has been measured and reported only sporadically and is not currently factored into U.S. estimates of vitamin D intake. Previously unavailable preliminary USDA data specifying the 25(OH)D content of a subset of foods allowed exploration of the potential change in the reported overall vitamin D content of foods when the presence of 25(OH)D was included. The issue of 25(OH)D potency was addressed, and available commodity intake estimates were used to outline trends in projected vitamin D intake when 25(OH)D in foods was taken into account. Given the data available, there were notable increases in the total vitamin D content of a number of animal-based foods when potency-adjusted 25(OH)D was included, and in turn there was a potentially meaningful increase (1.7-2.9 mu g or 15-30% of average requirement) in vitamin D intake estimates. The apparent increase could reduce discrepancies between intake estimates and serum 25(OH)D concentrations. The relevance to dietary interventions is discussed, and the need for continued exploration regarding 25(OH)D measurement is highlighted. C1 [Taylor, Christine L.; Merkel, Joyce M.; Yetley, Elizabeth A.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Patterson, Kristine Y.; Roseland, Janet M.; Pehrsson, Pamela R.] ARS, Nutr Data Lab, USDA, Beltsville, MD USA. [Wise, Stephen A.] NIST, Dept Commerce, Gaithersburg, MD 20899 USA. RP Taylor, CL (reprint author), NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA. EM TaylorCL3@od.nih.gov NR 34 TC 18 Z9 18 U1 1 U2 8 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD MAY PY 2014 VL 144 IS 5 BP 654 EP 659 DI 10.3945/jn.113.189811 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AF8MQ UT WOS:000334970700012 PM 24623845 ER PT J AU Major, JM Yu, K Weinstein, SJ Berndt, SI Hyland, PL Yeager, M Chanock, S Albanes, D AF Major, Jacqueline M. Yu, Kai Weinstein, Stephanie J. Berndt, Sonja I. Hyland, Paula L. Yeager, Meredith Chanock, Stephen Albanes, Demetrius TI Genetic Variants Reflecting Higher Vitamin E Status in Men Are Associated with Reduced Risk of Prostate Cancer SO JOURNAL OF NUTRITION LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; GENOME-WIDE ASSOCIATION; SERUM ALPHA-TOCOPHEROL; CARDIOVASCULAR-DISEASE; BETA-CAROTENE; SUPPLEMENTATION; PREVENTION; RETINOL; PLASMA; LYCOPENE AB Vitamin E (alpha-tocopherol) plays a key role in the regulation of cell growth and differentiation and has been studied as a potential chemopreventive agent for prostate cancer. The association of serum vitamin E concentrations with cancer risk may be modified by genetic variations in vitamin E related genes. We examined whether variants in vitamin E related genes were associated with risk of prostate cancer in a nested case-control study using 483 prostate cancer cases and 542 matched controls of European ancestry from a large U.S. multicenter trial that had available measurements of serum vitamin E concentrations and genotyping of 3 genome-wide association study meta-analysis identified single-nucleotide polymorphisms (SNPs) associated with circulating vitamin E. ORs and 95% CIs were calculated using unconditional logistic regression adjusted for age, family history of prostate cancer, and serum total cholesterol. Findings suggest lower prostate cancer risk for men whose genotypes reflect higher vitamin E (i.e., alpha-tocopherol) status. An SNP (rs964184) near budding-site selection protein 13 (yeast) (BUD13), zinc finger protein 259 (ZNF259), and apolipoprotein A5 (APOA5) on 11q23.3 was significantly associated with prostate cancer risk (per-allele OR = 0.75; 95% Cl: 0.58, 0.98; P-trend = 0.03). The association between rs964184 and prostate cancer risk was stronger among homozygous carriers of the minor allele (OR = 0.27; 95% Cl: 0.09, 0.83). Another variant, rs11057830 in scavenger receptor class-B member 1 (SCARB1) on 12p24.31, approached statistical significance (OR = 0.32; 95% Cl: 0.10, 1.01, P = 0.05; 2 minor allele copies). This study suggests that polymorphisms near BUD13/ZNF259/APOA5, involved in vitamin E transport and metabolism, may be associated with lower risk of prostate cancer. This trial was registered at clinicaltrials.gov as NCT00002540. C1 [Major, Jacqueline M.; Yu, Kai; Weinstein, Stephanie J.; Berndt, Sonja I.; Hyland, Paula L.; Yeager, Meredith; Chanock, Stephen; Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Major, Jacqueline M.] US FDA, Div Epidemiol, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Yeager, Meredith; Chanock, Stephen] NCI Frederick, Core Genotyping Facil, Frederick, MD USA. RP Major, JM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM Jacgueline.major@fda.hhs.gov RI Albanes, Demetrius/B-9749-2015 FU Intramural Research Program of the NIH; National Cancer Institute FX Supported in part by the Intramural Research Program of the NIH and the National Cancer Institute. This study was initiated at the National Cancer Institute. The views represented herein are those of the authors and do not necessarily represent those of the FDA or U.S. Department of Health and Human Services. NR 28 TC 6 Z9 6 U1 0 U2 4 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD MAY PY 2014 VL 144 IS 5 BP 729 EP 733 DI 10.3945/jn.113.189928 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AF8MQ UT WOS:000334970700022 PM 24623848 ER PT J AU Raju, TNK Mercer, BM Burchfield, DJ Joseph, GF AF Raju, T. N. K. Mercer, B. M. Burchfield, D. J. Joseph, G. F. TI Periviable birth: executive summary of a Joint Workshop by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, American Academy of Pediatrics, and American College of Obstetricians and Gynecologists SO JOURNAL OF PERINATOLOGY LA English DT Article ID EXTREMELY PREMATURE-INFANTS; EXTREMELY PRETERM INFANTS; WEEKS GESTATIONAL-AGE; WEIGHT INFANTS; UNITED-STATES; NEURODEVELOPMENTAL OUTCOMES; ANTENATAL CORTICOSTEROIDS; EMERGENCY CERCLAGE; NEONATAL OUTCOMES; MORTALITY RATES AB This is an executive summary of a workshop on the management and counseling issues of women anticipated to deliver at a periviable gestation (broadly defined as 20 0/7 through 25 6/7 weeks of gestation), and the treatment options for the newborn. Upon review of the available literature, the workshop panel noted that the rates of neonatal survival and neurodevelopmental disabilities among the survivors vary greatly across the periviable gestations and are significantly influenced by the obstetric and neonatal management practices (for example, antenatal steroid, tocolytic agents and antibiotic administration; cesarean birth; and local protocols for perinatal care, neonatal resuscitation and intensive care support). These are, in turn, influenced by the variations in local and regional definitions of limits of viability. Because of the complexities in making difficult management decisions, obstetric and neonatal teams should confer prior to meeting with the family, when feasible. Family counseling should be coordinated with the goal of creating mutual trust, respect and understanding, and should incorporate evidence-based counseling methods. Since clinical circumstances can change rapidly with increasing gestational age, counseling should include discussion of the benefits and risks of various maternal and neonatal interventions at the time of counseling. There should be a plan for follow-up counseling as clinical circumstances evolve. The panel proposed a research agenda and recommended developing educational curricula on the care and counseling of families facing the birth of a periviable infant. C1 [Raju, T. N. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Mercer, B. M.] Soc Maternal Fetal Med, Cleveland, OH USA. [Mercer, B. M.] Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA. [Burchfield, D. J.] Amer Acad Pediat, Gainesville, FL USA. [Burchfield, D. J.] Univ Florida, Gainesville, FL USA. [Joseph, G. F.] Amer Coll Obstetricians & Gynecologists, Washington, DC 20024 USA. RP Mercer, BM (reprint author), Metrohlth Med Ctr, Dept Obstet & Gynecol, Suite G267,2500 MetroHlth Dr, Cleveland, OH 44109 USA. EM bmercer@metrohealth.org NR 60 TC 26 Z9 26 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0743-8346 EI 1476-5543 J9 J PERINATOL JI J. Perinatol. PD MAY PY 2014 VL 34 IS 5 BP 333 EP 342 DI 10.1038/jp.2014.70 PG 10 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA AG4EU UT WOS:000335372900002 PM 24722647 ER EF