FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bloss, G AF Bloss, Gregory TI THE ALCOHOL POLICY INFORMATION SYSTEM (APIS) AND POLICY RESEARCH AT NIAAA SO ALCOHOL RESEARCH & HEALTH LA English DT Editorial Material ID TIME-SERIES ANALYSES; FATAL CRASHES; DRINKING; MORTALITY; TAXES; LAWS C1 NIAAA, Div Epidemiol & Prevent Res, Rockville, MD 20852 USA. RP Bloss, G (reprint author), NIAAA, Div Epidemiol & Prevent Res, Rockville, MD 20852 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2011 VL 34 IS 2 BP 246 EP 247 PG 2 WC Substance Abuse SC Substance Abuse GA 865IM UT WOS:000298304600014 PM 22330224 ER PT J AU Thanos, PK Gopez, V Delis, F Michaelides, M Grandy, DK Wang, GJ Kunos, G Volkow, ND AF Thanos, Panayotis K. Gopez, Vanessa Delis, Foteini Michaelides, Michael Grandy, David K. Wang, Gene-Jack Kunos, George Volkow, Nora D. TI Upregulation of Cannabinoid Type 1 Receptors in Dopamine D2 Receptor Knockout Mice Is Reversed by Chronic Forced Ethanol Consumption SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Cannabinoid; CB1; Dopamine; D2; Knockout; Ethanol; Autoradiography ID CONDITIONED PLACE PREFERENCE; PRENATAL HALOPERIDOL EXPOSURE; PREFERRING SP RATS; CB1 RECEPTOR; NUCLEUS-ACCUMBENS; SEX-DIFFERENCES; DEFICIENT MICE; ENERGY-EXPENDITURE; LOCOMOTOR-ACTIVITY; BRAIN-STIMULATION AB Background: The anatomical proximity of the cannabinoid type 1 (CNR1/CB1R) and the dopamine D2 receptors (DRD2), their ability to form CB1R-DRD2 heteromers, their opposing roles in locomotion, and their involvement in ethanol's reinforcing and addictive properties prompted us to study the levels and distribution of CB1R after chronic ethanol intake, in the presence and absence of DRD2. Methods: We monitored the drinking patterns and locomotor activity of Drd2+/+ and Drd2-/- mice consuming either water or a 20% (v/v) ethanol solution (forced ethanol intake) for 6 months and used the selective CB1 receptor antagonist [3H]SR141716A to quantify CB1R levels in different brain regions with in vitro receptor autoradiography. Results: We found that the lack of DRD2 leads to a marked upregulation (approximately 2-fold increase) of CB1R in the cerebral cortex, the caudate-putamen, and the nucleus accumbens, which was reversed by chronic ethanol intake. Conclusions: The results suggest that DRD2-mediated dopaminergic neurotransmission and chronic ethanol intake exert an inhibitory effect on cannabinoid receptor expression in cortical and striatal regions implicated in the reinforcing and addictive properties of ethanol. C1 [Thanos, Panayotis K.; Volkow, Nora D.] NIAAA, Dept Hlth & Human Serv, Lab Neuroimaging, NIH, Bethesda, MD USA. [Thanos, Panayotis K.; Gopez, Vanessa; Delis, Foteini; Michaelides, Michael; Wang, Gene-Jack] Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA. [Michaelides, Michael] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Grandy, David K.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. [Kunos, George] NIAAA, Dept Hlth & Human Serv, Lab Physiol Studies, NIH, Bethesda, MD USA. RP Thanos, PK (reprint author), NIAAA, Dept Hlth & Human Serv, Lab Neuroimaging, NIH, Bethesda, MD USA. EM thanos@bnl.gov RI Michaelides, Michael/K-4736-2013 OI Michaelides, Michael/0000-0003-0398-4917 FU NIAAA [AA 11034, AA07574, AA07611] FX This work was supported by the NIAAA (AA 11034 & AA07574, AA07611). NR 79 TC 14 Z9 14 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 2011 VL 35 IS 1 BP 19 EP 27 DI 10.1111/j.1530-0277.2010.01318.x PG 9 WC Substance Abuse SC Substance Abuse GA 696BS UT WOS:000285417500003 PM 20958329 ER PT S AU Miller, JC Hagberg, A AF Miller, Joel C. Hagberg, Aric BE Frieze, A Horn, P Pralat, P TI Efficient Generation of Networks with Given Expected Degrees SO ALGORITHMS AND MODELS FOR THE WEB GRAPH SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 8th International Workshop on Algorithms and Models for the Web Graph (WAW) CY MAY 27-29, 2011 CL Atlanta, GA SP Google, Internet Math, Microsoft Res New England, Natl Sci Fdn, Telefonica Res, W Virginia Univ, Yahoo Res ID RANDOM GRAPHS AB We present an efficient algorithm to generate random graphs with a given sequence of expected degrees. Existing algorithms run in O(N-2) time where N is the number of nodes. We prove that our algorithm runs in O(N + M) expected time where M is the expected number of edges. If the expected degrees are chosen from a distribution with finite mean, this is O(N) as N -> infinity. C1 [Miller, Joel C.] Boston Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA 02215 USA. [Miller, Joel C.] Natl Inst Hlth, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Hagberg, Aric] Alamos Natl Lab, Div Theoret, Los Alamos, NM 87545 USA. RP Miller, JC (reprint author), Boston Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA 02215 USA. EM joel.c.miller.research@gmail.com; hagberg@lanl.gov RI Frieze, Alan/B-8140-2017; OI Frieze, Alan/0000-0002-8481-5615; Miller, Joel/0000-0003-4426-0405 FU National Institute Of General Medical Sciences [U54GM088558]; Department of Energy at Los Alamos National Laboratory [DE- AC52- 06NA25396]; DOE Office of Science Advanced Computing Research ( ASCR) program in Applied Mathematics FX JCM was supported by 1) the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security and the Fogarty International Center, National Institutes of Health and 2) the Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard School of Public Health under Award Number U54GM088558 from the National Institute Of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute Of General Medical Sciences or the National Institutes of Health. Part of this work was funded by the Department of Energy at Los Alamos National Laboratory under contract DE- AC52- 06NA25396, and the DOE Office of Science Advanced Computing Research ( ASCR) program in Applied Mathematics. NR 17 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-21286-4 J9 LECT NOTES COMPUT SC PY 2011 VL 6732 BP 115 EP 126 PG 12 WC Computer Science, Theory & Methods; Mathematics, Applied SC Computer Science; Mathematics GA BB3JX UT WOS:000342821200010 ER PT J AU Freedman, ND Curto, TM Morishima, C Seeff, LB Goodman, ZD Wright, EC Sinha, R Everhart, JE AF Freedman, N. D. Curto, T. M. Morishima, C. Seeff, L. B. Goodman, Z. D. Wright, E. C. Sinha, R. Everhart, J. E. CA HALT-C Trial Grp TI Silymarin use and liver disease progression in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis trial SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID MORPHOMETRIC IMAGE-ANALYSIS; EVALUATING SILYMARIN; SILYBUM-MARIANUM; VIRUS-INFECTION; PLUS RIBAVIRIN; PEGINTERFERON; SILIBININ; FIBROSIS; INHIBITION; EXPRESSION AB P>Background Silymarin is the most commonly used herbal product for chronic liver disease; yet, whether silymarin protects against liver disease progression remains unclear. Aim To assess the effects of silymarin use on subsequent liver disease progression in 1049 patients of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had advanced fibrosis or cirrhosis and had failed prior peginterferon plus ribavirin treatment. Methods Patients recorded their use of silymarin at baseline and were followed up for liver disease progression (two point increase in Ishak fibrosis score across baseline, year 1.5, and year 3.5 biopsies) and over 8.65 years for clinical outcomes. Results At baseline, 34% of patients had used silymarin, half of whom were current users. Use of silymarin was associated (P < 0.05) with male gender; oesophageal varices; higher ALT and albumin; and lower AST/ALT ratio, among other features. Baseline users had less hepatic collagen content on study biopsies and had less histological progression (HR: 0.57, 95% CI: 0.33-1.00; P-trend for longer duration of use=0.026). No effect was seen for clinical outcomes. Conclusions Silymarin use among patients with advanced hepatitis C-related liver disease is associated with reduced progression from fibrosis to cirrhosis, but has no impact on clinical outcomes (Clinicaltrials.gov #NCT00006164). C1 [Freedman, N. D.; Sinha, R.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Curto, T. M.] New England Res Inst, Watertown, MA 02172 USA. [Morishima, C.] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. [Seeff, L. B.; Everhart, J. E.] NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Seeff, L. B.] NIDDK, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Goodman, Z. D.] Armed Forces Inst Pathol, Div Hepat Pathol, Washington, DC 20306 USA. [Wright, E. C.] NIDDK, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Freedman, ND (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 320,MSC 7232, Rockville, MD 20852 USA. EM freedmanne@mail.nih.gov RI Freedman, Neal/B-9741-2015 OI Freedman, Neal/0000-0003-0074-1098 FU University of Massachusetts Medical Center, Worcester, MA [N01-DK-9-2326]; University of Connecticut Health Center, Farmington, CT [M01RR-06192]; Saint Louis University School of Medicine, St Louis, MO [N01-DK-9-2324]; Massachusetts General Hospital, Boston, MA [N01-DK-9-2319, M01RR-01066, 1 UL1 RR025758-01]; University of Colorado Denver, School of Medicine, Aurora, CO [N01-DK-9-2327, M01RR-00051, 1 UL1 RR 025780-01]; University of California - Irvine, Irvine, CA [N01-DK-9-2320, M01RR-00827]; University of Texas Southwestern Medical Center, Dallas, TX [N01-DK-9-2321, M01RR-00633, 1 UL1 RR024982-01]; University of Southern California, Los Angeles, CA [N01-DK-9-2325, M01RR-00043]; University of Michigan Medical Center, Ann Arbor, MI [N01-DK-9-2323, M01RR-00042, 1 UL1 RR024986]; Virginia Commonwealth University Health System, Richmond, VA [N01-DK-9-2322, M01RR-00065]; University of Washington, Seattle, WA [N01-DK-9-2318]; New England Research Institutes, Watertown, MA [N01-DK-9-2328]; National Institute of Diabetes & Digestive & Kidney Diseases; National Cancer Institute; Hoffmann-La Roche, Inc., through National Institutes of Health FX University of Massachusetts Medical Center, Worcester, MA: (Contract N01-DK-9-2326) Gyongyi Szabo, MD, Barbara F. Banner, MD, Maureen Cormier, RN, Donna Giansiracusa, RN.; University of Connecticut Health Center, Farmington, CT: (Grant M01RR-06192) Herbert L. Bonkovsky, MD, Gloria Borders, RN, Michelle Kelley, RN, ANP.; Saint Louis University School of Medicine, St Louis, MO: (Contract N01-DK-9-2324) Adrian M. Di Bisceglie, MD, Bruce Bacon, MD, Brent Neuschwander-Tetri, MD, Elizabeth M. Brunt, MD, Debra King, RN.; Massachusetts General Hospital, Boston, MA: (Contract N01-DK-9-2319, Grant M01RR-01066; Grant 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center) Jules L. Dienstag, MD, Raymond T. Chung, MD, Andrea E. Reid, MD, Atul K. Bhan, MD, Wallis A. Molchen, David P. Lundmark.; University of Colorado Denver, School of Medicine, Aurora, CO: (Contract N01-DK-9-2327, Grant M01RR-00051, Grant 1 UL1 RR 025780-01), Gregory T. Everson, MD, Thomas Trouillot, MD, Marcelo Kugelmas, MD, S. Russell Nash, MD, Jennifer DeSanto, RN, Carol McKinley, RN.; University of California - Irvine, Irvine, CA: (Contract N01-DK-9-2320, Grant M01RR-00827) Timothy R. Morgan, MD, John C. Hoefs, MD, John R. Craig, MD, M. Mazen Jamal, MD, MPH, Muhammad Sheikh, MD, Choon Park, RN.; University of Texas Southwestern Medical Center, Dallas, TX: (Contract N01-DK-9-2321, Grant M01RR-00633, Grant 1 UL1 RR024982-01, North and Central Texas Clinical and Translational Science Initiative) William M. Lee, MD, Thomas E. Rogers, MD, Peter F. Malet, MD, Janel Shelton, Nicole Crowder, LVN, Rivka Elbein, RN, BSN, Nancy Liston, MPH.; University of Southern California, Los Angeles, CA: (Contract N01-DK-9-2325, Grant M01RR-00043) Karen L. Lindsay, MD, MMM, Sugantha Govindarajan, MD, Carol B. Jones, RN, Susan L. Milstein, RN.; University of Michigan Medical Center, Ann Arbor, MI: (Contract N01-DK-9-2323, Grant M01RR-00042, Grant 1 UL1 RR024986, Michigan Center for Clinical and Health Research) Anna S. Lok, MD, Robert J. Fontana, MD, Joel K. Greenson, MD, Pamela A. Richtmyer, LPN, CCRC, R. Tess Bonham, BS.; Virginia Commonwealth University Health System, Richmond, VA: (Contract N01-DK-9-2322, Grant M01RR-00065) Mitchell L. Shiffman, MD, Richard K. Sterling, MD, MSc, Melissa J. Contos, MD, A. Scott Mills, MD, Charlotte Hofmann, RN, Paula Smith, RN.; National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, MD: Patricia R. Robuck, PhD, Jay H. Hoofnagle, MD. University of Washington, Seattle, WA: (Contract N01-DK-9-2318) David R. Gretch, MD, PhD, Minjun Chung Apodaca, BS, ASCP, Rohit Shankar, BC, ASCP, Natalia Antonov, M. Ed.; New England Research Institutes, Watertown, MA: (Contract N01-DK-9-2328) Kristin K. Snow, MSc, ScD, Anne M. Stoddard, ScD, Margaret C. Bell, MS, MPH.; Declaration of funding interests: This study was funded in part by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed below). Additional support was provided by the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed in the Acknowledgement). This research was also supported in part by the Intramural Research Program of the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. NR 34 TC 30 Z9 31 U1 2 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD JAN PY 2011 VL 33 IS 1 BP 127 EP 137 DI 10.1111/j.1365-2036.2010.04503.x PG 11 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 690LV UT WOS:000285007200014 PM 21083592 ER PT B AU Cohen, JI AF Cohen, Jeffrey I. BE Weller, SK TI Varicella Zoster Virus Transcriptional Regulation and the Roles of VZV IE Proteins SO ALPHAHERPESVIRUSES: MOLECULAR VIROLOGY LA English DT Article; Book Chapter ID HERPES-SIMPLEX-VIRUS; IMMEDIATE-EARLY PROTEIN; REPLICATION IN-VITRO; OPEN READING FRAME-4; LATENCY-ASSOCIATED PROTEIN; HUMAN TRIGEMINAL GANGLIA; HUMAN MEDIATOR COMPLEX; HUMAN SKIN XENOGRAFTS; DNA-BINDING PROTEIN; HOST-CELL FACTOR AB Varicella-zoster virus (VZV) encodes three immediate-early proteins, IE4, IE62, and IE63; however, only IE62 has TAATGARAT-like sequences in its promoter which are present in the promoters of each of the herpes simplex virus immediate-early proteins. The TAATGARAT-like elements on the IE62 promoter bind to VZV ORF10 protein, Oct1, and HCF-1. In addition, histone methyltransferases are recruited to the IE62 promoter to modify chromatin to a transcriptionally active form. VZV IE62, the major VZV transactivator binds to VZV IE4 and IE63, and Med25, part of the mediator complex which upregulates gene expression. VZV IE62, IE4, and IE63 are present in the viral tegument where they may help to regulate transcription early in infection. IE63 binds to several cellular proteins including ASF1 and RNA polymerase II. Two hypotheses have been proposed for regulation of VZV gene expression during latency. First, relocalization of HCF-1 from the cytoplasm to the nucleus of sensory ganglia in response to stimuli associated with reactivation may help to augment transcription of IE62 to reactivate VZV from latency. Second, promoters of latent genes are maintained in a euchromatic state allowing their transcription, while promoters of genes not associated with latency are in a heterochromatic state resulting in repression of transcription. C1 NIH, Infect Dis Lab, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIH, Infect Dis Lab, Bldg 10, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov NR 124 TC 0 Z9 0 U1 1 U2 2 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-904455-76-9 PY 2011 BP 1 EP 16 PG 16 WC Virology SC Virology GA BTP60 UT WOS:000287717200001 ER PT J AU Silbergeld, EK Contreras, EQ Hartung, T Hirsch, C Hogberg, H Jachak, AC Jordan, W Landsiedel, R Morris, J Patri, A Pounds, JG Ruiz, AD Shvedova, A Tanguay, R Tatarazako, N van Vliet, E Walker, NJ Wiesner, M Wilcox, N Zurlo, J AF Silbergeld, Ellen K. Contreras, Elizabeth Q. Hartung, Thomas Hirsch, Cordula Hogberg, Helena Jachak, Ashish C. Jordan, William Landsiedel, Robert Morris, Jeffery Patri, Anil Pounds, Joel G. de Vizcaya Ruiz, Andrea Shvedova, Anna Tanguay, Robert Tatarazako, Norihasa van Vliet, Erwin Walker, Nigel J. Wiesner, Mark Wilcox, Neil Zurlo, Joanne TI Nanotoxicology: "The End of the Beginning" - Signs on the Roadmap to a Strategy for Assuring the Safe Application and Use of Nanomaterials SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Article DE nanomaterials; nanotoxicology; alternative methods; 3Rs; Tox-21c AB In October 2010, a group of experts met as part of the transatlantic think tank for toxicology (t(4)) to exchange ideas about the current status and future of safety testing of nanomaterials. At present, there is no widely accepted path forward to assure appropriate and effective hazard identification for engineered nanomaterials. The group discussed needs for characterization of nanomaterials and identified testing protocols that incorporate the use of innovative alternative whole models such as zebrafish or C. elegans, as well as in vitro or alternative methods to examine specific functional pathways and modes of action. The group proposed elements of a potential testing scheme for nanomaterials that works towards an integrated testing strategy, incorporating the goals of the NRC report Toxicity Testing in the 21(st) Century: A Vision and a Strategy by focusing on pathways of toxic response, and utilizing an evidence-based strategy for developing the knowledge base for safety assessment. Finally, the group recommended that a reliable, open, curated database be developed that interfaces with existing databases to enable sharing of information. C1 [Silbergeld, Ellen K.; Jachak, Ashish C.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. [Contreras, Elizabeth Q.] Rice Univ, Dept Chem, Houston, TX USA. [Hartung, Thomas; Hogberg, Helena; van Vliet, Erwin; Zurlo, Joanne] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing, Baltimore, MD USA. [Hirsch, Cordula] Empa Swiss Fed Labs Mat Sci & Technol, St Gallen, Switzerland. [Jordan, William; Morris, Jeffery] US EPA, Washington, DC 20460 USA. [Landsiedel, Robert] BASF, Ludwigshafen, Germany. [Patri, Anil] NCI, Nanotechnol Characterizat Lab, NIH, Frederick, MD 21701 USA. [Pounds, Joel G.] Pacific NW Natl Lab, Richland, WA 99352 USA. [de Vizcaya Ruiz, Andrea] CINVESTAV, Mexico City 14000, DF, Mexico. [Shvedova, Anna] CDC, Natl Inst Occupat Safety & Hlth, Morgantown, WV USA. [Tanguay, Robert] Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA. [Tatarazako, Norihasa] Natl Inst Environm Sci, Tsukuba, Ibaraki, Japan. [Walker, Nigel J.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Walker, Nigel J.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Wiesner, Mark] Duke Univ, Dept Civil & Environm Engn, Durham, NC 27706 USA. [Wilcox, Neil] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Zurlo, J (reprint author), Johns Hopkins Ctr Alternat Anim Testing, 615 N Wolfe St,W7032, Baltimore, MD 21205 USA. EM jzurlo@jhsph.edu RI Landsiedel, Robert/D-1960-2012; Walker, Nigel/D-6583-2012; Nanotechnology Characterization Lab, NCL/K-8454-2012 OI Landsiedel, Robert/0000-0003-3756-1904; Walker, Nigel/0000-0002-9111-6855; FU Doerenkamp-Zbinden Foundation FX We thank the Doerenkamp-Zbinden Foundation for sponsoring this workshop as part of the t4 activities. NR 5 TC 10 Z9 10 U1 1 U2 11 PU SPEKTRUM AKAD VERLAG PI HEIDELBERG PA SLEVOGTSTRASSE 3-5, D-69126 HEIDELBERG, GERMANY SN 1868-596X J9 ALTEX-ALTERN ANIM EX JI ALTEX-Altern. Anim. Exp. PY 2011 VL 28 IS 3 BP 236 EP 241 PG 6 WC Instruments & Instrumentation; Medicine, Research & Experimental SC Instruments & Instrumentation; Research & Experimental Medicine GA 829IZ UT WOS:000295573100006 PM 21993959 ER PT J AU Launer, LJ AF Launer, Lenore J. TI Counting dementia: There is no one "best" way SO ALZHEIMERS & DEMENTIA LA English DT Article; Proceedings Paper CT Conference on Prevalence and Trends of Alzheimers Disease and Other Age-Related Cognitive Impairment CY MAR 19-20, 2009 CL Washington, DC DE Dementia; Prevalence; Case ascertainment ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; OLDER PERSONS; US ADULTS; PREVALENCE; POPULATION; CRITERIA; NEUROPATHOLOGY; COHORTS; TRENDS AB The growing societal and individual burden of dementia means that counting the cases of dementia is critical. There are several approaches and methods that can be used to identify dementia cases. The ascertainment can range from very detailed characterization of the individual (deep) to a brief standardized assessment (wide) that emphasizes individual functioning. The choice of going deep or wide depends on the goal of the ascertainment. These goals are discussed, as well as the emerging issues that may change the way dementia cases are classified. (C) 2011 The Alzheimer's Association. All rights reserved. C1 NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Launer, LJ (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov FU Intramural NIH HHS [ZIA AG007280-10] NR 23 TC 10 Z9 10 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JAN PY 2011 VL 7 IS 1 BP 10 EP 14 DI 10.1016/j.jalz.2010.11.003 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 716XJ UT WOS:000287006500003 PM 21255740 ER PT J AU Seshadri, S Beiser, A Au, R Wolf, PA Evans, DA Wilson, RS Petersen, RC Knopman, DS Rocca, WA Kawas, CH Corrada, MM Plassman, BL Langa, KM Chui, HC AF Seshadri, Sudha Beiser, Alexa Au, Rhoda Wolf, Philip A. Evans, Denis A. Wilson, Robert S. Petersen, Ronald C. Knopman, David S. Rocca, Walter A. Kawas, Claudia H. Corrada, Maria M. Plassman, Brenda L. Langa, Kenneth M. Chui, Helena C. TI Operationalizing diagnostic criteria for Alzheimer's disease and other age-related cognitive impairment-Part 2 SO ALZHEIMERS & DEMENTIA LA English DT Article; Proceedings Paper CT Conference on Prevalence and Trends of Alzheimers Disease and Other Age-Related Cognitive Impairment CY MAR 19-20, 2009 CL Washington, DC DE Alzheimer's disease; Dementia; Mild cognitive impairment; Cognitive impairment not dementia; Diagnostic criteria; Population-based; Prevalence; Incidence ID COMMUNITY POPULATION; LIFETIME RISK; OLDER PERSONS; CLINICAL CHARACTERIZATION; INTERNATIONAL WORKSHOP; VASCULAR DEMENTIA; UNITED-STATES; FRAMINGHAM; PREVALENCE; NEUROPATHOLOGY AB This article focuses on the effects of operational differences in case ascertainment on estimates of prevalence and incidence of cognitive impairment and/or dementia of the Alzheimer type. Experience and insights are discussed by investigators from the Framingham Heart Study, the East Boston Senior Health Project, the Chicago Health and Aging Project, the Mayo Clinic Study of Aging, the Baltimore Longitudinal Study of Aging, and the Aging, Demographics, and Memory Study. There is a general consensus that the single most important factor determining prevalence estimates of Alzheimer's disease (AD) is the severity of cognitive impairment used as a threshold to define cases. Studies that require a level of cognitive impairment in which persons are unable to provide self-care will have much lower estimates than the studies aimed at identifying persons in the earliest stages of AD. There are limited autopsy data from the aforementioned epidemiological studies to address accuracy in the diagnosis of etiological subtype, namely the specification of AD alone or in combination with other types of pathology. However, other community-based cohort studies show that many persons with mild cognitive impairment and also some persons without dementia or mild cognitive impairment meet pathological criteria for AD, thereby suggesting that the number of persons who would benefit from an effective secondary prevention intervention is probably higher than the published prevalence estimates. Improved accuracy in the clinical diagnosis of AD is anticipated with the addition of molecular and structural biomarkers in the next generation of epidemiological studies. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Seshadri, Sudha; Beiser, Alexa; Au, Rhoda; Wolf, Philip A.] Boston Univ, Sch Med, Dept Neurol, Framingham Heart Study, Boston, MA 02118 USA. [Seshadri, Sudha; Beiser, Alexa; Au, Rhoda; Wolf, Philip A.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Beiser, Alexa] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Evans, Denis A.] Rush Univ, Rush Inst Healthy Aging, Med Ctr, Chicago, IL 60612 USA. [Evans, Denis A.] Rush Univ, Dept Internal Med, Med Ctr, Chicago, IL 60612 USA. [Wilson, Robert S.] Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Chicago, IL 60612 USA. [Wilson, Robert S.] Rush Univ, Dept Neurol Sci, Med Ctr, Chicago, IL 60612 USA. [Wilson, Robert S.] Rush Univ, Dept Behav Sci, Med Ctr, Chicago, IL 60612 USA. [Petersen, Ronald C.; Knopman, David S.; Rocca, Walter A.] Mayo Clin, Dept Neurol, Coll Med, Rochester, MN USA. [Petersen, Ronald C.; Knopman, David S.] Mayo Clin, Mayo Alzheimers Dis Res Ctr, Rochester, MN USA. [Petersen, Ronald C.; Rocca, Walter A.] Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Coll Med, Rochester, MN USA. [Kawas, Claudia H.; Corrada, Maria M.] Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. [Kawas, Claudia H.; Corrada, Maria M.] Univ Calif Irvine, Inst Memory Impairments & Neurol Disorders, Irvine, CA USA. [Kawas, Claudia H.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA USA. [Plassman, Brenda L.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Langa, Kenneth M.] Univ Michigan, Sch Med, Dept Med, Div Gen Med, Ann Arbor, MI 48104 USA. [Langa, Kenneth M.] Vet Affairs Ctr Practice Management & Outcomes Re, Ann Arbor, MI USA. [Langa, Kenneth M.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA. [Chui, Helena C.] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. RP Seshadri, S (reprint author), Boston Univ, Sch Med, Dept Neurol, Framingham Heart Study, Boston, MA 02118 USA. EM suseshad@bu.edu OI Seshadri, Sudha/0000-0001-6135-2622; Au, Rhoda/0000-0001-7742-4491; corrada, maria/0000-0002-8168-8593; Beiser, Alexa/0000-0001-8551-7778 FU NHLBI NIH HHS [N01HC25195, N01HC25195]; NIA NIH HHS [R01 AG033040-03, U01 AG009740, P01AG012435, P01 AG012435, R01 AG033040, R01 AG033193-03, R01AG034676, N01AG02107, R01AG031287, P50 AG005142, R01 AG031287-02, U01 AG006786, P50AG005142, R01AG033193, R01AG033040, R01AG16495, R01 AG016495, U01AG009740, R01 AG021055, R01 AG008122-22, R01 AG034676, R01AG008325, N01AG12106, R01 AG011101, U01AG06786, R01 AG008122, R01 AG031287, R01 AG033193, R01AG08122, R01AG021055, P50 AG016574, P50AG016574, R01AG011101]; NINDS NIH HHS [R01 NS017950, R01NS17950] NR 77 TC 23 Z9 23 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JAN PY 2011 VL 7 IS 1 BP 35 EP 52 DI 10.1016/j.jalz.2010.12.002 PG 18 WC Clinical Neurology SC Neurosciences & Neurology GA 716XJ UT WOS:000287006500005 PM 21255742 ER PT J AU Devlin, G Reynolds, HR Mark, DB Rankin, JM Carvalho, AC Vozzi, C Sopko, G Caramori, P Dzavik, V Ragosta, M Forman, SA Lamas, GA Hochman, JS AF Devlin, Gerard Reynolds, Harmony R. Mark, Daniel B. Rankin, James M. Carvalho, Antonio C. Vozzi, Carlos Sopko, George Caramori, Paulo Dzavik, Vladimir Ragosta, Michael Forman, Sandra A. Lamas, Gervasio A. Hochman, Judith S. TI Loss of short-term symptomatic benefit in patients with an occluded infarct artery is unrelated to non-protocol revascularization: Results from the Occluded Artery Trial (OAT) SO AMERICAN HEART JOURNAL LA English DT Article ID ELEVATION MYOCARDIAL-INFARCTION; STABLE CORONARY-DISEASE; ST-SEGMENT-ELEVATION; QUALITY-OF-LIFE; MEDICAL THERAPY; CLINICAL-OUTCOMES; RANDOMIZED-TRIAL; ANGIOPLASTY; INTERVENTION; REPERFUSION AB Background The OAT found that routine late (3-28 days post-myocardial infarction) percutaneous coronary intervention (PCI) of an occluded infarct-related artery did not reduce death, reinfarction, or heart failure relative to medical treatment (MED). Angina rates were lower in PCI early, but the advantage over MED was lost by 3 years. Methods Angina and revascularization status were collected at 4 months, then annually. We assessed whether non-protocol revascularization procedures in MED accounted for loss of the early symptomatic advantage of PCI. Results Seven per 100 more PCI patients were angina-free at 4 months (P < .001) and 5 per 100 at 12 months (P = .005) with the difference narrowing to 1 per 100 at 3 years (P = .34). Non-protocol revascularization was more frequent in MED (5-year rate 22% vs 19% PCI, P = .05). Indications for revascularization included acute coronary syndromes (39% PCI vs 38% MED), stable angina/inducible ischemia (39% in each group), and physician preference (17% PCI vs 15% MED). Revascularization rates among patients with angina at any time during follow-up (35% of cohort) did not differ by treatment group (5-year rates 26% PCI vs 28% MED). Most symptomatic patients were treated without revascularization during follow-up (77%). Conclusions In a large randomized clinical trial of stable post-myocardial infarction patients, the modest benefit on angina from PCI of an occluded infarct-related artery was lost by 3 years. Revascularization was slightly more common in MED during follow-up but was not driven by acute ischemia, and almost 1 in 5 procedures were attributed to physician preference alone. (Am Heart J 2011;161:84-90.) C1 [Hochman, Judith S.] NYU, Sch Med, Cardiovasc Clin Res Ctr, Leon Charney Div Cardiol, New York, NY 10016 USA. [Devlin, Gerard] Waikato Hosp, Hamilton, New Zealand. [Mark, Daniel B.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Rankin, James M.] Royal Perth Hosp, Perth, WA, Australia. [Carvalho, Antonio C.] Hosp Sao Paulo, Moema Sao Paulo, Brazil. [Vozzi, Carlos] Insto De Intervenc Cardiovasculares SA, Rosario, Argentina. [Sopko, George] NHLBI, Bethesda, MD 20892 USA. [Caramori, Paulo] Pontificia Univ Catolica Rio Sul, Hosp Sao Lucas, Porto Alegre, RS, Brazil. [Dzavik, Vladimir] Univ Hlth Network, Peter Munk Cardiac Ctr, Toronto, ON, Canada. [Ragosta, Michael] Univ Virginia Hlth Syst, Charlottesville, VI USA. [Forman, Sandra A.] Clin Trials & Surveys Corp, Owings Mills, MD USA. [Lamas, Gervasio A.] Columbia Univ, Div Cardiol, Mt Sinai Med Ctr, Miami Beach, FL USA. RP Hochman, JS (reprint author), NYU, Sch Med, Cardiovasc Clin Res Ctr, Leon Charney Div Cardiol, 530 1st Ave,Skirball 9R, New York, NY 10016 USA. EM judith.hochman@nyumc.org RI Caramori, Paulo/I-1370-2012; Reynolds, Harmony/M-4818-2013; OI Reynolds, Harmony/0000-0003-0284-0655; Mark, Daniel/0000-0001-6340-8087; Hochman, Judith/0000-0002-5889-5981 FU NHLBI NIH HHS [U01 HL062509, U01 HL062509-05, U01 HL062511, U01 HL062511-05] NR 22 TC 1 Z9 1 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JAN PY 2011 VL 161 IS 1 DI 10.1016/j.ahj.2010.09.009 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 695MZ UT WOS:000285376200008 PM 21167338 ER PT J AU Lai, WW Vetter, VL Richmond, M Li, JS Saul, JP Mital, S Colan, SD Newburger, JW Sleeper, LA McCrindle, BW Minich, LL Goldmuntz, E Marino, BS Williams, IA Pearson, GD Evans, F Scott, JD Cohen, MS AF Lai, Wyman W. Vetter, Victoria L. Richmond, Marc Li, Jennifer S. Saul, J. Philip Mital, Seema Colan, Steven D. Newburger, Jane W. Sleeper, Lynn A. McCrindle, Brian W. Minich, L. LuAnn Goldmuntz, Elizabeth Marino, Bradley S. Williams, Ismee A. Pearson, Gail D. Evans, Frank Scott, Jane D. Cohen, Meryl S. TI Clinical Research Careers: Reports from a NHLBI Pediatric Heart Network Clinical Research Skills Development Conference SO AMERICAN HEART JOURNAL LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; INSTITUTES-OF-HEALTH; RESEARCH QUESTION; HYPERTROPHIC CARDIOMYOPATHY; TRANSLATIONAL RESEARCH; PART I; ACADEMIC ADVANCEMENT; PHYSICIAN-SCIENTIST; BIOMEDICAL-RESEARCH; CHILDREN AB Background Wyman W. Lai, MD, MPH, and Victoria L. Vetter, MD, MPH. The Pediatric Heart Network (PHN), funded under the U. S. National Institutes of Health-National Heart, Lung, and Blood Institute (NIH-NHLBI), includes two Clinical Research Skills Development (CRSD) Cores, which were awarded to The Children's Hospital of Philadelphia and to the Morgan Stanley Children's Hospital of New York-Presbyterian. To provide information on how to develop a clinical research career to a larger number of potential young investigators in pediatric cardiology, the directors of these two CRSD Cores jointly organized a one-day seminar for fellows and junior faculty from all of the PHN Core sites. The participants included faculty members from the PHN and the NHLBI. The day-long seminar was held on April 29, 2009, at the NHLBI site, immediately preceding the PHN Steering Committee meeting in Bethesda, MD. Methods The goals of the seminar were 1) to provide fellows and early investigators with basic skills in clinical research 2) to provide a forum for discussion of important research career choices 3) to introduce attendees to each other and to established clinical researchers in pediatric cardiology, and 4) to publish a commentary on the future of clinical research in pediatric cardiology. Results The following chapters are compilations of the talks given at the 2009 PHN Clinical Research Skills Development Seminar, published to share the information provided with a broader audience of those interested in learning how to develop a clinical research career in pediatric cardiology. The discussions of types of clinical research, research skills, career development strategies, funding, and career management are applicable to research careers in other areas of clinical medicine as well. Conclusions The aim of this compilation is to stimulate those who might be interested in the research career options available to investigators. (Am Heart J 2011;161:13-67.) C1 [Vetter, Victoria L.] Childrens Hosp Philadelphia, Div Cardiol, Dept Pediat, Philadelphia, PA 19104 USA. [Lai, Wyman W.; Richmond, Marc; Williams, Ismee A.] Morgan Stanley Childrens Hosp New York Presbyteri, New York, NY USA. [Li, Jennifer S.] Duke Univ, Med Ctr, Durham, NC USA. [Saul, J. Philip] Med Univ S Carolina, Charleston, SC 29425 USA. [Mital, Seema; McCrindle, Brian W.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Colan, Steven D.; Newburger, Jane W.] Harvard Univ, Sch Med, Boston, MA USA. [Sleeper, Lynn A.] New England Res Inst, Watertown, MA 02172 USA. [Minich, L. LuAnn] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA. [Marino, Bradley S.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Pearson, Gail D.; Evans, Frank; Scott, Jane D.] NHLBI, Bethesda, MD 20892 USA. RP Vetter, VL (reprint author), Childrens Hosp Philadelphia, Div Cardiol, Dept Pediat, 34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM vetter@email.chop.edu FU National Heart, Lung, and Blood Institute [U01 HL068279] FX This work was supported by a grant from the National Heart, Lung, and Blood Institute (U01 HL068279). NR 107 TC 3 Z9 3 U1 2 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JAN PY 2011 VL 161 IS 1 DI 10.1016/j.ahj.2010.08.032 PG 55 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 695MZ UT WOS:000285376200005 PM 21167335 ER PT J AU Korn, EL Freidlin, B AF Korn, Edward L. Freidlin, Boris TI Inefficacy Interim Monitoring Procedures in Randomized Clinical Trials: The Need to Report SO AMERICAN JOURNAL OF BIOETHICS LA English DT Article DE futility interim monitoring; data and safety monitoring boards; early stopping; interim analysis; randomized trial; clinical research ID ACUTE CORONARY SYNDROMES; ACUTE MYOCARDIAL-INFARCTION; METASTATIC COLORECTAL-CANCER; STANDARD MEDICAL THERAPY; CONGESTIVE-HEART-FAILURE; CRITICALLY-ILL PATIENTS; ACUTE MYELOID-LEUKEMIA; ATRIAL-FIBRILLATION; PHASE-III; KIDNEY-TRANSPLANTATION AB If definitive evidence concerning treatment effectiveness becomes available from an ongoing randomized clinical trial, then the trial could be stopped early, with the public release of results benefiting current and future patients. However, stopping an ongoing trial based on accruing outcome data requires methodological rigor to preserve validity of the trial conclusions. This has led to the use of formal interim monitoring procedures, which include inefficacy monitoring that will stop a trial early when the experimental treatment appears not to be working. For participants, inefficacy monitoring is especially important as it ensures that they are not being treated worse than if they had not enrolled on the trial. We discuss the importance of reporting with trial results the formal interim inefficacy monitoring guidelines that were utilized, and, if none were used, the reasons for their absence. A survey of two leading medical journals suggests that this is not current practice. C1 [Korn, Edward L.] NCI, Biometr Res Branch, EPN 8129, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch, EPN 8129, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. EM korne@ctep.nci.nih.gov NR 112 TC 12 Z9 12 U1 2 U2 12 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2011 VL 11 IS 3 BP 2 EP 10 AR PII 934771991 DI 10.1080/15265161.2010.546471 PG 9 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 733PU UT WOS:000288275900002 PM 21400374 ER PT J AU Fleischman, A Levine, C Eckenwiler, L Grady, C Hammerschmidt, DE Sugarman, J AF Fleischman, Alan Levine, Carol Eckenwiler, Lisa Grady, Christine Hammerschmidt, Dale E. Sugarman, Jeremy TI Dealing With the Long-Term Social Implications of Research SO AMERICAN JOURNAL OF BIOETHICS LA English DT Article ID BIOETHICS; BEHAVIORS; DEBATE; HIV C1 [Fleischman, Alan] March Dimes Fdn, White Plains, NY 10605 USA. [Levine, Carol] United Hosp Fund, New York, NY USA. [Eckenwiler, Lisa] George Mason Univ, Fairfax, VA 22030 USA. [Grady, Christine] NIH, Bethesda, MD 20892 USA. [Hammerschmidt, Dale E.] Univ Minnesota, Minneapolis, MN 55455 USA. [Sugarman, Jeremy] Berman Inst Bioeth, Baltimore, MD USA. RP Fleischman, A (reprint author), March Dimes Fdn, 1275 Mamaroneck Ave, White Plains, NY 10605 USA. EM afleischman@marchofdimes.com FU Intramural NIH HHS [Z99 CL999999] NR 29 TC 16 Z9 16 U1 0 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2011 VL 11 IS 5 BP 5 EP 9 DI 10.1080/15265161.2011.560337 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 756ZN UT WOS:000290053400005 PM 21534138 ER PT J AU Schaefer, GO Wertheimer, A AF Schaefer, G. Owen Wertheimer, Alan TI Reevaluating the Right to Withdraw From Research Without Penalty SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 [Schaefer, G. Owen] Univ Oxford, St Cross Coll, Fac Philosophy, Oxford OX1 2LG, England. [Wertheimer, Alan] Natl Inst Hlth Clin Ctr, Bethesda, MD USA. RP Schaefer, GO (reprint author), Univ Oxford, St Cross Coll, Fac Philosophy, 6 St John St, Oxford OX1 2LG, England. EM owen.schaefer@stx.ox.ac.uk OI Schaefer, Gerald Owen/0000-0002-6915-6148 NR 3 TC 0 Z9 0 U1 0 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2011 VL 11 IS 4 BP 14 EP 16 AR PII 936108925 DI 10.1080/15265161.2011.560345 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 751SA UT WOS:000289636700004 PM 21480065 ER PT J AU Resnik, DB Master, Z AF Resnik, David B. Master, Zubin TI Criteria for Authorship in Bioethics SO AMERICAN JOURNAL OF BIOETHICS LA English DT Article DE accountability; authorship guidelines; bioethics; conceptual publications; fairness; multiple authorship ID MULTIPLE AUTHORSHIP; MEDICAL JOURNALS; TRENDS; PATTERNS; ARTICLE AB Multiple authorship is becoming increasingly common in bioethics research. There are well-established criteria for authorship in empirical bioethics research but not for conceptual research. It is important to develop criteria for authorship in conceptual publications to prevent undeserved authorship and uphold standards of fairness and accountability. This article explores the issue of multiple authorship in bioethics and develops criteria for determining who should be an author on a conceptual publication in bioethics. Authorship in conceptual research should be based on contributing substantially to: (1) identifying a topic, problem, or issue to study; (2) reviewing and interpreting the relevant literature; (3) formulating, analyzing, and evaluating arguments that support one or more theses; (4) responding to objections and counterarguments; and (5) drafting the manuscript and approving the final version. Authors of conceptual publications should participate substantially in at least two of areas (1)-(5). C1 [Resnik, David B.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Master, Zubin] Univ Alberta, Hlth Law Inst, Edmonton, AB T6G 2M7, Canada. RP Resnik, DB (reprint author), NIEHS, NIH, Mail Drop CU 03,Box 12233, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU Intramural NIH HHS [ZIA ES102646-03] NR 39 TC 8 Z9 8 U1 0 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2011 VL 11 IS 10 BP 17 EP 21 DI 10.1080/15265161.2011.603795 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 835VM UT WOS:000296064500009 PM 21943265 ER PT J AU Resnik, DB AF Resnik, David B. TI Reopening Old Divisions SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID CHILDREN; VACCINE; RISK C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Mail Drop NH 06,Box 12233, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU Intramural NIH HHS [ZIA ES102646-04, ZIA ES102646-03] NR 7 TC 1 Z9 1 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2011 VL 11 IS 6 BP 19 EP 20 AR PII 938608839 DI 10.1080/15265161.2011.566670 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 779UV UT WOS:000291808600006 PM 21678208 ER PT J AU Shah, S AF Shah, Seema TI The Dangers of Using a Relative Risk Standard for Minimal Risk SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Shah, S (reprint author), NIH, Dept Bioeth, 10 Ctr Dr,10-1C118, Bethesda, MD 20892 USA. EM shahse@cc.nih.gov FU Intramural NIH HHS NR 7 TC 3 Z9 3 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2011 VL 11 IS 6 BP 22 EP 23 AR PII 938601419 DI 10.1080/15265161.2011.572511 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 779UV UT WOS:000291808600008 PM 21678210 ER PT J AU Parnes, HL AF Parnes, Howard L. TI Prostate Cancer Prevention: Do the 5-ARIs Make the Grade? SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID 5-ALPHA-REDUCTASE INHIBITORS; FINASTERIDE; CHEMOPREVENTION; SENSITIVITY; TRIAL C1 NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Parnes, HL (reprint author), NCI, Canc Prevent Div, 6130 Execut Blvd,EPN 2100, Bethesda, MD 20892 USA. EM hp24c@nih.gov NR 8 TC 2 Z9 2 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2011 VL 11 IS 12 BP 30 EP 31 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 868BT UT WOS:000298499200012 PM 22146028 ER PT J AU Miller, FG AF Miller, Franklin G. TI On Authorship SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 2 TC 0 Z9 0 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2011 VL 11 IS 10 BP 32 EP 33 DI 10.1080/15265161.2011.605938 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 835VM UT WOS:000296064500015 PM 21943271 ER PT J AU Antin, JH Emmert-Buck, MR Aplin, AE Cheng, SY Cryns, VL Wang, DS AF Antin, Joseph H. Emmert-Buck, Michael R. Aplin, Andrew E. Cheng, Sheue-yann Cryns, Vincent L. Wang, Dengshun TI Launching of American Journal of Cancer Research SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Editorial Material C1 [Antin, Joseph H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02114 USA. [Emmert-Buck, Michael R.; Cheng, Sheue-yann] NCI, Bethesda, MD 20892 USA. [Aplin, Andrew E.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Cryns, Vincent L.] Northwestern Univ, Chicago, IL 60611 USA. [Wang, Dengshun] Univ Wisconsin, Madison, WI USA. RP Antin, JH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2011 VL 1 IS 1 BP I EP I PG 1 WC Oncology SC Oncology GA V30ZL UT WOS:000208853800001 ER PT J AU Lu, CX Mishra, A Zhu, YLJ Meltzer, P Cheng, SY AF Lu, Changxue Mishra, Alok Zhu, Yuelin J. Meltzer, Paul Cheng, Sheue-yann TI Genomic profiling of genes contributing to metastasis in a mouse model of thyroid follicular carcinoma SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE Metastasis; thyroid cancer; mouse model; microarray; gene expression AB Metastasis is the major cause of thyroid cancer-related death. However, little is known about the genes involved in the metastatic spread of thyroid carcinomas. We have created a mouse that spontaneously develops metastatic follicular thyroid carcinoma (FTC). This mouse harbors a targeted mutation (denoted TR beta PV) in the thyroid hormone receptor beta gene (Thrb(PV/PV) mice). Our recent studies show that the highly elevated level of thyroid stimulating hormone (TSH) in Thrb(PV/PV) mice promotes proliferation of thyroid tumor cells, but requires the collaboration of the oncogenic action of TR beta PV to empower the tumor cells to undergo distant metastasis. To uncover genes destined to drive the metastatic process, we used cDNA microarrays to compare the genomic expression profile of laser capture microdissected thyroid tumor lesions of Thrb(PV/PV) mice with that of hyperplastic thyroid cells of wild-type mice having elevated TSH induced by treatment with the anti-thyroid drug propylthiouracil (WT-PTU mice). Analyses of microarray data indicated that the expressions of 150 genes were significantly altered between Thrb(PV/PV) and WT-PTU mice (87 genes had higher expression and 63 genes had lower expression in Thrb(PV/PV) mice than in WT-PTU mice). Thirty-six percent of genes with altered expression function as key regulators in metastasis. The remaining genes were involved in various cellular processes including metabolism, intracellular trafficking, transcriptional regulation, post-transcriptional modification, and cell-cell/extracellular matrix signaling. The present studies have uncovered novel genes responsible for the metastatic spread of FTC and, furthermore, have shown that the metastatic process of thyroid cancer requires effective collaboration among genes with diverse cellular functions. Importantly, the present studies indicate that the tumor cells in the primary lesions are endowed with the genes destined to promote metastasis. Thus, our study has provided new insights into the understanding of the metastatic spread of human thyroid cancer. C1 [Lu, Changxue; Mishra, Alok; Cheng, Sheue-yann] NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Zhu, Yuelin J.; Meltzer, Paul] NCI, Canc Genet Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov FU 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. We thank Drs. Xiaolin Wu for assistance in the hybridization of the arrays and preliminary analysis of the data, Jaime Rodriguez-Canales and Jeffrey Hanson, for assistance with the laser capture microdissection experiments. NR 38 TC 6 Z9 6 U1 0 U2 1 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2011 VL 1 IS 1 BP 1 EP U22 PG 20 WC Oncology SC Oncology GA V30ZL UT WOS:000208853800002 PM 21562609 ER PT J AU Gannot, G Richardson, AM Rodriguez-Canales, J Pinto, PA Merino, MJ Chuaqui, RF Gillespie, JW Emmert-Buck, MR AF Gannot, Gallya Richardson, Annely M. Rodriguez-Canales, Jaime Pinto, Peter A. Merino, Maria J. Chuaqui, Rodrigo F. Gillespie, John W. Emmert-Buck, Michael R. TI Decrease in CD8+lymphocyte number and altered cytokine profile in human prostate cancer SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE Prostate cancer; lymphocytes; cytokines; histomathematics; histopathology AB The tumor microenvironment is comprised of multiple cell types arranged in a three-dimensional structure. Interactions amongst the various cell components play an important role in neoplasia, including the inflammatory reaction that occurs as part of the host response. In this study, the regional lymphocyte subpopulations and cytokine profiles associated with prostate cancer were examined using a quantitative imaging approach and expression microarray analysis. Lymphocytes were measured in four different epithelial phenotypes in prostate cancer specimens: carcinoma; prostatic intraepithelial neoplasia (PIN); benign prostate hyperplasia (BPH); and normal epithelium. The data indicate that CD8 positive, cytotoxic T lymphocytes are significantly decreased in regions adjacent to hyperplasia and carcinoma as compared to normal epithelium and PIN. In contrast the relative number of CD4 positive and CD20 positive lymphocytes did not change markedly. Parallel mRNA expression array analysis of the normal and tumor microenvironments identified a distinct cytokine profile in cancer, with 24 dysregulated genes in tumor epithelium and nine altered in tumor-associated stroma. Overall, these data indicate that the spatial distribution of CD8 positive, cytotoxic T lymphocytes is dysregulated in human prostate glands that contain cancer, and cytokine profiles are altered at the mRNA level. C1 [Gannot, Gallya; Richardson, Annely M.; Rodriguez-Canales, Jaime; Chuaqui, Rodrigo F.; Gillespie, John W.; Emmert-Buck, Michael R.] NCI, Pathogenet Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Richardson, Annely M.] NCI, Howard Hughes Med Inst Res Scholar, Bethesda, MD 20892 USA. [Pinto, Peter A.] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Emmert-Buck, MR (reprint author), NCI, Pathogenet Unit, Pathol Lab, Ctr Canc Res, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM buckm@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 19 TC 6 Z9 7 U1 0 U2 0 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2011 VL 1 IS 1 BP 120 EP 127 PG 8 WC Oncology SC Oncology GA V30ZL UT WOS:000208853800011 ER PT J AU Lu, CX Mishra, A Zhu, YJL Meltzer, P Cheng, SY AF Lu, Changxue Mishra, Alok Zhu, Yuelin J. Meltzer, Paul Cheng, Sheue-yann TI Global expression profiling reveals gain-of-function oncogenic activity of a mutated thyroid hormone receptor in thyroid carcinogenesis SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE Mutant TR; thyroid cancer; mouse model; microarray; gene expression AB Thyroid hormone receptors (TRs) are critical in regulating gene expression in normal physiological processes. Decreased expression and/or somatic mutations of TRs have been shown to be associated several types of human cancers including liver, breast, lung, and thyroid. To understand the molecular mechanisms by which mutated TRs promote carcinogenesis, an animal model of follicular thyroid carcinoma (FTC) (Thrb(PV/PV) mice) was used in the present study. The Thrb(PV/PV) mouse harbors a knockin dominant negative PV mutation, identified in a patient with resistance to thyroid hormone. To understand whether oncogenic actions of PV involve not only the loss of normal TR functions but also gain-of-function activities, we compared the gene expression profiles of thyroid lesions in Thrb(PV/PV) mice and Thra1(-/-)Thrb(-/-) mice that also spontaneously develop FTC, but with less severe malignancy. Analysis of the cDNA microarray data derived from microdissected thyroid tumor cells of these two mice showed contrasting global gene expression profiles. With stringent selection using 2.5- fold change (p<0.01) in cDNA microarray analysis, 241 genes with altered gene expression were identified. Nearly half of the genes (n=103: 42.7% of total) with altered gene expression in thyroid tumor cells of Thrb(PV/PV) mice were associated with tumorigenesis and metastasis; some of these genes function as oncogenes in human thyroid cancers. The remaining genes were found to function in transcriptional regulation, RNA processing, cell proliferation, apoptosis, angiogenesis, and cytoskeleton modification. These results indicate that the more aggressive thyroid tumor progression in Thrb(PV/PV) mice was not due simply to the loss of tumor suppressor functions of TR via mutation but also, importantly, to gain-of-function in the oncogenic activities of PV to drive thyroid carcinogenesis. Thus, the present study identifies a novel mechanism by which a mutated TR beta evolves with an oncogenic advantage to promote thyroid carcinogenesis. C1 [Lu, Changxue; Mishra, Alok; Cheng, Sheue-yann] NCI, Mol Biol Lab, Bethesda, MD 20892 USA. [Zhu, Yuelin J.; Meltzer, Paul] NCI, Ctr Canc Res, Canc Genet Lab, Bethesda, MD 20892 USA. RP Lu, CX (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. EM chengs@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. We thank Drs. Jaime Rodriguez-Canales and Jeffrey Hanson, for assistance with the laser capture microdissection experiments. NR 64 TC 5 Z9 5 U1 0 U2 0 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2011 VL 1 IS 2 BP 168 EP 191 PG 24 WC Oncology SC Oncology GA V30ZM UT WOS:000208853900004 PM 21547001 ER PT J AU Yan, W Wistuba, II Emmert-Buck, MR Erickson, HS AF Yan, Wusheng Wistuba, Ignacio I. Emmert-Buck, Michael R. Erickson, Heidi S. TI Squamous cell carcinoma - similarities and differences among anatomical sites SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Review DE Squamous cell carcinoma (SCC); non-melanoma skin cancer (NMSC); head and neck squamous cell carcinomas (HNSCC); esophageal squamous cell carcinoma (ESCC); non-small cell lung cancer (NSCLC); epidemiology; risk factors; molecular characteristics; prognostic markers; targeted therapy AB Squamous cell carcinoma (SCC) is an epithelial malignancy involving many anatomical sites and is the most common cancer capable of metastatic spread. Development of early diagnosis methods and novel therapeutics are important for prevention and mortality reduction. In this effort, numerous molecular alterations have been described in SCCs. SCCs share many phenotypic and molecular characteristics, but they have not been extensively compared. This article reviews SCC as a disease, including: epidemiology, pathology, risk factors, molecular characteristics, prognostic markers, targeted therapy, and a new approach to studying SCCs. Through this comparison, several themes are apparent. For example, HPV infection is a common risk factor among the four major SCCs (NMSC, HNSC, ESCC, and NSCLC) and molecular abnormalities in cell-cycle regulation and signal transduction predominate. These data reveal that the molecular insights, new markers, and drug targets discovered in individual SCCs may shed light on this type of cancer as a whole. C1 [Yan, Wusheng; Emmert-Buck, Michael R.] NCI, Pathogenet Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Wistuba, Ignacio I.] Univ Texas MD Anderson Canc Ctr, Thorac Mol Pathol Lab, Dept Pathol, Houston, TX 77030 USA. [Wistuba, Ignacio I.; Erickson, Heidi S.] Univ Texas MD Anderson Canc Ctr, Thorac Mol Pathol Lab, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. RP Erickson, HS (reprint author), UT MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. EM mbuck@helix.nih.gov; HSErick-son@mdanderson.org FU Cohen-Reinauch BATTLE-2 Fund; Intramural Program of the Center for Cancer Research, National Cancer Institute, NIH FX This work was supported by the Cohen-Reinauch BATTLE-2 Fund and the Intramural Program of the Center for Cancer Research, National Cancer Institute, NIH. NR 255 TC 25 Z9 26 U1 1 U2 4 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2011 VL 1 IS 3 BP 275 EP 300 PG 26 WC Oncology SC Oncology GA V30ZN UT WOS:000208854000001 PM 21938273 ER PT J AU Zhu, L Yan, WS Rodriguez-Canales, J Rosenberg, AM Hu, N Goldstein, AM Taylor, PR Erickson, HS Emmert-Buck, MR Tangrea, MA AF Zhu, Liang Yan, Wusheng Rodriguez-Canales, Jaime Rosenberg, Alex M. Hu, Nan Goldstein, Alisa M. Taylor, Philip R. Erickson, Heidi S. Emmert-Buck, Michael R. Tangrea, Michael A. TI MicroRNA analysis of microdissected normal squamous esophageal epithelium and tumor cells SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE Esophageal squamous cell carcinoma; laser capture microdissection; microRNA; basal layer; differentiated layer; miR-25; miR-106b; miR-21; miR-203; miR-145 AB Previous studies have identified several dysregulated microRNAs in esophageal squamous cell carcinoma (ESCC); however, to date there are no ex vivo analyses comparing expression levels of these regulatory molecules in esophageal squamous cell tumors versus patient-matched normal epithelium. We describe here a technical strategy to evaluate microRNAs in normal esophageal basal cells (NB), normal esophageal differentiated cells (ND), and tumor cells (T). Laser capture microdissection was used to procure target populations from five cases and 18 ESCC-associated microRNAs were measured by RT-qPCR. Five microRNAs (miR-25, miR-106b, miR-21, miR-203, and miR-145) demonstrated consistent differential expression in at least one of the three comparisons: T vs. NB, T vs. ND, or NB vs. ND. The potential regulatory role of the microRNAs in ESCC was further evaluated by correlating their expression with a matched mRNA dataset, which included the same five cases and cell populations. In conclusion, the present work demonstrates the feasibility of studying microRNA levels in precisely dissected cell populations from clinical samples, and sheds light on the molecular mechanisms associated with ESCC. C1 [Zhu, Liang; Yan, Wusheng; Rodriguez-Canales, Jaime; Rosenberg, Alex M.; Emmert-Buck, Michael R.; Tangrea, Michael A.] Ctr Canc Res, Pathol Lab, Pathogenet Unit, Bethesda, MD USA. [Hu, Nan; Goldstein, Alisa M.; Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Erickson, Heidi S.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. RP Emmert-Buck, MR (reprint author), NCI, Pathogenet Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM buckm@mail.nih.gov; tangream@mail.nih.gov FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This work was supported by the intramural program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 86 TC 23 Z9 28 U1 0 U2 0 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2011 VL 1 IS 5 BP 574 EP 584 PG 11 WC Oncology SC Oncology GA V30ZP UT WOS:000208854200001 PM 21796275 ER PT J AU Chan, PC Peckham, JC Malarkey, DE Kissling, GE Travlos, GS Fu, PP AF Chan, Po-Chuen Peckham, John C. Malarkey, David E. Kissling, Grace E. Travlos, Gregory S. Fu, Peter P. TI Two-Year Toxicity and Carcinogenicity Studies of Panax ginseng in Fischer 344 Rats and B6C3F1 Mice SO AMERICAN JOURNAL OF CHINESE MEDICINE LA English DT Article DE Panax ginseng; Toxicity; Carcinogenicity; Herbal Dietary Supplements ID ZERO-DOSE CONTROL; GENE-EXPRESSION CHANGES; EXTRACT; TESTS; KAVA; SUPPLEMENTS; METABOLISM; REGRESSION; MORTALITY; ANIMALS AB Ginseng is one of the most popular herbal supplements on the US market. Numerous reports of adverse effects from products containing ginseng have been filed with the US Food and Drug Administration (FDA) and the literature documents a "ginseng abuse syndrome" among regular users. However, the chronic toxic effects of ginseng are not well characterized. Because of its significant human exposure and the fact that little information on its toxicity is available, Panax ginseng was nominated by the US National Institutes of Health (NIH) to the US National Toxicology Program (NTP) to assess its carcinogenic potential. In this paper, we reported the results of NTP chronic toxicity and tumorigenicity bioassay. It shows that, under these experimental conditions, Panax ginseng is not toxic or tumorigenic. C1 [Chan, Po-Chuen; Peckham, John C.; Malarkey, David E.; Kissling, Grace E.; Travlos, Gregory S.] NIEHS, Res Triangle Pk, NC 27709 USA. [Fu, Peter P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chan, PC (reprint author), NIEHS, Res Triangle Pk, NC 27709 USA. EM chanp@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences FX We thank Drs. Frederick A. Beland, Rick Irwin, In Ok Surh and Charles Alden for critical review of this manuscript. This research was partly supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 54 TC 15 Z9 18 U1 0 U2 9 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0192-415X EI 1793-6853 J9 AM J CHINESE MED JI Am. J. Chin. Med. PY 2011 VL 39 IS 4 BP 779 EP 788 DI 10.1142/S0192415X11009184 PG 10 WC Integrative & Complementary Medicine; Medicine, General & Internal SC Integrative & Complementary Medicine; General & Internal Medicine GA 785CP UT WOS:000292205300012 PM 21721156 ER PT J AU Castells, M Metcalfe, DD Escribano, L AF Castells, Mariana Metcalfe, Dean D. Escribano, Luis TI Diagnosis and Treatment of Cutaneous Mastocytosis in Children Practical Recommendations SO AMERICAN JOURNAL OF CLINICAL DERMATOLOGY LA English DT Review ID INDOLENT SYSTEMIC MASTOCYTOSIS; BULLOUS URTICARIA PIGMENTOSA; H-3 RECEPTOR ANTAGONISTS; MAST-CELL DISEASE; DISODIUM-CROMOGLYCATE; PEDIATRIC MASTOCYTOSIS; ANESTHETIC MANAGEMENT; CONSENSUS PROPOSAL; HISTAMINE-RELEASE; CROMOLYN SODIUM AB Cutaneous mastocytosis in children is a generally benign disease that can present at birth and is often associated with mast cell mediator-related symptoms including pruritus, flushing, and abdominal pain with diarrhea. The most common form of presentation is urticaria pigmentosa, also referred to as maculopapular mastocytosis. Flares of lesions are induced by triggers such as physical stimuli, changes in temperature, anxiety, medications, and exercise. The skin lesions are typically present on the extremities. Symptoms respond to topical and systemic anti-mediator therapy including antihistamines and cromolyn sodium. Remission at puberty is seen in a majority of cases. Progression to systemic mastocytosis with involvement of extracutaneous organs is not common. The cause of cutaneous mastocytosis is unknown and familial cases are rare. Mutations of c-kit have been observed in the skin of those affected. The diagnosis is established on clinical grounds and the findings on skin biopsy. Bone marrow studies are recommended if there is suspicion of progression of disease to an adult form, if cytoreductive therapy is contemplated, or if skin lesions remain present and/or tryptase levels remain elevated after puberty. The use of chemotherapy, including kinase inhibitors, is strongly discouraged unless severe hematologic disease is present, since malignant evolution is extremely rare. C1 [Castells, Mariana] Harvard Univ, Dept Med, Div Rheumatol Immunol & Allergy, Brigham & Womens Hosp,Med Sch, Boston, MA 02115 USA. [Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Escribano, Luis] Hosp Virgen del Valle, Mastocytosis Inst Castilla La Mancha, Toledo, OH, Spain. RP Castells, M (reprint author), Harvard Univ, Dept Med, Div Rheumatol Immunol & Allergy, Brigham & Womens Hosp,Med Sch, 1 Jimmy Fund Way,Smith Bldg,Room 626D, Boston, MA 02115 USA. EM mcastells@partners.org FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH); Mastocytosis Society; Foundation for Research of Castilla La Mancha [FISCAM 2007/36, FISCAM 2008/46]; Ministry of Health [FIS PS09/00032]; Spanish Mastocytosis Foundation [FEM 2010] FX This work was in part supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH) and in part by a grant from The Mastocytosis Society towards funding the Mastocytosis Registry at BWH, headed by Dr Mariana Castells. Research funding was received from the Foundation for Research of Castilla La Mancha (FISCAM 2007/36, FISCAM 2008/46), the Ministry of Health (FIS PS09/00032), and the Spanish Mastocytosis Foundation (FEM 2010). NR 85 TC 53 Z9 55 U1 2 U2 10 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1175-0561 J9 AM J CLIN DERMATOL JI Am. J. Clin. Dermatol. PY 2011 VL 12 IS 4 BP 259 EP 270 PG 12 WC Dermatology SC Dermatology GA 790LG UT WOS:000292588900004 PM 21668033 ER PT J AU Hauser, NS Manoli, I Graf, JC Sloan, J Venditti, CP AF Hauser, Natalie S. Manoli, Irini Graf, Jennifer C. Sloan, Jennifer Venditti, Charles P. TI Variable dietary management of methylmalonic acidemia: metabolic and energetic correlations SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID BODY-COMPOSITION; PREDICTION EQUATIONS; PROPIONATE METABOLISM; SKELETAL-MUSCLE; OBESE CHILDREN; INBORN-ERRORS; AMINO-ACIDS; EXPENDITURE; GROWTH; YOUNG AB Background: Isolated methylmalonic acidemia (MMA) is managed by dietary protein restriction and medical food supplementation. Resting energy expenditure (REE) can be depressed in affected individuals for undefined reasons. Objective: The objective was to document the spectrum of nutritional approaches used to treat patients with MMA, measure REE, and analyze the dependence of REE on body composition, biochemical, and nutritional variables. Design: Twenty-nine patients with isolated MMA (22 mut, 5 cblA, 2 cblB; 15 males, 14 females; age range: 2-35 y) underwent evaluation. REE was measured with open-circuit calorimetry and compared with predicted values by using age-appropriate equations. Results: Nutritional regimens were as follows: protein restriction with medical food (n = 17 of 29), protein restriction with medical food and supplemental isoleucine or valine (n = 5 of 29), or the use of natural protein alone for dietary needs (n = 7 of 29). Most mut patients had short stature and higher percentage fat mass compared with reference controls. Measured REE decreased to 74 +/- 13.6% of predicted (P<0.001) in the <= 18-y group (n = 22) and to 83 +/- 11.1% (P = 0.004) in patients aged >18 y (n = 7). Linear regression modeling suggested that age (P = 0.001), creatinine clearance (P = 0.01), and height z score (P = 0.04) accounted for part of the variance of measured REE per kilogram of fat-free mass (model R-2 = 0.66, P<0.0001). Conclusions: There is wide variation in the dietary treatment of MMA. Standard predictive equations overestimate REE in this population primarily due to their altered body composition and decreased renal function. Defining actual energy needs will help optimize nutrition and protect individuals from overfeeding. This trial is registered at clinicaltrials.gov as NCT00078078. Am J Clin Nutr 2011;93:47-56. C1 [Venditti, Charles P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Graf, Jennifer C.] NIH, Dept Nutr, Bethesda, MD 20892 USA. RP Venditti, CP (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, Bldg 49,Room 4A18, Bethesda, MD 20892 USA. EM venditti@mail.nih.gov OI Manoli, Irini/0000-0003-1543-2941 FU National Human Genome Research Institute, Bethesda, MD; National Institutes of Health Clinical Center FX Supported by the Intramural Research Program of the National Human Genome Research Institute, Bethesda, MD (NSH, IM, JS, and CPV). JCG was supported by the National Institutes of Health Clinical Center. NR 57 TC 16 Z9 16 U1 1 U2 7 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2011 VL 93 IS 1 BP 47 EP 56 DI 10.3945/ajcn.110.004341 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 696PJ UT WOS:000285453500008 PM 21048060 ER PT J AU Li, HL Yang, G Shu, XO Xiang, YB Chow, WH Ji, BT Zhang, XL Cai, H Gao, J Gao, YT Zheng, W AF Li, Hong-Lan Yang, Gong Shu, Xiao-Ou Xiang, Yong-Bing Chow, Wong-Ho Ji, Bu-Tian Zhang, Xianglan Cai, Hui Gao, Jing Gao, Yu-Tang Zheng, Wei TI Dietary glycemic load and risk of colorectal cancer in Chinese women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID GROWTH-FACTOR-I; COLON-CANCER; CARBOHYDRATE INTAKE; DIABETES-MELLITUS; PHYSICAL-ACTIVITY; INDEX; HEALTH; INSULIN; COHORT; SHANGHAI AB Background: Mixed results have been reported in recent epidemiologic studies in Western populations that have investigated the hypothesis that high glycemic load may increase the risk of colorectal cancer. This association has not been prospectively evaluated in other populations. Objective: We examined the association of overall glycemic index and glycemic load with colorectal cancer risk in a prospective cohort of Chinese women. Design: A total of 73,061 women aged 40-70 y and free of cancer at enrollment were included in this analysis. Usual dietary intake was assessed at baseline (1997-2000) and reassessed during the first follow-up (2000-2002) through in-person interviews by using a validated food-frequency questionnaire. Results: During an average follow-up of 9.1 y, 475 incident colorectal cancer cases were identified. Glycemic load was not associated with colorectal cancer risk (P for trend = 0.84). The multivariable hazard ratio for the highest compared with the lowest quintile of glycemic load was 0.94 (95% CI: 0.71, 1.24). Similar results were also observed for associations with dietary glycemic index and total carbohydrate intake, and results did not vary by excluding individuals with a history of diabetes from the analysis. Conclusion: This prospective study, conducted in a population with a high intake of carbohydrates, provides no evidence that a high-glycemic index diet or high glycemic load is associated with an increased risk of colorectal cancer. Am J Clin Nutr 2011;93:101-7. C1 [Yang, Gong; Shu, Xiao-Ou; Zhang, Xianglan; Cai, Hui; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Dept Med,Div Epidemiol, Nashville, TN 37203 USA. [Li, Hong-Lan; Xiang, Yong-Bing; Gao, Jing; Gao, Yu-Tang] Shanghai Canc Inst, Shanghai, Peoples R China. [Chow, Wong-Ho; Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Yang, G (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Dept Med,Div Epidemiol, 6th Floor,Suite 600,2525 W End Ave, Nashville, TN 37203 USA. EM gong.yang@vanderbilt.edu FU US Public Health Service (USPHS) [R37CA70867, R01CA 122364, D43 TW008313] FX Supported by US Public Health Service (USPHS) grants R37CA70867 and R01CA 122364. H-LL was supported, in part, by USPHS grant D43 TW008313. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 45 TC 12 Z9 12 U1 0 U2 7 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2011 VL 93 IS 1 BP 101 EP 107 DI 10.3945/ajcn.110.003053 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 696PJ UT WOS:000285453500015 PM 20962156 ER PT J AU Meyer, PN Fu, K Greiner, T Smith, L Delabie, J Gascoyne, R Ott, G Rosenwald, A Braziel, R Campo, E Vose, J Lenz, G Staudt, L Chan, W Weisenburger, DD AF Meyer, Paul N. Fu, Kai Greiner, Timothy Smith, Lynette Delabie, Jan Gascoyne, Randy Ott, German Rosenwald, Andreas Braziel, Rita Campo, Elias Vose, Julie Lenz, Georg Staudt, Louis Chan, Wing Weisenburger, Dennis D. TI The Stromal Cell Marker SPARC Predicts for Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With Rituximab SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Diffuse large B-cell lymphoma; SPARC; Prognosis; CD68; Stromal cells; Microenvironment; Tumor markers, biological ID MACROPHAGE-ASSOCIATED ANTIGEN; TUMOR-ASSOCIATED MACROPHAGES; FOLLICULAR LYMPHOMA; EXPRESSION; TISSUE; CLASSIFICATION; SIGNATURE; NEOPLASMS; LEUKEMIA; BINDING AB The cellular composition of the tumor microenvironment may affect survival in diffuse large B-cell lymphoma (DLBCL). We performed immunostains for 2 stromal cell markers, CD68 and SPARC (secreted protein, acidic and rich in cysteine), in 262 patients with DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapies. Patients with any SPARC+ cells in the microenvironment had a significantly longer overall survival, and patients with high SPARC positivity in the microenvironment also had a significantly longer event free survival. Survival differences were mainly due to the prognostic effect of SPARC+ cells in activated B-cell (ABC)-type DLBCL, with no effect found in the germinal center B-cell type DLBCL. Of clinical features examined, only the number of extranodal sites was significantly associated with SPARC expression. Multivariate analysis revealed that SPARC expression predicted patient survival independent of the International Prognostic Index or tumor cell of origin. SPARC expression in the microenvironment of DLBCL can be used for prognostic purposes, determining a subgroup of patients with ABC DLBCL who have significantly longer survival. More aggressive chemotherapy protocols should be considered for patients with ABC DLBCL without SPARC+ stromal cells. CD68 expression by cells in the microenvironment did not predict survival. C1 [Meyer, Paul N.; Fu, Kai; Greiner, Timothy; Chan, Wing; Weisenburger, Dennis D.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. [Smith, Lynette] Univ Nebraska Med Ctr, Dept Biostat, Omaha, NE 68198 USA. [Vose, Julie] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE 68198 USA. [Delabie, Jan] Univ Oslo, Rikshosp, Radiumhosp Med Ctr, Dept Pathol, N-0027 Oslo, Norway. [Gascoyne, Randy] British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada. [Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany. [Ott, German] Inst Clin Pharmacol, Stuttgart, Germany. [Rosenwald, Andreas] Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. [Braziel, Rita] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Campo, Elias] Univ Barcelona, Dept Pathol, Hosp Clin, Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain. [Lenz, Georg] Univ Med Berlin, Mol Canc Res Ctr, Berlin, Germany. [Staudt, Louis] NCI, Dept Pathol, Div Canc Treatment & Diag, Ctr Canc Res, Bethesda, MD 20892 USA. RP Weisenburger, DD (reprint author), Univ Nebraska Med Ctr, Dept Pathol & Microbiol, 983135 Nebraska Med Ctr, Omaha, NE 68198 USA. RI Lenz, Georg/I-6844-2012; OI Delabie, Jan/0000-0001-5023-0689; Campo, elias/0000-0001-9850-9793 NR 35 TC 22 Z9 27 U1 1 U2 6 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 2011 VL 135 IS 1 BP 54 EP 61 DI 10.1309/AJCPJX4BJV9NLQHY PG 8 WC Pathology SC Pathology GA 697TB UT WOS:000285538700006 PM 21173124 ER PT J AU Flegal, KM Graubard, BI Williamson, DF Cooper, RS AF Flegal, Katherine M. Graubard, Barry I. Williamson, David F. Cooper, Richard S. TI Reverse Causation and Illness-related Weight Loss in Observational Studies of Body Weight and Mortality SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material DE bias (epidemiology); body mass index; body weight; confounding factors (epidemiology); epidemiologic methods; mortality; selection bias ID BREAST-CANCER DIAGNOSIS; EXCLUDING EARLY DEATHS; ALL-CAUSE MORTALITY; HIP FRACTURE RISK; ACUTE LUNG INJURY; MIDDLE-AGED MEN; MASS INDEX; FOLLOW-UP; PROSPECTIVE COHORT; OLDER WOMEN AB In studies of weight and mortality, the construct of reverse causation has come to be used to imply that the exposure-outcome relation is biased by weight loss due to preexisting illness. Observed weight-mortality associations are sometimes thought to result from this bias. Evidence for the occurrence of such bias is weak and inconsistent, suggesting that either the analytical methods used have been inadequate or else illness-related weight loss is not an important source of bias. Deleting participants has been the most frequent approach to control possible bias. As implemented, this can lead to deletion of almost 90% of all deaths in a sample and to deletion of more overweight and obese participants than participants with normal or below normal weight. Because it has not been demonstrated that the procedures used to adjust for reverse causation increase validity or have large or systematic effects on relative risks, it is premature to consider reverse causation as an important cause of bias. Further research would be useful to elucidate the potential effects and importance of reverse causation or illness-related weight loss as a source of bias in the observed associations between weight and mortality in cohort studies. C1 [Flegal, Katherine M.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Williamson, David F.] Emory Univ, Hubert Dept Global Hlth, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Cooper, Richard S.] Loyola Univ, Sch Med, Dept Prevent Med & Epidemiol, Maywood, IL 60153 USA. RP Flegal, KM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, 3311 Toledo Rd,Room 4336, Hyattsville, MD 20782 USA. EM kmf2@cdc.gov RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X NR 112 TC 63 Z9 63 U1 1 U2 11 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 JAN 1 PY 2011 VL 173 IS 1 BP 1 EP 9 DI 10.1093/aje/kwq341 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 695ZR UT WOS:000285412200001 PM 21059807 ER PT J AU Press, DJ Sullivan-Halley, J Ursin, G Deapen, D McDonald, JA Strom, BL Norman, SA Simon, MS Marchbanks, PA Folger, SG Liff, JM Burkman, RT Malone, KE Weiss, LK Spirtas, R Bernstein, L AF Press, David J. Sullivan-Halley, Jane Ursin, Giske Deapen, Dennis McDonald, Jill A. Strom, Brian L. Norman, Sandra A. Simon, Michael S. Marchbanks, Polly A. Folger, Suzanne G. Liff, Jonathan M. Burkman, Ronald T. Malone, Kathleen E. Weiss, Linda K. Spirtas, Robert Bernstein, Leslie TI Breast Cancer Risk and Ovariectomy, Hysterectomy, and Tubal Sterilization in the Women's Contraceptive and Reproductive Experiences Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE breast neoplasms; case-control studies; hysterectomy; ovariectomy; sterilization; tubal ID HORMONE REPLACEMENT THERAPY; FOLLICLE-STIMULATING-HORMONE; OVARIAN-FUNCTION; UNILATERAL OOPHORECTOMY; ABDOMINAL HYSTERECTOMY; RECEPTOR STATUS; FSH-LEVELS; SURGERY; AGE; MENOPAUSE AB Removal or impairment of ovaries before menopause may affect a woman's breast cancer risk by altering her cumulative exposure to ovarian hormones. The Women's Contraceptive and Reproductive Experiences Study, a population-based, multicenter case-control study of incident invasive breast cancer, recruited women aged 35-64 years (4,490 cases and 4,611 controls) who provided data on ovariectomy, hysterectomy, and tubal sterilization during in-person interviews. Controls were frequency-matched to cases by age, race, and study site. Unconditional logistic regression analysis was used. Women who had not undergone premenopausal reproductive surgery were the referent group. Bilateral ovariectomy was associated with reduced breast cancer risk overall (odds ratio (OR) = 0.59, 95% confidence interval (CI): 0.50, 0.69) and among women < 45 years of age (ORs ranged from 0.31 to 0.52), but not among those who were older at surgery. It was also associated with a reduced risk for estrogen and progesterone receptor-positive tumors (OR = 0.63, 95% CI: 0.52, 0.75) but not receptor-negative tumors. Hysterectomy with ovarian conservation (OR = 0.83, 95% CI: 0.72, 0.96) and hysterectomy with partial ovary removal (OR = 0.73, 95% CI: 0.59, 0.91) were also associated with lower risk. No association with breast cancer risk was observed with tubal sterilization only or partial ovariectomy without hysterectomy. Reproductive organ surgeries may alter ovarian hormone levels, thereby affecting breast cancer risk. C1 [Bernstein, Leslie] City Hope Comprehens Canc Ctr, Div Canc Etiol, Dept Populat Sci, Duarte, CA 91010 USA. [Sullivan-Halley, Jane; Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA. [Press, David J.; Ursin, Giske; Deapen, Dennis; Bernstein, Leslie] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Press, David J.; Ursin, Giske; Deapen, Dennis; Bernstein, Leslie] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [McDonald, Jill A.; Marchbanks, Polly A.; Folger, Suzanne G.] Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. [Strom, Brian L.; Norman, Sandra A.] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Simon, Michael S.] Wayne State Univ, Div Hematol & Oncol, Karmanos Canc Inst, Detroit, MI USA. [Simon, Michael S.] Wayne State Univ, Populat Studies & Prevent Program, Karmanos Canc Inst, Detroit, MI USA. [Liff, Jonathan M.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Burkman, Ronald T.] Tufts Univ, Sch Med, Dept Obstet & Gynecol, Springfield, MA 01199 USA. [Burkman, Ronald T.] Baystate Med Ctr, Springfield, MA USA. [Malone, Kathleen E.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Weiss, Linda K.] NCI, Canc Ctr Branch, Bethesda, MD 20892 USA. [Spirtas, Robert] NICHHD, Contracept & Reprod Hlth Branch, Populat Res Ctr, Bethesda, MD 20892 USA. RP Bernstein, L (reprint author), City Hope Comprehens Canc Ctr, Div Canc Etiol, Dept Populat Sci, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM lbernstein@coh.org FU National Institute of Child Health and Human Development; National Cancer Institute, through Emory University [N01-HD-2-3168]; Fred Hutchinson Cancer Research Center [N01-HD-2-3166]; Karmanos Cancer Institute at Wayne State University [N01-HD-3-3174]; University of Pennsylvania [1-HD-3-3176]; University of Southern California [N01-HD-3-3175]; Centers for Disease Control and Prevention [Y01-HD-7022]; California Department of Health Services FX Data collection for the Women's CARE Study was supported by the National Institute of Child Health and Human Development, with additional support from the National Cancer Institute, through contracts with Emory University (N01-HD-2-3168), the Fred Hutchinson Cancer Research Center (N01-HD-2-3166), the Karmanos Cancer Institute at Wayne State University (N01-HD-3-3174), the University of Pennsylvania (N01-HD-3-3176), and the University of Southern California (N01-HD-3-3175); and through an intraagency agreement with the Centers for Disease Control and Prevention (Y01-HD-7022). Support for use of Surveillance, Epidemiology, and End Results cancer registries for case identification was obtained through contracts N01-PC-67006 (Atlanta), N01-CN-65064 (Detroit), N01-PC-67010 (Los Angeles), and N01-CN-0532 (Seattle). The collection of cancer incidence data in California used in this publication (University of Southern California, Los Angeles County portion of this study) was also supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by the California Health and Safety Code, Section 103885. NR 52 TC 21 Z9 21 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2011 VL 173 IS 1 BP 38 EP 47 DI 10.1093/aje/kwq339 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 695ZR UT WOS:000285412200004 PM 21109566 ER PT J AU Waggoner, JK Kullman, GJ Henneberger, PK Umbach, DM Blair, A Alavanja, MCR Kamel, F Lynch, CF Knott, C London, SJ Hines, CJ Thomas, KW Sandler, DP Lubin, JH Freeman, LE Hoppin, JA AF Waggoner, Jenna K. Kullman, Greg J. Henneberger, Paul K. Umbach, David M. Blair, Aaron Alavanja, Michael C. R. Kamel, Freya Lynch, Charles F. Knott, Charles London, Stephanie J. Hines, Cynthia J. Thomas, Kent W. Sandler, Dale P. Lubin, Jay H. Beane Freeman, Laura E. Hoppin, Jane A. TI Mortality in the Agricultural Health Study, 1993-2007 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE agriculture; healthy worker effect; mortality; neoplasms; pesticides; wounds and injuries ID PESTICIDE APPLICATORS; PROSTATE-CANCER; INJURY MORTALITY; UNITED-STATES; FARMERS; RISK; EXPOSURE; METAANALYSES; COHORT; WIVES AB Comparing agricultural cohorts with the general population is challenging because the general healthiness of farmers may mask potential adverse health effects of farming. Using data from the Agricultural Health Study, a cohort of 89,656 pesticide applicators and their spouses (N = 89, 656) in North Carolina and Iowa, the authors computed standardized mortality ratios (SMRs) comparing deaths from time of the enrollment (1993-1997) through 2007 to state-specific rates. To compensate for the cohort's overall healthiness, relative SMRs were estimated by calculating the SMR for each cause relative to the SMR for all other causes. In 1,198,129 person-years of follow-up, 6,419 deaths were observed. The all-cause mortality rate was less than expected (SMRapplicators = 0.54, 95% confidence interval (CI): 0.52, 0.55; SMRspouses = 0.52, 95% CI: 0.50, 0.55). SMRs for all cancers, heart disease, and diabetes were significantly below 1.0. In contrast, applicators experienced elevated numbers of machine-related deaths (SMR = 4.15, 95% CI: 3.18, 5.31), motor vehicle nontraffic accidents (SMR = 2.80, 95% CI: 1.81, 4.14), and collisions with objects (SMR = 2.12, 95% CI: 1.25, 3.34). In the relative SMR analysis for applicators, the relative mortality ratio was elevated for lymphohematopoietic cancers, melanoma, and digestive system, prostate, kidney, and brain cancers. Among spouses, relative SMRs exceeded 1.0 for lymphohematopoietic cancers and malignancies of the digestive system, brain, breast, and ovary. Unintentional fatal injuries remain an important risk for farmers; mortality ratios from several cancers were elevated relative to other causes. C1 [Waggoner, Jenna K.; Kamel, Freya; London, Stephanie J.; Sandler, Dale P.; Hoppin, Jane A.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Waggoner, Jenna K.; Kullman, Greg J.; Henneberger, Paul K.] NIOSH, Div Resp Dis Studies, Morgantown, WV 26505 USA. [Umbach, David M.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Blair, Aaron; Alavanja, Michael C. R.; Lubin, Jay H.; Beane Freeman, Laura E.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Knott, Charles] Battelle Mem Inst, Durham, NC USA. [Hines, Cynthia J.] NIOSH, Div Surveillance Hazard Evaluat & Field Studies, Cincinnati, OH 45226 USA. [Thomas, Kent W.] US EPA, Natl Exposure Res Lab, Res Triangle Pk, NC 27711 USA. RP Hoppin, JA (reprint author), NIEHS, Epidemiol Branch, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM hoppin1@niehs.nih.gov RI Beane Freeman, Laura/C-4468-2015; OI Beane Freeman, Laura/0000-0003-1294-4124; Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018; London, Stephanie/0000-0003-4911-5290 FU Association of Schools of Public Health/Centers for Disease Control; National Institute for Occupational Safety and Health; National Institutes of Health; National Institutes of Health, National Institute of Environmental Health Sciences [Z01-ES049030]; National Institutes of Health National Cancer Institute [Z01-CP010119] FX This work was supported by the Association of Schools of Public Health/Centers for Disease Control fellowship program; the National Institute for Occupational Safety and Health; the Intramural Research Program of the National Institutes of Health; and the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (Z01-ES049030) and the National Institutes of Health National Cancer Institute (Z01-CP010119). NR 42 TC 36 Z9 37 U1 0 U2 19 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2011 VL 173 IS 1 BP 71 EP 83 DI 10.1093/aje/kwq323 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 695ZR UT WOS:000285412200008 PM 21084556 ER PT J AU Melton, PE Haack, K Goring, HH Laston, S Umans, JG Lee, ET Fabsitz, RR Devereux, RB Best, LG Maccluer, JW Almasy, L Cole, SA AF Melton, Phillip E. Haack, Karin Goering, Harald H. Laston, Sandy Umans, Jason G. Lee, Elisa T. Fabsitz, Richard R. Devereux, Richard B. Best, Lyle G. Maccluer, Jean W. Almasy, Laura Cole, Shelley A. TI Genetic Influences on Serum Bilirubin in American Indians: The Strong Heart Family Study SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; GENOME-WIDE ASSOCIATION; CARDIOVASCULAR-DISEASE; UGT1A1-ASTERISK-28 ALLELE; LINKAGE ANALYSIS; RISK-FACTORS; MAJOR GENE; UGT1A1; TRAIT; POLYMORPHISMS AB Objective: To identify genetic variation influencing serum bilirubin levels in American Indians, we performed genome-wide screening and association analyses in the Strong Heart Family Study. Bilirubin is an endogenous antioxidant that has demonstrated an inverse relationship with cardiovascular disease. Genetic variation within the promoter region of uridine diphosphate glucuronosyltransferase (UGT1A1) on chromosome 2q has been associated with elevated serum bilirubin levels in European populations. However, no study has investigated the UGT1A1 promoter in American Indians. Methods: Statistical analyses were carried out with 3,484 participants aged 14 to 93 years recruited from three geographic areas in the United States; Arizona, Oklahoma, and North and South Dakota. Results: Variance components linkage analysis detected a quantitative trait locus (QTL) for bilirubin on chromosome 2q in the combined centers (LOD = 6.61, P = 4.24 x 10(-6)) and in Oklahoma (LOD = 5.65, P = 4.57 24 x 10(-5)). Genetic association of the UGT1A1 promoter polymorphism was significant for all geographic locations. After adjustment using conditional linkage for UGT1A1 promoter variance, the linkage signal dropped to 1.10 in the combined sample and to 3.32 (P = 0.02) in Oklahoma, indicating this polymorphism is not completely responsible for the linkage signal in American Indians. We also detected suggestive linkage signals in the Dakotas on chromosome 10p12 (LOD = 2.18) and in the combined centers (LOD = 2.24) on chromosome 10q21. Conclusions: Replication of a serum bilirubin QTL on chromosome 2q in American Indians implicates UGT1A1 but further genotyping is warranted to identify additional causative polymorphisms. Evidence also supports a potential novel locus for bilirubin on chromosome 10. Am. J. Hum. Biol. 23: 118-125, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Melton, Phillip E.; Haack, Karin; Goering, Harald H.; Laston, Sandy; Maccluer, Jean W.; Almasy, Laura; Cole, Shelley A.] SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. [Umans, Jason G.] MedStar Res Inst, Washington, DC USA. [Lee, Elisa T.] Univ Oklahoma, Hlth Sci Ctr, Dept Biostat & Epidemiol, Oklahoma City, OK USA. [Devereux, Richard B.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Devereux, Richard B.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Best, Lyle G.] Missouri Breaks Ind Res Inc, Timber Lake, SD USA. RP Melton, PE (reprint author), SW Fdn Biomed Res, Dept Genet, POB 760549, San Antonio, TX 78245 USA. EM pmelton@sfbrgenetics.org RI Melton, Phillip/C-4773-2012; Melton, Phillip/A-5012-2013 OI Melton, Phillip/0000-0003-4026-2964 FU NIH (through the National Heart, Lung, and Blood Institute) [U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654, U01 HL65521]; NIH [MH59490]; Research Facilities Improvement Program [C06 RR013556, C06 RR017515] FX Contract grant sponsor: NIH (through the National Heart, Lung, and Blood Institute); Contract grant numbers: U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654, U01 HL65521; Contract grant sponsor: NIH; Contract grant number: MH59490; Contract grant sponsor: Research Facilities Improvement Program; Contract grant numbers: C06 RR013556, C06 RR017515. NR 36 TC 6 Z9 6 U1 2 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PD JAN-FEB PY 2011 VL 23 IS 1 SI SI BP 118 EP 125 DI 10.1002/ajhb.21114 PG 8 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA 695UA UT WOS:000285396900015 PM 21080475 ER PT J AU Watson, NL Sutton-Tyrrell, K Youk, AO Boudreau, RM Mackey, RH Simonsick, EM Rosano, C Hardy, SE Windham, BG Harris, TB Najjar, SS Lakatta, EG Atkinson, HH Johnson, KC Bauer, DC Nemwan, AB AF Watson, Nora L. Sutton-Tyrrell, Kim Youk, Ada O. Boudreau, Robert M. Mackey, Rachel H. Simonsick, Eleanor M. Rosano, Caterina Hardy, Susan E. Windham, B. Gwen Harris, Tamara B. Najjar, Samer S. Lakatta, Edward G. Atkinson, Hal H. Johnson, Karen C. Bauer, Douglas C. Nemwan, Anne B. CA Hlth ABC Study TI Arterial Stiffness and Gait Speed in Older Adults With and Without Peripheral Arterial Disease SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE aging; arterial stiffness; blood pressure; hypertension; peripheral arterial disease; physical function ID SMALL-VESSEL DISEASE; PULSE-WAVE VELOCITY; CARDIOVASCULAR-DISEASE; PHYSICAL PERFORMANCE; BLOOD-PRESSURE; HEART-DISEASE; INFLAMMATORY MARKERS; FUNCTIONAL DECLINE; BODY-COMPOSITION; ORGAN DAMAGE AB BACKGROUND Central arterial stiffness is increasingly recognized as an important predictor of cardiovascular events and mortality in older adults; however, few studies have evaluated the association of arterial stiffness with mobility decline, a common consequence of vascular disease. METHODS We analyzed the association of pulse wave velocity (PWV), a measure of aortic stiffness, with longitudinal gait speed over 7 years in 2,172 participants in the Health, Aging and Body Composition (ABC) Study (mean age +/- s.d. 73.6 +/- 2.9 years, 48% men, 39% black). RESULTS In mixed-effects models adjusted for demographics, each s.d. (396 cm/s) higher PWV was associated with 0.015 (s.e. 0.004) m/s slower gait at baseline and throughout the study period in the full cohort (P < 0.001); this relationship was largely explained by hypertension and other vascular risk factors. Among participants with peripheral arterial disease (PAD) (n = 261; 12.7%), each s.d. higher PWV was independently associated with 0.028 (s.e. 0.010) m/s slower gait speed at baseline and throughout the study period (P < 0.01). CONCLUSIONS These findings suggest that aortic stiffness may be especially detrimental to mobility in older adults with already compromised arterial function. C1 [Watson, Nora L.; Sutton-Tyrrell, Kim; Boudreau, Robert M.; Mackey, Rachel H.; Rosano, Caterina; Nemwan, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Youk, Ada O.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Simonsick, Eleanor M.; Najjar, Samer S.; Lakatta, Edward G.] Natl Inst Aging, Intramural Res Program, Baltimore, MD USA. [Hardy, Susan E.; Nemwan, Anne B.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. [Windham, B. Gwen] Univ Mississippi, Med Ctr, Dept Internal Med, Jackson, MS 39216 USA. [Harris, Tamara B.] Natl Inst Aging, Intramural Res Program, Bethesda, MD USA. [Atkinson, Hal H.] Wake Forest Univ, Sch Med, Dept Internal Med, Winston Salem, NC 27109 USA. [Johnson, Karen C.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. RP Watson, NL (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. EM norawatson@gmail.com RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Youk, Ada/0000-0001-6912-9759; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010; Boudreau, Robert/0000-0003-0162-5187; Mackey, Rachel/0000-0001-6088-2664 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institutes of Health, NIA FX This work was supported by National Institute on Aging (NIA) contract numbers N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; and, in part, by the Intramural Research Program of the National Institutes of Health, NIA. NR 43 TC 25 Z9 26 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JAN PY 2011 VL 24 IS 1 BP 90 EP 95 DI 10.1038/ajh.2010.193 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 697GS UT WOS:000285501800015 PM 20940711 ER PT J AU Rocco, MV Larive, B Eggers, PW Beck, GJ Chertow, GM Levin, NW Kliger, AS AF Rocco, Michael V. Larive, Brett Eggers, Paul W. Beck, Gerald J. Chertow, Glenn M. Levin, Nathan W. Kliger, Alan S. CA FHN Trial Grp TI Baseline Characteristics of Participants in the Frequent Hemodialysis Network (FHN) Daily and Nocturnal Trials SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Frequent hemodialysis; daily hemodialysis; nocturnal hemodialysis; left ventricular hypertrophy; physical functioning; randomized clinical trial ID QUALITY-OF-LIFE; MEMBRANE FLUX; DIALYSIS; HEMO AB Background: The annual mortality rate for maintenance hemodialysis patients in the United States is unacceptably high at 15%-20%. In 2004, we initiated the Frequent Hemodialysis Network (FHN) clinical trials. This report presents baseline characteristics of FHN Trial participants and compares them with hemodialysis patients tracked in US Renal Data System (USRDS) data. Study Design: 2 separate randomized clinical trials. Settings & Participants: FHN includes 332 patients with chronic kidney disease requiring long-term dialysis therapy enrolled in 2 separate randomized clinical trials. The FHN Daily Trial (245 randomly assigned participants) was designed to compare outcomes of 6-times-weekly in-center daily hemodialysis (1.5-2.75 h/session) with conventional 3-times-weekly in-center hemodialysis. The FHN Nocturnal Trial (87 randomly assigned participants) was designed to compare outcomes of 6-times-weekly home nocturnal (6-8 h/session) with conventional 3-times-weekly hemodialysis. USRDS data include 338,109 incident and prevalent long-term hemodialysis patients from the calendar year 2007. Results: Participants in both trials were on average younger than the average hemodialysis patient in the United States (Daily Trial, 50.4 years; P < 0.001; Nocturnal Trial, 52.8 years; P < 0.001). Compared with USRDS data, whites were under-represented in the Daily Trial (36% vs 55%; P < 0.001), whereas Hispanics were under-represented in the Nocturnal Trial and over-represented in the Daily Trial (0% vs 28%; P < 0.001). In addition, there were more fistulas and fewer catheters in the Daily Trial (61% and 20%, respectively; P < 0.001 for both) and fewer grafts and more catheters in the Nocturnal Trial (10% and 44%, respectively; P < 0.005 for both). Limitations: Clinical trial exclusion criteria and patient willingness to participate limit comparisons with the USRDS. Conclusions: FHN participants were younger and the racial composition for each study was different from the racial composition of the aggregate US dialysis population. Catheters for vascular access were more common in FHN Nocturnal Trial participants. Am J Kidney Dis. 57(1): 90-100. (C) 2010 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Rocco, Michael V.] Wake Forest Univ, Bowman Gray Sch Med, Nephrol Sect, Dept Med, Winston Salem, NC 27157 USA. [Larive, Brett; Beck, Gerald J.] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA. [Eggers, Paul W.] NIDDK, Div Kidney Urol & Hematol, Bethesda, MD USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA. [Levin, Nathan W.] Renal Res Inst, New York, NY USA. [Kliger, Alan S.] Yale Univ, Sch Med, Dept Med, Hosp St Raphael, New Haven, CT 06510 USA. RP Rocco, MV (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Nephrol Sect, Dept Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM mrocco@wfubmc.edu FU NIDDK [U01DK066597, 2U01DK066579, 3U01DK066481, 3U01DK066480]; CMS; National Institutes of Health (NIH) Research Foundation; Fresenius Medical Care; Renal Research Institute; Satellite Health Care FX Funds for these trials were received from the NIDDK, CMS, National Institutes of Health (NIH) Research Foundation, Fresenius Medical Care, Renal Research Institute, and Satellite Health Care. These trials were supported by NIDDK grants U01DK066597 (Data Coordinating Center), 2U01DK066579 (Dr Levin), 3U01DK066481 (Dr Chertow), and 3U01DK066480 (Dr Rocco). NR 17 TC 24 Z9 24 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 2011 VL 57 IS 1 BP 90 EP 100 DI 10.1053/j.ajkd.2010.08.024 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 698VP UT WOS:000285621600014 PM 21122961 ER PT J AU Carter, TC Pangilinan, F Troendle, JF Molloy, AM VanderMeer, J Mitchell, A Kirke, PN Conley, MR Shane, B Scott, JM Brody, LC Mills, JL AF Carter, Tonia C. Pangilinan, Faith Troendle, James F. Molloy, Anne M. VanderMeer, Julia Mitchell, Adam Kirke, Peadar N. Conley, Mary R. Shane, Barry Scott, John M. Brody, Lawrence C. Mills, James L. TI Evaluation of 64 Candidate Single Nucleotide Polymorphisms as Risk Factors for Neural Tube Defects in a Large Irish Study Population SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE congenital abnormalities; folic acid; neural tube defects; single nucleotide polymorphism; spina bifida ID SPINA-BIFIDA MENINGOMYELOCELE; ALPHA-RECEPTOR; BREAST-CANCER; HUMAN T; ASSOCIATION; GENE; GENOTYPE; METABOLISM; PREVENTION; MUTATIONS AB Individual studies of the genetics of neural tube defects (NTDs) contain results on a small number of genes in each report. To identify genetic risk factors for NTDs, we evaluated potentially functional single nucleotide polymorphisms (SNPs) that are biologically plausible risk factors for NTDs but that have never been investigated for an association with NTDs, examined SNPs that previously showed no association with NTDs in published studies, and tried to confirmpreviously reported associations in folate-related and non-folate-related genes. We investigated 64 SNPs in 34 genes for association with spina bifida in up to 558 case families (520 cases, 507 mothers, 457 fathers) and 994 controls in Ireland. Case-control and mother-control comparisons of genotype frequencies, tests of transmission disequilibrium, and log-linear regression models were used to calculate effect estimates. Spina bifida was associated with over-transmission of the LEPR (leptin receptor) rs1805134 minor C allele [genotype relative risk (GRR): 1.5; 95% confidence interval (CI): 1.0-2.1; P=0.0264] and the COMT (catechol-O-methyltransferase) rs737865 major T allele (GRR: 1.4; 95% CI: 1.1-2.0; P=0.0206). After correcting for multiple comparisons, these individual test P-values exceeded 0.05. Consistent with previous reports, spina bifida was associated with MTHFR 677C> T, T (Brachyury) rs3127334, LEPR K109R, and PDGFRA promoter haplotype combinations. The associations between LEPR SNPs and spina bifida suggest a possible mechanism for the finding that obesity is a NTD risk factor. The association between a variant in COMT and spina bifida implicates methylation and epigenetics in NTDs. (C) 2010 Wiley-Liss, Inc. C1 [Carter, Tonia C.; Troendle, James F.; Conley, Mary R.; Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Pangilinan, Faith; VanderMeer, Julia; Mitchell, Adam; Brody, Lawrence C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Molloy, Anne M.; Scott, John M.] Trinity Coll Dublin, Sch Immunol & Biochem, Dublin, Ireland. [Kirke, Peadar N.] Hlth Res Board Ireland, Child Hlth Epidemiol Unit, Dublin, Ireland. [Shane, Barry] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA. RP Carter, TC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, 6100 Execut Blvd,Room 7B03C,MSC 7510, Bethesda, MD 20892 USA. EM carterto@mail.nih.gov OI Molloy, Anne/0000-0002-1688-9049 FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Human Genome Research Institute FX Grant sponsor: Intramural Research Programs of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Human Genome Research Institute. NR 42 TC 17 Z9 19 U1 1 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JAN PY 2011 VL 155A IS 1 BP 14 EP 21 DI 10.1002/ajmg.a.33755 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 702IZ UT WOS:000285889100003 PM 21204206 ER PT J AU Tan, WH Bacino, CA Skinner, SA Anselm, I Barbieri-Welge, R Bauer-Carlin, A Beaudet, AL Bichell, TJ Gentile, JK Glaze, DG Horowitz, LT Kothare, SV Lee, HS Nespeca, MP Peters, SU Sahoo, T Sarco, D Waisbren, SE Bird, LM AF Tan, Wen-Hann Bacino, Carlos A. Skinner, Steven A. Anselm, Irina Barbieri-Welge, Rene Bauer-Carlin, Astrid Beaudet, Arthur L. Bichell, Terry Jo Gentile, Jennifer K. Glaze, Daniel G. Horowitz, Lucia T. Kothare, Sanjeev V. Lee, Hye-Seung Nespeca, Mark P. Peters, Sarika U. Sahoo, Trilochan Sarco, Dean Waisbren, Susan E. Bird, Lynne M. TI Angelman Syndrome: Mutations Influence Features in Early Childhood SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Angelman syndrome; genotype-phenotype correlation; behavioral genetics; growth; child development ID GENOTYPE-PHENOTYPE CORRELATIONS; PRADER-WILLI-SYNDROME; BEHAVIORAL PHENOTYPES; MOLECULAR CHARACTERIZATION; DOWN-SYNDROME; SYNDROME GENE; DELETION; UBE3A; UBE3A/E6-AP; EXPRESSION AB Angelman syndrome (AS) is a neurodevelopmental disorder caused by a lack of expression of the maternal copy of UBE3A. Although the "classic" features of AS are well described, few large-scale studies have delineated the clinical features in AS. We present baseline data from 92 children with a molecular diagnosis of AS between 5 and 60 months old who are enrolled in the National Institutes of Health Rare Diseases Clinical Research Network Angelman Syndrome Natural History Study from January 2006 to March 2008. Seventy-four percent of participants had deletions, 14% had either uniparental disomy (UPD) or imprinting defects, and 12% had UBE3A mutations. Participants with UPD/imprinting defects were heavier (P=0.0002), while those with deletions were lighter, than the general population (P<0.0001). Twenty out of 92 participants were underweight, all of whom had deletions or UBE3A mutations. Eight out of 92 participants (6/13 (46%) with UPD/imprinting defects and 2/11 (18%) with UBE3A mutations) were obese. Seventy-four out of 92 participants (80%) had absolute or relative microcephaly. No participant was macrocephalic. The most common behavioral findings were mouthing behavior (95%), short attention span (92%), ataxic or broad-based gait (88%), history of sleep difficulties (80%), and fascination with water 75%). Frequent, easily provoked laughter was observed in 60%. Clinical seizures were reported in 65% of participants but all electroencephalograms (EEGs) were abnormal. We conclude that the most characteristic feature of AS is the neurobehavioral phenotype, but specific EEG findings are highly sensitive for AS. Obesity is common among those with UPD/imprinting defects. (C) 2010 Wiley-Liss, Inc. C1 [Tan, Wen-Hann; Bacino, Carlos A.; Skinner, Steven A.; Anselm, Irina; Barbieri-Welge, Rene; Bauer-Carlin, Astrid; Beaudet, Arthur L.; Bichell, Terry Jo; Gentile, Jennifer K.; Glaze, Daniel G.; Horowitz, Lucia T.; Kothare, Sanjeev V.; Lee, Hye-Seung; Nespeca, Mark P.; Peters, Sarika U.; Sahoo, Trilochan; Sarco, Dean; Waisbren, Susan E.; Bird, Lynne M.] NIH, Rare Dis Clin Res Network, Angelman Rett & Prader Willi Syndromes Consortium, Bethesda, MD USA. [Tan, Wen-Hann] Harvard Univ, Childrens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [Bacino, Carlos A.; Beaudet, Arthur L.] Texas Childrens Hosp, Baylor Coll Med, Kleberg Genet Clin, Dept Mol & Human Genet, Houston, TX 77030 USA. [Skinner, Steven A.; Bauer-Carlin, Astrid; Horowitz, Lucia T.] Greenwood Genet Ctr, Greenwood, SC 29646 USA. [Anselm, Irina; Kothare, Sanjeev V.; Sarco, Dean] Harvard Univ, Childrens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Barbieri-Welge, Rene] Rady Childrens Hosp San Diego, Dev Serv, San Diego, CA USA. [Bichell, Terry Jo] Vanderbilt Univ, Vanderbilt Kennedy Ctr, Nashville, TN USA. [Gentile, Jennifer K.; Waisbren, Susan E.] Harvard Univ, Childrens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Glaze, Daniel G.] Texas Childrens Hosp, Baylor Coll Med, Neurol Sect, Dept Pediat, Houston, TX 77030 USA. [Lee, Hye-Seung] Univ S Florida, Dept Pediat, Pediat Epidemiol Ctr, Tampa, FL 33620 USA. [Nespeca, Mark P.] Univ Calif San Diego, Dept Neurosci, Div Neurol, Rady Childrens Hosp San Diego, San Diego, CA 92103 USA. [Peters, Sarika U.] Texas Childrens Hosp, Baylor Coll Med, Meyer Ctr Dev Pediat, Sect Dev Pediat, Houston, TX 77030 USA. [Bird, Lynne M.] Univ Calif San Diego, Dept Pediat, Div Genet Dysmorphol, Rady Childrens Hosp San Diego, San Diego, CA 92103 USA. RP Bird, LM (reprint author), 3020 Childrens Way 5031, San Diego, CA 92123 USA. EM lbird@rchsd.org OI Kothare, Sanjeev/0000-0001-7849-6649; Bichell, Terry Jo Vetters/0000-0002-1055-4993 FU National Center for Research Resources (NCRR); Office of Rare Diseases Research (ORDR); National Institutes of Health (NIH) [NIH U54 RR019478, NIH U54 RR019259]; Angelman Syndrome Foundation-Western Area Chapter; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH); NIH Office of Rare Diseases Research (ORDR); Angelman Syndrome Foundation Western Area Chapter; [NIHU54RR019259] FX The authors are grateful to the General Clinical Research Centers (GCRC) at Children's Hospital Boston and Texas Children's Hospital for their support. They greatly appreciate: the study coordinators/nurses for their invaluable assistance-Beverly M. Feldman (Baylor College of Medicine), Vera Anastasoaie, Sharyn Lincoln, and Janette Z. Lawrence (Children's Hospital Boston), Fran Annese and Joy Graham (Greenwood Genetic Center), Marla Hashiguchi (Rady Children's Hospital San Diego); the clinical research staff (Jennifer Pilger, Rachel Richesson, and June T. Tran) at the Data Management Coordinating Center (DMCC) for their technical support; and the parents and guardians of the participants, along with the Angelman Syndrome Foundation, for their interest and devotion to this long-term study. We would like to thank Daniel Tarquinio for his help with computing growth centiles, and Alan K. Percy (University of Alabama at Birmingham) for his leadership and support. We are grateful to Donna Neuberg for her critical and helpful review of this manuscript. We would like to acknowledge the support of Mary Lou Oster-Granite (National Institute of Child Health and Human Development) for our work. WHT would like to thank Virginia E. Kimonis (now at University of California, Irvine) for her assistance in initiating the study at Children's Hospital Boston, and Alison Clapp, Medical Librarian at Children's Hospital Boston, for her assistance in obtaining the many references. The project described was supported by Grant Number NIH U54 RR019478 (awarded to A. L. B.), NIHU54RR019259 (awarded to Jeffrey P. Krischer) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), the NIH Office of Rare Diseases Research (ORDR), and the Angelman Syndrome Foundation Western Area Chapter. Funding through NCRR was through the cooperative agreement mechanism. The protocol was reviewed and approved by the NCRR Protocol Review Committee and subsequent study progress was monitored by their Data Safety Monitoring Board (DSMB). Data were imported into the DMCC. Data analysis and interpretation was conducted cooperatively with the DMCC statistician (H-SL). Manuscript preparation, review, and approval were solely that of the authors. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR, ORDR, NIH, University of South Florida, or the Angelman Syndrome Foundation. NR 50 TC 34 Z9 37 U1 2 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JAN PY 2011 VL 155A IS 1 BP 81 EP 90 DI 10.1002/ajmg.a.33775 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 702IZ UT WOS:000285889100010 PM 21204213 ER PT J AU Martinez, AF Muenke, M Arcos-Burgos, M AF Martinez, Ariel F. Muenke, Maximilian Arcos-Burgos, Mauricio TI From the Black Widow Spider to Human Behavior: Latrophilins, a Relatively Unknown Class of G Protein-Coupled Receptors, Are Implicated in Psychiatric Disorders SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Review DE ADHD; LPHN3; latrophilin; G protein-coupled receptor; alpha-latrotoxin ID DEFICIT HYPERACTIVITY DISORDER; CALCIUM-INDEPENDENT RECEPTOR; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; ANGIOGENESIS INHIBITOR-1 BAI1; ALPHA-LATROTOXIN RECEPTOR; ADOLESCENT SUBSTANCE USE; SWISS-MODEL REPOSITORY; GENE-EXPRESSION; STRUCTURAL BASIS; 17-ALPHA-ETHYNYL ESTRADIOL AB The findings of a recent study associate LPHN3, a member of the latrophilin family, with an increased risk of developing attention deficit/hyperactivity disorder (ADHD), the most common psychiatric disorder in childhood and adolescence. Latrophilins comprise a new family of G protein-coupled receptors of unknown native physiological function that mediate the neurotoxic effects of alpha-latrotoxin, a potent toxin found in black widow spider venom. This receptor-toxin interaction has helped to elucidate the mechanistic aspects of neurotransmitter and hormone release in vertebrates. Such unprecedented discovery points to a new direction in the assessment of ADHD and suggest that further study of this receptor family may provide novel insights into the etiology and treatment of ADHD and other related psychiatric conditions. (C) 2010 Wiley-Liss, Inc. C1 [Martinez, Ariel F.; Muenke, Maximilian; Arcos-Burgos, Mauricio] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Arcos-Burgos, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,MSC 3717,Bldg 35,Room 1B209, Bethesda, MD 20892 USA. EM mauricio.arcos-burgos@nih.gov FU Intramural NIH HHS [ZIA HG000175-11] NR 117 TC 15 Z9 15 U1 1 U2 13 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JAN PY 2011 VL 156B IS 1 BP 1 EP 10 DI 10.1002/ajmg.b.31137 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 702JL UT WOS:000285890300001 PM 21184579 ER PT J AU Domene, S Stanescu, H Wallis, D Tinloy, B Pineda, DE Kleta, R Arcos-Burgos, M Roessler, E Muenke, M AF Domene, Sabina Stanescu, Horia Wallis, Deeann Tinloy, Bradford Pineda, Daniel E. Kleta, Robert Arcos-Burgos, Mauricio Roessler, Erich Muenke, Maximilian TI Screening of Human LPHN3 for Variants With a Potential Impact on ADHD Susceptibility SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE ADHD; latrophilin; behavioral genetics; complex inheritance ID PROTEIN-COUPLED RECEPTOR; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; ALPHA-LATROTOXIN RECEPTOR; FAMILY; EXOCYTOSIS; INTERACTS; RESOURCE; SIGNAL AB Attention deficit hyperactivity disorder (ADHD) is the most common behavioral disorder in childhood, and often has effects detectable into adulthood. Advances in genetic linkage and association analysis have begun to elucidate some of the genetic factors underlying this complex disorder. Recently, we identified LPHN3, a novel ADHD susceptibility gene harbored in 4q, and showed that a LPHN3 common haplotype confers susceptibility to ADHD and predicts effectiveness of stimulant medication. Here we present the mutational analysis of the entire coding region of LPHN3 in a cohort of 139 ADHD subjects and 52 controls from across the USA. We identified 21 variants, of which 14 have been reported and 7 are novel. These include 5 missense, 8 synonymous, and 8 intronic changes. Interestingly, neither susceptibility nor protective haplotype alleles are associated with obviously significant coding region changes, or canonical splice site alterations, suggesting that non-coding variations determining the quantity and/or quality of LPHN3 isoforms are the likely contributors to this common behavioral disorder. (C) 2010 Wiley-Liss, Inc. C1 [Domene, Sabina; Stanescu, Horia; Tinloy, Bradford; Pineda, Daniel E.; Kleta, Robert; Arcos-Burgos, Mauricio; Roessler, Erich; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Wallis, Deeann] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,MSC3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mmuenke@nhgri.nih.gov FU Division of Intramural Research (DIR) NHGRI FX We would like to thank the families who participated in this study, and the Division of Intramural Research (DIR) NHGRI for their support. NR 24 TC 23 Z9 25 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JAN PY 2011 VL 156B IS 1 BP 11 EP 18 DI 10.1002/ajmg.b.31141 PG 8 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 702JL UT WOS:000285890300002 PM 21184580 ER PT J AU Konig, IR Schumacher, J Hoffmann, P Kleensang, A Ludwig, KU Grimm, T Neuhoff, N Preis, M Roeske, D Warnke, A Propping, P Remschmidt, H Nothen, MM Ziegler, A Muller-Myhsok, B Schulte-Korne, G AF Koenig, Inke R. Schumacher, Johannes Hoffmann, Per Kleensang, Andre Ludwig, Kerstin U. Grimm, Tiemo Neuhoff, Nina Preis, Maike Roeske, Darina Warnke, Andreas Propping, Peter Remschmidt, Helmut Noethen, Markus M. Ziegler, Andreas Mueller-Myhsok, Bertram Schulte-Koerne, Gerd TI Mapping for Dyslexia and Related Cognitive Trait Loci Provides Strong Evidence for Further Risk Genes on Chromosome 6p21 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE dyslexia; genome scan; linkage; DYX2; DCDC2; KIAA0319 ID PHONOLOGICAL PROCESSING ABILITIES; READING-DISABILITY; DEVELOPMENTAL DYSLEXIA; LINKAGE ANALYSIS; QUANTITATIVE MEASURES; SUSCEPTIBILITY LOCUS; SKILLED READERS; NEURAL SYSTEMS; SIB-PAIRS; CHILDREN AB In a genome-wide linkage scan, we aimed at mapping risk loci for dyslexia in the German population. Our sample comprised 1,030 individuals from 246 dyslexia families which were recruited through a single-proband sib pair study design and a detailed assessment of dyslexia and related cognitive traits. We found evidence for a major dyslexia locus on chromosome 6p21. The cognitive trait rapid naming (objects/colors) produced a genome-wide significant LOD score of 5.87 (P = 1.00 x 10(-7)) and the implicated 6p-risk region spans around 10Mb. Although our finding maps close to DYX2, where the dyslexia candidate genes DCDC2 and KIAA0319 have already been identified, our data point to the presence of an additional risk gene in this region and are highlighting the impact of 6p21 in dyslexia and related cognitive traits. (C) 2010 Wiley-Liss, Inc. C1 [Neuhoff, Nina; Schulte-Koerne, Gerd] Univ Munich, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-80336 Munich, Germany. [Koenig, Inke R.; Kleensang, Andre; Ziegler, Andreas] Med Univ Lubeck, Inst Med Biometry & Stat, D-23538 Lubeck, Germany. [Schumacher, Johannes] NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA. [Schumacher, Johannes; Hoffmann, Per; Propping, Peter; Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Hoffmann, Per; Ludwig, Kerstin U.; Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Genom, D-5300 Bonn, Germany. [Kleensang, Andre] Commiss European Communities, DG Joint Res Ctr, Inst Hlth & Consumer Protect, ECVAM, Ispra, Italy. [Grimm, Tiemo] Univ Wurzburg, Inst Human Genet, D-8700 Wurzburg, Germany. [Preis, Maike; Warnke, Andreas] Univ Wurzburg, Dept Child & Adolescent Psychiat & Psychotherapy, D-8700 Wurzburg, Germany. [Roeske, Darina; Mueller-Myhsok, Bertram] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Remschmidt, Helmut] Univ Marburg, Dept Child & Adolescent Psychiat & Psychotherapy, Marburg, Germany. RP Schulte-Korne, G (reprint author), Univ Munich, Dept Child & Adolescent Psychiat Psychosomat & Ps, Pettenkofer Str 8A, D-80336 Munich, Germany. EM gerd.schulte-koerne@med.uni-muenchen.de RI Muller-Myhsok, Bertram/A-3289-2013; Schumacher, Johannes/F-4970-2015; Konig, Inke/A-4544-2009; OI Schumacher, Johannes/0000-0001-9217-6457; Kleensang, Andre/0000-0002-4564-7399; Ziegler, Andreas/0000-0002-8386-5397; Nothen, Markus/0000-0002-8770-2464; Hoffmann, Per/0000-0002-6573-983X FU Deutsche Forschungsgemeinschaft (DFG); National Genomic Network of the BMBF; NIH/DFG; Alfried Krupp von Bohlen und Halbach-Stiftung FX Grant sponsor: Deutsche Forschungsgemeinschaft (DFG); Grant sponsor: National Genomic Network of the BMBF; Grant sponsor: NIH/DFG Research Career Transition Awards Program; Grant sponsor: Alfried Krupp von Bohlen und Halbach-Stiftung. NR 59 TC 12 Z9 12 U1 2 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JAN PY 2011 VL 156B IS 1 BP 36 EP 43 DI 10.1002/ajmg.b.31135 PG 8 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 702JL UT WOS:000285890300005 PM 21184582 ER PT J AU Zornizki, T Schattner, A Coslovsky, R Collins, MT AF Zornizki, Taiba Schattner, Ami Coslovsky, Rafael Collins, Michael T. TI Height Loss and Generalized Pain in a 35-year-old Man SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter C1 [Zornizki, Taiba; Schattner, Ami; Coslovsky, Rafael] Hebrew Univ Jerusalem, Hadassah Med Sch, Kaplan Med Ctr, Dept Med, IL-76100 Rehovot, Jerusalem, Israel. [Zornizki, Taiba; Schattner, Ami; Coslovsky, Rafael] Hebrew Univ Jerusalem, Hadassah Med Sch, Kaplan Med Ctr, Endocrinol Unit, IL-76100 Rehovot, Jerusalem, Israel. [Collins, Michael T.] NIH, Skeletal Clin Studies Unit, Bethesda, MD 20892 USA. RP Schattner, A (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Kaplan Med Ctr, Dept Med, POV1, IL-76100 Rehovot, Jerusalem, Israel. EM amiMD@clalit.org.il NR 4 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 0002-9343 J9 AM J MED JI Am. J. Med. PD JAN PY 2011 VL 124 IS 1 BP E3 EP E5 DI 10.1016/j.amjmed.2010.05.029 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 698ZR UT WOS:000285634200002 PM 20887965 ER PT J AU Astor, BC Kottgen, A Hwang, SJ Bhavsar, NA Fox, CS Coresh, J AF Astor, Brad C. Koettgen, Anna Hwang, Shih-Jen Bhavsar, Nrupen A. Fox, Caroline S. Coresh, Josef TI Trefoil Factor 3 Predicts Incident Chronic Kidney Disease: A Case-Control Study Nested within the Atherosclerosis Risk in Communities (ARIC) Study SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Kidney disease; Tubulointerstitual disease; Biomarkers ID GLOMERULAR-FILTRATION-RATE; EPITHELIAL-CELLS; GASTRIC-MUCOSA; PROGRESSION; POPULATION; EXPRESSION; PEPTIDES AB Background: Early detection of individuals at high risk for chronic kidney disease (CKD) may aid prevention. Urinary levels of trefoil factor 3 (TFF3) are associated with acute kidney injury in animal models, but the association of TFF3 levels with incident CKD in humans is unknown. Methods: We conducted a case-control study nested within the Atherosclerosis Risk in Communities (ARIC) Study and the ARIC Carotid MRI Study to determine whether urinary TFF3 levels predict incident CKD over 8.6 years of follow-up. A total of 143 participants with incident CKD (eGFR decreasing by >= 25% to <60 ml/min/1.73 m(2)) were matched on age, sex and race to 143 non-cases. Results: Higher TFF3 levels at baseline were strongly associated with Black race, diabetes (both p = 0.002), and antihypertensive medication use (p = 0.02). Compared to participants with TFF3 levels in the lowest quartile, the odds ratio (OR) of incident CKD was 1.84 (95% confidence interval (CI): 0.80, 4.22) for individuals with TFF3 levels in the second quartile, 2.43 (95% CI: 1.06, 5.53) for the third quartile, and 2.77 (95% CI: 1.22, 6.28) for the fourth quartile (p trend = 0.02). Adjustment for covariates, including urinary albumin: creatinine ratio, did not markedly change the associations. Twofold higher TFF3 levels were strongly associated with incident CKD after adjustment for CKD risk factors (adjusted OR = 1.35; 95% CI: 1.11, 1.64). Conclusions: Higher urinary TFF3 levels may indicate ongoing repair of damage in the kidney. Additional studies are needed to confirm whether TFF3 can be useful as a marker of increased risk for CKD. Copyright (C) 2011 S. Karger AG, Basel C1 [Astor, Brad C.] Johns Hopkins Univ, Dept Epidemiol, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21287 USA. [Astor, Brad C.; Koettgen, Anna; Bhavsar, Nrupen A.; Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Astor, Brad C.; Coresh, Josef] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. [Koettgen, Anna] Univ Hosp Freiburg, Div Renal, Freiburg, Germany. [Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. [Hwang, Shih-Jen; Fox, Caroline S.] Ctr Populat Studies, Bethesda, MD USA. [Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Hwang, Shih-Jen; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. RP Astor, BC (reprint author), Johns Hopkins Univ, Dept Epidemiol, Welch Ctr Prevent Epidemiol & Clin Res, 2024 E Monument St,Suite 2-600, Baltimore, MD 21287 USA. EM bastor@jhsph.edu RI Kottgen, Anna/D-2920-2012 FU National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022]; National Institute of Diabetes and Digestive and Kidney Diseases [1 R01 DK076770-01]; [U01HL075572-01] FX The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022 with the ARIC carotid MRI examination funded by U01HL075572-01. The ARIC sample assays were supported by the National Institute of Diabetes and Digestive and Kidney Diseases (1 R01 DK076770-01). The authors thank the staff and participants of the ARIC Study for their important contributions. NR 33 TC 15 Z9 18 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2011 VL 34 IS 4 BP 291 EP 297 DI 10.1159/000330699 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 815RO UT WOS:000294545600001 PM 21829008 ER PT J AU Hurst, FP Altieri, M Nee, R Agodoa, LY Abbott, KC Jindal, RM AF Hurst, Frank P. Altieri, Maria Nee, Robert Agodoa, Lawrence Y. Abbott, Kevin C. Jindal, Rahul M. TI Poor Outcomes in Elderly Kidney Transplant Recipients Receiving Alemtuzumab Induction SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Alemtuzumab; Kidney transplantation; Elderly recipients; Induction agents, complications; Kidney transplants, outcomes ID RENAL-ALLOGRAFT SURVIVAL; RANDOMIZED-TRIAL; ANTITHYMOCYTE GLOBULIN; PANCREAS TRANSPLANTATION; BASILIXIMAB INDUCTION; THERAPY; CAMPATH-1H; IMMUNOSUPPRESSION; THYMOGLOBULIN; DACLIZUMAB AB Introduction: Alemtuzumab and rabbit antithymocyte globulin (rATG) are being used with increasing frequency as induction agents in kidney transplantation. Using the US Renal Data Base System, we analyzed the safety profile of these agents in the elderly. Methods: In a cohort of patients transplanted from January 2000 to July 2009 and followed through 2009, we assessed the effect of induction on allograft loss and death among elderly recipients. Recipients were censored at dates of allograft loss, death or the end of study. Independent associations between induction agents and allograft loss or death were examined using multivariate analysis with forward stepwise Cox regression. Results: Among 130,402 patients with first transplants, 14,907 were age 65 years or older. 4,466 (30%), 3,049 (20.5%), 1,501 (10.1%), and 999 (6.7%) were induced with thymoglobulin, basiliximab, daclizumab, and alemtuzumab, respectively. After adjusting for baseline differences, induction with alemtuzumab was associated with an increased risk of graft loss and death, with an adjusted hazard ratio (AHR) of 1.26 (95% CI 1.08-1.48). Risk was also present at other age cutoffs [age >60 (AHR 1.16; 95% CI 1.03-1.31; p = 0.014), age >70 (AHR 1.43; 95% CI 1.13-1.81; p = 0.003) and age >75 (AHR 1.68; 95% CI 1.07-2.63; p = 0.024)]. Conclusions: In the elderly, alemtuzumab is associated with an escalating risk of death and graft loss in recipients of kidney transplantations. Copyright (C) 2011 S. Karger AG, Basel C1 [Hurst, Frank P.; Nee, Robert; Abbott, Kevin C.] Walter Reed Army Med Ctr, Dept Nephrol, Washington, DC 20307 USA. [Altieri, Maria] Stony Brook Univ Hosp, Dept Surg, Long Isl City, NY USA. [Agodoa, Lawrence Y.] NIDDK, NIH, Bethesda, MD USA. [Jindal, Rahul M.] Walter Reed Army Med Ctr, Dept Organ Transplant, Washington, DC 20307 USA. [Jindal, Rahul M.] Walter Reed Army Med Ctr, Dept Surg, Washington, DC 20307 USA. George Washington Univ, Washington, DC USA. RP Jindal, RM (reprint author), Walter Reed Army Med Ctr, Dept Transplantat, 6900 Georgia Ave, Washington, DC 20307 USA. EM jindalr@msn.com OI Abbott, Kevin/0000-0003-2111-7112 NR 30 TC 4 Z9 5 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2011 VL 34 IS 6 BP 534 EP 541 DI 10.1159/000334092 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 867XA UT WOS:000298486900007 PM 22104284 ER PT J AU Weil, EJ Lemley, KV Yee, B Lovato, T Richardson, M Myers, BD Nelson, RG AF Weil, E. Jennifer Lemley, Kevin V. Yee, Berne Lovato, Tracy Richardson, Meghan Myers, Bryan D. Nelson, Robert G. TI Podocyte Detachment in Type 2 Diabetic Nephropathy SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article; Proceedings Paper CT Symposium on the Inaugural Stereology and Its Application in Kidney Disease CY MAY 19-21, 2010 CL Marina Del Rey, CA DE Diabetic kidney disease; Electron microscopy; Histology; Morphometry; Podocyte ID GLOMERULOSCLEROSIS; PROTEINURIA; EXCRETION; MELLITUS; DISEASE; INJURY AB Background: Glomerular podocyte number declines and urinary excretion of podocytes increases as kidney disease progresses in persons with type 2 diabetes mellitus (T2DM). Methods: Using high-power electron microscopy, we quantified podocyte detachment in T2DM. Results: We evaluated 106 glomeruli (range 1-6 per subject) from 40 Pima Indian subjects with T2DM enrolled in a clinical trial. On high-power electron micrographs, 35% of the subjects had no evidence of podocyte detachment. Among the remaining subjects, the median percentage of basement membrane with podocyte detachment was 0.62% (interquartile range = 0.32-1.52%). Conclusion: Podocyte detachment from the glomerular basement membrane has been described and measured in type 1 diabetes mellitus using a different method. We now document podocyte detachment microscopically and quantify it morphometrically in humans with T2DM. The findings offer quantitative histologic support to a potential mechanism for the functional impairment, and possibly the sclerosis of glomeruli, in diabetic glomerular injury. Copyright (C) 2011 S. Karger AG, Basel C1 [Weil, E. Jennifer; Lovato, Tracy; Richardson, Meghan; Nelson, Robert G.] NIDDK, NIH, Phoenix, AZ 85014 USA. [Lemley, Kevin V.] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Divi Nephrol,Dept Pediat, Los Angeles, CA 90033 USA. [Yee, Berne] SW Kidney Inst, Phoenix, AZ USA. [Myers, Bryan D.] Stanford Univ, Sch Med, Div Nephrol, Stanford, CA 94305 USA. RP Nelson, RG (reprint author), NIDDK, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM rnelson@nih.gov RI Nelson, Robert/B-1470-2012 FU Intramural NIH HHS NR 12 TC 10 Z9 15 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2011 VL 33 SU 1 BP 21 EP 24 DI 10.1159/000327047 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 776DK UT WOS:000291514500004 PM 21659731 ER PT J AU Dalal, M Semba, RD Sun, K Crasto, C Varadhan, R Bandinelli, S Fink, JC Guralnik, JM Ferrucci, L AF Dalal, Mansi Semba, Richard D. Sun, Kai Crasto, Candace Varadhan, Ravi Bandinelli, Stefania Fink, Jeffrey C. Guralnik, Jack M. Ferrucci, Luigi TI Endogenous Secretory Receptor for Advanced Glycation End Products and Chronic Kidney Disease in the Elderly Population SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Advanced glycation end products; Aging; Chronic kidney disease; Endogenous secretory receptor for advanced glycation end products ID GLOMERULAR-FILTRATION-RATE; DECREASED RENAL-FUNCTION; SOLUBLE RECEPTOR; HEMODIALYSIS-PATIENTS; SERUM CREATININE; RAGE; ATHEROSCLEROSIS; ENDPRODUCTS; INFLAMMATION; ASSOCIATION AB Background/Aims: The relationship of circulating endogenous secretory receptor for advanced glycation end products (esRAGE) and chronic kidney disease (CKD) has not been well characterized. The aim of the study was to determine whether plasma esRAGE is associated with CKD and is predictive of developing CKD in older adults. Methods: The relationship between plasma esRAGE and CKD (more than stage 3 of the National Kidney Foundation classification; estimated glomerular filtration rate <60 ml/min/1.73 m(2)) and CKD over 6 years of follow-up was examined in a cross-sectional and prospective study design in 1,016 men and women, 6 65 years, in the InCHIANTI study, a population-based cohort study of aging in Tuscany, Italy. Results: At enrollment, 158 (15.5%) had CKD. Mean (SD) plasma esRAGE was 0.45 (0.24) ng/ml. Plasma esRAGE (ng/ml) was associated with CKD (odds ratio per 1 SD = 1.30; 95% CI 1.1-1.6; p < 0.005) in a multivariable logistic regression model, adjusting for potential confounders. Plasma esRAGE was an independent predictor of incident CKD over 6 years of follow-up (hazard ratio per 1 SD = 1.37; 95% CI 1.1-1.7; p < 0.008) in a multivariable Cox proportional hazards model, adjusting for potential confounders. Conclusions: Elevated plasma esRAGE is independently associated with CKD and is an independent predictor of incident CKD in older community-dwelling adults. Copyright (C) 2011 S. Karger AG, Basel C1 [Dalal, Mansi; Semba, Richard D.; Sun, Kai; Crasto, Candace] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. [Varadhan, Ravi] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Bandinelli, Stefania] Azienda Sanit Firenze, Florence, Italy. [Fink, Jeffrey C.] Univ Maryland, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21201 USA. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Bethesda, MD 20892 USA. RP Semba, RD (reprint author), M015,Smith Bldg,400 N Broadway, Baltimore, MD 21287 USA. EM rdsemba@jhmi.edu OI Fink, Jeffrey/0000-0002-5622-5052 FU National Institute on Aging [R01 AG027012, R01 AG029148, R01 HL094507, 9164, 263, 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]; Italian Ministry of Health [ICS110.1/RF97.71]; National Institute on Aging, National Institutes of Health FX This work was supported by National Institute on Aging Grants R01 AG027012, R01 AG029148, R01 HL094507, the Italian Ministry of Health (ICS110.1/RF97.71), NIA contracts 263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, and N01-AG-5-0002, and the Intramural Research Program, National Institute on Aging, National Institutes of Health. NR 25 TC 6 Z9 6 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2011 VL 33 IS 4 BP 313 EP 318 DI 10.1159/000324846 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 760GR UT WOS:000290313300004 PM 21389696 ER PT J AU Igo, RP Iyengar, SK Nicholas, SB Goddard, KAB Langefeld, CD Hanson, RL Duggirala, R Divers, J Abboud, H Adler, SG Arar, NH Horvath, A Elston, RC Bowden, DW Guo, XQ Ipp, E Kao, WHL Kimmel, PL Knowler, WC Meoni, LA Molineros, J Nelson, RG Pahl, MV Parekh, RS Rasooly, RS Schelling, JR Shah, VO Smith, MW Winkler, CA Zager, PG Sedor, JR Freedman, BI AF Igo, Robert P., Jr. Iyengar, Sudha K. Nicholas, Susanne B. Goddard, Katrina A. B. Langefeld, Carl D. Hanson, Robert L. Duggirala, Ravindranath Divers, Jasmin Abboud, Hanna Adler, Sharon G. Arar, Nedal H. Horvath, Amanda Elston, Robert C. Bowden, Donald W. Guo, Xiuqing Ipp, Eli Kao, W. H. Linda Kimmel, Paul L. Knowler, William C. Meoni, Lucy A. Molineros, Julio Nelson, Robert G. Pahl, Madeline V. Parekh, Rulan S. Rasooly, Rebekah S. Schelling, Jeffrey R. Shah, Vallabh O. Smith, Michael W. Winkler, Cheryl A. Zager, Philip G. Sedor, John R. Freedman, Barry I. CA Family Invest Nephropathy Diabet TI Genomewide Linkage Scan for Diabetic Renal Failure and Albuminuria: The FIND Study SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Albuminuria; Diabetes mellitus; Renal failure; End-stage renal disease; Linkage; Allelic association ID PREPROGHRELIN LEU72MET POLYMORPHISM; GENES-CONTROLLING VARIATION; AFRICAN-AMERICANS; NEPHROPATHY; ASSOCIATION; DISEASE; MELLITUS; FAMILY; MYH9; SUSCEPTIBILITY AB Background: Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with type 1 and type 2 diabetes. The multicenter FIND consortium aims to identify genes for DN and its associated quantitative traits, e.g. the urine albumin:creatinine ratio (ACR). Herein, the results of whole-genome linkage analysis and a sparse association scan for ACR and a dichotomous DN phenotype are reported in diabetic individuals. Methods: A genomewide scan comprising more than 5,500 autosomal single nucleotide polymorphism markers (average spacing of 0.6 cM) was performed on 1,235 nuclear and extended pedigrees (3,972 diabetic participants) ascertained for DN from African-American (AA), American-Indian (AI), European-American (EA) and Mexican-American (MA) populations. Results: Strong evidence for linkage to DN was detected on chromosome 6p (p = 8.0 x 10(-5) LOD = 3.09) in EA families as well as suggestive evidence for linkage to chromosome 7p in Al families. Regions on chromosomes 3p in AA, 7q in EA, 16q in AA and 22q in MA displayed suggestive evidence of linkage for urine ACR. The linkage peak on chromosome 22q overlaps the MYH9/APOL1 gene region, previously implicated in AA diabetic and nondiabetic nephropathies. Conclusion:These results strengthen the evidence for previously identified genomic regions and implicate several novel loci potentially involved in the pathogenesis of DN. Copyright (C) 2011 S. Karger AG, Basel C1 [Iyengar, Sudha K.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Genet Anal & Data Coordinating Ctr, Cleveland, OH 44106 USA. [Nicholas, Susanne B.] Univ Calif Los Angeles, Los Angeles, CA USA. [Goddard, Katrina A. B.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. [Langefeld, Carl D.; Divers, Jasmin; Bowden, Donald W.; Freedman, Barry I.] Wake Forest Sch Med, Winston Salem, NC USA. [Hanson, Robert L.; Knowler, William C.; Nelson, Robert G.] NIDDKD, Phoenix, AZ USA. [Duggirala, Ravindranath] Texas Biomed Res Inst, San Antonio, TX USA. [Abboud, Hanna; Arar, Nedal H.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Adler, Sharon G.; Ipp, Eli] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Guo, Xiuqing] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Kao, W. H. Linda; Meoni, Lucy A.; Parekh, Rulan S.] Johns Hopkins Univ, Baltimore, MD USA. [Kimmel, Paul L.; Rasooly, Rebekah S.] NIDDK, NIH, Bethesda, MD USA. [Molineros, Julio] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Pahl, Madeline V.] Univ Calif Irvine, Irvine, CA USA. [Shah, Vallabh O.; Zager, Philip G.] Univ New Mexico, Albuquerque, NM 87131 USA. [Winkler, Cheryl A.] NCI, Basic Res Lab, Ctr Canc Res, SAIC Frederick, Frederick, MD 21701 USA. [Smith, Michael W.] NCI, Genet & Genom Grp, Adv Technol Program, SAIC Frederick, Frederick, MD 21701 USA. RP Iyengar, SK (reprint author), Case Western Reserve Univ, Dept Epidemiol & Biostat, Genet Anal & Data Coordinating Ctr, Wolstein Res Bldg,Rm 1300,10900 Euclid Ave, Cleveland, OH 44106 USA. EM ski@case.edu RI Nelson, Robert/B-1470-2012; Smith, Michael/B-5341-2012; Hanson, Robert/O-3238-2015; OI Hanson, Robert/0000-0002-4252-7068; Rasooly, Rebekah/0000-0002-6357-5528 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [U01DK57292, U01DK57329, U01DK057300, U01DK057298, U0IDK057249, U0IDK57295, U01DK057303, U0IDK070657, U01DK57304, DK57292-05]; National Cancer Institute, National Institutes of Health (NIH) [N01-CO-12400]; Center for Cancer Research; National Center for Research Resources for the General Clinical Research Center; Case Western Reserve University [M01-RR-000080]; Wake Forest University [M01-RR-07122]; Harbor-University of California; Los Angeles Medical Center [M01-RR-00425]; College of Medicine, University of California, Irvine [M01-RR-00827-29]; University of New Mexico [HSC M01-RR-00997]; Frederic C. Bartter [M01-RR-01346]; Johns Hopkins University [N01-HG-65403]; National Center for Research Resources [RR03655] FX We thank all FIND participants. This study was supported by grants U01DK57292, U01DK57329,U01DK057300,U01DK057298, U0IDK057249, U0IDK57295, U0IDK070657, U01DK057303, U0IDK070657, U01DK57304 and DK57292-05 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and, in part, by the Intramural Research Program of the NIDDK. 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 N01-CO-12400 and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This work was also supported by the National Center for Research Resources for the General Clinical Research Center grants: Case Western Reserve University, M01-RR-000080; Wake Forest University, M01-RR-07122; Harbor-University of California, Los Angeles Medical Center, M01-RR-00425; College of Medicine, University of California, Irvine, M01-RR-00827-29; University of New Mexico, HSC M01-RR-00997; and Frederic C. Bartter, M01-RR-01346. Genotyping was performed by the Center for Inherited Disease Research, which is fully funded through a federal contract from the NIH to Johns Hopkins University (N01-HG-65403). The results of this analysis were obtained using the S.A.G.E. package of genetic epidemiology software, which is supported by a U.S. Public Health Service Resource Grant (RR03655) from the National Center for Research Resources. NR 29 TC 23 Z9 27 U1 2 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2011 VL 33 IS 5 BP 381 EP 389 DI 10.1159/000326763 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 767FQ UT WOS:000290841100001 PM 21454968 ER PT J AU Morrison, TE Oko, L Montgomery, SA Whitmore, AC Lotstein, AR Gunn, BM Elmore, SA Heise, MT AF Morrison, Thomas E. Oko, Lauren Montgomery, Stephanie A. Whitmore, Alan C. Lotstein, Alina R. Gunn, Bronwyn M. Elmore, Susan A. Heise, Mark T. TI A Mouse Model of Chikungunya Virus-Induced Musculoskeletal Inflammatory Disease Evidence of Arthritis, Tenosynovitis, Myositis, and Persistence SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID INDIAN-OCEAN ISLANDS; REUNION ISLAND; INFECTION; EPIDEMIC; FEVER; RHEUMATISM AB Chikungunya virus (CHIKV), an emerging mosquitoborne Alphavirus, causes debilitating rheumatic disease in humans that can last for weeks to months. Starting in 2004, a CHIKV outbreak in the Indian Ocean region affected millions of people, and infected travelers introduced CHIKV to new regions. The pathogenesis of CHIKV is poorly understood, and no approved vaccines or specific therapies exist. A major challenge to the study of CHIKV disease is the lack of a small animal model that recapitulates the major outcomes of human infection. In this study, the pathogenesis of CHIKV in C57BL/6J mice was investigated using biological and molecular clones of CHIKV isolated from human serum (CHIKV SL15649). After 14-day-old mice were inoculated with CHIKV SL15649 in the footpad, they displayed reduced weight gain and swelling of the inoculated limb. Histologic analysis of hind limb sections revealed severe necrotizing myositis, mixed inflammatory cell arthritis, chronic active tenosynovitis, and multifocal vasculitis. Interestingly, these disease signs and viral RNA persisted in musculoskeletal tissues for at least 3 weeks after inoculation. This work demonstrates the development of a mouse model of CHIKV infection with clinical manifestations and histopathologic findings that are consistent with the disease signs of CHIKV-infected humans, providing a useful tool for studying viral and host factors that drive CHIKV pathogenesis and for evaluating potential therapeutics against this emerging viral disease. (Am J Pathol 2011, 178:32-40; DOI: 10.1016/j.ajpath.2010.11.018) C1 [Morrison, Thomas E.; Oko, Lauren] Univ Colorado, Dept Microbiol, Sch Med, Aurora, CO 80045 USA. [Montgomery, Stephanie A.] N Carolina State Univ, Coll Vet Med, Raleigh, NC USA. [Elmore, Susan A.] NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, Raleigh, NC USA. [Whitmore, Alan C.; Lotstein, Alina R.; Gunn, Bronwyn M.; Heise, Mark T.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Whitmore, Alan C.; Lotstein, Alina R.; Gunn, Bronwyn M.; Heise, Mark T.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. [Whitmore, Alan C.; Lotstein, Alina R.; Gunn, Bronwyn M.; Heise, Mark T.] Univ N Carolina, Carolina Vaccine Inst, Chapel Hill, NC USA. RP Morrison, TE (reprint author), Univ Colorado, Dept Microbiol, Sch Med, 12800 E 19th Ave,Mail Stop 833, Aurora, CO 80045 USA. EM thomas.morrison@ucdenver.edu FU National Institutes of Health (NIH) [K22 AI079163, U54 AI 057157-07, 2 R01 AR 047190]; NIH, National Institute of Environmental Health Sciences FX Supported by National Institutes of Health (NIH) research grant K22 AI079163 (T.E.M.), NIH research grants U54 AI 057157-07 (SERCEB Project 2.1) and 2 R01 AR 047190 (M.T.H.), and in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 38 TC 83 Z9 83 U1 2 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2011 VL 178 IS 1 BP 32 EP 40 DI 10.1016/j.ajpath.2010.11.018 PG 9 WC Pathology SC Pathology GA 710EM UT WOS:000286493700006 PM 21224040 ER PT J AU Estrada-Gutierrez, G Cappello, RE Mishra, N Romero, R Strauss, JF Walsh, SW AF Estrada-Gutierrez, Guadalupe Cappello, Renato E. Mishra, Nikita Romero, Roberto Strauss, Jerome F., III Walsh, Scott W. TI Increased Expression of Matrix Metalloproteinase-1 in Systemic Vessels of Preeclamptic Women A Critical Mediator of Vascular Dysfunction SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SMOOTH-MUSCLE-CELLS; PROTEASE-ACTIVATED RECEPTOR-1; EXTRACELLULAR-MATRIX; TRANSENDOTHELIAL MIGRATION; CLINICAL-MANIFESTATIONS; NEUTROPHIL ACTIVATION; MOLECULAR-MECHANISMS; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; TNF-ALPHA AB This study was conducted to determine the following: (1) whether matrix metalloproteinase-1 (MMP-1) Is increased in systemic vessels of preeclamptic women, (2) whether this increase might be mediated by neutrophils, and (3) whether MMP-1 could be responsible for vascular dysfunction. Omental arteries and plasma were collected from healthy pregnant and preeclamptic women. Omental arteries were evaluated for gene and protein expression of MMP-1, collagen type la, tissue inhibitor of metalloproteinase-1, and vascular reactivity to MMP-1. Gene and protein expression levels were also evaluated in human vascular smooth muscle cells (VSMCs) co-cultured with activated neutrophils, reactive oxygen species, or tumor necrosis factor a. Vessel expression of MMP-1 and circulating MMP-1 levels were increased in preeclamptic women, whereas vascular expression of collagen or tissue inhibitor of metalloproteinase-1 were down-regulated or unchanged. In cultured VSMCs, the unbalance in collagen-regulating genes of preeclamptic vessels was reproduced by treatment with neutrophils, tumor necrosis factor a, or reactive oxygen species. Chemotaxis studies with cultured cells revealed that MMP-1 promoted recruitment of neutrophils via vascular smooth muscle release of interleukin-8. Furthermore, MMP-1 induced vasoconstriction via protease-activated receptor-1, whose expression was significantly increased in omental arteries of preeclamptic women and in VSMCs co-cultured with neutrophils. Collectively, these findings disclose a novel role for MMP-1 as a mediator of vasoconstriction and vascular dysfunction in preeclampsia. (Am J Pathol 2011, 178:451-460; DOI: 10.1016/j.ajpath.2010.11.003) C1 [Estrada-Gutierrez, Guadalupe; Cappello, Renato E.; Mishra, Nikita; Strauss, Jerome F., III; Walsh, Scott W.] Virginia Commonwealth Univ, Dept Obstet & Gynecol, Med Ctr, Richmond, VA 23298 USA. [Mishra, Nikita; Walsh, Scott W.] Virginia Commonwealth Univ, Dept Physiol & Biophys, Med Ctr, Richmond, VA 23298 USA. [Estrada-Gutierrez, Guadalupe] Inst Nacl Perinatol, Dept Perinatal Infectol & Immunol, Mexico City, DF, Mexico. [Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Walsh, SW (reprint author), Virginia Commonwealth Univ, Dept Obstet & Gynecol, Med Ctr, POB 980034, Richmond, VA 23298 USA. EM swwalsh@vcu.edu FU Fogarty [1D43 TW007692]; National Center on Minority Health and Health Disparities [P60 MD002256]; Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services [N01 HD-2-3342]; National Heart, Lung, and Blood Institute [R01 HL069851] FX Supported in part by Fogarty grant 1D43 TW007692 (G.E.-G.); the National Center on Minority Health and Health Disparities grant P60 MD002256 (J.F.S.); the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services grant N01 HD-2-3342 (J.F.S.); and the National Heart, Lung, and Blood Institute grant R01 HL069851 (S.W.W.). NR 59 TC 10 Z9 11 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2011 VL 178 IS 1 BP 451 EP 460 DI 10.1016/j.ajpath.2010.11.003 PG 10 WC Pathology SC Pathology GA 710EM UT WOS:000286493700048 PM 21224082 ER PT J AU Ikeda, Y Taveira-DaSilva, AM Pacheco-Rodriguez, G Steagall, WK El-Chemaly, S Gochuico, BR May, RM Hathaway, OM Li, SW Wang, JA Darling, TN Stylianou, M Moss, J AF Ikeda, Yoshihiko Taveira-DaSilva, Angelo M. Pacheco-Rodriguez, Gustavo Steagall, Wendy K. El-Chemaly, Souheil Gochuico, Bernadette R. May, Rose M. Hathaway, Olanda M. Li, Shaowei Wang, Ji-an Darling, Thomas N. Stylianou, Mario Moss, Joel TI Erythropoietin-driven proliferation of cells with mutations in the tumor suppressor gene TSC2 SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE smooth muscle cell; tuberous sclerosis complex; cystic lung disease; hypoxia ID OBSTRUCTIVE PULMONARY-DISEASE; KINASE-DEPENDENT PATHWAY; FIBROBLAST-GROWTH-FACTOR; RECEPTOR EXPRESSION; ERYTHROID PROGENITORS; TRANSCRIPTION FACTORS; TUBEROUS-SCLEROSIS; LYMPHANGIOLEIOMYOMATOSIS; HYPOXIA; CANCER AB Ikeda Y, Taveira-DaSilva AM, Pacheco-Rodriguez G, Steagall WK, El-Chemaly S, Gochuico BR, May RM, Hathaway OM, Li S, Wang J, Darling TN, Stylianou M, Moss J. Erythropoietin-driven proliferation of cells with mutations in the tumor suppressor gene TSC2. Am J Physiol Lung Cell Mol Physiol 300: L64-L72, 2011. First published October 29, 2010; doi:10.1152/ajplung.00095.2010.-Lymphangioleiomyomatosis (LAM) is characterized by cystic lung destruction, resulting from proliferation of smooth-muscle-like cells, which have mutations in the tumor suppressor genes TSC1 or TSC2. Among 277 LAM patients, severe disease was associated with hypoxia and elevated red blood cell indexes that accompanied reduced pulmonary function. Because high red cell indexes could result from hypoxemia-induced erythropoietin (EPO) production, and EPO is a smooth muscle cell mitogen, we investigated effects of EPO in human cells with genetic loss of tuberin function, and we found that EPO increased proliferation of human TSC2-/-, but not of TSC2+/-, cells. A discrete population of cells grown from explanted lungs was characterized by the presence of EPO receptor and loss of heterozygosity for TSC2, consistent with EPO involvement. In LAM cells from lung nodules, EPO was localized to the extracellular matrix, supporting evidence for activation of an EPO-driven signaling pathway. Although the high red cell mass of LAM patients could be related to advanced disease, we propose that EPO, synthesized in response to episodic hypoxia, may increase disease progression by enhancing the proliferation of LAM cells. C1 [Ikeda, Yoshihiko; Taveira-DaSilva, Angelo M.; Pacheco-Rodriguez, Gustavo; Steagall, Wendy K.; El-Chemaly, Souheil; Gochuico, Bernadette R.; May, Rose M.; Hathaway, Olanda M.; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. [Stylianou, Mario] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. [Li, Shaowei; Wang, Ji-an; Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. RP Moss, J (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10,Rm 6D05,MSC 1590, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov OI Darling, Thomas/0000-0002-5161-1974 FU National Institutes of Health, National Heart, Lung, and Blood Institute; Doris Duke Charitable Foundation; Oak Ridge Institute for Science and Education; [RO1 CA100907] FX The research was supported by the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute, and by RO1 CA100907, and a Clinical Scientist Development Award from the Doris Duke Charitable Foundation (to T. N. Darling). Y. Ikeda was contracted through a Senior Fellowship from the Oak Ridge Institute for Science and Education. NR 51 TC 8 Z9 8 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JAN PY 2011 VL 300 IS 1 BP L64 EP L72 DI 10.1152/ajplung.00095.2010 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 695YC UT WOS:000285407800008 PM 21036916 ER PT J AU Peters, T Potter, R Li, XR He, Z Hoskins, G Flessner, MF AF Peters, Toni Potter, Rebecca Li, Xiarong He, Zhi Hoskins, Glenn Flessner, Michael F. TI Mouse model of foreign body reaction that alters the submesothelium and transperitoneal transport SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE peritoneum; mesothelium; solute transport; water transport; peritoneal dialysis catheter ID ACUTE INFLAMMATORY RESPONSES; PERITONEAL-DIALYSIS; IN-VIVO; MESENCHYMAL TRANSITION; BIOMATERIALS; INFECTION; PERMEABILITY; EXPOSURE; CATHETER; SOLUTE AB Peters T, Potter R, Li X, He Z, Hoskins G, Flessner MF. Mouse model of foreign body reaction that alters the submesothelium and transperitoneal transport. Am J Physiol Renal Physiol 300: F283-F289, 2011. First published October 13, 2010; doi: 10.1152/ajprenal.00328.2010.-To address the hypothesis that sterile intraperitoneal (ip) catheters alone promote a progressive foreign body reaction (FBR), silicone catheters were surgically implanted in C57BL mice. Controls (CON) underwent sham operations. After 1-5 wk (E1-E5 for catheter-bearing mice), catheters were recovered, and the adherent cell layer (ACL) was separated and cultured to demonstrate sterility. Transperitoneal transport experiments were performed to determine the mass transfer coefficients of mannitol (MTCM) and albumin (MTCA) and the osmotic filtration flux (J(osm)). After euthanasia, tissue samples were analyzed for submesothelial thickness, angiogenesis, and cytokine immunohistochemistry (IHC). Progressive increases with time were observed in submesothelial thickness (mu m: CON, 18.8 +/- 12.3; E1, 46.1 +/- 20.0; E2, 72.0 +/- 17.9; E4, 97.3 +/- 20.0; E5, 131.7 +/- 10.3; P < 0.003), angiogenesis (no. of vessels/mm of peritoneum: CON, 10.7 +/- 9.4; E1, 15.4 +/- 15.6; E2, 27.0 +/- 14.0; E4, 39.8 +/- 15.7; E5, 90.1 +/- 8.1; P < 0.0003), MTCA (6.5 +/- 1.5 X 10(-5) cm/min, mean CON; 18.0 +/- 1.1 < 10(-5) cm/min, mean E1-E5, P < 0.0001), J(osm) (0.0013 +/- 0.0001 cm/min, mean CON; 0.0017 +/- 0.0001 cm/min, mean E1-E5, P < 0.01). No significant differences were found for MTCM. IHC demonstrated strong staining for all treated animals and correlated with the ACL. This mouse model demonstrates that ip silicone catheters result in progressive FBR, altering the submesothelial anatomy and transperitoneal transport, and will form the basis for mechanistic studies in genetically-altered animals. C1 [Peters, Toni; Potter, Rebecca; Li, Xiarong; He, Zhi; Hoskins, Glenn; Flessner, Michael F.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. RP Flessner, MF (reprint author), NIDDK, NIH, 2 DEM,6707 Democracy Blvd, Bethesda, MD 20892 USA. EM flessnermf@niddk.nih.gov FU American Heart Association FX This work was supported by an American Heart Association Grant-in-Aid to M. F. Flessner. NR 30 TC 7 Z9 9 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2011 VL 300 IS 1 BP F283 EP F289 DI 10.1152/ajprenal.00328.2010 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 703FP UT WOS:000285964000032 PM 20943771 ER PT J AU Boyce, CA Olster, DH AF Boyce, Cheryl Anne Olster, Deborah H. TI Strengthening the Public Research Agenda for Social Determinants of Health SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material C1 [Boyce, Cheryl Anne] NIDA, NIH, USDHHS, Bethesda, MD 20892 USA. [Olster, Deborah H.] NIH, Off Behav & Social Sci Res, USDHHS, Bethesda, MD 20892 USA. RP Boyce, CA (reprint author), NIDA, NIH, DHHS, 6001 Execut Blvd,Room 3161, Bethesda, MD 20892 USA. EM cboyce@mail.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 21 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JAN PY 2011 VL 40 IS 1 SU 1 BP S86 EP S88 DI 10.1016/j.amepre.2010.10.006 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 692XM UT WOS:000285189200012 PM 21146786 ER PT J AU Brown, TM Fee, E AF Brown, Theodore M. Fee, Elizabeth TI C. Arden Miller: Advocate for Children's Health SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Brown, Theodore M.] Univ Rochester, Dept Hist, Rochester, NY 14627 USA. [Brown, Theodore M.] Univ Rochester, Dept Community & Prevent Med, Rochester, NY 14627 USA. [Fee, Elizabeth] NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. RP Brown, TM (reprint author), Univ Rochester, Dept Hist, 601 Elmwood Ave, Rochester, NY 14627 USA. EM Theodore_Brown@urmc.rochester.edu NR 2 TC 0 Z9 0 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2011 VL 101 IS 1 BP 37 EP 37 DI 10.2105/AJPH.2010.207316 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 699LN UT WOS:000285665000011 PM 21148713 ER PT J AU Konrad, K Fee, E AF Konrad, Kevin Fee, Elizabeth TI Old Bear: Mandan Medicine Man SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Fee, Elizabeth] NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. RP Konrad, K (reprint author), Care of Chang BB, Natl Lib Med, Hist Med Div, 8600 Rockville Pike,MSC-3819,Bldg 38,Room 1E21, Bethesda, MD 20894 USA. EM changb@mail.nih.gov NR 8 TC 0 Z9 0 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2011 VL 101 IS 1 BP 38 EP 39 DI 10.2105/AJPH.2010.195362 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 699LN UT WOS:000285665000012 PM 21148714 ER PT J AU Brown, TM Fee, E AF Brown, Theodore M. Fee, Elizabeth TI Paul B. Cornely (1906-2002): Civil Rights Leader and Public Health Pioneer SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Biographical-Item C1 [Brown, Theodore M.] Univ Rochester, Dept Hist, Rochester, NY 14627 USA. [Brown, Theodore M.] Univ Rochester, Dept Community & Prevent Med, Rochester, NY 14627 USA. [Fee, Elizabeth] NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. RP Brown, TM (reprint author), Univ Rochester, Dept Hist, 601 Elmwood Ave, Rochester, NY 14627 USA. EM Theodore_Brown@urmc.rochester.edu NR 1 TC 1 Z9 1 U1 0 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PY 2011 VL 101 SU 1 BP S164 EP S164 DI 10.2105/AJPH.2010.300052 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 849QU UT WOS:000297141000025 PM 21778476 ER PT J AU Bu, LP Fee, E AF Bu, Liping Fee, Elizabeth TI Get Well and Go Back to Work! SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Bu, Liping] Alma Coll, Dept Hist, Alma, MI 48801 USA. [Fee, Elizabeth] NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Bu, LP (reprint author), Alma Coll, Dept Hist, 614 W Super St, Alma, MI 48801 USA. EM bulipi@alma.edu NR 2 TC 1 Z9 1 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PY 2011 VL 101 SU 1 BP S165 EP S165 DI 10.2105/APH.2010.300007 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 849QU UT WOS:000297141000026 PM 21778478 ER PT J AU Casagrande, SS Gittelsohn, J Zonderman, AB Evans, MK Gary-Webb, TL AF Casagrande, Sarah Stark Gittelsohn, Joel Zonderman, Alan B. Evans, Michele K. Gary-Webb, Tiffany L. TI Association of Walkability With Obesity in Baltimore City, Maryland SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PHYSICAL-ACTIVITY; BUILT ENVIRONMENT; US ADULTS; SOCIOECONOMIC-STATUS; NEIGHBORHOOD DESIGN; URBAN FORM; HEALTH; WOMEN; RACE; OVERWEIGHT AB Objectives. To investigate the association between walkability and obesity, we studied adults residing in Baltimore City, Maryland, in neighborhoods of varying racial and socioeconomic composition. Methods. We conducted a cross-sectional study of 3493 participants from the study Healthy Aging in Neighborhoods of Diversity across the Life Span. We used the Pedestrian Environment Data Scan to measure neighborhood walkability in 34 neighborhoods of diverse racial and socioeconomic composition in which the study participants lived. Confirmatory factor analysis was used to determine walkability scores. Multilevel modeling was used to determine prevalence ratios for the association between walkability and obesity. Results. Among individuals living in predominately White and high-socioeconomic status (SES) neighborhoods, residing in highly walkable neighborhoods was associated with a lower prevalence of obesity when compared with individuals living in poorly walkable neighborhoods, after adjusting for individual-level demographic variables (prevalence ratio-[PR]=0.58; P=<.001 vs PR=0.80; P=.004). Prevalence ratios were similar after controlling for the perception of crime, physical activity, and main mode of transportation. The association between walkability and obesity for individuals living in low-SES neighborhoods was not significant after accounting for main mode of transportation (PR=0.85; P=.060). Conclusions. Future research is needed to determine how differences in associations by neighborhood characteristics may contribute to racial disparities in obesity. (Am J Public Health. 2011;101:S318-S324. doi:10.2105/AJPH.2009.187492) C1 [Casagrande, Sarah Stark; Gary-Webb, Tiffany L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Gittelsohn, Joel] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Zonderman, Alan B.] NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. [Evans, Michele K.] NIA, Lab Cellular & Mol Biol, Baltimore, MD 21224 USA. RP Casagrande, SS (reprint author), Social & Sci Syst, 8757 Georgia Ave, Silver Spring, MD 20910 USA. EM scasagrande@s-3.com OI Zonderman, Alan B/0000-0002-6523-4778 FU National Institutes of Health, National Institute on Aging; Center for a Livable Future at the Johns Hopkins Bloomberg School of Public Health [1602500081]; National Heart, Lung, and Blood Institute [K01-HL084700] FX The Healthy Aging in Neighborhoods of Diversity across the Life Span study was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. Data collection for walkability measures was supported by the Center for a Livable Future at the Johns Hopkins Bloomberg School of Public Health (Innovation Grant 1602500081). T. I. Gary-Webb was funded by a grant from the National Heart, Lung, and Blood Institute (K01-HL084700). In addition, we would like to thank Andrea Livi Smith for her help with training the data collectors to implement the PEDS audit. NR 47 TC 13 Z9 14 U1 2 U2 17 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PY 2011 VL 101 SU 1 BP S318 EP S324 DI 10.2105/AJPH.2009.187492 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 849QU UT WOS:000297141000045 PM 21164099 ER PT J AU Nweke, OC Garcia, L Lee, C Case, H Payne-Sturges, D Sanders, WH Zenick, H Grevatt, P Dankwa-Mullan, I AF Nweke, Onyemaechi C. Garcia, Lisa Lee, Charles Case, Heather Payne-Sturges, Devon Sanders, William H., III Zenick, Hal Grevatt, Peter Dankwa-Mullan, Irene TI Symposium on Integrating the Science of Environmental Justice into Decision-Making at the Environmental Protection Agency: An Overview SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID NEIGHBORHOOD PSYCHOSOCIAL HAZARDS; COMBINED MATERNAL LEAD; AMBIENT AIR-POLLUTION; HEALTH DISPARITIES; RISK-ASSESSMENT; DIFFERENTIAL VULNERABILITY; PRETERM BIRTH; CARDIOVASCULAR-DISEASE; COGNITIVE FUNCTION; BALTIMORE-MEMORY AB In March 2010, the Environmental Protection Agency (EPA) collaborated with government and nongovernmental organizations to host a groundbreaking symposium, "Strengthening Environmental Justice Research and Decision Making: A Symposium on the Science of Disproportionate Environmental Health Impacts." The symposium provided a forum for discourse on the state of scientific knowledge about factors identified by EPA that may contribute to higher burdens of environmental exposure or risk in racial/ethnic minorities and low-income populations. Also featured were discussions on how environmental justice considerations may be integrated into EPA's analytical and decision-making frameworks and on research needs for advancing the integration of environmental justice into environmental policymaking. We summarize key discussions and conclusions from the symposium and briefly introduce the articles in this issue. (Am J Public Health. 2011;101:S19-S26. doi:10.2105/AJPH.2011.300368) C1 [Nweke, Onyemaechi C.; Garcia, Lisa; Lee, Charles; Case, Heather] US EPA, Off Environm Justice, Washington, DC 20460 USA. [Payne-Sturges, Devon; Sanders, William H., III] Natl Ctr Erwimnm Res, Washington, DC USA. [Zenick, Hal] Natl Hlth & Environm Res Lab, Washington, DC USA. [Grevatt, Peter] US EPA, Off Childrens Hlth Protect, Washington, DC 20460 USA. [Dankwa-Mullan, Irene] Natl Inst Minor Hlth & Hlth Dispar, Off Innovat & Coordinat, Bethesda, MD USA. RP Nweke, OC (reprint author), US EPA, Off Environm Justice, MC 2201A,1200 Penn Ave NW, Washington, DC 20460 USA. EM nweke.onyemaechi@epa.gov NR 83 TC 7 Z9 7 U1 6 U2 18 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PY 2011 VL 101 SU 1 BP S19 EP S26 DI 10.2105/AJPH.2011.300368 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 849QU UT WOS:000297141000007 PM 22028456 ER PT J AU Ruffin, J AF Ruffin, John TI A Renewed Commitment to Environmental Justice in Health Disparities Research SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 Natl Inst Minor Hlth & Hlth Dispar, NIH, Bethesda, MD USA. RP Ruffin, J (reprint author), Natl Inst Minor Hlth & Hlth Dispar, NIH, 6707 Democracy Blvd, Bethesda, MD USA. EM RuffinJ@nimhd.nih.gov NR 9 TC 2 Z9 2 U1 0 U2 6 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PY 2011 VL 101 SU 1 BP S12 EP S14 DI 10.2105/AJPH.2011.300480 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 849QU UT WOS:000297141000004 PM 22039043 ER PT J AU Sorensen, G Landsbergis, P Hammer, L Amick, BC Linnan, L Yancey, A Welch, LS Goetzel, RZ Flannery, KM Pratt, C AF Sorensen, Glorian Landsbergis, Paul Hammer, Leslie Amick, Benjamin C., III Linnan, Laura Yancey, Antronette Welch, Laura S. Goetzel, Ron Z. Flannery, Kelly M. Pratt, Charlotte CA Workshop Working Grp Worksite Chro TI Preventing Chronic Disease in the Workplace: A Workshop Report and Recommendations SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID WORKSITE HEALTH-PROMOTION; DUAL-EARNER COUPLES; RE-AIM FRAMEWORK; FAMILY-CONFLICT; UNITED-STATES; BEHAVIOR-CHANGE; SOCIOECONOMIC-STATUS; OCCUPATIONAL-HEALTH; WELLNESS-PROGRAMS; PHYSICAL-ACTIVITY AB Chronic disease is the leading cause of death in the United States. Risk factors and work conditions can be addressed through health promotion aimed at improving individual health behaviors; health protection, including occupational safety and health interventions; and efforts to support the work family interface. Responding to the need to address chronic disease at worksites, the National Institutes of Health and the Centers for Disease Control and Prevention convened a workshop to identify research priorities to advance knowledge and implementation of effective strategies to reduce chronic disease risk. Workshop participants outlined a conceptual framework and corresponding research agenda to address chronic disease prevention by integrating health promotion and health protection in the workplace. (Am J Public Health. 2011;101:S196-S207. doi:10.2105/AJPH.2010.300075) C1 [Sorensen, Glorian] Dana Farber Canc Inst, Boston, MA 02215 USA. [Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Landsbergis, Paul] SUNY Downstate Sch Publ Hlth, Brooklyn, NY USA. [Hammer, Leslie] Portland State Univ, Portland, ME USA. [Amick, Benjamin C., III] Univ Texas Hlth Sci Ctr San Antonio, Sch Publ Hlth, San Antonio, TX 78229 USA. [Linnan, Laura] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Yancey, Antronette] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Welch, Laura S.] Ctr Construct Res & Training, Silver Spring, MD USA. [Goetzel, Ron Z.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Pratt, Charlotte] NHLBI, NIH, Bethesda, MD 20892 USA. [Flannery, Kelly M.] Univ Maryland, Baltimore, MD 21201 USA. RP Sorensen, G (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Glorian_Sorensen@dfci.harvard.edu FU National Cancer Institute [5 K05 CA108663-05]; National Institute for Occupational Safety and Health [5U19 OH008861-04]; National Heart, Lung and Blood Institute; National Institute of Occupational Safety and Health; Centers for Disease Control and Prevention; National Institute for Child Health and Human Development FX We thank the National Heart, Lung and Blood Institute; the National Institute of Occupational Safety and Health; the Centers for Disease Control and Prevention; the National Institute for Child Health and Human Development; and the National Cancer Institute for their support. Glorian Sorensen's contributions were funded by the National Cancer Institute (grant 5 K05 CA108663-05) and the National Institute for Occupational Safety and Health (grant 5U19 OH008861-04). NR 157 TC 37 Z9 37 U1 7 U2 37 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PY 2011 VL 101 SU 1 BP S196 EP S207 DI 10.2105/AJPH.2010.300075 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 849QU UT WOS:000297141000030 PM 21778485 ER PT J AU Zhu, AP Romero, R Huang, JB Clark, A Petty, HR AF Zhu, Aiping Romero, Roberto Huang, Ji-Biao Clark, Andrea Petty, Howard R. TI Maltooligosaccharides from JEG-3 Trophoblast-Like Cells Exhibit Immunoregulatory Properties SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE Immune regulation; leukocytes; saccharides ID PLASMA-MEMBRANE VESICLES; HUMAN-PREGNANCY URINE; IN-VITRO; HLA-G; OLIGOSACCHARIDES; PROLIFERATION; INFLAMMATION; RECOGNITION; GLYCOCALYX; INHIBITION AB Problem To better understand the immunoregulatory properties of trophoblasts, we have searched for small immunologically active carbohydrates derived from intact trophoblast-like cells. Method of study Using solid phase extraction coupled with HPLC and mass spectrometry methods, we have characterized a low molecular weight carbohydrate-rich fraction associated with JEG-3 cells. We have also tested the bioactivities of selected authentic oligosaccharides found in the oligosaccharide fraction. Results The most abundant components of the low molecular weight carbohydrate-rich fraction were maltotriose and maltotetraose, with detectable amounts of maltopentaose. When authentic maltooligosaccharides were tested using lymphocytes, IL-2 inhibition was observed. This activity was dependent upon the number of saccharide subunits, stereochemistry, and concentration. To further test maltooligosaccharide properties, maltopentose was attached to glass cover slips. Although spontaneous neutrophil motility was observed on unmodified and control surfaces, it was inhibited on maltooligosaccharide-derivatized surfaces. Conclusion Maltooligosaccharides are associated with the trophoblast's surface where they may exhibit immunoregulatory activities. C1 [Zhu, Aiping; Huang, Ji-Biao; Clark, Andrea; Petty, Howard R.] Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. [Zhu, Aiping; Huang, Ji-Biao; Clark, Andrea; Petty, Howard R.] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48105 USA. [Romero, Roberto] Eunice Kennedy Schriver Natl Inst Child Hlth & Hu, Perinatol Res Branch, Div Intramural Res, NIH, Bethesda, MD USA. [Romero, Roberto] Eunice Kennedy Schriver Natl Inst Child Hlth & Hu, Perinatol Res Branch, Div Intramural Res, NIH, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Romero, Roberto] Hutzel Womens Hosp, Detroit Med Ctr, Detroit, MI USA. RP Petty, HR (reprint author), Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA. EM hpetty@umich.edu FU Division of Intramural Research of the Eunice Kennedy Schriver National Instutute of Child Health and Human Development; NIH; DHHS; [N01-HD-2-3342]; [WSU04055] FX We thank Hongpeng Liu for technical assistance. This work was supported, in part, by the Division of Intramural Research of the Eunice Kennedy Schriver National Instutute of Child Health and Human Development, NIH, DHHS, contract number N01-HD-2-3342 and subcontract WSU04055. NR 29 TC 6 Z9 6 U1 2 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1046-7408 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD JAN PY 2011 VL 65 IS 1 BP 54 EP 64 DI 10.1111/j.1600-0897.2010.00851.x PG 11 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 693DS UT WOS:000285205400007 PM 20455875 ER PT J AU Eberlein, M Permutt, S Brown, RH Brooker, A Chahla, MF Bolukbas, S Nathan, SD Pearse, DB Orens, JB Brower, RG AF Eberlein, Michael Permutt, Solbert Brown, Robert H. Brooker, Allison Chahla, Mayy F. Bolukbas, Servet Nathan, Steven D. Pearse, David B. Orens, Jonathan B. Brower, Roy G. TI Supranormal Expiratory Airflow after Bilateral Lung Transplantation Is Associated with Improved Survival SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE lung transplantation; flow volume loops; lung size mismatch; dysanapsis; surface tension ID BRONCHIOLITIS-OBLITERANS-SYNDROME; HEART-LUNG; PHYSIOLOGICAL-ASPECTS; PULMONARY-FUNCTION; RESIDUAL VOLUME; RECOIL PRESSURE; SURFACE-TENSION; MECHANICS; DONOR; SIZE AB Rationale Flow volume loops (FVL) in some bilateral lung transplant (BLT) and heart-lung transplant (HLT) patients suggest variable extrathoracic obstruction in the absence of identifiable causes. These FVLs usually have supranormal expiratory and normal inspiratory flow rates (SUPRA pattern). Objectives: Characterize the relationship of the SUPRA pattern to predicted donor and recipient lung volumes, airway size, and survival. Methods: We performed a retrospective review of adult BLT/HLT patients. We defined the SUPRA FVL pattern as: (1) mid-vital capacity expiratory to inspiratory flow ratio (Ve50:Vi50) > 1.0, (2) absence of identifiable causes of extrathoracic obstruction, and (3) Ve50/FVC >= 1.5 s(-1). We calculated predicted total lung capacity (pTLC) ratio by dividing the donor pTLC by the recipient pTLC. We measured airway luminal areas on thoracic computer tomographic scans. We compared survival in patients with and without the SUPRA pattern. Measurements and Main Results: The SUPRA FVL pattern occurred in 56% of the 89 patients who qualified for the analysis. The pTLC ratio of SUPRA and non-SUPRA patients was 1.11 and 0.99, respectively (P = 0.004). A higher pTLC ratio was correlated with increased probability of the SUPRA pattern (P = 0.0072). Airway luminal areas were larger in SUPRA patients (P = 0.009). Survival was better in the SUPRA cohort (P = 0.009). Conclusions: The SUPRA FVL pattern was frequent in BLT/HLT patients. High expiratory flows in SUPRA patients could result from increased lung elastic recoil or reduced airway resistance, both of which could be caused by the pTLC mismatch. Improved survival in the SUPRA cohort suggests potential therapeutic approaches to improve outcomes in BLT/HLT patients. C1 [Eberlein, Michael; Permutt, Solbert; Pearse, David B.; Orens, Jonathan B.; Brower, Roy G.] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA. [Brown, Robert H.; Brooker, Allison] Johns Hopkins Univ, Sch Med, Div Physiol, Baltimore, MD 21205 USA. [Brown, Robert H.] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. [Brown, Robert H.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Chahla, Mayy F.] Johns Hopkins Univ, Sch Med, Div Hosp Med, Baltimore, MD 21205 USA. [Eberlein, Michael] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Bolukbas, Servet] Dr Horst Schmidt Klin, Dept Thorac Surg, Wiesbaden, Germany. [Nathan, Steven D.] Inova Fairfax Hosp, Adv Lung Dis Program, Falls Church, VA USA. RP Eberlein, M (reprint author), Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, 1830 E Monument St,5th Floor, Baltimore, MD 21205 USA. EM meberle3@jhmi.edu FU NIH; Actelion; Gilead Sciences; United Therapeutics; Nektar Therapeutics; Intermune; Bayer Schering; APT Pharmaceuticals; Astellas Pharmaceuticals; AstraZeneca FX M.E. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. S.P. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. R.H.B. received a sponsored grant from NIH for more than $100,001. A.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. M.F.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. S.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. S.D.N. received consultancy fees from Actelion for $1,001-$5,000, Gilead Sciences for $5,001-$10,000, United Therapeutics for $5,001-$10,000, Nektar Therapeutics for $10,001-$50,000, and Intermune for 55,001-$10,000. S.D.N. received consultancy fees from Actelion for $1,001-$5,000, Gilead Sciences for $5,001-$10,000, United Therapeutics for $5,001-$10,000, Bayer Schering for 51,001-$5,000, and Intermune for 51,001-$5,000. S.D.N. received lecture fees from United Therapeutics for 55,001-$10,000, Actelion for 51,001-$5,000, and Gilead Sciences for $5,001-$10,000. S.D.N. received sponsored grants from United Therapeutics for $50,001-$100,000, Intermune for $50,001-$100,000, Actelion for $50,001-$100,000, and Gilead for 55,001-$10,000. D.B.P. received sponsored grants from NIH for $50,001-$100,000 and FAMRI for more than $100,001, and has a patent pending from AHA for more than $100,001. J.B.O. received consultancy fees from APT Pharmaceuticals and Astellas Pharmaceuticals for 51,001-$5,000 each and served on the advisory board of Vectura Pharmaceuticals for $1,001-$5,000. J.B.O. also received a sponsored grant from NIH for 510,001-$50,000. R.G.B. received consultancy fees from AstraZeneca for $1,001-$5,000 and served on the advisory board of Pfizer for $1,001-$5,000. R.G.B. also received a sponsored grant from NIH for more than $100,001. NR 38 TC 16 Z9 16 U1 1 U2 4 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 JAN 1 PY 2011 VL 183 IS 1 BP 79 EP 87 DI 10.1164/rccm.201004-0593OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 705RM UT WOS:000286155600014 PM 20693376 ER PT J AU Goto, K Iso, T Hanaoka, H Suga, T Matsui, H Arai, M Endo, K Gonzalez, FJ Kurabayashi, M AF Goto, K. Iso, T. Hanaoka, H. Suga, T. Matsui, H. Arai, M. Endo, K. Gonzalez, F. J. Kurabayashi, M. TI PPAR-gamma regulates trans-endothelial fatty acid transport via induction of fatty acid binding protein 4 in capillary endothelial cells in heart, red skeletal muscles and adipose tissue SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Goto, K.; Iso, T.; Hanaoka, H.; Suga, T.; Matsui, H.; Arai, M.; Endo, K.; Kurabayashi, M.] Gunma Univ, Sch Med, Gunma, Japan. [Gonzalez, F. J.] NIH, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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. PY 2011 VL 183 BP 687 EP 687 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TI UT WOS:000208770305193 ER PT J AU Shehata, ML Lossnitzer, D Skrok, J Boyce, D Lechtzin, N Mathai, SC Girgis, RE Osman, N Lima, JAC Bluemke, DA Hassoun, PM Vogel-Claussen, J AF Shehata, Monda L. Lossnitzer, Dirk Skrok, Jan Boyce, Danielle Lechtzin, Noah Mathai, Stephen C. Girgis, Reda E. Osman, Nael Lima, Joao A. C. Bluemke, David A. Hassoun, Paul M. Vogel-Claussen, Jens TI Myocardial Delayed Enhancement in Pulmonary Hypertension: Pulmonary Hemodynamics, Right Ventricular Function, and Remodeling SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE delayed enhancement; fast strain-encoded imaging; MRI; pulmonary hypertension; tagging ID CARDIOVASCULAR MAGNETIC-RESONANCE; HYPERTROPHIC CARDIOMYOPATHY; CONTRAST-ENHANCEMENT; CONTRACTILE FUNCTION; PRESSURE-OVERLOAD; MRI; ECHOCARDIOGRAPHY; ANATOMY; HEART; DYSFUNCTION AB OBJECTIVE. The purpose of this study was to assess predictors of MRI-identified septal delayed enhancement mass at the right ventricular (RV) insertion sites in relation to RV remodeling, altered regional mechanics, and pulmonary hemodynamics in patients with suspected pulmonary hypertension (PH). SUBJECTS AND METHODS. Thirty-eight patients with suspected PH were evaluated with right heart catheterization and cardiac MRI. Ten age- and sex-matched healthy volunteers acted as controls for MRI comparison. Septal delayed enhancement mass was quantified at the RV insertions. Systolic septal eccentricity index, global RV function, and remodeling indexes were quantified with cine images. Peak systolic circumferential and longitudinal strain at the sites corresponding to delayed enhancement were measured with conventional tagging and fast strain-encoded MRI acquisition, respectively. RESULTS. PH was diagnosed in 32 patients. Delayed enhancement was found in 31 of 32 patients with PH and in one of six patients in whom PH was suspected but proved absent (p = 0.001). No delayed enhancement was found in controls. Delayed enhancement mass correlated with pulmonary hemodynamics, reduced RV function, increased RV remodeling indexes, and reduced eccentricity index. Multiple linear regression analysis showed RV mass index was an independent predictor of total delayed enhancement mass (p = 0.017). Regional analysis showed delayed enhancement mass was associated with reduced longitudinal strain at the basal anterior septal insertion (r = 0.6, p < 0.01). Regression analysis showed that basal longitudinal strain remained an independent predictor of delayed enhancement mass at the basal anterior septal insertion (p = 0.02). CONCLUSION. In PH, total delayed enhancement burden at the RV septal insertions is predicted by RV remodeling in response to increased afterload. Local fibrosis mass at the anterior septal insertion is associated with reduced regional longitudinal contractility at the base. C1 [Shehata, Monda L.; Skrok, Jan; Osman, Nael; Vogel-Claussen, Jens] Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21287 USA. [Lossnitzer, Dirk] Univ Heidelberg Hosp, Dept Cardiol, Heidelberg, Germany. [Boyce, Danielle; Lechtzin, Noah; Mathai, Stephen C.; Girgis, Reda E.; Hassoun, Paul M.] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Dept Med, Baltimore, MD 21287 USA. [Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Div Cardiol, Dept Med, Baltimore, MD 21287 USA. [Bluemke, David A.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Vogel-Claussen, Jens] Univ Tubingen, Dept Diagnost & Intervent Radiol, Univ Tubingen Hosp, Tubingen, Germany. RP Vogel-Claussen, J (reprint author), Johns Hopkins Univ, Dept Radiol, 600 N Wolfe St,Nelson Basement,MRI 143, Baltimore, MD 21287 USA. OI Bluemke, David/0000-0002-8323-8086 FU National Institutes of Health [NIH 1P50HL08946] FX Supported by grant NIH 1P50HL08946 from the National Institutes of Health. NR 35 TC 42 Z9 46 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2011 VL 196 IS 1 BP 87 EP 94 DI 10.2214/AJR.09.4114 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 703YV UT WOS:000286018800012 PM 21178051 ER PT J AU Lu, Y Liu, PY Wen, WD Grubbs, CJ Townsend, RR Malone, JP Lubet, RA You, M AF Lu, Yan Liu, Pengyuan Wen, Weidong Grubbs, Clinton J. Townsend, Reid R. Malone, James P. Lubet, Ronald A. You, Ming TI Cross-species comparison of orthologous gene expression in human bladder cancer and carcinogen-induced rodent models SO AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH LA English DT Article DE Human bladder cancer; rodent models; gene expression; proteomics; and cross-species comparison AB Genes differentially expressed by tumor cells represent promising drug targets for anti-cancer therapy. Such candidate genes need to be validated in appropriate animal models. This study examined the suitability of rodent models of bladder cancer in B6D2F1 mice and Fischer-344 rats to model clinical bladder cancer specimens in humans. Using a global gene expression approach cross-species analysis showed that 13 similar to 34% of total genes in the genome were differentially expressed between tumor and normal tissues in each of five datasets from humans, rats, and mice. About 20% of these differentially expressed genes overlapped among species, corresponding to 2.6 to 4.8% of total genes in the genome. Several genes were consistently dysregulated in bladder tumors in both humans and rodents. Notably, CNN1, MYL9, PDLIM3, ITIH5, MYH11, PCP4 and FMO5 were found to commonly downregulated; while TOP2A, CCNB2, KIF20A and RRM2 were up-regulated. These genes are likely to have conserved functions contributing to bladder carcinogenesis. Gene set enrichment analysis detected a number of molecular path-ways commonly activated in both humans and rodent bladder cancer. These pathways affect the cell cycle, HIF-1 and MYC expression, and regulation of apoptosis. We also compared expression changes at mRNA and protein levels in the rat model and identified several genes/proteins exhibiting concordant changes in bladder tumors, including ANXA1, ANXA2, CA2, KRT14, LDHA, LGALS4, SERPINA1, KRT18 and LDHB. In general, rodent models of bladder cancer represent the clinical disease to an extent that will allow successful mining of target genes and permit studies on the molecular mechanisms of bladder carcinogenesis. C1 [Lu, Yan; Liu, Pengyuan; Wen, Weidong; You, Ming] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Lu, Yan; Liu, Pengyuan; Wen, Weidong; You, Ming] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. [Grubbs, Clinton J.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. [Grubbs, Clinton J.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. [Grubbs, Clinton J.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Townsend, Reid R.; Malone, James P.] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. [Lubet, Ronald A.] NCI, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. [Lu, Yan; Liu, Pengyuan] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. [Lu, Yan; Liu, Pengyuan; You, Ming] Med Coll Wisconsin, Ctr Canc, Milwaukee, WI 53226 USA. [You, Ming] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA. RP You, M (reprint author), Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA. EM myou@mcw.edu FU NCI [HHSN-261200433008C (N01-CN43308)]; National Centers of Research Resources of the National Institutes of Health [P41-RR00954] FX The authors thank Alan Davis, Petra Erdmann-Gilmore and Julia Gross for expert technical assistance. This work was supported, in part, by NCI Contract Number HHSN-261200433008C (N01-CN43308) and the National Centers of Research Resources of the National Institutes of Health (P41-RR00954). NR 31 TC 10 Z9 10 U1 0 U2 7 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1943-8141 J9 AM J TRANSL RES JI Am. J. Transl. Res. PY 2011 VL 3 IS 1 BP 8 EP 27 PG 20 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA V28QE UT WOS:000208694500002 ER PT J AU Burbelo, PD Ching, KH Bren, KE Iadarola, MJ AF Burbelo, Peter D. Ching, Kathryn H. Bren, Kathleen E. Iadarola, Michael J. TI Emerging tactical strategies for fighting the war on cancer based on the genetic landscape SO AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH LA English DT Review DE Genetic mutations; cancer; diagnosis; therapy; oncogenes; tumor suppressors; high through-put DNA sequencing; review AB Although it is well-established that cancer is driven by genetic mutations resulting in the acquisition of oncogenes and the loss of tumor suppressors, until recently many of the genomic details remained obscure. As a result of recent high-throughput DNA sequencing, basic insights into the spectrum of protein coding mutations in many cancers are now known. These findings provide an unprecedented framework of understanding and present new avenues for diagnosis, treatment, and prevention of cancer. In this article we discuss several high impact areas of global sequencing projects including developing drugs that specifically target cancer cells, creating personalized tools for better treatment and monitoring, and developing pre-symptomatic diagnostic tests. Capitalizing on these and other advances represent a new turning point in the war on cancer. C1 [Burbelo, Peter D.; Ching, Kathryn H.; Bren, Kathleen E.; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA. RP Burbelo, PD (reprint author), Bldg 49,Room 1C36,49 Convent Dr, Bethesda, MD 20892 USA. EM burbelop@nidcr.nih.gov FU Intramural Research Program of the NIDCR, NIH FX This research was supported by the Intramural Research Program of the NIDCR, NIH. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 40 TC 0 Z9 0 U1 0 U2 0 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1943-8141 J9 AM J TRANSL RES JI Am. J. Transl. Res. PY 2011 VL 3 IS 3 BP 251 EP 258 PG 8 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA V28QG UT WOS:000208694700004 PM 21654880 ER PT J AU Kalil, AC Sun, J Florescu, DF AF Kalil, A. C. Sun, J. Florescu, D. F. TI IMPACT Trial Results Should Not Change Current Standard of Care of 100 Days for Cytomegalovirus Prophylaxis SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Cytomegalovirus; prophylaxis; valganciclovir ID ORGAN TRANSPLANT RECIPIENTS; RANDOMIZED TRIALS; DISEASE; EFFICACY; METAANALYSIS; GANCICLOVIR; PREVENTION; SAFETY; RISK; BIAS AB The results of the IMPACT trial showed a significant reduction in cytomegalovirus disease with 200-day valganciclovir prophylaxis compared to the standard 100-day regimen with the same drug. These results may have the potential to change the standard of care in most transplant centers. However, we have concerns with the design, execution and statistical analysis of this trial. Our study aimed to describe each of these issues and to provide possible solutions for the better understanding of the IMPACT trial. We conclude that the IMPACT trial does not have the strength of evidence to change current clinical practice of 100-day cytomegalovirus prophylaxis. Further, based on all available evidence, we consider that another clinical trial to test 200-day CMV prophylaxis is not necessary. C1 [Kalil, A. C.; Florescu, D. F.] Univ Nebraska Med Ctr, Div Infect Dis, Omaha, NE USA. [Sun, J.] NIH, Bethesda, MD 20892 USA. RP Kalil, AC (reprint author), Univ Nebraska Med Ctr, Div Infect Dis, Omaha, NE USA. EM akalil@unmc.edu FU Intramural NIH HHS [Z99 CL999999] NR 16 TC 13 Z9 13 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2011 VL 11 IS 1 BP 18 EP 21 DI 10.1111/j.1600-6143.2010.03342.x PG 4 WC Surgery; Transplantation SC Surgery; Transplantation GA 700ZG UT WOS:000285783500007 PM 21199346 ER PT J AU Bowman, NM Kawai, V Gilman, RH Bocangel, C Cardenas, GG Cabrera, L Levy, MZ del Carpio, JGC Delgado, F Rosenthal, L Pinedo-Cancino, VV Steurer, F Seitz, AE Maguire, JH Bern, C AF Bowman, Natalie M. Kawai, Vivian Gilman, Robert H. Bocangel, Cesar Galdos Cardenas, Gerson Cabrera, Lilia Levy, Michael Z. Geny Cornejo del Carpio, Juan Delgado, Freddy Rosenthal, Lauren Pinedo-Cancino, Vivian V. Steurer, Francis Seitz, Amy E. Maguire, James H. Bern, Caryn TI Autonomic Dysfunction and Risk Factors Associated with Trypanosoma cruzi Infection among Children in Arequipa, Peru SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID CHAGAS-DISEASE CONTROL; HOUSEHOLD PREVALENCE; NORTHWEST ARGENTINA; TRIATOMA-INFESTANS; SEROPREVALENCE; PREDICTORS; MORTALITY; COMMUNITY; HUMANS; BRAZIL AB Chagas disease affects an estimated 8 million people in Latin America Infected individuals have 20-30% lifetime risk of developing cardiomyopathy, but more subtle changes in autonomic responses may be more frequent We conducted a matched case control study of children in Arequipa, Peru, where triatomine infestation and Trypanosoma cruzi infection are emerging problems We collected data on home environment, history physical examination, electrocardiogram, and autonomic testing Signs of triatomine infestation and/or animals sleeping in the child's room and household members with Chagas disease were associated with Increased infection risk Electrocardiogram findings did not differ between cases and controls However, compared with control children, infected children had blunted auto nomic responses by three different measures, the Valsalva maneuver, the cold pressor test, and the orthostatic test T cruzi-infected children show autonomic dysfunction, although the prognostic value of this finding is not clear Sustained vector control programs are essential to decreasing future 7 cruzi infections C1 [Bowman, Natalie M.; Gilman, Robert H.; Galdos Cardenas, Gerson] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Bowman, Natalie M.] Univ N Carolina, Div Infect Dis, Chapel Hill, NC USA. [Bowman, Natalie M.] Johns Hopkins Univ Hosp, Dept Internal Med, Baltimore, MD 21287 USA. [Kawai, Vivian; Gilman, Robert H.; Cabrera, Lilia; Pinedo-Cancino, Vivian V.] Asociac Benef PRISMA, Lima, Peru. [Bocangel, Cesar; Galdos Cardenas, Gerson; Geny Cornejo del Carpio, Juan; Delgado, Freddy] Arequipa Minis Hlth, Arequipa, Peru. [Levy, Michael Z.] Univ Penn, Philadelphia, PA 19104 USA. [Levy, Michael Z.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Rosenthal, Lauren] Morgan Stanley Childrens Hosp New York, New York, NY USA. [Steurer, Francis; Bern, Caryn] Ctr Dis Control & Prevent, Atlanta, GA USA. [Seitz, Amy E.] NIAID, NIH, Bethesda, MD 20892 USA. [Maguire, James H.] Harvard Univ, Sch Med, Boston, MA USA. RP Bowman, NM (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, 615 N Wolfe St,Room W5515, Baltimore, MD 21205 USA. FU Fogarty Ellison Fellowship in Global Health and Clinical Research; Centers for Disease Control and Prevention Foundation; O C Hubert Fellowship; National Institutes of Health (NIH) [5T35 AI 007646 03, 1K01AI079162, U19 AI 33061, 5P50AI074285 02] FX N M B was supported by the Fogarty Ellison Fellowship in Global Health and Clinical Research the Centers for Disease Control and Prevention Foundation O C Hubert Fellowship and the National Institutes of Health (NIH) timing Grant 5T35 AI 007646 03 M Z L is supported by Grant 1K01AI079162 This work was funded by a grant from the International Society for Infectious Diseases NIH International Collaborations in Infectious Disease Research Opportunity Grant U19 AI 33061 and NIH Grant 5P50AI074285 02 The funding source had no role in the study design collection, analysis and interpretation of the data preparation of the manuscript or the decision to submit for publication NR 46 TC 8 Z9 8 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JAN PY 2011 VL 84 IS 1 BP 85 EP 90 DI 10.4269/ajtmh.2011.10-0303 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 702OK UT WOS:000285903800016 PM 21212207 ER PT J AU Ramanathan, R Talaat, KR Fedorko, DP Mahanty, S Nash, TE AF Ramanathan, Roshan Talaat, Kawsar R. Fedorko, Daniel P. Mahanty, Siddhartha Nash, Theodore E. TI A Species-Specific Approach to the Use of Non-Antimony Treatments for Cutaneous Leishmaniasis SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID LIPOSOMAL AMPHOTERICIN-B; SODIUM STIBOGLUCONATE PENTOSTAM; POLYMERASE-CHAIN-REACTION; VISCERAL LEISHMANIASIS; ORAL MILTEFOSINE; MUCOCUTANEOUS LEISHMANIASIS; IMMUNOCOMPROMISED PATIENTS; KETOCONAZOLE THERAPY; LIPID FORMULATIONS; EMPIRICAL THERAPY AB We used a species specific approach to treat 10 patients with cutaneous leishmaniasis diagnosed using polymerase chain reaction Non-antimony treatments (oral miltefosine, ketoconazole, and liposomal amphotericin B) were chosen as an alternative to pentavalent antimony drugs based on likely or proven drug efficacy against the infecting species Letshmania Viannia panamensis was diagnosed in three patients and treated successfully with oral ketoconazole Miltefosine treatment cured two patients with L infantum chagasi A wide variety of Leishmania responded to liposomal amphotericin B administered for 5-7 days Three patients with L V braziliensis, one patient with L tropica, and two patients with L infantum chagasi were treated successfully One person with L V braziliensis healed slowly because of a resistant bacterial superinfection and a second patient with L infantum chagasi relapsed and was retreated with miltefosine These drugs were reasonably well-tolerated In this limited case series, alternative non antimony based regimens were convenient, safe, and effective C1 [Ramanathan, Roshan] NIAID, Clin Parasitol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20902 USA. [Talaat, Kawsar R.] Johns Hopkins Bloomberg Sch Publ Hlth, Int Hlth Ctr Immunizat Res, Baltimore, MD USA. [Fedorko, Daniel P.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Nash, Theodore E.] NIAID, Gastrointestinal Parasites Sect, Parasit Dis Lab, NIH, Bethesda, MD 20902 USA. NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20902 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Baltimore, MD USA. RP Ramanathan, R (reprint author), NIAID, Clin Parasitol Unit, Parasit Dis Lab, NIH, 4 Ctr Dr,Bldg 4,Room B 105, Bethesda, MD 20902 USA. OI Mahanty, Siddhartha/0000-0003-1068-0524 FU National Institutes of Health; National Institute of Allergy and Infectious Diseases FX This study was supported by the National Institutes of Health and intramural programs of National Institute of Allergy and Infectious Diseases The authors thank Peter J Weina (Walter Reed Army Institute of Research Bethesda MD) Francis J Steurer and Alexandre De Silva (Centers for Disease Control and Prevention Atlanta, GA) for molecular sequencing of Leishmania species performed at their laboratories The authors acknowledge the expert care provided by members of our clinical staff Melissa Law Cheryl Talar Williams Eunice Fox and Amara Pabon We also thank National Institute of Allergy and Infectious Diseases intramural editor Brenda Rae Marshall for assistance NR 76 TC 9 Z9 9 U1 0 U2 3 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JAN PY 2011 VL 84 IS 1 BP 109 EP 117 DI 10.4269/ajtmh.2011.10-0437 PG 9 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 702OK UT WOS:000285903800021 PM 21212212 ER PT J AU Choi, YY Seo, D Choi, D Kim, JH Lee, KJ Ok, SY AF Choi, Yoon Young Seo, Daekwan Choi, Dongho Kim, Jung Hoon Lee, Kyung-Jae Ok, Si Young TI Comparison of Blood Transfusion Free Pancreaticoduodenectomy to Transfusion-Eligible Pancreaticoduodenectomy SO AMERICAN SURGEON LA English DT Article ID LONG-TERM SURVIVAL; JEHOVAH-WITNESS; PANCREATIC-CANCER; MEDICAL PROGRESS; 2 PARTS; MORTALITY; CARCINOMA; ADENOCARCINOMA; THERAPY; SURGERY AB Even though the surgical techniques and perioperative care have improved, blood transfusions are still often required for the patients undergoing pancreaticoduodenectomy (PD). But complications from blood transfusions, poor prognosis of blood transfused patients, cost, and availability of blood products demand transfusion free (TF) surgery in the PD patients. The purpose of this study is to compare clinical outcome of TF pancreaticoduodenectomy with transfusion-eligible (TE) PD. We had investigated the possibility of blood TF treatments for the patients who underwent PD from December 2005 to August 2007. There were 41 cases of PD performed by one surgeon with the same method: 14 patients of the TF group and 27 patients of the TE group. Most of the TF group patients received perioperative blood augmentation and intraoperative acute normovolemic hemodilution. The results of statistical analysis between TF and TE group showed that there were no statistical differences in intraoperative data and postoperative outcomes, except preoperative hemoglobin levels, type of operations, and transfusion amount. To our best knowledge, this is the first successful PD program in selected patients as a series of operations without blood transfusion. TF PD can be done successfully in selected patients without severe complications. C1 [Choi, Yoon Young; Choi, Dongho] Soonchunhyang Univ, Coll Med, Dept Surg, Seoul, South Korea. [Seo, Daekwan] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Lee, Kyung-Jae] Soonchunhyang Univ, Coll Med, Dept Occupat Med, Seoul, South Korea. [Ok, Si Young] Soonchunhyang Univ, Coll Med, Dept Anesthesiol, Seoul, South Korea. [Kim, Jung Hoon] Seoul Natl Univ Hosp, Dept Radiol, Seoul 110744, South Korea. RP Choi, D (reprint author), Soonchunhyang Univ Hosp, Dept Surg, Seoul 140743, South Korea. EM dhchoi@hosp.sch.ac.kr NR 31 TC 3 Z9 3 U1 0 U2 2 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD JAN PY 2011 VL 77 IS 1 BP 81 EP 87 PG 7 WC Surgery SC Surgery GA 710WP UT WOS:000286548000017 PM 21396312 ER PT J AU Jackson, SN Colsch, B Egan, T Lewis, EK Schultz, JA Woods, AS AF Jackson, Shelley N. Colsch, Benoit Egan, Thomas Lewis, Ernest K. Schultz, J. Albert Woods, Amina S. TI Gangliosides' analysis by MALDI-ion mobility MS SO ANALYST LA English DT Article ID FLIGHT MASS-SPECTROMETRY; THIN-LAYER-CHROMATOGRAPHY; BRAIN-TISSUE; TOF MS; LIPIDS; PHOSPHOLIPIDS; LOCALIZATION; LIPIDOMICS AB The combination of ion mobility with matrix-assisted laser desorption/ionization allows for the rapid separation and analysis of biomolecules in complex mixtures (such as tissue sections and cellular extracts), as isobaric lipid, peptide, and oligonucleotide molecular ions are pre-separated in the mobility cell before mass analysis. In this study, MALDI-IM MS is used to analyze gangliosides, a class of complex glycosphingolipids that has different degrees of sialylation. Both GD1a and GD1b, structural isomers, were studied to see the effects on gas-phase structure depending upon the localization of the sialic acids. A total ganglioside extract from mouse brain was also analyzed to measure the effectiveness of ion mobility to separate out the different ganglioside species in a complex mixture. C1 [Jackson, Shelley N.; Colsch, Benoit; Woods, Amina S.] NIDA IRP, NIH, Struct Biol Unit, Cellular Neurobiol Branch, Baltimore, MD 21224 USA. [Egan, Thomas; Lewis, Ernest K.; Schultz, J. Albert] Ionwerks Inc, Houston, TX USA. RP Woods, AS (reprint author), NIDA IRP, NIH, Struct Biol Unit, Cellular Neurobiol Branch, 333 Cassell Dr, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov FU National Institute on Drug Abuse, NIH; Office of National Drug Control Policy (ONDCP); SBIR under NCRR [5R44RR020238-04] FX This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, NIH. We thank the Office of National Drug Control Policy (ONDCP) for instrumentation funding, without which this and other projects could not have been accomplished. Ionwerks is grateful for SBIR phase II support under NCRR grant 5R44RR020238-04. NR 27 TC 19 Z9 19 U1 6 U2 31 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0003-2654 J9 ANALYST JI Analyst PY 2011 VL 136 IS 3 BP 463 EP 466 DI 10.1039/c0an00732c PG 4 WC Chemistry, Analytical SC Chemistry GA 707YG UT WOS:000286326800007 PM 21113547 ER PT J AU Tung, YC Hsiao, AY Allen, SG Torisawa, YS Ho, M Takayama, S AF Tung, Yi-Chung Hsiao, Amy Y. Allen, Steven G. Torisawa, Yu-suke Ho, Mitchell Takayama, Shuichi TI High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array SO ANALYST LA English DT Article ID ANTIBODY-PRODUCTION; TUMOR SPHEROIDS; CELL; MODEL; OSMOLARITY; METABOLISM; TISSUE; 3-D AB Culture of cells as three-dimensional (3D) aggregates can enhance in vitro tests for basic biological research as well as for therapeutics development. Such 3D culture models, however, are often more complicated, cumbersome, and expensive than two-dimensional (2D) cultures. This paper describes a 384-well format hanging drop culture plate that makes spheroid formation, culture, and subsequent drug testing on the obtained 3D cellular constructs as straightforward to perform and adapt to existing high-throughput screening (HTS) instruments as conventional 2D cultures. Using this platform, we show that drugs with different modes of action produce distinct responses in the physiological 3D cell spheroids compared to conventional 2D cell monolayers. Specifically, the anticancer drug 5-fluorouracil (5-FU) has higher anti-proliferative effects on 2D cultures whereas the hypoxia activated drug commonly referred to as tirapazamine (TPZ) are more effective against 3D cultures. The multiplexed 3D hanging drop culture and testing plate provides an efficient way to obtain biological insights that are often lost in 2D platforms. C1 [Tung, Yi-Chung; Hsiao, Amy Y.; Allen, Steven G.; Torisawa, Yu-suke; Takayama, Shuichi] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. [Tung, Yi-Chung] Acad Sinica, Res Ctr Appl Sci, Taipei 11529, Taiwan. [Ho, Mitchell] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Takayama, Shuichi] UNIST, Sch Nanobiotechnol & Chem Engn, WCU Project, Ulsan 689798, South Korea. RP Takayama, S (reprint author), Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. EM takayama@umich.edu RI Ho, Mitchell/F-5059-2015; Tung, Yi-Chung/A-1163-2007; OI Tung, Yi-Chung/0000-0002-6170-2992; Allen, Steven/0000-0002-7402-4633 FU Coulter Foundation; College of Engineering; NIH, National Cancer Institute, Center for Cancer Research FX We thank Dr Keisuke Suzuki for helpful discussion. This material is based upon work supported by the Coulter Foundation, the College of Engineering Translational Research Fund, and gifts from Jacque Passino. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 21 TC 238 Z9 240 U1 19 U2 113 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0003-2654 J9 ANALYST JI Analyst PY 2011 VL 136 IS 3 BP 473 EP 478 DI 10.1039/c0an00609b PG 6 WC Chemistry, Analytical SC Chemistry GA 707YG UT WOS:000286326800009 PM 20967331 ER PT J AU Zhang, DM Vangala, K Li, SY Yanney, M Xia, H Zou, S Sygula, A AF Zhang, Dongmao Vangala, Karthikeshwar Li, Shaoyong Yanney, Michael Xia, Hao Zou, Sige Sygula, Andrzej TI Acid cleavable surface enhanced raman tagging for protein detection SO ANALYST LA English DT Article ID SCATTERING; SPECTROSCOPY; ADSORPTION; QUANTIFICATION; FLUORESCENCE; PROBES; IDENTIFICATION; NANOPARTICLES; IMMUNOASSAY; BINDING AB Dye conjugation is a common strategy improving the surface enhanced Raman detection sensitivity of biomolecules. Reported is a proof-of-concept study of a novel surface enhanced Raman spectroscopic tagging strategy termed as acid-cleavable SERS tag (ACST) method. Using Rhodamine B as the starting material, we prepared the first ACST prototype that consisted of, from the distal end, a SERS tag moiety (STM), an acid-cleavable linker, and a protein reactive moiety. Complete acid cleavage of the ACST tags was achieved at a very mild condition that is 1.5% trifluoroacetic acid (TFA) aqueous solution at room temperature. SERS detection of this ACST tagged protein was demonstrated using bovine serum albumin (BSA) as the model protein. While the SERS spectrum of intact ACST-BSA was entirely dominated by the fluorescent signal of STM, quality SERS spectra can be readily obtained with the acid cleaved ACST-BSA conjugates. Separation of the acid cleaved STM from protein further enhances the SERS sensitivity. Current SERS detection sensitivity, achieved with the acid cleaved ACST-BSA conjugate is similar to 5 nM in terms of the BSA concentration and similar to 1.5 nM in ACST content. The dynamic range of the cleaved ACST-BSA conjugate spans four orders of magnitudes from similar to 10 nM to similar to 100 mu M in protein concentrations. Further improvement in the SERS sensitivity can be achieved with resonance Raman acquisition. This cleavable tagging strategy may also be used for elimination of protein interference in fluorescence based biomolecule detection. C1 [Zhang, Dongmao; Vangala, Karthikeshwar; Li, Shaoyong; Yanney, Michael; Xia, Hao; Sygula, Andrzej] Mississippi State Univ, Dept Chem, Mississippi State, MS 39762 USA. [Zou, Sige] NIA, NIH, Baltimore, MD 21224 USA. RP Zhang, DM (reprint author), Mississippi State Univ, Dept Chem, Mississippi State, MS 39762 USA. EM dz33@msstate.edu FU Department of Chemistry at Mississippi State University; Office of Research at Mississippi State University; NIA, NIH FX This work was supported by a start-up fund provided by the Department of Chemistry and Office of Research both at Mississippi State University to D.Z and partly by the Intramural Research Program of NIA, NIH to S.Z. NR 40 TC 3 Z9 3 U1 2 U2 23 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0003-2654 J9 ANALYST JI Analyst PY 2011 VL 136 IS 3 BP 520 EP 526 DI 10.1039/c0an00708k PG 7 WC Chemistry, Analytical SC Chemistry GA 707YG UT WOS:000286326800016 PM 21109888 ER PT J AU Dreyfuss, JM Jacobs, C Gindin, Y Benson, G Staples, GO Zaia, J AF Dreyfuss, Jonathan M. Jacobs, Christopher Gindin, Yevgeniy Benson, Gary Staples, Gregory O. Zaia, Joseph TI Targeted analysis of glycomics liquid chromatography/mass spectrometry data SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Glycomics; Glycosaminoglycan; Heparan sulfate; Mass spectrometry; Bioinformatics; Proteoglycan ID RESOLUTION LC-MS; MASS-SPECTROMETRY; HEPARAN-SULFATE; CRYSTAL-STRUCTURE; SOFTWARE; GLYCOSAMINOGLYCANS; PLATFORM; BINDING; OLIGOSACCHARIDES; LIGAND AB Hydrophilic interaction chromatography (HILIC) liquid chromatography/mass spectrometry (LC/MS) is appropriate for all native and reductively aminated glycan classes. HILIC carries the advantage that retention times vary predictably according to oligosaccharide composition. Chromatographic conditions are compatible with sensitive and reproducible glycomics analysis of large numbers of samples. The data are extremely useful for quantitative profiling of glycans expressed in biological tissues. With these analytical developments, the rate-limiting factor for widespread use of HILIC LC/MS in glycomics is the analysis of the data. In order to eliminate this problem, a Java-based open source software tool, Manatee, was developed for targeted analysis of HILIC LC/MS glycan datasets. This tool uses user-defined lists of compositions that specify the glycan chemical space in a given biological context. The program accepts high-resolution LC/MS data using the public mzXML format and is capable of processing a large data file in a few minutes on a standard desktop computer. The program allows mining of HILIC LC/MS data with an output compatible with multivariate statistical analysis. It is envisaged that the Manatee tool will complement more computationally intensive LC/MS processing tools based on deconvolution and deisotoping of LC/MS data. The capabilities of the tool were demonstrated using a set of HILIC LC/MS data on organ-specific heparan sulfates. C1 [Staples, Gregory O.; Zaia, Joseph] Boston Univ, Dept Biochem, Ctr Biomed Mass Spectrometry, Boston, MA 02218 USA. [Gindin, Yevgeniy] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. [Dreyfuss, Jonathan M.; Jacobs, Christopher; Gindin, Yevgeniy; Benson, Gary] Boston Univ, Grad Program Bioinformat, Boston, MA 02218 USA. RP Zaia, J (reprint author), Boston Univ Med Campus,670 Albany St,Rm 509, Boston, MA 02118 USA. EM jzaia@bu.edu OI Zaia, Joseph/0000-0001-9497-8701; Dreyfuss, Jonathan/0000-0001-7242-3991 FU NIH [P41RR10888, R01HL098950]; NSF; NIH National Center for Research Resources [RR018522]; W.R. Wiley Environmental Molecular Science Laboratory; US Department of Energy's Office of Biological and Environmental Research; National Institute of Allergy and Infectious Diseases (NIH/DHHS) [Y1-AI-4894-01]; Battelle Memorial Institute for the US Department of Energy [DE-AC05-76RL0 1830] FX Matthew Walsh tested the Manatee program and provided helpful comments on the manuscript. Funding was provided by NIH grants P41RR10888 and R01HL098950 and by an NSF Integrative Graduate Education and Research Traineeship.; This research utilized the Isotope Distribution Calculator developed by the Pacific Northwest National Laboratory, supported by the NIH National Center for Research Resources (Grant RR018522), the W.R. Wiley Environmental Molecular Science Laboratory (a national scientific user facility sponsored by the US Department of Energy's Office of Biological and Environmental Research and located at PNNL), and the National Institute of Allergy and Infectious Diseases (NIH/DHHS through interagency agreement Y1-AI-4894-01). PNNL is operated by Battelle Memorial Institute for the US Department of Energy under contract DE-AC05-76RL0 1830. NR 32 TC 9 Z9 9 U1 1 U2 12 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD JAN PY 2011 VL 399 IS 2 BP 727 EP 735 DI 10.1007/s00216-010-4235-1 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 700YQ UT WOS:000285781900020 PM 20953780 ER PT J AU Hipp, J Cheng, J Daignault, S Sica, J Dugan, MC Lucas, D Yagi, Y Hewitt, S Balis, UJ AF Hipp, Jason Cheng, Jerome Daignault, Stephanie Sica, Jefferey Dugan, Michael C. Lucas, David Yagi, Yukako Hewitt, Stephen Balis, Ulysses J. TI Automated area calculation of histopathologic features using SIVQ SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article DE SIVQ; area calculation; WSI; digital slide ID GENECHIP EXPRESSION MEASURES AB Recently, with the advent of the 7th edition of the AJCC Cancer Staging manual, at least one set of criteria (e.g. breast) were modified to now require the measurement of maximal depth of stromal invasion. With the current manual interpretive morphological approaches typically employed by surgical pathologists to assess tumor extent, the specialty now potentially has stumbled upon a crossroads of practice, where the diagnostic criteria have exceeded the capabilities of our commonly available tools. While whole slide imaging (WSI) technology holds the potential to offer many improvements in clinical workflow over conventional slide microscopy including unambiguous utility for facilitating quantitative diagnostic tasks with one important example being the determination of both linear dimension and surface area. However, the availability of histology data in digital form is of little utility if time-consuming and cumbersome manual workflow steps are necessarily imposed upon the pathologist in order to generate such measurements, especially as encountered with the complex and ill-defined shapes inherent to infiltrative tumors. In this communication, we demonstrate the utility of the recently described SIVQ algorithm to serve as the basis of a highly accurate, precise and semi-automated tool for direct surface area measurement of tumor infiltration from WSI data sets. By anticipating the current trend in cancer staging that emphasizes increasingly precise feature characterization, as witnessed by the recent publication of AJCC's 7th edition of the Cancer Staging Manual, this tool holds promise to will be of value to pathologists for clinical utility. C1 [Hipp, Jason; Cheng, Jerome; Daignault, Stephanie; Sica, Jefferey; Lucas, David; Balis, Ulysses J.] Univ Michigan Hlth Syst, Dept Pathol, Ann Arbor, MI 48109 USA. [Hewitt, Stephen] NCI, Pathol Lab, Adv Technol Ctr, NIH, Gaithersburg, MD USA. [Dugan, Michael C.; Yagi, Yukako] MGH Pathol Imaging & Commun Technol PICT, Boston, MA USA. [Dugan, Michael C.] Esoterix Genet Labs LLC, Pathol Serv, Los Angeles, CA USA. [Lucas, David] Roche Mol Syst Inc, Pleasanton, CA USA. RP Balis, UJ (reprint author), Univ Michigan Hlth Syst, Dept Pathol, M4233A Med Sci 1,1301 Catherine, Ann Arbor, MI 48109 USA. EM ulysses@umich.edu OI Hewitt, Stephen/0000-0001-8283-1788 NR 10 TC 2 Z9 2 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 2210-7177 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2011 VL 34 IS 5 BP 265 EP 275 DI 10.3233/ACP-2011-0025 PG 11 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 851WS UT WOS:000297303000005 PM 21988889 ER PT J AU Lim, MD Dickherber, A Compton, CC AF Lim, Mark David Dickherber, Anthony Compton, Carolyn C. TI Before You Analyze a Human Specimen, Think Quality, Variability, and Bias SO ANALYTICAL CHEMISTRY LA English DT Article ID BLOOD COLLECTION DEVICES; LONG-TERM STORAGE; PREANALYTICAL VARIABLES; TOURNIQUET APPLICATION; PROTEOMIC ANALYSIS; SAMPLE COLLECTION; PERIPHERAL-BLOOD; PROSTATE-CANCER; ARTERIAL-BLOOD; FROZEN TISSUE AB Personalized medicine requires capabilities to detect and measure health-associated biomarkers with increasingly specific and sensitive methods, putting analytical chemists at the front lines of translational research. Analytical scientists must be upstream in the experimental design process because the analysis of a biospecimen (tissue, blood, etc.) presents technical and experimental design complexities. (To listen to a podcast about this feature, please go to the Analytical Chemistry multimedia page at pubs.acs.org/page/ancham/audio/index.html.) C1 [Compton, Carolyn C.] NCI, NIH, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. [Lim, Mark David] NCI, Program Innovat Mol Anal Technol, NIH, Bethesda, MD 20892 USA. [Dickherber, Anthony] NCI, AAAS Sci & Technol Policy, Bethesda, MD 20892 USA. RP Compton, CC (reprint author), 11400 Rockville Pike,Suite 700, Rockville, MD 20892 USA. EM biospecimens@mail.nih.gov OI Lim, Mark David/0000-0002-6036-467X FU American Association for the Advancement of Science (AAAS) at NCI Office of Biorepositories and Biospecimen Research FX The authors would like to thank Prof. David Ransohoff (University of North Carolina Chapel Hill) for his comments on this article, his continuous discussions, and willingness to be a valuable resource on the clinical research aspects of biospecimen science. M. D. L. and A. D. would also like to thank the American Association for the Advancement of Science (AAAS) for supporting both with Science and Technology Policy Fellowships at the NCI Office of Biorepositories and Biospecimen Research. NR 61 TC 23 Z9 23 U1 0 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JAN 1 PY 2011 VL 83 IS 1 BP 8 EP 13 DI 10.1021/ac1018974 PG 6 WC Chemistry, Analytical SC Chemistry GA 698DB UT WOS:000285570600003 PM 21114268 ER PT J AU Sander, LC Sharpless, KE Wise, SA Nelson, BC Phinney, KW Porter, BJ Rimmer, CA Thomas, JB Wood, LJ Yen, JH Duewer, DL Atkinson, R Chen, P Goldschmidt, R Wolf, WR Ho, IP Betz, JM AF Sander, L. C. Sharpless, K. E. Wise, S. A. Nelson, B. C. Phinney, K. W. Porter, B. J. Rimmer, C. A. Thomas, J. B. Wood, L. J. Yen, J. H. Duewer, D. L. Atkinson, R. Chen, P. Goldschmidt, R. Wolf, W. R. Ho, I. -P. Betz, J. M. TI Certification of Vitamins and Carotenoids in SRM 3280 Multivitamin/Multielement Tablets SO ANALYTICAL CHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; STANDARD REFERENCE MATERIALS; TANDEM MASS-SPECTROMETRY; ISOTOPE DILUTION ASSAYS; WATER-SOLUBLE VITAMINS; DIETARY-SUPPLEMENTS; PHARMACEUTICAL FORMULATIONS; PYRIDOXINE HYDROCHLORIDE; FLUORESCENCE DETECTION; MULTIVITAMIN TABLETS AB A new multivitamin/multielement dietary supplement Standard Reference Material (SRM) has been issued by the National Institute of Standards and Technology (NIST), with certified and reference concentration values for 13 vitamins, 24 elements, and 2 carotenoids. The constituents have been measured by multiple analytical methods with data contributed by NIST and by collaborating laboratories. This effort included the first use of isotope dilution mass spectrometry for value assignment of both fat-soluble vitamins (FSVs) and water-soluble vitamins (WSVs). Excellent agreement was obtained among the methods, with relative expanded uncertainties for the certified concentration values typically ranging from <2% to 15% for vitamins. C1 [Sander, L. C.; Sharpless, K. E.; Wise, S. A.; Phinney, K. W.; Porter, B. J.; Rimmer, C. A.; Thomas, J. B.; Wood, L. J.; Duewer, D. L.] NIST, Div Analyt Chem, Gaithersburg, MD 20899 USA. [Nelson, B. C.] NIST, Div Biochem Sci, Gaithersburg, MD 20899 USA. [Yen, J. H.] NIST, Stat Engn Div, Gaithersburg, MD 20899 USA. [Atkinson, R.; Chen, P.; Goldschmidt, R.; Wolf, W. R.] USDA, Food Composit & Methods Dev Lab, Beltsville, MD 20705 USA. [Ho, I. -P.] GMA, Washington, DC 20005 USA. [Betz, J. M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Sander, LC (reprint author), NIST, Div Analyt Chem, 100 Bur Dr,MS 8311, Gaithersburg, MD 20899 USA. FU National Institutes of Health, Office of Dietary Supplements; National Institute of Standards and Technology FX Partial funding for this work was provided by the National Institutes of Health, Office of Dietary Supplements. Certain commercial equipment, instruments, or materials are identified in this report to specify adequately the experimental procedure. Such identification does not imply recommendation or endorsement by the National Institute of Standards and Technology or other governmental agency, nor does it imply that the materials or equipment identified are necessarily the best available for the purpose. NR 36 TC 12 Z9 12 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JAN 1 PY 2011 VL 83 IS 1 BP 99 EP 108 DI 10.1021/ac101953u PG 10 WC Chemistry, Analytical SC Chemistry GA 698DB UT WOS:000285570600016 PM 21128589 ER PT S AU Titus, M Tomer, KB AF Titus, Mark Tomer, Kenneth B. BE Saatcioglu, F TI Androgen Quantitation in Prostate Cancer Tissue Using Liquid Chromatography Tandem Mass Spectrometry SO ANDROGEN ACTION: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Androgen; testosterone; dihydrotestosterone; biomarker; castration-recurrent prostate cancer; metabonomics; prostate cancer; tandem mass spectrometry ID DIHYDROTESTOSTERONE LEVELS; HORMONAL-THERAPY; TESTOSTERONE; CASTRATION AB Prostate cancer that recurs after androgen deprivation therapy is the second leading cause of cancer-related death in North American men. Clinical and experimental evidences indicate that the development of recurrent prostate cancer is dependent on re-activation of the androgen receptor signaling pathway. Androgen is required for androgen receptor translocation to the nucleus, interaction with androgen response elements, expression of target genes, and prostate cancer cell proliferation. The intra-tissue and serum testosterone and dihydrotestosterone levels are important biomarkers to monitor androgen deprivation therapy efficacy in prostate cancer and recurrent prostate cancer. We have measured testosterone and dihydrotestosterone in procured recurrent prostate cancer specimens using liquid chromatography tandem mass spectrometry. The measured androgen levels are sufficient to activate androgen receptor and suggest that the recurrent prostate cancer microenvironment is capable of intracrine androgen biosynthesis. C1 [Titus, Mark] Roswell Pk Canc Inst, Dept Urol, Buffalo, NY 14263 USA. [Tomer, Kenneth B.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Titus, M (reprint author), Roswell Pk Canc Inst, Dept Urol, Buffalo, NY 14263 USA. FU Intramural NIH HHS; NCI NIH HHS [P01 CA-77739] NR 17 TC 6 Z9 8 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-242-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 776 BP 47 EP 57 DI 10.1007/978-1-61779-243-4_3 D2 10.1007/978-1-61779-243-4 PG 11 WC Andrology; Biochemical Research Methods; Biochemistry & Molecular Biology SC Endocrinology & Metabolism; Biochemistry & Molecular Biology GA BWM91 UT WOS:000294269400003 PM 21796519 ER PT J AU Lin, X Xie, J Zhu, L Lee, S Niu, G Ma, Y Kim, K Chen, XY AF Lin, Xin Xie, Jin Zhu, Lei Lee, Seulki Niu, Gang Ma, Ying Kim, Kwangmeyung Chen, Xiaoyuan TI Hybrid Ferritin Nanoparticles as Activatable Probes for Tumor Imaging SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE ferritin; fluorescent probes; imaging agents; metalloenzymes; nanoparticles ID IN-VIVO; MATRIX METALLOPROTEINASES; MOLECULAR PROBES; PROTEASE SENSORS; QUANTUM DOTS; CANCER; CELLS; LIGHT; OXIDE; CAGE C1 [Lin, Xin; Xie, Jin; Zhu, Lei; Lee, Seulki; Niu, Gang; Ma, Ying; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD USA. [Kim, Kwangmeyung] Korea Inst Sci & Technol, Biomed Res Ctr, Seoul, South Korea. RP Lee, S (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD USA. EM seulki.lee@nih.gov; shawn.chen@nih.gov RI Xie, Jin/E-8193-2010; Zhu, Lei/P-9786-2016 OI Zhu, Lei/0000-0002-1820-4795 FU National Institute of Biomedical Imaging and Bioengineering, NIH; NIH [K99/R00]; NIBIB/NIST FX This work was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, NIH. J.X. is partially supported by the NIH pathway to independence (K99/R00) award; S.L. is partially supported by a NIBIB/NIST fellowship; G.N. is an Imaging Sciences Training Program (ISTP) Fellow. We thank Dr. Henry S. Eden for proofreading the manuscript. NR 33 TC 57 Z9 62 U1 5 U2 74 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2011 VL 50 IS 7 BP 1569 EP 1572 DI 10.1002/anie.201006757 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 718YP UT WOS:000287162900008 PM 21308906 ER PT J AU Micklitsch, CM Knerr, PJ Branco, MC Nagarkar, R Pochan, DJ Schneider, JP AF Micklitsch, Christopher M. Knerr, Patrick J. Branco, Monica C. Nagarkar, Radhika Pochan, Darrin J. Schneider, Joel P. TI Zinc-Triggered Hydrogelation of a Self-Assembling beta-Hairpin Peptide SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE hydrogels; materials; peptides; self-assembly; zinc ID AMINO-ACIDS; METAL COORDINATION; DESIGNED PEPTIDE; BIOMATERIALS; COMPLEXES; PROTEINS; OXIDE; DRUG C1 [Branco, Monica C.; Schneider, Joel P.] NCI, NIH, Frederick, MD 21701 USA. [Micklitsch, Christopher M.; Knerr, Patrick J.; Nagarkar, Radhika; Pochan, Darrin J.] Univ Delaware, Newark, DE 19716 USA. RP Schneider, JP (reprint author), NCI, NIH, Frederick, MD 21701 USA. EM schneiderjp@mail.nih.gov RI Schneider, Joel/N-2610-2014 FU National Science Foundation [CHE 0348323]; Arnold and Mabel Beckman Foundation FX This work was supported in part by the National Science Foundation (CHE 0348323, JPS) and the Arnold and Mabel Beckman Foundation. NR 44 TC 77 Z9 78 U1 5 U2 69 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2011 VL 50 IS 7 BP 1577 EP 1579 DI 10.1002/anie.201006652 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 718YP UT WOS:000287162900010 PM 21308908 ER PT J AU Sloman, DL Mitasev, B Scully, SS Beutler, JA Porco, JA AF Sloman, David L. Mitasev, Branko Scully, Stephen S. Beutler, John A. Porco, John A., Jr. TI Synthesis and Biological Evaluation of ABCD Ring Fragments of the Kibdelones SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE antitumor agents; kibdelone; natural products; photochemistry; platinum ID DIELS-ALDER REACTIONS; INTRAMOLECULAR PHOTOCYCLIZATION; 2-VINYLBIPHENYL-LIKE COMPOUNDS; ORGANIC TRANSFORMATIONS; XANTHONE ANTIBIOTICS; SIMAOMICIN-ALPHA; CHIRAL DIENES; ACIDS; ACETALS; ANALOGS C1 [Sloman, David L.; Mitasev, Branko; Scully, Stephen S.; Porco, John A., Jr.] Boston Univ, Dept Chem, Ctr Chem Methodol & Lib Dev CMLD BU, Boston, MA 02215 USA. [Beutler, John A.] NCI, Mol Targets Lab, Frederick, MD 21702 USA. RP Porco, JA (reprint author), Boston Univ, Dept Chem, Ctr Chem Methodol & Lib Dev CMLD BU, 590 Commonwealth Ave, Boston, MA 02215 USA. EM porco@bu.edu RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU National Institutes of Health [R01 CA137270]; Merck Research Laboratories FX Financial support from the National Institutes of Health (R01 CA137270) and Merck Research Laboratories is gratefully acknowledged. We thank Andrew Little and Dr. Stephane Roche for extremely helpful and stimulating discussions, and Drs. Richard Ball and Jeff Bacon for X-ray crystallographic data. NR 66 TC 30 Z9 31 U1 0 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2011 VL 50 IS 11 BP 2511 EP 2515 DI 10.1002/anie.201007613 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 730MO UT WOS:000288037600010 PM 21370327 ER PT J AU Goguen, BN Hoffman, BD Sellers, JR Schwartz, MA Imperiali, B AF Goguen, Brenda N. Hoffman, Brenton D. Sellers, James R. Schwartz, Martin A. Imperiali, Barbara TI Light-Triggered Myosin Activation for Probing Dynamic Cellular Processes SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE bioorganic chemistry; enzymes; phosphorylation; protein design; semisynthesis ID SMOOTH-MUSCLE MYOSIN; HEAVY-MEROMYOSIN; CHAIN KINASE; ZIP KINASE; PHOSPHORYLATION; PROTEIN; MIGRATION; CELLS; DEPHOSPHORYLATION; CYTOKINESIS C1 [Goguen, Brenda N.; Imperiali, Barbara] MIT, Dept Biol & Chem, Cambridge, MA 02139 USA. [Hoffman, Brenton D.; Schwartz, Martin A.] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. [Sellers, James R.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Imperiali, B (reprint author), MIT, Dept Biol & Chem, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM imper@mit.edu OI schwartz, martin/0000-0002-2071-1243 FU NIH Cell Migration Consortium [GM064346]; NIGMS; AHA FX We thank Dr. Andreas Aemissegger for synthesis of the caged amino acids. This research was supported by the NIH Cell Migration Consortium (GM064346). B.N.G. was supported by the NIGMS Biotechnology Training Grant, and B. D. H. was supported by an AHA Fellowship. NR 34 TC 16 Z9 16 U1 0 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2011 VL 50 IS 25 BP 5666 EP 5669 DI 10.1002/anie.201100674 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 782HM UT WOS:000291999100011 PM 21542072 ER PT J AU Zhang, L Li, Y Li, DW Jing, C Chen, XY Lv, M Huang, Q Long, YT Willner, I AF Zhang, Lei Li, Yang Li, Da-Wei Jing, Chao Chen, Xiaoyuan Lv, Min Huang, Qing Long, Yi-Tao Willner, Itamar TI Single Gold Nanoparticles as Real-Time Optical Probes for the Detection of NADH-Dependent Intracellular Metabolic Enzymatic Pathways SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE gold nanoparticles; metabolic pathways; NADH; plasmon resonance Rayleigh scattering ID RESONANCE ENERGY-TRANSFER; PLASMON RESONANCE; SILVER NANOPARTICLES; CELL; NANOSPECTROSCOPY; NANOCRYSTALS; SCATTERING; TRANSPORT; SENSORS C1 [Zhang, Lei; Li, Yang; Li, Da-Wei; Jing, Chao; Long, Yi-Tao] E China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China. [Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Lv, Min; Huang, Qing] Chinese Acad Sci, Phys Biol Lab, Shanghai Inst Appl Phys, Shanghai 201800, Peoples R China. [Willner, Itamar] Hebrew Univ Jerusalem, Inst Chem, IL-91904 Jerusalem, Israel. RP Long, YT (reprint author), E China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China. EM ytlong@ecust.edu.cn RI Zhang, Lei/G-5123-2010; Qing, Huang/B-8796-2014; Long, Yitao/P-4089-2014; Jing, Chao/F-5992-2016; OI Zhang, Lei/0000-0002-0045-2539; Qing, Huang/0000-0001-6620-168X; Long, Yitao/0000-0002-4466-3119; Jing, Chao/0000-0003-0339-9742; Long, Yitao/0000-0003-2571-7457 FU National Natural Science Foundation of China [91027035]; National Natural Science of China [20933007]; Shanghai Pujiang Program Grant of China [09PJ1403300] FX This research is supported by the Major Research Plan of National Natural Science Foundation of China (91027035), Key Program of National Natural Science of China (20933007), and Shanghai Pujiang Program Grant of China (09PJ1403300). NR 28 TC 70 Z9 71 U1 10 U2 123 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2011 VL 50 IS 30 BP 6789 EP 6792 DI 10.1002/anie.201102151 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 792TV UT WOS:000292774200010 PM 21661084 ER PT J AU Trigo-Mourino, P Navarro-Vazquez, A Ying, JF Gil, RR Bax, A AF Trigo-Mourino, Pablo Navarro-Vazquez, Armando Ying, Jinfa Gil, Roberto R. Bax, Ad TI Structural Discrimination in Small Molecules by Accurate Measurement of Long-Range Proton-Carbon NMR Residual Dipolar Couplings SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE configuration determination; J couplings; NMR spectroscopy; residual dipolar couplings; structure elucidation ID ONE-BOND COUPLINGS; ORGANIC-MOLECULES; STRUCTURE ELUCIDATION; TUNABLE ALIGNMENT; METHYLENE PROTONS; SPECTROSCOPY; CONFIGURATION; SENSITIVITY; ASSIGNMENT; PARAMETERS C1 [Trigo-Mourino, Pablo; Gil, Roberto R.] Carnegie Mellon Univ, Dept Chem, Pittsburgh, PA 15213 USA. [Trigo-Mourino, Pablo; Navarro-Vazquez, Armando] Univ Vigo, Dept Quim Organ, Vigo 36310, Spain. [Ying, Jinfa; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Gil, RR (reprint author), Carnegie Mellon Univ, Dept Chem, 4400 5th Ave, Pittsburgh, PA 15213 USA. EM rgil@andrew.cmu.edu; bax@nih.gov RI Gil, Roberto/A-4758-2008; OI Gil, Roberto/0000-0002-8810-5047; Navarro-Vazquez, Armando/0000-0003-4364-516X; Trigo-Mourino, Pablo/0000-0003-0822-882X FU NSF [CHE-0130903]; Xunta de Galicia/FEDER (Conselleria de Educacion) [2009/071]; Spanish Government [CTQ2007-65310]; Ramon y Cajal; NIDDK; NIH; Office of the Director, NIH FX NMR instrumentation at CMU is partially supported by the NSF (CHE-0130903). A.N. thanks Centro de Supercomputacion de Galicia (CESGA) for computer time, Xunta de Galicia/FEDER (Conselleria de Educacion 2009/071) for financial support, the Spanish Government for a research grant (CTQ2007-65310), and a "Ramon y Cajal" research contract. We thank Dr. N. V. Tsarevsky from Southern Methodist University (Dallas, TX) for PMMA gels and Dr. V. E. Nicotra from Cordoba National University (Cordoba, Argentina) for the authentic sample of 10-epi (1). This work was supported by the Intramural Research Program of the NIDDK, the NIH, and the Intramural AIDS-Targeted Antiviral Program of the Office of the Director, NIH. NR 41 TC 32 Z9 32 U1 1 U2 25 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2011 VL 50 IS 33 BP 7576 EP 7580 DI 10.1002/anie.201101739 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 809YH UT WOS:000294092100019 PM 21751308 ER PT J AU Munge, BS Coffey, AL Doucette, JM Somba, BK Malhotra, R Patel, V Gutkind, JS Rusling, JF AF Munge, Bernard S. Coffey, Amy L. Doucette, Jaimee M. Somba, Brian K. Malhotra, Ruchika Patel, Vyomesh Gutkind, J. Silvio Rusling, James F. TI Nanostructured Immunosensor for Attomolar Detection of Cancer Biomarker Interleukin-8 Using Massively Labeled Superparamagnetic Particles SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE cancer; electrochemistry; immunosensors; interleukin-8; magnetic beads ID PROSTATE-SPECIFIC ANTIGEN; CARBON NANOTUBE FOREST; GROWTH-FACTOR; AMPLIFICATION; HEAD; NECK; MICROARRAY; PROTEINS; MARKERS; STRATEGIES C1 [Munge, Bernard S.; Coffey, Amy L.; Doucette, Jaimee M.; Somba, Brian K.] Salve Regina Univ, Dept Chem, Newport, RI 02840 USA. [Malhotra, Ruchika; Rusling, James F.] Univ Connecticut, Dept Chem, Storrs, CT 06269 USA. [Malhotra, Ruchika; Rusling, James F.] Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT 06232 USA. [Patel, Vyomesh; Gutkind, J. Silvio] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Munge, BS (reprint author), Salve Regina Univ, Dept Chem, 100 Ochre Point Ave, Newport, RI 02840 USA. EM bernard.munge@salve.edu RI Gutkind, J. Silvio/A-1053-2009 FU NCRR/NIH [P20RR016457]; NIEHS/NIH [ES013557]; NIDCR/NIH FX This research was financially supported by the NCRR/NIH (grant P20RR016457) awarded to B.S.M. and in part by the NIEHS/NIH (US PHS grant ES013557) awarded to J.F.R. Manuscript preparation was supported in part by the Intramural Research Program of NIDCR/NIH. NR 29 TC 89 Z9 91 U1 10 U2 103 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2011 VL 50 IS 34 BP 7915 EP 7918 DI 10.1002/anie.201102941 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 811BA UT WOS:000294175700036 PM 21721091 ER PT J AU Fan, BL Huang, PH Zheng, SY Sun, YM Fang, CG Sun, Z AF Fan, Baoliang Huang, Peihua Zheng, Suyue Sun, Yingmin Fang, Changge Sun, Zhen TI ASSEMBLY AND IN VITRO FUNCTIONAL ANALYSIS OF ZINC FINGER NUCLEASE SPECIFIC TO THE 3 ' UNTRANSLATED REGION OF CHICKEN OVALBUMIN GENE SO ANIMAL BIOTECHNOLOGY LA English DT Article DE Gene targeting; Transgenic chicken; Zinc finger nuclease ID ARTIFICIAL TRANSCRIPTION FACTORS; PRIMORDIAL GERM-CELLS; HOMOLOGOUS RECOMBINATION; TRANSGENIC CHICKENS; VECTOR; DNA; CONSTRUCTION; CATTLE; TOOL AB Synthetic zinc finger nucleases (ZFNs) are useful for the improvement of site directed integration of foreign gene into vertebrate chromosomes. To facilitate site-directed integration of foreign genes into the 3'-untranslated region of the chicken ovalbumin gene, we have constructed ZFN expression vectors using Zinc Finger Consortium Vector Kits and tested the functionality of these ZFN constructs. Coding sequences for 6 zinc fingers were assembled following the modular assembly method. The zinc finger assembly was fused to two FokI catalytic domains. Various configurations of linker regions between domains were tested for their influence on enzymatic activity, using plasmid substrate containing the target sequence. Results indicated that ZFN with an elongated linker between two nuclease domains had a high catalytic activity. C1 [Fan, Baoliang; Sun, Yingmin; Sun, Zhen] Hebei Agr Univ, Anim Sci & Technol Dept, Baoding, Peoples R China. [Fan, Baoliang; Zheng, Suyue] Hebei Univ Engn, Coll Agr, Handan, Peoples R China. [Huang, Peihua] Hebei Univ Engn, Modern Educ Technol Ctr, Handan, Peoples R China. [Fang, Changge] NCI, Adv Technol Ctr, NIH, Gaithersburg, MD USA. RP Fan, BL (reprint author), Hebei Agr Univ, Anim Sci & Technol Dept, Room 2524,Bldg D,Jian She Nan Lu 215, Baoding City 071000, Hebei, Peoples R China. EM fanbl119@vip.sina.com FU 863 National Key Project [2007AA100504]; Major National ST Project [2008ZX08006004, 2008ZX08007-001]; National Natural Science Foundation [30972081] FX This work was supported by an 863 National Key Project (2007AA100504), the Major National S&T Project (2008ZX08006004 and 2008ZX08007-001), and the National Natural Science Foundation (30972081). NR 21 TC 3 Z9 3 U1 0 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1049-5398 J9 ANIM BIOTECHNOL JI Anim. Biotechnol. PY 2011 VL 22 IS 4 BP 211 EP 222 DI 10.1080/10495398.2011.626885 PG 12 WC Agriculture, Dairy & Animal Science; Biotechnology & Applied Microbiology SC Agriculture; Biotechnology & Applied Microbiology GA 857EL UT WOS:000297698800004 PM 22132814 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS Summary SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Editorial Material; Book Chapter C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 1 EP 5 PG 5 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700001 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS Introduction SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Editorial Material; Book Chapter ID YERSINIA-PESTIS; EVOLUTION; PLAGUE; TSG101 C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 7 EP 13 PG 7 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700002 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI Evaluation of Current and Future TMT-Used Animal Models SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Article; Book Chapter ID EBOLA-VIRUS-INFECTION; MARBURG HEMORRHAGIC-FEVER; VERVET MONKEY DISEASE; HUMAN ANTHRAX VACCINE; GUINEA-PIGS; BACILLUS-ANTHRACIS; FRANCISELLA-TULARENSIS; DRUG DEVELOPMENT; CYNOMOLGUS MACAQUES; PRIMATE MODELS C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 115 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 15 EP 37 PG 23 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700003 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI Ethical and Regulatory Challenges in the Development of Countermeasures SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Article; Book Chapter ID VACCINE; CONSENT; ANTHRAX C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 37 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 39 EP 49 PG 11 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700004 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI Developing New Animal Models for Biodefense Research SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Article; Book Chapter ID ANTHRAX C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 51 EP 59 PG 9 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700005 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI Alternative Approaches to Animal Testing for Biodefense Countermeasures SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Article; Book Chapter ID MONKEYPOX VIRUS; NONHUMAN-PRIMATES; GENE-EXPRESSION; COMPLEX; RESPONSES; SMALLPOX; DESIGN; TRAITS; CELLS; HEMAGGLUTININ C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 66 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 61 EP 76 PG 16 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700006 ER PT S AU Panlilio, LV AF Panlilio, Leigh V. BE Olmstead, MC TI Stimulant Self-Administration SO ANIMAL MODELS OF DRUG ADDICTION SE Neuromethods LA English DT Article; Book Chapter DE Animal models; Drug abuse; Methodology; Stimulus; Reinforcement; Behavior; Learning ID DRUG-SEEKING BEHAVIOR; INTRAVENOUS COCAINE; RHESUS-MONKEYS; D-AMPHETAMINE; ADMINISTERED COCAINE; REINFORCING EFFICACY; 2ND-ORDER SCHEDULES; RATS; DOPAMINE; MODEL AB Stimulants such as cocaine and the amphetamines are widely abused due to their rewarding effects. Much of what we know about drug abuse and drug reward comes from research involving stimulants, and much of this research involves using drug self-administration as an animal model of drug abuse. In this chapter, the example of stimulant self-administration is used to illustrate: (1) the basic methodology of drug self-administration procedures and (2) the behavioral principles that apply to addiction and animal models of addiction. Many variations of the self-administration procedure have been developed to model specific aspects of drug abuse, to assess the rewarding effects of drugs, and to assess the effects of treatments. The chapter describes how these variations are devised by stipulating the behavioral requirements for receiving the drug (i.e., the schedule of reinforcement) and incorporating drug-related environmental cues analogous to those that Occur in the human drug-abuse environment. C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Panlilio, LV (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, 251 Bayview Blvd, Baltimore, MD 21224 USA. NR 73 TC 3 Z9 3 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 0893-2336 BN 978-1-60761-933-8 J9 NEUROMETHODS JI Neuromethods PY 2011 VL 53 BP 57 EP 81 DI 10.1007/978-1-60761-934-5_2 D2 10.1007/978-1-60761-934-5 PG 25 WC Cell Biology; Neurosciences; Psychology SC Cell Biology; Neurosciences & Neurology; Psychology GA BSV19 UT WOS:000285892500002 ER PT S AU Marder, SR Roth, B Sullivan, PF Scolnick, EM Nestler, EJ Geyer, MA Welnberger, DR Karayiorgou, M Guidotti, A Gingrich, J Akbarian, S Buchanan, RW Lieberman, JA Conn, PJ Haggarty, SJ Law, AJ Campbell, B Krystal, JH Moghaddam, B Saw, A Caron, MG George, SR Allen, JA Solis, M AF Marder, Stephen R. Roth, Bryan Sullivan, Patrick F. Scolnick, Edward M. Nestler, Eric J. Geyer, Mark A. Welnberger, Daniel R. Karayiorgou, Maria Guidotti, Alessandro Gingrich, Jay Akbarian, Schahram Buchanan, Robert W. Lieberman, Jeffrey A. Conn, P. Jeffrey Haggarty, Stephen J. Law, Amanda J. Campbell, Brian Krystal, John H. Moghaddam, Bita Saw, Akira Caron, Marc G. George, Susan R. Allen, John A. Solis, Michelle BE Braaten, D TI Advancing drug discovery for schizophrenia SO ANNALS MEETING REPORTS SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE schizophrenia; genetics; GWAS; neuronal function; small molecules; therapeutics ID METHYLATION; PSYCHIATRY; DISORDERS; INDUCTION; CELLS AB Sponsored by the New York Academy of Sciences and with support from the National Institute of Mental Health, the Life Technologies Foundation, and the Josiah Macy Jr. Foundation, "Advancing Drug Discovery for Schizophrenia" was held March 9-11 at the New York Academy of Sciences in New York City. The meeting, comprising individual talks and panel discussions, highlighted basic, clinical, and translational research approaches, all of which contribute to the overarching goal of enhancing the pharmaceutical armamentarium for treating schizophrenia. This report surveys work by the vanguard of schizophrenia research in such topics as genetic and epigenetic approaches; small molecule therapeutics; and the relationships between target genes, neuronal function, and symptoms of schizophrenia. C1 [Marder, Stephen R.] Univ Calif Los Angeles, Semel Inst Neurosci, Los Angeles, CA 90095 USA. [Marder, Stephen R.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Roth, Bryan; Allen, John A.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Scolnick, Edward M.] Broad Inst MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Scolnick, Edward M.] Harvard Univ, Cambridge, MA 02138 USA. [Nestler, Eric J.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Geyer, Mark A.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Welnberger, Daniel R.; Haggarty, Stephen J.; Law, Amanda J.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA. [Karayiorgou, Maria; Lieberman, Jeffrey A.] Columbia Univ, Dept Psychiat, New York, NY USA. [Karayiorgou, Maria; Gingrich, Jay] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Guidotti, Alessandro] Univ Illinois, Chicago, IL USA. [Akbarian, Schahram] Univ Massachusetts, Sch Med, Res Inst, Worcester, MA USA. [Akbarian, Schahram] Univ Massachusetts, Sch Med, Program Bioinformat & Integrat Biol, Worcester, MA USA. [Buchanan, Robert W.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Conn, P. Jeffrey] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Vanderbilt Program Drug Discovery, Nashville, TN 37232 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Campbell, Brian; Allen, John A.] Pfizer Neurosci, Groton, CT USA. [Krystal, John H.] Yale Univ, Sch Med, New Haven, CT USA. [Moghaddam, Bita] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA USA. [Saw, Akira] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Saw, Akira] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Caron, Marc G.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. [George, Susan R.] Univ Toronto, Dept Med, Ctr Addict & Mental Hlth, Toronto, ON, Canada. [George, Susan R.] Univ Toronto, Dept Pharmacol, Ctr Addict & Mental Hlth, Toronto, ON, Canada. RP Marder, SR (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci, Los Angeles, CA 90095 USA. RI Conn, Peter/D-7848-2012; Law, Amanda/G-6372-2012; Allen, John/D-6141-2011; OI Haggarty, Stephen J./0000-0002-7872-168X; Law, Amanda/0000-0002-2574-1564 FU NIDA NIH HHS [R01 DA007223]; NIMH NIH HHS [R01 MH095088]; NINDS NIH HHS [R01 NS031373] NR 20 TC 14 Z9 14 U1 0 U2 7 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-853-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2011 VL 1236 BP 30 EP 43 DI 10.1111/j.1749-6632.2011.06216.x PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BYL80 UT WOS:000299291300003 PM 22032400 ER PT J AU Riordan, JT Dupre, JM Cantore-Matyi, SA Kumar-Singh, A Song, Y Zaman, S Horan, S Helal, NS Nagarajan, V Elasri, MO Wilkinson, BJ Gustafson, JE AF Riordan, James T. Dupre, JoAnne M. Cantore-Matyi, Stephanie A. Kumar-Singh, Atul Song, Yang Zaman, Shahrear Horan, Sonia Helal, Nada S. Nagarajan, Vijayaraj Elasri, Mohamed O. Wilkinson, Brian J. Gustafson, John E. TI Alterations in the transcriptome and antibiotic susceptibility of Staphylococcus aureus grown in the presence of diclofenac SO ANNALS OF CLINICAL MICROBIOLOGY AND ANTIMICROBIALS LA English DT Article DE Diclofenac; S. aureus; antibiotic resistance; non-steroidal anti-inflammatory drugs (NSAIDs) AB Background: Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) which has been shown to increase the susceptibility of various bacteria to antimicrobials and demonstrated to have broad antimicrobial activity. This study describes transcriptome alterations in S. aureus strain COL grown with diclofenac and characterizes the effects of this NSAID on antibiotic susceptibility in laboratory, clinical and diclofenac reduced-susceptibility (Dc(RS)) S. aureus strains. Methods: Transcriptional alterations in response to growth with diclofenac were measured using S. aureus gene expression microarrays and quantitative real-time PCR. Antimicrobial susceptibility was determined by agar diffusion MICs and gradient plate analysis. Ciprofloxacin accumulation was measured by fluorescence spectrophotometry. Results: Growth of S. aureus strain COL with 80 mu g/ml (0.2 x MIC) of diclofenac resulted in the significant alteration by >= 2-fold of 458 genes. These represented genes encoding proteins for transport and binding, protein and DNA synthesis, and the cell envelope. Notable alterations included the strong down-regulation of antimicrobial efflux pumps including mepRAB and a putative emrAB/qacA-family pump. Diclofenac up-regulated sigB (sigma(B)), encoding an alternative sigma factor which has been shown to be important for antimicrobial resistance. Staphylococcus aureus microarray metadatabase (SAMMD) analysis further revealed that 46% of genes differentially-expressed with diclofenac are also sigma(B)-regulated. Diclofenac altered S. aureus susceptibility to multiple antibiotics in a strain-dependent manner. Susceptibility increased for ciprofloxacin, ofloxacin and norfloxacin, decreased for oxacillin and vancomycin, and did not change for tetracycline or chloramphenicol. Mutation to Dc(RS) did not affect susceptibility to the above antibiotics. Reduced ciprofloxacin MICs with diclofenac in strain BB255, were not associated with increased drug accumulation. Conclusions: The results of this study suggest that diclofenac influences antibiotic susceptibility in S. aureus, in part, by altering the expression of regulatory and structural genes associated with cell wall biosynthesis/turnover and transport. C1 [Riordan, James T.; Helal, Nada S.] Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL 33620 USA. [Dupre, JoAnne M.; Cantore-Matyi, Stephanie A.; Zaman, Shahrear; Horan, Sonia; Gustafson, John E.] New Mexico State Univ, Dept Biol, Microbiol Grp, Las Cruces, NM 88003 USA. [Dupre, JoAnne M.; Cantore-Matyi, Stephanie A.; Zaman, Shahrear; Horan, Sonia; Gustafson, John E.] New Mexico State Univ, Program Mol Biol, Las Cruces, NM 88003 USA. [Kumar-Singh, Atul; Song, Yang; Wilkinson, Brian J.] Illinois State Univ, Dept Biol, Normal, IL 61790 USA. [Nagarajan, Vijayaraj; Elasri, Mohamed O.] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. [Nagarajan, Vijayaraj] NIAID, BCBB, OCICB, OSMO,OD,NIH, Bethesda, MD 20892 USA. RP Riordan, JT (reprint author), Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL 33620 USA. EM jtriordan@usf.edu RI song, yang/P-1033-2015 FU National Institutes of Health [SC1GM083882-01, R25 GM07667-30, S06-GM61222-05]; NM-INBRE Program of the National Center for Research Resource [P20RR016480] FX All authors wish to acknowledge prior and ongoing support from the National Institutes of Health: SC1GM083882-01 (J.E.G.); R25 GM07667-30 (NMSU-MARC PROGRAM); S06-GM61222-05 (NMSU-MBRS-RISE PROGRAM); and P20RR016480 from the NM-INBRE Program of the National Center for Research Resource. NR 87 TC 4 Z9 4 U1 2 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-0711 J9 ANN CLIN MICROB ANTI JI Ann. Clin. Microbiol. Antimicrob. PY 2011 VL 10 AR 30 DI 10.1186/1476-0711-10-30 PG 11 WC Microbiology SC Microbiology GA V28AZ UT WOS:000208655000030 PM 21774834 ER PT J AU Al Ghatrif, M Kuo, YF Al Snih, S Raji, MA Ray, LA Markides, KS AF Al Ghatrif, Majd Kuo, Yong-Fang Al Snih, Soham Raji, Mukaila A. Ray, Laura A. Markides, Kyriakos S. TI Trends in Hypertension Prevalence, Awareness, Treatment and Control in Older Mexican Americans, 1993-2005 SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Awareness; Control; Hypertension; Mexican American elders; Treatment; Trends ID ANTIHYPERTENSIVE DRUG-TREATMENT; ISOLATED SYSTOLIC HYPERTENSION; JOINT NATIONAL COMMITTEE; UNITED-STATES ADULTS; HIGH BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; RISK-FACTORS; OBESITY; PREVENTION; MORTALITY AB PURPOSE: To describe trends in hypertension prevalence, awareness, treatment, and control among older Mexican Americans living in the Southwestern United States from 1993-1994 to 2004-2005. METHODS: This study is a comparison between two separate cross-sectional cohorts of non-institutionalized Mexican Americans 75 years of age or older from the Hispanic Established Population for the Epidemiological Study of the Elderly (919 subjects from the 1993-1994 cohort and 738 from the 2004-2005 cohort). Data were collected on self-reported hypertension, measured blood pressure, medications, as well as sociodemographic and other health-related factors. RESULTS: Hypertension prevalence increased from 73.0% in the period 1993-1994 to 78.4% in 2004-2005. Cross-cohort multivariate analyses showed that the higher odds of hypertension in the 2004-2005 cohort was attenuated by adding diabetes and obesity to the model. There was a significant increase in hypertension awareness among hypertensives (63.0% to 82.6%) and in control among treated hypertensives (42.5% to 55.4%). Cross-cohort multivariate analyses showed that the higher odds of control in 2004-2005 cohorts were accentuated by adding diabetes to the model. There were no significant changes in treatment rates (62.2% to 65.6%) CONCLUSION: Hypertension prevalence in very old Mexican Americans residing in the Southwestern United States was higher in 2004-2005 than in 1993-1994 and was accompanied by a significant increase in awareness and control rates. Ann Epidemiol 2011;21:15-25. (C) 2011 Elsevier Inc. All rights reserved. C1 [Al Ghatrif, Majd] Union Mem Hosp, Dept Internal Med, Baltimore, MD 21218 USA. [Al Ghatrif, Majd; Kuo, Yong-Fang; Al Snih, Soham; Ray, Laura A.; Markides, Kyriakos S.] UTMB, Sealy Ctr Aging, Galveston, TX USA. [Kuo, Yong-Fang; Al Snih, Soham; Raji, Mukaila A.; Markides, Kyriakos S.] UTMB, Div Geriatr, Dept Internal Med, Galveston, TX USA. [Al Snih, Soham] UTMB, Rehabil Sci Div, Rehabil Sci Div, Galveston, TX USA. [Al Ghatrif, Majd] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP Al Ghatrif, M (reprint author), Union Mem Hosp, Dept Internal Med, 201 E Univ Pkwy, Baltimore, MD 21218 USA. EM majd.alghatrif@nih.gov FU NIH; National Institute on Aging, USA [AG10939, 1R01AG031178-01A1S1]; UTMB Center for Health and Health Disparities [5P50CA105631-05]; Robert Wood Johnson Foundation's Network for Multicultural Research on Health and Healthcare at UCLA; Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [K12HD52023]; National Institute of Allergy and Infectious Diseases (NIAID); Office of the Director (OD), National Institutes of Health FX The research reported in this manuscript was funded in whole or in part by NIH funding and is subject to the NIH public access policy, Division G, Title II, Section 218 of PL 110-161 (Consolidated Appropriations Act, 2008). The University of Texas Medical Branch at Galveston previously obtained non-exclusive rights in this manuscript that allow the final peer-reviewed manuscript to be submitted to the NIH upon acceptance for publication, including all modifications from the peer review process, to be made available to the public in PubMed Central as soon as possible but no later than 12 months after the official date of publication.; Supported by grants AG10939, 1R01AG031178-01A1S1 from the National Institute on Aging, USA; UTMB Center for Health and Health Disparities (5P50CA105631-05); the Robert Wood Johnson Foundation's Network for Multicultural Research on Health and Healthcare at UCLA. Dr. Al Snih is supported by a research career development award (K12HD52023: Building Interdisciplinary Research Careers in Women's Health Program) from the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); the National Institute of Allergy and Infectious Diseases (NIAID); and the Office of the Director (OD), National Institutes of Health. NR 35 TC 13 Z9 14 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 2011 VL 21 IS 1 BP 15 EP 25 DI 10.1016/j.annepidem.2010.06.002 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 702NX UT WOS:000285902500002 PM 20727787 ER PT J AU Cupul-Uicab, LA Ye, XB Skjaerven, R Haug, K Longnecker, MP AF Cupul-Uicab, Lea A. Ye, Xibiao Skjaerven, Rolv Haug, Kjell Longnecker, Matthew P. TI Reproducibility of Reported In Utero Exposure to Tobacco Smoke SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Tobacco Smoking; Prenatal Exposure; Reproducibility ID MATERNAL SMOKING; WEIGHTED KAPPA; FOLLOW-UP; PREGNANCY; AGREEMENT; MOTHER; WOMEN; AGE; COEFFICIENT; LIFETIME AB PURPOSE: In studies of the fetal origins of disease and life course epidemiology, measures of fetal exposure may be based on information reported by the adults who were exposed in utero. In particular, the full spectrum of consequences of in utero exposure to maternal tobacco smoking is now an area of active investigation, and the ability to report such exposure reproducibly is of interest. We evaluated the reproducibility of in utero exposure to tobacco smoke, reported by the adult daughter during consecutive pregnancies. METHODS: This study was based on 11,257 women who enrolled for more than one pregnancy in the Norwegian Mother and Child Cohort Study (MoBa). Participants completed a questionnaire around 17 weeks of gestation, which asked about their in utero exposure to tobacco smoke. Kappa statistics were calculated. Determinants of agreement were evaluated using logistic regression. RESULTS: Weighted Kappa for in utero exposure for the first and second reports was 0.80. Determinants of agreement were higher education (better) and longer time between reports (worse). CONCLUSIONS: Information on in utero exposure to maternal tobacco smoking provided by adult women was highly reproducible in this population. Ann Epidemiol 2011;21:48-52. Published by Elsevier Inc. C1 [Cupul-Uicab, Lea A.; Longnecker, Matthew P.] NIEHS, NIH, DHHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Ye, Xibiao] Canadian Blood Serv, Natl Epidemiol & Surveillance, Ottawa, ON, Canada. [Skjaerven, Rolv] Univ Bergen, Sect Med Stat, Bergen, Norway. [Skjaerven, Rolv] Univ Bergen, Med Birth Registry Norway, Bergen, Norway. [Skjaerven, Rolv] Norwegian Inst Publ Hlth, Oslo, Norway. [Haug, Kjell] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway. RP Cupul-Uicab, LA (reprint author), NIEHS, NIH, DHHS, Epidemiol Branch, 111 TW Alexander Dr,Bldg 101,Room A353A,MD A3-05, Res Triangle Pk, NC 27709 USA. EM cupuluicabl@niehs.nih.gov RI CUPUL UICAB, LEA/C-8699-2014; OI CUPUL UICAB, LEA/0000-0001-6190-4474; Longnecker, Matthew/0000-0001-6073-5322 FU National Institute of Environmental Health Sciences (NIEHS), the National Institutes of Health (NIH) [N01-ES-85433]; Norwegian Ministry of Health; NIH/NINDS [1 UO1 NS 047537-01]; Norwegian Research Council/FUGE [151918/S10] FX This study was supported in part by the Intramural Research Program, the National Institute of Environmental Health Sciences (NIEHS), the National Institutes of Health (NIH). The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health, NIH/NIEHS (N01-ES-85433), NIH/NINDS (1 UO1 NS 047537-01), and the Norwegian Research Council/FUGE (151918/S10). NR 24 TC 5 Z9 5 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 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 2011 VL 21 IS 1 BP 48 EP 52 DI 10.1016/j.annepidem.2010.10.008 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 702NX UT WOS:000285902500006 PM 21130369 ER PT J AU Foley, AR Hu, Y Zou, YQ Yang, MC Medne, L Leach, M Conlin, LK Spinner, N Shaikh, TH Falk, M Neumeyer, AM Bliss, L Tseng, BS Winder, TL Bonnemann, CG AF Foley, A. Reghan Hu, Ying Zou, Yaqun Yang, Michele Medne, Livija Leach, Meganne Conlin, Laura K. Spinner, Nancy Shaikh, Tamim H. Falk, Marni Neumeyer, Ann M. Bliss, Laurie Tseng, Brian S. Winder, Thomas L. Boennemann, Carsten G. TI Large Genomic Deletions: A Novel Cause of Ullrich Congenital Muscular Dystrophy SO ANNALS OF NEUROLOGY LA English DT Article ID COLLAGEN TYPE-VI; BETHLEM MYOPATHY; VONWILLEBRAND-FACTOR; GLOBULAR DOMAINS; COL6A1; MUTATIONS; SEQUENCE; CHAINS; GENES AB Two mutational mechanisms are known to underlie Ullrich congenital muscular dystrophy (UCMD): heterozygous dominant negatively-acting mutations and recessively-acting loss-of-function mutations. We describe large genomic deletions on chromosome 21q22.3 as a novel type of mutation underlying recessively inherited UCMD in 2 families. Clinically unaffected parents carrying large genomic deletions of COL6A1 and COL6A2 also provide conclusive evidence that haploinsufficiency for COL6A1 and COL6A2 is not a disease mechanism for Bethlem myopathy. Our findings have important implications for the genetic evaluation of patients with collagen VI related myopathies as well as for potential therapeutic interventions for this patient population. C1 [Boennemann, Carsten G.] NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, Neurogenet Branch, NIH,Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. [Foley, A. Reghan; Hu, Ying; Zou, Yaqun; Yang, Michele; Medne, Livija; Leach, Meganne; Boennemann, Carsten G.] Univ Penn, Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Medne, Livija; Conlin, Laura K.; Falk, Marni] Univ Penn, Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA. [Spinner, Nancy] Univ Penn, Childrens Hosp Philadelphia, Div Pathol, Philadelphia, PA 19104 USA. [Foley, A. Reghan] UCL, Inst Child Hlth, Dubowitz Neuromuscular Ctr, London, England. [Foley, A. Reghan] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Yang, Michele; Shaikh, Tamim H.] Univ Colorado Denver, Dept Pediat, Aurora, CO USA. [Spinner, Nancy; Shaikh, Tamim H.; Falk, Marni; Boennemann, Carsten G.] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. [Neumeyer, Ann M.; Bliss, Laurie; Tseng, Brian S.] Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Winder, Thomas L.] Prevent Genet, Marshfield, WI USA. RP Bonnemann, CG (reprint author), NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, Neurogenet Branch, NIH,Porter Neurosci Res Ctr, Bldg 35,Room 2A-116,MSC 35 Convent Dr, Bethesda, MD 20892 USA. EM carsten.bonnemann@nih.gov FU NIH/NIAMS [R01AR051999]; MDA USA [MDA3896]; NIH/NIGMS [GM081519] FX This research was supported by grants from NIH/NIAMS (R01AR051999 to C.G.B.) and from MDA USA (MDA3896 to C.G.B.); NIH/NIGMS grant (GM081519 to T.H.S.). NR 19 TC 11 Z9 13 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2011 VL 69 IS 1 BP 206 EP 211 DI 10.1002/ana.22283 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 714ZS UT WOS:000286850800028 PM 21280092 ER PT J AU Steingrimsdottir, L Haraldsdottir, A Valdimarsdottir, U Torfadottir, J Harris, T Launer, L Gudnason, V AF Steingrimsdottir, L. Haraldsdottir, A. Valdimarsdottir, U. Torfadottir, J. Harris, T. Launer, L. Gudnason, V. TI Women's fish and fish oil intake in adolescence and midlife and coronary heart disease risk SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract DE fish oil; fish; coronary heart disease; adolescent diet; midlife diet C1 [Steingrimsdottir, L.] Univ Iceland, Unit Nutr Res, Reykjavik, Iceland. [Steingrimsdottir, L.] Landspitali Natl Hosp, Reykjavik, Iceland. [Haraldsdottir, A.; Valdimarsdottir, U.; Torfadottir, J.] Univ Iceland, Ctr Publ Hlth Sci, Reykjavik, Iceland. [Harris, T.; Launer, L.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Gudnason, V.] Univ Iceland, Iceland Heart Assoc, Reykjavik, Iceland. [Gudnason, V.] Univ Iceland, Fac Med, Reykjavik, Iceland. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2011 VL 58 SU 3 BP 339 EP 340 PG 2 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 861IF UT WOS:000298011900757 ER PT J AU Lattka, E Koletzko, B Zeilinger, S Hibbeln, J Klopp, N Ring, S Steer, C AF Lattka, E. Koletzko, B. Zeilinger, S. Hibbeln, J. Klopp, N. Ring, S. Steer, C. TI Genetic variants in the fads gene cluster determine umbilical cord plasma polyunsaturated fatty acid amounts SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract DE FADS; desaturase; cord blood; single nucleotide polymorphism; long-chain polyunsaturated fatty acids C1 [Lattka, E.; Zeilinger, S.; Klopp, N.] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany. [Koletzko, B.] Univ Munich, Med Ctr, Dept Pediat, Dr von Hauner Childrens Hosp, Munich, Germany. [Hibbeln, J.] NIAAA, NIH, Bethesda, MD USA. [Ring, S.; Steer, C.] Univ Bristol, Ctr Child & Adolescent Hlth, Sch Social & Community Med, Bristol, Avon, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2011 VL 58 SU 3 BP 396 EP 396 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 861IF UT WOS:000298011900882 ER PT J AU Roescher, N Kingman, A Shirota, Y Chiorini, JA Illei, GG AF Roescher, N. Kingman, A. Shirota, Y. Chiorini, J. A. Illei, G. G. TI Peptide-based ELISAs are not sensitive and specific enough to detect muscarinic receptor type 3 autoantibodies in serum from patients with Sjogren's syndrome SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Letter ID ACETYLCHOLINE-RECEPTOR; ANTIMUSCARINIC ANTIBODIES AB Objectives The detection of autoantibodies to the muscarinic receptor type 3 (M3R) in the serum of patients with Sjogrens syndrome (SS) by ELISA is controversial. A study was undertaken to test whether modification of M3R peptides could enhance the antigenicity and increase the detection of specific antibodies using an ELISA. Methods A series of controlled ELISAs was performed with serum from 71 patients with SS and 37 healthy volunteers (HV) on linear, citrullinated and/or cyclised and multi-antigenic peptides (MAP) of the three extracellular M3R loops to detect specific binding. Results Significant differences (p < 0.05) in optical density (OD) between serum from patients and HV were detected for a cyclised loop 1-derived peptide and the negative control peptide. Furthermore, there were no statistically significant differences between the frequency of positive patients (defined as OD > 2SDs above the mean of the HV) and HV on any of the peptides tested. Conclusions Binding of serum from patients with SS to M3R-derived peptides does not differ from binding to a control peptide in an ELISA and no significant binding to M3R-derived peptides was found in the serum from individual patients compared with HV. These data suggest that peptide-based ELISAs are not sufficiently sensitive and/or specific to detect anti-MR3 autoantibodies. C1 [Roescher, N.] NIDCR, NIH, MPTB, Bethesda, MD 20892 USA. [Roescher, N.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. RP Roescher, N (reprint author), NIDCR, NIH, MPTB, 10 Ctr Dr,Bldg 10,Room 1A21, Bethesda, MD 20892 USA. EM roeschern@mail.nih.gov FU Intramural NIH HHS NR 11 TC 14 Z9 14 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2011 VL 70 IS 1 BP 235 EP 236 DI 10.1136/ard.2010.129049 PG 2 WC Rheumatology SC Rheumatology GA 695OH UT WOS:000285381100041 PM 20498204 ER PT S AU Schultz, ZD Levin, IW AF Schultz, Zachary D. Levin, Ira W. BE Cooks, RG Yeung, ES TI Vibrational Spectroscopy of Biomembranes SO ANNUAL REVIEW OF ANALYTICAL CHEMISTRY, VOL 4 SE Annual Review of Analytical Chemistry LA English DT Article; Book Chapter DE IR; Raman; lipid bilayer; protein ID THERMOTROPIC PHASE-BEHAVIOR; CONFOCAL-RAMAN MICROSCOPY; HYBRID BILAYER-MEMBRANES; REFLECTION-ABSORPTION SPECTROSCOPY; DIFFERENTIAL SCANNING CALORIMETRY; NICOTINIC ACETYLCHOLINE-RECEPTOR; POLARIZED INFRARED-SPECTROSCOPY; HELICAL TRANSMEMBRANE PEPTIDE; SUPPORTED LIPID-BILAYERS; STRATUM-CORNEUM LIPIDS AB Vibrational spectroscopy, commonly associated with IR absorption and Raman scattering, has provided a powerful approach for investigating interactions between biomolecules that make up cellular membranes. Because the IR and Raman signals arise from the intrinsic properties of these molecules, vibrational spectroscopy probes the delicate interactions that regulate biomembranes with minimal perturbation. Numerous innovative measurements, including nonlinear optical processes and confined bilayer assemblies, have provided new insights into membrane behavior. In this review, we highlight the use of vibrational spectroscopy to study lipid-lipid interactions. We also examine recent work in which vibrational measurements have been used to investigate the incorporation of peptides and proteins into lipid bilayers, and we discuss the interactions of small molecules and drugs with membrane structures. Emerging techniques and measurements on intact cellular membranes provide a prospective on the future of vibrational spectroscopic studies of biomembranes. C1 [Schultz, Zachary D.] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. [Levin, Ira W.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Schultz, ZD (reprint author), Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. EM Schultz.41@nd.edu; iwl@helix.nih.gov RI Schultz, Zachary/L-5724-2013 OI Schultz, Zachary/0000-0003-1741-8801 NR 149 TC 30 Z9 31 U1 5 U2 57 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1936-1327 BN 978-0-8243-4404-7 J9 ANNU REV ANAL CHEM JI Annu. Rev. Anal. Chem. PY 2011 VL 4 BP 343 EP 366 DI 10.1146/annurev-anchem-061010-114048 PG 24 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA BVY60 UT WOS:000293148400016 PM 21456972 ER PT S AU Lippincott-Schwartz, J AF Lippincott-Schwartz, Jennifer BE Kornberg, RD Raetz, CRH Rothman, JE Thorner, JW TI Emerging In Vivo Analyses of Cell Function Using Fluorescence Imaging SO ANNUAL REVIEW OF BIOCHEMISTRY, VOL 80 SE Annual Review of Biochemistry LA English DT Review; Book Chapter DE green fluorescent protein; photoactivation; signal transduction; fluorescence resonance energy transfer (FRET); zinc chemistry; nitric oxide sensing ID LIVING CELLS; PROTEIN DYNAMICS; NITRIC-OXIDE; BIOLOGY; ZINC; BIOSENSORS; PATHWAYS; REVEALS; PROBES AB Understanding how cells of all types sense external and internal signals and how these signals are processed to yield particular responses is a major goal of biology. Genetically encoded fluorescent proteins (FPs) and fluorescent sensors are playing an important role in achieving this comprehensive knowledge base of cell function. Providing high sensitivity and immense versatility while being minimally perturbing to a biological specimen, the probes can be used in different microscopy techniques to visualize cellular processes on many spatial scales. Three review articles in this volume discuss recent advances in probe design and applications. These developments help expand the range of biochemical processes in living systems suitable for study. They provide researchers with exciting new tools to explore how cellular processes are organized and their activity regulated in vivo. C1 Eunice Shriver Natl Inst Child Hlth & Human Dev, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), Eunice Shriver Natl Inst Child Hlth & Human Dev, NIH, Bethesda, MD 20892 USA. EM lippincj@mail.nih.gov FU Intramural NIH HHS [ZIA HD008850-03] NR 34 TC 18 Z9 18 U1 0 U2 13 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4154 BN 978-0-8243-0880-3 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem.. PY 2011 VL 80 BP 327 EP 332 DI 10.1146/annurev-biochem-121010-125553 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BVV52 UT WOS:000292895600015 PM 21513458 ER PT S AU Hurley, JH Stenmark, H AF Hurley, James H. Stenmark, Harald BE Rees, DC Dill, KA Williamson, JR TI Molecular Mechanisms of Ubiquitin-Dependent Membrane Traffic SO ANNUAL REVIEW OF BIOPHYSICS, VOL 40 SE Annual Review of Biophysics LA English DT Review; Book Chapter DE lysosome; EGF receptor; ENaC; RING domain; HECT domain; JAMM domain; ubiquitin-binding domain ID EPIDERMAL-GROWTH-FACTOR; EPITHELIAL SODIUM-CHANNEL; 63-LINKED POLYUBIQUITIN CHAINS; MULTIVESICULAR BODY PATHWAY; RECEPTOR DOWN-REGULATION; DOA4 DEUBIQUITINATING ENZYME; ESCRT-III RECOGNITION; CLATHRIN-COATED PITS; STRUCTURAL BASIS; EGF RECEPTOR AB Over the past 14 years, ubiquitination has emerged as a centrally important mechanism governing the subcellular trafficking of proteins. Ubiquitination, interaction with sorting factors that contain ubiquitin-binding domains, and deubiquitination govern the itineraries of cargo proteins that include yeast carboxypeptidase S, the epithelial sodium channel ENaC, and epidermal growth factor receptor. The molecular structures and mechanisms of the paradigmatic HECT and RING domain ubiquitin ligases, of JAMM- and USP-domain-deubiquitinating enzymes, and of numerous ubiquitin-binding domains involved in these pathways have been worked out in recent years and are described. C1 [Hurley, James H.] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Stenmark, Harald] Univ Oslo, Fac Med, Ctr Canc Biomed, N-0310 Oslo, Norway. [Stenmark, Harald] Oslo Univ Hosp, Inst Canc Res, N-0310 Oslo, Norway. RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM hurley@helix.nih.gov; stenmark@ulrik.uio.no FU Intramural NIH HHS [ZIA DK036126-05] NR 128 TC 49 Z9 51 U1 1 U2 18 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1936-122X BN 978-0-8243-1840-6 J9 ANNU REV BIOPHYS JI Annu. Rev. Biophys. PY 2011 VL 40 BP 119 EP 142 DI 10.1146/annurev-biophys-042910-155404 PG 24 WC Biophysics SC Biophysics GA BVP41 UT WOS:000292217600006 PM 21332354 ER PT S AU Kang, CS Drayna, D AF Kang, Changsoo Drayna, Dennis BE Chakravarti, A Green, E TI Genetics of Speech and Language Disorders SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 12 SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE stuttering; dyspraxia; specific language impairment; dyslexia; linkage; lysosomal targeting pathway; FOXP2; mouse vocalization ID DEFICIT HYPERACTIVITY DISORDER; CHROMOSOME 6P INFLUENCES; TAY-SACHS-DISEASE; DEVELOPMENTAL DYSLEXIA; READING-DISABILITY; SUSCEPTIBILITY GENE; ULTRASONIC VOCALIZATION; SIGNIFICANT LINKAGE; LYSOSOMAL-ENZYMES; MAPPING PROVIDES AB Vocal communication mediated by speech and language is a uniquely human trait, and has served an important evolutionary role in the development of our species. Deficits in speech and language functions can be of numerous types, including aphasia, stuttering, articulation disorders, verbal dyspraxia, and specific language impairment; language deficits are also related to dyslexia. Most communication disorders are prominent in children, where they are common. A number of these disorders have been shown to cluster in families, suggesting that genetic factors are involved, but their etiology at the molecular level is not well understood. In the past decade, genetic methods have proven to be powerful for understanding these etiologies. Linkage studies and molecular genetic analyses in a large family containing multiple individuals affected with verbal dyspraxia led to the discovery of mutations in the FOXP2 gene. This gene encodes a forkhead domain transcription factor, a finding that has led researchers to a new avenue of investigation into the substrates and mechanisms that underlie human speech development. In studies of stuttering, linkage and candidate gene approaches in consanguineous families identified mutations in the lysosomal enzyme-targeting pathway genes GNPTAB, GNPTG, and NAGPA, revealing a role for inherited defects in cell metabolism in this disorder. In specific language impairment, linkage studies have identified several loci, and candidate gene association studies are making progress in identifying causal variants at these loci. Although only a small fraction of all cases of speech and language disorders can be explained by genetic findings to date, the significant progress made thus far suggests that genetic approaches will continue to provide important avenues for research on this group of disorders. C1 [Kang, Changsoo; Drayna, Dennis] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. RP Kang, CS (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. EM drayna@nidcd.nih.gov FU Intramural NIH HHS; NIDCD NIH HHS [DC-000046-11] NR 112 TC 25 Z9 27 U1 4 U2 45 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1527-8204 BN 978-0-8243-3712-4 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2011 VL 12 BP 145 EP 164 DI 10.1146/annurev-genom-090810-183119 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA BXD58 UT WOS:000295819900007 PM 21663442 ER PT S AU Ouyang, WJ Rutz, S Crellin, NK Valdez, PA Hymowitz, SG AF Ouyang, Wenjun Rutz, Sascha Crellin, Natasha K. Valdez, Patricia A. Hymowitz, Sarah G. BE Paul, WE Littman, DR Yokoyama, WM TI Regulation and Functions of the IL-10 Family of Cytokines in Inflammation and Disease SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 29 SE Annual Review of Immunology LA English DT Review; Book Chapter DE psoriasis; IBD; infectious diseases; autoimmune diseases; Th17 ID CD4(+) T-CELLS; ARYL-HYDROCARBON RECEPTOR; ROR-GAMMA-T; CHRONIC MUCOCUTANEOUS CANDIDIASIS; CENTRAL-NERVOUS-SYSTEM; PLAQUE-TYPE PSORIASIS; GROWTH-FACTOR-BETA; HEPATITIS-C VIRUS; PROINFLAMMATORY GENE-EXPRESSION; ENTERICA SEROVAR ENTERITIDIS AB The IL-10 family of cytokines consists of nine members: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, and the more distantly related IL-28A, IL-28B, and IL-29. Evolutionarily, IL-10 family cytokines emerged before the adaptive immune response. These cytokines elicit diverse host defense mechanisms, especially from epithelial cells, during various infections. IL-10 family cytokines are essential for maintaining the integrity and homeostasis of tissue epithelial layers. Members of this family can promote innate immune responses from tissue epithelia to limit the damage caused by viral and bacterial infections. These cytokines can also facilitate the tissue-healing process in injuries caused by infection or inflammation. Finally, IL-10 itself can repress proinflammatory responses and limit unnecessary tissue disruptions caused by inflammation. Thus, IL-10 family cytokines have indispensable functions in many infectious and inflammatory diseases. C1 [Ouyang, Wenjun; Rutz, Sascha; Crellin, Natasha K.] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA. [Hymowitz, Sarah G.] Genentech Inc, Dept Biol Struct, San Francisco, CA 94080 USA. [Valdez, Patricia A.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Ouyang, WJ (reprint author), Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA. EM ouyang@gene.com OI Ouyang, Wenjun/0000-0002-1811-5864 NR 316 TC 446 Z9 465 U1 6 U2 85 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3029-3 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2011 VL 29 BP 71 EP 109 DI 10.1146/annurev-immunol-031210-101312 PG 39 WC Immunology SC Immunology GA BUP23 UT WOS:000289959200004 PM 21166540 ER PT S AU Bashirova, AA Thomas, R Carrington, M AF Bashirova, Arman A. Thomas, Rasmi Carrington, Mary BE Paul, WE Littman, DR Yokoyama, WM TI HLA/KIR Restraint of HIV: Surviving the Fittest SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 29 SE Annual Review of Immunology LA English DT Review; Book Chapter DE CTL; escape mutations; NK cells; GWAS; host genetics; viral evolution ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL RESPONSES; HLA CLASS-I; NATURAL-KILLER-CELLS; MHC CLASS-I; EXPOSED UNINFECTED INDIVIDUALS; LONG-TERM NONPROGRESSORS; NK-CELLS; VIRAL LOAD; DISEASE PROGRESSION AB Multiple epidemiological studies have demonstrated associations between the human leukocyte antigen (HLA) loci and human immunodeficiency virus (HIV) disease, and more recently the killer cell immunoglobulin-like (KIR) locus has been implicated in differential responses to the virus. Genome-wide association studies have convincingly shown that the HLA class I locus is the most significant host genetic contributor to the variation in HIV control, underscoring a central role for CD8 T cells in resistance to the virus. However, both genetic and functional data indicate that part of the HLA effect on HIV is due to interactions between KIR and HLA genes, also implicating natural killer cells in defense against viral infection and viral expansion prior to initiation of an adaptive response. We review the HLA and KIR associations with HIV disease and the progress that has been made in understanding the mechanisms that explain these associations. C1 [Bashirova, Arman A.] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02129 USA. Harvard Univ, Boston, MA 02129 USA. NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Bashirova, AA (reprint author), Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02129 USA. EM Arman.Bashirova@nih.gov; thomasrasmi@mail.nih.gov; carringm@mail.nih.gov FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS; NCI NIH HHS [HHSN261200800001E]; PHS HHS [HHSN261200800001E] NR 153 TC 68 Z9 69 U1 0 U2 12 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3029-3 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2011 VL 29 BP 295 EP 317 DI 10.1146/annurev-immunol-031210-101332 PG 23 WC Immunology SC Immunology GA BUP23 UT WOS:000289959200012 PM 21219175 ER PT S AU Germain, RN Meier-Schellersheim, M Nita-Lazar, A Fraser, IDC AF Germain, Ronald N. Meier-Schellersheim, Martin Nita-Lazar, Aleksandra Fraser, Iain D. C. BE Paul, WE Littman, DR Yokoyama, WM TI Systems Biology in Immunology: A Computational Modeling Perspective SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 29 SE Annual Review of Immunology LA English DT Review; Book Chapter DE high-throughput analysis; modeling; genomics; proteomics; RNAi ID PROTEIN-PROTEIN INTERACTIONS; T-CELL-RECEPTORS; INFLUENZA-VIRUS REPLICATION; HOST-PATHOGEN INTERACTIONS; FUNCTIONAL GENOMIC SCREEN; RESONANCE ENERGY-TRANSFER; HYBRID MASS-SPECTROMETER; INNATE IMMUNE-RESPONSES; TRAP-ORBITRAP HYBRID; WIDE RNAI SCREEN AB Systems biology is an emerging discipline that combines high-content, multiplexed measurements with informatic and computational modeling methods to better understand biological function at various scales. Here we present a detailed review of the methods used to create computational models and to conduct simulations of immune function. We provide descriptions of the key data-gathering techniques employed to generate the quantitative and qualitative data required for such modeling and simulation and summarize the progress to date in applying these tools and techniques to questions of immunological interest, including infectious disease. We include comments on what insights modeling can provide that complement information obtained from the more familiar experimental discovery methods used by most investigators and the reasons why quantitative methods are needed to eventually produce a better understanding of immune system operation in health and disease. C1 [Germain, Ronald N.; Meier-Schellersheim, Martin; Nita-Lazar, Aleksandra; Fraser, Iain D. C.] NIAID, Program Syst Immunol & Infect Dis Modeling, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Program Syst Immunol & Infect Dis Modeling, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM rgermain@nih.gov FU Intramural NIH HHS [ZIA AI000974-05, ZIA AI001106-04, ZIA AI001107-04, ZIA AI001108-03] NR 329 TC 75 Z9 75 U1 6 U2 36 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3029-3 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2011 VL 29 BP 527 EP 585 DI 10.1146/annurev-immunol-030409-101317 PG 59 WC Immunology SC Immunology GA BUP23 UT WOS:000289959200019 PM 21219182 ER PT S AU Murphy, BR Whitehead, SS AF Murphy, Brian R. Whitehead, Stephen S. BE Paul, WE Littman, DR Yokoyama, WM TI Immune Response to Dengue Virus and Prospects for a Vaccine SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 29 SE Annual Review of Immunology LA English DT Review; Book Chapter DE DENV; antibody-dependent enhancement; DHF/DSS; immunization ID WEST-NILE-VIRUS; CROSS-REACTIVE ANTIBODIES; NONSTRUCTURAL PROTEIN NS1; TICK-BORNE ENCEPHALITIS; HEALTHY ADULT VOLUNTEERS; BLOOD MONONUCLEAR-CELLS; PRINCIPAL TARGET-CELLS; INFECTION IN-VITRO; HEMORRHAGIC-FEVER; ENVELOPE GLYCOPROTEIN AB Dengue virus (DENV) is a mosquito-borne member of the Flavivirus genus and includes four serotypes (DENV-1, DENV-2, DENV-3, and DENV-4), each of which is capable of causing dengue fever and dengue hemorrhagic fever/dengue shock syndrome. Serious disease can be seen during primary infection but is more frequent following second infection with a serotype different from that of a previous infection. Infection with wild-type DENV induces high-titered neutralizing antibody that can provide long-term immunity to the homotypic virus and can provide short-term immunity (only several months duration) to a heterotypic DENV. The high level of virus replication seen during both secondary infection with a heterotypic virus and during primary DENV infection in late infancy is a direct consequence of antibody-dependent enhancement of replication. This enhanced virus replication is mediated primarily by preexisting, nonneutralizing, or subneutralizing antibodies to the virion surface antigens that enhance access of the virion-antibody complex to Fc gamma R-bearing cells. Vaccines will need to provide long-term protection against each of the four DENV serotypes by inducing neutralizing antibodies, and live, attenuated and various nonliving virus vaccines are in development. C1 [Murphy, Brian R.; Whitehead, Stephen S.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Murphy, BR (reprint author), NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. EM swhitehead@niaid.nih.gov FU Intramural NIH HHS NR 204 TC 180 Z9 187 U1 3 U2 88 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3029-3 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2011 VL 29 BP 587 EP 619 DI 10.1146/annurev-immunol-031210-101315 PG 33 WC Immunology SC Immunology GA BUP23 UT WOS:000289959200020 PM 21219187 ER PT S AU Cannons, JL Tangye, SG Schwartzberg, PL AF Cannons, Jennifer L. Tangye, Stuart G. Schwartzberg, Pamela L. BE Paul, WE Littman, DR Yokoyama, WM TI SLAM Family Receptors and SAP Adaptors in Immunity SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 29 SE Annual Review of Immunology LA English DT Review; Book Chapter DE XLP; cytotoxicity; germinal centers; autoimmunity; innate lymphocytes ID LINKED LYMPHOPROLIFERATIVE-DISEASE; LYMPHOCYTIC ACTIVATION MOLECULE; NATURAL-KILLER-CELLS; GENE-PRODUCT SAP; CD4(+) T-CELLS; HUMAN NK CELLS; HUMAN B-LYMPHOCYTES; COMMON VARIABLE IMMUNODEFICIENCY; THYMOCYTE-THYMOCYTE INTERACTION; PROTEIN-TYROSINE-PHOSPHATASE AB The signaling lymphocyte activation molecule (SLAM)-associated protein, SAP, was first identified as the protein affected in most cases of X-linked lymphoproliferative (XLP) syndrome, a rare genetic disorder characterized by abnormal responses to Epstein-Barr virus infection, lymphoproliferative syndromes, and dysgammaglobulinemia. SAP consists almost entirely of a single SH2 protein domain that interacts with the cytoplasmic tail of SLAM and related receptors, including 2B4, Ly108, CD84, Ly9, and potentially CRACC. SLAM family members are now recognized as important immunomodulatory receptors with roles in cytotoxicity, humoral immunity, autoimmunity, cell survival, lymphocyte development, and cell adhesion. In this review, we cover recent findings on the roles of SLAM family receptors and the SAP family of adaptors, with a focus on their regulation of the pathways involved in the pathogenesis of XLP and other immune disorders. C1 [Cannons, Jennifer L.; Schwartzberg, Pamela L.] NHGRI, NIH, Bethesda, MD 20892 USA. [Tangye, Stuart G.] Garvan Inst Med Res, Program Immunol, Darlinghurst, NSW 2010, Australia. RP Cannons, JL (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM jcannons@mail.nih.gov; s.tangye@garvan.org.au; pams@nhgri.nih.gov RI Tangye, Stuart/H-4023-2014 NR 301 TC 164 Z9 170 U1 4 U2 17 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3029-3 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2011 VL 29 BP 665 EP 705 DI 10.1146/annurev-immunol-030409-101302 PG 41 WC Immunology SC Immunology GA BUP23 UT WOS:000289959200022 PM 21219180 ER PT S AU Omsland, A Heinzen, RA AF Omsland, Anders Heinzen, Robert A. BE Gottesman, S Harwood, CS TI Life on the Outside: The Rescue of Coxiella burnetii from Its Host Cell SO ANNUAL REVIEW OF MICROBIOLOGY, VOL 65 SE Annual Review of Microbiology LA English DT Review; Book Chapter DE metabolism; lysosome; axenic; obligate intracellular bacterium; acidophile ID Q-FEVER; MYCOBACTERIUM-TUBERCULOSIS; PHASE-I; CHOLESTEROL-METABOLISM; LEGIONELLA-PNEUMOPHILA; CHLAMYDIA-TRACHOMATIS; BORDETELLA-PERTUSSIS; PHOSPHATASE-ACTIVITY; LYSOSOMAL RESPONSE; ESCHERICHIA-COLI AB For over seven decades, Coxiella burnetii, the causative agent of human Q fever, has been considered a prototypical obligate intracellular bacterium that relies exclusively on a eukaryotic cell for growth. Intracellularly, the organism prospers in an acidified, phagolysosome-like vacuole. C. burnetii has evolved to replicate in this harsh compartment by a mechanism involving acid activation of metabolism. The similar to 2Mb genome of C. burnetii is about twice the size of genomes of most obligate intracellular bacteria, and the organism's central metabolic pathways are largely intact. The absence of extensive genome reduction suggests the adaptation of C. burnetii to an obligate intracellular lifestyle is a recent evolutionary event. Indeed, insight from early work on C. burnetii metabolism, along with new information gained from metabolic pathway reconstructions, nutrient typing, and expression profiling, allowed the rescue of C. burnetii from its host cell to regain the axenic growth capacity of its ancestors. This advance removes the extensive experimental obstacles associated with intracellular obligatism and opens the door for a renaissance in C. burnetii research. C1 [Omsland, Anders; Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Omsland, A (reprint author), NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov FU Intramural NIH HHS NR 97 TC 21 Z9 21 U1 0 U2 7 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4227 BN 978-0-8243-1165-0 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2011 VL 65 BP 111 EP 128 DI 10.1146/annurev-micro-090110-102927 PG 18 WC Microbiology SC Microbiology GA BYN77 UT WOS:000299463800008 PM 21639786 ER PT S AU Battesti, A Majdalani, N Gottesman, S AF Battesti, Aurelia Majdalani, Nadim Gottesman, Susan BE Gottesman, S Harwood, CS TI The RpoS-Mediated General Stress Response in Escherichia coli SO ANNUAL REVIEW OF MICROBIOLOGY, VOL 65 SE Annual Review of Microbiology LA English DT Review; Book Chapter DE Hfq; (p)ppGpp; RssB; sRNA; ClpXP ID SIGMA-FACTOR RPOS; PROTEIN H-NS; RNA-POLYMERASE HOLOENZYME; HIS-ASP PHOSPHORELAY; DNA-BINDING PROTEIN; STATIONARY-PHASE; SALMONELLA-TYPHIMURIUM; SIGNAL-TRANSDUCTION; RCS PHOSPHORELAY; REGULATOR RSSB AB Under conditions of nutrient deprivation or stress, or as cells enter stationary phase, Escherichia coli and related bacteria increase the accumulation of RpoS, a specialized sigma factor. RpoS-dependent gene expression leads to general stress resistance of cells. During rapid growth, RpoS translation is inhibited and any RpoS protein that is synthesized is rapidly degraded. The complex transition from exponential growth to stationary phase has been partially dissected by analyzing the induction of RpoS after specific stress treatments. Different stress conditions lead to induction of specific sRNAs that stimulate RpoS translation or to induction of small-protein antiadaptors that stabilize the protein. Recent progress has led to a better, but still far from complete, understanding of how stresses lead to RpoS induction and what RpoS-dependent genes help the cell deal with the stress. C1 [Battesti, Aurelia; Majdalani, Nadim; Gottesman, Susan] NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Battesti, A (reprint author), NCI, Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. EM battestia@mail.nih.gov; nadim@helix.nih.gov; susang@helix.nih.gov FU Intramural NIH HHS NR 168 TC 229 Z9 233 U1 6 U2 106 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4227 BN 978-0-8243-1165-0 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2011 VL 65 BP 189 EP 213 DI 10.1146/annurev-micro-090110-102946 PG 25 WC Microbiology SC Microbiology GA BYN77 UT WOS:000299463800012 PM 21639793 ER PT S AU Gerfen, CR Surmeier, DJ AF Gerfen, Charles R. Surmeier, D. James BE Hyman, SE Jessell, TM Shatz, CJ Stevens, CF Zoghbi, HY TI Modulation of Striatal Projection Systems by Dopamine SO ANNUAL REVIEW OF NEUROSCIENCE, VOL 34 SE Annual Review of Neuroscience LA English DT Review; Book Chapter DE basal ganglia; synaptic plasticity; movement disorders; Parkinson's disease; motor learning ID MEDIUM SPINY NEURONS; FAST-SPIKING INTERNEURONS; LONG-TERM POTENTIATION; NEOSTRIATAL CHOLINERGIC INTERNEURONS; PARVALBUMIN-IMMUNOREACTIVE NEURONS; ACTIVITY-DEPENDENT PLASTICITY; BASAL GANGLIA CIRCUITRY; D-ASPARTATE RESPONSES; PROTEIN-KINASE-C; SYNAPTIC-TRANSMISSION AB The basal ganglia are a chain of subcortical nuclei that facilitate action selection. Two striatal projection systems-so-called direct and indirect pathways-form the functional backbone of the basal ganglia circuit. Twenty years ago, investigators proposed that the striatum's ability to use dopamine (DA) rise and fall to control action selection was due to the segregation of D(1) and D(2) DA receptors in direct- and indirect-pathway spiny projection neurons. Although this hypothesis sparked a debate, the evidence that has accumulated since then clearly supports this model. Recent advances in the means of marking neural circuits with optical or molecular reporters have revealed a clear-cut dichotomy between these two cell types at the molecular, anatomical, and physiological levels. The contrast provided by these studies has provided new insights into how the striatum responds to fluctuations in DA signaling and how diseases that alter this signaling change striatal function. C1 [Gerfen, Charles R.] NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. [Surmeier, D. James] Northwestern Univ, Feinberg Sch Med, Dept Physiol, Chicago, IL 60611 USA. RP Gerfen, CR (reprint author), NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. EM gerfenc@mail.nih.gov; j-surmeier@northwestern.edu FU Intramural NIH HHS [ZIA MH002497-22] NR 176 TC 390 Z9 397 U1 13 U2 83 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0147-006X BN 978-0-8243-2434-6 J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2011 VL 34 BP 441 EP 466 DI 10.1146/annurev-neuro-061010-113641 PG 26 WC Neurosciences SC Neurosciences & Neurology GA BWE70 UT WOS:000293772100019 PM 21469956 ER PT S AU Brannon, PM Picciano, MF AF Brannon, Patsy M. Picciano, Mary Frances BE Cousins, RJ Bier, DM Bowman, BA TI Vitamin D in Pregnancy and Lactation in Humans SO ANNUAL REVIEW OF NUTRITION, VOL 31 SE Annual Review of Nutrition LA English DT Review; Book Chapter DE 25-hydroxyvitamin D; bone health; Dietary Reference Intake; nutritional status; developmental programming; adverse outcomes ID BREAST-FED INFANTS; D-BINDING PROTEIN; GROWTH-FACTOR-I; 25-HYDROXYVITAMIN D CONCENTRATION; CALCIUM-REGULATING HORMONES; BONE TURNOVER MARKERS; FAT-SOLUBLE VITAMINS; OFFSPRING BIRTH SIZE; D DEFICIENCY; D SUPPLEMENTATION AB Concerns exist about the adequacy of vitamin D in pregnant and lactating women. This review assesses the evidence that maternal vitamin D status influences maternal, fetal, and breast-fed infant bone health; maternal adverse outcomes (preeclampsia, gestational diabetes, obstructed labor, and infectious disease); fetal adverse outcomes (growth, gestational age, and developmental programming); and infant adverse outcomes. The evidence for all of these outcomes is contradictory (except for maternal infectious disease) and lacking causality; thus, it is inconclusive. The 2011 Dietary Reference Intakes for vitamin D and their implications for assessing vitamin D status are discussed. An estimated 5% to 29% of American pregnant women may have inadequate vitamin D status, with the higher prevalence in African Americans. Little is known about the prevalence of inadequacy in American lactating women. Research needs are also identified, especially the need for rigorous and well-designed randomized clinical trials to determine the role of vitamin D in nonbone health outcomes in pregnancy and lactation. C1 [Brannon, Patsy M.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. [Picciano, Mary Frances] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Brannon, PM (reprint author), Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. EM pmb22@cornell.edu NR 144 TC 72 Z9 73 U1 2 U2 24 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0199-9885 BN 978-0-8243-2831-3 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 2011 VL 31 BP 89 EP 115 DI 10.1146/annurev.nutr.012809.104807 PG 27 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BWR85 UT WOS:000294692100006 PM 21756132 ER PT S AU Moir, S Chun, TW Fauci, AS AF Moir, Susan Chun, Tae-Wook Fauci, Anthony S. BE Abbas, AK Galli, SJ Howley, PM TI Pathogenic Mechanisms of HIV Disease SO ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 6 SE Annual Review of Pathology-Mechanisms of Disease LA English DT Review; Book Chapter DE persistent infection; immune activation; immune dysfunction; AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; ACTIVE ANTIRETROVIRAL THERAPY; CHRONIC VIRAL-INFECTION; PNEUMOCYSTIS-CARINII PNEUMONIA; TYPE-1 INFECTION; IMMUNE RECONSTITUTION; GASTROINTESTINAL-TRACT; LYMPHOID-TISSUE; RHESUS MACAQUES AB Human immunodeficiency virus (HIV) infection is generally characterized by inefficient viral transmission; an acute phase of intense viral replication and dissemination to lymphoid tissues; a chronic, often asymptomatic phase of sustained immune activation and viral replication; and an advanced phase of marked depletion of CD4(+) T cells that leads to acquired immune deficiency syndrome. Major insight into HIV transmission and each phase of infection has been gained from studies on blood and tissue specimens obtained from HIV-infected individuals, as well as from animal and ex vivo models. Not only has the introduction of effective antiretroviral therapy greatly diminished the morbidity and mortality associated with HIV disease progression, it has also provided new avenues of research toward delineating the mechanisms of HIV-induced pathogenesis. Further advances in therapeutics and informative technologies, combined with a better understanding of the immunologic and virologic components of HIV disease, hold promise for new preventative and even curative strategies. C1 [Moir, Susan; Chun, Tae-Wook; Fauci, Anthony S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Moir, S (reprint author), NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. EM smoir@niaid.nih.gov; twchun@nih.gov; afauci@niaid.nih.gov FU Intramural NIH HHS NR 150 TC 103 Z9 110 U1 3 U2 54 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1553-4006 BN 978-0-8243-4306-4 J9 ANNU REV PATHOL-MECH JI Annu. Rev. Pathol.-Mech Dis. PY 2011 VL 6 BP 223 EP 248 DI 10.1146/annurev-pathol-011110-130254 PG 26 WC Pathology SC Pathology GA BUD40 UT WOS:000288922800010 PM 21034222 ER PT S AU Allen, JA Roth, BL AF Allen, John A. Roth, Bryan L. BE Cho, AK TI Strategies to Discover Unexpected Targets for Drugs Active at G Protein-Coupled Receptors SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 51, 2011 SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE high-throughput screening; polypharmacology; receptorome; valvulopathy; drug side effects; similarity ensemble approach ID KAPPA-OPIOID-RECEPTOR; VALVULAR HEART-DISEASE; ATYPICAL ANTIPSYCHOTIC-DRUGS; SALVINORIN-A; FUNCTIONAL SELECTIVITY; SEROTONIN RECEPTORS; CRYSTAL-STRUCTURE; BETA-ARRESTIN; DOUBLE-BLIND; PHARMACOLOGICAL CHARACTERIZATION AB G protein-coupled receptors (GPCRs) are an evolutionarily conserved family of signaling molecules comprising approximately 2% of the human genome; this receptor family remains a central focus in basic pharmacology studies and drug discovery efforts. Detailed studies of drug action at GPCRs over the past decade have revealed existing and novel ligands that exhibit polypharmacology-that is, drugs with activity at more than one receptor target for which they were designed. These "off-target" drug actions can be a liability that causes adverse side effects; however, in several cases, drugs with less selectivity demonstrate better clinical efficacy. Here we review physical screening and cheminformatic approaches that define drug activity at the GPCR receptorome. In many cases, such profiling has revealed unexpected targets that explain therapeutic actions as well as off-targets underlying drug side effects. Such drug-receptor profiling has also provided new insights into mechanisms of action of existing drugs and has suggested directions for future drug development. C1 [Allen, John A.; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Sch Pharm, Dept Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. [Allen, John A.; Roth, Bryan L.] Univ N Carolina, Sch Pharm, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Sch Pharm, Dept Psychiat, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Sch Pharm, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Sch Med, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA. RP Allen, JA (reprint author), Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. EM bryan_roth@med.unc.edu RI Roth, Bryan/F-3928-2010; Allen, John/D-6141-2011 FU NICHD NIH HHS [T32HD040127-07]; NIDA NIH HHS [R01 DA027170, R01 DA017204, R01DA017204]; NIMH NIH HHS [R01 MH061887, R01MH61887, U19 MH082441, U19MH82441]; PHS HHS [HHSN-271-2008-00025-C] NR 139 TC 92 Z9 93 U1 5 U2 34 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0362-1642 BN 978-0-8243-0451-5 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2011 VL 51 BP 117 EP 144 DI 10.1146/annurev-pharmtox-010510-100553 PG 28 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BTS31 UT WOS:000287956600006 PM 20868273 ER PT S AU Tycko, R AF Tycko, Robert BE Leone, SR Cremer, PS Groves, JT Johnson, MA TI Solid-State NMR Studies of Amyloid Fibril Structure SO ANNUAL REVIEW OF PHYSICAL CHEMISTRY, VOL 62 SE Annual Review of Physical Chemistry LA English DT Review; Book Chapter DE Alzheimer's disease; protein structure; prion; nuclear magnetic resonance ID NUCLEAR-MAGNETIC-RESONANCE; HUMAN PRION PROTEIN; BETA-SHEET STRUCTURE; ALPHA-SYNUCLEIN FIBRILS; HET-S PRION; TRANSMISSION ELECTRON-MICROSCOPY; ALZHEIMERS-DISEASE BRAIN; MOLECULAR-LEVEL; SACCHAROMYCES-CEREVISIAE; SECONDARY-STRUCTURE AB Current interest in amyloid fibrils stems from their involvement in neurodegenerative and other diseases and from their role as an alternative structural state for many peptides and proteins. Solid-state nuclear magnetic resonance (NMR) methods have the unique capability of providing detailed structural constraints for amyloid fibrils, sufficient for the development of full molecular models. In this article, recent progress in the application of solid-state NMR to fibrils associated with Alzheimer's disease, prion fibrils, and related systems is reviewed, along with relevant developments in solid-state NMR techniques and technology. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov FU Intramural NIH HHS NR 115 TC 240 Z9 244 U1 4 U2 127 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-426X BN 978-0-8243-1062-2 J9 ANNU REV PHYS CHEM JI Annu. Rev. Phys. Chem. PY 2011 VL 62 BP 279 EP 299 DI 10.1146/annurev-physchem-032210-103539 PG 21 WC Chemistry, Physical SC Chemistry GA BUX68 UT WOS:000290636800014 PM 21219138 ER PT J AU Wycoff, KL Belle, A Deppe, D Schaefer, L Maclean, JM Haase, S Trilling, AK Liu, SH Leppla, SH Geren, IN Pawlik, J Peterson, JW AF Wycoff, Keith L. Belle, Archana Deppe, Dorothee Schaefer, Leah Maclean, James M. Haase, Simone Trilling, Anke K. Liu, Shihui Leppla, Stephen H. Geren, Isin N. Pawlik, Jennifer Peterson, Johnny W. TI Recombinant Anthrax Toxin Receptor-Fc Fusion Proteins Produced in Plants Protect Rabbits against Inhalational Anthrax SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CAPILLARY MORPHOGENESIS PROTEIN-2; MONOCLONAL-ANTIBODY; CELLULAR RECEPTOR; LETHAL FACTOR; IGG-FC; ANTIGEN; VACCINE; MODEL; AGROBACTERIUM; SPECIFICITY AB Inhalational anthrax, a zoonotic disease caused by the inhalation of Bacillus anthracis spores, has a similar to 50% fatality rate even when treated with antibiotics. Pathogenesis is dependent on the activity of two toxic noncovalent complexes: edema toxin (EdTx) and lethal toxin (LeTx). Protective antigen (PA), an essential component of both complexes, binds with high affinity to the major receptor mediating the lethality of anthrax toxin in vivo, capillary morphogenesis protein 2 (CMG2). Certain antibodies against PA have been shown to protect against anthrax in vivo. As an alternative to anti-PA antibodies, we produced a fusion of the extracellular domain of human CMG2 and human IgG Fc, using both transient and stable tobacco plant expression systems. Optimized expression led to the CMG2-Fc fusion protein being produced at high levels: 730 mg/kg fresh leaf weight in Nicotiana benthamiana and 65 mg/kg in N. tabacum. CMG2-Fc, purified from tobacco plants, fully protected rabbits against a lethal challenge with B. anthracis spores at a dose of 2 mg/kg body weight administered at the time of challenge. Treatment with CMG2-Fc did not interfere with the development of the animals' own immunity to anthrax, as treated animals that survived an initial challenge also survived a rechallenge 30 days later. The glycosylation of the Fc (or lack thereof) had no significant effect on the protective potency of CMG2-Fc in rabbits or on its serum half-life, which was about 5 days. Significantly, CMG2-Fc effectively neutralized, in vitro, LeTx-containing mutant forms of PA that were not neutralized by anti-PA monoclonal antibodies. C1 [Wycoff, Keith L.; Belle, Archana; Deppe, Dorothee; Schaefer, Leah; Maclean, James M.; Haase, Simone; Trilling, Anke K.] Planet Biotechnol Inc, Hayward, CA 94545 USA. [Pawlik, Jennifer; Peterson, Johnny W.] Univ Texas Med Branch, Galveston, TX USA. [Liu, Shihui; Leppla, Stephen H.] NIAID, Bacterial Toxins & Therapeut Sect, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA. [Geren, Isin N.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Anesthesia & Pharmaceut Chem, San Francisco, CA USA. RP Wycoff, KL (reprint author), Planet Biotechnol Inc, 25571 Clawiter Rd, Hayward, CA 94545 USA. EM kwycoff@planetbiotechnology.com FU Public Health Service [R43AI053005]; National Institute of Allergy and Infectious Diseases [U01AI082161] FX This work was supported by Public Health Service grants R43AI053005 and U01AI082161 from the National Institute of Allergy and Infectious Diseases. NR 49 TC 17 Z9 17 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2011 VL 55 IS 1 BP 132 EP 139 DI 10.1128/AAC.00592-10 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 698FB UT WOS:000285577400016 PM 20956592 ER PT J AU Mahanty, S Paredes, A Marzal, M Gonzalez, E Rodriguez, S Dorny, P Guerra-Giraldez, C Garcia, HH Nash, T AF Mahanty, S. Paredes, A. Marzal, M. Gonzalez, E. Rodriguez, S. Dorny, P. Guerra-Giraldez, C. Garcia, H. H. Nash, T. TI Sensitive In Vitro System To Assess Morphological and Biochemical Effects of Praziquantel and Albendazole on Taenia solium Cysts SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ECHINOCOCCUS-MULTILOCULARIS METACESTODES; COMBINATION THERAPY; CRASSICEPS CYSTS; GRANULOSUS; NEUROCYSTICERCOSIS; SULFOXIDE; INVITRO; CYSTICERCOSIS; VIVO; PROTOSCOLECES AB Neurocysticercosis resulting from Taenia solium infections is a major cause of adult-acquired seizures worldwide. Disease is caused by larval cysts, and treatment consists of the anthelmintic drugs albendazole or praziquantel. There are no standard methods to assess drug activity to T. solium cysts in vitro. Morphological, functional, and biochemical changes that might reflect damaging (inhibiting, cytotoxic) drug effects were analyzed after exposure of cysts to albendazole sulfoxide (ABZ-SO), the major active metabolite of the drug in vivo, praziquantel (PZQ), or combinations of both. PZQ exposure led to a decrease in cyst size and inhibition of evagination, whereas ABZ-SO exposure resulted in minimal changes. Alkaline phosphatase (AP) is normally secreted by cysts, and both drugs inhibited AP secretion at concentrations of 5 and 50 ng/ml for PZQ and ABZ-SO, respectively. Some combinations of both drugs resulted in additive and/or synergistic activities. Parasite-specific antigen, detected in the cerebrospinal fluid and blood of infected patients, is also normally secreted by T. solium cysts. Antigen secretion was similarly inhibited by ABZ-SO and PZQ and a combination of both drugs, suggesting that inhibition of secretion is a common downstream consequence of the activities of both drugs. These studies establish quantitative methods to measure in vitro anthelmintic activity and suggest combination therapy with ABZ-SO and PZQ may have clinical benefit. C1 [Mahanty, S.; Nash, T.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Paredes, A.; Marzal, M.; Rodriguez, S.; Guerra-Giraldez, C.; Garcia, H. H.] Univ Peruana Cayetano Heredia, Sch Sci, Lab Expt Immunopathol, Lima, Peru. [Gonzalez, E.] Univ Nacl Mayor San Marcos, Fac Vet Sci, Lima 14, Peru. [Dorny, P.] Inst Trop Med, B-2000 Antwerp, Belgium. RP Mahanty, S (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr, Bethesda, MD 20892 USA. EM smahanty@niaid.nih.gov OI Guerra-Giraldez, Cristina/0000-0002-9287-9838; Mahanty, Siddhartha/0000-0003-1068-0524 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This research was supported (in part) by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 33 TC 13 Z9 13 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2011 VL 55 IS 1 BP 211 EP 217 DI 10.1128/AAC.00761-10 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 698FB UT WOS:000285577400026 PM 21041508 ER PT J AU Simmons, HA Mattison, JA AF Simmons, Heather A. Mattison, Julie A. TI The Incidence of Spontaneous Neoplasia in Two Populations of Captive Rhesus Macaques (Macaca mulatta) SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID AMPULLARY CARCINOMA; MONKEYS; CANCER; ADENOCARCINOMA; PREDICTORS; TUMORS; VATER AB Rhesus macaques (Macaca mulatta) are genetically similar to humans and share many characteristics of aging and age-related diseases. They age at approximately three times the rate of humans and develop spontaneous cancers. In both humans and rhesus macaques, cancer incidence increases with age with the greatest incidence in those over 60 years of age and 20 years, respectively. The current survey reports on the incidence of spontaneous neoplasia in two colonies of captive rhesus macaques: the Wisconsin National Primate Research Center colony with 28 years of records and a National Institute on Aging colony with 21 years of records. When categorized by organ and histologic diagnosis, the average age at diagnosis was greater than 20 years for all categories except oral squamous cell carcinoma. Neoplasms of the gastrointestinal system were the most commonly diagnosed, accounting for 48.8% of the cases. Adenocarcinomas of the large intestine were the most prevalent tumor identified. Although there are differences in the biological behavior of cancer in the rhesus macaque when compared with humans, they are a valuable model of comparative oncology. Antioxid. Redox Signal. 14, 221-227. C1 [Simmons, Heather A.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA. [Mattison, Julie A.] NIA, Lab Expt Gerontol, NIH, Poolesville, MD USA. RP Simmons, HA (reprint author), Univ Wisconsin, Wisconsin Natl Primate Res Ctr, 1220 Capitol Court, Madison, WI 53715 USA. EM hsimmons@primate.wisc.edu FU NIH [RR000167]; NIH, NIA FX This work was supported by the NIH grant RR000167 and in part by the Intramural Research Program of the NIH, NIA. We thank the animal care and veterinary staff at both sites for their care of the primates. Additionally, thanks to the individuals who have worked in the WNPRC Pathology unit over the past 28 years. Additional thanks to Jennifer Young for editorial assistance and Dan Longo for his suggestions. NIA is grateful for the contributions of their primary pathologist Dr. Mark Bryant. NR 19 TC 28 Z9 29 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JAN PY 2011 VL 14 IS 2 BP 221 EP 227 DI 10.1089/ars.2010.3311 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 695RR UT WOS:000285390800005 PM 20524847 ER PT J AU Boyd, SD Maldarelli, F Sereti, I Ouedraogo, GL Rehm, CA Boltz, V Shoemaker, D Pau, AK AF Boyd, Sarita D. Maldarelli, Frank Sereti, Irini Ouedraogo, G. Laissa Rehm, Catherine A. Boltz, Valerie Shoemaker, Diana Pau, Alice K. TI Transmitted raltegravir resistance in an HIV-1 CRF_AG-infected patient SO ANTIVIRAL THERAPY LA English DT Article ID ANTIRETROVIRAL DRUG-RESISTANCE; REVERSE-TRANSCRIPTASE; INTEGRASE INHIBITORS; MUTATIONS; NAIVE; THERAPY; SUSCEPTIBILITY; INDIVIDUALS; PREVALENCE; CITIES AB Here, we describe an HIV-infected patient with pretreatment resistance to raltegravir, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors, and the ultimate ability to achieve viral suppression. Pretreatment integrase resistance testing is not routinely performed because transmitted integrase mutations conferring resistance to raltegravir are currently thought to be negligible. We suggest obtaining a pretreatment integrase genotype in patients with transmitted multiclass drug resistance in order to create an optimal first regimen and increase the chance for virological suppression. C1 [Boyd, Sarita D.; Sereti, Irini; Ouedraogo, G. Laissa; Rehm, Catherine A.; Shoemaker, Diana; Pau, Alice K.] NIAID, NIH, Bethesda, MD 20892 USA. [Boyd, Sarita D.; Ouedraogo, G. Laissa] SAIC Frederick Inc, Frederick, MD USA. [Maldarelli, Frank; Boltz, Valerie] NCI, HIV Drug Resistance Program, NIH, Bethesda, MD 20892 USA. RP Boyd, SD (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM sarita.boyd@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This work was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. It is also funded, in part, with federal funds from the National Cancer Institute, National Institutes of Health, 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 United States Government. NR 22 TC 29 Z9 31 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2011 VL 16 IS 2 BP 257 EP 261 DI 10.3851/IMP1749 PG 5 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 813NZ UT WOS:000294375500017 PM 21447876 ER PT J AU Pilotto, JH Velasque, LS Friedman, RK Moreira, RI Veloso, VG Grinsztejn, B Morgado, MG Watts, DH Currier, JS Hoffman, RM AF Pilotto, Jose H. Velasque, Luciane S. Friedman, Ruth K. Moreira, Ronaldo I. Veloso, Valdilea G. Grinsztejn, Beatriz Morgado, Mariza G. Watts, D. Heather Currier, Judith S. Hoffman, Risa M. TI Maternal outcomes after HAART for the prevention of mother-to-child transmission in HIV-infected women in Brazil SO ANTIVIRAL THERAPY LA English DT Article ID ANTIRETROVIRAL THERAPY; VIRAL LOAD; HIV-1-INFECTED WOMEN; RANDOMIZED-TRIAL; CELL COUNTS; PREGNANCY; POSTPARTUM; PROGRESSION; MORTALITY; INTERRUPTION AB Background: Information is lacking on outcomes in HIV-infected Brazilian women with CD4(+) T-cell counts >200 cells/mm(3) who initiate HAART for the prevention of mother-to-child transmission, and discontinue after delivery. Methods: Clinical event rates after postpartum HAART discontinuation were calculated for all WHO stage 2-3 events, as well as for HIV progression warranting HAART re-initiation, defined by a WHO stage 4 event and/or CD4(+) T-cell decrease to <= 200 cells/mm(3). Predictors of the WHO stage 2-3 events and HIV progression outcomes were evaluated with Cox's proportional hazards models. Results: A total of 120 women were followed for a mean of 1.5 years after delivery. Overall, 26 women had 30 events as follows: 20 developed WHO stage 2-3 events, yielding an incidence rate of 13/100 person-years (PY; 95% CI 8-20); 10 developed HIV progression requiring HAART re-initiation (incidence ratio 6/100 PY, 95% CI 3-11). Among progressors, a single woman developed a WHO stage 4 clinical event and the remainder had CD4(+) T-cell decreases. Women who had baseline CD4(+) T-cell counts between 200-500 cells/mm(3) had a hazard ratio for WHO stage 2-3 events of 2.5 compared to women with baseline >= 500 cells/mm(3) (95% CI 1.0-6.3; P=0.05). The only significant predictor of HIV progression was baseline CD4(+) T-cell count (hazard ratio 0.99, 95% CI 0.98-0.99; P=0.02). Conclusions: In this observational study, a baseline CD4(+) T-cell count <500 cells/mm(3) was associated with an increased risk of postpartum WHO stage 2-3 clinical events and HIV disease progression. Randomized studies are needed to further evaluate the effect of postpartum treatment discontinuation on maternal health. C1 [Currier, Judith S.; Hoffman, Risa M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, Los Angeles, CA 90095 USA. [Currier, Judith S.; Hoffman, Risa M.] Univ Calif Los Angeles, Ctr Clin AIDS Res & Educ, Los Angeles, CA 90095 USA. [Pilotto, Jose H.; Velasque, Luciane S.; Friedman, Ruth K.; Moreira, Ronaldo I.; Veloso, Valdilea G.; Grinsztejn, Beatriz] Fundacao Oswaldo Cruz, Inst Pesquisa Clin Evandro Chagas IPEC, Rio De Janeiro, Brazil. [Pilotto, Jose H.] Hosp Geral Nova Iguacu HGNI, HIV Family Care Clin HHFCC, Rio De Janeiro, Brazil. [Pilotto, Jose H.; Morgado, Mariza G.] Fiocruz MS, Inst Oswaldo Cruz, AIDS & Mol Immunol Lab, BR-21045900 Rio De Janeiro, Brazil. [Velasque, Luciane S.] Univ Fed Estado Rio de Janeiro UNIRIO, Dept Math & Stat, Rio De Janeiro, Brazil. [Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, NICHD, NIH, Bethesda, MD USA. RP Hoffman, RM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, Los Angeles, CA 90095 USA. EM rhoffman@mednet.ucla.edu FU Ministry of Health [CSV 086/06]; Merck and Company; Tibotec Therapeutics; Schering-Plough FX Support was provided by the HIV/AIDS Brazilian National AIDS Program, Ministry of Health (Grant CSV 086/06). We gratefully acknowledge the clinical staff of the Hospital Geral de Nova Iguacu, Rio de Janeiro, for following-up the cohort of pregnant women, as well as the laboratory team of the AIDS and Molecular Immunology Laboratory/Instituto Oswaldo Cruz/FIOCRUZ, Rio de Janeiro, for their technical support in processing and analysing the blood samples.; JC has received research grant support to UCLA for clinical trials from Merck and Company, Tibotec Therapeutics and Schering-Plough in the past 48 months. In addition, she is involved in clinical trials in which drugs have been donated to NIH from Tibotec, Merck, Gilead, Abbott, GlaxoSmithKline and Bristol-Myers Squibb. All other authors declare no competing interests. NR 23 TC 5 Z9 5 U1 0 U2 4 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2011 VL 16 IS 3 BP 349 EP 356 DI 10.3851/IMP1779 PG 8 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 813OA UT WOS:000294375600008 PM 21555817 ER PT J AU Stabinski, L Reynolds, SJ Ocama, P Laeyendecker, O Ndyanabo, A Kiggundu, V Boaz, I Gray, RH Wawer, M Thio, C Thomas, DL Quinn, TC Kirk, GD AF Stabinski, Lara Reynolds, Steven J. Ocama, Ponsiano Laeyendecker, Oliver Ndyanabo, Anthony Kiggundu, Valerian Boaz, Iga Gray, Ron H. Wawer, Maria Thio, Chloe Thomas, David L. Quinn, Thomas C. Kirk, Gregory D. CA Rakai Hlth Sci Program TI High prevalence of liver fibrosis associated with HIV infection: a study in rural Rakai, Uganda SO ANTIVIRAL THERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-B-VIRUS; TRANSIENT ELASTOGRAPHY; ANTIRETROVIRAL THERAPY; COINFECTED PATIENTS; VIRAL-HEPATITIS; CIRRHOSIS; DISEASE; IMPACT; COHORT AB Background: Liver disease is a leading cause of mortality among HIV-infected persons in the United States and Europe. However, data regarding the effects of HIV and antiretroviral therapy (ART) on liver disease in Africa are sparse. Methods: A total of 500 HIV-infected participants in an HIV care programme in rural Rakai, Uganda were frequency-matched by age, gender and site to 500 HIV-uninfected participants in a population cohort. All participants underwent transient elastography (FibroScan (R)) to quantify liver stiffness measurements (LSM) and identify participants with significant liver fibrosis, defined as LSM >= 9.3 kPa (approximate to Metavir F >= 2). Risk factors for liver fibrosis were identified by estimating adjusted prevalence risk ratios (adjPRR) and 95% CI using modified Poisson multivariate regression. Results: The prevalence of hepatitis B coinfection in the study population was 5%. The prevalence of significant fibrosis was 17% among HIV-infected and 11% in HIV-uninfected participants (P=0.008). HIV infection was associated with a 50% increase in liver fibrosis (adjPRR 1.5, 95% CI 1.1-2.1; P=0.010). Fibrosis was also associated with male gender (adjPRR 1.4, 95% CI 1.0-1.9; P=0.045), herbal medicine use (adjPRR 2.0, 95% CI 1.2-3.3; P=0.005), heavy alcohol consumption (adjPRR 2.3, 95% CI 1.3-3.9; P=0.005), occupational fishing (adjPRR 2.5, 95% CI 1.2-5.3; P=0.019) and chronic HBV infection (adjPRR 1.7, 95% CI 1.0-3.1; P=0.058). Among HIV-infected participants, ART reduced fibrosis risk (adjPRR 0.6, 95% CI 0.4-1.0; P=0.030). Conclusions: The burden of liver fibrosis among HIV-infected rural Ugandans is high. These data suggest that liver disease may represent a significant cause of HIV-related morbidity and mortality in Africa. C1 [Stabinski, Lara; Reynolds, Steven J.; Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Reynolds, Steven J.; Thio, Chloe; Thomas, David L.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Ocama, Ponsiano] Makerere Univ, Dept Med, Kampala, Uganda. [Ndyanabo, Anthony; Kiggundu, Valerian; Boaz, Iga; Gray, Ron H.; Wawer, Maria] Rakai Hlth Sci Program, Entebbe, Uganda. [Gray, Ron H.; Wawer, Maria] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD USA. [Kirk, Gregory D.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Stabinski, L (reprint author), NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM stabinskil@niaid.nih.gov RI Laeyendecker, Oliver/B-9331-2009; OI Laeyendecker, Oliver/0000-0002-6429-4760 FU NIH; Division of Intramural Research, National Institutes of Allergy and Infectious Diseases National Institutes of Health; National Institute on Drug Abuse [R01-AI-16078]; American Cancer Society [MRSG-07-284-01-CCE]; President's Emergency Fund for AIDS Relief (PEPFAR); Department of the Army, United States Army Medical Research and Material Command [DAMD17-98-2-8007]; National Institute of Allergy and Infectious Diseases [R01 A134826, R01 A134265]; National Institute of Child and Health Development [5P30HD06826] FX The study was primarily funded by the NIH Bench to Bedside Program. Additional support was provided by the Division of Intramural Research, National Institutes of Allergy and Infectious Diseases National Institutes of Health. Additional support was also provided by the National Institute on Drug Abuse (PI: DLT, R01-AI-16078) and the American Cancer Society (PI: GDK, MRSG-07-284-01-CCE). The study was jointly conducted and benefited from close collaboration of researchers from the intramural NIH Laboratory of Immunoregulation (LIR), Johns Hopkins University, Makerere University and the Rakai Health Sciences Program. Support for the RHSP HIV Care Program was provided by the President's Emergency Fund for AIDS Relief (PEPFAR) and support for the Rakai Cohort Study was provided by the Department of the Army, United States Army Medical Research and Material Command Cooperative Agreement DAMD17-98-2-8007; grants R01 A134826 and R01 A134265 from the National Institute of Allergy and Infectious Diseases; and grant 5P30HD06826 from the National Institute of Child and Health Development. We thank the laboratory and clinical staff at RHSP, for their excellence and dedication to this study, and especially our study nurses Denis Ssenyondwa and Gladys Namuyaba and data editor Violet Nkalubo. We thank Fred Nalugoda for his management advice, Barbara Sekasi and Vivien Okanya Kateregga for help with logistics, Kevin Newell (SAIC, Inc.) for his help with oversight, Andrew Redd (NIH/LIR) for his invaluable advice, and the study participants whose commitment and cooperation made the study possible. NR 32 TC 37 Z9 37 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2011 VL 16 IS 3 BP 405 EP 411 DI 10.3851/IMP1783 PG 7 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 813OA UT WOS:000294375600014 PM 21555823 ER PT J AU Dlamini, J Ledwaba, L Mokwena, N Mokhathi, T Orsega, S Tsoku, M Kowo, H Proschan, M Khabo, P Maja, P Hadigan, C AF Dlamini, Judith Ledwaba, Lotty Mokwena, Nthabiseng Mokhathi, Thabo Orsega, Susan Tsoku, Mary Kowo, Hedwig Proschan, Michael Khabo, Paul Maja, Patrick Hadigan, Colleen TI Lactic acidosis and symptomatic hyperlactataemia in a randomized trial of first-line therapy in HIV-infected adults in South Africa SO ANTIVIRAL THERAPY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HEPATIC CELLS; RISK-FACTORS; REGIMENS; WOMEN AB Background: Lactic acidosis (LA) is a potentially life-threatening complication of antiretroviral (ARV) therapy. Few randomized prospective studies have compared LA between different ARV regimens. Methods: Characterization of cases of LA (serum lactate >5 mmol/l and arterial pH<7.35 or bicarbonate <20 mmol/l) and symptomatic hyperlactataemia (SH; serum lactate >2.2 mmol/l and symptoms) was made in a randomized open-label 2x2 factorial study of stavudine/lamivudine (d4T/3TC)-based versus didanosine/zidovudine-based therapy and lopinavir/ritonavir-based versus efavirenz (EFV)-based therapy in 1,771 HIV-infected adults initiating therapy between 2004 and 2008. Results: The LA incident rate was 3.5/1,000 person-years (95% CI 1.8-5.9), and for combined LA/SH was 11.0/1,000 person-years (95% CI 7.9-14.9). There were two deaths (15% mortality) among 13 LA cases; all 11 survivors experienced symptom resolution and started new ARV regimens. LA cases were more likely to be female (OR 7.19, 95% CI 1.84-40.75; P=0.001) and had a higher body mass index (BMI; P<0.0001) compared with non-cases. There was no increase in LA according to ARV regimen, age or CD4(+) T-cell count at randomization. When combined, LA/SH cases (n=41) were more often female (OR 4.76, 95% CI 2.36-10.08; P<0.0001), had increased BMI (P<0.0001), were more likely to be assigned d4T/3TC (OR 3.17, 95% CI 1.50-7.28; P=0.001) and were more likely to be assigned EFV (OR 2.18, 95% CI 1.08-4.61; P=0.026). Conclusions: Female sex and increased BMI were associated with severe LA in this large randomized trial of first-line ARV in South Africa. While female sex, increased BMI and d4T are previously described risk factors for the development of clinically significant lactate elevations, the independent risk associated with EFV is a novel observation warranting further investigation. C1 [Orsega, Susan; Proschan, Michael; Hadigan, Colleen] NIAID, NIH, Bethesda, MD 20892 USA. [Dlamini, Judith; Ledwaba, Lotty; Mokwena, Nthabiseng; Mokhathi, Thabo; Tsoku, Mary; Kowo, Hedwig; Khabo, Paul; Maja, Patrick] S African Natl Def Force, S African Mil Hlth Serv, Project PHIDISA, Pretoria, South Africa. RP Hadigan, C (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM hadiganc@niaid.nih.gov FU South African Military Health Service (SAMHS); United States Department of Defense (US DOD); United States Department of Health and Human Services (HHS); National Institutes of Health (NIH) through the National Institute of Allergy and Infectious Diseases (NIAID); NIAID FX The study was supported by the South African Military Health Service (SAMHS), the United States Department of Defense (US DOD), the United States Department of Health and Human Services (HHS) and the National Institutes of Health (NIH) through the National Institute of Allergy and Infectious Diseases (NIAID). The Government of the United States through the US DOD and HHS and the Government of the Republic of South Africa through its Department of Defence signed a cooperative agreement to conduct this research project. Salary support for CH, SO and MP was provided by the NIAID Intramural Program. NR 14 TC 4 Z9 4 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2011 VL 16 IS 4 BP 605 EP 609 DI 10.3851/IMP1790 PG 5 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 813OB UT WOS:000294375700018 PM 21685549 ER PT J AU McKinnon, JE Delgado, R Pulido, F Shao, W Arribas, JR Mellors, JW AF McKinnon, John E. Delgado, Rafael Pulido, Federico Shao, Wei Arribas, Jose R. Mellors, John W. TI Single genome sequencing of HIV-1 gag and protease resistance mutations at virologic failure during the OK04 trial of simplified versus standard maintenance therapy SO ANTIVIRAL THERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; LOPINAVIR-RITONAVIR MONOTHERAPY; ANTIRETROVIRAL THERAPY; DRUG-RESISTANCE; CLEAVAGE SITES; VIRAL FITNESS; RANDOMIZED-TRIAL; IN-VIVO; HIV-1-INFECTED PATIENTS; REGIMEN SIMPLIFICATION AB Background: Ritonavir-boosted lopinavir (LPV/RTV) alone has been evaluated as simplified maintenance therapy for HIV-1 infection, but there are concerns about greater potential for emergence of protease inhibitor (PI) resistance. The OK04 trial evaluated maintenance therapy with LPV/RTV alone versus standard therapy (ST) with two NRTIs plus LPV/RTV in 205 patients, of whom 15 had virological rebound by week 48 (11 versus 4 patients, respectively). We developed a single genome sequencing (SOS) assay of HIV-1 gag and protease to assess the emergence of low frequency drug-resistant variants during virological rebound. Methods: Plasma samples from 15 subjects at virological rebound were analysed by SGS of HIV-1 gag and protease genes. A total of 45 SOS sequences were planned per sample, providing 90% power to detect variants comprising >5% of the virus population. Results: Overall, 521 single sequences obtained from 13 patients (range 4-48 sequences/patient) revealed similar frequencies of major protease resistance mutations in samples from the LPV/RTV alone (3/11) and ST (3/4) arms (P=0.10), with a median number of minor protease resistance mutations of 3.0 versus 3.5, respectively (P=0.23). Median number of gag PI resistance mutations were similar between the LPV/RTV alone and ST arms at cleavage sites (3.0 versus 2.5; P=0.83), non-cleavage sites (21 versus 16.5; P=0.71) and the transframe protein-p6 pol region cleavage sites (4.0 versus 3.0; P=0.6). Conclusions: Although more subjects with simplified maintenance therapy with LPV/RTV alone had virological rebound compared to the ST arm, this was not associated with more frequent emergence of variants encoding PI resistance mutations in gag or protease detected by SGS. C1 [McKinnon, John E.; Mellors, John W.] Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA 15260 USA. [Delgado, Rafael; Pulido, Federico] Hosp 12 Octubre, Inst Invest, E-28041 Madrid, Spain. [Shao, Wei] NCI, ISP Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21701 USA. [Arribas, Jose R.] Hosp La Paz, IdiPAZ, Unidad VIH, Serv Med Intern, Madrid, Spain. RP McKinnon, JE (reprint author), Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA 15260 USA. EM jem44@pitt.edu RI Pulido, Federico/B-8417-2009; Arribas, Jose/A-1595-2015; Delgado, Rafael/C-4910-2016 OI Pulido, Federico/0000-0002-7414-8812; Arribas, Jose/0000-0002-7410-9450; Delgado, Rafael/0000-0002-6912-4736 FU NIH [1 KL2 RR024154-03, UL1 RR024153]; National Center for Research Resources (NCRR); National Cancer Institute [25XS119]; Instituto de Salud Carlos III, Spanish Ministry of Health [BA06/90001]; Abbott Laboratories; Fundacion de Investigacion Medica Mutua Madrilena [MUTUA 2005-066]; [1R21AI084423-01]; [FIPSE 36749/2008]; [ISCIII-FIS PI080806] FX We thank all the patients and investigators for their contributions to this project. Financial support for this manuscript was received for JEM from NIH grants 1 KL2 RR024154-03, UL1 RR024153 from the National Center for Research Resources (NCRR) and 1R21AI084423-01, and for JWM from the National Cancer Institute (SAIC contract 25XS119). FP is the recipient of a BAE grant from the Instituto de Salud Carlos III, Spanish Ministry of Health (BA06/90001). JRA is an investigator from the Programa de Intensificacion de la Actividad Investigadora en el SNS (I3SNS) 2009. The OK04 trial was supported by grants from Abbott Laboratories and the Fundacion de Investigacion Medica Mutua Madrilena (MUTUA 2005-066). Additional financial support was provided by grants FIPSE 36749/2008 and ISCIII-FIS PI080806 to RD. The funding sources had no role in the study designs, data collection, analysis and interpretation of the data, preparation of the manuscript or the decision to submit for publication. NR 49 TC 10 Z9 10 U1 0 U2 3 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2011 VL 16 IS 5 BP 725 EP 732 DI 10.3851/IMP1812 PG 8 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 813OC UT WOS:000294375800012 PM 21817194 ER PT J AU Grinsztejn, B Smeaton, L Barnett, R Klingman, K Hakim, J Flanigan, T Kumarasamy, N Campbell, T Currier, J AF Grinsztejn, Beatriz Smeaton, Laura Barnett, Ronald Klingman, Karin Hakim, James Flanigan, Timothy Kumarasamy, N. Campbell, Thomas Currier, Judith CA PEARLS Study Team ACTG TI Sex-associated differences in pre-antiretroviral therapy plasma HIV-1 RNA in diverse areas of the world vary by CD4(+) T-cell count SO ANTIVIRAL THERAPY LA English DT Article ID VIRAL LOAD; INDIVIDUALS; PROGRESSION; WOMEN; MEN; EXPRESSION; INFECTION; COHORT; AIDS AB Background: Sex differences in the natural history of HIV infection may vary between resource-rich and resource-limited settings. Methods: Baseline characteristics from a randomized clinical trial of treatment-naive subjects conducted at sites in Africa, Asia, the Caribbean, and North and South America were analysed to determine if there were significant differences by sex. Results: Of the 1,571 participants, 740 (47.1%) were women. Women had higher mean screening CD4(+) T-cell counts (mean 15 cells higher; P<0.001), lower mean haemoglobin and creatinine clearance, a lower mean baseline HIV-1 viral load (4.85 log(10) versus 5.05 log(10) copies/ml; P<0.001) and were less likely to have a prior AIDS diagnosis than men. The sex difference in viral load was related to CD4(+) T-cell count; however, it was independent of country and persisted within the strata with CD4(+) T-cell count <200 cells/mm(3). Conclusions: Women in resource-limited settings have lower levels of plasma HIV-1 RNA and appear to present for enrolment into clinical trials at an earlier stage of disease than men. The biological basis for lower viral load in women compared to men remains unexplained. It will be important to determine if the sex differences observed at baseline impact clinical outcomes once the PEARLS clinical trial is completed. C1 [Grinsztejn, Beatriz] Fundacao Oswaldo Cruz, Evandro Chagas Clin Res Inst, Manguinho, Brazil. [Smeaton, Laura] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. [Barnett, Ronald] NIH, Off Biotechnol Act, Bethesda, MD 20892 USA. [Klingman, Karin] NIAID, HIV Res Branch, Div Aids, NIH, Bethesda, MD 20892 USA. [Hakim, James] Univ Zimbabwe, Coll Hlth Sci, Harare, Zimbabwe. [Flanigan, Timothy] Brown Univ, Sch Med, Miriam Hosp, Providence, RI 02912 USA. [Kumarasamy, N.] YRG Ctr AIDS Res & Educ, Chennai, Tamil Nadu, India. [Campbell, Thomas] Univ Colorado, Aurora, CO USA. [Currier, Judith] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Grinsztejn, B (reprint author), Fundacao Oswaldo Cruz, Evandro Chagas Clin Res Inst, Manguinho, Brazil. EM gbeatriz@ipec.fiocruz.br FU National Institute of Allergy and Infectious Diseases [U01A1068636]; National Institute of Mental Health (NIMH); National Institute of Dental and Craniofacial Research (NIDCR); Boehringer Ingelheim Pharmaceuticals Inc.; BristolMyers Squibb Inc.; Gilead Sciences Inc.; GlaxoSmithKline; Merck Co. Inc.; [AI69532]; [AI69424]; [AI69511]; [AI69428]; [AI27661]; [AI69484]; [AI69495]; [AI69474]; [AI69513]; [AI69471]; [AI25915]; [AI46370]; [AI69472]; [AI46381]; [AI69423]; [AI25868]; [AI69439]; [AI46376]; [AI38858-09S1]; [AI34853]; [AI69450]; [AI69467]; [AI32782]; [AI69419]; [AI69463]; [AI69426]; [AI69438]; [AI69399]; [AI69417]; [AI69432]; [AI69518] FX The project described was supported by Award Number U01A1068636 from the National Institute of Allergy and Infectious Diseases and supported by National Institute of Mental Health (NIMH), National Institute of Dental and Craniofacial Research (NIDCR). This work was supported by grants AI69532, AI69424, AI69511, AI69428, AI27661, AI69484, AI69495, AI69474, AI69513, AI69471, AI25915, AI46370, AI69472, AI46381, AI69423, Al25868, AI69439, AI46376, AI38858-09S1, AI34853, AI69450, AI69467, AI32782, AI69419, AI69463, AI69426, AI69438, AI69399, AI69417, AI69432, AI69518, AI69476, AI69401, AI69421, AI69518, AI69436 and AI69470.; The collaborating pharmaceutical supporters were Boehringer Ingelheim Pharmaceuticals Inc., BristolMyers Squibb Inc., Gilead Sciences Inc., GlaxoSmithKline and Merck & Co. Inc. The authors declare no competing interests. NR 22 TC 15 Z9 15 U1 0 U2 5 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2011 VL 16 IS 7 BP 1057 EP 1062 DI 10.3851/IMP1872 PG 6 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 846ZO UT WOS:000296941900014 PM 22024521 ER PT J AU Chokephaibulkit, K Cressey, TR Capparelli, E Sirisanthana, V Muresan, P Hongsiriwon, S Ngampiyaskul, C Limwongse, C Wittawatmongkol, O Aurpibul, L Kabat, B Toye, M Smith, ME Eksaengsri, A McIntosh, K Yogev, R AF Chokephaibulkit, Kulkanya Cressey, Tim R. Capparelli, Edmund Sirisanthana, Virat Muresan, Petronella Hongsiriwon, Suchat Ngampiyaskul, Chaiwat Limwongse, Chanin Wittawatmongkol, Orasri Aurpibul, Linda Kabat, Bill Toye, MariPat Smith, Mary Elizabeth Eksaengsri, Achara McIntosh, Kenneth Yogev, Ram CA IMPAACT P1069 Team TI Pharmacokinetics and safety of a new paediatric fixed-dose combination of zidovudine/lamivudine/nevirapine in HIV-infected children SO ANTIVIRAL THERAPY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; NEVIRAPINE PHARMACOKINETICS; HIV-1-INFECTED INDIVIDUALS; LAMIVUDINE; PLASMA; STAVUDINE; ZIDOVUDINE; VARIANTS; PHARMACOGENETICS; FORMULATIONS AB Background: Alternatives to the available stavudine-containing paediatric fixed-dose combination (FDC) tablets are rapidly needed due to concerns regarding the cumulative toxicity of long-term stavudine exposure. We report the bioavailability and short-term safety of a novel paediatric FDC tablet of zidovudine (ZDV)/lamivudine (3TC)/nevirapine (NVP; 30/15/28 mg) in HIV-infected children. Methods: In this Phase I/II open-label pharmacokinetic study, 42 children weighing 6-30 kg treated with NVP-based HAART for >= 4 weeks were randomized to receive the FDC tablets (GPO-VIR Z30) or the liquid formulations. Dosing was weight-based. Intensive 12-h blood sampling was performed after 2 weeks; subjects then crossed-over to the alternate formulation at equal doses and sampling repeated 2 weeks later. Pharmacokinetic parameters were determined by non-compartmental analysis. Buccal-swab samples were collected for cytochrome P450 (CYP)2B6 polymorphism analysis. Results: With the FDC tablet, the geometric mean (90% CI) area under the curve (AUC) for ZDV, 3TC and NVP was 1.58 (1.49-1.68), 7.78 (7.38-8.19) and 68.88 (62.13-76.36) mu g.h/ml, respectively. Rules for NVP therapeutic inadequacy were defined a priori, and despite lower NVP exposure with the tablet (P<0.001), the levels remained therapeutically adequate. ZDV AUC was similar between formulations. 3TC exposure was significantly higher with the tablet but comparable to historical data in adults and children taking branded tablets. While receiving the tablet, NVP AUC in children with CYP2B 516 GG (45%), GT (45%) and TT (10%) genotypes were 67.0, 74.5 and 106.4 mu g.h/ml, respectively (P=0.04). Conclusions: Disparities in drug exposure between formulations were observed; however, the FDC tablet delivered therapeutically adequate exposures of each drug and could well play an important role in simplifying antiretroviral treatment for children. C1 [Chokephaibulkit, Kulkanya; Limwongse, Chanin; Wittawatmongkol, Orasri] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Pediat, Bangkok 10700, Thailand. [Cressey, Tim R.] Chiang Mai Univ, Fac Associated Med Sci, Div Med Technol, PHPT, Chiang Mai 50000, Thailand. [Cressey, Tim R.; Muresan, Petronella; McIntosh, Kenneth] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Cressey, Tim R.] IRD, Marseille, France. [Capparelli, Edmund] Univ Calif San Diego, Dept Pediat Pharm & Drug Discovery, La Jolla, CA 92093 USA. [Sirisanthana, Virat; Aurpibul, Linda] Chiang Mai Univ, Fac Med, Res Inst Hlth Sci, Chiang Mai 50000, Thailand. [Hongsiriwon, Suchat] Chonburi Hosp, Dept Pediat, Chon Buri, Thailand. [Ngampiyaskul, Chaiwat] Prapokklao Hosp, Dept Pediat, Chanthaburi, Thailand. [Kabat, Bill; Yogev, Ram] Childrens Mem Hosp, Chicago, IL 60614 USA. [Toye, MariPat] Baystate Med Ctr, Springfield, MA USA. [Smith, Mary Elizabeth] NIAID, Pediat Med Branch, Div AIDS, Bethesda, MD USA. [Eksaengsri, Achara] Thai Govt Pharmaceut Org, Bangkok, Thailand. [McIntosh, Kenneth] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Chokephaibulkit, K (reprint author), Mahidol Univ, Siriraj Hosp, Fac Med, Dept Pediat, Bangkok 10700, Thailand. EM sikch@mahidol.ac.th FU International Maternal Pediatric Adolescent AIDS Clinical Trial Group (IMPAACT); National Institute of Allergy and Infectious Disease, National Institutes of Health; Thai GPO; National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH) [AI068632]; Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases [5 U01 AI41110]; Pediatric AIDS Clinical Trials Group (PACTG) [1 U01 AI068616]; NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network; NICHD [N01-DK-9-001/HHSN267200800001C] FX This study was supported by the International Maternal Pediatric Adolescent AIDS Clinical Trial Group (IMPAACT) funded by the National Institute of Allergy and Infectious Disease, National Institutes of Health and the Thai GPO. Pharmaceutical support was also provided by GPO.; Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632], the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH) [AI068632]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement number 5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and number 1 U01 AI068616 with the IMPAACT Group. Support of the sites was provided by the National Institute of Allergy and Infectious Diseases (NIAID) and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C). NR 35 TC 20 Z9 21 U1 0 U2 9 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2011 VL 16 IS 8 BP 1287 EP 1295 DI 10.3851/IMP1931 PG 9 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 871EE UT WOS:000298719900013 PM 22155910 ER PT J AU Eggesbo, M Moen, B Peddada, S Baird, D Rugtveit, J Midtvedt, T Bushel, PR Sekelja, M Rudi, K AF Eggesbo, Merete Moen, Birgitte Peddada, Shyamal Baird, Donna Rugtveit, Jarle Midtvedt, Tore Bushel, Pierre R. Sekelja, Monika Rudi, Knut TI Development of gut microbiota in infants not exposed to medical interventions SO APMIS LA English DT Article DE Gut microbiota; infants; colonization; bifidobacterium; enterobacterium; microarray ID HUMAN GASTROINTESTINAL-TRACT; FORMULA-FED INFANTS; BOTTLE-FED INFANTS; REAL-TIME PCR; INTESTINAL MICROFLORA; CESAREAN DELIVERY; ESCHERICHIA-COLI; FECAL FLORA; BACTERIAL-COLONIZATION; BIRTH-WEIGHT AB Knowledge of the composition of a normal healthy gut microbiota during infancy is important for understanding the role of gut microbiota in disease. A limitation of previous studies is that they are based on infants who have been subject to factors, which can have a profound disruptive effect on the natural colonization process. We describe the colonization process, during the first 4 months after birth, in 85 infants who have experienced no major medical or dietary interventions. They were all vaginally delivered, healthy, term infants, who were not exposed to antibiotics, exclusively breastfed during their first month of life and at least partially breastfed up to 4 months. Selected microbial groups were identified by targeting small subunit microbial ribosomal RNA genes. In contrast to more recent studies, but in agreement with older studies, almost all our infants harbored gamma-Proteobacteria and Bifidobacterium. Yet undefined non-cultivable species belonging to Bacteroides, as well as microbes identified as Lachnospiraceae 2, were common. Strong associations were observed between some specific constituents of microbiota at day 4 and the concentration of specific microbial groups at day 120, indicating that early gut microbiota may influence later microbiota. Novel information of the undisturbed composition of early gut microbiota in babies is presented. C1 [Eggesbo, Merete] Norwegian Inst Publ Hlth, Div Epidemiol, Dept Genes & Environm, N-0403 Oslo, Norway. [Eggesbo, Merete; Baird, Donna] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Moen, Birgitte; Sekelja, Monika; Rudi, Knut] Norwegian Inst Food Fisheries & Aquaculture, Nofima, Norway. [Peddada, Shyamal; Bushel, Pierre R.] NIEHS, Biostat Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Rugtveit, Jarle] Oslo Univ Hosp, Dept Pediat, Oslo, Norway. [Midtvedt, Tore] Karolinska Inst, Lab Med Microbial Ecol, Stockholm, Sweden. RP Eggesbo, M (reprint author), Norwegian Inst Publ Hlth, Div Epidemiol, Dept Genes & Environm, POB 4404 Nydalen, N-0403 Oslo, Norway. EM merete.eggesbo@fhi.no RI Peddada, Shyamal/D-1278-2012; OI Eggesbo, Merete/0000-0002-0006-5336; Baird, Donna/0000-0002-5544-2653 FU South-Eastern Norway Regional Health Authority; NIH, National Institute of Environmental Health Sciences [Z01 ES045005-14] FX This project has been partly financed by a grant from the South-Eastern Norway Regional Health Authority and, in part, by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [Z01 ES045005-14]. The authors thank Bente Kvenshagen for her contribution in the recruitment process, and for organizing sample pick up. Finally, they thank Palmer et al. for access to their clone library and Sue Edelstein for graphic design. NR 62 TC 45 Z9 49 U1 0 U2 27 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0903-4641 J9 APMIS JI APMIS PD JAN PY 2011 VL 119 IS 1 BP 17 EP 35 DI 10.1111/j.1600-0463.2010.02688.x PG 19 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 692LF UT WOS:000285153600003 PM 21143523 ER PT J AU Itsko, M Ben-Dov, E Rabinovitch, A Zaritsky, A AF Itsko, Mark Ben-Dov, Eitan Rabinovitch, Avinoam Zaritsky, Arieh BE Mizutani, T TI Tandem DNA Repeats: Generation and Propagation in the Microgene Polymerization Reaction and in vivo SO APPLICATION OF THERMODYNAMICS TO BIOLOGICAL AND MATERIALS SCIENCE LA English DT Article; Book Chapter ID DOUBLE-STRAND BREAKS; REPETITIVE DNA; BACILLUS-THURINGIENSIS; THERMOCOCCUS-LITORALIS; IONIZING-RADIATION; ESCHERICHIA-COLI; HUMAN-DISEASE; SEQUENCES; REPAIR; POLYMERASE C1 [Itsko, Mark; Zaritsky, Arieh] Ben Gurion Univ Negev, Dept Life Sci, IL-84105 Beer Sheva, Israel. [Rabinovitch, Avinoam] Ben Gurion Univ Negev, Dept Phys, IL-84105 Beer Sheva, Israel. [Ben-Dov, Eitan] Achva Acad Coll, IL-79800 Mobile Post Shikmim, Israel. RP Itsko, M (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NR 51 TC 1 Z9 1 U1 0 U2 0 PU INTECH EUROPE PI RIJEKA PA JANEZA TRDINE9, RIJEKA, 51000, CROATIA BN 978-953-307-980-6 PY 2011 BP 175 EP 202 PG 28 WC Biophysics; Thermodynamics; Materials Science, Multidisciplinary; Physics, Applied SC Biophysics; Thermodynamics; Materials Science; Physics GA BD8EM UT WOS:000363883700007 ER PT J AU Phansalkar, S Wright, A Kuperman, GJ Vaida, AJ Bobb, AM Jenders, RA Payne, TH Halamka, J Bloomrosen, M Bates, DW AF Phansalkar, S. Wright, A. Kuperman, G. J. Vaida, A. J. Bobb, A. M. Jenders, R. A. Payne, T. H. Halamka, J. Bloomrosen, M. Bates, D. W. TI Towards Meaningful Medication-Related Clinical Decision Support: Recommendations for an Initial Implementation SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Clinical decision support; decision support systems; CDS; medication alerting; drug-drug interactions; therapeutic duplication; medical informatics AB Clinical decision support (CDS) can improve safety, quality, and cost-effectiveness of patient care, especially when implemented in computerized provider order entry (CPOE) applications. Medication-related decision support logic forms a large component of the CDS logic in any CPOE system. However, organizations wishing to implement CDS must either purchase the computable clinical content or develop it themselves. Content provided by vendors does not always meet local expectations. Most organizations lack the resources to customize the clinical content and the expertise to implement it effectively. In this paper, we describe the recommendations of a national expert panel on two basic medication-related CDS areas, specifically, drug-drug interaction (DDI) checking and duplicate therapy checking. The goals of this study were to define a starter set of medication-related alerts that health-care organizations can implement in their clinical information systems. We also draw on the experiences of diverse institutions to highlight the realities of implementing medication decision support. These findings represent the experiences of institutions with a long history in the domain of medication decision support, and the hope is that this guidance may improve the feasibility and efficiency CDS adoption across healthcare settings. C1 [Phansalkar, S.; Wright, A.; Bates, D. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gen Internal Med, Boston, MA 02115 USA. [Phansalkar, S.; Wright, A.; Bates, D. W.] Partners HealthCare Syst, Wellesley, MA USA. [Kuperman, G. J.] New York Presbyterian Hosp, New York, NY USA. [Vaida, A. J.] Inst Safe Medicat Practices, Huntingdon Valley, PA USA. [Bobb, A. M.] NW Mem Hosp, Chicago, IL 60611 USA. [Jenders, R. A.] US Natl Inst Hlth, Natl Lib Med, Bethesda, MD USA. [Payne, T. H.] Univ Washington, Seattle, WA 98195 USA. [Payne, T. H.] Univ Washington, UW Med Informat Technol Serv, Seattle, WA 98195 USA. [Halamka, J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Halamka, J.] Harvard Univ, Sch Med, Boston, MA USA. [Bloomrosen, M.] Amer Med Informat Assoc, Bethesda, MD USA. [Jenders, R. A.] Georgetown Univ, Washington, DC USA. RP Phansalkar, S (reprint author), Partners Healthcare Syst Inc, CIRD, 2nd Floor,93 Worcester St,POB 81905, Wellesley, MA 02481 USA. EM sphansalkar@partners.org FU Center for Education and Research on Therapeutics on Health Information Technology (CERT-HIT) grant; Agency for Healthcare Research and Quality (AHRQ) [U18HS016970] FX This study was sponsored by the Center for Education and Research on Therapeutics on Health Information Technology (CERT-HIT) grant [PI: David W. Bates], Grant # U18HS016970 from the Agency for Healthcare Research and Quality (AHRQ). AHRQ was not involved in the design or execution of the project or the decision to publish the results. The authors are grateful for the assistance of Christine Soran and Francine Maloney for transcribing the meeting recordings, and Marianne Zachariah who helped with the preparation of the manuscript and improving its readability through editorial revisions. NR 27 TC 6 Z9 6 U1 8 U2 11 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 1869-0327 J9 APPL CLIN INFORM JI Appl. Clin. Inform. PY 2011 VL 2 IS 1 BP 50 EP 62 DI 10.4338/ACI-2010-04-RA-0026 PG 13 WC Medical Informatics SC Medical Informatics GA V28NC UT WOS:000208686500004 PM 23616860 ER PT J AU Mirabelli, MC Hoppin, JA Chatterjee, AB Isom, S Chen, HY Grzywacz, JG Howard, TD Quandt, SA Vallejos, QM Arcury, TA AF Mirabelli, Maria C. Hoppin, Jane A. Chatterjee, Arjun B. Isom, Scott Chen, Haiying Grzywacz, Joseph G. Howard, Timothy D. Quandt, Sara A. Vallejos, Quirina M. Arcury, Thomas A. TI Job Activities and Respiratory Symptoms Among Farmworkers in North Carolina SO ARCHIVES OF ENVIRONMENTAL & OCCUPATIONAL HEALTH LA English DT Article DE agriculture; asthma; epidemiology; occupational lung disease; respiratory diseases ID AGRICULTURAL HEALTH; WORKING ENVIRONMENT; FARMERS EXPOSURE; MIGRANT; DUST; PESTICIDES; RISK AB Respiratory health is an important component of the ability to perform physically demanding work. The authors assessed respiratory symptom prevalence among Latino farmworkers engaged in crop production, and investigated work activities as risk factors for respiratory symptoms. During June to September 2008, 122 farmworkers completed up to 3 questionnaires. The authors estimated associations between work activities and wheezing symptoms using alternating logistic regression, controlling for age and smoking. At the first data collection, 29 (24%) farmworkers reported ever wheezing and 10 (8%) reported wheezing within the past month. Though not statistically significant, the odds of wheezing were elevated for individuals who reported performing tobacco-related work in the last 3 days. The odds were decreased among individuals who reported harvesting activities (odds ratio: 0.3, 95% confidence interval: 0.1, 1.0). Among Latino farmworkers, respiratory symptoms may be associated with work activities. C1 [Mirabelli, Maria C.; Quandt, Sara A.] Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Hoppin, Jane A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Res Triangle Pk, NC USA. [Chatterjee, Arjun B.] Wake Forest Sch Med, Dept Internal Med, Sect Pulm Crit Care Allergy & Immunol Dis, Winston Salem, NC 27157 USA. [Isom, Scott; Chen, Haiying] Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Grzywacz, Joseph G.; Vallejos, Quirina M.; Arcury, Thomas A.] Wake Forest Sch Med, Dept Family & Community Med, Winston Salem, NC 27157 USA. [Chatterjee, Arjun B.; Grzywacz, Joseph G.; Quandt, Sara A.; Vallejos, Quirina M.] Wake Forest Sch Med, Ctr Worker Hlth, Winston Salem, NC 27157 USA. [Howard, Timothy D.] Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA. RP Mirabelli, MC (reprint author), Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM mmirabel@wakehealth.edu RI chatterjee, arjun/H-2689-2013; OI chatterjee, arjun/0000-0001-8221-873X; Mirabelli, Maria/0000-0002-3540-0085; Grzywacz, Joseph/0000-0002-2308-7781 FU National Institutes of Health, National Institute of Environmental Health Sciences [R01ES008739, Z01ES049030] FX This work was supported by the National Institutes of Health, National Institute of Environmental Health Sciences (grant number: R01ES008739) and the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (grant number: Z01ES049030). NR 21 TC 5 Z9 5 U1 0 U2 11 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1933-8244 J9 ARCH ENVIRON OCCUP H JI Arch. Environ. Occup. Health PY 2011 VL 66 IS 3 BP 178 EP 182 DI 10.1080/19338244.2010.539637 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 888HO UT WOS:000299994700006 PM 21864106 ER PT J AU Oquendo, MA Feldman, S Silverman, E Currier, D Brown, GK Chen, DN Chiapella, P Fischbach, R Gould, M Stanley, B Strauss, D Zelazny, J Pearson, J AF Oquendo, Maria A. Feldman, Sarah Silverman, Emily Currier, Dianne Brown, Gregory K. Chen, Donna Chiapella, Page Fischbach, Ruth Gould, Madelyn Stanley, Barbara Strauss, David Zelazny, Jamie Pearson, Jane TI Variability in the Definition and Reporting of Adverse Events in Suicide Prevention Trials: An Examination of the Issues and a Proposed Solution SO ARCHIVES OF SUICIDE RESEARCH LA English DT Article DE Adverse Events; safety; Serious Adverse Events; study evaluation; suicide research ID TOWER-OF-BABEL; CLINICAL-TRIALS; SAFETY; INTERVENTION; NOMENCLATURE; MULTICENTER; IMPROVEMENT; BEHAVIOR; LESSONS; CARE AB Adverse events (AEs) and serious adverse events (SAEs) are important outcomes of any intervention study yet are under-researched. Vague and variable definitions and substantial underreporting make comparisons of risk between studies difficult and evaluation of the safety of a particular intervention almost impossible. These realities may deter researchers from studying at-risk populations. Suicidal behavior is an adverse event in any study, and potentially a very serious one. Thus the issues of reporting and definition are particularly salient for researchers who work with populations at risk for suicidal behavior, especially when the suicidal behavior is the outcome of interest. We conducted a qualitative study with experienced suicide researchers and intervention experts to delineate the issues related to reporting serious adverse events faced by investigators conducting trials in suicide prevention. Participants from multiple sites were interviewed by phone, interviews transcribed and coded for definition and reporting issues and suggested solutions. A narrative synthesis was prepared and validated by all participants. Participants highlighted the difficulties in defining AEs and SAEs and stressed the importance and complexity of ensuring the AE was related to the study and reported properly, and were in agreement about the consequences of AEs to both institutions and individuals. Participants identified the need for the development of clear and consistent AE definitions and reporting requirements. Clear and consistently applied definitions of adverse and serious adverse events and reporting requirements would enhance the comparability of intervention studies in suicidal populations. C1 [Oquendo, Maria A.; Feldman, Sarah; Silverman, Emily; Fischbach, Ruth; Gould, Madelyn; Stanley, Barbara; Strauss, David] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Currier, Dianne] Columbia Univ, Dept Psychiat, New York, NY USA. [Brown, Gregory K.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Chen, Donna] Univ Virginia, Ctr Biomed Eth & Humanities, Charlottesville, VA USA. [Chiapella, Page] NIAAA, Bethesda, MD USA. [Zelazny, Jamie] Univ Pittsburgh, Pittsburgh, PA USA. [Pearson, Jane] NIMH, Bethesda, MD 20892 USA. RP Oquendo, MA (reprint author), New York State Psychiat Inst & Hosp, 1051 Riverside Dr,Unit 42, New York, NY 10032 USA. EM mao4@columbia.edu RI Stanley, Barbara/J-8736-2013; OI Currier, Dianne/0000-0002-6614-271X FU NIAAA NIH HHS [P20 AA15630]; NIMH NIH HHS [P20 MH071897, P20 MH71905] NR 27 TC 2 Z9 2 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1381-1118 J9 ARCH SUICIDE RES JI Arch. Suicide Res. PY 2011 VL 15 IS 1 BP 29 EP 42 AR PII 933023088 DI 10.1080/13811118.2011.541146 PG 14 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 715MU UT WOS:000286889400003 PM 21293998 ER PT J AU Feng, Y Shen, JY Streaker, ED Lockwood, M Zhu, ZY Low, PS Dimitrov, DS AF Feng, Yang Shen, Jiayin Streaker, Emily D. Lockwood, Michael Zhu, Zhongyu Low, Philip S. Dimitrov, Dimiter S. TI A folate receptor beta-specific human monoclonal antibody recognizes activated macrophage of rheumatoid patients and mediates antibody-dependent cell-mediated cytotoxicity SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; TRANS-RETINOIC ACID; OVARIAN-CARCINOMA; BINDING-PROTEIN; EXPRESSION; ANTIFOLATE; INDUCTION; THERAPY; CANCER; ALPHA AB Introduction: Folate receptor beta (FR beta) is only detectable in placenta and limited to some hematopoietic cells of myeloid lineage in healthy people. Studies have indicated that FR beta is over-expressed in activated macrophages in autoimmune diseases and some cancer cells. In this study we aimed to develop an FR beta-specific human monoclonal antibody (mAb) that could be used as a therapeutic agent to treat rheumatoid arthritis and other autoimmune diseases, as well as FR beta positive cancers. Methods: Functional recombinant FR beta protein was produced in insect cells and used as antigen to isolate a mAb, m909, from a human naive Fab phage display library. Binding of Fab and IgG1 m909 to FR beta was measured by ELISA, surface plasmon resonance, immune fluorescence staining, and flow cytometry. Antibody-dependent cell-mediated cytotoxicity (ADCC) was evaluated with FR beta positive CHO cells as target cells and isolated peripheral blood monocytes as effector cells in an in vitro assay. Results: Fab m909 bound with relatively high affinity (equilibrium dissociation constant 57 nM) to FR beta. The IgG1 m909 showed much higher (femtomolar) avidity as measured by ELISA, and it bound to FR beta positive cells in a dose-dependent manner, but not to parental FR beta negative cells. m909 did not compete with folate for the binding to FR beta on cells. m909 was not only able to select FR beta positive, activated macrophages from synovial fluid cells of arthritis patients as efficiently as folate, but also able to mediate ADCC in FR beta positive cells. Conclusions: Unlike folate-drug conjugates, m909 selectively binds to FR beta, does not recognize FR alpha, and has at least one effector function. m909 alone has potential to eliminate FR beta positive cells. Because m909 does not compete with folate for receptor binding, it can be used with folate-drug conjugates in a combination therapy. m909 can also be a valuable research reagent. C1 [Feng, Yang; Zhu, Zhongyu; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, CCRNP, NIH, Frederick, MD 21702 USA. [Shen, Jiayin; Low, Philip S.] Purdue Univ, Dept Chem, W Lafayette, IN 47906 USA. [Streaker, Emily D.] NCI, BRP, SAIC Frederick, Frederick, MD 21702 USA. [Lockwood, Michael] Indiana Univ Hlth Arnett Phys, Lafayette, IN 47904 USA. RP Feng, Y (reprint author), NCI, Prot Interact Grp, CCRNP, NIH, 1050 Boyle St, Frederick, MD 21702 USA. EM fengya@mail.nih.gov OI Low, Philip/0000-0001-9042-5528 FU National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research; National Cancer Institute, NIH [N01-CO-12400]; Endocyte Inc. (West Lafayette, IN, USA) FX We thank members of our groups for helpful discussions. This project was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research, and by federal funds from the National Cancer Institute, NIH, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.; PSL has received fees and stocks from Endocyte Inc. (West Lafayette, IN, USA), a company that he founded in 1995 to develop treatments for cancer. Because Endocyte plans to develop drugs (but not antibodies) for treatment of autoimmune and inflammatory diseases, this relationship could constitute a conflict of interest. The National Institutes of Health and Purdue University have applied for a patent claiming m909; however, the authors receive no benefits from the patent application. The authors declare that they have no other competing interests. NR 28 TC 26 Z9 26 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2011 VL 13 IS 2 AR R59 DI 10.1186/ar3312 PG 12 WC Rheumatology SC Rheumatology GA 788MS UT WOS:000292449700024 PM 21477314 ER PT J AU O'Hanlon, TP Rider, LG Gan, L Fannin, R Paules, RS Umbach, DM Weinberg, CR Shah, RR Mav, D Gourley, MF Miller, FW AF O'Hanlon, Terrance P. Rider, Lisa G. Gan, Lu Fannin, Rick Paules, Richard S. Umbach, David M. Weinberg, Clarice R. Shah, Ruchir R. Mav, Deepak Gourley, Mark F. Miller, Frederick W. TI Gene expression profiles from discordant monozygotic twins suggest that molecular pathways are shared among multiple systemic autoimmune diseases SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID PERIPHERAL-BLOOD CELLS; RHEUMATOID-ARTHRITIS PATIENTS; GENOME-WIDE ASSOCIATION; LUPUS-ERYTHEMATOSUS; INFLAMMATORY MYOPATHIES; FAMILIAL AGGREGATION; MONONUCLEAR-CELLS; IDENTIFICATION; DERMATOMYOSITIS; SIGNATURES AB Introduction: The objective of this study is to determine if multiple systemic autoimmune diseases (SAID) share gene expression pathways that could provide insights into pathogenic mechanisms common to these disorders. Methods: RNA microarray analyses (Agilent Human 1A(V2) 20K oligo arrays) were used to quantify gene expression in peripheral blood cells from 20 monozygotic (MZ) twin pairs discordant for SAID. Six affected probands with systemic lupus erythematosus (SLE), six with rheumatoid arthritis (RA), eight with idiopathic inflammatory myopathies (IIM), and their same-gendered unaffected twins, were enrolled. Comparisons were made between discordant twin pairs and these were also each compared to 40 unrelated control subjects (matched 2: 1 to each twin by age, gender and ethnicity) using statistical and molecular pathway analyses. Relative quantitative PCR was used to verify independently measures of differential gene expression assessed by microarray analysis. Results: Probands and unrelated, matched controls differed significantly in gene expression for 104 probes corresponding to 92 identifiable genes (multiple-comparison adjusted P values < 0.1). Differentially expressed genes involved several overlapping pathways including immune responses (16%), signaling pathways (24%), transcription/translation regulators (26%), and metabolic functions (15%). Interferon (IFN)-response genes (IFI27, OASF, PLSCR1, EIF2AK2, TNFAIP6, and TNFSF10) were up-regulated in probands compared to unrelated controls. Many of the abnormally expressed genes played regulatory roles in multiple cellular pathways. We did not detect any probes expressed differentially in comparisons among the three SAID phenotypes. Similarly, we found no significant differences in gene expression when comparing probands to unaffected twins or unaffected twins to unrelated controls. Gene expression levels for unaffected twins appeared intermediate between that of probands and unrelated controls for 6535 probes (32% of the total probes) as would be expected by chance. By contrast, in unaffected twins intermediate ordering was observed for 84 of the 104 probes (81%) whose expression differed significantly between probands and unrelated controls. Conclusions: Alterations in expression of a limited number of genes may influence the dysregulation of numerous, integrated immune response, cell signaling and regulatory pathways that are common to a number of SAID. Gene expression profiles in peripheral blood suggest that for genes in these critical pathways, unaffected twins may be in a transitional or intermediate state of immune dysregulation between twins with SAID and unrelated controls, perhaps predisposing them to the development of SAID given the necessary and sufficient environmental exposures. C1 [O'Hanlon, Terrance P.; Rider, Lisa G.; Gan, Lu; Miller, Frederick W.] Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, Bethesda, MD 20892 USA. [Fannin, Rick; Paules, Richard S.] Natl Inst Environm Hlth Sci, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. [Umbach, David M.; Weinberg, Clarice R.] Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. [Shah, Ruchir R.; Mav, Deepak] SRA Int Inc, Durham, NC 27713 USA. [Gourley, Mark F.] Natl Inst Arthrit & Musculoskeletal Dis, NIH, Bethesda, MD 20892 USA. RP O'Hanlon, TP (reprint author), Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ohanlont@niehs.nih.gov RI Gan, Lu/L-5395-2014; OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU National Institute of Environmental Health Sciences FX The authors thank Robert Colbert and Nina Raben for their critical review of the manuscript. This work was supported by the intramural research program of the National Institute of Environmental Health Sciences. The funding sponsors had no role in the design, conduct, or interpretation of the study. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 37 TC 19 Z9 19 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2011 VL 13 IS 2 AR R69 DI 10.1186/ar3330 PG 13 WC Rheumatology SC Rheumatology GA 788MS UT WOS:000292449700034 PM 21521520 ER PT J AU Wallen, GR Middleton, KR Rivera-Goba, MV Mittleman, BB AF Wallen, Gwenyth R. Middleton, Kimberly R. Rivera-Goba, Migdalia V. Mittleman, Barbara B. TI Validating English- and Spanish-language patient-reported outcome measures in underserved patients with rheumatic disease SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID COGNITIVE INTERVIEWS; ALTERNATIVE MEDICINE; ARTHRITIS PATIENTS; SELF-EFFICACY; SCALE; PAIN; RHEUMATOLOGISTS; COMPLEMENTARY; THERAPIES; COMMUNITY AB Introduction: Rheumatic diseases are among the most common and debilitating health problems in the United States. These diseases are chronic, can result in severe decrements of physical and psychosocial functioning and affect patients' overall quality of life. A consensus regarding the best patient outcomes to be measured in randomized, controlled trials and prospective natural history studies is essential to provide best estimates of efficacy and safety of interventions across diverse patient populations. Methods: Face-to-face English- and Spanish-language cognitive interviews were conducted among urban Hispanic and African American patients with rheumatic disease to develop a questionnaire booklet. Six measures validating patient-reported outcomes were included: the Arthritis Self-Efficacy Scale, the Stanford Health Assessment Questionnaire Disability Index, the Wong-Baker Faces Pain Scale, the Short Acculturation Scale, the Center for Epidemiologic Studies Depression Scale and the Inventory of Complementary and Alternative Medicine Practices. A sample of patients (n = 15) attending the National Institute of Arthritis and Musculoskeletal and Skin Diseases Community Health Center participated in the initial interviews. Revised measures were further tested for reliability in a separate sample of patients (n = 109) upon enrollment at the health center. Results: Cognitive interviews provided feedback for questionnaire modifications and methods to enhance content validity and data quality, including discarding redundant questions, providing visual aids and concrete examples when appropriate and increasing the use of racially and ethnically concordant interviewers. The cognitive interviews further elucidated that some contextual assumptions and language usage in the original questionnaires may not have taken each respondent's environmental and sociocultural context into consideration. Internal reliability for previously tested measures remained high (Cronbach's alpha = 0.87-0.94). Conclusions: Cognitive interviewing techniques are useful in a diverse sample of racial and ethnic minority patients with rheumatic disease as a method to assess the content validity of the specific outcome measures selected. The data collection approaches and methods described here ultimately enhance data quality. Vigilance is required in the selection of outcome measures in studies or in practice, particularly with each new language translation and/or culturally unique or diverse sample. C1 [Wallen, Gwenyth R.; Middleton, Kimberly R.; Rivera-Goba, Migdalia V.] NIH, Ctr Clin, Nursing & Patient Care Serv, Bethesda, MD 20892 USA. [Mittleman, Barbara B.] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Wallen, GR (reprint author), NIH, Ctr Clin, Nursing & Patient Care Serv, 10 Ctr Dr,Room 2B14,MSC-115, Bethesda, MD 20892 USA. EM gwallen@cc.nih.gov FU National Institutes of Health Clinical Center; National Institute of Arthritis and Musculoskeletal and Skin Diseases FX The authors gratefully acknowledge the interdisciplinary collaboration and support of Gregory Dennis, Margarita Velarde, Kelli Carrington, Reva C Lawrence, Janet Austin, Blakely Denkinger, Madeline Michael, Robert Miranda-Acevedo, Nicole Schuett and Deloris E Koziol. This work was supported by the intramural research program at the National Institutes of Health Clinical Center and by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. NR 36 TC 7 Z9 7 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2011 VL 13 IS 1 AR R1 DI 10.1186/ar3219 PG 11 WC Rheumatology SC Rheumatology GA 750DA UT WOS:000289523500012 PM 21208400 ER PT J AU Zhao, FH Varanasi, AP Cunningham, CA Graubard, BI Hu, SY Chen, F Barrett, CJ Qiao, YL Forman, MR AF Zhao, Fang-Hui Varanasi, Arti Patel Cunningham, Courtney A. Graubard, Barry I. Hu, Shang-Ying Chen, Feng Barrett, Carl J. Qiao, You-Lin Forman, Michele R. TI Tuberculosis and Oncogenic HPV: Potential Co-infections in Women at High-risk of Cervical Cancer in Rural China SO ASIAN PACIFIC JOURNAL OF CANCER PREVENTION LA English DT Article DE Cervical cancer; CIN; inflammation; HPV; vaginal trichomoniasis; tuberculosis ID HUMAN-PAPILLOMAVIRUS INFECTIONS; LUNG-CANCER; TIN MINERS; INTRAEPITHELIAL NEOPLASIA; CHLAMYDIA-TRACHOMATIS; END; SEASONALITY; PROGRESSION; COFACTOR; ETIOLOGY AB The study was embedded in Shanxi Province Cervical Cancer Screening Study II with the aim of examining the association between history of diagnosed tuberculosis or cervical inflammation and oncogenic human papillomavirus (HPV) infection, persistent oncogenic HPV infection, cervical intraepithelial neoplasia grade 3 or cervical cancer (CIN3+) in an isolated rural population of China. A total of 8,798 women were recruited for cervical cancer screening and an interviewer-administered questionnaire. Of the women in the study, 2.7% and 34% reported a diagnosis of tuberculosis and cervical inflammation, respectively. In the model for HPV infection, HPV persistence and CIN3+, we show an increasing magnitude of effect of tuberculosis with increasing severity of disease, as demonstrated by the increasing odds ratios from 1.68 for HPV positivity, to 1.75 for persistent HPV and then 2.08 for CIN3+. Women reporting a diagnosis of tuberculosis, cervical inflammation or both tuberculosis and cervical inflammation were at 75%, 22% and 113% higher odds of persistent HPV infection, respectively. One percent of the study population was diagnosed with tuberculosis and cervical inflammation, placing them at 90% and 113% higher odds of infection with HPV and persistent HPV, respectively. Tuberculosis and oncogenic HPV are identified for the first time as co-infections in rural unscreened women in Shanxi Province, China, highlighting the importance of infection history in assessing an individual's risk for HPV infection, persistence and CIN3+. C1 [Varanasi, Arti Patel] WESTAT Corp, Hlth Studies Sect, Rockville, MD 20850 USA. [Zhao, Fang-Hui; Hu, Shang-Ying; Chen, Feng; Qiao, You-Lin] Peking Union Med Coll, Dept Epidemiol, Inst Canc, Chinese Acad Med Sci, Beijing 100021, Peoples R China. [Cunningham, Courtney A.] NYU, Sch Med, New York, NY USA. [Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Barrett, Carl J.] NCI, Lab Biosyst & Canc, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Forman, Michele R.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. RP Varanasi, AP (reprint author), WESTAT Corp, Hlth Studies Sect, Rockville, MD 20850 USA. EM ArtiVaranasi@westat.com; qiaoy@cicams.ac.cn RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 44 TC 0 Z9 0 U1 0 U2 2 PU ASIAN PACIFIC ORGANIZATION CANCER PREVENTION PI GYEONGGI-DO PA APJCP HEAD OFFICE, KOREAN NATL CANCER CENTER, 323 ILAN -RO, ILSANDONG-GU, GOYANG-SI, GYEONGGI-DO, 410-769, SOUTH KOREA SN 1513-7368 J9 ASIAN PAC J CANCER P JI Asian Pac. J. Cancer Prev. PY 2011 VL 12 IS 6 BP 1409 EP 1415 PG 7 WC Oncology SC Oncology GA 878MV UT WOS:000299262100009 PM 22126473 ER PT B AU Ramachandran, G AF Ramachandran, Gurumurthy BE Ramachandran, G TI Assessing Nanoparticle Risks to Human Health Preface SO ASSESSING NANOPARTICLE RISKS TO HUMAN HEALTH LA English DT Editorial Material; Book Chapter C1 [Ramachandran, Gurumurthy] Univ Minnesota, Div Environm Hlth Sci, Sch Publ Hlth, Minneapolis, MN 55455 USA. [Ramachandran, Gurumurthy] Univ Minnesota, Ind Hyg Program, Sch Publ Hlth, Minneapolis, MN 55455 USA. [Ramachandran, Gurumurthy] NIH, Bethesda, MD 20892 USA. RP Ramachandran, G (reprint author), Univ Minnesota, Div Environm Hlth Sci, Sch Publ Hlth, Minneapolis, MN 55455 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILLIAM ANDREW INC PI NORWICH PA 13 EATON AVE, NORWICH, NY 13815 USA BN 978-1-4377-7864-9 PY 2011 BP IX EP X PG 2 WC Public, Environmental & Occupational Health; Nanoscience & Nanotechnology SC Public, Environmental & Occupational Health; Science & Technology - Other Topics GA BFK38 UT WOS:000320229200001 ER PT B AU Ramachandran, G Park, JY Raynor, PC AF Ramachandran, Gurumurthy Park, Ji Young Raynor, Peter C. BE Ramachandran, G TI Assessing Exposures to Nanomaterials in the Occupational Environment SO ASSESSING NANOPARTICLE RISKS TO HUMAN HEALTH LA English DT Article; Book Chapter ID WALL CARBON NANOTUBES; PARTICLE SURFACE-AREA; ULTRAFINE PARTICLES; AIR-POLLUTION; DAILY MORTALITY; FINE PARTICLES; ENGINEERED NANOMATERIALS; MASS CONCENTRATIONS; HEALTH-RISK; IN-VITRO C1 [Ramachandran, Gurumurthy; Raynor, Peter C.] Univ Minnesota, Div Environm Hlth Sci, Sch Publ Hlth, Minneapolis, MN 55455 USA. [Ramachandran, Gurumurthy] Univ Minnesota, Ind Hyg Program, Sch Publ Hlth, Minneapolis, MN 55455 USA. [Ramachandran, Gurumurthy] NIH, Bethesda, MD USA. [Ramachandran, Gurumurthy] NIOSH Study Sect, Washington, DC 20201 USA. [Park, Ji Young] Univ Minnesota, Minneapolis, MN 55455 USA. RP Ramachandran, G (reprint author), Univ Minnesota, Div Environm Hlth Sci, Sch Publ Hlth, Minneapolis, MN 55455 USA. NR 91 TC 0 Z9 0 U1 1 U2 1 PU WILLIAM ANDREW INC PI NORWICH PA 13 EATON AVE, NORWICH, NY 13815 USA BN 978-1-4377-7864-9 PY 2011 BP 21 EP 64 DI 10.1016/B978-1-4377-7863-2.00002-9 PG 44 WC Public, Environmental & Occupational Health; Nanoscience & Nanotechnology SC Public, Environmental & Occupational Health; Science & Technology - Other Topics GA BFK38 UT WOS:000320229200003 ER PT B AU Warheit, DB AF Warheit, David B. BE Ramachandran, G TI Pulmonary Bioassay Methods for Evaluating Hazards Following Exposures to Nanoscale or Fine Particulate Materials SO ASSESSING NANOPARTICLE RISKS TO HUMAN HEALTH LA English DT Article; Book Chapter ID TITANIUM-DIOXIDE PARTICLES; SUBCHRONIC INHALATION; ULTRAFINE PARTICLES; IN-VIVO; RATS; RESPONSES; TOXICITY; SIZE; LUNG; MICE C1 [Warheit, David B.] NIH Study Sect, Bethesda, MD USA. RP Warheit, DB (reprint author), DuPont Haskell Global Ctr, Newark, DE USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU WILLIAM ANDREW INC PI NORWICH PA 13 EATON AVE, NORWICH, NY 13815 USA BN 978-1-4377-7864-9 PY 2011 BP 99 EP 108 DI 10.1016/B978-1-4377-7863-2.00004-2 PG 10 WC Public, Environmental & Occupational Health; Nanoscience & Nanotechnology SC Public, Environmental & Occupational Health; Science & Technology - Other Topics GA BFK38 UT WOS:000320229200005 ER PT B AU Beaudrie, CEH Kandlikar, M Ramachandran, G AF Beaudrie, Christian E. H. Kandlikar, Milind Ramachandran, Gurumurthy BE Ramachandran, G TI Using Expert Judgment For Risk Assessment SO ASSESSING NANOPARTICLE RISKS TO HUMAN HEALTH LA English DT Article; Book Chapter ID PARTICLE SURFACE-AREA; PARTICULATE AIR-POLLUTION; POORLY SOLUBLE PARTICLES; ULTRAFINE CARBON-BLACK; EXPOSURE ASSESSMENT; LAY JUDGMENTS; PROBABILITY-DISTRIBUTIONS; INTUITIVE TOXICOLOGY; OXIDATIVE STRESS; PERCEIVED RISK C1 [Beaudrie, Christian E. H.] Univ British Columbia, Inst Resources Environm & Sustainabil, Vancouver, BC V5Z 1M9, Canada. [Kandlikar, Milind] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Ramachandran, Gurumurthy] Univ Minnesota, Div Environm Hlth Sci, Sch Publ Hlth, Minneapolis, MN 55455 USA. [Ramachandran, Gurumurthy] Univ Minnesota, Ind Hyg Program, Sch Publ Hlth, Minneapolis, MN 55455 USA. [Ramachandran, Gurumurthy] NIH, Bethesda, MD USA. [Ramachandran, Gurumurthy] NIOSH Study Sect, Washington, DC 20201 USA. RP Beaudrie, CEH (reprint author), Univ British Columbia, Inst Resources Environm & Sustainabil, Vancouver, BC V5Z 1M9, Canada. NR 110 TC 1 Z9 1 U1 0 U2 3 PU WILLIAM ANDREW INC PI NORWICH PA 13 EATON AVE, NORWICH, NY 13815 USA BN 978-1-4377-7864-9 PY 2011 BP 109 EP 138 DI 10.1016/B978-1-4377-7863-2.00005-4 PG 30 WC Public, Environmental & Occupational Health; Nanoscience & Nanotechnology SC Public, Environmental & Occupational Health; Science & Technology - Other Topics GA BFK38 UT WOS:000320229200006 ER PT J AU Koh, KK Quon, MJ Lim, S Lee, Y Sakuma, I Lee, YH Han, SH Shin, EK AF Koh, Kwang Kon Quon, Michael J. Lim, Soo Lee, Yonghee Sakuma, Ichiro Lee, Youn Hee Han, Seung Hwan Shin, Eak Kyun TI Effects of fenofibrate therapy on circulating adipocytokines in patients with primary hypertriglyceridemia SO ATHEROSCLEROSIS LA English DT Article; Proceedings Paper CT Congress of the European-Society-of-Cardiology CY AUG 31, 2010 CL Stockholm, SWEDEN SP European Soc Cardiol DE Fenofibrate; Endothelial function; Adipocytokines; Insulin resistance; Hypertriglyceridemia ID CARDIOVASCULAR-DISEASE; INSULIN SENSITIVITY; PPAR-ALPHA; OLETF RATS; INFLAMMATION; ADIPONECTIN; INTERVENTIONS; COMBINATION; RESISTANCE; ACTIVATION AB Background: We investigated effects of fenofibrate therapy on endothelial dysfunction and adipocytokine profiles. Methods: A randomized, single-blind, placebo-controlled, cross-over study was conducted in 53 patients with primary hypertriglyceridemia. We administered placebo or fenofibrate 160 mg daily for 8 weeks. Results: When compared with placebo, fenofibrate therapy substantially lowered plasma levels of TNF-alpha by 6 +/- 3% (P = 0.014) and hsCRP from 1.10 to 0.90 mg/l (P = 0.004). When compared with placebo, fenofibrate therapy increased plasma levels of adiponectin by 17 +/- 4% (P = 0.001), insulin sensitivity by 4 +/- 1% (as assessed by QUICKI, P = 0.009), and decreased plasma levels of leptin and resistin by 4 + 7% (P = 0.022) and 10 +/- 3% (P = 0.001), respectively. There were correlations between percent changes in QUICKI and percent changes in adiponectin levels (r = 0.279, P = 0.043) or leptin (r = -0.280, P = 0.042). Conclusions: Fenofibrate therapy significantly reduced pro-inflammatory biomarkers and improved adipocytokines levels and insulin sensitivity in hypertriglyceridemic patients. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Koh, Kwang Kon] Gachon Univ, Gil Med Ctr, Vasc Med & Atherosclerosis Unit, Inchon 405760, South Korea. [Quon, Michael J.] NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Lim, Soo] Seoul Natl Univ, Coll Med, Bundang Hosp, Div Endocrinol, Songnam, South Korea. [Lee, Yonghee] Univ Seoul, Dept Stat, Seoul, South Korea. [Sakuma, Ichiro] Hokko Mem Clin, Sapporo, Hokkaido, Japan. RP Koh, KK (reprint author), Gachon Univ, Gil Med Ctr, Vasc Med & Atherosclerosis Unit, 1198 Kuwol Dong, Inchon 405760, South Korea. EM kwangk@gilhospital.com OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 15 TC 16 Z9 16 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JAN PY 2011 VL 214 IS 1 BP 144 EP 147 DI 10.1016/j.atherosclerosis.2010.10.023 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 703QK UT WOS:000285994600023 PM 21075373 ER PT B AU Storz, G Spiro, S AF Storz, Gisela Spiro, Stephen BE Storz, G Hengge, R TI Sensing and Responding to Reactive Oxygen and Nitrogen Species SO BACTERIAL STRESS RESPONSES, 2ND EDITION LA English DT Article; Book Chapter ID ENTERICA SEROVAR TYPHIMURIUM; HYBRID CLUSTER PROTEIN; NITRIC-OXIDE REDUCTASE; TRUNCATED DENITRIFICATION PATHWAY; RHODOBACTER-SPHAEROIDES 2.4.3; DEPENDENT GENE-EXPRESSION; DISULFIDE BOND FORMATION; RALSTONIA-EUTROPHA H16; ESCHERICHIA-COLI K-12; IRON-SULFUR CLUSTERS AB All bacterial cells need to protect themselves against the detrimental effects of reactive oxygen and reactive nitrogen species that are released by one species to inhibit another or are generated during normal metabolism, by antibiotics, or by other redox-active compounds. Although some prominent oxidative stress regulons have been studied for many years, the past 10 years have shown that there are more regulators and regulons than initially imagined. In addition, these recent studies have shown that there is variety in the chemistry by which proteins detect reactive oxygen and nitrogen species, although all of the sensing mechanisms involve reactive cysteine, histidine residues, or metals, predominantly iron. Overlap between the oxidative and nitrosative stress responses and other stress responses has always been known, but the recent studies have shown that the boundaries are even less clear than they were at the outset of the studies. C1 [Storz, Gisela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. [Spiro, Stephen] Univ Texas Dallas, Dept Mol & Cell Biol, Richardson, TX 75080 USA. RP Storz, G (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, 18 Lib Dr, Bethesda, MD 20892 USA. RI Spiro, Stephen/B-1838-2009 OI Spiro, Stephen/0000-0001-5975-9984 NR 154 TC 35 Z9 35 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-621-6 PY 2011 BP 157 EP 173 PG 17 WC Microbiology SC Microbiology GA BSJ67 UT WOS:000284726100010 ER PT B AU Bouveret, E Battesti, A AF Bouveret, Emmanuelle Battesti, Aurelia BE Storz, G Hengge, R TI The Stringent Response SO BACTERIAL STRESS RESPONSES, 2ND EDITION LA English DT Article; Book Chapter ID COLI RNA-POLYMERASE; GUANOSINE 5'-DIPHOSPHATE 3'-DIPHOSPHATE; RIBONUCLEIC-ACID SYNTHESIS; GTP-BINDING-PROTEIN; 50S RIBOSOMAL-SUBUNIT; SPOT-DEPENDENT ACCUMULATION; II INTRON RETROMOBILITY; ESCHERICHIA-COLI; BACILLUS-SUBTILIS; GENE-EXPRESSION AB In response to nutritional limitation, bacteria stop growing and display major gene expression reprogramming in order to face the starvation and difficult times to come. In most bacteria, the first level of this response is the stringent response, mediated by the increase in (p)ppGpp nucleotides. (p)ppGpp controls growth by a variety of mechanisms depending on the bacteria, ranging from the global reprogramming of genes involved in growth or stress response by a direct or indirect modulation of RNA polymerase activity, to the inhibition of enzymes involved in cell cycle control. The (p)ppGpp levels in the cell are regulated by the widely conserved RelA/SpoT homolog enzymes, which synthesize or degrade (p)ppGpp in function of the nutritional quality of the environment. C1 [Bouveret, Emmanuelle] Univ Aix Marseille, CNRS, LISM, UPR9027, F-13009 Marseille, France. [Battesti, Aurelia] NCI, NIH, Bethesda, MD 20892 USA. RP Bouveret, E (reprint author), Univ Aix Marseille, CNRS, LISM, UPR9027, 31 Chemin Joseph Aiguier, F-13009 Marseille, France. NR 209 TC 2 Z9 2 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-621-6 PY 2011 BP 231 EP 250 PG 20 WC Microbiology SC Microbiology GA BSJ67 UT WOS:000284726100014 ER PT S AU Quaia, C Ying, HS Optican, LM AF Quaia, Christian Ying, Howard S. Optican, Lance M. BE Rucker, J Zee, DS TI The nonlinearity of passive extraocular muscles SO BASIC AND CLINICAL OCULAR MOTOR AND VESTIBULAR RESEARCH SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Symposium on Basic and Clinical Ocular Motor and Vestibular Research CY MAR 25-27, 2011 CL Buenos Aires, ARGENTINA SP Univ Hosp Cleveland, Evenor Armington Fund, Fdn FAPS, Fdn Interacoust DE viscoelasticity; model; control; quasilinear; superposition ID OCULOMOTOR PLANT; VISCOELASTIC PROPERTIES; STRESS-RELAXATION; RECTUS MUSCLES; OCULAR DRIFT; EYE-MOVEMENT; LIGAMENT; PRIMATE; CREEP; BEHAVIOR AB Passive extraocular muscles (EOMs), like most biological tissues, are hyperelastic, that is, their stiffness increases as they are stretched. It has always been assumed, and in a few occasions argued, that this is their only nonlinearity and that it can be ignored in central gaze. However, using novel measurement techniques in anesthetized paralyzed monkeys, we have recently demonstrated that EOMs are characterized by another prominent nonlinearity: the forces induced by sequences of stretches do not sum. Thus, superposition, a central tenet of linear and quasi-linear models, does not hold in passive EOMs. Here, we outline the implications of this finding, especially in light of the common assumption that it is easier for the brain to control a linear than a nonlinear plant. We argue against this common belief: the specific nonlinearity of passive EOMs may actually make it easier for the brain to control the plant than if muscles were linear. C1 [Quaia, Christian; Optican, Lance M.] NEI, Lab Sensorimolor Res, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Ying, Howard S.] Johns Hopkins Univ Hosp, Dept Ophthalmol, Baltimore, MD 21287 USA. RP Optican, LM (reprint author), NEI, Lab Sensorimolor Res, NIH, US Dept HHS, 49 Convent Dr,Room 2A50, Bethesda, MD 20892 USA. EM LanceOptican@nih.gov FU NTH [EY19347]; Research to Prevent Blindness; NET FX This research was supported by NTH EY19347 (HSY), Research to Prevent Blindness core grant (HSY), and the intramural research program of the NET (CQ, LMO). NR 53 TC 2 Z9 2 U1 0 U2 4 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-843-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2011 VL 1233 BP 17 EP 25 DI 10.1111/j.1749-6632.2011.06111.x PG 9 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BXY20 UT WOS:000297604800003 PM 21950971 ER PT S AU Rucker, JC Ying, SH Moore, W Optican, LM Buttner-Ennever, J Keller, EL Shapiro, BE Leigh, RJ AF Rucker, Janet C. Ying, Sarah H. Moore, Willa Optican, Lance M. Buettner-Ennever, Jean Keller, Edward L. Shapiro, Barbara E. Leigh, R. John BE Rucker, J Zee, DS TI Do brainstem omnipause neurons terminate saccades? SO BASIC AND CLINICAL OCULAR MOTOR AND VESTIBULAR RESEARCH SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Symposium on Basic and Clinical Ocular Motor and Vestibular Research CY MAR 25-27, 2011 CL Buenos Aires, ARGENTINA SP Univ Hosp Cleveland, Evenor Armington Fund, Fdn FAPS, Fdn Interacoust DE Tay-Sachs disease; saccades; omnipause neurons; fastigial nucleus; Muller paradigm ID CAUDAL FASTIGIAL NUCLEUS; PONTINE RETICULAR-FORMATION; EXCITATORY BURST NEURONS; VERGENCE EYE-MOVEMENTS; ALERT SQUIRREL-MONKEY; CEREBELLAR VERMIS; EFFERENT CONNECTIONS; OCULAR OSCILLATIONS; SUPERIOR COLLICULUS; OCULOMOTOR REGION AB Saccade-generating burst neurons (BN) are inhibited by omnipause neurons (OPN), except during saccades. OPN activity pauses before saccade onset and resumes at the saccade end. Microstimulation of OPN stops saccades in mid-flight, which shows that OPN can end saccades. However, OPN pause duration does not correlate well with saccade duration, and saccades are normometric after OPN lesions. We tested whether OPN were responsible for stopping saccades both in late-onset Tay-Sachs, which causes premature saccadic termination, and in individuals with cerebellar hypermetria. We studied gaze shifts between two targets at different distances aligned on one eye, which consist of a disjunctive saccade followed by vergence. High-frequency conjugate oscillations during the vergence movements that followed saccades were present in all subjects studied, indicating OPN silence. Thus, mechanisms other than OPN discharge (e.g., cerebellar caudal fastigial nucleus-promoting inhibitory BN discharge) must contribute to saccade termination. C1 [Rucker, Janet C.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Rucker, Janet C.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY 10029 USA. [Ying, Sarah H.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Moore, Willa; Shapiro, Barbara E.; Leigh, R. John] Dept Neurol, Cleveland, OH USA. [Leigh, R. John] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. [Leigh, R. John] Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USA. [Leigh, R. John] Vet Affairs Med Ctr, Cleveland, OH USA. [Leigh, R. John] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA. [Optican, Lance M.] NEI, Bethesda, MD 20892 USA. [Buettner-Ennever, Jean] Univ Munich, Inst Anat 1, Munich, Germany. [Keller, Edward L.] Smith Kettlewell Eye Inst, San Francisco, CA USA. RP Rucker, JC (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl,POB 1052, New York, NY 10029 USA. EM janet.rucker@mssm.edu FU Office of Research and Development, Medical Research Service, Department of Veterans Affairs; NIH [EY06717]; NEI, NIH, DHHS; Evenor Armington Fund; Deutsche Forschungsgemeinschaft (DFG) [1639/4-3] FX This work was supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs (R.J.L.); NIH Grant EY06717 (R.J.L.); Intramural research program, NEI, NIH, DHHS (R.J.L.); the Evenor Armington Fund (R.J.L.); and Deutsche Forschungsgemeinschaft (DFG) Grant 1639/4-3 (J.B.E.). NR 50 TC 4 Z9 4 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-843-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2011 VL 1233 BP 48 EP 57 DI 10.1111/j.1749-6632.2011.06170.x PG 10 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BXY20 UT WOS:000297604800007 PM 21950975 ER PT S AU Shaikh, AG Zee, DS Optican, LM Miura, K Ramat, S Leigh, RJ AF Shaikh, Aasef G. Zee, David S. Optican, Lance M. Miura, Kenichiro Ramat, Stefano Leigh, R. John BE Rucker, J Zee, DS TI The effects of ion channel blockers validate the conductance-based model of saccadic oscillations SO BASIC AND CLINICAL OCULAR MOTOR AND VESTIBULAR RESEARCH SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Symposium on Basic and Clinical Ocular Motor and Vestibular Research CY MAR 25-27, 2011 CL Buenos Aires, ARGENTINA SP Univ Hosp Cleveland, Evenor Armington Fund, Fdn FAPS, Fdn Interacoust DE burst neurons; hyperpolarization-activated cation current; low-threshold calcium current; reciprocal innervations ID ACTIVATED CATION CURRENT; BURST NEURONS; EXCITABILITY AB Conductance-based models of reciprocally inhibiting burst neurons suggest that intrinsic membrane properties and postinhibitory rebound (PIR) determine the amplitude and frequency of saccadic oscillations. Reduction of the low-threshold calcium currents (I-T) in the model decreased the amplitude but increased the frequency of the simulated oscillations. Combined reduction of hyperpolarization-activated cation current (I-h) and I-T in the model abolished the simulated oscillations. We measured the effects of a selective blocker of I-T (ethosuximide) in healthy subjects on the amplitude and frequency of saccadic oscillations evoked by eye closure and of a nonselective blocker of I-h and I-T (propronolol) in a patient with microsaccadic oscillation and limb tremor syndrome (mSOLT). Ethosuximide significantly reduced the amplitude but increased the frequency of the saccadic oscillations during eye closure in healthy subjects. Propranolol abolished saccadic oscillations in the mSOLT patient. These results support the hypothetical role of postinhibitory rebound, I-h, and I-T, in generation of saccadic oscillations and determining their kinematic properties. C1 [Shaikh, Aasef G.; Leigh, R. John] Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. [Zee, David S.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Optican, Lance M.] NEI, Lab Sensorimotor Res, NIH, Bethesda, MD 20892 USA. [Miura, Kenichiro] Kyoto Univ, Kyoto, Japan. [Ramat, Stefano] Univ Pavia, I-27100 Pavia, Italy. RP Shaikh, AG (reprint author), Univ Hosp Cleveland, Dept Neurol, Case Med Ctr, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM aasefshaikh@gmail.com RI Ramat, Stefano/E-6495-2011 OI Ramat, Stefano/0000-0001-5932-186X FU NIH [EY01849, EY06717]; Department of Veterans Affairs; EvenorArmington Fund FX The authors thank Mr. Dale Roberts for assistance. This work was supported by grants from NIH EY01849, EY06717, the Department of Veterans Affairs, and the EvenorArmington Fund. NR 16 TC 5 Z9 5 U1 0 U2 3 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-843-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2011 VL 1233 BP 58 EP 63 DI 10.1111/j.1749-6632.2011.06130.x PG 6 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BXY20 UT WOS:000297604800008 PM 21950976 ER PT S AU Shaikh, AG Thurtell, MJ Optican, LM Leigh, RJ AF Shaikh, Aasef G. Thurtell, Matthew J. Optican, Lance M. Leigh, R. John BE Rucker, J Zee, DS TI Pharmacological tests of hypotheses for acquired pendular nystagmus SO BASIC AND CLINICAL OCULAR MOTOR AND VESTIBULAR RESEARCH SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Symposium on Basic and Clinical Ocular Motor and Vestibular Research CY MAR 25-27, 2011 CL Buenos Aires, ARGENTINA SP Univ Hosp Cleveland, Evenor Armington Fund, Fdn FAPS, Fdn Interacoust DE cerebellum; inferior olive; plasticity; learning; Guillain-Mollaret triangle; multiple sclerosis ID INFERIOR OLIVARY HYPERTROPHY; OCULAR OSCILLATIONS; OCULOPALATAL TREMOR; PALATAL MYOCLONUS; CHANNEL MUTATION; PURKINJE-CELLS; CEREBELLAR; GABAPENTIN; NEURONS; MEMANTINE AB Acquired pendular nystagmus (APN) occurs with multiple sclerosis (MS) and oculopalatal tremor (OPT); distinct features of the nystagmus have led to the development of separate models for their pathogenesis. APN in MS has been attributed to instability in the neural integrator, which normally ensures steady gaze. APN in OPT may result from electrotonic coupling between neurons in the hypertrophied inferior olivary nucleus, which induces maladaptive learning in cerebellar cortex. We tested these two hypotheses by analyzing the effects of gabapentin, memantine, and baclofen on both forms of nystagmus. No drug changed the dominant frequency of either form of APN, but the variability of frequency was affected with gabapentin and memantine in patients with OPT. The amplitude of APN in both MS and OPT was reduced with gabapentin and memantine, but not baclofen. Analyzing the effects of drug therapies on ocular oscillations provides a novel approach to test models of nystagmus. C1 [Optican, Lance M.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. [Shaikh, Aasef G.; Leigh, R. John] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Shaikh, Aasef G.; Leigh, R. John] Ctr Vet Med, Neurol Serv, Cleveland, OH USA. [Thurtell, Matthew J.] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA USA. RP Optican, LM (reprint author), NEI, Sensorimotor Res Lab, NIH, 49 Convent Dr,Room 2A50, Bethesda, MD 20892 USA. EM lanceoptican@nih.gov FU Intramural NIH HHS [ZIA EY000302-16]; NEI NIH HHS [EY06717, R01 EY006717] NR 28 TC 9 Z9 9 U1 0 U2 3 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-843-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2011 VL 1233 BP 320 EP 326 DI 10.1111/j.1749-6632.2011.06118.x PG 7 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BXY20 UT WOS:000297604800043 PM 21951011 ER PT J AU Miller, B McCardle, P AF Miller, Brett McCardle, Peggy TI Moving Closer to a Public Health Model of Language and Learning Disabilities: The Role of Genetics and the Search for Etiologies SO BEHAVIOR GENETICS LA English DT Article DE Learning disabilities; Literacy; Language development; Genetics; Diversity ID DEVELOPMENTAL DYSLEXIA; NEURONAL MIGRATION; READING-DISABILITY; DISORDER; IMPAIRMENT; EDUCATION; GENES; BRAIN AB Continued progress in language and learning disabilities (LDs) research requires a renewed focused on issues of etiology. Genetics research forms a central tenet of such an agenda and is critical in clarifying relationships among oral language development, acquisition of literacy and mathematics, executive function skills, and comorbid conditions. For progress to be made, diversified efforts must continue to emphasize molecular and behavioral genetics (including quantitative genetics) approaches, in concert with multi-disciplinary and multi-modal projects, to provide an integrated understanding of the behavioral and biological manifestations of language and learning disabilities. Critically, increased efforts to include ethnic, socio-economic, and linguistically diverse participant samples across a range of developmental stages is required to meet the public health needs of learners in the US and across the world. Taken together, this body of work will continue to enhance our understanding of LDs and help us move toward a truly prevention based approach to language and learning disabilities. C1 [Miller, Brett; McCardle, Peggy] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Miller, Brett; McCardle, Peggy] US Dept HHS, Washington, DC 20201 USA. RP Miller, B (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 6100 Execut Blvd,Suite 4B05,MSC 7510, Bethesda, MD 20892 USA. EM millerbre@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 35 TC 3 Z9 3 U1 0 U2 22 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD JAN PY 2011 VL 41 IS 1 BP 1 EP 5 DI 10.1007/s10519-010-9439-9 PG 5 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 712JA UT WOS:000286661500001 PM 21229298 ER PT S AU Wendland, JR McMahon, FJ AF Wendland, Jens R. McMahon, Francis J. BE Manji, HK Zarate, CA TI Genetics of Bipolar Disorder SO BEHAVIORAL NEUROBIOLOGY OF BIPOLAR DISORDER AND ITS TREATMENT SE Current Topics in Behavioral Neurosciences LA English DT Article; Book Chapter ID GENOME-WIDE ASSOCIATION; PSYCHIATRIC-ILLNESS; TWIN; IDENTIFICATION; SCHIZOPHRENIA; HERITABILITY; DISEASES; METAANALYSIS; INDIVIDUALS; ETIOLOGY AB In this chapter we will attempt to outline the current state of genetic knowledge for bipolar disorder and briefly summarize the main findings from genetic epidemiology studies We then review the most recent original literature, based largely on genome-wide association study methods We conclude with some ideas about future directions C1 [Wendland, Jens R.; McMahon, Francis J.] NIMH, Genet Basis Mood & Anxiety Disorders Sect, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Wendland, JR (reprint author), NIMH, Genet Basis Mood & Anxiety Disorders Sect, NIH, US Dept HHS, Bethesda, MD 20892 USA. OI McMahon, Francis/0000-0002-9469-305X NR 39 TC 1 Z9 1 U1 1 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1866-3370 BN 978-3-642-15756-1 J9 CURR TOP BEHAV NEURO JI Cur. Top. Behav. Neurosci. PY 2011 VL 5 BP 19 EP 30 DI 10.1007/7854_2010_74 D2 10.1007/978-3-642-15757-8 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BSM87 UT WOS:000284977600002 PM 25236547 ER PT J AU Jacobs, RH Pine, DS Schoeny, ME Henry, DB Gollan, JK Moy, G Cook, EH Wakschlag, LS AF Jacobs, Rachel H. Pine, Daniel S. Schoeny, Michael E. Henry, David B. Gollan, Jackie K. Moy, Gregory Cook, Edwin H. Wakschlag, Lauren S. TI Maternal depressive history, teen 5HTTLPR genotype, and the processing of emotional faces: Exploring mechanisms of risk SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Intergenerational transmission; Depression; 5HT; Adolescence; Face processing; G X E ID SEROTONIN TRANSPORTER GENE; FACIAL EXPRESSIONS; AMYGDALA-FUNCTION; MAJOR DEPRESSION; 5-HTT GENE; INFORMATION; CHILDREN; ANXIETY; POLYMORPHISM; METAANALYSIS AB Variations in the serotonin transporter gene (5HTTLPR) and biased processing of face-emotion displays both have been implicated in the transmission of depression risk, but little is known about developmental influences on these relationships. Within a community sample of adolescents, we examine whether 5HTTLPR genotype moderates the link between maternal depressive history and errors in face-emotion labeling. When controlling for current levels of depression and anxiety among youth, a two-way interaction between maternal depressive history and 5HTTLPR genotype was detected. Specifically, adolescents whose mothers reported a depressive history and who had a low expressing genotype made more errors in classifying emotional faces when compared with adolescents with an intermediate or high expressing genotype, with or without maternal depression history. These findings highlight the complex manner in which maternal depression and genetic risk may interact to predict individual differences in social information processing. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Jacobs, Rachel H.] Columbia Univ, New York, NY 10032 USA. [Jacobs, Rachel H.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA. [Schoeny, Michael E.] Univ Chicago, Chicago, IL 60637 USA. [Henry, David B.; Moy, Gregory] Univ Illinois, Inst Hlth Res & Policy, Chicago, IL 60608 USA. [Gollan, Jackie K.] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60601 USA. [Wakschlag, Lauren S.] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. [Cook, Edwin H.] Univ Illinois, Inst Juvenile Res, Dept Psychiat, Chicago, IL 60608 USA. RP Jacobs, RH (reprint author), Columbia Univ, 1051 Riverside Dr,Unit 74, New York, NY 10032 USA. EM jacobsr@childpsych.columbia.edu; pined@mail.nih.gov; mschoeny@chapinhall.org; dhenry@psych.uic.edu; j-gollan@northwestern.edu; gmoy.17@gmail.com; ecook@psych.uic.edu; lauriew@northwestern.edu OI Cook, Edwin/0000-0002-5848-5114 FU NIDA NIH HHS [DA15223, R01 DA015223, R01 DA015223-06] NR 27 TC 13 Z9 13 U1 3 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD JAN PY 2011 VL 49 IS 1 BP 80 EP 84 DI 10.1016/j.brat.2010.10.004 PG 5 WC Psychology, Clinical SC Psychology GA 717QC UT WOS:000287061500012 PM 21092937 ER PT J AU Roullet, FI Wohr, M Crawley, JN AF Roullet, Florence I. Woehr, Markus Crawley, Jacqueline N. TI Female urine-induced male mice ultrasonic vocalizations, but not scent-marking, is modulated by social experience SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Olfaction; Scent-marking; Ultrasonic vocalization; Communication; Mice ID EPHEMERAL SEX-PHEROMONE; MALE-TYPICAL BEHAVIORS; MUS-DOMESTICUS RUTTY; BTBR-T+TF/J MICE; MALE HOUSE MICE; AGGRESSIVE-BEHAVIOR; INDIVIDUAL RECOGNITION; MATING-BEHAVIOR; INBRED STRAINS; OLFACTORY CUES AB Despite the evidence for a communicative function of rodent scent marks and ultrasonic vocalizations, relatively little is known about the impact of social factors on these two forms of communication. Here, we tested the effects of two important social factors, prior exposure to a female and freshness of female urine, on male scent marks and ultrasonic vocalizations elicited by female urine. We also asked whether a recently reported strain difference between the highly social strain C57BL/6J (B6) and the mouse model of autism BTBR T+tf/J (BTBR) herein is specifically seen in response to female urine or also detectable in response to male urine traces. Results show that the emission of female urine-elicited ultrasonic vocalizations was dependent on previous female experience, while scent-marking behavior was not affected. A positive correlation was detected between scent-marking behavior and ultrasonic calling in the most biologically relevant context, male mice exposed to fresh female urine after female experience. Correlations were less prominent or missing in less biologically relevant contexts, e.g. in male mice exposed to fresh female urine without previous female experience, indicating that previous female experience is affecting both the emission of female urine-elicited ultrasonic vocalizations and the correlation between olfactory and acoustic communication. The strain difference in scent-marking behavior and ultrasonic calling between B6 and BTBR appears to be specific to female urine-elicited behavior as it was not seen in response to male urine traces, highlighting the relevance of the social context in which mouse communication is evaluated. Published by Elsevier B.V. C1 [Roullet, Florence I.; Woehr, Markus; Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Roullet, FI (reprint author), NIMH, Lab Behav Neurosci, Intramural Res Program, NIH, PNRC Bldg 35,Room 1C903, Bethesda, MD 20892 USA. EM firoullet@gmail.com FU National Institute of Mental Health FX Supported by the National Institute of Mental Health Intramural Research Program. NR 81 TC 32 Z9 33 U1 2 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 EI 1872-7549 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD JAN 1 PY 2011 VL 216 IS 1 BP 19 EP 28 DI 10.1016/j.bbr.2010.06.004 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 694SG UT WOS:000285318500003 PM 20540967 ER PT J AU Alexander, N Osinsky, R Mueller, E Schmitz, A Guenthert, S Kuepper, Y Hennig, J AF Alexander, Nina Osinsky, Roman Mueller, Eva Schmitz, Anja Guenthert, Sarah Kuepper, Yvonne Hennig, Juergen TI Genetic variants within the dopaminergic system interact to modulate endocrine stress reactivity and recovery SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE COMT val(158)Met; DAT1 VNTR; Gene-gene interaction; HPA-axis; Stress reactivity; Cortisol ID CATECHOL-O-METHYLTRANSFERASE; MEDIAL PREFRONTAL CORTEX; PSYCHOLOGICAL STRESS; TRANSPORTER AVAILABILITY; NUCLEUS-ACCUMBENS; CORTICAL DOPAMINE; AVERSIVE STIMULI; MATERNAL-CARE; IN-VIVO; COMT AB Catecholamines modulate endocrine stress reactivity by affecting regulatory influences of extra-hypothalamic brain structures on hypothalamus-pituitary-adrenal (HPA)-axis. Therefore, we aimed to investigate combined effects of functional allelic variations that affect dopamine availability in both cortical (COMTVal(158)Met polymorphism) and subcortical (DAT1 VNTR) brain regions on HPA-axis reactivity to psychosocial stress. By using a standardized laboratory stress task (public speaking) we obtained saliva cortisol samples during stress exposure and an extended recovery period in 100 healthy male adults. We report for the first time significant epistasis between COMT Val(158)Met and DAT1 VNTR on cortisol response patterns. Subjects homozygous for both the Met(158) and the 10-repeat allele of DAT1 VNTR were characterized by markedly elevated cortisol reactivity and impaired stress recovery compared to all other groups. Our results indicate a crucial role of functional genetic variants within the dopaminergic system in the modulation of HPA-axis response patterns and highlight the need to investigate combined effects of specific candidate genes on stress-related endophenotypes. (C) 2010 Elsevier B.V. All rights reserved. C1 [Alexander, Nina; Osinsky, Roman; Mueller, Eva; Guenthert, Sarah; Kuepper, Yvonne; Hennig, Juergen] Univ Giessen, Ctr Psychobiol & Behav Med, Dept Psychol, D-35394 Giessen, Germany. [Schmitz, Anja] NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA. RP Alexander, N (reprint author), Univ Giessen, Ctr Psychobiol & Behav Med, Dept Psychol, Otto Behaghel Str 10, D-35394 Giessen, Germany. EM nina.alexander@psychol.uni-giessen.de RI Osinsky, Roman/H-5064-2011 FU DFG (graduate school "Brain & Behavior, Neuroact") FX Role of the funding source: This study was supported by a research grant from the DFG (graduate school "Brain & Behavior, Neuroact") to the first author. NR 56 TC 22 Z9 22 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD JAN 1 PY 2011 VL 216 IS 1 BP 53 EP 58 DI 10.1016/j.bbr.2010.07.003 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 694SG UT WOS:000285318500007 PM 20620172 ER PT J AU Nelson, DE AF Nelson, David E. BE Gigerenzer, G Gray, JAM TI Health Research Agendas and Funding SO BETTER DOCTORS, BETTER PATIENTS, BETTER DECISIONS: ENVISIONING HEALTH CARE 2020 SE Strungmann Forum Reports LA English DT Proceedings Paper CT Ernst-Strungmann Forum on Better Doctors, Better Patients, Better Decisions - Envisioning Health Care 2020 CY OCT 25-30, 2009 CL Frankfurt, GERMANY AB There is a large range of national public funding support for health research across countries. By contrast, allocations for overall funding for health literacy and related research areas are limited. Health research agendas and resource allocation are policy decisions that involve the use of power. There are strong incentives to maintain the status quo, especially in the face of level or declining funding. Many macro-and micro-level factors influence research agendas and funding support. These range from broader societal values and health care delivery systems, to the individuals themselves who make decisions. There is a great need for more research in areas such as implementation of simple interventions in "real-world" settings and the effects of communication technologies on receipt, processing, and seeking of health information by the public. There is some reason for optimism: awareness and support for more transdisciplinary and applied research relevant to health literacy is increasing, and some countries have adopted effective approaches to assess new health technology and treatment prior to introduction into clinical and public health practice. C1 [Nelson, David E.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-26229-985-5 J9 STRUNGMANN FORUM REP PY 2011 BP 61 EP 81 PG 21 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA BYT82 UT WOS:000300216300006 ER PT J AU Lee, SB Park, JH Folk, JE Deck, JA Pegg, AE Sokabe, M Fraser, CS Park, MH AF Lee, Seung Bum Park, Jong Hwan Folk, John E. Deck, Jason A. Pegg, Anthony E. Sokabe, Masaaki Fraser, Christopher S. Park, Myung Hee TI Inactivation of eukaryotic initiation factor 5A (eIF5A) by specific acetylation of its hypusine residue by spermidine/spermine acetyltransferase 1 (SSAT1) SO BIOCHEMICAL JOURNAL LA English DT Article DE acetylation; eukaryotic translation initiation factor 5A (eIF5A); hypusine; polyamine metabolism; post-translational modification; spermidine/spermine-N(1-)acetyltransferase 1 (SSAT1) ID YEAST SACCHAROMYCES-CEREVISIAE; ENHANCES CELL-MIGRATION; CONTAINING PROTEIN; AMINO-ACID; POLYAMINE METABOLISM; POSTTRANSLATIONAL SYNTHESIS; FACTOR EIF-4D; TRANSLATION; DEOXYHYPUSINE; N-1-ACETYLTRANSFERASE AB eIF5A (eukaryotic translation initiation factor 5A) is the only cellular protein containing hypusine [N-epsilon-(4-amino-2-hydroxybutyl)lysine]. eIF5A is activated by the post-translational synthesis of hypusine and the hypusine modification is essential for cell proliferation. In the present study, we report selective acetylation of the hypusine and/or deoxyhypusine residue of eIF5A by a key polyamine catabolic enzyme SSAT1 (spermidine/spermine-N-1-acetyltransferase 1). This enzyme normally catalyses the N-1 -acetylation of spermine and spermidine to form acetyl-derivatives, which in turn are degraded to lower polyamines. Although SSAT1 has been reported to exert other effects in cells by its interaction with other cellular proteins, eIF5A is the first target protein specifically acetylated by SSAT1. Hypusine or deoxyhypusine, as the free amino acid, does not act as a substrate for SSAT1, suggesting a macromolecular interaction between eIF5A and SSAT1. Indeed, the binding of eIF5A and SSAT1 was confirmed by pull-down assays. The effect of the acetylation of hypusine on eIF5A activity was assessed by comparison of acetylated with non-acetylated bovine testis eIF5A in the methionyl-puromycin synthesis assay. The loss of eIF5A activity by this SSAT1-mediated acetylation confirms the strict structural requirement for the hypusine side chain and suggests a possible regulation of eIF5A by hypusine acetylation/deacetylation. C1 [Lee, Seung Bum; Park, Jong Hwan; Park, Myung Hee] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Folk, John E.; Deck, Jason A.] Natl Inst Drug Abuse, Chem Biol Res Branch, Bethesda, MD 20892 USA. [Folk, John E.; Deck, Jason A.] NIAAA, NIH, Bethesda, MD 20892 USA. [Pegg, Anthony E.] Penn State Univ, Milton S Hershey Med Ctr, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. [Sokabe, Masaaki] Univ Calif Davis, Dept Biochem & Mol Med, Davis, CA 95616 USA. [Fraser, Christopher S.] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA. RP Park, MH (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. EM mhpark@nih.gov RI Fraser, Christopher/H-9186-2013 FU National Institute of Dental and Craniofacial Research (NIDCR); National Institute of Drug Abuse (NIDA); National Institute on Alcohol Abuse and Alcoholism (NIAA); National Institutes of Health (NIH) [R01 GM092927]; Human Frontier Science Program fellowship [LT00575/2007-L] FX The research was supported in part by the Intramural Research Program of National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Drug Abuse (NIDA) and National Institute on Alcohol Abuse and Alcoholism (NIAA), National Institutes of Health (NIH), NIH extramural grant [grant number R01 GM092927 (to C.S.F.)] and by the Human Frontier Science Program fellowship [fellowship number LT00575/2007-L (to M.S.)]. NR 51 TC 14 Z9 15 U1 0 U2 7 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 1 PY 2011 VL 433 BP 205 EP 213 DI 10.1042/BJ20101322 PN 1 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 757AH UT WOS:000290055700021 PM 20942800 ER PT J AU Lada, AG Krick, CF Kozmin, SG Mayorov, VI Karpova, TS Rogozin, IB Pavlov, YI AF Lada, A. G. Krick, C. Frahm Kozmin, S. G. Mayorov, V. I. Karpova, T. S. Rogozin, I. B. Pavlov, Y. I. TI Mutator effects and mutation signatures of editing deaminases produced in bacteria and yeast SO BIOCHEMISTRY-MOSCOW LA English DT Article DE editing deaminases; mutagenesis; immunity; DNA repair ID CLASS-SWITCH RECOMBINATION; SINGLE-STRANDED-DNA; POLYNUCLEOTIDE (DEOXY)CYTIDINE DEAMINASES; IMMUNOGLOBULIN GENE CONVERSION; APOBEC3 CYTIDINE DEAMINASES; CRYSTAL-STRUCTURE; SOMATIC HYPERMUTATION; ADENOSINE-DEAMINASE; ESCHERICHIA-COLI; POLYMERASE-DELTA AB Enzymatic deamination of bases in DNA or RNA leads to an alteration of flow of genetic information. Adenosine deaminases edit RNA (ADARs, TADs). Specialized cytidine deaminases are involved in RNA/DNA editing in lipid metabolism (APOBEC1) and in innate (APOBEC3 family) and humoral (AID) immunity. APOBEC2 is required for proper muscle development and, along with AID, was implicated in demethylation of DNA. The functions of APOBEC4, APOBEC5, and other deaminases recently discovered by bioinformatics approaches are unknown. What is the basis for the diverse biological functions of enzymes with similar enzyme structure and the same principal enzymatic reaction? AID, APOBEC1, lamprey CDA1, and APOBEC3G enzymes cause uracil DNA glycosylase-dependent induction of mutations when overproduced ectopically in bacteria or yeast. APOBEC2, on the contrary, is nonmutagenic. We studied the effects of the expression of various deaminases in yeast and bacteria. The mutagenic specificities of four deaminases, hAID, rAPOBEC1, hAPOBEC3G, and lamprey CDA1, are strikingly different. This suggests the existence of an intrinsic component of deaminase targeting. The expression of yeast CDD1 and TAD2/TAD3, human APOBEC4, Xanthomonas oryzae APOBEC5, and deaminase encoded by Micromonas sp. gene MICPUN_56782 was nonmutagenic. A lack of a mutagenic effect for Cdd1 is expected because the enzyme functions in the salvage of pyrimidine nucleotides, and it is evolutionarily distant from RNA/DNA editing enzymes. The reason for inactivity of deaminases grouped with APOBEC2 is not obvious from their structures. This cannot be explained by protein insolubility and peculiarities of cellular distribution and requires further investigation. C1 [Lada, A. G.; Krick, C. Frahm; Pavlov, Y. I.] Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. [Kozmin, S. G.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. [Mayorov, V. I.] Mercer Univ, Sch Med, Macon, GA 31207 USA. [Karpova, T. S.] NCI, Ctr Canc Res Core Imaging Facil, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. [Rogozin, I. B.] Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Rogozin, I. B.] Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. RP Pavlov, YI (reprint author), Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. EM ypavlov@unmc.edu RI Kozmin, Stanislav/J-6849-2012 OI Kozmin, Stanislav/0000-0002-4128-4447 FU UNMC; National Cancer Institute Eppley Cancer Center [P30CA036727]; National Library of Medicine at the National Institutes of Health/DHHS FX This work has been supported, in part, by a UNMC pilot grant awarded in 2008 (YIP, Co-PI) and National Cancer Institute Eppley Cancer Center Support Grant P30CA036727. IBR was supported in part by the Intramural Research Program of the National Library of Medicine at the National Institutes of Health/DHHS. NR 102 TC 14 Z9 14 U1 0 U2 5 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0006-2979 J9 BIOCHEMISTRY-MOSCOW+ JI Biochem.-Moscow PD JAN PY 2011 VL 76 IS 1 BP 131 EP 146 DI 10.1134/S0006297911010135 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 722DO UT WOS:000287411600013 PM 21568845 ER PT J AU Yavlovich, A Singh, A Blumenthal, R Puri, A AF Yavlovich, Amichai Singh, Alok Blumenthal, Robert Puri, Anu TI A novel class of photo-triggerable liposomes containing DPPC:DC8,9PC as vehicles for delivery of doxorubcin to cells SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE Polymerizable lipids; Laser; Triggered drug release; Diacetylene phospholipid; Radiation-sensitive liposome; Lipid modification ID SMALL UNILAMELLAR LIPOSOMES; PHOTOSENSITIVE LIPOSOMES; DRUG-DELIVERY; LIPID BILAYERS; SOLUTE RELEASE; CARRIERS; SYSTEMS; ASSEMBLIES; EFFICIENT; VESICLES AB Success of nanoparticle-mediated drug delivery is subject to development of optimal drug release strategies within defined space and time (triggered release). Recently, we reported a novel class of photo-triggerable liposomes prepared from dipalmitoyl phosphatidylcholine (DPPC) and photopolymerizable diacetylene phospholipid (DC8,9PC), that efficiently released entrapped calcein (a water soluble fluorescent dye) upon UV (254 nm) treatment. To develop these formulations for in vivo applications, we have examined phototriggering of these liposomes by visible light, and the effect of released anticancer drugs on cellular toxicity. Sonicated liposomes containing various ratios of DPPC:DC8,9PC and 4 mol% DSPE-PEG2000 were loaded with calcein (Ex/Em, 485/517 nm) or a chemotherapy drug, Doxorubicin (DOX, Ex/Em 490/590 nm). Our initial experiments showed that 514 nm laser treatment of liposomes containing 10 or 20 mol% DC8,9PC for 1-3 min resulted in significant release of calcein. Based on these results, we performed studies with DOX-loaded liposomes. First, biophysical properties (including liposome size and stability) and DOX encapsulation efficiency of the liposomes were determined. Subsequently, the effect of 514 nm laser on DOX release, and cellular toxicity by released DOX were examined. Since liposomes using the 86:10:04 mole ratio of DPPC: DC8,9PC:DSPE-PEG2000, showed highest encapsulation of DOX, these formulations were investigated further. We report that (i) liposomes retained about 70% of entrapped DOX at 37 degrees C in the presence of 0-50% serum. (ii) 514 nm laser treatment resulted in DOX release from liposomes in a wavelength-specific manner. (iii) Laser treatment of co-cultures containing DOX-loaded liposomes and cells (Raji and MCF-7) resulted in at least 2-3 fold improved cell killing as compared to untreated samples. Taken together, the photo-triggerable liposomes described here may provide a platform for future drug delivery applications. To our knowledge, this is the first report demonstrating improved cell killing following light-triggered release of an encapsulated anticancer agent from photosensitive liposomes. Published by Elsevier B.V. C1 [Puri, Anu] NCI Frederick, Membrane Struct & Funct Sect, CCRNP, NIH,Nanobiol Program, Frederick, MD 21702 USA. [Singh, Alok] USN, Res Lab, Ctr Bio Mol Sci & Engn, Washington, DC 20375 USA. RP Puri, A (reprint author), NCI Frederick, Membrane Struct & Funct Sect, CCRNP, NIH,Nanobiol Program, Frederick, MD 21702 USA. EM apuri@helix.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 42 TC 45 Z9 46 U1 3 U2 52 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD JAN PY 2011 VL 1808 IS 1 BP 117 EP 126 DI 10.1016/j.bbamem.2010.07.030 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 701VX UT WOS:000285853800013 PM 20691151 ER PT J AU Nechaev, S Adelman, K AF Nechaev, Sergei Adelman, Karen TI Pol II waiting in the starting gates: Regulating the transition from transcription initiation into productive elongation SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Review DE RNA polymerase II; Gene regulation; Transcription elongation; Polymerase pausing ID RNA-POLYMERASE-II; HEAT-SHOCK GENES; BROMODOMAIN PROTEIN BRD4; CARBOXYL-TERMINAL DOMAIN; MAJOR LATE PROMOTER; P-TEFB; DROSOPHILA-MELANOGASTER; IN-VIVO; C-MYC; CAPPING ENZYME AB Proper regulation of gene expression is essential for the differentiation, development and survival of all cells and organisms. Recent work demonstrates that transcription of many genes, including key developmental and stimulus-responsive genes, is regulated after the initiation step, by pausing of RNA polymerase II during elongation through the promoter-proximal region. Thus, there is great interest in better understanding the events that follow transcription initiation and the ways in which the efficiency of early elongation can be modulated to impact expression of these highly regulated genes. Here we describe our current understanding of the steps involved in the transition from an unstable initially transcribing complex into a highly stable and processive elongation complex. We also discuss the interplay between factors that affect early transcript elongation and the potential physiological consequences for genes that are regulated through transcriptional pausing. Published by Elsevier B.V. C1 [Nechaev, Sergei; Adelman, Karen] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Adelman, K (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. EM adelmank@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences [Z01 ES101987] FX We thank D. Gilchrist and G. Hu for critical reading of the manuscript, G. dos Santos for help with the figures, and J. Lis, D. Price and D. Gilmour for thought-provoking discussions that helped shape this review. This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01 ES101987). NR 135 TC 141 Z9 144 U1 4 U2 34 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD JAN PY 2011 VL 1809 IS 1 BP 34 EP 45 DI 10.1016/j.bbagrm.2010.11.001 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 716WG UT WOS:000287003600003 PM 21081187 ER PT J AU Yang, MY Chaudhary, A Seaman, S Dunty, J Stevens, J Elzarrad, MK Frankel, AE Croix, BS AF Yang, Mi Young Chaudhary, Amit Seaman, Steven Dunty, Jill Stevens, Janine Elzarrad, Mohammed K. Frankel, Arthur E. Croix, Brad St. TI The cell surface structure of tumor endothelial marker 8 (TEM8) is regulated by the actin cytoskeleton SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE Angiogenesis; Endothelial; Actin cytoskeleton; TEM8; ANTXR1 ID TOXIN PROTECTIVE ANTIGEN; ANTHRAX TOXIN; CAPILLARY MORPHOGENESIS; HUMAN-MELANOMA; SMOOTH-MUSCLE; LETHAL FACTOR; RECEPTOR; MICE; GROWTH; VASCULATURE AB Tumor endothelial marker 8 (TEM8) is an integrin-like cell surface protein upregulated on tumor blood vessels and a potential vascular target for cancer therapy. Here, we found that the ability of an anti-TEM8 antibody, clone SB5, to recognize the extracellular domain of TEM8 on the cell surface depends on other host-cell factors. By taking advantage of SB5's ability to distinguish different forms of cell surface TEM8, we identified alpha-smooth muscle actin and transgelin, an actin binding protein, as intracellular factors able to alter TEM8 cell surface structure. Overexpression of either of these proteins in cells converted TEM8 from an SB5-exposed to an SB5-masked form and protected cells from SB5-saporin immunotoxins. Because the predominant form of TEM8 on the cell surface is not recognized by SB5, we also developed a new monoclonal antibody, called AF334, which is able to recognize both the SB5-exposed and the SB5-masked forms of TEM8. AF334-saporin selectively killed TEM8-positive cells independent of TEM8 cell surface structure. These studies reveal that TEM8 exists in different forms at the cell surface, a structure dependent on interactions with components of the actin cytoskeleton, and should aid in the rational design of the most effective diagnostic and therapeutic anti-TEM8 monoclonal antibodies. Published by Elsevier B.V. C1 [Yang, Mi Young; Chaudhary, Amit; Seaman, Steven; Dunty, Jill; Stevens, Janine; Elzarrad, Mohammed K.; Croix, Brad St.] NCI Frederick, Tumor Angiogenesis Sect, MCGP, Frederick, MD 21702 USA. [Frankel, Arthur E.] Scott & White Canc Res Inst, Temple, TX USA. RP Croix, BS (reprint author), NCI Frederick, Tumor Angiogenesis Sect, MCGP, Bldg 560,1050 Boyles St, Frederick, MD 21702 USA. EM stcroix@ncifcrf.gov RI Seaman, Steven/A-2755-2013 OI Seaman, Steven/0000-0003-3349-3334 FU NIH, National Cancer Institute FX We thank Dr. Karlyne Reilly for helpful suggestions and Dr. Lino Tessarollo for critical evaluation of the manuscript. This research was supported by the intramural research program of the NIH, National Cancer Institute. NR 30 TC 19 Z9 19 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JAN PY 2011 VL 1813 IS 1 BP 39 EP 49 DI 10.1016/j.bbamcr.2010.11.013 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 715GC UT WOS:000286867800004 PM 21129411 ER PT J AU Song, MO Freedman, JH AF Song, Min Ok Freedman, Jonathan H. TI Role of hepatocyte nuclear factor 4 alpha in controlling copper-responsive transcription SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE Copper; HNF4 alpha; HepG2 cell; Transcription; p53; Gene expression; ATF3 ID GENE-EXPRESSION; WILSON-DISEASE; HEPG2 CELLS; DNA-BINDING; METAL-IONS; P53; TOXICITY; FACTOR-4-ALPHA; HOMEOSTASIS; MECHANISMS AB Previous global transcriptome and interactome analyses of copper-treated HepG2 cells identified hepatocyte nuclear factor 4 alpha (HNF4 alpha) as a potential master regulator of copper-responsive transcription. Copper exposure caused a decrease in the expression of HNF4 alpha at both mRNA and protein levels, which was accompanied by a decrease in the level of HNF4 alpha binding to its consensus DNA binding sequence. qRT-PCR and RNAi studies demonstrated that changes in HNF4 alpha expression ultimately affected the expressions of its down-stream target genes. Analysis of upstream regulators of HNF4 alpha expression, including p53 and ATF3, showed that copper caused an increase in the steady-state levels of these proteins. These results support a model for copper-responsive transcription in which the metal affects ATF3 expression and stabilizes p53 resulting in the down-regulation of HNF4 alpha expression. In addition, copper may directly affect p53 protein levels. The suppression of HNF4 alpha activity may contribute to the molecular mechanisms underlying the physiological and toxicological consequences of copper toxicity in hepatic-derived cells. Published by Elsevier B.V. C1 [Song, Min Ok; Freedman, Jonathan H.] Natl Inst Environm Hlth Sci, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA. RP Freedman, JH (reprint author), Natl Inst Environm Hlth Sci, Lab Toxicol & Pharmacol, Mail Drop E1-05,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM freedma1@niehs.nih.gov FU NIH; NIEHS [Z01ES102045] FX This work was supported (in part) by the Intramural Research Program of the NIH and NIEHS (Z01ES102045). NR 48 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JAN PY 2011 VL 1813 IS 1 BP 102 EP 108 DI 10.1016/j.bbamcr.2010.09.009 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 715GC UT WOS:000286867800010 PM 20875833 ER PT J AU Aid, S Bosetti, F AF Aid, Saba Bosetti, Francesca TI Targeting cyclooxygenases-1 and-2 in neuroinflammation: Therapeutic implications SO BIOCHIMIE LA English DT Review DE Cyclooxygenase; Neuroinflammation; Prostanoids; Neuroprotection; Microglia; Brain ID INNATE IMMUNE ACTIVATION; INFLAMMATORY RESPONSE; DOCOSAHEXAENOIC ACID; ALZHEIMERS-DISEASE; LIPID MEDIATORS; INDUCIBLE CYCLOOXYGENASE; COX-2 INHIBITION; NERVOUS-SYSTEM; CONTROL BRAIN; RAT AB Neuroinflammation has been implicated in the pathogenesis or the progression of a variety of acute and chronic neurological and neurodegenerative disorders, including Alzheimer's disease. Prostaglandin H synthases or cyclooxygenases (COX -1 and COX-2) play a central role in the inflammatory cascade by converting arachidonic acid into bioactive prostanoids. In this review, we highlighted recent experimental data that challenge the classical view that the inducible isoform COX-2 is the most appropriate target to treat neuroinflammation. First, we discuss data showing that COX-2 activity is linked to anti-inflammatory and neuroprotective actions and is involved in the generation of novel lipid mediators with pro-resolution properties. Then, we review recent data demonstrating that COX-1, classically viewed as the homeostatic isoform, is actively involved in brain injury induced by pro-inflammatory stimuli including A beta, lipopolysaccharide, IL-1 beta, and TNF-alpha. Overall, we suggest revisiting the traditional views on the roles of each COX during neuroinflammation and we propose COX-1 inhibition as a viable therapeutic approach to treat CNS diseases with a marked inflammatory component. Published by Elsevier Masson SAS. C1 [Aid, Saba; Bosetti, Francesca] NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Bosetti, F (reprint author), NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, 9 Mem Dr,Bldg 9,Room 1S126, Bethesda, MD 20892 USA. EM frances@mail.nih.gov FU Intramural NIH HHS [Z99 NS999999] NR 55 TC 64 Z9 72 U1 1 U2 17 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD JAN PY 2011 VL 93 IS 1 SI SI BP 46 EP 51 DI 10.1016/j.biochi.2010.09.009 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 710TG UT WOS:000286539300009 PM 20868723 ER PT J AU Ohashi, N Nomura, W Narumi, T Lewin, NE Itotani, K Blumberg, PM Tamamura, H AF Ohashi, Nami Nomura, Wataru Narumi, Tetsuo Lewin, Nancy E. Itotani, Kyoko Blumberg, Peter M. Tamamura, Hirokazu TI Fluorescent-Responsive Synthetic C1b Domains of Protein Kinase C delta as Reporters of Specific High-Affinity Ligand Binding SO BIOCONJUGATE CHEMISTRY LA English DT Article ID CONFORMATIONALLY CONSTRAINED ANALOGS; PHORBOL ESTER BINDING; INCLUSION PHENOMENA; BETA-CYCLODEXTRIN; DAG-LACTONES; PK-C; ISOZYMES; DIACYLGLYCEROL; ACTIVATION; APOPTOSIS AB Protein kinase C (PKC) is a critical cell signaling pathway involved in many disorders such as cancer and Alzheimer-type dementia. To date, evaluation of PKC ligand binding affinity has been performed by competitive studies against radiolabeled probes that are problematic for high-throughput screening. In the present study, we have developed a fluorescent-based binding assay system for identifying ligands that target the PKC ligand binding domain (C1 domain). An environmentally sensitive fluorescent dye (solvatochromic fluorophore), which has been used in multiple applications to assess protein-binding interactions, was inserted in proximity to the binding pocket of a novel PKC delta C1b domain. These resultant fluorescent-labeled delta C1b domain analogues underwent a significant change in fluorescent intensity upon ligand binding, and we further demonstrate that the fluorescent delta C1b domain analogues can be used to evaluate ligand binding affinity. C1 [Ohashi, Nami; Nomura, Wataru; Narumi, Tetsuo; Itotani, Kyoko; Tamamura, Hirokazu] Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Dept Med Chem, Chiyoda Ku, Tokyo 1010062, Japan. [Lewin, Nancy E.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Nomura, W (reprint author), Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Dept Med Chem, Chiyoda Ku, 2-3-10 Kandasurugadai, Tokyo 1010062, Japan. EM nomura.mr@tmd.ac.jp; tamamura.mr@tmd.ac.jp RI Nomura, Wataru/F-5812-2015 FU Naito Foundation for Science; NIH, Center for Cancer Research, National Cancer Institute; Japan Society for Promotion of Science FX The authors thank Professor Kazunari Akiyoshi (Graduate School of Engineering, Kyoto University) for assistance in the CD experiments. This study was supported in part by the Naito Foundation for Science (to W. N.) and in part by the Intramural Research Program of the NIH, Center for Cancer Research, National Cancer Institute. N. O. is supported by the Japan Society for Promotion of Science. NR 28 TC 2 Z9 2 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN PY 2011 VL 22 IS 1 BP 82 EP 87 DI 10.1021/bc100414a PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 707SM UT WOS:000286306300011 PM 21175182 ER PT S AU Ramakrishnan, B Boeggeman, E Pasek, M Qasba, PK AF Ramakrishnan, Boopathy Boeggeman, Elizabeth Pasek, Maria Qasba, Pradman K. BE Mark, SS TI Bioconjugation Using Mutant Glycosyltransferases for the Site-Specific Labeling of Biomolecules with Sugars Carrying Chemical Handles SO BIOCONJUGATION PROTOCOLS: STRATEGIES AND METHODS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Glycosyltransferase; Monoclonal antibody (mAb); Asn-linked glycan (N-glycan); Single-chain antibody (scFv); Human polypeptidyl-alpha-N-acetylgalactosaminyltransferase (h-pp alpha Gal-NAc-T); alpha 1,3-Galactosyltransferase (alpha 3Gal-T); 2-Acetonyl-2-deoxy-galactose (C2-keto-Gal) ID MONOCLONAL-ANTIBODIES; N-GLYCANS; CONJUGATION; GLYCOSYLATION; DESIGN; FC AB This chapter presents a technique that employs mutant glycosyltransferase enzymes for the site-specific bioconjugation of biomolecules via a glycan moiety to facilitate the development of a targeted drug delivery system. The target specificity of this methodology is based on unique sugar residues that are present on glycoproteins or engineered glycopeptides. The glycosyltransferases used in this approach have been manipulated in a way that confers the ability to transfer a modified sugar residue with a chemical handle to a sugar moiety of the glycoprotein or to a polypeptide tag of an engineered nonglycoprotein. The availability of the modified sugar moiety thus makes it possible to link cargo molecules at specific sites. The cargo may be comprised of for example, biotin or fluorescent tags for detection, imaging agents for magnetic resonance imaging (MRI), or cytotoxic drugs for cancer therapy. C1 [Ramakrishnan, Boopathy; Boeggeman, Elizabeth; Pasek, Maria; Qasba, Pradman K.] NCI, Struct Glycobiol Sect, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA. [Ramakrishnan, Boopathy; Boeggeman, Elizabeth] SAIC Frederick Inc, Basic Sci Program, Frederick, MD USA. RP Ramakrishnan, B (reprint author), NCI, Struct Glycobiol Sect, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA. NR 14 TC 8 Z9 8 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-150-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 751 BP 281 EP 296 DI 10.1007/978-1-61779-151-2_17 D2 10.1007/978-1-61779-151-2 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BVR26 UT WOS:000292530300017 PM 21674337 ER PT S AU Kubler-Kielb, J AF Kubler-Kielb, Joanna BE Mark, SS TI Conjugation of LPS-Derived Oligosaccharides to Proteins Using Oxime Chemistry SO BIOCONJUGATION PROTOCOLS: STRATEGIES AND METHODS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE LPS; Vaccine; Conjugate; Kdo; Aminooxy; Hydroxylamine; Oxime ID O-SPECIFIC POLYSACCHARIDE; SHIGELLA-DYSENTERIAE TYPE-1; FLEXNERI TYPE-2A; VACCINES; IMMUNOGENICITY; EFFICACY; CHILDREN; SAFETY; ADULTS; MICE AB Conjugates of bacterial polysaccharides covalently bound to a carrier protein are among licensed human vaccines. Immunization of adults and children with these vaccines results in induction of saccharide-specific antibodies composed mainly of the IgG class. Depending on the choice of coupling technique, saccharides can be attached to a protein by either multiple- or single-point attachments. While the first method is suitable for high molecular mass polysaccharides, the second one is beneficial for low-molecular mass compounds such as synthetic carbohydrates or bacterial oligosaccharides obtained by different degradation procedures. This chapter describes a method for coupling low-molecular mass lipopolysaccharide (LPS)-derived oligosaccharides composed of a core or a short O-specific polysaccharide-core fragment (O-SPC) to a carrier protein by a single-point attachment. Conjugation is performed between the carbonyl group of the reducing terminal of 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) exposed after acid hydrolyses of LPS and the aminooxy group of a bifunctional linker bound to the protein. This is an efficient reaction that can be carried out quickly and under mild conditions. Conjugates thus prepared using this approach preserve the external nonreducing end of the sugar chain and can induce antibodies to both conjugate components. Consequently, this method is highly suitable for the preparation of LPS-based human vaccines. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev & Mol Immun, NIH, Bethesda, MD USA. RP Kubler-Kielb, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev & Mol Immun, NIH, Bethesda, MD USA. FU Intramural NIH HHS NR 17 TC 2 Z9 2 U1 0 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-150-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 751 BP 317 EP 327 DI 10.1007/978-1-61779-151-2_20 D2 10.1007/978-1-61779-151-2 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BVR26 UT WOS:000292530300020 PM 21674340 ER PT J AU Wehby, GL Fletcher, JM Lehrer, SF Moreno, LM Murray, JC Wilcox, A Lie, RT AF Wehby, George L. Fletcher, Jason M. Lehrer, Steven F. Moreno, Lina M. Murray, Jeffrey C. Wilcox, Allen Lie, Rolv T. TI A Genetic Instrumental Variables Analysis of the Effects of Prenatal Smoking on Birth Weight: Evidence from Two Samples SO BIODEMOGRAPHY AND SOCIAL BIOLOGY LA English DT Article ID MATERNAL SMOKING; NICOTINE DEPENDENCE; WEAK INSTRUMENTS; UNITED-STATES; TOBACCO USE; MENDELIAN RANDOMIZATION; ORAL CLEFTS; PREGNANCY; ASSOCIATION; CHILDREN AB There is a large literature showing the detrimental effects of prenatal smoking on birth and childhood health outcomes. It is somewhat unclear, though, whether these effects are causal or reflect other characteristics and choices by mothers who choose to smoke that may also affect child health outcomes or biased reporting of smoking. In this paper, we use genetic markers that predict smoking behaviors as instruments to address the endogeneity of smoking choices in the production of birth and childhood health outcomes. Our results indicate that prenatal smoking produces more dramatic declines in birth weight than estimates that ignore the endogeneity of prenatal smoking, which is consistent with previous studies with non-genetic instruments. We use data from two distinct samples from Norway and the United States with different measured instruments and find nearly identical results. The study provides a novel application that can be extended to study several behavioral impacts on health and social and economic outcomes. C1 [Wehby, George L.] Univ Iowa, Dept Hlth Management & Policy, Coll Publ Hlth, Iowa City, IA 52242 USA. [Fletcher, Jason M.] Yale Univ, Dept Epidemiol & Publ Hlth, Div Hlth Policy & Adm, New Haven, CT 06520 USA. [Lehrer, Steven F.] Queens Univ, Sch Policy Studies, Kingston, ON, Canada. [Moreno, Lina M.] Univ Iowa, Dept Orthodont, Dows Inst, Iowa City, IA 52242 USA. [Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Wilcox, Allen] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Lie, Rolv T.] Univ Bergen, Sect Med Stat, Bergen, Norway. RP Wehby, GL (reprint author), Univ Iowa, Dept Hlth Management & Policy, Coll Publ Hlth, 200 Hawkins Dr,E205 GH, Iowa City, IA 52242 USA. EM george-wehby@uiowa.edu; jason.fletcher@yale.edu OI Wilcox, Allen/0000-0002-3376-1311 FU Intramural NIH HHS; NICHD NIH HHS [P01 HD031921, P01-HD31921]; NIDCR NIH HHS [R01 DE020895-01, 1 R01 DE020895-01, 1 R03 DE018394, R01 DE020895, R03 DE018394, R03 DE018394-02] NR 73 TC 10 Z9 10 U1 2 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1948-5565 J9 BIODEMOGR SOC BIOL JI Biodemography Soc. Biol. PY 2011 VL 57 IS 1 SI SI BP 3 EP 32 AR PII 937662953 DI 10.1080/19485565.2011.564468 PG 30 WC Demography; Social Sciences, Biomedical; Sociology SC Demography; Biomedical Social Sciences; Sociology GA 765BX UT WOS:000290679500002 PM 21845925 ER PT J AU Ho, M AF Ho, Mitchell TI Advances in Liver Cancer Antibody Therapies A Focus on Glypican-3 and Mesothelin SO BIODRUGS LA English DT Article ID HUMAN HEPATOCELLULAR-CARCINOMA; GOLABI-BEHMEL-SYNDROME; DEVELOPMENTALLY-REGULATED TRANSCRIPT; HUMAN MONOCLONAL-ANTIBODY; OVARIAN-CANCER; HIGH-AFFINITY; ANTITUMOR-ACTIVITY; PANCREATIC-CANCER; MOLECULAR-CLONING; IMMUNOTOXIN SS1P AB Liver cancer is one of the most common malignancies worldwide. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the two most common primary liver cancers, yet there have been no significant advances in effective therapeutics. There is an urgent need to identify molecular targets for the development of novel therapeutic approaches. In this review, glypican-3 (GPC3) and mesothelin are discussed, with a focus on their potential as targets for antibody therapy in liver cancer. GPC3 and mesothelin are glycosylphosphatidylinositol-anchored proteins present on the cell surface. They are attractive candidates for liver cancer therapy given that GPC3 and mesothelin show high expression in HCC and CCA, respectively. Antibody drugs targeting GPC3 or mesothelin have shown anti-cancer activity in mice. Humanized or chimeric IgG molecules based on first-generation murine monoclonal antibodies against these antigens are being evaluated in clinical studies. Recently, fully human monoclonal antibodies against GPC3 and mesothelin have been isolated by antibody phage display technology that may provide opportunities for novel cancer therapy. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH,Intramural Res Program, Bethesda, MD 20892 USA. RP Ho, M (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH,Intramural Res Program, Bldg 37, Bethesda, MD 20892 USA. RI Ho, Mitchell/F-5059-2015 FU National Institutes of Health, National Cancer Institute (NCI), Center for Cancer Research; Ovarian Cancer Research Fund Individual Investigator Award; Mesothelioma Applied Research Foundation; NCI; China Normal University (Shanghai, China) FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute (NCI), Center for Cancer Research. Dr Mitchell Ho is also supported by an Ovarian Cancer Research Fund Individual Investigator Award, a Mesothelioma Applied Research Foundation Grant in Honor of Craig Kozicki, a Zi-jiang Lecture Professorship from East China Normal University (Shanghai, China), and the NCI Director's Intramural Innovation Award for Principal Investigators. Dr Ho is a co-inventor on patents assigned to the US, as represented by the Department of Health and Human Services, for the investigational products. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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. The author has no conflict of interest directly relevant to the content of this review. NR 83 TC 14 Z9 17 U1 2 U2 6 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1173-8804 J9 BIODRUGS JI Biodrugs PY 2011 VL 25 IS 5 BP 275 EP 284 PG 10 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA 835MK UT WOS:000296040300001 PM 21942912 ER PT J AU Moitra, K Dean, M AF Moitra, Karobi Dean, Michael TI Evolution of ABC transporters by gene duplication and their role in human disease SO BIOLOGICAL CHEMISTRY LA English DT Review DE drug resistance; gene birth; gene death; human health ID MAJOR HISTOCOMPATIBILITY COMPLEX; BINDING CASSETTE TRANSPORTER; MULTIDRUG-RESISTANCE; BREAST-CANCER; DIETARY-CHOLESTEROL; P-GLYCOPROTEIN; SUPERFAMILY; FAMILY; DEATH; CELLS AB The ATP-binding cassette (ABC) transporter genes represent the largest family of transporters and these genes are abundant in the genome of all vertebrates. Through analysis of the genome sequence databases we have characterized the full complement of ABC genes from several mammals and other vertebrates. Multiple gene duplication and deletion events were identified in ABC genes in different lineages indicating that the process of gene evolution is still ongoing. Gene duplication resulting in either gene birth or gene death plays a major role in the evolution of the vertebrate ABC genes. The understanding of this mechanism is important in the context of human health because these ABC genes are associated with human disease, involving nearly all organ systems of the body. In addition, ABC genes play an important role in the development of drug resistance in cancer cells. Future genetic, functional, and evolutionary studies of ABC transporters will provide important insight into human and animal biology. C1 [Moitra, Karobi; Dean, Michael] Natl Canc Inst, Expt Immunol Lab, Human Genet Sect, Canc & Inflammat Program, Frederick, MD 21702 USA. RP Dean, M (reprint author), Natl Canc Inst, Expt Immunol Lab, Human Genet Sect, Canc & Inflammat Program, Frederick, MD 21702 USA. EM deanm@mail.nih.gov RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU National Institutes of Health, National Cancer Institute FX We would like to thank Katy Limpert for help with compiling sequence data. This research was supported (in part) by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 40 TC 29 Z9 33 U1 1 U2 15 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD JAN PY 2011 VL 392 IS 1-2 BP 29 EP 37 DI 10.1515/BC.2011.006 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 706AN UT WOS:000286183700005 PM 21194360 ER PT S AU Volokhov, DV Kong, H Herold, K Chizhikov, VE Rasooly, A AF Volokhov, Dmitriy V. Kong, Hyesuk Herold, Keith Chizhikov, Vladimir E. Rasooly, Avraham BE Khademhosseini, A Suh, KY Zourob, M TI Oligonucleotide Microarrays for Identification of Microbial Pathogens and Detection of Their Virulence-Associated or Drug-Resistance Determinants SO BIOLOGICAL MICROARRAYS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Microarray; Microbial pathogens; Virulence factors; Food safety ID ESCHERICHIA-COLI O157-H7; BACTERIAL PHYLOGENY; SIGNATURE SEQUENCES; QUANTITATIVE ASSAY; DNA PROBES; HYBRIDIZATION; GENE; MULTIANALYTE; IMMUNOASSAY; STABILITY AB Microarrays are spatially ordered arrays with ligands chemically immobilized in discrete spots on a solid matrix, usually a microscope slide. Microarrays are a high-throughput large-scale screening system enabling simultaneous identification fa large number of labeled target molecules (up to several hundred thousand) that bind specifically to the immobilized ligands of the array. DNA microarrays represent a promising tool for clinical, environmental, and industrial microbiology since the technology allows relatively rapid identification of large number of genetic determinants simultaneously, providing detailed genomic level information regarding the pathogen species, including identification of their virulence-associated factors and the presence of antibiotic resistance genes. In this chapter, we describe key aspects and methodologies important for the development and use of DNA microarrays for microbial diagnostics. C1 [Volokhov, Dmitriy V.; Kong, Hyesuk; Chizhikov, Vladimir E.] US FDA, Ctr Biol Evaluat & Res, Kensington, MD USA. [Herold, Keith] Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA. [Rasooly, Avraham] NCI, NIH, US FDA, Bethesda, MD 20892 USA. RP Volokhov, DV (reprint author), US FDA, Ctr Biol Evaluat & Res, Kensington, MD USA. NR 60 TC 3 Z9 3 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-934115-95-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 671 BP 55 EP 94 DI 10.1007/978-1-59745-551-0_3 D2 10.1007/978-1-59745-551-0 PG 40 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BSA51 UT WOS:000284031200003 PM 20967623 ER PT J AU Matsumoto, A Matsumoto, K Matsumoto, S Hyodo, F Sowers, AL Koscielniak, JW Devasahayam, N Subramanian, S Mitchell, JB Krishna, MC AF Matsumoto, Atsuko Matsumoto, Ken-ichiro Matsumoto, Shingo Hyodo, Fuminori Sowers, Anastasia L. Koscielniak, Janusz W. Devasahayam, Nallathamby Subramanian, Sankaran Mitchell, James B. Krishna, Murali C. TI Intracellular Hypoxia of Tumor Tissue Estimated by Noninvasive Electron Paramagnetic Resonance Oximetry Technique Using Paramagnetic Probes SO BIOLOGICAL & PHARMACEUTICAL BULLETIN LA English DT Article DE electron paramagnetic resonance oximetry; tissue oxygen concentration; nitroxide; tumor hypoxia; hyperoxia ID IN-VIVO; LITHIUM PHTHALOCYANINE; REDOX STATUS; OXYGEN CONCENTRATION; EPR OXIMETRY; SPECTROSCOPY; MRI; CARBOGEN; BLOOD; CELLS AB Electron paramagnetic resonance (EPR) oximetry at 700 MHz operating frequency employing a surface coil resonator is used to assess tissue partial pressure of oxygen (pO(2)) using paramagnetic media whose linewidth and decay constant are related to oxygen concentration. Differences in extracellular and intracellular pO(2) in squamous cell carcinoma (SCC) tumor tissue were tested using several types of water-soluble paramagnetic media, which localize extracellularly or permeate through the cell membrane. The nitroxide carboxy-PROXYL (CxP) can only be distributed in blood plasma and extracellular fluids whereas the nitroxides carbamoyl-PROXYL (CmP) and TEMPOL (TPL) can permeate cell membranes and localize intracellularly. EPR signal decay constant and the linewidth of the intravenously administered nitroxides in SCC tumor tissues implanted in mouse thigh and the contralateral normal muscle of healthy mice breathing gases with different pO(2) were compared. The pO(2) in the blood can depend on the oxygen content in the breathing gas while tissue PO2 was not directly influenced by pO(2) in the breathing gas. The decay constants of CmP and TPL in tumor tissue were significantly larger than in the normal muscles, and lower linewidths of CmP and TPL in tumor tissue was observed. The SCC tumor showed intracellular hypoxia even though the extracellular pO(2) is similar to normal tissue in the peripheral region. C1 [Matsumoto, Atsuko; Matsumoto, Ken-ichiro; Matsumoto, Shingo; Hyodo, Fuminori; Sowers, Anastasia L.; Koscielniak, Janusz W.; Devasahayam, Nallathamby; Subramanian, Sankaran; Mitchell, James B.; Krishna, Murali C.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Matsumoto, Atsuko; Matsumoto, Ken-ichiro] Natl Inst Radiol Sci, Heavy Ion Radiobiol Res Grp, Res Ctr Charged Particle Therapy, Chiba 2638555, Japan. [Hyodo, Fuminori] Kyushu Univ, Innovat Ctr Med Redox Nav, Fukuoka 8128582, Japan. RP Matsumoto, K (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM matsumok@nirs.go.jp NR 25 TC 9 Z9 9 U1 0 U2 10 PU PHARMACEUTICAL SOC JAPAN PI TOKYO PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN SN 0918-6158 J9 BIOL PHARM BULL JI Biol. Pharm. Bull. PD JAN PY 2011 VL 34 IS 1 BP 142 EP 145 DI 10.1248/bpb.34.142 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 699YP UT WOS:000285699100024 PM 21212532 ER PT J AU Papaleo, F Weinberger, DR AF Papaleo, Francesco Weinberger, Daniel R. TI Dysbindin and Schizophrenia: It's Dopamine and Glutamate All Over Again SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID PREFRONTAL CORTEX; HIPPOCAMPAL-FORMATION; SUSCEPTIBILITY GENE; MESSENGER-RNA; DTNBP1; EXPRESSION; SANDY; MICE C1 [Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA. [Papaleo, Francesco] Italian Inst Technol, Dept Neurosci & Brain Technol, Genoa, Italy. RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Room 45-235, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov OI Papaleo, Francesco/0000-0002-6326-0657 FU Intramural NIH HHS [Z01 MH002904-01] NR 19 TC 22 Z9 22 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 2011 VL 69 IS 1 BP 2 EP 4 DI 10.1016/j.biopsych.2010.10.028 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 702RH UT WOS:000285911300001 PM 21145442 ER PT J AU Morgan, HL Turner, DC Corlett, PR Absalom, AR Adapa, R Arana, FS Pigott, J Gardner, J Everitt, J Haggard, P Fletcher, PC AF Morgan, Hannah L. Turner, Danielle C. Corlett, Philip R. Absalom, Anthony R. Adapa, Ram Arana, Fernando S. Pigott, Jennifer Gardner, Jenny Everitt, Jessica Haggard, Patrick Fletcher, Paul C. TI Exploring the Impact of Ketamine on the Experience of Illusory Body Ownership SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Body ownership; ketamine; psychosis; rubber hand ID RUBBER-HAND ILLUSION; PSYCHOTIC SYMPTOMS RSPS; HEALTHY-VOLUNTEERS; RATING-SCALE; DELUSIONS; BRAIN; SCHIZOPHRENIA; PERSONALITY; INTEGRATION; RESPONSES AB Background: Our sense of body ownership is profound and familiar, yet it may be misleading. In the rubber-hand illusion, synchronous tactile and visual stimulation lead to the experience that a rubber hand is actually one's own. This illusion is stronger in schizophrenia. Given the evidence that ketamine, a noncompetitive N-methyl-D-aspartate antagonist reproduces symptoms of schizophrenia, we sought to determine whether the rubber-hand illusion is augmented by ketamine. Methods: We studied 15 healthy volunteers in a within-subjects placebo-controlled study. All volunteers carried out two versions of the rubber-hand task, each under both placebo and ketamine infusions. In one task, they saw a rubber hand being stroked in synchrony with tactile stimulation of their real, hidden hand. In the other, stroking of the real and rubber hands was asynchronous. We recorded subjective changes in sense of ownership, as well as participants' ability to localize their hidden hand. Results: Ketamine was associated with significant increases in subjective measures of the illusion and in hand mislocalization. Although asynchronous visuotactile stimulation attenuates the strength of the illusion during both placebo and ketamine, there remained a significant illusory effect during asynchronous visuotactile stimulation under ketamine compared with placebo. The strength of the illusion during asynchronous visuotactile stimulation correlated with other subjective effects of the drug. Conclusions: Ketamine mimics the perturbed sense of body ownership seen in schizophrenia, suggesting that it produces a comparable alteration in integration of information across sensory domains and in the subjective and behavioral consequences of such integration. C1 [Morgan, Hannah L.; Arana, Fernando S.; Everitt, Jessica; Fletcher, Paul C.] Univ Cambridge, Dept Psychiat, Brain Mapping Unit, Cambridge CB2 2QQ1, England. [Turner, Danielle C.] St Johns Coll, Cambridge, England. [Corlett, Philip R.] Yale Univ, Dept Psychiat, Ribicoff Res Facil, Connecticut Mental Hlth Ctr, New Haven, CT 06520 USA. [Absalom, Anthony R.] Univ Groningen, Univ Med Ctr Groningen, Dept Anaesthet, NL-9713 AV Groningen, Netherlands. [Absalom, Anthony R.; Adapa, Ram] Addenbrookes Hosp, Univ Div Anaesthesia, Cambridge, England. [Arana, Fernando S.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. [Gardner, Jenny] Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Cambridge CB2 2QQ1, England. [Pigott, Jennifer] UCL, Sch Med, London W1N 8AA, England. [Haggard, Patrick] UCL, Sch Med, London W1N 8AA, England. RP Fletcher, PC (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Box 189, Cambridge CB2 2QQ1, England. EM pcf22@cam.ac.uk RI Adapa, Ram/D-7925-2012; OI Adapa, Ram/0000-0002-9845-8532; Corlett, Philip/0000-0002-5368-1992; Absalom, Anthony/0000-0001-7563-9157 FU Wellcome Trust; Bernard Wolfe Health Neuroscience Fund; Medical Research Council-Wellcome Trust; Biotechnology and Biological Sciences Research Council; Leverhulme Trust FX This work was supported by the Wellcome Trust and the Bernard Wolfe Health Neuroscience Fund. It was carried out within the Wellcome Trust Clinical Research Facility (Addenbrooke's Hospital, Cambridge) and Medical Research Council-Wellcome Trust funded Behavioral and Clinical Neuroscience Institute.; PCF has received a consultancy fee for unrelated work with GlaxoSmithKline. PRC receives unrelated research support from AstraZeneca Pharmaceuticals and Pfizer. PH was supported by a Biotechnology and Biological Sciences Research Council project grant and a Leverhulme Trust Major Research Fellowship. All other authors report no biomedical financial interests or potential conflicts of interest. NR 41 TC 32 Z9 34 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 2011 VL 69 IS 1 BP 35 EP 41 DI 10.1016/j.biopsych.2010.07.032 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 702RH UT WOS:000285911300007 PM 20947068 ER PT J AU Gonzalez-Nilo, F Perez-Acle, T Guinez-Molinos, S Geraldo, DA Sandoval, C Yevenes, A Santos, LS Laurie, VF Mendoza, H Cachau, RE AF Gonzalez-Nilo, Fernando Perez-Acle, Tomas Guinez-Molinos, Sergio Geraldo, Daniela A. Sandoval, Claudia Yevenes, Alejandro Santos, Leonardo S. Felipe Laurie, V. Mendoza, Hegaly Cachau, Raul E. TI Nanoinformatics: an emerging area of information technology at the intersection of bioinformatics, computational chemistry and nanobiotechnology SO BIOLOGICAL RESEARCH LA English DT Article DE Bioinformatics; molecular simulation; nanobiotechnology; nanoinformatics; nanomedicine ID MOLECULAR-DYNAMICS SIMULATIONS; HIV-1 REVERSE-TRANSCRIPTASE; HR-LIKE RESPONSE; STRUCTURAL GENOMICS; FORCE-FIELDS; PENICILLIUM-PURPUROGENUM; CARBON NANOTUBES; PROTEIN; INHIBITORS; DELIVERY AB After the progress made during the genomics era, bioinformatics was tasked with supporting the flow of information generated by nanobiotechnology efforts. This challenge requires adapting classical bioinformatic and computational chemistry tools to store, standardize, analyze, and visualize nanobiotechnological information. Thus, old and new bioinformatic and computational chemistry tools have been merged into a new sub-discipline: nanoinformatics. This review takes a second look at the development of this new and exciting area as seen from the perspective of the evolution of nanobiotechnology applied to the life sciences. The knowledge obtained at the nano-scale level implies answers to new questions and the development of new concepts in different fields. The rapid convergence of technologies around nanobiotechnologies has spun off collaborative networks and web platforms created for sharing and discussing the knowledge generated in nanobiotechnology. The implementation of new database schemes suitable for storage, processing and integrating physical, chemical, and biological properties of nanoparticles will be a key element in achieving the promises in this convergent field. In this work, we will review some applications of nanobiotechnology to life sciences in generating new requirements for diverse scientific fields, such as bioinformatics and computational chemistry. C1 [Gonzalez-Nilo, Fernando] Univ Talca, Ctr Bioinformat & Mol Simulat, 2 Norte 685,Casilla 721, Talca, Chile. [Perez-Acle, Tomas] Univ Chile, Fac Ciencias Fis & Matemat, CMM, Computat Biol Lab DLab, Santiago, Chile. [Cachau, Raul E.] NCI, ABCC ISP, Sci Applicat Int Corp, Frederick Inc, Frederick, MD 21702 USA. RP Gonzalez-Nilo, F (reprint author), Univ Talca, Ctr Bioinformat & Mol Simulat, 2 Norte 685,Casilla 721, Talca, Chile. EM dgonzalez@utalca.cl RI Santos, Leonardo/A-7953-2008; Laurie, V. Felipe/C-4041-2012; Perez-Acle, Tomas/F-7176-2012; Gonzalez-Nilo, Fernando/M-5671-2016; OI Santos, Leonardo/0000-0003-0908-0134; Perez-Acle, Tomas/0000-0002-3769-390X; Yevenes, Alejandro/0000-0003-3799-1509; Gonzalez-Nilo, Fernando/0000-0001-6857-3575; Laurie, Felipe/0000-0003-4465-2337 FU ACTION-GRID project; PBCT Anillo Cientifico [ACT/24]; Fondecyt [3100037, 1100882]; Instituto Milenio Centro Interdisciplinario de Neurociencias de Valparaiso (CINV); National Cancer Institute, National Institutes of Health [N01-CO-12400, HHSN261200800001E] FX This review was supported in part by ACTION-GRID project, PBCT Anillo Cientifico ACT/24, Fondecyt Project 3100037 and 1100882, and Instituto Milenio Centro Interdisciplinario de Neurociencias de Valparaiso (CINV). We thank Fabian Avila (UTalca) and Raul Araya-Secchi (UChile) for their great support to this initiative.r This work was funded in part with funds from the National Cancer Institute, National Institutes of Health, under contracts No. N01-CO-12400 and HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies IF the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NR 85 TC 5 Z9 6 U1 1 U2 18 PU SOC BIOLGIA CHILE PI SANTIAGO PA CASILLA 16164, SANTIAGO 9, CHILE SN 0716-9760 EI 0717-6287 J9 BIOL RES JI Biol. Res. PY 2011 VL 44 IS 1 BP 43 EP 51 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 750JF UT WOS:000289541700006 PM 21720680 ER PT J AU Wolff, D Schleuning, M von Harsdorf, S Bacher, U Gerbitz, A Stadler, M Ayuk, F Kiani, A Schwerdtfeger, R Vogelsang, GB Kobbe, G Gramatzki, M Lawitschka, A Mohty, M Pavletic, SZ Greinix, H Holler, E AF Wolff, Daniel Schleuning, Michael von Harsdorf, Stephanie Bacher, Ulrike Gerbitz, Armin Stadler, Michael Ayuk, Francis Kiani, Alexander Schwerdtfeger, Rainer Vogelsang, Georgia B. Kobbe, Guido Gramatzki, Martin Lawitschka, Anita Mohty, Mohamad Pavletic, Steven Z. Greinix, Hildegard Holler, Ernst TI Consensus Conference on Clinical Practice in Chronic GVHD: Second-Line Treatment of Chronic Graft-versus-Host Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic hematopoietic stem cell transplantation; Chronic GVHD; Bone marrow transplantation; Immunosuppressive therapy ID STEM-CELL TRANSPLANTATION; WORKING GROUP-REPORT; STEROID-REFRACTORY ACUTE; BONE-MARROW-TRANSPLANTATION; LOW-DOSE METHOTREXATE; MONOCLONAL-ANTIBODY TREATMENT; RECEPTOR FUSION PROTEIN; RESISTANT CHRONIC GVHD; REGULATORY T-CELLS; MYCOPHENOLATE-MOFETIL AB Steroid refractory chronic graft-versus-host disease (cGVHD) is associated with a significant morbidity and mortality. Although first-line treatment of cGVHD is based on controlled trials, second-line treatment is almost solely based on phase II trials or retrospective analyses. The consensus conference on clinical practice in cGVHD held in Regensburg aimed to achieve a consensus on the current evidence of treatment options as well as to provide guidelines for daily clinical practice. Treatment modalities are the use of steroids and calcineurin inhibitors as well as immunomodulating modalities (photopheresis, mTOR-inhibitors, thalidomide, hydroxychloroquine, vitamin A analogs, clofazimine), and cytostatic agents (mycophenolate mofetil, methotrexate, cyclophosphamide, pentostatin). Recent reports showed some efficacy of rituximab, alemtuzumab, and etanercept in selected patients. Moreover, tyrosine kinase inhibitors such as imatinib came into the field because of their ability to interfere with the platelet-derived growth factor (PDGF-R) pathway involved in fibrosis. An other treatment option is low-dose thoracoabdominal irradiation. Although different treatment options are available, the "trial-and-error system" remains the only way to identify the drug effective in the individual patient, and valid biomarkers are eagerly needed to identify the likelihood of response to a drug in advance. Moreover, the sparse evidence for most treatment entities indicates the urgent need for systematic evaluation of second-line treatment options in cGVHD. Biol Blood Marrow Transplant 17: 1-17 (2011) (C) 2011 American Society for Blood and Marrow Transplantation C1 [Wolff, Daniel; Holler, Ernst] Univ Regensburg, Dept Hematol & Clin Oncol, D-93053 Regensburg, Germany. [Schleuning, Michael; Schwerdtfeger, Rainer] DKD, Wiesbaden, Germany. [von Harsdorf, Stephanie] Univ Ulm, Dept Internal Med 3, D-89069 Ulm, Germany. [Bacher, Ulrike; Ayuk, Francis] UCCH, Interdisciplinaiy Clin Stem Cell Transplantat, Hamburg, Germany. [Gerbitz, Armin] Charite, Dept Internal Med 3, Berlin, Germany. [Stadler, Michael] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, D-3000 Hannover, Germany. [Kiani, Alexander] Univ Dresden, Dept Internal Med 1, Dresden, Germany. [Vogelsang, Georgia B.] Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. [Kobbe, Guido] Univ Duesseldorf, Dept Hematol, Dusseldorf, Germany. [Gramatzki, Martin] Univ Kiel, Dept Hematol, D-24098 Kiel, Germany. [Lawitschka, Anita] St Anna Childrens Hosp, A-1090 Vienna, Austria. [Mohty, Mohamad] Univ Nantes, Dept Hematol, F-44035 Nantes, France. [Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Greinix, Hildegard] Med Univ Vienna, Dept Internal Med 1, Vienna, Austria. RP Wolff, D (reprint author), Univ Regensburg, Dept Hematol & Oncol, FJ Strauss Allee 11, D-93053 Regensburg, Germany. EM daniel.wolff@klinik.uni-regensburg.de RI Gramatzki, Martin/A-9533-2010 FU Jose Carreras Foundation; Wyeth FX The authors thank all participating transplantation centers of conferences and surveys including representatives from HCT centers in Augsburg, Basel, Berlin, Cologne, Dresden, Duesseldorf, Erlangen, Essen, Freiburg, Greifswald, Hamburg, Hannover, Heidelberg, Jena, Kiel, Leipzig, Linz, Mainz, Munster, Munich, Nantes, Nuernberg, Oldenburg, Paris, Regensburg, Rostock, Tuebingen, Ulm, Vienna, Wiesbaden, and Wuerzburg. The authors thank Anna Hackl for evaluating the survey on treatment of cGVHD. The conference was supported by the Jose Carreras Foundation project "Competence center GvHD Regensburg."; Michael Schleuning received research support from Wyeth and honoraria from Novartis. Hildegard Greinix served as member of a steering committee for a cGVHD study of Therakos and received honoraria from Therakos for research presentations in corporate symposia at international scientific meetings. NR 160 TC 123 Z9 129 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2011 VL 17 IS 1 BP 1 EP 17 DI 10.1016/j.bbmt.2010.05.011 PG 17 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 705XG UT WOS:000286173400001 PM 20685255 ER PT J AU Barrett, J Gluckman, E Handgretinger, R Madrigal, A AF Barrett, John Gluckman, Eliane Handgretinger, Rupert Madrigal, Alejandro TI Point-Counterpoint: Haploidentical Family Donors versus Cord Blood Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID STEM-CELL TRANSPLANTATION; ACUTE-LEUKEMIA; PERIPHERAL-BLOOD; HEMATOPOIETIC TRANSPLANTS; IMMUNE RECONSTITUTION; VIVO EXPANSION; T-LYMPHOCYTES; GRAFT; DEPLETION; ADULTS C1 [Barrett, John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Gluckman, Eliane] Hosp St Louis, Paris, France. [Handgretinger, Rupert] Univ Tubingen, Childrens Univ Hosp, D-72074 Tubingen, Germany. [Madrigal, Alejandro] Anthony Nolan Res Labs, London, England. RP Barrett, J (reprint author), NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. EM barrettjj@mail.nih.gov NR 45 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2011 VL 17 IS 1 SU 1 BP S89 EP S93 DI 10.1016/j.bbmt.2010.10.024 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 794DZ UT WOS:000292877000018 PM 21195317 ER PT J AU Bonini, C Brenner, MK Heslop, HE Morgan, RA AF Bonini, Chiara Brenner, Malcolm K. Heslop, Helen E. Morgan, Richard A. TI Genetic Modification of T Cells SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Gene transfer; T lymphocytes; Suicide genes ID CHIMERIC ANTIGEN RECEPTOR; ENGINEERED DONOR LYMPHOCYTES; NON-HODGKIN-LYMPHOMA; ADOPTIVE IMMUNOTHERAPY; SUICIDE-GENE; ANTITUMOR-ACTIVITY; CANCER REGRESSION; PHASE-I; EFFECTOR-CELLS; ADVERSE EVENT AB Adoptively transferred T cells have shown activity in treating viral infections after hemopoietic transplantation and anti-tumor activity against some malignancies such as melanoma and lymphoma. Current research focuses on defining the optimum type of cell for transfer to improve persistence and genetically modifying infused T cells to augment function, overcome tumor evasion strategies and allow ablation should adverse effects occur. Biol Blood Marrow Transplant 17: S15-S20 (2011) (C) 2011 American Society for Blood and Marrow Transplantation C1 [Brenner, Malcolm K.; Heslop, Helen E.] Methodist Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Brenner, Malcolm K.; Heslop, Helen E.] Texas Childrens Hosp, Houston, TX 77030 USA. [Bonini, Chiara] Ist Sci San Raffaele, Dept Oncol, Hematol & BMT Unit, Expt Hematol Unit,Res Div Regenerat Med Gene Ther, I-20132 Milan, Italy. [Morgan, Richard A.] NCI, Surg Branch, Bethesda, MD 20892 USA. RP Heslop, HE (reprint author), Methodist Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, 1102 Bates St,Suite 1630, Houston, TX 77030 USA. EM hheslop@bcm.edu RI bonini, chiara/I-9202-2012; OI BONINI, Maria Chiara/0000-0002-0772-1674 FU NCI NIH HHS [P01 CA094237-09, P01 CA094237, P50 CA126752, P50 CA126752-05]; NCRR NIH HHS [U42 RR016578-04]; NHLBI NIH HHS [U54 HL081007-05] NR 47 TC 21 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2011 VL 17 IS 1 SU 1 BP S15 EP S20 DI 10.1016/j.bbmt.2010.09.019 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 794DZ UT WOS:000292877000006 PM 21195304 ER PT J AU Kroger, N Miyamura, K Bishop, MR AF Kroeger, Nicolaus Miyamura, Koichi Bishop, Michael R. TI Minimal Residual Disease following Allogeneic Hematopoietic Stem Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Minimal residual disease; Allogeneic; Relapse; Graft-versus-tumor; DLI ID ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; CHRONIC MYELOGENOUS LEUKEMIA; 1ST INTERNATIONAL WORKSHOP; CHRONIC MYELOID-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; MULTIPLE-MYELOMA; REDUCED INTENSITY; CLINICAL RELAPSE AB Minimal residual disease (MRD), both before and after transplantation, is a clinically important yet relatively poorly defined aspect of allogeneic hematopoietic stem cell transplantation (alloHSCT). The clinical relevance of MRD in the context of alloHSCT has been demonstrated by its association with the development of clinical relapse. However, with the possible exception of chronic myeloid leukemia (CML), the specific techniques, timing, frequency, and clinical utility, relative to improvement in patient outcomes, for monitoring MRD in the setting of alloHSCT has yet to be clearly defined. A concise overview of monitoring techniques for detecting MRD, as well as treatment strategies and biological and clinical research initiatives for MRD suggested by the National Cancer Institute First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation, is covered in this article. Biol Blood Marrow Transplant 17: S94-S100 (2011) (C) 2011 American Society for Blood and Marrow Transplantation C1 [Bishop, Michael R.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Kroeger, Nicolaus] Univ Hosp Hamburg Eppendorf, Hamburg, Germany. [Miyamura, Koichi] Japanese Red Cross Nagoya First Hosp, Nagoya, Aichi, Japan. RP Bishop, MR (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, 10 Ctr Dr,CRC Room 4-3152, Bethesda, MD 20892 USA. EM mbishop@mail.nih.gov FU Center for Cancer Research, National Cancer Institute FX This work was supported in part by the Center for Cancer Research, National Cancer Institute, Intramural Research Program. NR 44 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2011 VL 17 IS 1 SU 1 BP S94 EP S100 DI 10.1016/j.bbmt.2010.10.031 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 794DZ UT WOS:000292877000019 PM 21047560 ER PT J AU Segal, BH Veys, P Malech, H Cowan, MJ AF Segal, Brahm H. Veys, Paul Malech, Harry Cowan, Morton J. TI Chronic Granulomatous Disease: Lessons from a Rare Disorder SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Chronic granulomatous disease; NADPH oxidase; Hematopoietic cell transplantation; Gene therapy ID CELL GENE-THERAPY; SEVERE COMBINED IMMUNODEFICIENCY; LENTIVIRAL VECTOR; UNRELATED-DONOR; HEMATOPOIETIC ALLOGRAFT; EUROPEAN EXPERIENCE; BONE-MARROW; TRANSPLANTATION; SCID-X1; ACTIVATION AB Chronic granulomatous disease (CGD) is a rare primary immunodeficiency with X-linked or autosomal recessive inheritance involving defects in genes encoding phox proteins, which are the subunits of the phagocyte NADPH oxidase. This results in failure to produce superoxide anion and downstream antimicrobial oxidant metabolites and to activate antimicrobial proteases. Affected patients are susceptible to severe, life-threatening bacterial and fungal infections and excessive inflammation characterized by granulomatous enteritis resembling Crohn's disease and genitourinary obstruction. Early diagnosis of CGD and rapid treatment of infections are critical. Prophylaxis with antibacterial and mold-active antifungal agents and the administration of interferon-gamma has significantly improved the natural history of CGD. Currently, the only cure is allogeneic hematopoietic cell transplant (HCT), although there remains controversy as to which patients with CGD should get a transplant. Allele-based HLA typing of alternative donors, improved supportive care measures, and use of reduced toxicity conditioning have resulted in event-free survival (EFS) of at least 80% even with an unrelated donor and even better when the patient has no active infections/inflammation. Gene correction of CGD would eliminate the risks of graft-versus-host disease (GVHD) and the immunoablative chemotherapy required for allogeneic HCT. Based on gene therapy trials in patients with SCID-X1, ADA-SCID, and the early experience with CGD, it is clear that at least some degree of myeloablation will be necessary for CGD as there is no inherent selective growth advantage for gene-corrected cells. Current efforts for gene therapy focus on use of lentivector constructs, which are thought to be safer from the standpoint of insertional mutagenesis and more efficient in transducing hematopoietic stem cells (HSCs). Biol Blood Marrow Transplant 17: S123-S131 (2011) (C) 2011 American Society for Blood and Marrow Transplantation C1 [Cowan, Morton J.] UCSF Childrens Hosp San Francisco, Blood & Marrow Transplant Div, San Francisco, CA 94143 USA. [Segal, Brahm H.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Veys, Paul] Great Ormand St Hosp Children, London, England. [Malech, Harry] NIAID, NIH, Bethesda, MD 20892 USA. RP Cowan, MJ (reprint author), UCSF Childrens Hosp San Francisco, Blood & Marrow Transplant Div, San Francisco, CA 94143 USA. EM mcowan@peds.ucsf.edu OI Malech, Harry/0000-0001-5874-5775 FU NIAID NIH HHS [U54 AI082973, U54 AI082973-01] NR 45 TC 49 Z9 49 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2011 VL 17 IS 1 SU 1 BP S123 EP S131 DI 10.1016/j.bbmt.2010.09.008 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 794DZ UT WOS:000292877000023 PM 21195301 ER PT B AU Collins, PL AF Collins, Peter L. BE Samal, SK TI Human Respiratory Syncytial Virus SO BIOLOGY OF PARAMYXOVIRUSES LA English DT Article; Book Chapter ID SMALL HYDROPHOBIC PROTEIN; REPLICATION IN-VITRO; ATTACHMENT G-PROTEIN; T-CELL RESPONSES; VACCINE-ENHANCED DISEASE; RSV F-PROTEIN; NF-KAPPA-B; INTERCELLULAR-ADHESION MOLECULE-1; TRANSCRIPTION ELONGATION-FACTOR; INTERFERON SIGNAL-TRANSDUCTION AB Human respiratory syncytial virus (RSV) is a ubiquitous pathogen that infects essentially everyone worldwide during infancy and early childhood and is a leading cause of paediatric hospitalization for respiratory disease. RSV also is a frequent cause of less severe disease in healthy adults and is an important cause of morbidity and mortality in the elderly and in severely immunosuppressed individuals. RSV is an enveloped non-segmented negative strand RNA virus classified in the Paramyxovridae family, and its genome organization is one of the more complex of this family. The genome includes: two separate genes encoding type I and type III interferon (IFN) antagonists (NS1 and NS2); a gene (M2) with two open reading frames encoding novel proteins (M2-1 and M2-2) involved in RNA synthesis; and a glycoprotein G that has a number of unusual features, including high sequence variability, heavy glycosylation, cytokine mimicry, and a shed form that helps the virus evade neutralizing antibodies. RSV is able to efficiently infect and cause disease in very young infants, with the peak of hospitalization at 2-3 months of age, despite the presence of maternally derived virus-neutralizing serum antibodies. RSV has a single serotype but is able to re-infect symptomatically throughout life without the need for significant antigenic change, although immunity from prior infection reduces disease. It is widely thought that re-infection is due to an ability of RSV to inhibit or subvert the host immune response, but this remains largely speculative. The development of an effective vaccine or specific antiviral therapy against RSV is considered a high priority, but these goals remain unfulfilled. RSV is notable for a historic vaccine failure: a formalin-inactivated RSV vaccine that was evaluated in infants and children in the 1960s was poorly protective and paradoxically primed for enhanced RSV disease upon subsequent natural RSV infection. However, RSV also is notable because of the development of a successful strategy for passive immunoprophylaxis of infants at high risk for serious RSV disease using an RSV-neutralizing monoclonal antibody (MAb). C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Collins, PL (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM pcollins@niaid.nih.gov NR 454 TC 3 Z9 3 U1 1 U2 2 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-904455-85-1 PY 2011 BP 341 EP 410 PG 70 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA BVP39 UT WOS:000292216900011 ER PT J AU Liu, G Wang, ZY Lu, J Xia, CC Gao, FB Gong, QY Song, B Zhao, XN Shuai, XT Chen, XY Ai, H Gu, ZW AF Liu, Gang Wang, Zhiyong Lu, Jian Xia, Chunchao Gao, Fabao Gong, Qiyong Song, Bin Zhao, Xuna Shuai, Xintao Chen, Xiaoyuan Ai, Hua Gu, Zhongwei TI Low molecular weight alkyl-polycation wrapped magnetite nanoparticle clusters as MRI probes for stem cell labeling and in vivo imaging SO BIOMATERIALS LA English DT Article DE Superparamagnetic iron oxide; Controlled clustering; Mesenchymal stem cells; Magnetic resonance imaging; Cell tracking ID SUPERPARAMAGNETIC IRON-OXIDE; GENE DELIVERY; TRANSFERRIN RECEPTOR; POLYMERIC MICELLES; PARTICLES; DIFFERENTIATION; OSTEOGENESIS; EFFICIENCY; EXPRESSION; TRACKING AB Superparamagnetic Iron oxide (SPIO) nanoparticles are potential probes for noninvasive cell tracking but the design of safe probes coupled with high labeling efficiency is still an important objective for such application In this study an efficient SPIO probe has been developed for mesenchymal stem cells (MSCs) labeling and tracking Different from many other systems involving high molecular polycations we chose low molecular weight amphiphilic PEI2k to form stable nanocomplexes with SPIO nanoparticles The probe can hold multiple SPIO nanoparticles with a controlled clustering structure leading to much higher T(2) relaxivities compared to single SPIO nanoparticles Labeled MSCs are unaffected in their viability proliferation or differentiation capacity The iron uptake process in MSCs displays a time- and dose-dependent behavior Transmission electron microscopy reveals that the nanoprobes are internalized into the cytoplasm of MSCs Subcutaneous injection of the labeled MSCs dispersed in a collagen type I hydrogel showed strong image contrast against unlabeled cells under a clinical 3T magnetic resonance imaging (MRI) scanner up to 19 days post-transplantation This study provides an important alternative to label MSCs at optimized low dosages with high efficiency and the probe may be useful to label other biologically important cells for imaging studies (C) 2010 Elsevier Ltd All rights reserved C1 [Liu, Gang; Wang, Zhiyong; Lu, Jian; Ai, Hua; Gu, Zhongwei] Sichuan Univ, Natl Engn Res Ctr Biomat, Chengdu 610064, Peoples R China. [Xia, Chunchao; Gao, Fabao; Gong, Qiyong; Song, Bin; Ai, Hua] Sichuan Univ, W China Hosp, Dept Radiol, Chengdu 610041, Peoples R China. [Zhao, Xuna] Philips Healthcare, Beijing 100020, Peoples R China. [Shuai, Xintao] Sun Yat Sen Univ, Sch Chem & Chem Engn, Guangzhou 510275, Guangdong, Peoples R China. [Liu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Ai, H (reprint author), Sichuan Univ, Natl Engn Res Ctr Biomat, Chengdu 610064, Peoples R China. RI Shuai, Xintao/C-5819-2008 FU Program for New Century Excellent Talents in University [NCET-06-0781]; Distinguished Young Scholars Project of Sichuan Province [06ZQ026-007]; National Natural Science Foundation of China [20974065, 50603015, 50830107]; National Basic Research Program of China [2005CB623903] FX The work was supported by Program for New Century Excellent Talents in University (NCET-06-0781) Distinguished Young Scholars Project of Sichuan Province (06ZQ026-007) National Natural Science Foundation of China (20974065 50603015 and 50830107) and National Basic Research Program of China (2005CB623903) NR 43 TC 74 Z9 78 U1 8 U2 65 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD JAN PY 2011 VL 32 IS 2 BP 528 EP 537 DI 10.1016/j.biomaterials.2010.08.099 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 695VU UT WOS:000285401500021 PM 20869767 ER PT J AU Heffernan, MJ Zaharoff, DA Fallon, JK Schlom, J Greiner, JW AF Heffernan, Michael J. Zaharoff, David A. Fallon, Jonathan K. Schlom, Jeffrey Greiner, John W. TI In vivo efficacy of a chitosan/IL-12 adjuvant system for protein-based vaccines SO BIOMATERIALS LA English DT Article DE Chitosan; Drug delivery; Immunostimulation; Interleukin 12; Polysaccharide; Vaccine ID T-CELL RESPONSES; INTERLEUKIN-12; IMMUNITY; IL-12; IMMUNOTHERAPY; INDUCTION AB Vaccines based on recombinant proteins require adjuvant systems in order to generate Th1-type immune responses We have developed a vaccine adjuvant system using a viscous chitosan solution and inter-leukin (IL)-12 a Th1-inducing cytokine The chitosan solution is designed to create a depot of antigen and IL-12 at a subcutaneous injection site We measured the in vivo immune response of a vaccine containing 025 1 or 4 mu g murine IL-12 and 75 mu g ovalbumin (OVA) formulated in a 1 5% chitosan glutamate solution The chitosan/IL-12/OVA vaccine in comparison to chitosan/OVA IL-12/OVA or OVA alone elicited greater antigen-specific CD4(+) and CD8(+) T-cell responses as determined by CD4(+) splenocyte proliferation Th1 cytokine release CD8(+) T-cell interferon-gamma release and MHC class I peptide pentamer staining The combination of chitosan and IL-12 also enhanced IgG2a and IgG2b antibody responses to OVA Co-formulation of chitosan and IL-12 thus promoted the generation of a Th1 immune response to a model protein vaccine Published by Elsevier Ltd C1 [Heffernan, Michael J.; Zaharoff, David A.; Fallon, Jonathan K.; Schlom, Jeffrey; Greiner, John W.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Greiner, JW (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. OI Zaharoff, David/0000-0001-6885-6727 FU Center for Cancer Research at the National Cancer Institute NIH FX The authors acknowledge Garland Davis Bertina Gibbs and Curtis Randolph for their excellent technical support in performing vaccine injections and immunological assays and Bonnie L Casey for editorial assistance in the preparation of this manuscript This work was funded by the Intramural Research Program of the Center for Cancer Research at the National Cancer Institute NIH NR 24 TC 23 Z9 25 U1 0 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD JAN PY 2011 VL 32 IS 3 BP 926 EP 932 DI 10.1016/j.biomaterials.2010.09.058 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 694TT UT WOS:000285322600028 PM 20965561 ER PT J AU Kalish, H AF Kalish, Heather BE Komorowska, MA OlsztynskaJanus, S TI Application of Micro-Fluidic Devices for Biomarker Analysis in Human Biological Fluids SO BIOMEDICAL ENGINEERING, TRENDS, RESEARCH AND TECHNOLOGIES LA English DT Article; Book Chapter ID IMMUNOAFFINITY CAPILLARY-ELECTROPHORESIS; LASER-INDUCED FLUORESCENCE; MICELLAR ELECTROKINETIC CHROMATOGRAPHY; HUMAN CEREBROSPINAL-FLUID; MALDI-TOF/TOF MS; BODY-FLUIDS; CHEMILUMINESCENCE DETECTION; GEL-ELECTROPHORESIS; AMINO-ACIDS; HUMAN SERUM C1 [Kalish, Heather] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Kalish, H (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. NR 57 TC 0 Z9 0 U1 0 U2 0 PU INTECH EUROPE PI RIJEKA PA JANEZA TRDINE9, RIJEKA, 51000, CROATIA BN 978-953-307-514-3 PY 2011 BP 121 EP 138 PG 18 WC Engineering, Biomedical SC Engineering GA BE3PF UT WOS:000371132600006 ER PT S AU Xie, J Chen, XY AF Xie, Jin Chen, Xiaoyuan BE Braddock, M TI Magnetic Resonance Imaging in Drug Development SO BIOMEDICAL IMAGING: THE CHEMISTRY OF LABELS, PROBES AND CONTRAST AGENTS SE RSC Drug Discovery Series LA English DT Article; Book Chapter ID IRON-OXIDE NANOPARTICLES; CONTRAST-ENHANCED MRI; ANTIGEN-INDUCED ARTHRITIS; VEGF-SIGNALING INHIBITOR; MESENCHYMAL STEM-CELLS; IN-VIVO; PULMONARY-EDEMA; ATHEROSCLEROTIC PLAQUES; PHARMACEUTICAL RESEARCH; DIFFUSION-COEFFICIENT C1 [Xie, Jin; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. RP Xie, J (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. NR 118 TC 0 Z9 0 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 2041-3203 BN 978-1-84973-014-3; 978-1-84973-291-8 J9 RSC DRUG DISCOV JI RSC Drug Discov. PY 2011 IS 15 BP 441 EP 464 D2 10.1039/9781849732918 PG 24 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BIE26 UT WOS:000327851900015 ER PT S AU Clos, LJ Butcher, SE Wang, YX AF Clos, Lawrence J., II Butcher, Samuel E. Wang, Yun-Xing BE Dingley, AJ Pascal, SM TI NMR Spectroscopy for Investigating Larger Nucleic Acids SO BIOMOLECULAR NMR SPECTROSCOPY SE Advances in Biomedical Spectroscopy LA English DT Article; Book Chapter DE CSA; DNA; NMR; RDCs; RNA; SAXS; Structure; TROSY ID RESIDUAL DIPOLAR COUPLINGS; X-RAY-SCATTERING; RELAXATION OPTIMIZED SPECTROSCOPY; TETRALOOP-RECEPTOR COMPLEX; CHEMICAL-SHIFT ANISOTROPY; DNA 3-WAY JUNCTION; RNA OLIGONUCLEOTIDES; DIMERIC QUADRUPLEX; GLOBAL STRUCTURE; HYDROGEN-BONDS AB Investigation of large nucleic acids (> 30 kDa) challenges the current limits of NMR spectroscopy. Extended helical regions in RNA and DNA increase correlation times more so than for proteins of comparable size, resulting in line broadening and reduced sensitivity. Also, the lower proton density and poor proton spectral dispersion in nucleic acids can reduce the effectiveness of traditional solution NMR methods in studies of large nucleic acids. These limitations represent a substantial hindrance to the future investigation of biologically relevant large nucleic acid structures. Herein we describe methods that have been implemented to help overcome these challenges and extend the size limits of nucleic acid NMR spectroscopy, including construct design, selective isotopic labeling, multi-dimensional NMR experiments and complementary techniques. C1 [Clos, Lawrence J., II; Butcher, Samuel E.] Univ Wisconsin, Dept Biochem, Madison, WI 53705 USA. [Wang, Yun-Xing] NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, Ctr Canc Res,NIH, Ft Detrick, MD 21702 USA. RP Butcher, SE (reprint author), Univ Wisconsin, Dept Biochem, 420 Henry Mall, Madison, WI 53705 USA. EM butcher@biochem.wisc.edu NR 121 TC 0 Z9 0 U1 1 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1875-0656 BN 978-1-60750-695-9; 978-1-60750-694-2 J9 ADV BIOMED SPECTROSC PY 2011 VL 3 BP 229 EP 248 DI 10.3233/978-1-60750-695-9-229 PG 20 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA BB7WU UT WOS:000346073900014 ER PT S AU Zuo, XB Wang, JB Wang, YX AF Zuo, Xiaobing Wang, Jinbu Wang, Yun-Xing BE Dingley, AJ Pascal, SM TI NMR and SAXS: A Perfect Marriage and New Approach for RNA Structure Determination SO BIOMOLECULAR NMR SPECTROSCOPY SE Advances in Biomedical Spectroscopy LA English DT Article; Book Chapter DE NMR; RDC; RNA three-dimensional structures; SAXS ID X-RAY-SCATTERING; RESIDUAL DIPOLAR COUPLINGS; SMALL-ANGLE SCATTERING; BIOLOGICAL MACROMOLECULES; CRYSTALLOGRAPHY; ASSIGNMENT; PROTEINS; MOTIFS; VIRUS AB RNAs are versatile molecules and play important roles in various biological processes. Their functions are embedded in their structures and dynamics, yet there is little propensity correlation between a primary sequence of an RNA and its three-dimensional structure except in the case of simple RNA hairpins and the special case of tRNAs. Despite more than a decade of significant progress in both X-ray crystallography and NMR spectroscopy, structure determination and elucidation of large RNAs with complex folds, using either experimental, computational or combined approaches, remains a major interest as well as a challenge to the research community in contemporary biology. In this chapter we outline a new strategy for solution structure determination of RNA using restraints that are derived from experimental NMR measurements and small-angle X-ray scattering data. In addition, we present practical details on how to prepare RNA sample solutions for successful SAXS experiments. C1 [Zuo, Xiaobing; Wang, Jinbu; Wang, Yun-Xing] NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, NIH, Bethesda, MD 20892 USA. RP Wang, YX (reprint author), NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, NIH, Bethesda, MD 20892 USA. EM wangyunx@mail.nih.gov NR 37 TC 2 Z9 2 U1 1 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1875-0656 BN 978-1-60750-695-9; 978-1-60750-694-2 J9 ADV BIOMED SPECTROSC PY 2011 VL 3 BP 457 EP 467 DI 10.3233/978-1-60750-695-9-457 PG 11 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA BB7WU UT WOS:000346073900023 ER PT J AU LaLonde, JM Elban, MA Courter, JR Sugawara, A Soeta, T Madani, N Princiotto, AM Do Kwon, Y Kwong, PD Schon, A Freire, E Sodroski, J Smith, AB AF LaLonde, Judith M. Elban, Mark A. Courter, Joel R. Sugawara, Akihiro Soeta, Takahiro Madani, Navid Princiotto, Amy M. Do Kwon, Young Kwong, Peter D. Schoen, Arne Freire, Ernesto Sodroski, Joseph Smith, Amos B., III TI Design, synthesis and biological evaluation of small molecule inhibitors of CD4-gp120 binding based on virtual screening SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE HIV; gp120; CD4; Entry inhibitor; Virtual screening; Docking; Shape-based similarity ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN; HIV-1 ENTRY; ACCURATE DOCKING; CD4; GP120; RECEPTOR; RETROVIRUS; VALIDATION; CORECEPTOR AB The low-molecular-weight compound JRC-II-191 inhibits infection of HIV-1 by blocking the binding of the HIV-1 envelope glycoprotein gp120 to the CD4 receptor and is therefore an important lead in the development of a potent viral entry inhibitor. Reported here is the use of two orthogonal screening methods, GOLD docking and ROCS shape-based similarity searching, to identify amine-building blocks that, when conjugated to the core scaffold, yield novel analogs that maintain similar affinity for gp120. Use of this computational approach to expand SAR produced analogs of equal inhibitory activity but with diverse capacity to enhance viral infection. The novel analogs provide additional lead scaffolds for the development of HIV-1 entry inhibitors that employ protein-ligand interactions in the vestibule of gp120 Phe 43 cavity. (C) 2010 Elsevier Ltd. All rights reserved. C1 [LaLonde, Judith M.] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA. [Elban, Mark A.; Courter, Joel R.; Sugawara, Akihiro; Soeta, Takahiro; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Madani, Navid; Princiotto, Amy M.; Sodroski, Joseph] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Do Kwon, Young; Kwong, Peter D.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Schoen, Arne; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP LaLonde, JM (reprint author), Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA. EM jlalonde@brynmawr.edu RI Kwon, Young Do/A-6957-2010; SOETA, Takahiro/E-7060-2015; OI SOETA, Takahiro/0000-0001-9883-4772; Sugawara, Akihiro/0000-0003-1266-7497 FU NIH [GM 56550]; Japan Society for the Promotion of Science FX We thank Irwin Chaiken and Wayne Hendrickson and all the members of the PO1 Consortium Structure-Based Antagonism of HIV-1 Envelope Function in Cell Entry. Funding was provided by NIH GM 56550 to JL, EF, ABS, and JS. A. Sugawara thanks the Japan Society for the Promotion of Science for research fellowship support. JL thanks the Pittsburgh Supercomputing Center for an allocation for computing resources #MCB090108. NR 44 TC 38 Z9 40 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 1 PY 2011 VL 19 IS 1 BP 91 EP 101 DI 10.1016/j.bmc.2010.11.049 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 700GA UT WOS:000285724800009 PM 21169023 ER PT J AU Matts, RL Brandt, GEL Lu, YM Dixit, A Mollapour, M Wang, SQ Donnelly, AC Neckers, L Verkhivker, G Blagg, BSJ AF Matts, Robert L. Brandt, Gary E. L. Lu, Yuanming Dixit, Anshuman Mollapour, Mehdi Wang, Suiquan Donnelly, Alison C. Neckers, Leonard Verkhivker, Gennady Blagg, Brian S. J. TI A systematic protocol for the characterization of Hsp90 modulators SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Heat shock protein 90; Novobiocin; Geldanamycin; Celastrol; Gedunin ID HEAT-SHOCK-PROTEIN; C-TERMINAL DOMAIN; MOLECULAR CHAPERONE; NOVOBIOCIN ANALOGS; ANTIPROLIFERATIVE ACTIVITY; CARBOXYL-TERMINUS; FOLDING MACHINERY; DIMER FORMATION; INHIBITORS; MECHANISM AB Several Hsp90 modulators have been identified including the N-terminal ligand geldanamycin (GDA), the C-terminal ligand novobiocin (NB), and the co-chaperone disruptor celastrol. Other Hsp90 modulators elicit a mechanism of action that remains unknown. For example, the natural product gedunin and the synthetic anti-spermatogenic agent H2-gamendazole, recently identified Hsp90 modulators, manifest biological activity through undefined mechanisms. Herein, we report a series of biochemical techniques used to classify such modulators into identifiable categories. Such studies provided evidence that gedunin and H2-gamendazole both modulate Hsp90 via a mechanism similar to celastrol, and unlike NB or GDA. (C) 2010 Published by Elsevier Ltd. C1 [Brandt, Gary E. L.; Lu, Yuanming; Donnelly, Alison C.; Blagg, Brian S. J.] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA. [Matts, Robert L.] Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74078 USA. [Dixit, Anshuman; Verkhivker, Gennady] Univ Kansas, Ctr Bioinformat, Lawrence, KS 66045 USA. [Mollapour, Mehdi; Wang, Suiquan; Donnelly, Alison C.; Neckers, Leonard] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Blagg, BSJ (reprint author), Univ Kansas, Dept Med Chem, 1251 Wescoe Hall Dr,Malott 4070, Lawrence, KS 66045 USA. EM bblagg@ku.edu FU National Institutes of Health [HD055763, CA109265, CA125392]; Madison and Lila Self Graduate Fellowship; American Foundation for Pharmaceutical Education FX The authors are grateful to the National Institutes of Health (HD055763, CA109265, and CA125392), the Madison and Lila Self Graduate Fellowship (GELB), and the American Foundation for Pharmaceutical Education (GELB) for financial support of this project. NR 49 TC 36 Z9 36 U1 0 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 1 PY 2011 VL 19 IS 1 BP 684 EP 692 DI 10.1016/j.bmc.2010.10.029 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 700GA UT WOS:000285724800070 PM 21129982 ER PT J AU Lim, KS Kang, DW Kim, YS Kim, MS Park, SG Choi, S Pearce, LV Blumberg, PM Lee, J AF Lim, Kwang Su Kang, Dong Wook Kim, Yong Soo Kim, Myeong Seop Park, Seul-Gi Choi, Sun Pearce, Larry V. Blumberg, Peter M. Lee, Jeewoo TI Receptor activity and conformational analysis of 5 '-halogenated resiniferatoxin analogs as TRPV1 ligands SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE TRPV1 agonist; TRPV1 antagonist; Partial agonist; Halogenation; Resiniferatoxin; Molecular modeling ID IODO-RESINIFERATOXIN; VANILLOID RECEPTORS; GANGLION NEURONS; CAPSAICIN; ANTAGONIST; VR1; DESENSITIZATION; AGONIST; BINDING; POTENT AB A series of 5'-halogenated resiniferatoxin analogs have been investigated in order to examine the effect of halogenation in the A-region on their binding and the functional pattern of agonism/antagonism for rat TRPV1 heterologously expressed in Chinese hamster ovary cells. Halogenation at the 5-position in the A-region of RTX and of 4-amino RTX shifted the agonism of parent compounds toward antagonism. The extent of antagonism was greater as the size of the halogen increased (I > Br > Cl > F) while the binding affinities were similar, as previously observed for our potent agonists. In this series, 5-bromo-4-amino RTX (39) showed very potent antagonism with K(i) (ant) = 2.81 nM, which was thus 4.5-fold more potent than 5'-iodo RTX, previously reported as a potent TRPV1 antagonist. Molecular modeling analyses with selected agonists and the corresponding halogenated antagonists revealed a striking conformational difference. The 3-methoxy of the A-region in the agonists remained free to interact with the receptor whereas in the case of the antagonists, the compounds assumed a bent conformation, permitting the 3-methoxy to instead form an internal hydrogen bond with the C4-hydroxyl of the diterpene. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Lim, Kwang Su; Kang, Dong Wook; Kim, Yong Soo; Kim, Myeong Seop; Lee, Jeewoo] Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea. [Pearce, Larry V.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Park, Seul-Gi; Choi, Sun] Ewha Womans Univ, Coll Pharm, Div Life & Pharmaceut Sci, Seoul 120750, South Korea. [Park, Seul-Gi; Choi, Sun] Ewha Womans Univ, Natl Core Res Ctr Cell Signaling & Drug Discovery, Seoul 120750, South Korea. RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea. EM jeewoo@snu.ac.kr FU National Research Foundation of Korea (NRF) [R11-2007-107-02001-0]; National Core Research Center (NCRC), MEST [R15-2006-020]; NRF through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University; National Institutes of Health, Center for Cancer Research, National Cancer Institute FX This research was supported by Grant R11-2007-107-02001-0 from the National Research Foundation of Korea (NRF), the National Core Research Center (NCRC) program (R15-2006-020) of MEST and NRF through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University (to S. Choi), and by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute. We thank numerous research fellows for some of the biological analyses. NR 24 TC 4 Z9 4 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN PY 2011 VL 21 IS 1 BP 299 EP 302 DI 10.1016/j.bmcl.2010.11.012 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 697UN UT WOS:000285544400059 PM 21111618 ER PT J AU Yao, ZY Xu, YJ Zhang, MM Jiang, S Nicklaus, MC Liao, CZ AF Yao, Zhiyi Xu, Yingjun Zhang, Minmin Jiang, Sheng Nicklaus, Marc C. Liao, Chenzhong TI Discovery of a novel hybrid from finasteride and epristeride as 5 alpha-reductase inhibitor SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Hybrid; Finasteride; Epristeride; 5 alpha-reductase inhibitor; Combination principles ID PROSTATE AB Finasteride and epristeride both inhibit 5 alpha-reductase with high potency via competitive and non-competitive mechanism, respectively. A new hybrid of finasteride and epristeride was designed as a new 5a-reductase inhibitor based on combination principles in medicinal chemistry. Human 5 beta-reductase was chosen as a plausible surrogate of 5 alpha-reductase type II and the results indicate that although the hybrid compound possesses the main bulk of epristeride, its inhibitory mechanism is same as of finasteride. The hybrid turned out to be a potent 5 alpha-reductase inhibitor in low IC(50) ranges. Published by Elsevier Ltd. C1 [Nicklaus, Marc C.; Liao, Chenzhong] NCI, Biol Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA. [Yao, Zhiyi; Xu, Yingjun; Zhang, Minmin; Jiang, Sheng] Shanghai Inst Technol, Coll Chem & Environm Engn, Shanghai 210032, Peoples R China. [Liao, Chenzhong] Nankai Univ, Coll Pharm, Tianjin 300071, Peoples R China. RP Liao, CZ (reprint author), NCI, Biol Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA. EM chenzhongliao@yahoo.com RI Nicklaus, Marc/N-4183-2014 FU Shanghai University [DF2009-02]; Pujiang Talent Plan Project [09PJ1409200] FX We thank the Shanghai University Distinguished Professor (Eastern scholars) Program (DF2009-02), and Pujiang Talent Plan Project (09PJ1409200) for financial support. NR 19 TC 9 Z9 9 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN PY 2011 VL 21 IS 1 BP 475 EP 478 DI 10.1016/j.bmcl.2010.10.112 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 697UN UT WOS:000285544400098 PM 21094046 ER PT J AU Gustafson, KR AF Gustafson, Kirk R. TI HIV Inhibitory Cyclic Depsipeptides from Marine Sponges: New Structural Features, Biological Activity Profiles, and Stereochemical Challenges SO BIOPOLYMERS LA English DT Meeting Abstract CT 22nd American Peptide Symposium CY JUN 25-30, 2011 CL San Diego, CA SP Amer Peptide Soc C1 [Gustafson, Kirk R.] NCI Frederick, Ctr Canc Res, Mol Targets Lab, Frederick, MD USA. EM gustafki@mail.nih.gov NR 0 TC 0 Z9 0 U1 2 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2011 VL 96 IS 4 BP 422 EP 422 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 779FL UT WOS:000291763400054 ER PT J AU Castanho, MARB Freire, JM Santos, NC Veiga, AS Da Poian, AT AF Castanho, Miguel A. R. B. Freire, Joao M. Santos, Nuno C. Veiga, Ana Salome Da Poian, Andrea T. TI Dengue: viral cellular infection reappraised SO BIOPOLYMERS LA English DT Meeting Abstract CT 22nd American Peptide Symposium CY JUN 25-30, 2011 CL San Diego, CA SP Amer Peptide Soc C1 [Castanho, Miguel A. R. B.; Freire, Joao M.; Santos, Nuno C.; Veiga, Ana Salome] Univ Lisbon, Sch Med, Inst Mol Med, P-1699 Lisbon, Portugal. [Veiga, Ana Salome] CCR NCI, Biol Chem Lab, Frederick, MD 21702 USA. [Da Poian, Andrea T.] Univ Fed Rio de Janeiro, Inst Bioquim Med, Rio De Janeiro, Brazil. RI Santos, Nuno/N-7248-2013 OI Santos, Nuno/0000-0002-0580-0475 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2011 VL 96 IS 4 BP 425 EP 425 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 779FL UT WOS:000291763400064 ER PT J AU Geisler, I Schneider, JP AF Geisler, Iris Schneider, Joel P. TI Simple, Linear, Amphiphilic, Self-assembling Peptides for the Formation of Hydrogels SO BIOPOLYMERS LA English DT Meeting Abstract CT 22nd American Peptide Symposium CY JUN 25-30, 2011 CL San Diego, CA SP Amer Peptide Soc C1 [Geisler, Iris; Schneider, Joel P.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2011 VL 96 IS 4 BP 432 EP 432 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 779FL UT WOS:000291763400090 ER PT J AU Giano, MC Schneider, JP AF Giano, Michael C. Schneider, Joel P. TI Controlled Degradation of Self-Assembled beta-hairpin Hydrogels by Proteolysis with Matrix Metalloproteinase-13 SO BIOPOLYMERS LA English DT Meeting Abstract CT 22nd American Peptide Symposium CY JUN 25-30, 2011 CL San Diego, CA SP Amer Peptide Soc C1 [Giano, Michael C.; Schneider, Joel P.] NCI, Biol Chem Lab, Frederick, MD 21701 USA. [Giano, Michael C.] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2011 VL 96 IS 4 BP 450 EP 450 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 779FL UT WOS:000291763400167 ER PT J AU Nagy, KJ Schneider, JP AF Nagy, Katelyn J. Schneider, Joel P. TI Enhancement of Material Properties and Control of Degradation Through Utilization of Enantiomeric Peptide Hydrogels SO BIOPOLYMERS LA English DT Meeting Abstract CT 22nd American Peptide Symposium CY JUN 25-30, 2011 CL San Diego, CA SP Amer Peptide Soc C1 [Nagy, Katelyn J.] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA. [Nagy, Katelyn J.; Schneider, Joel P.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2011 VL 96 IS 4 BP 452 EP 452 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 779FL UT WOS:000291763400176 ER PT J AU Sinthuvanich, C Schneider, JP AF Sinthuvanich, Chomdao Schneider, Joel P. TI Net charge modulation of injectable beta-hairpin peptide: Peptide design for cartilage engineering application SO BIOPOLYMERS LA English DT Meeting Abstract CT 22nd American Peptide Symposium CY JUN 25-30, 2011 CL San Diego, CA SP Amer Peptide Soc C1 [Sinthuvanich, Chomdao] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA. [Sinthuvanich, Chomdao; Schneider, Joel P.] NCI Frederick, CCR, Chem Biol Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2011 VL 96 IS 4 BP 453 EP 453 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 779FL UT WOS:000291763400180 ER PT J AU Smith, D Schneider, J Kelley, J Yap, G AF Smith, Daniel Schneider, Joel Kelley, James Yap, Glenn TI Enhanced Stereoselectivity of a Cu(II) Complex Chiral Auxiliary in the Synthesis of Fmoc-L-gamma-carboxyglutamic Acid SO BIOPOLYMERS LA English DT Meeting Abstract CT 22nd American Peptide Symposium CY JUN 25-30, 2011 CL San Diego, CA SP Amer Peptide Soc C1 [Smith, Daniel; Schneider, Joel; Kelley, James; Yap, Glenn] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2011 VL 96 IS 4 BP 453 EP 453 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 779FL UT WOS:000291763400181 ER PT J AU Sonmez, C Schneider, JP AF Sonmez, Cem Schneider, Joel P. TI Bacterial Expression of a Self-Assembling Peptide That Can Undergo Hydrogelation SO BIOPOLYMERS LA English DT Meeting Abstract CT 22nd American Peptide Symposium CY JUN 25-30, 2011 CL San Diego, CA SP Amer Peptide Soc C1 [Sonmez, Cem; Schneider, Joel P.] NCI Frederick, CCR, Biol Chem Lab, Frederick, MD USA. [Sonmez, Cem] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA. RI Sonmez, Cem/C-2730-2015 OI Sonmez, Cem/0000-0002-6071-641X NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2011 VL 96 IS 4 BP 453 EP 454 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 779FL UT WOS:000291763400182 ER PT J AU Veiga, AS Schneider, JP AF Veiga, Ana Salome Schneider, Joel P. TI Design of Arginine Containing Peptide-Based Hydrogels with Improved Material Properties and Inherent Antibacterial Activity SO BIOPOLYMERS LA English DT Meeting Abstract CT 22nd American Peptide Symposium CY JUN 25-30, 2011 CL San Diego, CA SP Amer Peptide Soc C1 [Veiga, Ana Salome; Schneider, Joel P.] NCI, Biol Chem Lab, NIH, Frederick, MD 21702 USA. [Veiga, Ana Salome] Univ Lisbon, Fac Med, Inst Med Mol, P-1649028 Lisbon, Portugal. NR 0 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2011 VL 96 IS 4 BP 455 EP 456 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 779FL UT WOS:000291763400190 ER PT J AU Bang, JK Murugan, RN Park, JH Lee, KS AF Bang, Jeong Kyu Murugan, Ravichandran N. Park, Jae Hoon Lee, Kyung S. TI Cyclic Peptomers as Targeting the Polo-Box Domain of Polo-Like kinase1 SO BIOPOLYMERS LA English DT Meeting Abstract CT 22nd American Peptide Symposium CY JUN 25-30, 2011 CL San Diego, CA SP Amer Peptide Soc C1 [Bang, Jeong Kyu; Murugan, Ravichandran N.; Park, Jae Hoon] Korea Basic Sci Inst, Div Magnet Resonance Team, Chungbuk 363883, South Korea. [Lee, Kyung S.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2011 VL 96 IS 4 BP 466 EP 466 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 779FL UT WOS:000291763400229 ER PT J AU Murugan, RN Park, JH Lee, KS Bang, JK AF Murugan, Ravichandran N. Park, Jae Hoon Lee, Kyung S. Bang, Jeong Kyu TI Design, Synthesis and Structure of Peptidomimetic Inhibitors of Polo-like Kinase 1: A Target for Cancer Chemotherapy SO BIOPOLYMERS LA English DT Meeting Abstract CT 22nd American Peptide Symposium CY JUN 25-30, 2011 CL San Diego, CA SP Amer Peptide Soc C1 [Murugan, Ravichandran N.; Park, Jae Hoon; Bang, Jeong Kyu] Korea Basic Sci Inst, Div Magnet Resonance Team, Chungbuk 363883, South Korea. [Lee, Kyung S.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2011 VL 96 IS 4 BP 484 EP 484 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 779FL UT WOS:000291763400302 ER PT J AU Qian, WJ Liu, F Giubellino, A Simister, P Feller, SM Bottaro, DP Burke, TR AF Qian, Wenjian Liu, Fa Giubellino, Alessio Simister, Philip Feller, Stephan M. Bottaro, Donald P. Burke, Terrence R., Jr. TI Application of Ring-Closing Metathesis to Grb2 SH3 Domain-Binding Peptides SO BIOPOLYMERS LA English DT Meeting Abstract CT 22nd American Peptide Symposium CY JUN 25-30, 2011 CL San Diego, CA SP Amer Peptide Soc C1 [Qian, Wenjian; Liu, Fa; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA. [Giubellino, Alessio; Bottaro, Donald P.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20989 USA. [Simister, Philip; Feller, Stephan M.] Univ Oxford, Canc Res UK Cell Signalling Grp, Weatherall Inst Mol Med, Oxford OX3 9DS, England. RI Bottaro, Donald/F-8550-2010; Burke, Terrence/N-2601-2014 OI Bottaro, Donald/0000-0002-5057-5334; NR 5 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2011 VL 96 IS 4 BP 486 EP 487 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 779FL UT WOS:000291763400311 ER PT J AU Basava, C Czerwinski, A Dauter, Z AF Basava, C. Czerwinski, A. Dauter, Z. TI Crystal structure of a tripeptide aldehyde proteasome inhibitor, Ac-Leu-Leu-Norleucinal SO BIOPOLYMERS LA English DT Meeting Abstract CT 22nd American Peptide Symposium CY JUN 25-30, 2011 CL San Diego, CA SP Amer Peptide Soc C1 [Basava, C.; Czerwinski, A.] Peptides Int Inc, Louisville, KY 40299 USA. [Dauter, Z.] Argonne Natl Lab, Natl Canc Inst, Macromol Crystallog Lab, Argonne, IL 60439 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2011 VL 96 IS 4 BP 502 EP 502 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 779FL UT WOS:000291763400373 ER PT J AU Franquelim, HG Veiga, AS Santos, NC Castanho, M AF Franquelim, Henri G. Salome Veiga, A. Santos, Nuno C. Castanho, Miguel TI Membrane mode of action of HIV inhibitor peptides enfuvirtide and T-1249 unraveled by atomic force microscopy and dipole potential fluorescence spectroscopy SO BIOPOLYMERS LA English DT Meeting Abstract CT 22nd American Peptide Symposium CY JUN 25-30, 2011 CL San Diego, CA SP Amer Peptide Soc C1 [Franquelim, Henri G.; Salome Veiga, A.; Santos, Nuno C.; Castanho, Miguel] Fac Med Univ Lisbon, Inst Mol Med, Lisbon, Portugal. [Salome Veiga, A.] NCI, Biol Chem Lab, Frederick, MD 21701 USA. EM hgfranquelim@fm.ul.pt RI Santos, Nuno/N-7248-2013 OI Santos, Nuno/0000-0002-0580-0475 NR 0 TC 0 Z9 0 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2011 VL 96 IS 4 BP 504 EP 504 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 779FL UT WOS:000291763400379 ER PT J AU Harlen, K Gupta, K Banco, M Blumenthal, R Schneider, J AF Harlen, K. Gupta, K. Banco, M. Blumenthal, R. Schneider, J. TI The Development of a Thermally Controlled Drug Release System using SelfAssembling Peptides and LipidBased Drug Carriers SO BIOPOLYMERS LA English DT Meeting Abstract CT 22nd American Peptide Symposium CY JUN 25-30, 2011 CL San Diego, CA SP Amer Peptide Soc C1 [Harlen, K.; Banco, M.; Schneider, J.] NCI, Biol Chem Lab, Mol Discovery Program, NIH, Bethesda, MD 20892 USA. [Gupta, K.; Blumenthal, R.] NCI, CCR Nanobiol Program, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2011 VL 96 IS 4 BP 514 EP 515 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 779FL UT WOS:000291763400425 ER PT J AU Liu, F Giubellino, A Simister, PC Qian, WJ Giano, MC Feller, SM Bottaro, DP Burke, TR AF Liu, Fa Giubellino, Alessio Simister, Philip C. Qian, Wenjian Giano, Michael C. Feller, Stephan M. Bottaro, Donald P. Burke, Terrence R., Jr. TI Application of Ring-Closing Metathesis to Grb2 SH3 Domain-Binding Peptides SO BIOPOLYMERS LA English DT Article DE peptide macrocyclization; ring-closing metathesis; polyproline type II helix; Grb2; Sos1; SH3 domain ID HYDROGEN-BOND-SURROGATE; MOLECULAR RECOGNITION; II CONFORMATION; CELL MOTILITY; ALPHA; SOS; AFFINITY; STABILIZATION; GROWTH; STRATEGIES AB Molecular processes depending on protein protein interactions can use consensus recognition sequences that possess defined secondary structures. Left-handed polyproline II (PPII) helices are a class of secondary structure commonly involved with cellular signal transduction. However, unlike a-helices, for which a substantial body of work exists regarding applications of ring-closing metathesis (RCM), there are few reports on the stabilization of PPII helices by RCM methodologies. The current study examined the effects of RCM macrocyclization on left-handed PPII helices involved with the SH3 domain-mediated binding of Sos1-Grb2. Starting with the Sos1-derived peptide "Ac-V(1-)P(2)-P(3)-P(4)-V(5)-P(6)-P(7)-R(8)-R(9)-R(10)-amide," RCM macrocyclizations were conducted using alkenyl chains of varying lengths originating from the pyrrolidine rings of the Pro(4) and Pro(7) residues. residues: The resulting macrocyclic peptide's showed increased helicity as indicated by circular dichroism and enhanced abilities to block Grb2-Sos1 interactions in cell lysate pull-down assays. The synthetic approach may be useful in RCM macrocyclizations, where maintenance of proline integrity at both ring junctures is desired. (C) 2011 Wiley Periodicals, Inc.* Biopolymers (Pept Sci) 96: 780-788, 2011. C1 [Liu, Fa; Qian, Wenjian; Giano, Michael C.; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH,NCI Frederick, Frederick, MD 21702 USA. [Giubellino, Alessio; Bottaro, Donald P.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20989 USA. [Simister, Philip C.; Feller, Stephan M.] Univ Oxford, Cell Signalling Grp, Weatherall Inst Mol Med, Oxford OX3 9DS, England. RP Burke, TR (reprint author), NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH,NCI Frederick, Frederick, MD 21702 USA. EM tburke@helix.nih.gov RI Bottaro, Donald/F-8550-2010; Burke, Terrence/N-2601-2014; OI Bottaro, Donald/0000-0002-5057-5334; Giubellino, Alessio/0000-0002-5352-0662 FU NIH, Center for Cancer Research, NCI-Frederick; National Cancer Institute, National Institutes of Health; Cancer Research UK FX Contract grant sponsors: Intramural Research Program of the NIH, Center for Cancer Research, NCI-Frederick and the National Cancer Institute, National Institutes of Health and by a Cancer Research UK, and a Heads Up Programme Grant NR 39 TC 6 Z9 6 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2011 VL 96 IS 6 BP 780 EP 788 DI 10.1002/bip.21692 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 854XK UT WOS:000297527900008 PM 21830199 ER PT J AU Taylor-Robinson, D Lamont, RF AF Taylor-Robinson, D. Lamont, R. F. TI Mycoplasmas in pregnancy SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Review DE Genital mycoplasmas; pregnancy outcome; treatment ID PELVIC-INFLAMMATORY-DISEASE; POLYMERASE-CHAIN-REACTION; UREAPLASMA-UREALYTICUM COLONIZATION; CHRONIC LUNG-DISEASE; PRETERM PREMATURE RUPTURE; BIRTH-WEIGHT INFANTS; BACTERIAL VAGINOSIS; GENITAL MYCOPLASMAS; AMNIOTIC-FLUID; INTRAAMNIOTIC INFECTION AB The genital mycoplasmas have been implicated in a number of adverse outcomes of pregnancy. Spontaneous preterm labour and preterm birth is an important contributor to perinatal mortality and morbidity. If Mycoplasma hominis plays an integral part in this problem, it is likely to contribute through its involvement with bacterial vaginosis. Ureaplasmas induce cytokines and inflammation, making a casual association compelling. The role of Mycoplasma genitalium and Mycoplasma fermentans is less clear, but M. genitalium is potentially pathogenic and should be treated if detected. There is considerable evidence for the role of M. hominis in post-partum and post-abortal sepsis, and for ureaplasmas causing chronic lung disease or death in very low birthweight infants. The role of the genital mycoplasmas in adverse outcomes of pregnancy is complicated by the presence or absence of bacterial vaginosis, and this association requires further research. C1 [Taylor-Robinson, D.] Univ London Imperial Coll Sci Technol & Med, St Marys Hosp Campus, Div Med, London W2 1NY, England. [Lamont, R. F.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Lamont, R. F.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Lamont, R. F.] Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI USA. RP Taylor-Robinson, D (reprint author), Univ London Imperial Coll Sci Technol & Med, St Marys Hosp Campus, Div Med, London W2 1NY, England. EM taylorrobinsondavid@googlemail.com FU Medical Research Council FX DT-R was funded by the Medical Research Council for topics covered by the review. NR 126 TC 23 Z9 27 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 EI 1471-0528 J9 BJOG-INT J OBSTET GY JI BJOG PD JAN PY 2011 VL 118 IS 2 BP 164 EP 174 DI 10.1111/j.1471-0528.2010.02766.x PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 695FT UT WOS:000285356700008 PM 21091927 ER PT J AU Lamont, RF Sobel, JD Vaisbuch, E Kusanovic, JP Mazaki-Tovi, S Kim, SK Uldbjerg, N Romero, R AF Lamont, R. F. Sobel, J. D. Vaisbuch, E. Kusanovic, J. P. Mazaki-Tovi, S. Kim, S. K. Uldbjerg, N. Romero, R. TI Parvovirus B19 infection in human pregnancy SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Review DE Fetal anaemia; human; nonimmune hydrops; hydrops-fetalis; parvovirus; pregnancy ID INTRAUTERINE FETAL-DEATH; PEAK SYSTOLIC VELOCITY; POLYMERASE CHAIN-REACTION; SERUM ALPHA-FETOPROTEIN; DAY-CARE PERSONNEL; RED-CELL APLASIA; RIO-DE-JANEIRO; HYDROPS-FETALIS; ERYTHEMA-INFECTIOSUM; TWIN PREGNANCY AB Human parvovirus B19 infection is widespread. Approximately 30-50% of pregnant women are nonimmune, and vertical transmission is common following maternal infection in pregnancy. Fetal infection may be associated with a normal outcome, but fetal death may also occur without ultrasound evidence of infectious sequelae. B19 infection should be considered in any case of nonimmune hydrops. Diagnosis is mainly through serology and polymerase chain reaction. Surveillance requires sequential ultrasound and Doppler screening for signs of fetal anaemia, heart failure and hydrops. Immunoglobulins, antiviral and vaccination are not yet available, but intrauterine transfusion in selected cases can be life saving. C1 [Lamont, R. F.; Vaisbuch, E.; Kusanovic, J. P.; Mazaki-Tovi, S.; Kim, S. K.; Uldbjerg, N.; Romero, R.] Wayne State Univ, Hutzel Womens Hosp, NICHD, Perinatol Res Branch,NIH,DHHS, Detroit, MI 48201 USA. [Lamont, R. F.; Vaisbuch, E.; Kusanovic, J. P.; Mazaki-Tovi, S.; Kim, S. K.; Uldbjerg, N.; Romero, R.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Lamont, R. F.; Vaisbuch, E.; Kusanovic, J. P.; Mazaki-Tovi, S.; Romero, R.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Sobel, J. D.] Wayne State Univ, Sch Med, Dept Infect Dis, Detroit, MI 48201 USA. [Romero, R.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Lamont, RF (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, Perinatol Res Branch,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM rlamont@med.wayne.edu; prbchiefstaff@med.wayne.edu RI Uldbjerg, Niels/O-2038-2016; OI Uldbjerg, Niels/0000-0002-6449-6426; Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH); Department of Health and Human Services (DHHS) FX This research was supported in part by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH) and Department of Health and Human Services (DHHS). NR 206 TC 38 Z9 43 U1 1 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD JAN PY 2011 VL 118 IS 2 BP 175 EP 186 DI 10.1111/j.1471-0528.2010.02749.x PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 695FT UT WOS:000285356700009 PM 21040396 ER PT J AU Lamont, RF Sobel, JD Kusanovic, JP Vaisbuch, E Mazaki-Tovi, S Kim, SK Uldbjerg, N Romero, R AF Lamont, R. F. Sobel, J. D. Kusanovic, J. P. Vaisbuch, E. Mazaki-Tovi, S. Kim, S. K. Uldbjerg, N. Romero, R. TI Current debate on the use of antibiotic prophylaxis for caesarean section SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Review DE Antibiotics; caesarean section; endometritis; pregnancy; prophylaxis; surgical site infections ID SURGICAL-SITE INFECTIONS; HIGH-RISK PATIENTS; POSTCESAREAN DELIVERY ENDOMETRITIS; EARLY POSTPARTUM ENDOMETRITIS; HOSPITAL-ACQUIRED INFECTIONS; RANDOMIZED CONTROLLED-TRIAL; WOUND-INFECTION; POSTDISCHARGE SURVEILLANCE; ANTIMICROBIAL PROPHYLAXIS; UREAPLASMA-UREALYTICUM AB Caesarean delivery is frequently complicated by surgical site infections, endometritis and urinary tract infection. Most surgical site infections occur after discharge from the hospital, and are increasingly being used as performance indicators. Worldwide, the rate of caesarean delivery is increasing. Evidence-based guidelines recommended the use of prophylactic antibiotics before surgical incision. An exception is made for caesarean delivery, where narrow-range antibiotics are administered after umbilical cord clamping because of putative neonatal benefit. However, recent evidence supports the use of pre-incision, broad-spectrum antibiotics, which result in a lower rate of maternal morbidity with no disadvantage to the neonate. C1 [Lamont, R. F.; Kusanovic, J. P.; Vaisbuch, E.; Mazaki-Tovi, S.; Kim, S. K.; Uldbjerg, N.; Romero, R.] Wayne State Univ, Hutzel Womens Hosp, NICHD, Perinatol Res Branch,NIH,DHHS, Detroit, MI 48201 USA. [Lamont, R. F.; Kusanovic, J. P.; Vaisbuch, E.; Mazaki-Tovi, S.; Kim, S. K.; Uldbjerg, N.; Romero, R.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Lamont, R. F.; Kusanovic, J. P.; Vaisbuch, E.; Mazaki-Tovi, S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Sobel, J. D.] Wayne State Univ, Sch Med, Dept Infect Dis, Detroit, MI 48201 USA. [Romero, R.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Lamont, RF (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, Perinatol Res Branch,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM rlamont@med.wayne.edu; prbchiefstaff@med.wayne.edu RI Uldbjerg, Niels/O-2038-2016; OI Uldbjerg, Niels/0000-0002-6449-6426; Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported in part by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 164 TC 32 Z9 37 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD JAN PY 2011 VL 118 IS 2 BP 193 EP 201 DI 10.1111/j.1471-0528.2010.02729.x PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 695FT UT WOS:000285356700011 PM 21159119 ER PT J AU Turkbey, B Xu, S Kruecker, J Locklin, J Pang, YX Bernardo, M Merino, MJ Wood, BJ Choyke, PL Pinto, PA AF Turkbey, Baris Xu, Sheng Kruecker, Jochen Locklin, Julia Pang, Yuxi Bernardo, Marcelino Merino, Maria J. Wood, Bradford J. Choyke, Peter L. Pinto, Peter A. TI Documenting the location of prostate biopsies with image fusion SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; MRI; TRUS-guided sextant biopsy; MRI-TRUS fusion; biopsy mapping ID MAPPING BIOPSY; CANCER AB What's known on the subject? and What does the study add? Currently, systematic prostate biopsies are obtained with minimal information about their actual location. This study demonstrates that a electromagnetically tracked ultrasound probe can be used to guide biopsies into specific areas of the prostate. By registering the ultrasound to an MRI scan of the prostate, obtained prior to biopsy, it is possible to accurately map the location of biopsies. Thus, if a patient requires a repeat biopsy, or there is a question about whether a specific area of the prostate was sampled, this system can be used to more accurately guide biopsies in the future. OBJECTIVE To develop a system that documents the location of transrectal ultrasonography (TRUS)-guided prostate biopsies by fusing them to MRI scans obtained prior to biopsy, as the actual location of prostate biopsies is rarely known. PATIENTS AND METHODS Fifty patients (median age 61) with a median prostate-specific antigen (PSA) of 5.8 ng/ml underwent 3T endorectal coil MRI prior to biopsy. 3D TRUS images were obtained just prior to standard TRUS-guided 12-core sextant biopsies wherein an electromagnetic positioning device was attached to the needle guide and TRUS probe in order to track the position of each needle pass. The 3D-TRUS image documenting the location of each biopsy was fused electronically to the T2-weighted MRI. Each biopsy needle track was marked on the TRUS images and these were then transposed onto the MRI. Each biopsy site was classified pathologically as positive or negative for cancer and the Gleason score was determined. RESULTS The location of all (n = 605) needle biopsy tracks was successfully documented on the T2-weighted (T2W) MRI. Among 50 patients, 20 had 56 positive cores. At the sites of biopsy, T2W signal was considered 'positive' for cancer (i.e. low in signal intensity) in 34 of 56 sites. CONCLUSION It is feasible to document the location of TRUS-guided prostate biopsies on pre-procedure MRI by fusing the pre-procedure TRUS to an endorectal coil MRI using electromagnetic needle tracking. This procedure may be useful in documenting the location of prior biopsies, improving quality control and thereby avoiding under-sampling of the prostate as well as directing subsequent biopsies to regions of the prostate not previously sampled. C1 [Turkbey, Baris; Bernardo, Marcelino; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Locklin, Julia; Wood, Bradford J.] NCI, Ctr Intervent Oncol, Bethesda, MD 20892 USA. [Locklin, Julia; Wood, Bradford J.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Xu, Sheng; Kruecker, Jochen] Philips Res N Amer, Briarcliff Manor, NY USA. [Pang, Yuxi] Philips Healthcare, Cleveland, OH USA. [Bernardo, Marcelino] NCI Frederick, SAIC Frederick, Frederick, MD USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182,Bldg 10,Room 1B40, Bethesda, MD 20892 USA. EM pchoyke@mail.nih.gov FU NIH; NCI [HHSN261200800001E] FX NIH and Philips have intellectual property in the field. This study was supported in part by the Intramural Research Program of the NIH. NCI contract number HHSN261200800001E. NR 10 TC 33 Z9 33 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JAN PY 2011 VL 107 IS 1 BP 53 EP 57 DI 10.1111/j.1464-410X.2010.09483.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 696CB UT WOS:000285418400006 PM 20590543 ER PT J AU Ziegelberger, G Baum, C Borkhardt, A Cobaleda, C Dasenbrock, C Dehos, A Grosche, B Hauer, J Hornhardt, S Jung, T Kammertoens, T Lagroye, I Lehrach, H Lightfoot, T Little, MP Rossig, C Sanchez-Garcia, I Schrappe, M Schuez, J Shalapour, S Slany, R Stanulla, M Weiss, W AF Ziegelberger, G. Baum, C. Borkhardt, A. Cobaleda, C. Dasenbrock, C. Dehos, A. Grosche, B. Hauer, J. Hornhardt, S. Jung, T. Kammertoens, T. Lagroye, I. Lehrach, H. Lightfoot, T. Little, M. P. Rossig, C. Sanchez-Garcia, I. Schrappe, M. Schuez, J. Shalapour, S. Slany, R. Stanulla, M. Weiss, W. TI Research recommendations toward a better understanding of the causes of childhood leukemia SO BLOOD CANCER JOURNAL LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; STEM-CELLS; BIRTH-WEIGHT; RISK; CANCER; METAANALYSIS; CHILDREN; ORIGIN; GENOME; MODEL C1 [Ziegelberger, G.; Dehos, A.; Grosche, B.; Hornhardt, S.; Jung, T.; Weiss, W.] Fed Off Radiat Protect BfS, Dept Radiat & Hlth, D-85764 Oberschleissheim, Germany. [Baum, C.] Hannover Med Sch, Dept Expt Hematol, D-3000 Hannover, Germany. [Borkhardt, A.; Hauer, J.] Univ Dusseldorf, Ctr Child & Adolescent Hlth, Dept Paediat Oncol Haematol & Clin Immunol, Dusseldorf, Germany. [Cobaleda, C.] Univ Autonoma Madrid, Spanish Res Council CSIC, CBMSO, Madrid, Spain. [Dasenbrock, C.] Fraunhofer Inst Toxicol & Expt Med ITEM, Hannnover, Germany. [Kammertoens, T.; Shalapour, S.] Charite, Inst Immunol, D-13353 Berlin, Germany. [Kammertoens, T.; Shalapour, S.] Charite, Dept Paediat Oncol & Haematol, D-13353 Berlin, Germany. [Lagroye, I.] Univ Bordeaux, Lab IMS UMR 5218, Bordeaux, France. [Lehrach, H.] Max Planck Inst Mol Genet, D-14195 Berlin, Germany. [Lightfoot, T.] Univ York, Dept Hlth Sci, Epidemiol & Genet Unit, York YO10 5DD, N Yorkshire, England. [Little, M. P.] NCI, Radiat Epidemiol Branch, Rockville, MD USA. [Rossig, C.] Univ Childrens Hosp Muenster, Munster, Germany. [Sanchez-Garcia, I.] Univ Salamanca, Spanish Res Council CSIC, IBMCC, E-37008 Salamanca, Spain. [Schrappe, M.; Stanulla, M.] Univ Med Ctr Schleswig Holstein, Dept Gen Paediat, Kiel, Germany. [Schuez, J.] Int Agcy Res Canc, Sect Environm & Radiat, F-69372 Lyon, France. [Slany, R.] Univ Erlangen Nurnberg, Dept Genet, D-91054 Erlangen, Germany. RP Ziegelberger, G (reprint author), Fed Off Radiat Protect BfS, Dept Radiat & Hlth, Ingolstaedter Landstr 1, D-85764 Oberschleissheim, Germany. EM gziegelberger@bfs.de OI SANCHEZ-GARCIA, ISIDRO/0000-0001-6989-9905 NR 47 TC 4 Z9 4 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-5385 J9 BLOOD CANCER J JI Blood Cancer J. PD JAN PY 2011 VL 1 AR e1 DI 10.1038/bcj.2010.1 PG 6 WC Oncology SC Oncology GA 872KL UT WOS:000298808200001 ER PT J AU Jhamb, M Tamura, MK Gassman, J Garg, AX Lindsay, RM Suri, RS Ting, G Finkelstein, FO Beach, S Kimmel, PL Unruh, M AF Jhamb, Manisha Tamura, Manjula K. Gassman, Jennifer Garg, Amit X. Lindsay, Robert M. Suri, Rita S. Ting, George Finkelstein, Fredric O. Beach, Scott Kimmel, Paul L. Unruh, Mark CA Frequent Hemodialysis Network Tria TI Design and Rationale of Health-Related Quality of Life and Patient-Reported Outcomes Assessment in the Frequent Hemodialysis Network Trials SO BLOOD PURIFICATION LA English DT Article; Proceedings Paper CT 13th International Conference oin Dialysis, Advances CY 2011 CL Renal Res Inst, Miami, FL HO Renal Res Inst DE Health-related quality of life; Frequent Hemodialysis Network; End-stage renal disease ID STAGE RENAL-DISEASE; DIALYSIS PATIENTS; SLEEP QUALITY; CONVENTIONAL HEMODIALYSIS; NOCTURNAL HEMODIALYSIS; MAINTENANCE DIALYSIS; MEDICATION ADHERENCE; HOME HEMODIALYSIS; FUNCTIONAL HEALTH; SYMPTOMS AB Background: End-stage renal disease patients experience significant impairments in health-related quality of life (HRQOL). Testing various strategies to improve patient HRQOL in multicenter clinical trials, such as the Frequent Hemodialysis Network (FHN) trials is vitally important. Aims: The aim of this paper is to describe the design and conduct of HRQOL and patient-reported outcomes (PRO) assessment in the FHN trials. Methods: In the FHN trials, HRQOL was examined as a multidimensional concept, and the SF-36 RAND Physical Health Composite score was one of the co-primary outcomes. The instruments completed to assess HRQOL included the Medical Outcomes Study Short Form SF-36, Health Utilities Index 3, Sleep Problems Index, Beck Depression Inventory and feeling thermometer. These instruments have been shown to have high reliability, validity and responsiveness to change in the end-stage renal disease population. Additional items evaluating PRO including sexual function, time to recovery after dialysis and patients' self-perceived burden to caregiver were also assessed. All questionnaires were administered by trained interviewers using computer-assisted telephone interviewing to ensure blinding and minimizing selection bias. Interim analysis reveals that these instruments can be used to collect a comprehensive set of HRQOL measures with minimal patient burden. Conclusions: Accurate measurement of HRQOL and PRO can help us test whether hemodialysis interventions improve the health and well-being of this compromised patient population. We have shown that a comprehensive set of HRQOL measures can be centrally collected through telephone interviews in a blinded fashion, in a way that is well tolerated with minimum respondent burden. Copyright (c) 2011 S. Karger AG, Basel C1 [Unruh, Mark] Univ Pittsburgh, Sch Med, Div Nephrol, Med Ctr, Pittsburgh, PA 15213 USA. [Garg, Amit X.; Lindsay, Robert M.; Suri, Rita S.] Univ Western Ontario, Div Nephrol, London, ON, Canada. [Beach, Scott] Univ Pittsburgh, Univ Ctr Social & Urban Res, Pittsburgh, PA 15213 USA. [Tamura, Manjula K.] Stanford Univ, Sch Med, Div Nephrol, Palo Alto, CA 94304 USA. [Gassman, Jennifer] Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. [Ting, George] El Camino Hosp, Mountain View, CA USA. [Finkelstein, Fredric O.] Yale Univ, Sch Med, Dept Med, Hosp St Raphael, New Haven, CT 06510 USA. [Kimmel, Paul L.] NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Unruh, M (reprint author), Univ Pittsburgh, Sch Med, Div Nephrol, Med Ctr, 200 Lothrop St,PUH C-1111, Pittsburgh, PA 15213 USA. EM unruh@pitt.edu RI Jhamb, Manisha/E-4169-2013; Suri, Rita/G-3348-2011 OI Suri, Rita/0000-0002-0519-3927 FU NIDDK NIH HHS [U01 DK03005, DK077785, R01 DK077785] NR 66 TC 10 Z9 10 U1 3 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0253-5068 J9 BLOOD PURIFICAT JI Blood Purif. PY 2011 VL 31 IS 1-3 BP 151 EP 158 DI 10.1159/000321855 PG 8 WC Hematology; Urology & Nephrology SC Hematology; Urology & Nephrology GA 725SS UT WOS:000287667000026 PM 21228584 ER PT J AU Minassian, AM Rowland, R Beveridge, NER Poulton, ID Satti, I Harris, S Poyntz, H Hamill, M Griffiths, K Sander, CR Ambrozak, DR Price, DA Hill, BJ Casazza, JP Douek, DC Koup, RA Roederer, M Winston, A Ross, J Sherrard, J Rooney, G Williams, N Lawrie, AM Fletcher, HA Pathan, AA McShane, H AF Minassian, Angela M. Rowland, Rosalind Beveridge, Natalie E. R. Poulton, Ian D. Satti, Iman Harris, Stephanie Poyntz, Hazel Hamill, Matthew Griffiths, Kristin Sander, Clare R. Ambrozak, David R. Price, David A. Hill, Brenna J. Casazza, Joseph P. Douek, Daniel C. Koup, Richard A. Roederer, Mario Winston, Alan Ross, Jonathan Sherrard, Jackie Rooney, Guy Williams, Nicola Lawrie, Alison M. Fletcher, Helen A. Pathan, Ansar A. McShane, Helen TI A Phase I study evaluating the safety and immunogenicity of MVA85A, a candidate TB vaccine, in HIV-infected adults SO BMJ OPEN LA English DT Article AB Objectives: Control of the tuberculosis (TB) epidemic is a global health priority and one that is likely to be achieved only through vaccination. The critical overlap with the HIV epidemic requires any effective TB vaccine regimen to be safe in individuals who are infected with HIV. The objectives of this clinical trial were to evaluate the safety and immunogenicity of a leading candidate TB vaccine, MVA85A, in healthy, HIV-infected adults. Design: This was an open-label Phase I trial, performed in 20 healthy HIV-infected, antiretroviral-naive subjects. Two different doses of MVA85A were each evaluated as a single immunisation in 10 subjects, with 24 weeks of follow-up. The safety of MVA85A was assessed by clinical and laboratory markers, including regular CD4 counts and HIV RNA load measurements. Vaccine immunogenicity was assessed by ex vivo interferon gamma (IFN-gamma) ELISpot assays and flow-cytometric analysis. Results: MVA85A was safe in subjects with HIV infection, with an adverse-event profile comparable with historical data from previous trials in HIV-uninfected subjects. There were no clinically significant vaccine-related changes in CD4 count or HIV RNA load in any subjects, and no evidence from qPCR analyses to indicate that MVA85A vaccination leads to widespread preferential infection of vaccine-induced CD4 T cell populations. Both doses of MVA85A induced an antigen-specific IFN-gamma response that was durable for 24 weeks, although of a lesser magnitude compared with historical data from HIV-uninfected subjects. The functional quality of the vaccine-induced T cell response in HIV-infected subjects was remarkably comparable with that observed in healthy HIV-uninfected controls, but less durable. Conclusion: MVA85A is safe and immunogenic in healthy adults infected with HIV. Further safety and efficacy evaluation of this candidate vaccine in TB-and HIV-endemic areas is merited. C1 [Minassian, Angela M.; Rowland, Rosalind; Beveridge, Natalie E. R.; Poulton, Ian D.; Satti, Iman; Harris, Stephanie; Poyntz, Hazel; Hamill, Matthew; Griffiths, Kristin; Sander, Clare R.; Lawrie, Alison M.; Fletcher, Helen A.; Pathan, Ansar A.; McShane, Helen] Univ Oxford, Jenner Inst, Oxford, England. [Ambrozak, David R.; Casazza, Joseph P.; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Price, David A.; Hill, Brenna J.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Price, David A.] Cardiff Univ, Sch Med, Dept Infect Immun & Biochem, Cardiff CF10 3AX, S Glam, Wales. [Roederer, Mario] NIAID, Immunotechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Winston, Alan] Imperial Coll Healthcare NHS Trust, London, England. [Ross, Jonathan] Univ Hosp Birmingham NHS Fdn Trust, Selly Oak Hosp, Birmingham, W Midlands, England. [Sherrard, Jackie; McShane, Helen] Oxford Radcliffe Hosp NHS Trust, Churchill Hosp, Dept Genitourinary Med, Oxford, England. [Rooney, Guy] Great Western Hosp NHS Fdn, Great Western Hosp, Swindon, Wilts, England. [Williams, Nicola] Univ Oxford, Ctr Stat Med, Oxford, England. [Pathan, Ansar A.] Brunel Univ, Sch Hlth Sci & Social Care, Ctr Infect Immun & Dis Mech, Uxbridge UB8 3PH, Middx, England. RP McShane, H (reprint author), Univ Oxford, Jenner Inst, Oxford, England. EM helen.mcshane@ndm.ox.ac.uk RI Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Beveridge, Natalie/0000-0002-1160-2600; /0000-0002-6008-2955; Fletcher, Helen/0000-0002-0435-1006 FU Oxford University; Wellcome Trust [WT076943MA]; TBVAC (an EU 6th Framework programme grant); National Institute of Health Research Oxford Biomedical Research Centre FX We thank J Scott and the clinical research nurses in Oxford, at St Mary's Hospital in London and at Selly Oak Hospital in Birmingham, especially K Legg and J Harding, for their invaluable assistance in identification, recruitment and follow-up of eligible subjects. We also thank A Hill for discussions. Oxford University was the sponsor for this clinical trial.; This study was supported by The Wellcome Trust (grant no WT076943MA), TBVAC (an EU 6th Framework programme grant) and The National Institute of Health Research Oxford Biomedical Research Centre. NR 27 TC 23 Z9 24 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2011 VL 1 IS 2 AR e000223 DI 10.1136/bmjopen-2011-000223 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA V27UQ UT WOS:000208638500030 PM 22102640 ER PT J AU Olafsdottir, E Aspelund, T Sigurdsson, G Thorsson, B Eiriksdottir, G Harris, TB Launer, LJ Benediktsson, R Gudnason, V AF Olafsdottir, Elin Aspelund, Thor Sigurdsson, Gunnar Thorsson, Bolli Eiriksdottir, Gudny Harris, Tamara B. Launer, Lenore J. Benediktsson, Rafn Gudnason, Vilmundur TI Effects of statin medication on mortality risk associated with type 2 diabetes in older persons: the population-based AGES-Reykjavik Study SO BMJ OPEN LA English DT Article AB Objective: To examine if the beneficial effect of statin medication on mortality seen in randomised clinical trials of type 2 diabetes applies equally to observational studies in the general population of older people. Design: A prospective, population-based cohort study. Setting: Reykjavik, Iceland. Participants: 5152 men and women from the Age, Gene/Environment Susceptibility-Reykjavik Study, mean age 77 years, range of 66-96 years. Main outcome measure: Cardiovascular and all-cause mortalities and the RR of dying according to statin use and history of coronary heart disease (CHD) in persons with type 2 diabetes and those without diabetes with a median follow-up time of 5.3 years, until end of 2009. Results: The prevalence of type 2 diabetes was 12.4% of which 35% used statins. Statin use was associated with a 50% (95% CI 8% to 72%) lower cardiovascular mortality and 53% (29% to 68%) lower all-cause mortalities in persons with diabetes. For those without diabetes, statin use was associated with a 16% (-24% to 43%) lower cardiovascular and 30% (11% to 46%) lower all-cause mortalities. Persons with diabetes using statins had a comparable risk of cardiovascular and all-cause mortality to that of the general population without diabetes. The effect was independent of the level of glycaemic control. Conclusion: This observational study lends important support to existing data from randomised clinical trials. These data suggest that in the general population of older people with diabetes, statin medication markedly reduces the excess cardiovascular and all-cause mortality risk, irrespective of the presence or absence of coronary heart disease or glucose-lowering medication. C1 [Olafsdottir, Elin; Aspelund, Thor; Thorsson, Bolli; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Res Inst, Kopavogur, Iceland. [Olafsdottir, Elin] Univ Iceland, Ctr Publ Hlth Sci, Reykjavik, Iceland. [Aspelund, Thor; Sigurdsson, Gunnar; Benediktsson, Rafn; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Sigurdsson, Gunnar; Benediktsson, Rafn] Landspitali Univ Hosp, Dept Endocrinol & Metab, Reykjavik, Iceland. [Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. RP Gudnason, V (reprint author), Iceland Heart Assoc, Res Inst, Kopavogur, Iceland. EM v.gudnason@hjarta.is RI Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 FU NIH [N01-AG-1-2100]; NIA Intramural Research Program; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic parliament) FX This study has been funded by NIH contract N01-AG-1-2100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and Althingi (the Icelandic parliament). The study is approved by the Icelandic National Bioethics Committee, VSN: 00-063. The researchers are indebted to the participants for their willingness to participate in the study. NR 22 TC 21 Z9 23 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2011 VL 1 IS 1 AR e000132 DI 10.1136/bmjopen-2011-000132 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA V27UL UT WOS:000208638000054 PM 22021772 ER PT J AU Dietz, AC Orchard, PJ Baker, KS Giller, RH Savage, SA Alter, BP Tolar, J AF Dietz, A. C. Orchard, P. J. Baker, K. S. Giller, R. H. Savage, S. A. Alter, B. P. Tolar, J. TI Disease-specific hematopoietic cell transplantation: nonmyeloablative conditioning regimen for dyskeratosis congenita SO BONE MARROW TRANSPLANTATION LA English DT Article DE dyskeratosis congenita; hematopoietic cell transplantation; reduced-intensity conditioning regimen ID BONE-MARROW-TRANSPLANTATION; CORD BLOOD TRANSPLANTATION; HOYERAAL-HREIDARSSON-SYNDROME; APLASTIC-ANEMIA; FANCONI-ANEMIA; ANTITHYMOCYTE GLOBULIN; FLUDARABINE; FAILURE; ALEMTUZUMAB; MELPHALAN AB Dyskeratosis congenita (DC) is characterized by reticular skin pigmentation, oral leukoplakia and abnormal nails. Patients with DC have very short telomeres and approximately one-half have mutations in telomere biology genes. A majority of patients with DC develop BM failure (BMF). Hematopoietic cell transplantation (HCT) represents the only known cure for BMF in DC, but poses significant toxicities. We report six patients who underwent allogeneic HCT with a novel nonmyeloablative conditioning regimen specifically designed for DC patients. Graft sources included related PBSCs (1), unrelated BM (2) and unrelated double umbilical cord blood (3). Complete donor engraftment was achieved in five of six patients. One patient had initial autologous hematopoietic recovery, which was followed by a second transplant that resulted in 88% donor chimerism. With a median follow-up of 26.5 months, four patients are alive, three of whom were recipients of unrelated grafts. We conclude with this small study that encouraging short-term survival can be achieved with HCT in patients with DC using a preparative regimen designed to promote donor engraftment and minimize life-threatening disease-specific complications such as pulmonary fibrosis. Long-term follow-up will be crucial with respect to individualized patient care with each of the transplanted individuals. Bone Marrow Transplantation (2011) 46, 98-104; doi: 10.1038/bmt.2010.65; published online 12 April 2010 C1 [Dietz, A. C.; Orchard, P. J.; Tolar, J.] Univ Minnesota, Div Hematol Oncol Blood & Marrow Transplantat, Dept Pediat, Minneapolis, MN 55455 USA. [Baker, K. S.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Giller, R. H.] Univ Colorado, Dept Pediat, Pediat Bone Marrow Transplant Program, Denver, CO 80202 USA. [Giller, R. H.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Savage, S. A.; Alter, B. P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. RP Tolar, J (reprint author), Univ Minnesota, Div Hematol Oncol Blood & Marrow Transplantat, Dept Pediat, 420 Delaware St SE,MMC 366, Minneapolis, MN 55455 USA. EM tolar003@umn.edu RI Savage, Sharon/B-9747-2015; OI Savage, Sharon/0000-0001-6006-0740; Tolar, Jakub/0000-0002-0957-4380 FU Children's Cancer Research Fund in Minneapolis, MN; National Institutes of Health; National Cancer Institute FX This work was supported in part by the Children's Cancer Research Fund in Minneapolis, MN and the Intramural Program of the National Institutes of Health and the National Cancer Institute. NR 44 TC 50 Z9 52 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JAN PY 2011 VL 46 IS 1 BP 98 EP 104 DI 10.1038/bmt.2010.65 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 705MC UT WOS:000286136000018 PM 20383216 ER PT S AU Lin, ZC Canales, JJ Bjorgvinsson, T Thomsen, M Qu, H Liu, QR Torres, GE Caine, SB AF Lin, Zhicheng Canales, Juan J. Bjoergvinsson, Throestur Thomsen, Morgane Qu, Hong Liu, Qing-Rong Torres, Gonzalo E. Caine, S. Barak BE Rahman, S TI Monoamine Transporters: Vulnerable and Vital Doorkeepers SO BRAIN AS A DRUG TARGET SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID HUMAN DOPAMINE TRANSPORTER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; HUMAN SEROTONIN TRANSPORTER; KNOCK-OUT MICE; DEFICIT HYPERACTIVITY DISORDER; MAJOR DEPRESSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; DEPENDENT NEUROTRANSMITTER TRANSPORTERS; SINGLE NUCLEOTIDE POLYMORPHISMS C1 [Lin, Zhicheng; Thomsen, Morgane; Caine, S. Barak] Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. [Lin, Zhicheng; Thomsen, Morgane; Caine, S. Barak] McLean Hosp, Div Alcohol & Drug Abuse, Belmont, MA 02178 USA. [Canales, Juan J.] Univ Canterbury, Dept Psychol Behav Neurosci, Christchurch 1, New Zealand. [Bjoergvinsson, Throestur] Harvard Univ, McLean Hosp, Sch Med, Behav Hlth Partial Hosp, Belmont, MA 02178 USA. [Bjoergvinsson, Throestur] Harvard Univ, McLean Hosp, Sch Med, Psychol Internship Programs, Belmont, MA 02178 USA. [Qu, Hong] Peking Univ, Coll Life Sci, Natl Lab Prot Engn & Plant Genet Engn, Ctr Bioinformat, Beijing 100871, Peoples R China. [Liu, Qing-Rong] Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH DHHS, Baltimore, MD USA. [Torres, Gonzalo E.] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA USA. RP Lin, ZC (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. RI Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 FU Intramural NIH HHS; NIDA NIH HHS [R01 DA021409-05, K01 DA016710-04, R00 DA027825, DA027825, K99 DA027825-01, R01 DA021409, K99 DA027825, K01 DA016710, DA016710, DA021409] NR 350 TC 17 Z9 19 U1 7 U2 20 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-385506-0 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2011 VL 98 BP 1 EP 46 DI 10.1016/B978-0-12-385506-0.00001-6 PG 46 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BTC88 UT WOS:000286531200001 PM 21199769 ER PT J AU DePamphilis, ML AF DePamphilis, Melvin L. TI Spotlight on Geminin SO BREAST CANCER RESEARCH LA English DT Editorial Material ID DNA-REPLICATION; CELLS; CANCER; CHROMATIN AB In the previous issue of Breast Cancer Research, Gardner and co-workers describe a novel interaction between Geminin, a protein that prevents reinitiation of DNA replication, and Topoisomerase II alpha (TopoII alpha), an enzyme essential for removing catenated intertwines between sister chromatids. Geminin facilitates the action of TopoII alpha, thereby promoting termination of DNA replication at the same time it inhibits initiation. In this manner, Geminin ensures that cells duplicate their genome once, but only once, each time they divide. Remarkably, either depletion of Geminin or overexpression of Geminin inhibits the action of TopoII alpha, thereby making Geminin an excellent target for cancer chemotherapy. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP DePamphilis, ML (reprint author), NICHHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM depamphm@mail.nih.gov NR 16 TC 2 Z9 2 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2011 VL 13 IS 3 AR 109 DI 10.1186/bcr2881 PG 2 WC Oncology SC Oncology GA 832ID UT WOS:000295797100026 PM 21639956 ER PT J AU Luo, J AF Luo, Ji TI Cancer's sweet tooth for serine SO BREAST CANCER RESEARCH LA English DT Editorial Material ID METABOLISM AB Exemplified by the cancer cell's preference for glycolysis (the Warburg effect), altered metabolism has taken centerstage as an emerging hallmark of cancer. Charting the landscape of cancer metabolic addictions should reveal new avenues for therapeutic attack. Two recent studies found subsets of human melanoma and breast cancers to have high levels of phosphoglycerate dehydrogenase (PHGDH), a key enzyme for serine biosynthesis, and these cancer cells are dependent on PHGDH for their growth and survival. Tumors may thus harbor distinct metabolic alterations to support their malignancy, and targeting enzymes such as PHGDH might prove a viable therapeutic strategy in this scenario. C1 NCI, NIH, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Luo, J (reprint author), NCI, NIH, Med Oncol Branch, Ctr Canc Res, 10 Ctr Dr,12N226, Bethesda, MD 20892 USA. EM Ji.luo@nih.gov NR 6 TC 11 Z9 12 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2011 VL 13 IS 6 AR 317 DI 10.1186/bcr2932 PG 3 WC Oncology SC Oncology GA 904DK UT WOS:000301173700037 PM 22189202 ER PT J AU Nyante, SJ Faupel-Badger, JM Sherman, ME Pfeiffer, RM Gaudet, MM Falk, RT Andaya, AA Lissowska, J Brinton, LA Peplonska, B Vonderhaar, BK Chanock, S Garcia-Closas, M Figueroa, JD AF Nyante, Sarah J. Faupel-Badger, Jessica M. Sherman, Mark E. Pfeiffer, Ruth M. Gaudet, Mia M. Falk, Roni T. Andaya, Abegail A. Lissowska, Jolanta Brinton, Louise A. Peplonska, Beata Vonderhaar, Barbara K. Chanock, Stephen Garcia-Closas, Montserrat Figueroa, Jonine D. TI Genetic variation in PRL and PRLR, and relationships with serum prolactin levels and breast cancer risk: results from a population-based case-control study in Poland SO BREAST CANCER RESEARCH LA English DT Article ID TUMOR CHARACTERISTICS; POSTMENOPAUSAL WOMEN; RECEPTOR; POLYMORPHISM; EXPRESSION; CARCINOMA; PREMENOPAUSAL; ASSOCIATIONS; HAPLOTYPES; HORMONES AB Introduction: Studies suggest that high circulating levels of prolactin increase breast cancer risk. It is unclear if genetic variations in prolactin (PRL) or prolactin receptor (PRLR) genes also play a role. Thus, we examined the relationship between single nucleotide polymorphisms (SNPs) in PRL and PRLR, serum prolactin levels and breast cancer risk in a population-based case-control study. Methods: We genotyped 8 PRL and 20 PRLR tag SNPs in 1965 breast cancer cases and 2229 matched controls, aged 20-74, and living in Warsaw or Lodz, Poland. Serum prolactin levels were measured by immunoassay in a subset of 773 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for genotype associations with breast cancer risk were estimated using unconditional logistic regression, adjusted for age and study site. Geometric mean prolactin levels were estimated using linear regression models adjusted for age, study site, blood collection time, and menstrual cycle day (premenopausal women). Results: Three SNPs were associated with breast cancer risk: in premenopausal women, PRLR rs249537 (T vs. C per allele OR 1.39, 95% CI 1.07 - 1.80, P = 0.01); and in postmenopausal women, PRLR rs7718468 (C vs. T per-allele OR 1.16, 95% CI 1.03 - 1.30, P = 0.01) and PRLR rs13436213 (A vs. G per-allele OR 1.13 95% CI 1.01 - 1.26, P = 0.04). However, mean serum prolactin levels for these SNPs did not vary by genotype (P-trend > 0.05). Other SNPs were associated with serum prolactin levels: PRLR rs62355518 (P-trend = 0.01), PRLR rs10941235 (P-trend = 0.01), PRLR rs1610218 (P-trend = 0.01), PRLR rs34024951 (P-trend = 0.02), and PRLR rs9292575 (P-trend = 0.03) in premenopausal controls and PRL rs849872 (P-trend = 0.01) in postmenopausal controls. Conclusions: Our data provide limited support for an association between common variations in PRLR and breast cancer risk. Altered serum prolactin levels were not associated with breast cancer risk-associated variants, suggesting that common genetic variation is not a strong predictor of prolactin-associated breast cancer risk in this population. C1 [Nyante, Sarah J.; Sherman, Mark E.; Pfeiffer, Ruth M.; Falk, Roni T.; Andaya, Abegail A.; Brinton, Louise A.; Figueroa, Jonine D.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Faupel-Badger, Jessica M.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, Rockville, MD 20852 USA. [Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30316 USA. [Lissowska, Jolanta] Ctr Canc, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland. [Lissowska, Jolanta] M Sklodowska Curie Inst Oncol, PL-02781 Warsaw, Poland. [Peplonska, Beata] Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, PL-91348 Lodz, Poland. [Vonderhaar, Barbara K.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, Gaithersburg, MD 20852 USA. [Garcia-Closas, Montserrat] Inst Canc Res, Sutton SM2 5NG, Surrey, England. RP Nyante, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA. EM sarah.nyante@nih.gov RI Pfeiffer, Ruth /F-4748-2011; Peplonska, Beata/F-6004-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Lissowska, Jolanta/0000-0003-2695-5799 FU National Cancer Institute (USA) FX The authors would like to thank Pei Chao and Michael Stagner, of Information Management Services, Inc. (Silver Spring, MD, USA), for their work on data management and the study participants and interviewers who took part in the Polish Breast Cancer Study as well as the physicians, pathologists, and nurses from participating centers for their efforts during field work. This research was supported by the Intramural Research Program of the National Cancer Institute (USA). NR 30 TC 9 Z9 9 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2011 VL 13 IS 2 AR R42 DI 10.1186/bcr2864 PG 11 WC Oncology SC Oncology GA 791VI UT WOS:000292694600031 PM 21470416 ER PT J AU Smits, BMG Sharma, D Samuelson, DJ Woditschka, S Mau, B Haag, JD Gould, MN AF Smits, Bart M. G. Sharma, Deepak Samuelson, David J. Woditschka, Stephan Mau, Bob Haag, Jill D. Gould, Michael N. TI The non-protein coding breast cancer susceptibility locus Mcs5a acts in a non-mammary cell-autonomous fashion through the immune system and modulates T-cell homeostasis and functions SO BREAST CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; MAMMARY-CARCINOMA SUSCEPTIBILITY; QUANTITATIVE TRAIT LOCUS; CONFER SUSCEPTIBILITY; COMMON VARIANTS; RISK; RAT; CARCINOGENESIS; ALLELES; MODEL AB Introduction: Mechanisms underlying low-penetrance, common, non-protein coding variants in breast cancer risk loci are largely undefined. We showed previously that the non-protein coding mammary carcinoma susceptibility locus Mcs5a/MCS5A modulates breast cancer risk in rats and women. The Mcs5a allele from the Wistar-Kyoto (WKy) rat strain consists of two genetically interacting elements that have to be present on the same chromosome to confer mammary carcinoma resistance. We also found that the two interacting elements of the resistant allele are required for the downregulation of transcript levels of the Fbxo10 gene specifically in T-cells. Here we describe mechanisms through which Mcs5a may reduce mammary carcinoma susceptibility. Methods: We performed mammary carcinoma multiplicity studies with three mammary carcinoma-inducing treatments, namely 7,12-dimethylbenz(a) anthracene (DMBA) and N-nitroso-N-methylurea (NMU) carcinogenesis, and mammary ductal infusion of retrovirus expressing the activated HER2/neu oncogene. We used mammary gland and bone marrow transplantation assays to assess the target tissue of Mcs5a activity. We used immunophenotyping assays on well-defined congenic rat lines carrying susceptible and resistant Mcs5a alleles to identify changes in T-cell homeostasis and function associated with resistance. Results: We show that Mcs5a acts beyond the initial step of mammary epithelial cell transformation, during early cancer progression. We show that Mcs5a controls susceptibility in a non-mammary cell-autonomous manner through the immune system. The resistant Mcs5a allele was found to be associated with an overabundance of gd T-cell receptor (TCR)+ T-cells as well as a CD62L (L-selectin)-high population of all T-cell classes. In contrast to in mammary carcinoma, gdTCR+ T-cells are the predominant T-cell type in the mammary gland and were found to be overabundant in the mammary epithelium of Mcs5a resistant congenic rats. Most of them simultaneously expressed the CD4, CD8, and CD161 alpha markers. In cultured T-cells of Mcs5a resistant congenic rats we found increased mitogen-induced proliferation and production of Th1 cytokines IFNg, IL-2, and Tumor Necrosis Factor (TNF), but not Th2 cytokines IL-4 and IL-6, or Th17 cytokine IL-17 when compared with susceptible control rats. Conclusions: These data support a hypothesis that Mcs5a displays a non-mammary cell-autonomous mechanism of action to modulate breast cancer risk through the immune system. The resistant Mcs5a allele is associated with alterations in T-cell homeostasis and functions, and overabundance of gamma delta TCR+ T-cells in carcinogen-exposed mammary epithelium. C1 [Smits, Bart M. G.; Sharma, Deepak; Woditschka, Stephan; Mau, Bob; Haag, Jill D.; Gould, Michael N.] Univ Wisconsin, McArdle Lab Canc Res, Dept Oncol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Samuelson, David J.] Univ Louisville, Sch Med, Dept Biochem & Mol Biol, Louisville, KY 40292 USA. [Woditschka, Stephan] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. RP Gould, MN (reprint author), Univ Wisconsin, McArdle Lab Canc Res, Dept Oncol, Sch Med & Publ Hlth, 1400 Univ Ave, Madison, WI 53706 USA. EM gould@oncology.wisc.edu RI Gould, Michael/C-7414-2014 FU National Institutes of Health/National Cancer Institute [R01-CA123272]; US Department of Defense (DOD) [W81XWH-07-1-0404]; DOD [DAMD17-03-1-0280, W81XWH-04-1-0312] FX We thank Kathy Schell, Joel Puchalski, and Dagna Sheerar of the Paul P. Carbone Comprehensive Cancer Center Flow Cytometry Core for their expertise, assistance, and service. This research was supported by National Institutes of Health/National Cancer Institute grant R01-CA123272, US Department of Defense (DOD) Postdoctoral Award W81XWH-07-1-0404 to BMGS, DOD Postdoctoral Fellowship DAMD17-03-1-0280 to DJS, and DOD Predoctoral Traineeship W81XWH-04-1-0312 to SW. NR 23 TC 15 Z9 15 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2011 VL 13 IS 4 AR R81 DI 10.1186/bcr2933 PG 13 WC Oncology SC Oncology GA 850BP UT WOS:000297169700010 PM 21846333 ER PT J AU Takebe, N Warren, RQ Ivy, SP AF Takebe, Naoko Warren, Ronald Q. Ivy, S. Percy TI Breast cancer growth and metastasis: interplay between cancer stem cells, embryonic signaling pathways and epithelial-to-mesenchymal transition SO BREAST CANCER RESEARCH LA English DT Review ID E-CADHERIN EXPRESSION; TRANSCRIPTION FACTOR SNAIL; GENE-EXPRESSION; PANCREATIC-CANCER; INITIATING CELLS; MAMMARY-CARCINOMA; TUMOR PROGRESSION; DOWN-REGULATION; CROSS-TALK; TGF-BETA AB Induction of epithelial-to-mesenchymal transition (EMT) in cancer stem cells (CSCs) can occur as the result of embryonic pathway signaling. Activation of Hedgehog (Hh), Wnt, Notch, or transforming growth factor-beta leads to the upregulation of a group of transcriptional factors that drive EMT. This process leads to the transformation of adhesive, non-mobile, epithelial-like tumor cells into cells with a mobile, invasive phenotype. CSCs and the EMT process are currently being investigated for the role they play in driving metastatic tumor formation in breast cancer. Both are very closely associated with embryonic signaling pathways that stimulate self-renewal properties of CSCs and EMT-inducing transcription factors. Understanding these mechanisms and embryonic signaling pathways may lead to new opportunities for developing therapeutic agents to help prevent metastasis in breast cancer. In this review, we examine embryonic signaling pathways, CSCs, and factors affecting EMT. C1 [Takebe, Naoko; Ivy, S. Percy] NCI, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Invest Drug Branch, Rockville, MD 20852 USA. [Warren, Ronald Q.] PSI Int Inc, Bethesda, MD 20817 USA. RP Takebe, N (reprint author), NCI, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Invest Drug Branch, EPN 7131,6130 Execut Blvd, Rockville, MD 20852 USA. EM takeben@mail.nih.gov; ivyp@ctep.nci.nih.gov NR 95 TC 80 Z9 90 U1 1 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2011 VL 13 IS 3 AR 211 DI 10.1186/bcr2876 PG 11 WC Oncology SC Oncology GA 832ID UT WOS:000295797100030 PM 21672282 ER PT J AU Korde, LA Mueller, CM Loud, JT Struewing, JP Nichols, K Greene, MH Mai, PL AF Korde, Larissa A. Mueller, Christine M. Loud, Jennifer T. Struewing, Jeffery P. Nichols, Kathy Greene, Mark H. Mai, Phuong L. TI No evidence of excess breast cancer risk among mutation-negative women from BRCA mutation-positive families SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE BRCA mutation; Breast cancer risk; Mutation negative; Cohort ID CARRIERS AB This analysis addresses risk of breast cancer among women in BRCA-positive families who test negative for the family mutation. We compared the number of prospectively diagnosed breast cancers in 395 mutation-negative women from 28 BRCA1/2-positive families to an age-, race-, and calendar time-specific expected number of breast cancers derived from the SEER 9 Cancer Registry. Study participants contributed a total of 7008.1 person-years of follow-up. The mean age at study entry was 31.3 years; mean follow-up was 17.7 years. Ten women developed breast cancer yielding an observed-to-expected ratio of 0.82 (95% CI 0.39-1.51). Adjustment for possible reduction in breast cancer risk due to oophorectomy by two different methods resulted in O/E ratios in the range of 0.80-0.99. Stratification by degree of relatedness to the nearest mutation carrier did not substantially alter these results, however, women with at least one-first degree relative with breast cancer appeared to have a slightly increased, though not statistically significant, risk of breast cancer (O/E ratio = 1.33, 95% CI 0.41-2.91). Our data suggest that breast cancer risk among mutation-negative women from BRCA1/2 mutation-positive families is similar to that observed in the general population, with a possible slight increase in risk among mutation-negative women with a family history of breast cancer in a first degree relative. Although this is the largest prospective cohort yet assembled to address this important question, the number of breast cancer events is still relatively small. C1 [Korde, Larissa A.] Univ Washington, Seattle Canc Care Alliance, Div Med Oncol, Seattle, WA 98109 USA. [Mueller, Christine M.; Loud, Jennifer T.; Greene, Mark H.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Struewing, Jeffery P.] NHGRI, Bethesda, MD 20892 USA. [Nichols, Kathy] Westat Corp, Rockville, MD USA. RP Korde, LA (reprint author), Univ Washington, Seattle Canc Care Alliance, Div Med Oncol, 825 Eastlake Ave E,G3-630, Seattle, WA 98109 USA. EM Lkorde@u.washington.edu RI Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 FU National Cancer Institute; Westat; [NO2-CP-11019]; [NO2-CP-65504] FX We are grateful to the families who participated in National Cancer Institute protocols 78-C-0039 [NCT00004007]: Clinical, Laboratory, and Epidemiologic Characterization of Individuals and Families at High Risk of Cancer, and 02-C-0212 [NCT00045214]: Study of Clinical, Genetic, Behavioral, Laboratory and Epidemiologic Characteristics of Individuals and Families at High Risk of Breast or Ovarian Cancer. Without their sustained commitment to this research effort, this work would have been impossible. We would also like to acknowledge the contributions of June Peters, Ron Kase and Ann Carr to the study, and Dr. Mitch Gail for thoughtful comments on the manuscript. This research was supported, in part, by funding from the Intramural Research Program of the National Cancer Institute to the Clinical Genetics Branch, and by support services contracts NO2-CP-11019 and NO2-CP-65504 with Westat. NR 10 TC 16 Z9 16 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2011 VL 125 IS 1 BP 169 EP 173 DI 10.1007/s10549-010-0923-y PG 5 WC Oncology SC Oncology GA 689UV UT WOS:000284956400019 PM 20458532 ER PT J AU Monsees, GM Kraft, P Chanock, SJ Hunter, DJ Han, JL AF Monsees, Genevieve M. Kraft, Peter Chanock, Stephen J. Hunter, David J. Han, Jiali TI Comprehensive screen of genetic variation in DNA repair pathway genes and postmenopausal breast cancer risk SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Polymorphism; DNA repair; Breast cancer; Postmenopausal women; Pathway ID NUCLEOTIDE EXCISION-REPAIR; PROGESTERONE-RECEPTOR STATUS; GENOME-WIDE ASSOCIATION; ESTROGEN-RECEPTOR; SUSCEPTIBILITY; POLYMORPHISMS; PROFICIENCY; CULTURES; ALLELES; BRCA2 AB Mistakes in DNA repair can result in sustained damage and genetic instability. We comprehensively evaluated common variants in DNA repair pathway genes for their association with postmenopausal breast cancer risk with and without respect to estrogen receptor (ER) and progesterone receptor (PR) subtypes. In this study of 1,145 prospectively ascertained breast cancer cases and 1,142 matched controls from the Nurses' Health Study Cancer Genetic Markers of Susceptibility project, we evaluated 1,314 common genetic variants in 68 candidate genes. These variants were chosen to represent five DNA repair pathways including base excision repair, nucleotide excision repair, double-strand break repair (homologous recombination and non-homologous end-joining), direct reversal repair, and mismatch repair, along with candidate DNA polymerases, Fanconi Anemia complementation groups, and other genes relevant to DNA damage recognition and response. Main effects, pathway effects, and pair-wise interactions were evaluated using Logistic Regression, and the Admixture Maximum Likelihood (AML) and Kernel Machine tests. Eight linked loci within XRCC4 were associated with susceptibility to PR- breast cancer (main effect p-values corrected for multiple testing at the within-gene level < 0.04). These loci drove the association between the non-homologous end-joining pathway, and PR- breast cancer (AML p-value for the full pathway = 0.002; p-value when the eight loci were removed = 0.86). A Kernel machine test of no linear or quadratic effects, or pairwise interaction, yielded a p-value of 0.85. Common variation alone in DNA repair genes plays at most a small role in determining postmenopausal breast cancer risk among women of European ancestry. C1 [Monsees, Genevieve M.; Kraft, Peter; Hunter, David J.; Han, Jiali] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Monsees, Genevieve M.; Hunter, David J.; Han, Jiali] Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA 02115 USA. [Monsees, Genevieve M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Monsees, Genevieve M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Han, Jiali] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. RP Han, JL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, 665 Huntington Ave, Boston, MA 02115 USA. EM jiali.han@channing.harvard.edu FU NCI [CA118 447]; PHS [T32-ES016645-01] FX This project was funded by NCI grant CA118 447. Genevieve Monsees was supported by PHS T32-ES016645-01. The authors would like to thank Constance Chen for preparing the data and for producing Fig. 1. We also thank the participants of the Nurses' Health Study for their dedication and commitment. NR 33 TC 12 Z9 12 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2011 VL 125 IS 1 BP 207 EP 214 DI 10.1007/s10549-010-0947-3 PG 8 WC Oncology SC Oncology GA 689UV UT WOS:000284956400024 PM 20496165 ER PT J AU Dean, A AF Dean, Ann TI In the loop: long range chromatin interactions and gene regulation SO BRIEFINGS IN FUNCTIONAL GENOMICS LA English DT Article DE long range interactions; chromosome conformation capture; enhancers; silencers; insulators ID BETA-GLOBIN LOCUS; DEPENDENT ENHANCER-BLOCKING; CONTROL REGION; CHROMOSOME CONFORMATION; CTCF-BINDING; ERYTHROID-DIFFERENTIATION; NUCLEAR-ORGANIZATION; HISTONE MODIFICATION; PROTEIN CTCF; HUMAN GENOME AB Enhancers, silencer and insulators are DNA elements that play central roles in regulation of the genome that are crucial for development and differentiation. In metazoans, these elements are often separated from target genes by distances that can reach 100 Kb. How regulation can be accomplished over long distances has long been intriguing. Current data indicate that although the mechanisms by which these diverse regulatory elements affect gene transcription may vary, an underlying feature is the establishment of close contacts or chromatin loops. With the generalization of this principle, new questions emerge, such as how the close contacts are formed and stabilized and, importantly, how they contribute to the regulation of transcriptional output at target genes. This review will concentrate on examples where a functional role and a mechanistic understanding has been explored for loops formed between genes and their regulatory elements or among the elements themselves. C1 NIDDK, Sect Gene Regulat & Dev, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Dean, A (reprint author), NIDDK, Sect Gene Regulat & Dev, Lab Cellular & Dev Biol, NIH, Bldg 50,Room 3154,50 South Dr,MSC 8028, Bethesda, MD 20892 USA. EM anndean@helix.nih.gov FU National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health FX Work in the author's laboratory is supported by the Intramural Program of the National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health. NR 60 TC 41 Z9 43 U1 3 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2041-2649 J9 BRIEF FUNCT GENOMICS JI Brief. Funct. Genomics PD JAN PY 2011 VL 10 IS 1 SI SI BP 3 EP 10 DI 10.1093/bfgp/elq033 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 723DQ UT WOS:000287486900002 PM 21258045 ER PT J AU Rosado, LAR Rodriguez-Canales, J Zhang, BL AF Rosado, Leslie A. Rivera Rodriguez-Canales, Jaime Zhang, Baolin TI Association of D4-GDI expression with breast cancer progression SO CANCER BIOMARKERS LA English DT Article DE D4-GDI; breast cancer; progression; immunohistochemistry ID GDP-DISSOCIATION INHIBITOR; DRUG-INDUCED APOPTOSIS; CELL-LINES; RHO-GTPASES; GENE-EXPRESSION; METASTASIS; TUMOR; INVASIVENESS; PROTEINS; RHOGDI2 AB D4-GDI is a key regulator of Rho GTPases that have been implicated in several aspects of breast tumorigenesis. We have previously found that D4-GDI was selectively expressed in breast cancer cell lines over normal mammary epithelial cells [45]. In this study, we investigated the expression level of D4-GDI in breast tumor specimens (n = 165) by immunohistochemistry using a validated antibody that specifically recognizes the full-length D4-GDI protein. D4-GDI was predominantly expressed in the luminal cells of the duct in contrast to the myoepithelial cells of the outer layer. The percentage of D4-GDI positive samples were found to be higher in the early stages of breast cancers followed by a significant decrease in malignant tumors and metastatic lesions when compared to normal breast tissues (p < 0.01). Analysis of matched samples confirmed the lower expression of D4-GDI in malignant tumors than normal adjacent tissues, while there was no further decrease in metastatic lesions. These results suggest that D4-GDI may function as a biphasic regulator of breast cancer progression and metastasis. C1 [Rosado, Leslie A. Rivera; Zhang, Baolin] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Rodriguez-Canales, Jaime] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Zhang, BL (reprint author), 29 Lincoln Dr,Bldg 29A,Rm 2A01,HFD 122, Bethesda, MD 20892 USA. EM Baolin.Zhang@fda.hhs.gov OI Rodriguez-Canales, Jaime/0000-0002-0885-2377 FU FDA FX We thank Dr. John Gillespie from Pathology Consultant Services for tissue microarray analysis and scoring and helpful discussions on the pathology of breast tissues. This research was supported by the FDA Critical Path funding. NR 46 TC 3 Z9 3 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2011 VL 10 IS 3-4 BP 163 EP 173 DI 10.3233/CBM-2012-0240 PG 11 WC Oncology SC Oncology GA 957JK UT WOS:000305157500006 ER PT J AU Grizzle, WE Srivastava, S Manne, U AF Grizzle, William E. Srivastava, Sudhir Manne, Upender TI Translational pathology of neoplasia SO CANCER BIOMARKERS LA English DT Article DE Sensitivity; specificity; early detection; prognosis; risk assessment; surrogate endpoints; diagnosis; receiver operating characteristic; prediction; biomarkers; prevalence; medical costs; side effects; histopathology; molecular features; imaging; prevention; treatment; personalized medicine; individualized medical care ID PROSTATE-SPECIFIC ANTIGEN; FATTY-ACID SYNTHASE; GROWTH-FACTOR-ALPHA; CELL LUNG-CANCER; BREAST-CANCER; COLORECTAL ADENOCARCINOMAS; PHENOTYPIC-EXPRESSION; BIOMARKER MODULATION; POSTMENOPAUSAL WOMEN; AFRICAN-AMERICANS AB With the increasing use of individualized medical care (personalized medicine) in treating and managing patients with cancer, the utilization of biomarkers in selecting and tailoring such medical approaches also is increasing and becoming more important. Specifically, many therapies are effective against only a subgroup of a specific type of tumors and exposing patients with different non-responsive subgroups of the same tumor to ineffective therapies, not only exposes these patients needlessly to acute and chronic side effects of the therapy, but also adds to the costs of medical care. For example, the Oncotype Dx test for estrogen receptor positive tumors that are node negative has been used to identify low risk tumors for which surgery alone is an adequate therapy. Biomarkers may be used to aid in multiple aspects of medical care related to cancer, including early detection, diagnosis, risk assessment, as well as in predicting the aggressiveness of cancers (i.e., prognosis) and predicting the therapeutic efficacy of treatments (i.e., prediction). Biomarkers may be also used as surrogate endpoints to aid in evaluating therapies and preventive approaches. Types of biomarkers vary greatly and include histopathologic appearance, stage of the lesion, quantitative morphologic features, size of the lesion, metastatic pattern and extent of metastasis, as well as imaging and molecular features. The types of measurements of biomarkers also vary; for example, molecular features can be measured at the DNA, mRNA or protein levels as well as at regulatory levels (e. g., microRNA). The usefulness of each biomarker is limited by its sensitivity and specificity in fulfilling its role (e. g., in early detection) and the requirements of sensitivity and specificity to accomplish specific tasks are affected by multiple variables. For example, both very high specificity and sensitivity of a test are required to screen a population with a low prevalence of a specific tumor. The goal of this manuscript is to introduce the reader to how biomarkers may be used and the limitations on the uses of biomarkers in translational research. C1 [Grizzle, William E.; Manne, Upender] Univ Alabama, Dept Pathol, Div Anat Pathol, Birmingham, AL 35294 USA. [Srivastava, Sudhir] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, Rockville, MD USA. RP Grizzle, WE (reprint author), Univ Alabama, Dept Pathol, Div Anat Pathol, Zeigler Res Bldg,ZRB 408,703 S 19th St, Birmingham, AL 35294 USA. EM wgrizzle@uab.edu FU Early Detection Research Network (EDRN) [5U24 CA86359]; Department of Defense [PC093309]; Breast [5P50CA089019]; Pancreatic SPORES at UAB [2P50CA101955]; Susan G. Komen Breast Cancer Foundation [BCTR0600484]; Skin Disease Research Center at UAB [5P30AR50948, POP138306] FX Supported in part by the Early Detection Research Network (EDRN) (5U24 CA86359), Department of Defense, "Biomarkers in the Detection of Prostate Cancer in African-Americans" (PC093309), the Breast (5P50CA089019) and Pancreatic (2P50CA101955) SPORES at UAB, the Susan G. Komen Breast Cancer Foundation (BCTR0600484), the Skin Disease Research Center at UAB (5P30AR50948) to William E. Grizzle, and (POP138306) to Upender Manne. NR 70 TC 2 Z9 2 U1 2 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2011 VL 9 IS 1-6 BP 7 EP 20 DI 10.3233/CBM-2011-0159 PG 14 WC Oncology SC Oncology GA 856ZB UT WOS:000297682300002 ER PT J AU Grizzle, WE Srivastava, S Manne, U AF Grizzle, William E. Srivastava, Sudhir Manne, Upender TI The biology of incipient, pre-invasive or intraepithelial neoplasia SO CANCER BIOMARKERS LA English DT Article DE Intraepithelial neoplasia; pre-invasive neoplasia; prostatic intraepithelial neoplasia; pancreatic intraepithelial neoplasia; cervical intraepithelial neoplasia; adenomatous polyps; ductal carcinoma in situ; lobular carcinoma in situ; inflammation; radiation; viral infections; carcinogens; dysplasia; actinic keratosis; repair; angiogenesis; LOCDIR ID GROWTH-FACTOR-ALPHA; NORMAL HUMAN SKIN; COLORECTAL-CANCER; ULCERATIVE-COLITIS; MICROSATELLITE INSTABILITY; SUPPRESSOR-CELLS; P53 MUTATIONS; IN-SITU; BIOMARKER EXPRESSION; MUTATOR PHENOTYPE AB Invasive tumors (cancers or malignant lesions) typically develop in the setting in which there is the presence of putative non-invasive lesions and the development of these non-invasive lesions frequently precedes the development of cancers. For some organs, such as the oral cavity, cervix and skin, the respective putative pre-invasive lesions can be observed over time and documented to progress to invasive lesions. However, for less readily observable lesions, such as those of the prostate, the progression of the pre-invasive lesions, e. g., prostatic intraepithelial neoplasia (PIN) and prostatic proliferative inflammatory atrophy (PIA) to prostatic cancer are more difficult to document. Thus, for most organ systems, specific pre-invasive neoplastic lesions have been proposed based upon the apparent observations of one or more of the following: 1) microinvasive disease developing from a pre-invasive neoplastic lesion, 2) the general association of the pre-invasive lesion with invasive lesions, 3) the subsequent development of invasive lesions following diagnosis of the pre-invasive lesion, 4) correlations of the molecular features of the putative pre-invasive lesion with the matching invasive lesions, and 5) reductions in the rate of cancer following removal of the pre-invasive lesion. When there are mixtures of pre-invasive lesions with actual cancers in the same case, some of the above specific associations are more difficult to make. Several terms have been used to describe pre-invasive lesions, many of which are now less useful as our knowledge of these lesions increases. It is now commonly accepted that these lesions are a features of the spectrum of neoplastic development and most are accepted as "neoplastic lesions" with associated molecular features, even though they may be reversible even if they have mutations in suppressor genes (e. g., p53) or are associated with viral etiologies (e. g., cervical intraepithelial neoplasia). The overall term, "pre-invasive neoplasia", seems to best describe these putative pre-invasive lesions. Thus, terms such as incipient neoplasia should be abandoned. The term "intra-epithelial neoplasia" with an associated grade, which has been developed for pre-invasive neoplastic lesions of the cervix, i.e. cervical intraepithelial neoplasia (CIN), seems to be a terminology that adds consistency across epithelial organs. Thus, adoption of these terms for the additional organ sites of pancreas (PanIN) and prostate (PIN) seems accepted. Less descriptive terms such as the degrees of dysplasia of the oral cavity and bronchopulmonary system and actinic keratosis and Bowen's disease of the skin might be better designated as oral intraepithelial neoplasia (OIN), pulmonary intraepithelial neoplasia (PulIN) and dermal intraepithelial neoplasia (DIN). The etiology of pre-invasive neoplasia is the etiology of the matching cancers. Some obvious initiating factors include exposure to the whole range of ionizing and non-ionizing radiation, tobacco abuse and a broad range of other carcinogens (e. g., benzene). A frequent initiation factor is the setting of long standing continuing damage, inflammation and repair (LOCDIR) which leads to early molecular features associated with neoplasia after about one year. An excellent example of this is ulcerative colitis (UC) in which dysregulation of microsatellite repair enzymes have been documented one year following diagnosis of UC. While the nomenclature, description, diagnosis and etiology of pre-invasive neoplasia has advanced, approaches to therapy of such lesions have no progressed adequately even though it has been identified that, for example, removal of polyps periodically from the colorectum, DCIS from the breast, and high grade CIN from the cervix, results in a reduction in the development of cancers of the colorectum, breast, and cervix, respectively. With the development of more molecularly targeted therapy with fewer side effects, preventive therapies may be more successfully targeted to pre-invasive neoplastic lesions. C1 [Grizzle, William E.; Manne, Upender] Univ Alabama, Dept Pathol, Div Anat Pathol, Birmingham, AL 35294 USA. [Srivastava, Sudhir] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, Rockville, MD USA. RP Grizzle, WE (reprint author), Univ Alabama, Dept Pathol, Div Anat Pathol, Zeigler Res Bldg,ZRB 408,703 S 19th St, Birmingham, AL 35294 USA. EM wgrizzle@uab.edu FU Early Detection Research Network (EDRN) [5U24 CA86359]; Department of Defense [PC093309]; SPORES at UAB [5P50CA089019, 2P50CA101955]; Susan G. Komen Breast Cancer Foundation [BCTR0600484]; Skin Disease Research Center at UAB [5P30AR50948, POP138306] FX Supported in part by the Early Detection Research Network (EDRN) (5U24 CA86359), Department of Defense, "Biomarkers in the Detection of Prostate Cancer in African-Americans" (PC093309), the Breast (5P50CA089019) and Pancreatic (2P50CA101955) SPORES at UAB, the Susan G. Komen Breast Cancer Foundation (BCTR0600484), the Skin Disease Research Center at UAB (5P30AR50948) to William E. Grizzle, and (POP138306) to UpenderManne. NR 73 TC 6 Z9 6 U1 2 U2 7 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2011 VL 9 IS 1-6 BP 21 EP 39 DI 10.3233/CBM-2011-0172 PG 19 WC Oncology SC Oncology GA 856ZB UT WOS:000297682300003 ER PT J AU Srivastava, S Grizzle, WE AF Srivastava, Sudhir Grizzle, William E. TI Biomarkers and the genetics of early neoplastic lesions SO CANCER BIOMARKERS LA English DT Article DE Intraepithelial neoplasia; dysplasia; methylation; microsatellite instability; mutations; insertions; deletions; oncogenes; suppressor genes; aneuploidy; translocations; caretakers; gatekeepers; landscapers; mismatch repair genes; LOCDIR; epigenetics; immunoregulation; tumor associated fibroblasts; exosomes; angiogenesis; clonal selection; viral insertions; biomarkers; validation ID ENDOTHELIAL GROWTH-FACTOR; CELL LUNG-CANCER; TUMOR-SUPPRESSOR GENES; BREAST-CARCINOMA-CELLS; NORMAL HUMAN SKIN; DNA METHYLATION; COLORECTAL-CANCER; PROSTATE-CANCER; MICROSATELLITE INSTABILITY; INTRAEPITHELIAL NEOPLASIA AB It has become increasingly evident that the study of DNA is inadequate to explain many, if not most, aspects of the development and progression of neoplastic lesions from pre-invasive lesions to metastasis. Thus, the term "genetic" can no longer refer to just the study of the genome. Much of the action in genetic research now shifts to the methods by which the pre-mRNA from one gene is processed to yield multiple different proteins, different quantities of the same protein as well as other forms of regulating RNA. Thus, the age of post-transcriptional processing and epigenetic control of the transfer of information from the genome has arrived. The mechanisms of post-transcriptional processing and epigenetic control that must be characterized in greater detail including alternate splicing, regulation of mRNA degradation, RNA regulatory factors including those factors which extensively edit mRNAs, control of translation, and control of protein stability and degradation. This chapter reviews many of the processes that control information from the genome to proteins and how these factors lead from less than 40,000 genes to more than an order of magnitude increase more proteins which actually control the phenotypes of cells - normal or neoplastic. It is usually the products of genes (e. g., mRNA, microRNA and proteins) that are the molecular markers that will control translational research and ultimately, individualized (personal) medical approaches to disease. This chapter emphasizes how the process of neoplasia "hijacks" the normal processes of cellular operations, especially those processes that are important in the normal development of the organisms - including proliferation, cellular death, angiogenesis, cellular mobility and invasion, and immunoregulation to ensure neoplastic development, survival and progression. This chapter reviews the wide range of processes controlling the information that flows from the genome to proteins and emphasizes how molecular steps in pure processes can be used as biomarkers to study prevention, treatment and/or management of diseases. C1 [Srivastava, Sudhir] NCI, NIH, Bethesda, MD 20892 USA. [Grizzle, William E.] Univ Alabama Birmingham, Div Anat Pathol, Dept Pathol, Birmingham, AL USA. RP Srivastava, S (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM ss1a@nih.gov FU Early Detection Research Network (EDRN) [5U24 CA86359]; Department of Defense [PC093309]; SPORES at UAB [5P50CA089019, 2P50CA101955]; Susan G. Komen Breast Cancer Foundation [BCTR0600484]; Skin Disease Research Center at UAB [5P30AR50948] FX Supported in part by the Early Detection Research Network (EDRN) (5U24 CA86359), Department of Defense, "Biomarkers in the Detection of Prostate Cancer in African-Americans" (PC093309), the Breast (5P50CA089019) and Pancreatic (2P50CA101955) SPORES at UAB, the Susan G. Komen Breast Cancer Foundation (BCTR0600484), and the Skin Disease Research Center at UAB (5P30AR50948). NR 189 TC 2 Z9 2 U1 3 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2011 VL 9 IS 1-6 BP 41 EP 64 DI 10.3233/CBM-2011-0204 PG 24 WC Oncology SC Oncology GA 856ZB UT WOS:000297682300004 PM 22112469 ER PT J AU Wang, W Srivastava, S AF Wang, Wendy Srivastava, Sudhir TI Noncoding RNAs in molecular characterization of cancer preneoplasia SO CANCER BIOMARKERS LA English DT Article DE Noncoding RNAs (ncRNAs); microRNAs (miRNAs); cancer; biomarkers; early detection; diagnosis; biomarker validation; cancer risk assessment; oncogene; tumor suppressor ID MICRORNA EXPRESSION PROFILES; ACUTE MYELOID-LEUKEMIA; CAPTURE PROBES; BREAST-CANCER; DRUG TARGETS; HUMAN-CELLS; CLUSTER; MICHIP; ONCOGENE; PATHWAYS AB Molecular biomarkers are widely recognized as having tremendous utility in cancer early detection, prediction, and prevention. Huge efforts have been put into searching of various molecular biomarkers for these purposes, yet there are few molecular biomarkers that have been approved by the Food and Drug Administration for clinical use. Discovery of novel molecular biomarkers is still urgently needed to create biological insights into early events of carcinogenesis and to predict the aggressiveness of early cancer. Noncoding RNAs (ncRNAs) are relatively unexplored molecules identified only one decade ago. With research on the basic biology and mechanisms of ncRNAs, they have rapidly been linked to etiology of diseases, particularly cancer. In this chapter, we will summarize ncRNAs, particularly microRNAs (miRNAs), a type of ncRNAs, as a new frontier for the discovery of cancer biomarkers in preneoplastic lesions and their usefulness as markers for the risk assessment, early detection, and diagnosis of cancer. C1 [Wang, Wendy; Srivastava, Sudhir] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Wang, W (reprint author), NCI, Canc Biomarkers Res Grp, Canc Prevent Div, NIH, 6130 Execut Blvd, Bethesda, MD 20892 USA. EM ww70q@nih.gov; srivasts@mail.nih.gov NR 44 TC 1 Z9 1 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2011 VL 9 IS 1-6 BP 133 EP 140 DI 10.3233/CBM-2011-0179 PG 8 WC Oncology SC Oncology GA 856ZB UT WOS:000297682300008 ER PT J AU Chatterjee, N Park, JH Caporaso, N Gail, MH AF Chatterjee, Nilanjan Park, Ju-Hyun Caporaso, Neil Gail, Mitchell H. TI Predicting the Future of Genetic Risk Prediction SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER RISK; MODELS; SUSCEPTIBILITY; PERFORMANCE; PREVENTION; DISEASE C1 [Chatterjee, Nilanjan; Park, Ju-Hyun; Caporaso, Neil; Gail, Mitchell H.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. RP Chatterjee, N (reprint author), 6120 Execut Blvd,EPS 8052, Rockville, MD 20852 USA. EM chattern@mail.nih.gov FU Intramural NIH HHS [ZIA CP010181-10, ] NR 22 TC 10 Z9 10 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2011 VL 20 IS 1 BP 3 EP 8 DI 10.1158/1055-9965.EPI-10-1022 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 703IY UT WOS:000285972800001 PM 21212066 ER PT J AU van Zitteren, M van der Net, JB Kundu, S Freedman, AN van Duijn, CM Janssens, ACJW AF van Zitteren, Moniek van der Net, Jeroen B. Kundu, Suman Freedman, Andrew N. van Duijn, Cornelia M. Janssens, A. Cecile J. W. TI Genome-Based Prediction of Breast Cancer Risk in the General Population: A Modeling Study Based on Meta-Analyses of Genetic Associations SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; COMMON VARIANTS; PROSTATE-CANCER; ROC CURVE; CONSORTIUM; VALIDATION; DISEASE; RECLASSIFICATION AB Background: Genome-wide association studies identified novel breast cancer susceptibility variants that could be used to predict breast cancer in asymptomatic women. This review and modeling study aimed to investigate the current and potential predictive performance of genetic risk models. Methods: Genotypes and disease status were simulated for a population of 10,000 women. Genetic risk models were constructed from polymorphisms from meta-analysis including, in separate scenarios, all polymorphisms or statistically significant polymorphisms only. We additionally investigated the magnitude of the odds ratios (OR) for 1 to 100 hypothetical polymorphisms that would be needed to achieve similar discriminative accuracy as available prediction models [modeled range of area under the receiver operating characteristic curve (AUC) 0.70-0.80]. Results: Of the 96 polymorphisms that had been investigated in meta-analyses, 41 showed significant associations. AUC was 0.68 for the genetic risk model based on all 96 polymorphisms and 0.67 for the 41 significant polymorphisms. Addition of 50 additional variants, each with risk allele frequencies of 0.30, requires per-allele ORs of 1.2 to increase this AUC to 0.70, 1.3 to increase AUC to 0.75, and 1.5 to increase AUC to 0.80. To achieve AUC of 0.80, even 100 additional variants would need per-allele ORs of 1.3 to 1.7, depending on risk allele frequencies. Conclusion: The predictive ability of genetic risk models in breast cancer has the potential to become comparable to that of current breast cancer risk models. Impact: Risk prediction based on low susceptibility variants becomes a realistic tool in prevention of nonfamilial breast cancer. Cancer Epidemiol Biomarkers Prev; 20(1); 9-22. (C) 2011 AACR. C1 [van Zitteren, Moniek; Kundu, Suman; van Duijn, Cornelia M.; Janssens, A. Cecile J. W.] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [van der Net, Jeroen B.; Janssens, A. Cecile J. W.] Erasmus Univ, Med Ctr, Dept Publ Hlth, NL-3000 CA Rotterdam, Netherlands. [van der Net, Jeroen B.] Erasmus Univ, Med Ctr, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Freedman, Andrew N.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Janssens, ACJW (reprint author), Erasmus Univ, Med Ctr, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM a.janssens@erasmusmc.nl RI janssens, cecile/L-1075-2015; OI Kundu, Suman/0000-0002-6305-2559; Janssens, A Cecile/0000-0002-6153-4976 FU Erasmus University Medical Center Rotterdam; Center for Medical Systems Biology; Netherlands Organisation for Scientific Research (NWO) FX This study was financially supported by grants from the Erasmus University Medical Center Rotterdam and by the Center for Medical Systems Biology in the framework of the Netherlands Genomics Initiative (NGI). A.C.J.W. Janssens was additionally sponsored by the Vidi grant of the Netherlands Organisation for Scientific Research (NWO). NR 97 TC 18 Z9 18 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2011 VL 20 IS 1 BP 9 EP 22 DI 10.1158/1055-9965.EPI-10-0329 PG 14 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 703IY UT WOS:000285972800002 PM 21212067 ER PT J AU Chang, BL Spangler, E Gallagher, S Haiman, CA Henderson, B Isaacs, W Benford, ML Kidd, LR Cooney, K Strom, S Ingles, SA Stern, MC Corral, R Joshi, AD Xu, JF Giri, VN Rybicki, B Neslund-Dudas, C Kibel, AS Thompson, IM Leach, RJ Ostrander, EA Stanford, JL Witte, J Casey, G Eeles, R Hsing, AW Chanock, S Hu, JJ John, EM Park, J Stefflova, K Zeigler-Johnson, C Rebbeck, TR AF Chang, Bao-Li Spangler, Elaine Gallagher, Stephen Haiman, Christopher A. Henderson, Brian Isaacs, William Benford, Marnita L. Kidd, LaCreis R. Cooney, Kathleen Strom, Sara Ingles, Sue Ann Stern, Mariana C. Corral, Roman Joshi, Amit D. Xu, Jianfeng Giri, Veda N. Rybicki, Benjamin Neslund-Dudas, Christine Kibel, Adam S. Thompson, Ian M. Leach, Robin J. Ostrander, Elaine A. Stanford, Janet L. Witte, John Casey, Graham Eeles, Rosalind Hsing, Ann W. Chanock, Stephen Hu, Jennifer J. John, Esther M. Park, Jong Stefflova, Klara Zeigler-Johnson, Charnita Rebbeck, Timothy R. TI Validation of Genome-Wide Prostate Cancer Associations in Men of African Descent SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RISK-ASSOCIATED LOCI; ENDOMETRIAL STROMAL SARCOMA; 94 AMINO-ACIDS; SEQUENCE VARIANTS; AMERICAN MEN; SUSCEPTIBILITY LOCUS; FUNCTIONAL-ANALYSIS; SECRETORY PROTEIN; COMMON VARIANT; MULTIPLE LOCI AB Background: Genome-wide association studies (GWAS) have identified numerous prostate cancer susceptibility alleles, but these loci have been identified primarily in men of European descent. There is limited information about the role of these loci in men of African descent. Methods: We identified 7,788 prostate cancer cases and controls with genotype data for 47 GWAS-identified loci. Results: We identified significant associations for SNP rs10486567 at JAZF1, rs10993994 at MSMB, rs12418451 and rs7931342 at 11q13, and rs5945572 and rs5945619 at NUDT10/11. These associations were in the same direction and of similar magnitude as those reported in men of European descent. Significance was attained at all reported prostate cancer susceptibility regions at chromosome 8q24, including associations reaching genome-wide significance in region 2. Conclusion: We have validated in men of African descent the associations at some, but not all, prostate cancer susceptibility loci originally identified in European descent populations. This may be due to the heterogeneity in genetic etiology or in the pattern of genetic variation across populations. Impact: The genetic etiology of prostate cancer in men of African descent differs from that of men of European descent. Cancer Epidemiol Biomarkers Prev; 20(1); 23-32. (C) 2011 AACR. C1 [Chang, Bao-Li; Spangler, Elaine; Gallagher, Stephen; Stefflova, Klara; Zeigler-Johnson, Charnita; Rebbeck, Timothy R.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Haiman, Christopher A.; Henderson, Brian] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Haiman, Christopher A.; Henderson, Brian] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Isaacs, William] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Isaacs, William] Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Benford, Marnita L.; Kidd, LaCreis R.] Univ Louisville, Louisville, KY 40292 USA. [Cooney, Kathleen] Univ Michigan, Med Ctr, Dept Med, Ann Arbor, MI 48109 USA. [Strom, Sara] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ingles, Sue Ann; Stern, Mariana C.; Corral, Roman; Joshi, Amit D.; Casey, Graham] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Xu, Jianfeng] Wake Forest Univ, Winston Salem, NC 27109 USA. [Giri, Veda N.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Rybicki, Benjamin; Neslund-Dudas, Christine] Henry Ford Hosp, Detroit, MI 48202 USA. [Kibel, Adam S.] Washington Univ, Sch Med, Dept Surg & Genet, St Louis, MO USA. [Thompson, Ian M.; Leach, Robin J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX USA. [Thompson, Ian M.; Leach, Robin J.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX USA. [Ostrander, Elaine A.] NHGRI, Bethesda, MD 20892 USA. [Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Witte, John] Univ Calif San Francisco, Dept Epidemiol & Biostat, Inst Human Genet, San Francisco, CA 94143 USA. [Witte, John] Univ Calif San Francisco, Dept Urol, Inst Human Genet, San Francisco, CA 94143 USA. [Eeles, Rosalind] Inst Canc Res, Sutton, Surrey, England. [Eeles, Rosalind] Royal Marsden NHS Trust, Sutton, Surrey, England. [Hsing, Ann W.; Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [John, Esther M.] No Calif Canc Ctr, Union City, CA USA. [Hu, Jennifer J.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Park, Jong] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Rebbeck, Timothy R.] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Rebbeck, TR (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, 217 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rebbeck@mail.med.upenn.edu OI Eeles, Rosalind/0000-0002-3698-6241; Giri, Veda/0000-0002-7268-5913; Zeigler-Johnson, Charnita/0000-0003-2641-7755; Ostrander, Elaine/0000-0001-6075-9738 FU National Institutes of Health [CA88164, CA127298, P50CA69568, R01 CA056678, R01 CA092579, R01-ES011126, R03 CA128028, UO1 CA86402]; PA Department of Health [98-PADMOH-ME-98155]; Fred Hutchinson Cancer Research Center; National Human Genome Research Institute; MD Anderson Cancer Center (MDACC) [RO1CA68578, DAMD W81XWH-07-1-0645-01, P50-CA140388]; National Cancer Institute (NCI) [R01CA128813, CA63464, CA54281, R01CA84979, R01CA112028]; California Cancer Research Fund [99-00527V-10182]; (University of California) with the Department of Health Services; Cancer Research UK [C5047/A7357]; Institute of Cancer Research and The Everyman Campaign; Prostate Cancer Research Foundation; Prostate Research Campaign UK; National Cancer Research Network UK; National Cancer Research Institute (NCRI) UK; NHS; James Graham Brown Cancer Center; Bucks for Brains "Our Highest Potential" in Cancer Research Endowment; American Cancer Society [TURSG-03-152-01-CCE]; St. Louis Men's Group against Cancer and the Par for the Cure Foundation; [R01-CA08574]; [P01-CA105641] FX Prostate Cancer Genetics Studies (CAP Genes) at the University of California, San Francisco: National Institutes of Health Grants CA88164, CA127298.; FlintMen's Health study (FMHS): This study was funded by a National Institutes of Health Specialized Project of Research Excellence grant in Prostate Cancer; grant number: P50CA69568. We thank Anna Ray, Dr. Ethan Lange, Kimberly Zuhlke, Joe Washburn, and the University of Michigan CDNA/Microarray Core for their help with this project.; Fox Chase Cancer Center (FCCC) Prostate Risk Assessment Program (PRAP): PA Department of Health Grant 98-PADMOH-ME-98155. We are grateful to all participants of the Prostate Cancer Risk Assessment Program at Fox Chase Cancer Center.; Fred Hutchinson Cancer Research Center (FHCRC) Prostate Cancer Studies: NIH grants R01 CA056678 and R01 CA092579 to J.L. Stanford, with additional support from the Fred Hutchinson Cancer Research Center and the National Human Genome Research Institute.; Gene-Environment Interaction in Prostate Cancer (GECAP): This study was supported by NIH grant R01-ES011126. The authors thank the GECAP study staff for their help in recruiting cases and controls, data processing and management: K. Amend, M. Aubuchon, M. Beavers, K. Bohn, J. Broderick, J. Clayton, A. Jolly, J. Mitchell, R. Rose, and D. Thomas. The authors also thank the Medical Genetics Laboratory staff for DNA processing: N. Ballard, M. McDaniel.; MD Anderson Cancer Center (MDACC): RO1CA68578, DAMD W81XWH-07-1-0645-01, P50-CA140388; Moffitt Cancer Center: Thomas Sellers, Julio Pow-Sang, Hyun Y. Park, Selina Radein, Maria Rincon, Babu Zachariah. The Moffitt group was supported by the National Cancer Institute (R01CA128813, PI: J.Y. Park).; Multiethnic Cohort (MEC) Study: Supported by National Cancer Institute (NCI) grants CA63464 and CA54281.; San Francisco Area Prostate Cancer Study (SFAPCS): Grant 99-00527V-10182 from the California Cancer Research Fund.; Los Angeles County Study (LACS): Funded by grant 99-00524V-10258 (to SAI) from the Cancer Research Fund, under Interagency Agreement 97-12013 (University of California contract 98-00924V) with the Department of Health Services Cancer Research Program and by grant R01CA84979 (to SAI) from the National Cancer Institute, National Institutes of Health.; UK Genetic Prostate Cancer Study (UKGPCS): This work was supported by Cancer Research UK Grant C5047/A7357. We thank the following for funding support: The Institute of Cancer Research and The Everyman Campaign, The Prostate Cancer Research Foundation, Prostate Research Campaign UK, The National Cancer Research Network UK, The National Cancer Research Institute (NCRI) UK. We acknowledge NHS funding to the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. We acknowledge the NCRN nurses and Consultants for their work in the UKGPCS study.; Prostate Cancer Clinical Outcome Study (PC2OS) at the University of Louisville: The authors thank Tiva Van Cleave and Nicole Lavender for data collection and analysis. Rick A. Kittles for generously donating DNA samples collected from men of African descent. This study was supported in part by the NIH R03 CA128028 and the James Graham Brown Cancer Center and the Bucks for Brains "Our Highest Potential" in Cancer Research Endowment.; University of Pennsylvania Study of Clinical Outcomes, Risk, and Ethnicity (SCORE): This work was supported by R01-CA08574 and P01-CA105641. The authors thank Drs. D. Goldmann, W. Greer, G.W. Crooks, D.A. Horowitz, D. Farhadi, M.D. Cirigliano, M. Rusk, V. Weil, S.J. Gluckman, C. Bridges, M.L. Walker, and C. Guerra for their invaluable assistance in ascertaining study participants.; University of Texas San Antonio Center for Biomarkers of Risk for Prostate Cancer (SABOR): SABOR is a Clinical and Epidemiologic Center of the Early Detection Research Network of the National Cancer Institute, supported by NIH UO1 CA86402. Prevalence samples obtained through support from the American Cancer Society (TURSG-03-152-01-CCE). The authors thank Dr. Joke Beuten for assistance with these genetic studies.; Wake Forest Consortium: The work at Washington University was supported by NCI R01CA112028, the St. Louis Men's Group against Cancer and the Par for the Cure Foundation. NR 57 TC 39 Z9 41 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2011 VL 20 IS 1 BP 23 EP 32 DI 10.1158/1055-9965.EPI-10-0698 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 703IY UT WOS:000285972800003 PM 21071540 ER PT J AU Wang, SS Menashe, I Cerhan, JR Cozen, W Severson, RK Davis, S Hutchinson, A Rothman, N Chanock, SJ Bernstein, L Hartge, P Morton, LM AF Wang, Sophia S. Menashe, Idan Cerhan, James R. Cozen, Wendy Severson, Richard K. Davis, Scott Hutchinson, Amy Rothman, Nathaniel Chanock, Stephen J. Bernstein, Leslie Hartge, Patricia Morton, Lindsay M. TI Variations in Chromosomes 9 and 6p21.3 with Risk of Non-Hodgkin Lymphoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID B-CELL LYMPHOMA; GENETIC-VARIATION; POOLED ANALYSIS; VARIANTS; POLYMORPHISMS; ASSOCIATION; DNA AB Background: There is growing evidence linking genetic variations to non-Hodgkin lymphoma (NHL) etiology. To complement ongoing agnostic approaches for identifying susceptibility genes, we evaluated 488 candidate gene regions and their relation to risk for NHL and NHL subtypes. Methods: We genotyped 6,679 tag single nucleotide polymorphisms (SNPs) in 947 cases and 826 population-based controls from a multicenter U. S. case-control study. Gene-level summary of associations were obtained by computing the minimum P value ("minP test") on the basis of 10,000 permutations. We used logistic regression to evaluate the association between genotypes and haplotypes with NHL. For NHL subtypes, we conducted polytomous multivariate unconditional logistic regression (adjusted for sex, race, age). We calculated P-trends under the codominant model for each SNP. Results: Fourteen gene regions were associated with NHL (P < 0.01). The most significant SNP associated with NHL maps to the SYK gene (rs2991216, P-trend = 0.00005). The three most significant gene regions were on chromosome 6p21.3 (RING1/RXRB; AIF1; BAT4). Accordingly, SNPs in RING1/RXRB (rs2855429), AIF1 (rs2857597), and BAT4 (rs3115667) were associated with NHL (P-trends <= 0.0002) and both diffuse large B-cell and follicular lymphomas (P-trends < 0.05). Conclusions: Our results suggest potential importance for SYK on chromosome 9 with NHL etiology. Our results further implicate 6p21.3 gene variants, supporting the need for full characterization of this chromosomal region in relation to lymphomagenesis. Impact: Gene variants on chromosome 9 may represent a new region of interesting for NHL etiology. The independence of the reported variants in 6p21.3 from implicated variants (TNF/HLA) supports the need to confirm causal variants in this region Cancer Epidemiol Biomarkers Prev; 20(1); 42-9. (C) 2011 AACR. C1 [Wang, Sophia S.; Bernstein, Leslie] Beckman Res Inst & City Hope, Div Canc Etiol, Dept Populat Sci, Duarte, CA USA. [Menashe, Idan; Rothman, Nathaniel; Chanock, Stephen J.; Hartge, Patricia; Morton, Lindsay M.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD USA. [Cerhan, James R.] Mayo Clin, Div Epidemiol, Coll Med, Rochester, MN USA. [Cozen, Wendy] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Severson, Richard K.] Wayne State Univ, Dept Family Med, Detroit, MI USA. [Severson, Richard K.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Davis, Scott] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Davis, Scott] Univ Washington, Seattle, WA 98195 USA. [Hutchinson, Amy; Chanock, Stephen J.] NCI, Core Genotyping Facil, SAIC Frederick Inc, NIH,DHHS, Gaithersburg, MD USA. RP Wang, SS (reprint author), Beckman Res Inst & City Hope, Div Canc Etiol, Dept Populat Sci, 500 Duarte Rd, Duarte, CA USA. EM sowang@coh.org RI Morton, Lindsay/B-5234-2015; OI Morton, Lindsay/0000-0001-9767-2310; Cerhan, James/0000-0002-7482-178X FU NIH [National Cancer Institute (NCI)] [HHSN261200800001E]; Public Health Service (PHS) [N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105] FX The NCI-SEER study was supported by the Intramural Research Program of the NIH (NCI), and by Public Health Service (PHS) contracts N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, and N02-PC-71105. DNA extraction, genotyping and statistical analysis for this project were supported by the Intramural Research Program of the NIH [National Cancer Institute (NCI)]. This project has been funded in part with federal funds from the NCI, NIH, under contract no. 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 U.S. Government. NR 26 TC 10 Z9 10 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2011 VL 20 IS 1 BP 42 EP 49 DI 10.1158/1055-9965.EPI-10-0638 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 703IY UT WOS:000285972800005 PM 21148756 ER PT J AU Brown, JC Huedo-Medina, TB Pescatello, LS Pescatello, SM Ferrer, RA Johnson, BT AF Brown, Justin C. Huedo-Medina, Tania B. Pescatello, Linda S. Pescatello, Shannon M. Ferrer, Rebecca A. Johnson, Blair T. TI Efficacy of Exercise Interventions in Modulating Cancer-Related Fatigue among Adult Cancer Survivors: A Meta-Analysis SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; RECEIVING RADIATION-THERAPY; PHYSICAL-ACTIVITY TRIALS; BREAST-CANCER; AEROBIC EXERCISE; RESISTANCE EXERCISE; PROSTATE-CANCER; MULTIPLE-MYELOMA; PUBLICATION BIAS AB Background: The purpose of this meta-analysis was to explore the efficacy of exercise as a nonpharmacologic intervention to reduce cancer-related fatigue (CRF) among adult cancer survivors. We also investigated how different components of the exercise prescription (Ex R-x), methodologic considerations, and subject characteristics modulate CRF. Methods: A systematic search for randomized controlled trials was conducted using words related to cancer, exercise, and fatigue. Results: In total, 44 studies with 48 interventions qualified, including 3,254 participants of varying cancer types, stages of diagnosis, treatments, and exercise interventions. Cancer survivors in exercise interventions reduced their CRF levels to a greater extent than usual care controls, d(+) = 0.31 (95% CI = 0.22-0.40), an effect that appeared to generalize across several types of cancer. CRF levels improved in direct proportion to the intensity of resistance exercise (beta = 0.60, P = 0.01), a pattern that was stronger in higher quality studies (beta = 0.23, P < 0.05). CRF levels also reduced to a greater extent when interventions were theoretically driven (beta = 0.48, P < 0.001) or cancer survivors were older (beta = 0.24, P = 0.04). Conclusions: Exercise reduced CRF especially in programs that involved moderate-intensity, resistance exercise among older cancer survivors and that were guided by theory. Impact: Our results indicate exercise interventions for adult cancer survivors should be multi-dimensional and individualized according to health outcome and cancer type. Cancer Epidemiol Biomarkers Prev; 20(1); 123-33. (C) 2011 AACR. C1 [Brown, Justin C.] Univ Connecticut, Dept Kinesiol, Storrs, CT 06269 USA. [Pescatello, Shannon M.] Western New England Coll, Springfield, MA USA. [Ferrer, Rebecca A.] NCI, Bethesda, MD 20892 USA. RP Brown, JC (reprint author), Univ Connecticut, Dept Kinesiol, 2095 N Hillside Rd,U-1110, Storrs, CT 06269 USA. EM justin.brown@uconn.edu FU University of Connecticut Research Foundation [433527] FX This research was supported by University of Connecticut Research Foundation Grant 433527 (PIs: B.T. Johnson and L.S. Pescatello) NR 99 TC 120 Z9 121 U1 3 U2 31 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2011 VL 20 IS 1 BP 123 EP 133 DI 10.1158/1055-9965.EPI-10-0988 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 703IY UT WOS:000285972800013 PM 21051654 ER PT J AU Kreimer, AR Villa, A Nyitray, AG Abrahamsen, M Papenfuss, M Smith, D Hildesheim, A Villa, LL Lazcano-Ponce, E Giuliano, AR AF Kreimer, Aimee R. Villa, Alessandro Nyitray, Alan G. Abrahamsen, Martha Papenfuss, Mary Smith, Danelle Hildesheim, Allan Villa, Luisa L. Lazcano-Ponce, Eduardo Giuliano, Anna R. TI The Epidemiology of Oral HPV Infection among a Multinational Sample of Healthy Men SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HUMAN-PAPILLOMAVIRUS INFECTION; UNITED-STATES; SEXUAL-BEHAVIOR; CERVICAL NEOPLASIA; PREVALENCE; WOMEN; DNA; SMOKING; CANCERS; RISK AB Background: Oral human papillomavirus type-16 (HPV16) infection is a risk factor for oropharyngeal cancer. We examined oral HPV infection among healthy men. Methods: Oral rinse/gargle specimens and questionnaire data were collected from 1,688 healthy men aged 18 to 74 (median = 31 years), from the United States, Mexico, and Brazil. HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59, and noncarcinogenic HPV types were detected using Roche Linear Array. Results: Oral HPV DNA was detected in 67 of 1,680 (4.0%, 95% CI = 3.1%-5.0%) beta-globin-positive specimens; carcinogenic HPVs were detected in 1.3% (95% CI = 0.8%-2.0%; n = 22) and HPV16 was the most commonly detected carcinogenic HPV type (0.6%, 95% CI = 0.2%-1.1%; n = 10). The prevalence of oral HPV infection was similar by country except for HPV55, which had notably higher prevalence in Mexico (3.0%) than Brazil (0%) or the United States (0.2%). Oral HPV prevalence nonsignificantly increased over increasing age categories (P(trend) = 0.096). The strongest predictor of oral HPV was current tobacco use, which increased the odds 2.5-fold (95% CI = 1.4-4.4). Oral sexual behaviors were not associated with oral HPV infection. Conclusions: Oral HPV16 infection was rare in healthy men, especially at younger ages, and was positively associated with current tobacco use. Impact: Oral HPV appears to be about 10-fold less prevalent than infection at genital sites in men (4% vs. similar to 40%, respectively). It remains unclear whether this reflects reduced exposure or if the oral region is more resistant to HPV infection compared with anogenital sites. Cancer Epidemiol Biomarkers Prev; 20(1); 172-82. (C) 2011 AACR. C1 [Kreimer, Aimee R.; Villa, Alessandro; Hildesheim, Allan] NCI, NIH, Bethesda, MD 20892 USA. [Nyitray, Alan G.; Abrahamsen, Martha; Papenfuss, Mary; Smith, Danelle; Giuliano, Anna R.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Villa, Luisa L.] Ludwig Inst Canc Res, Sao Paulo, Brazil. [Lazcano-Ponce, Eduardo] Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico. RP Kreimer, AR (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS-7084, Rockville, MD 20852 USA. EM kreimera@mail.nih.gov RI Hildesheim, Allan/B-9760-2015; Kreimer, Aimee/H-1687-2015; OI Hildesheim, Allan/0000-0003-0257-2363; Villa, Alessandro/0000-0002-1966-6000 FU National Cancer Institute, National Institutes of Health, CA [RO1CA098803]; NCI; Merck Inc FX Grant Support: This infrastructure of the HIM cohort was supported through a grant from the National Cancer Institute, National Institutes of Health, CA RO1CA098803 to A.R. Giuliano. Funding for oral specimen collection and a subset of the HPV testing was provided by the NCI Intramural Program (ARK); additional funding for testing of the remaining oral specimens was provided by Merck Inc through an investigator grant to A.R. Giuliano. A.R. NR 30 TC 82 Z9 83 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2011 VL 20 IS 1 BP 172 EP 182 DI 10.1158/1055-9965.EPI-10-0682 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 703IY UT WOS:000285972800018 PM 21148755 ER PT J AU Nakayama, A Alladin, KP Igbokwe, O White, JD AF Nakayama, Akiko Alladin, Karen P. Igbokwe, Obianuju White, Jeffrey D. TI Systematic Review: Generating Evidence-Based Guidelines on the Concurrent Use of Dietary Antioxidants and Chemotherapy or Radiotherapy SO CANCER INVESTIGATION LA English DT Review DE Treatment; Supportive care and symptom control; Chemotherapy ID HIGH-DOSE CISPLATIN; INTENSIVE WEEKLY CHEMOTHERAPY; CELL LUNG-CANCER; ADVANCED COLORECTAL-CANCER; ADVANCED GASTRIC-CANCER; ADVANCED OVARIAN-CANCER; DIGESTIVE-TRACT CANCER; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; VITAMIN-E SUCCINATE AB The risk-benefit ratio for concurrent use of dietary antioxidants with chemotherapy or radiation therapy is a controversial topic. In this review, the medical literature on concurrent antioxidant use with chemotherapy or radiotherapy was assessed and further steps for generating evidence-based guidelines are suggested. The clinical cancer research community should cooperate and focus new studies on the use of a specific combination of antioxidant and chemotherapy or radiotherapy, and determine optimal doses for a specific cancer setting. Mechanistic studies on the interaction between antioxidants and conventional cancer therapy could lead to novel biomarkers for assessing dose adequacy. C1 [Alladin, Karen P.; Igbokwe, Obianuju; White, Jeffrey D.] NCI, Off Canc Complementary & Alternat Med, Bethesda, MD 20892 USA. [Nakayama, Akiko] Preferred Staffing Grp Inc, Washington, DC USA. RP White, JD (reprint author), NCI, Off Canc Complementary & Alternat Med, 6116 Execut Blvd,Suite 609, Bethesda, MD 20892 USA. EM jeffreyw@mail.nih.gov FU NCI, National Institutes of Health; United States Department of Health and Human Services FX The authors report no declarations of interest. This work was supported by the NCI, the National Institutes of Health, and the United States Department of Health and Human Services. NR 91 TC 16 Z9 18 U1 5 U2 12 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2011 VL 29 IS 10 BP 655 EP 667 DI 10.3109/07357907.2011.626479 PG 13 WC Oncology SC Oncology GA 848CA UT WOS:000297024000002 PM 22085269 ER PT J AU Veronesi, G Szabo, E DeCensi, A Guerrieri-Gonzaga, A Bellomi, M Radice, D Ferretti, S Pelosi, G Lazzeroni, M Serrano, D Lippman, SM Spaggiari, L Nardi-Pantoli, A Harari, S Varricchio, C Bonanni, B AF Veronesi, Giulia Szabo, Eva DeCensi, Andrea Guerrieri-Gonzaga, Aliana Bellomi, Massimo Radice, Davide Ferretti, Stefania Pelosi, Giuseppe Lazzeroni, Matteo Serrano, Davide Lippman, Scott M. Spaggiari, Lorenzo Nardi-Pantoli, Angela Harari, Sergio Varricchio, Clara Bonanni, Bernardo TI Randomized Phase II Trial of Inhaled Budesonide versus Placebo in High-Risk Individuals with CT Screen-Detected Lung Nodules SO CANCER PREVENTION RESEARCH LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; GROUND-GLASS OPACITY; BRONCHIAL EPITHELIUM; CANCER; CHEMOPREVENTION; TUMORS; CORTICOSTEROIDS; CARCINOGENESIS; FLUTICASONE; PROGRESSION AB Screening CT identifies small peripheral lung nodules, some of which may be pre- or early invasive neoplasia. Secondary end point analysis of a previous chemoprevention trial in individuals with bronchial dysplasia showed reduction in size of peripheral nodules by inhaled budesonide. We performed a randomized, double-blind, placebo-controlled phase IIb trial of inhaled budesonide in current and former smokers with CT-detected lung nodules that were persistent for at least 1 year. A total of 202 individuals received inhaled budesonide, 800 mu g twice daily or placebo for 1 year. The primary endpoint was the effect of treatment on target nodule size in a per person analysis after 1 year. The per person analysis showed no significant difference between the budesonide and placebo arms (response rate 2% and 1%, respectively). Although the per lesion analysis revealed a significant effect of budesonide on regression of existing target nodules (P = 0.02), the appearance of new lesions was similar in both groups and thus the significance was lost in the analysis of all lesions. The evaluation by nodule type revealed a nonsignificant trend toward regression of nonsolid and partially solid lesions after budesonide treatment. Budesonide was well tolerated, with no unexpected side effects identified. Treatment with inhaled budesonide for 1 year did not significantly affect peripheral lung nodule size. There was a trend toward regression of nonsolid and partially solid nodules after budesonide treatment. Because a subset of these nodules is more likely to represent precursors of adenocarcinoma, additional follow-up is needed. Cancer Prev Res; 4(1); 34-42. (C) 2010 AACR. C1 [Veronesi, Giulia] European Inst Oncol, Div Thorac Surg, Dept Thorac Surg, I-20141 Milan, Italy. [Szabo, Eva] NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [DeCensi, Andrea; Guerrieri-Gonzaga, Aliana; Lazzeroni, Matteo; Serrano, Davide; Nardi-Pantoli, Angela; Varricchio, Clara; Bonanni, Bernardo] European Inst Oncol, Div Canc Prevent & Genet, Milan, Italy. [DeCensi, Andrea] Galliera Hosp, Div Oncol, Genoa, Italy. [Bellomi, Massimo; Ferretti, Stefania] European Inst Oncol, Dept Radiol, Milan, Italy. [Bellomi, Massimo; Pelosi, Giuseppe] Univ Milan, Sch Med, Milan, Italy. [Radice, Davide] European Inst Oncol, Div Epidemiol & Biostat, Milan, Italy. [Pelosi, Giuseppe] European Inst Oncol, Dept Pathol, Milan, Italy. [Lazzeroni, Matteo] Univ Rome, Sch Med, I-00100 Rome, Italy. [Lippman, Scott M.] Univ Texas MD Anderson Canc Ctr, Clin Canc Prevent Ctr, Houston, TX 77030 USA. [Harari, Sergio] San Giuseppe Hosp, Div Pneumol, Milan, Italy. RP Veronesi, G (reprint author), European Inst Oncol, Div Thorac Surg, Dept Thorac Surg, Via Ripamonti 435, I-20141 Milan, Italy. EM giulia.veronesi@ieo.it RI Lazzeroni, Matteo/I-8001-2012; Spaggiari, Lorenzo/G-7915-2012; Pelosi, Giuseppe/F-5073-2012; OI Pelosi, Giuseppe/0000-0003-4725-4692; Lazzeroni, Matteo/0000-0002-2162-4002; Harari, Sergio/0000-0001-8629-7391 FU National Cancer Institute [N01-CN-35159] FX This work was supported by the National Cancer Institute (grant N01-CN-35159). NR 38 TC 26 Z9 26 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 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2011 VL 4 IS 1 BP 34 EP 42 DI 10.1158/1940-6207.CAPR-10-0182 PG 9 WC Oncology SC Oncology GA 702BS UT WOS:000285870200005 PM 21163939 ER PT J AU Whitlock, NC Bahn, JH Lee, SH Eling, TE Baek, SJ AF Whitlock, Nichelle C. Bahn, Jae Hoon Lee, Seong-Ho Eling, Thomas E. Baek, Seung Joon TI Resveratrol-Induced Apoptosis Is Mediated by Early Growth Response-1, Kruppel-Like Factor 4, and Activating Transcription Factor 3 SO CANCER PREVENTION RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; PROSTATE-CANCER CELLS; GENE-EXPRESSION; REPRESSOR ATF3; UP-REGULATION; CYCLE ARREST; DNA-DAMAGE; IN-VIVO; EGR-1; INDUCTION AB Resveratrol, a dietary phytoalexin readily available in the diet, is reported to possess antitumorigenic properties in several cancers, including colorectal. However, the underlying mechanism(s) involved is not completely understood. In the present study, we investigated the effect of resveratrol treatment on gene modulation in human colorectal cancer cells and identified activating transcription factor 3 (ATF3) as the most highly induced gene after treatment. We confirmed that resveratrol upregulates ATF3 expression, both at the mRNA and protein level, and showed resveratrol involvement in ATF3 transcriptional regulation. Analysis of the ATF3 promoter revealed the importance of early growth response-1 (Egr-1; located at -245 to -236) and Kruppel-like factor 4 (KLF4; located at -178 to -174) putative binding sites in resveratrol-mediated ATF3 transactivation. Specificity of these sites to the Egr-1 and KLF4 protein was confirmed by electrophoretic mobility shift and chromatin immunoprecipitation assays. Resveratrol increased Egr-1 and KLF4 expression, which preceded ATF3 expression, and further suggests Egr-1 and KLF4 involvement in resveratrol-mediated activity. We provide evidence for Egr-1 and KLF4 interaction in the presence of resveratrol, which may facilitate ATF3 transcriptional regulation by this compound. Furthermore, we demonstrate that induction of apoptosis by resveratrol is mediated, in part, by increased ATF3 expression. Taken together, these results provide a novel mechanism by which resveratrol induces ATF3 expression and represent an additional explanation of how resveratrol exerts its antitumorigenic effects in human colorectal cancer cells. Cancer Prev Res; 4(1); 116-27. (C) 2011 AACR. C1 [Whitlock, Nichelle C.; Bahn, Jae Hoon; Lee, Seong-Ho; Baek, Seung Joon] Univ Tennessee, Coll Vet Med, Dept Pathobiol, Lab Environm Carcinogenesis, Knoxville, TN 37996 USA. [Eling, Thomas E.] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC USA. RP Baek, SJ (reprint author), Univ Tennessee, Coll Vet Med, Dept Pathobiol, Lab Environm Carcinogenesis, 2407 River Dr, Knoxville, TN 37996 USA. EM sbaek2@utk.edu FU American Cancer Society [CNE-111611]; NIH [RO1CA108975]; University of Tennessee Center of Excellence in Livestock Diseases and Human Health; NIEHS/NIH FX American Cancer Society grant CNE-111611, NIH grant RO1CA108975, The University of Tennessee Center of Excellence in Livestock Diseases and Human Health (S.J. Baek), and in part by NIEHS/NIH intramural research program (T.E. Eling). NR 52 TC 20 Z9 21 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2011 VL 4 IS 1 BP 116 EP 127 DI 10.1158/1940-6207.CAPR-10-0218 PG 12 WC Oncology SC Oncology GA 702BS UT WOS:000285870200013 PM 21205742 ER PT J AU Wang, XY Kingsley, PJ Marnett, LJ Eling, TE AF Wang, Xingya Kingsley, Philip J. Marnett, Larry J. Eling, Thomas E. TI The Role of NAG-1/GDF15 in the Inhibition of Intestinal Polyps in APC/Min Mice by Sulindac SO CANCER PREVENTION RESEARCH LA English DT Article ID ACTIVATED GENE NAG-1; FAMILIAL ADENOMATOUS POLYPOSIS; BETA SUPERFAMILY MEMBER; GROWTH-FACTOR-BETA; COLON-CANCER CELLS; COLORECTAL-CANCER; CYCLOOXYGENASE INHIBITORS; MORPHOGENETIC PROTEIN; CARCINOMA CELLS; TRANSGENIC MICE AB The antitumor effects of nonsteroidal anti-inflammatory drugs (NSAID) are assumed to be due to the inhibition of COX activity, but COX-independent mechanisms may also play an important role. NSAID-activated gene (NAG-1/GDF15) is induced by NSAIDs and has antitumorigenic activities. To determine the contribution of COX-2 inhibition and NAG-1/GDF15 expression to the prevention of colon carcinogenesis by NSAIDs, we evaluated several sulindac derivatives [des-methyl (DM)-sulindac sulfide and its prodrug DM-sulindac] that do not inhibit COX-2 activity. Sulindac sulfide and DM-sulindac induced the expression of NAG-1/GDF15 in HCT116 cells as determined by quantitative real-time PCR and Western blot. We fed APC/Min mice with 320 ppm of sulindac and doses of DM-sulindac. Only sulindac significantly inhibited tumor formation in APC/Min mice. To determine the pharmacokinetic properties of sulindac and DM-sulindac in vivo, wild-type C57/B6 mice were fed with sulindac and DM-sulindac at 80, 160, and 320 ppm. High-performance liquid chromatography analysis revealed that the conversion of DM-sulindac to DM-sulindac sulfide (active form) was less efficient than the conversion of sulindac to sulindac sulfide (active form) in the mice. Lower levels of DM-sulindac sulfide accumulated in intestinal and colon tissues in comparison with sulindac sulfide. In addition, NAG-1/GDF15 was induced in the liver of sulindac-fed mice but not in the DM-sulindac-fed mice. Collectively, our results suggest that the tumor-inhibitory effects of sulindac in APC/Min mice may be due to, in part, NAG-1/GDF15 induction in the liver. Our study also suggests that pharmacologic properties should be carefully evaluated when developing drug candidates. Cancer Prev Res; 4(1); 150-60. (C) 2011 AACR. C1 [Wang, Xingya; Eling, Thomas E.] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Kingsley, Philip J.; Marnett, Larry J.] Vanderbilt Univ, Sch Med, AB Hancock Jr Mem Lab Canc Res,Vanderbilt Ingram, Ctr Mol Toxicol,Dept Biochem,Vanderbilt Inst Chem, Nashville, TN 37212 USA. [Kingsley, Philip J.; Marnett, Larry J.] Vanderbilt Univ, Sch Med, AB Hancock Jr Mem Lab Canc Res,Vanderbilt Ingram, Ctr Mol Toxicol,Dept Chem,Vanderbilt Inst Chem Bi, Nashville, TN 37212 USA. [Kingsley, Philip J.; Marnett, Larry J.] Vanderbilt Univ, Sch Med, AB Hancock Jr Mem Lab Canc Res,Vanderbilt Ingram, Ctr Mol Toxicol,Dept Pharmacol,Vanderbilt Inst Ch, Nashville, TN 37212 USA. RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM eling@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences; NIH [CA89450]; National Foundation for Cancer Research FX This research was supported by the intramural Research Program of the NIH, National Institute of Environmental Health Sciences; NIH grant CA89450, and funds from National Foundation for Cancer Research. NR 41 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2011 VL 4 IS 1 BP 150 EP 160 DI 10.1158/1940-6207.CAPR-10-0196 PG 11 WC Oncology SC Oncology GA 702BS UT WOS:000285870200016 PM 21205743 ER PT J AU Woldemichael, GM Turbyville, TJ Linehan, WM McMahon, JB AF Woldemichael, Girma M. Turbyville, Thomas J. Linehan, W. Marston McMahon, James B. TI Carminomycin I Is an Apoptosis Inducer That Targets the Golgi Complex in Clear Cell Renal Carcinoma Cells SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; MEDIATED APOPTOSIS; IDENTIFICATION; ADRIAMYCIN; EXPRESSION; INDUCTION; ERGIC-53; ASSAYS; LINE AB Clear cell renal cell carcinoma (CCRCC) evolves due to mutations in the Von Hippel-Lindau (VHL) tumor suppressor gene. Although the loss of VHL enables survival and proliferation of CCRCC cells, it is also expected to introduce vulnerabilities that may be exploited for therapeutics discovery. To this end, we developed a high-throughput screen to identify small molecules derived from plants, microorganisms, and marine organisms to which CCRCC cells are sensitive. Screening over 8,000 compounds using this approach, we report here the identification of the microbially derived compound carminomycin I (CA) as an effective inhibitor of VHL-defective (VHL(-/-)) CCRCC cell proliferation. CA also induced apoptosis in CCRCC cells by a mechanism independent of p53 or hypoxia-inducible factor 2. We found that P-glycoprotein (P-gp) sequestered CA within the Golgi complex. Interestingly, Golgi sequestration was critical for the antiproliferative effects of CA and P-gp inhibitors abrogated this activity. Furthermore, CA induced cleavage of the Golgi protein p115 and the translocation of its C-terminal fragment to the nucleus. Finally, examination of the activity of the VHL-interacting Golgi protein, endoplasmic reticulum-Golgi intermediate compartment, ERGIC-53 showed that VHL could mediate protection from CA in CCRCC cells. Our natural product-based screening approach has revealed the P-gp-mediated localization of anticancer compounds within the Golgi in CCRCC cells as a potential strategy of targeting VHL-deficient CCRCC cells. Cancer Res; 71(1); 134-42. (C) 2011 AACR. C1 [Woldemichael, Girma M.] NCI, Mol Targets Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. [Turbyville, Thomas J.] NCI, Opt Microscopy & Anal Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. [Linehan, W. Marston] NCI, Urol Oncol Branch, Clin Res Ctr, Bethesda, MD 20892 USA. [McMahon, James B.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Woldemichael, GM (reprint author), NCI, Mol Targets Lab, SAIC Frederick Inc, 1053 Boyles St,Bldg 538,Room 131, Frederick, MD 21702 USA. EM woldemichaelg@mail.nih.gov FU National Cancer Institute, National Institutes of Health [N01-CO-12400]; 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, under contract N01-CO-12400. This Research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 25 TC 9 Z9 10 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN PY 2011 VL 71 IS 1 BP 134 EP 142 DI 10.1158/0008-5472.CAN-10-0757 PG 9 WC Oncology SC Oncology GA 701NW UT WOS:000285826800016 PM 21199801 ER PT B AU Jin, P Liu, QZ Sabatino, M Stroncek, DF Marincola, FM Wang, E AF Jin, Ping Liu, Qiuzhen Sabatino, Marianna Stroncek, David F. Marincola, Francesco M. Wang, Ena BE Allan, AL TI Cancer Stem Cells in Melanoma SO CANCER STEM CELLS IN SOLID TUMORS SE Stem Cell Biology and Regenerative Medicine LA English DT Article; Book Chapter ID MALIGNANT-MELANOMA; INITIATING CELLS; BREAST-CANCER; TUMOR-GROWTH; METASTATIC MELANOMA; GENE-EXPRESSION; STROMAL CELLS; MULTIDRUG-RESISTANCE; DELIVERY VEHICLES; HUMAN MELANOCYTES AB Malignant melanoma is a significant health problem worldwide. Disease relapse due to the heterogeneity and instability of cancer cells may explain the persistence of disease in spite of primary response to therapy. Recent progress in cancer research suggests that melanomas, similar to other solid tumors, contain a subpopulation of cells which have unlimited self-renewal capability directly descending from the original founder cell and characterized by relatively stable genetic properties throughout disease evolution. This model also applies to the development of metastasis and may be responsible for drug resistance and cancer recurrence. These cells with tumor-initiating ability are termed cancer stem cells (CSCs). CSCs as well as tumor cells interact with their microenvironment (niche) to modulate the malignant phenotype. This chapter provides an overview of melanoma stem cell characterization and the interactions between melanoma stem cells and their niche. C1 [Liu, Qiuzhen; Stroncek, David F.; Wang, Ena] NIH, Infect Dis & Immunogenet Sect IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Jin, Ping; Sabatino, Marianna; Stroncek, David F.] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Wang, E (reprint author), NIH, Infect Dis & Immunogenet Sect IDIS, Dept Transfus Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. EM ewang@mail.cc.nih.gov NR 102 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-61779-245-8 J9 STEM CELLS BIOL REG JI Stem Cell Biol. Regen. Med. PY 2011 BP 117 EP 138 DI 10.1007/978-1-61779-246-5_7 D2 10.1007/978-1-61779-246-5 PG 22 WC Oncology; Developmental Biology SC Oncology; Developmental Biology GA BWP52 UT WOS:000294444700007 ER PT B AU Langan, RC Avital, I AF Langan, Russell C. Avital, Itzhak BE Allan, AL TI Cancer Stem Cells in Hepatocellular Cancer SO CANCER STEM CELLS IN SOLID TUMORS SE Stem Cell Biology and Regenerative Medicine LA English DT Article; Book Chapter ID SIDE POPULATION CELLS; HEPATIC PROGENITOR CELLS; LIVER-CANCER; HEMATOPOIETIC STEM; CARCINOMA CELLS; BRAIN-TUMORS; IN-VITRO; STEM/PROGENITOR CELLS; VIRUS-INFECTION; REGENERATION AB Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and typically portends a poor prognosis with a median survival ranging from 6 to 16 months. In the United States, a total of 24,120 new cases of primary liver cancers and 18,910 deaths are projected to occur in 2010. Associated factors potentially contributing to this abysmal prognosis include delayed diagnosis, underlying cirrhosis, and resistance to chemotherapy. Recently, compelling evidence has emerged in support of the cancer stem cell (CSC) hypothesis for many solid organ cancers including hepatocellular cancer (HCC). CSCs are postulated to account for tumor initiation, therapeutic resistance, and relapse following surgery or therapy. Identification, proper characterization, and understanding the biology of the HCC-derived CSCs (HCSCs) are imperative for improving early detection and treatment outcomes. If proven correct, the CSC hypothesis may herald a paradigm shift in the treatment of this deadly disease. This chapter summarizes the differences between HCSCs and normal liver stem cells through state-of-the-art identification and characterization, and then assesses the clinical correlation and potential novel therapeutic strategies based on HCSCs. C1 [Langan, Russell C.; Avital, Itzhak] NCI, NIH, Surg Branch, Bethesda, MD 20892 USA. RP Avital, I (reprint author), NCI, NIH, Surg Branch, Bethesda, MD 20892 USA. EM avitali@mail.nih.gov NR 78 TC 0 Z9 0 U1 0 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-61779-245-8 J9 STEM CELLS BIOL REG JI Stem Cell Biol. Regen. Med. PY 2011 BP 177 EP 195 DI 10.1007/978-1-61779-246-5_10 D2 10.1007/978-1-61779-246-5 PG 19 WC Oncology; Developmental Biology SC Oncology; Developmental Biology GA BWP52 UT WOS:000294444700010 ER PT J AU Xu, HL Cheng, JR Andreotti, G Gao, YT Rashid, A Wang, BS Shen, MC Chu, LW Yu, K Hsing, AW AF Xu, Hong-Li Cheng, Jia-Rong Andreotti, Gabriella Gao, Yu-Tang Rashid, Asif Wang, Bing-Sheng Shen, Ming-Chang Chu, Lisa W. Yu, Kai Hsing, Ann W. TI Cholesterol metabolism gene polymorphisms and the risk of biliary tract cancers and stones: a population-based case-control study in Shanghai, China SO CARCINOGENESIS LA English DT Article ID RECEPTOR-ASSOCIATED PROTEIN; GALLSTONE DISEASE; LIPOPROTEIN RECEPTOR; ABCG8; ASSOCIATION; HYPERCHOLESTEROLEMIA; TRANSPORTERS; GENOME; LIVER; TWINS AB Biliary tract cancers are rare but fatal malignancies, with increasing incidence in Shanghai, China. Gallstones, the primary risk factor for biliary tract cancer, typically result from oversaturation of cholesterol in bile. We examined the association of five variants in three lipid metabolism-related genes (CETP, ABCG8 and LRPAP1) and biliary tract cancers and stones in a population-based case-control study in Shanghai, China. We included 439 biliary tract cancer cases (253 gallbladder, 133 extrahepatic bile duct and 53 ampulla of Vater cancer cases), 429 biliary stone cases and 447 population controls. Carriers of the CG genotype of ABCG8 rs11887534 had higher risk of biliary stones [odds ratio (OR) = 2.3, 95% confidence interval (CI) 0.82-6.5), gallbladder cancer (OR = 4.3, 95% CI 1.7-10.4) and bile duct cancer (OR = 1.94, 95% CI 0.64-5.91), compared with carriers of the GG genotype. Analysis stratified by gender showed both male and female carriers of CG rs11887534 had higher risks of biliary stones and gallbladder cancer, although the association was statistically significant only for women and gallbladder cancer (OR = 6.3, 95% CI 1.86-22.3). Carriers of the ABCG8 haplotype C-C (rs4148217-rs11887534) had a 4.16-fold (95% CI 1.71-10.1) risk of gallbladder cancer compared with those carrying the C-G haplotype. Our findings suggest that ABCG8 rs11887534, identified as a gallstone risk single-nucleotide polymorphism by whole genome scan, is also associated with an increased risk of biliary tract cancer. C1 [Xu, Hong-Li; Cheng, Jia-Rong; Andreotti, Gabriella; Gao, Yu-Tang; Rashid, Asif; Wang, Bing-Sheng; Shen, Ming-Chang; Chu, Lisa W.; Yu, Kai; Hsing, Ann W.] Shanghai Jiao Tong Univ, Inst Canc, Shanghai Canc Inst, Dept Epidemiol, Shanghai 200032, Peoples R China. [Andreotti, Gabriella; Chu, Lisa W.; Yu, Kai; Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Rashid, Asif] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Wang, Bing-Sheng] Fudan Univ, Zhongshan Hosp, Dept Gen Surg, Shanghai 200032, Peoples R China. [Shen, Ming-Chang] Fudan Univ, Canc Hosp, Dept Pathol, Shanghai 200032, Peoples R China. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 7078, Bethesda, MD 20952 USA. EM hsinga@mail.nih.gov FU National Institute of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, USA FX Intramural Research Program of the National Institute of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, USA. NR 34 TC 13 Z9 13 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2011 VL 32 IS 1 BP 58 EP 62 DI 10.1093/carcin/bgq194 PG 5 WC Oncology SC Oncology GA 707RF UT WOS:000286303000009 PM 21062971 ER PT J AU Sigurdson, AJ Jones, IM Wei, QY Wu, XF Spitz, MR Stram, DA Gross, MD Huang, WY Wang, LE Gu, JA Thomas, CB Reding, DJ Hayes, RB Caporaso, NE AF Sigurdson, Alice J. Jones, Irene M. Wei, Qingyi Wu, Xifeng Spitz, Margaret R. Stram, Douglas A. Gross, Myron D. Huang, Wen-Yi Wang, Li-E Gu, Jian Thomas, Cynthia B. Reding, Douglas J. Hayes, Richard B. Caporaso, Neil E. TI Prospective analysis of DNA damage and repair markers of lung cancer risk from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial SO CARCINOGENESIS LA English DT Article ID LYMPHOBLASTOID CELL-LINES; MUTAGEN SENSITIVITY; CHROMOSOMAL RADIOSENSITIVITY; MOLECULAR EPIDEMIOLOGY; ISOLATED LYMPHOCYTES; WHOLE-BLOOD; INDIVIDUALS; SUSCEPTIBILITY; BLEOMYCIN; CAPACITY AB Mutagen challenge and DNA repair assays have been used in case-control studies for nearly three decades to assess human cancer risk. The findings still engender controversy because blood was drawn after cancer diagnosis so the results may be biased, a type called 'reverse causation'. We therefore used Epstein-Barr virus-transformed lymphoblastoid cell lines established from prospectively collected peripheral blood samples to evaluate lung cancer risk in relation to three DNA repair assays: alkaline Comet assay, host cell reactivation (HCR) assay with the mutagen benzo[a]pyrene diol epoxide and the bleomycin mutagen sensitivity assay. Cases (n = 117) were diagnosed with lung cancer between 0.3 and 6 years after blood collection and controls (n = 117) were frequency matched on calendar year and age at blood collection, gender and smoking history; all races were included. Case and control status was unknown to laboratory investigators. In unconditional logistic regression analyses, statistically significantly increased lung cancer odds ratios (OR(adjusted)) were observed for bleomycin mutagen sensitivity as quartiles of chromatid breaks/cell [relative to the lowest quartile, OR = 1.2, 95% confidence interval (CI): 0.5-2.5; OR = 1.4,95% CI: 0.7-3.1; OR = 2.1,95% CI: 1.0-4.4, respectively, P(trend) = 0.04]. The magnitude of the association between the bleomycin assay and lung cancer risk was modest compared with those reported in previous lung cancer studies but was strengthened when we included only incident cases diagnosed more than a year after blood collection (P(trend) = 0.02), supporting the notion the assay may be a measure of cancer susceptibility. The Comet and HCR assays were unrelated to lung cancer risk. C1 [Sigurdson, Alice J.; Stram, Douglas A.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Jones, Irene M.; Thomas, Cynthia B.] Lawrence Livermore Natl Lab, Livermore, CA USA. [Wei, Qingyi; Wu, Xifeng; Spitz, Margaret R.; Wang, Li-E; Gu, Jian] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Gross, Myron D.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN USA. [Huang, Wen-Yi; Hayes, Richard B.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. [Reding, Douglas J.] Marshfield Clin Fdn Med Res & Educ, Dept Oncol & Hematol, Marshfield, WI 54449 USA. [Hayes, Richard B.] NYU, Langone Med Ctr, Div Epidemiol, Dept Environm Med, New York, NY 10016 USA. [Caporaso, Neil E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Sigurdson, AJ (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7060,MSC 7238, Bethesda, MD 20892 USA. EM sigurdsa@mail.nih.gov OI Hayes, Richard/0000-0002-0918-661X FU Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services; US Department of Energy by Lawrence Livermore National Laboratory [DE-AC52-07NA27344, Y1-CP-6010-02] FX This research was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics; by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services; in part under the auspices of the US Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344 and Inter-Agency Agreement-Y1-CP-6010-02. NR 34 TC 14 Z9 16 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2011 VL 32 IS 1 BP 69 EP 73 DI 10.1093/carcin/bgq204 PG 5 WC Oncology SC Oncology GA 707RF UT WOS:000286303000011 PM 20929901 ER PT J AU Li, GW Zhang, P Wang, JP An, YL Gong, QH Gregg, E Roglic, G Yang, WY Zhang, B Hu, YH Bennett, PH AF Li, Guangwei Zhang, Ping Wang, Jinping An, Yali Gong, Qiuhong Gregg, Edward Roglic, Gojka Yang, Wenying Zhang, Bo Hu, Yinghua Bennett, Peter H. TI Cardiovascular incidence in an incipient population-based cohort with newly diagnosed diabetes and impaired glucose tolerance in China: The DaQing Diabetes Study SO CARDIOLOGY LA English DT Meeting Abstract C1 [Li, Guangwei; An, Yali; Gong, Qiuhong] CAMS, Fu Wai Hosp, Endocrinol & Cardiovasc Dis Ctr, Beijing 100037, Peoples R China. [Li, Guangwei; An, Yali; Gong, Qiuhong] PUMC, Beijing 100037, Peoples R China. [Li, Guangwei; Yang, Wenying; Zhang, Bo] China Japan Friendship Hosp, Dept Endocrinol, Beijing 10029, Peoples R China. [Zhang, Ping; Gregg, Edward] CDC, Atlanta, GA 30341 USA. [Wang, Jinping; Hu, Yinghua] DaQing First Hosp, Da Qing 163316, Peoples R China. [Bennett, Peter H.] NIDDK, Phoenix, AZ 85014 USA. [Roglic, Gojka] WHO Geneva, Geneva, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2011 VL 120 SU 1 BP 6 EP 6 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 865IR UT WOS:000298305100009 ER PT J AU Li, GW Zhang, P Wang, JP An, YL Gong, QH Gregg, E Roglic, G Yang, WY Zhang, B Hu, YH Bennett, PH AF Li, Guangwei Zhang, Ping Wang, Jinping An, Yali Gong, Qiuhong Gregg, Edward Roglic, Gojka Yang, Wenying Zhang, Bo Hu, Yinghua Bennett, Peter H. TI Modifiable predictors of cardiovascular disease and mortality in Chinese with impaired glucose tolerance: 23-year follow-up of the Daqing Diabetes Prevention Study SO CARDIOLOGY LA English DT Meeting Abstract C1 [Li, Guangwei; An, Yali; Gong, Qiuhong] CAMS, Fu Wai Hosp, Endocrinol & Cardiovasc Dis Ctr, Beijing 100037, Peoples R China. [Li, Guangwei; An, Yali; Gong, Qiuhong] PUMC, Beijing 100037, Peoples R China. [Li, Guangwei; Yang, Wenying; Zhang, Bo] China Japan Friendship Hosp, Dept Endocrinol, Beijing 10029, Peoples R China. [Zhang, Ping; Gregg, Edward] CDC, Atlanta, GA 30341 USA. [Wang, Jinping; Hu, Yinghua] DaQing First Hosp, Da Qing 163316, Peoples R China. [Bennett, Peter H.] NIDDK, Phoenix, AZ 85014 USA. [Roglic, Gojka] WHO Geneva, Geneva, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2011 VL 120 SU 1 BP 15 EP 16 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 865IR UT WOS:000298305100028 ER PT J AU Glasser, SP Willard, J Defelice, A Lawrence, J Hung, J Obot, E Girton, J Targum, S Throckmorton, D Mangano, D Lipicky, RJ AF Glasser, Stephen P. Willard, James Defelice, Albert Lawrence, John Hung, James Obot, Evelyn Girton, John Targum, Shari Throckmorton, Douglas Mangano, Dennis Lipicky, Raymond J. TI Is Randomization to Placebo Safe? Risk in Placebo-Controlled Angina Trials: Angina Risk Meta-Analysis SO CARDIOLOGY LA English DT Article DE Angina; Arrhythmia; Congestive heart failure; Placebo; Stroke; Transient ischemic attack; Ventricular tachycardia ID CLINICAL-TRIALS; HYPERTENSION AB Objective: It was the aim of this study to document the risks of symptomatic patients with angina in placebo-controlled, anti-anginal drug development trials in which symptom-limited exercise testing was used as the primary endpoint. Patients and Methods: The original case report forms submitted to the United States Food and Drug Administration in support of approval of new or supplemental new drug applications between 1973 and 2001 were identified and subjected to a by-patient meta-analysis, utilizing both a maximum likelihood analysis and classical Mantel-Haenszel methods. Results: There were 63 placebo-controlled, clinical trials that randomized 10,865 patients, with 1,047 patient-years of observation time. The trials involved 21 different chemical entities from 4 different drug classes. The relative risk (RR) for withdrawal (placebo compared to drug-treated patients) was not increased [RR = 0.92, 95% confidence interval (CI) 0.78-1.08; p = 0.28]. Of interest, a RR of 0.54 (95% CI 0.26-1.04; p < 0.068) for irreversible harm (a combination of cerebrovascular accidents, myocardial infarction and death) and a RR of 0.89 (95% CI 0.61-1.30; p = 0.56) for serious cardiovascular events (myocardial infarction, congestive heart failure, cerebrovascular accidents) both non-statistically significantly favored being randomized to placebo. Conclusions:For the development of current or future drugs for the treatment of angina, there is no obvious contraindication to the use of placebo controls and exercise tolerance testing. Copyright (C) 2012 S. Karger AG, Basel C1 [Glasser, Stephen P.] Univ Alabama, Birmingham, AL 35202 USA. [Willard, James; Defelice, Albert; Lawrence, John; Hung, James; Targum, Shari; Throckmorton, Douglas] US FDA, Rockville, MD 20857 USA. [Obot, Evelyn] NIH, Bethesda, MD 20892 USA. [Mangano, Dennis] Ischemia Res & Educ Fdn, San Francisco, CA USA. [Lipicky, Raymond J.] Lipicky LLC, N Potomac, MD USA. RP Glasser, SP (reprint author), Univ Alabama, 1717 11th Ave S, Birmingham, AL 35202 USA. EM sglasser@uab.edu OI Glasser, Stephen/0000-0001-9620-6406 NR 17 TC 0 Z9 0 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2011 VL 120 IS 3 BP 174 EP 181 DI 10.1159/000335522 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 888AM UT WOS:000299976200012 PM 22261892 ER PT J AU Griffioen, KJ Wan, RQ Okun, E Wang, X Lovett-Barr, MR Li, YZ Mughal, MR Mendelowitz, D Mattson, MP AF Griffioen, Kathleen J. Wan, Ruiqian Okun, Eitan Wang, Xin Lovett-Barr, Mary Rachael Li, Yazhou Mughal, Mohamed R. Mendelowitz, David Mattson, Mark P. TI GLP-1 receptor stimulation depresses heart rate variability and inhibits neurotransmission to cardiac vagal neurons SO CARDIOVASCULAR RESEARCH LA English DT Article DE Nucleus ambiguus; Parasympathetic; Glucagon-like peptide 1; Medulla; Vagus ID GLUCAGON-LIKE PEPTIDE-1; NUCLEUS AMBIGUUS; BLOOD-PRESSURE; BRAIN-STEM; BAROREFLEX SENSITIVITY; MYOCARDIAL-INFARCTION; DIABETES-MELLITUS; CONSCIOUS MICE; SUDDEN-DEATH; ACTIVATION AB Aims Glucagon-like peptide 1 (GLP-1) is an incretin hormone released from the gut in response to food intake. Whereas GLP-1 acts in the periphery to inhibit glucagon secretion and stimulate insulin release, it also acts in the central nervous system to mediate autonomic control of feeding, body temperature, and cardiovascular function. Because of its role as an incretin hormone, GLP-1 receptor analogs are used as a treatment for type 2 diabetes. Central or peripheral administration of GLP-1 increases blood pressure and heart rate, possibly by activating brainstem autonomic nuclei and increasing vagus nerve activity. However, the mechanism(s) by which GLP-1 receptor stimulation affects cardiovascular function are unknown. We used the long-lasting GLP-1 receptor agonist Exendin-4 (Ex-4) to test the hypothesis that GLP-1 signalling modulates central parasympathetic control of heart rate. Methods and results Using a telemetry system, we assessed heart rate in mice during central Ex-4 administration. Heart rate was increased by both acute and chronic central Ex-4 administration. Spectral analysis indicated that the high frequency and low frequency powers of heart rate variability were diminished by Ex-4 treatment. Finally, Ex-4 decreased both excitatory glutamatergic and inhibitory glycinergic neurotransmission to preganglionic parasympathetic cardiac vagal neurons. Conclusion These data suggest that central GLP-1 receptor stimulation diminishes parasympathetic modulation of the heart thereby increasing heart rate. C1 [Griffioen, Kathleen J.; Wan, Ruiqian; Okun, Eitan; Li, Yazhou; Mughal, Mohamed R.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Wang, Xin; Lovett-Barr, Mary Rachael; Mendelowitz, David] George Washington Univ, Dept Physiol & Pharmacol, Washington, DC 20037 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012; okun, eitan/K-1314-2016 OI okun, eitan/0000-0001-8474-1487 FU NIH [HL59895]; National Institute on Aging FX This work was supported by NIH grant HL59895 to D. M. and the Intramural Research Program of the National Institute on Aging. NR 49 TC 39 Z9 43 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD JAN PY 2011 VL 89 IS 1 BP 72 EP 78 DI 10.1093/cvr/cvq271 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 696BH UT WOS:000285416400011 PM 20736238 ER PT S AU Lui, JLC Nilsson, O Baron, J AF Lui, Julian C. Nilsson, Ola Baron, Jeffrey BE CamachoHebner, C Nilsson, O Savendahl, L TI Growth Plate Senescence and Catch-Up Growth SO CARTILAGE AND BONE DEVELOPMENT AND ITS DISORDERS SE Endocrine Development LA English DT Proceedings Paper CT 4th European-Society-for-Paediatric-Endocrinology Advanced Seminar in Developmental Endocrinology CY JUN 30-JUL 01, 2010 CL Stockholm, GERMANY SP European Soc Paediatr Endocrinol, Ipsen ID LONGITUDINAL BONE-GROWTH; TEMPORAL REGULATION; EPIPHYSEAL FUSION; GENE-EXPRESSION; RESTING ZONE; CHONDROCYTES; CARTILAGE; MECHANISM AB Longitudinal bone growth is rapid in prenatal and early postnatal life, but then slows with age and eventually ceases. This growth deceleration is caused primarily by a decrease in chondrocyte proliferation, and is associated with other structural, functional, and molecular changes collectively termed growth plate senescence. Current evidence suggests that growth plate senescence occurs because the progenitor chondrocytes in the resting zone have a limited replicative capacity which is gradually exhausted with increasing cell division. In addition, recent experimental findings from laboratory and clinical studies suggest that growth plate senescence explains the phenomenon of catch-up growth. Growth-inhibiting conditions such as glucocorticoid excess and hypothyroidism delay the program of growth plate senescence. Consequently, growth plates are less senescent after these conditions resolve and therefore grow more rapidly than is normal for age, resulting in catch-up growth. Copyright (C) 2011 S. Karger AG, Basel C1 [Baron, Jeffrey] NIH, CRC, Bethesda, MD 20892 USA. RP Baron, J (reprint author), NIH, CRC, Room 1-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA. EM jeffrey.baron@nih.gov RI Lui, Chun Kin Julian/E-2253-2012 FU Intramural NIH HHS [ZIA HD000640-16] NR 25 TC 17 Z9 18 U1 1 U2 6 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1421-7082 BN 978-3-8055-9792-0 J9 ENDOCR DEV JI Endocr. Dev. PY 2011 VL 21 BP 23 EP 29 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BXY37 UT WOS:000297616000003 PM 21865751 ER PT J AU Kaur, S Roberts, DD AF Kaur, Sukhbir Roberts, David D. TI CD47 applies the brakes to angiogenesis via vascular endothelial growth factor receptor-2 SO CELL CYCLE LA English DT Editorial Material ID THROMBOSPONDIN-1; TRAFFICKING; ACTIVATION; CELLS C1 [Kaur, Sukhbir; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU Intramural NIH HHS NR 15 TC 8 Z9 9 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 1 PY 2011 VL 10 IS 1 BP 10 EP 12 DI 10.4161/cc.10.1.14324 PG 3 WC Cell Biology SC Cell Biology GA 701RV UT WOS:000285841300006 PM 21191182 ER PT S AU Kalab, P Solc, P Motlik, J AF Kalab, Petr Solc, Petr Motlik, Jan BE Kubiak, JZ TI The Role of RanGTP Gradient in Vertebrate Oocyte Maturation SO CELL CYCLE IN DEVELOPMENT SE Results and Problems in Cell Differentiation LA English DT Article; Book Chapter ID NUCLEAR-PORE COMPLEX; IMPORTIN-ALPHA FAMILY; AURORA-A KINASE; MICROTUBULE-ORGANIZING CENTERS; GTPASE-ACTIVATING PROTEIN; MEIOSIS-I PROGRESSION; XENOPUS EGG EXTRACTS; COHESIN SUBUNIT SMC1; CELL-CYCLE CONTROL; MOUSE OOCYTES AB The maturation of vertebrate oocyte into haploid gamete, the egg, consists of two specialized asymmetric cell divisions with no intervening S-phase. Ran GTPase has an essential role in relaying the active role of chromosomes in their own segregation by the meiotic process. In addition to its conserved role as a key regulator of macromolecular transport between nucleus and cytoplasm, Ran has important functions during cell division, including in mitotic spindle assembly and in the assembly of nuclear envelope at the exit from mitosis. The cellular functions of Ran are mediated by RanGTP interactions with nuclear transport receptors (NTRs) related to importin beta and depend on the existence of chromosome-centered RanGTP gradient. Live imaging with FRET biosensors indeed revealed the existence of RanGTP gradient throughout mouse oocyte maturation. NTR-dependent transport of cell cycle regulators including cyclin B1, Wee2, and Cdc25B between the oocyte cytoplasm and germinal vesicle (GV) is required for normal resumption of meiosis. After GVBD in mouse oocytes, RanGTP gradient is required for timely meiosis I (MI) spindle assembly and provides long-range signal directing egg cortex differentiation. However, RanGTP gradient is not required for MI spindle migration and may be dispensable for MI spindle function in chromosome segregation. In contrast, MII spindle assembly and function in maturing mouse and Xenopus laevis eggs depend on RanGTP gradient, similar to X. laevis MII-derived egg extracts. C1 [Kalab, Petr] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Solc, Petr; Motlik, Jan] Acad Sci Czech Republic, Inst Anim Physiol & Genet, Libechov 27721, Czech Republic. RP Kalab, P (reprint author), NCI, Cellular & Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM kalab@mail.nih.gov RI Motlik, Jan/G-7148-2014; Solc, Petr/G-7154-2014 FU Intramural NIH HHS NR 227 TC 9 Z9 9 U1 0 U2 6 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-1844 BN 978-3-642-19064-3 J9 RESULTS PROBL CELL D JI Results Probl. Cell Differ. PY 2011 VL 53 BP 235 EP 267 DI 10.1007/978-3-642-19065-0_12 D2 10.1007/978-3-642-19065-0 PG 33 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BVP45 UT WOS:000292219600012 PM 21630149 ER PT S AU Sixt, M Lammermann, T AF Sixt, Michael Laemmermann, Tim BE Wells, CM Parsons, M TI In Vitro Analysis of Chemotactic Leukocyte Migration in 3D Environments SO CELL MIGRATION: DEVELOPMENTAL METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE 3D; Interstitial migration; Chemotaxis; Chemokine gradient; Cell motility; Collagen; Extracellular matrix; Interstitium; Connective tissue ID DENDRITIC CELLS; MORPHOGENESIS; MECHANISM; CANCER AB Cell migration on two-dimensional (21)) substrates follows entirely different rules than cell migration in three-dimensional (3D) environments. This is especially relevant for leukocytes that are able to migrate in the absence of adhesion receptors within the confined geometry of artificial 313 extracellular matrix scaffolds and within the interstitial space in vivo. Here, we describe in detail a simple and economical protocol to visualize dendritic cell migration in 3D collagen scaffolds along chemotactic gradients. This method can be adapted to other cell types and may serve as a physiologically relevant paradigm for the directed locomotion of most amoeboid cells. C1 [Sixt, Michael] IST Austria, Klosterneuburg, Austria. [Laemmermann, Tim] NIAID, Lab Syst Biol, Lymphocyte Biol Sect, NIH, Bethesda, MD 20892 USA. RP Sixt, M (reprint author), IST Austria, Campus 1, Klosterneuburg, Austria. OI Sixt, Michael/0000-0002-6620-9179 NR 21 TC 19 Z9 19 U1 1 U2 10 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-206-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 769 BP 149 EP 165 DI 10.1007/978-1-61779-207-6_11 D2 10.1007/978-1-61779-207-6 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BVZ36 UT WOS:000293200700011 PM 21748675 ER PT J AU Sun, SC Liu, ZG AF Sun, Shao-Cong Liu, Zheng-Gang TI A special issue on NF-kappa B signaling and function SO CELL RESEARCH LA English DT Editorial Material C1 [Sun, Shao-Cong] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. [Sun, Shao-Cong] Univ Texas Grad Sch Biomed Sci Houston, Houston, TX 77030 USA. [Liu, Zheng-Gang] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Sun, SC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Immunol, 7455 Fannin St,Box 902, Houston, TX 77030 USA. EM ssun@mdanderson.org; zgliu@box-z.nih.gov NR 0 TC 3 Z9 6 U1 1 U2 4 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD JAN PY 2011 VL 21 IS 1 BP 1 EP 2 DI 10.1038/cr.2011.1 PG 2 WC Cell Biology SC Cell Biology GA 702AX UT WOS:000285867600001 PM 21196938 ER PT J AU Morgan, MJ Liu, ZG AF Morgan, Michael J. Liu, Zheng-gang TI Crosstalk of reactive oxygen species and NF-kappa B signaling SO CELL RESEARCH LA English DT Review DE reactive oxygen species (ROS); NF-kappa B; oxidative stress; antioxidants ID TUMOR-NECROSIS-FACTOR; MANGANESE SUPEROXIDE-DISMUTASE; DNA-BINDING ACTIVITY; HYDROGEN-PEROXIDE FORMATION; TERMINAL KINASE ACTIVATION; EARLY EMBRYONIC LETHALITY; PROTEIN-TYROSINE KINASE; ALPHA-INDUCED APOPTOSIS; NITRIC-OXIDE SYNTHASE; INDUCED CELL-DEATH AB NF-kappa B proteins are a family of transcription factors that are of central importance in inflammation and immunity. NF-kappa B also plays important roles in other processes, including development, cell growth and survival, and proliferation, and is involved in many pathological conditions. Reactive Oxygen Species (ROS) are created by a variety of cellular processes as part of cellular signaling events. While certain NF-kappa B-regulated genes play a major role in regulating the amount of ROS in the cell, ROS have various inhibitory or stimulatory roles in NF-kappa B signaling. Here we review the regulation of ROS levels by NF-kappa B targets and various ways in which ROS have been proposed to impact NF-kappa B signaling pathways. C1 [Morgan, Michael J.; Liu, Zheng-gang] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Liu, ZG (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, 37 Convent Dr,RM1130, Bethesda, MD 20892 USA. EM zgliu@helix.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX The authors' research is supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 164 TC 461 Z9 480 U1 10 U2 56 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD JAN PY 2011 VL 21 IS 1 BP 103 EP 115 DI 10.1038/cr.2010.178 PG 13 WC Cell Biology SC Cell Biology GA 702AX UT WOS:000285867600009 PM 21187859 ER PT J AU Bendriem, RM Lee, CT Worden, LT Freed, WJ AF Bendriem, R. M. Lee, C. -T. Worden, L. T. Freed, W. J. TI A Model of Human Embryonic Stem Cell (hESC)-Based Neocortical Development SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 11th International Neural Transplantation and Repair Meeting/18th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY MAY 04-08, 2011 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Bendriem, R. M.; Lee, C. -T.; Worden, L. T.; Freed, W. J.] Natl Inst Drug Abuse, Cellular Neurobiol Res Branch, Intramural Res Program, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2011 VL 20 IS 4 BP 546 EP 546 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 758VZ UT WOS:000290196600017 ER PT J AU Dillon-Carter, O Coggiano, M Errico, S Lee, CT Freed, WJ AF Dillon-Carter, O. Coggiano, M. Errico, S. Lee, C. -T. Freed, W. J. TI Cocaine Effects on Tumor Cell Proliferation SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 11th International Neural Transplantation and Repair Meeting/18th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY MAY 04-08, 2011 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Dillon-Carter, O.; Coggiano, M.; Errico, S.; Lee, C. -T.; Freed, W. J.] Natl Inst Drug Abuse, Cellular Neurobiol Res Branch, Intramural Res Program, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2011 VL 20 IS 4 BP 552 EP 553 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 758VZ UT WOS:000290196600036 ER PT J AU Harvey, BK Howard, DB Wang, Y AF Harvey, B. K. Howard, D. B. Wang, Y. TI BMP7 Activates Gelatinase Activity and Alters Neuronal Morphology in Rat Primary Cortical Neurons SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 11th International Neural Transplantation and Repair Meeting/18th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY MAY 04-08, 2011 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Harvey, B. K.; Howard, D. B.; Wang, Y.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2011 VL 20 IS 4 BP 562 EP 562 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 758VZ UT WOS:000290196600061 ER PT J AU Lee, CT Bendriem, R Drgon, T Worden, L Chen, J Errico, S Tsai, SY Uhl, G Freed, WJ AF Lee, C. -T. Bendriem, R. Drgon, T. Worden, L. Chen, J. Errico, S. Tsai, S. -Y. Uhl, G. Freed, W. J. TI hESC Differentiation to Midbrain Dopaminergic Neurons Is Enhanced in Lines With Amplified 17q21.31 Wnt Signaling Genes SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 11th International Neural Transplantation and Repair Meeting/18th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY MAY 04-08, 2011 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Drgon, T.; Uhl, G.] Natl Inst Drug Abuse, Mol Neurobiol Res Branches, Intramural Res Program, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2011 VL 20 IS 4 BP 568 EP 568 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 758VZ UT WOS:000290196600079 ER PT J AU Chou, J Greig, NH Reiner, D Hoffer, BJ Wang, Y AF Chou, J. Greig, N. H. Reiner, D. Hoffer, B. J. Wang, Y. TI Enhanced Survival of Dopaminergic Neuronal Transplants in Hemiparkinsonian Rats by the p53 Inactivator PFT-alpha SO CELL TRANSPLANTATION LA English DT Article DE Parkinson's disease; Transplantation; Apoptosis; p53; Neuroprotection ID VENTRAL MESENCEPHALIC GRAFTS; TIME-COURSE; NEUROTROPHIC FACTOR; SUBSTANTIA-NIGRA; CELL-DEATH; 6-HYDROXYDOPAMINE LESION; CASPASE INHIBITION; REDUCES APOPTOSIS; IMPROVES SURVIVAL; STRIATUM AB A key limiting factor impacting the success of cell transplantation for Parkinson's disease is the survival of the grafted cells, which are often short lived. The focus of this study was to examine a novel strategy to optimize the survival of exogenous fetal ventromesencephalic (VM) grafts by treatment with the p53 inhibitor, pifithrin-alpha (PFT-alpha), to improve the biological outcome of parkinsonian animals. Adult male Sprague-Dawley rats were given 6-hydroxydopamine into the left medial forebrain bundle to induce a hemiparkinsonian state. At 7 weeks after lesioning, animals were grafted with fetal VM or cortical tissue into the lesioned striatum and, thereafter, received daily PFT-alpha or vehicle injections for 5 days. Apomorphine-induced rotational behavior was examined at 2, 6, 9, and 12 weeks after grafting. Analysis of TUNEL or tyrosine hydroxylase (TH) immunostaining was undertaken at 5 days or 4 months after grafting. The transplantation of fetal VM tissue into the lesioned striatum reduced rotational behavior. A further reduction in rotation was apparent in animals receiving PET-alpha and VM transplants. By contrast, no significant reduction in rotation was evident in animals receiving cortical grafts or cortical grafts + PET-alpha. PET-alpha treatment reduced TUNEL labeling and increased TH(+) cell and fiber density in the VM transplants. In conclusion, our data indicate that early postgrafting treatment with PET-alpha enhances the survival of dopamine cell transplants and augments behavioral recovery in parkinsonian animals. C1 [Wang, Y.] NIDA, IRP, Neural Protect & Regenerat Sect, Baltimore, MD 21224 USA. [Greig, N. H.] NIA, Bethesda, MD 20892 USA. RP Wang, Y (reprint author), NIDA, IRP, Neural Protect & Regenerat Sect, 251 Bayview Blvd,06-721A, Baltimore, MD 21224 USA. EM ywang@intra.nida.nih.gov FU NIDA; NIA, NIH, DHHS FX This research was supported by the Intramural Research Program of NIDA and NIA, NIH, DHHS. The authors declare no conflicts of interest. NR 29 TC 7 Z9 7 U1 0 U2 2 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2011 VL 20 IS 9 BP 1351 EP 1359 DI 10.3727/096368910X557173 PG 9 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 869SX UT WOS:000298619600004 PM 21294958 ER PT J AU Fisher, LW AF Fisher, Larry W. TI DMP1 and DSPP: Evidence for Duplication and Convergent Evolution of Two SIBLING Proteins SO CELLS TISSUES ORGANS LA English DT Article DE SIBLINGs; DSPP; DMP1 ID DENTIN SIALOPHOSPHOPROTEIN DSPP; BONE SIALOPROTEIN; GENE; PHOSPHOPROTEIN; OSTEOPONTIN; TEETH AB Since first being proposed as a tandem gene family in 2001, the relatedness of the 5 SIBLING proteins (BSP, DMP1, DSPP, MEPE, and SPP1/OPN) has predominantly depended on arguments involving shared intron/exon properties as well as conserved protein biochemical properties (e.g. unstructured and acidic) and specific peptide motifs (e.g. phosphorylation and integrin-binding RGD). This report discusses the evidence that an ancient DMP1 gene underwent a simple duplication in the common ancestor of mammals and reptiles and then separately evolved into DSPP-like paralogs in the 2 classes. Genomic sequence analyses show that different copies of the original DMP1 duplication process were selected by mammalian and reptilian (anole lizard) classes to acquire genetically different but biochemically similar phos-phoserine-rich repeat domains by convergent evolution. Mammals, for example, expanded phosphoserine motifs encoded exclusively using motifs containing AGC/T serine codons while the reptile line's repeats also used TCN-encoding serine codons. A similar analysis of the origins of the other 4 SIBLINGs will require even more detailed analysis as genome sequences of various fish and amphibia become available. Copyright (C) 2011 S. Karger AG, Basel C1 CSDB NIDCR NIH, Matrix Biochem Sect, Bethesda, MD 20892 USA. RP Fisher, LW (reprint author), CSDB NIDCR NIH, Matrix Biochem Sect, Room 228,Bldg 30,9000 Rockville Pike, Bethesda, MD 20892 USA. EM lfisher@dir.nidcr.nih.gov FU NIH/NIDCR FX This research was supported by the Intramural Research Program of the NIH/NIDCR. NR 13 TC 13 Z9 13 U1 0 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2011 VL 194 IS 2-4 BP 113 EP 118 DI 10.1159/000324254 PG 6 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 806VH UT WOS:000293842500006 PM 21555860 ER PT J AU Goldberg, M Marchadier, A Vidal, C Harichane, Y Kamoun-Goldrat, A Kellermann, O Kilts, T Young, M AF Goldberg, Michel Marchadier, Arnaud Vidal, Catherine Harichane, Yassine Kamoun-Goldrat, Agnes Kellermann, Odile Kilts, Tina Young, Marian TI Differential Effects of Fibromodulin Deficiency on Mouse Mandibular Bones and Teeth: A Micro-CT Time Course Study SO CELLS TISSUES ORGANS LA English DT Article DE Fibromodulin; Mandible; Molar; Micro-CT; Mineralization ID LEUCINE-RICH PROTEOGLYCANS; COLLAGEN FIBRILLOGENESIS; MINERALIZATION; ENAMEL; PREDENTIN AB Fibromodulin (Fmod) is a keratan sulfate small leucine-rich proteoglycan which is enriched in bones and teeth. In order to determine its functions on bone and tooth mineralization we characterized the phenotype of Fmod-deficient (Fmod-KO) mice using a new-generation microfocus computerized tomography system (micro-CT) and software allowing advanced visualization of 3-D data. Three-week-old and 10-week-old Fmod-KO mandibles and teeth were compared with those of age-matched wild-type (WT) mice. In both young and mature mice the Fmod-KO mandibles were hypomineralized, especially the posterior (proximal) part of the mandible as it appeared to be the main target of the molecule deficiency whereas less extensive alterations were found in the alveolar bone. In transverse sections, larger marrow spaces were observed in the Fmod-KO mice compared with age-matched young or mature WT mice. Quantitative evaluation of the pulp volume of the first molar and 3-D reconstructions suggested that dentinogenesis was diminished in 3-week-old Fmod-KO teeth. In contrast, increased dentin formation was found in 10-week-old Fmod-KO mice and it was accompanied by a reduced pulp volume. Thus, the differential effects of Fmod deficiency on bones and teeth appear to diverge in adult mice. This may result from the previously reported differences in the molecular weight of Fmod in the 2 tissues or from compensatory mechanisms due to the overexpression of DSP and DMP-1 in the dental pulp of Fmod-KO. It is also possible that a single molecule plays diverging roles in a tissue-specific or region-specific manner. Copyright (C) 2011 S. Karger AG, Basel C1 [Goldberg, Michel; Marchadier, Arnaud; Vidal, Catherine; Harichane, Yassine; Kamoun-Goldrat, Agnes; Kellermann, Odile] Univ Paris 05, INSERM, UMR S U747, FR-75006 Paris, France. [Vidal, Catherine] Inst Pasteur, Paris, France. [Kilts, Tina; Young, Marian] NIH, NIDCR, Bethesda, MD 20892 USA. RP Goldberg, M (reprint author), Univ Paris 05, INSERM, UMR S U747, 45 Rue St Peres, FR-75006 Paris, France. EM michel.goldberg@parisdescartes.fr RI marchadier, arnaud/L-5386-2013 OI marchadier, arnaud/0000-0003-0329-2005 FU NIDCR/NIH; Fondation de l'Avenir [ETO-576] FX This research was supported by the IRP Program of the NIDCR/NIH and by the Fondation de l'Avenir, Etude No. ETO-576. NR 13 TC 5 Z9 6 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2011 VL 194 IS 2-4 BP 205 EP 210 DI 10.1159/000324397 PG 6 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 806VH UT WOS:000293842500022 PM 21597266 ER PT J AU Wright, JT Torain, M Long, K Seow, K Crawford, P Aldred, MJ Hart, PS Hart, TC AF Wright, J. Timothy Torain, Melody Long, Kimberly Seow, Kim Crawford, Peter Aldred, Michael J. Hart, P. Suzanne Hart, Tom C. TI Amelogenesis Imperfecta: Genotype-Phenotype Studies in 71 Families SO CELLS TISSUES ORGANS LA English DT Article DE Enamel; Amelogenesis imperfecta; Phenotype; Genotype; Gene; Mutation ID NORTHERN SWEDISH COUNTY; MUTATIONS; AMELOBLASTIN; PROTEIN; GENE AB Amelogenesis imperfecta (AI) represents hereditary conditions affecting the quality and quantity of enamel. Six genes are known to cause AI (AMELX, ENAM, MMP20, KLK4, FAM83H, and WDR72). Our aim was to determine the distribution of different gene mutations in a large AI population and evaluate phenotype-genotype relationships. Affected and unaffected family members were evaluated clinically and radiographically by one examiner. Genotyping was completed using genomic DNA obtained from blood or saliva. A total of 494 individuals were enrolled, with 430 (224 affected, 202 unaffected, and 4 not definitive) belonging to 71 families with conditions consistent with the diagnosis of AI. Diverse clinical phenotypes were observed (i.e. hypoplastic, hypocalcified, and hypomaturation). Genotyping revealed mutations in all 6 candidate genes. A molecular diagnosis was made in 132 affected individuals (59%) and in 26 of the families (37%). Mutations involved 12 families with FAM83H (46%), 6 families with AMELX (23%), 3 families with ENAM (11%), 2 families with KLK4 and MMP20 (8% for each gene), and 1 family with a WDR72 mutation (4%). Phenotypic variants were associated with allelic FAM83H and AMELX mutations. Two seemingly unrelated families had the same KLK4 mutation. Families affected with AI where candidate gene mutations were not identified could have mutations not identifiable by traditional gene sequencing (e.g. exon deletion) or they could have promoter sequence mutations not evaluated in this study. However, the results suggest that there remain new AI causative genes to be identified. Copyright (C) 2011 S. Karger AG, Basel C1 [Wright, J. Timothy; Torain, Melody; Long, Kimberly] Univ N Carolina, Sch Dent, Dept Pediat Dent, Chapel Hill, NC 27599 USA. [Hart, P. Suzanne] NHGRI, Bethesda, MD 20892 USA. [Hart, Tom C.] Univ Chicago, Dept Periodontol, Chicago, IL 60637 USA. [Seow, Kim] Univ Queensland, Brisbane, Qld, Australia. [Aldred, Michael J.] Dorevitch Pathol, Melbourne, Vic, Australia. [Crawford, Peter] Univ Bristol, Bristol, Avon, England. RP Wright, JT (reprint author), Univ N Carolina, Sch Dent, Dept Pediat Dent, Brauer Hall 7450, Chapel Hill, NC 27599 USA. EM tim_wright@dentistry.unc.edu FU NIH [RO1 DE12202] FX We would like to thank the many families and individuals that participated in these investigations as well as the referring clinicians. This study was supported by NIH grant No. RO1 DE12202. NR 29 TC 53 Z9 53 U1 1 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2011 VL 194 IS 2-4 BP 279 EP 283 DI 10.1159/000324339 PG 5 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 806VH UT WOS:000293842500035 PM 21597265 ER PT J AU Kirby, KA Singh, K Michailidis, E Marchand, B Kodama, EN Ashida, N Mitsuya, H Parniak, MA Sarafianos, SG AF Kirby, K. A. Singh, K. Michailidis, E. Marchand, B. Kodama, E. N. Ashida, N. Mitsuya, H. Parniak, M. A. Sarafianos, S. G. TI THE SUGAR RING CONFORMATION OF 4 '-ETHYNYL-2-FLUORO-2 '-DEOXYADENOSINE AND ITS RECOGNITION BY THE POLYMERASE ACTIVE SITE OF HIV REVERSE TRANSCRIPTASE SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article DE EFdA; Translocation Defective Reverse Transcriptase Inhibitors; Sugar Ring Conformation; Reverse Transcriptase; HIV; Antivirals ID NMR COUPLING-CONSTANTS; NUCLEOSIDE ANALOGS; SUBSTITUENT ELECTRONEGATIVITIES; KARPLUS EQUATION; PSEUDOROTATION; VARIANTS; NUCLEOTIDES; INHIBITION; RESISTANCE; NORTH AB 4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is the most potent inhibitor of HIV reverse transcriptase (RT). We have recently named EFdA a Translocation Defective RT Inhibitor (TDRTI) because after its incorporation in the nucleic acid it blocks DNA polymerization, primarily by preventing translocation of RT on the template/primer that has EFdA at the 3'-primer end (T/P-EFdA). The sugar ring conformation of EFdA may also influence RT inhibition by a) affecting the binding of EFdA triphosphate (EFdATP) at the RT active site and/or b) by preventing proper positioning of the 3'-OH of EFdA in T/P-EFdA that is required for efficient DNA synthesis. Specifically, the North (C2'-exo/C3'-endo), but not the South (C2'-endo/C3'-exo) nucleotide sugar ring conformation is required for efficient binding at the primer-binding and polymerase active sites of RT. In this study we use nuclear magnetic resonance (NMR) spectroscopy experiments to determine the sugar ring conformation of EFdA. We find that unlike adenosine nucleosides unsubstituted at the 4'-position, the sugar ring of EFdA is primarily in the North conformation. This difference in sugar ring puckering likely contributes to the more efficient incorporation of EFdATP by RT than dATP. In addition, it suggests that the 3'-OH of EFdA in T/P-EFdA is not likely to prevent incorporation of additional nucleotides and thus it does not contribute to the mechanism of RT inhibition. This study provides the first insights into how structural attributes of EFdA affect its antiviral potency through interactions with its RT target. C1 [Kirby, K. A.; Singh, K.; Michailidis, E.; Marchand, B.; Sarafianos, S. G.] Univ Missouri, Christopher S Bond Life Sci Ctr, Dept Mol Microbiol & Immunol, Sch Med, Columbia, MO 65211 USA. [Kodama, E. N.] Tohoku Univ, Div Emerging Infect Dis, Sch Med, Sendai, Miyagi 9808575, Japan. [Ashida, N.] Yamasa Corp, Chiba 2880056, Japan. [Mitsuya, H.] Kumamoto Univ, Dept Hematol & Infect Dis, Kumamoto 8608556, Japan. [Mitsuya, H.] NIH, Expt Retrovirol Sect, HIV AIDS Malignancy Branch, Bethesda, MD 20892 USA. [Parniak, M. A.] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. RP Sarafianos, SG (reprint author), 471D Christopher S Bond Life Sci Ctr, 1201 Rollins St, Columbia, MO 65211 USA. EM sarafianoss@missouri.edu RI Kodama, Eiichi /C-4032-2009; OI Kodama, Eiichi /0000-0002-6622-2752; Sarafianos, Stefan G/0000-0002-5840-154X; Kirby, Karen A./0000-0003-2468-4796 FU NSF [CHE-89-08304]; NIH/NCRR [S10 RR022341-01]; NIH [AI074389, AI076119, AI076119-S1, AI076119-02S1, AI094715, AI079801]; GeneMatrix; Korea Food & Drug Administration; Ministry of Knowledge and Economy; amfAR Mathilde Krim Fellowship FX We would like to thank Dr. Wei Wycoff for assistance with variable temperature NMR data collection. The purchase of the 500 MHz NMR spectrometer was partially supported by NSF grant CHE-89-08304, and NIH/NCRR grant S10 RR022341-01 (cold probe). This work was supported in part by NIH grants AI074389, AI076119, AI076119-S1, AI076119-02S1, and AI094715 (to S. G. S.) and AI079801 (to M. A. P.). We also acknowledge support from GeneMatrix and the Korea Food & Drug Administration and the Ministry of Knowledge and Economy, Bilateral International Collaborative R&D Program. B. M. is a recipient of the amfAR Mathilde Krim Fellowship. We are grateful to Yamasa Corporation for providing EFdA. NR 54 TC 23 Z9 23 U1 2 U2 11 PU C M B ASSOC PI POITIERS PA 40 AVENUE RECTEUR PINEAU, BAT MECANIQUE, 86022 POITIERS, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PY 2011 VL 57 IS 1 BP 40 EP 46 DI 10.1170/T900 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 893RN UT WOS:000300373200006 PM 21366961 ER PT J AU Haas, AK Kleinau, G Hoyer, I Neumann, S Furkert, J Rutz, C Schulein, R Gershengorn, MC Krause, G AF Haas, Ann-Karin Kleinau, Gunnar Hoyer, Inna Neumann, Susanne Furkert, Jens Rutz, Claudia Schuelein, Ralf Gershengorn, Marvin C. Krause, Gerd TI Mutations that silence constitutive signaling activity in the allosteric ligand-binding site of the thyrotropin receptor SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE G-protein-coupled receptor (GPCR); Thyrotropin receptor; Signal transduction; Allosteric binding pocket; Antagonist; Silencing mutations ID THYROID-STIMULATING HORMONE; PROTEIN-COUPLED-RECEPTORS; TSH RECEPTOR; GERMLINE MUTATIONS; INVERSE AGONIST; GRAVES-DISEASE; LH RECEPTOR; EXPRESSION; INSIGHTS; TISSUES AB The thyrotropin receptor (TSHR) exhibits elevated cAMP signaling in the basal state and becomes fully activated by thyrotropin. Previously we presented evidence that small-molecule ligands act allosterically within the transmembrane region in contrast to the orthosteric extracellular hormone-binding sites. Our goal in this study was to identify positions that surround the allosteric pocket and that are sensitive for inactivation of TSHR. Homology modeling combined with site-directed mutagenesis and functional characterization revealed seven mutants located in the allosteric binding site that led to a decrease of basal cAMP signaling activity. The majority of these silencing mutations, which constrain the TSHR in an inactive conformation, are found in two clusters when mapped onto the 3D structural model. We suggest that the amino acid positions identified herein are indicating locations where small-molecule antagonists, both neutral antagonists and inverse agonists, might interfere with active TSHR conformations. C1 [Haas, Ann-Karin; Kleinau, Gunnar; Hoyer, Inna; Furkert, Jens; Rutz, Claudia; Schuelein, Ralf; Krause, Gerd] Leibniz Inst Mol Pharmacol, D-13125 Berlin, Germany. [Neumann, Susanne; Gershengorn, Marvin C.] NIDDK, NIH, Clin Endocrinol Branch, Bethesda, MD 20892 USA. RP Krause, G (reprint author), Leibniz Inst Mol Pharmacol, Robert Rossle Str 10, D-13125 Berlin, Germany. EM haas@fmp-berlin.de; Kleinau@fmp-berlin.de; hoyer@fmp-berlin.de; susanneN@intra.niddk.nih.gov; furkert@fmp-berlin.de; rutz@fmp-berlin.de; schuelein@fmp-berlin.de; MarvinG@intra.niddk.nih.gov; gkrause@fmp-berlin.de FU Deutsche Forschungsgemeinschaft [KR1273/4-1]; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX This work was supported by the Deutsche Forschungsgemeinschaft (KR1273/4-1) and by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 54 TC 11 Z9 13 U1 0 U2 3 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD JAN PY 2011 VL 68 IS 1 BP 159 EP 167 DI 10.1007/s00018-010-0451-2 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 701AL UT WOS:000285786600013 PM 20652618 ER PT J AU Stumpf, JD Copeland, WC AF Stumpf, Jeffrey D. Copeland, William C. TI Mitochondrial DNA replication and disease: insights from DNA polymerase gamma mutations SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Mitochondria; mtDNA replication; DNA polymerase gamma; POLG; DNA repair ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; BASE EXCISION-REPAIR; P55 ACCESSORY SUBUNIT; ENCODING MIP1 GENE; SACCHAROMYCES-CEREVISIAE; MTDNA MUTATIONS; POLG MUTATIONS; MUTATOR MICE; HEARING-LOSS; AUTOSOMAL-DOMINANT AB DNA polymerase gamma (pol gamma), encoded by POLG, is responsible for replicating human mitochondrial DNA. About 150 mutations in the human POLG have been identified in patients with mitochondrial diseases such as Alpers syndrome, progressive external ophthalmoplegia, and ataxia-neuropathy syndromes. Because many of the mutations are described in single citations with no genotypic family history, it is important to ascertain which mutations cause or contribute to mitochondrial disease. The vast majority of data about POLG mutations has been generated from biochemical characterizations of recombinant pol gamma. However, recently, the study of mitochondrial dysfunction in Saccharomyces cerevisiae and mouse models provides important in vivo evidence for the role of POLG mutations in disease. Also, the published 3D-structure of the human pol gamma assists in explaining some of the biochemical and genetic properties of the mutants. This review summarizes the current evidence that identifies and explains disease-causing POLG mutations. C1 [Stumpf, Jeffrey D.; Copeland, William C.] NIEHS, NIH, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Copeland, WC (reprint author), NIEHS, NIH, Mol Genet Lab, 111 TW Alexander Dr,Bldg 101,Rm E316, Res Triangle Pk, NC 27709 USA. EM copelan1@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences [ES 065078] FX We thank Margaret Humble for maintaining and updating the Pol Gamma mutation database (http://tools.niehs.nih.gov/polg) and for her help in generating Fig. 3 of this review. We thank Dr. Rachelle Bienstock for help with the structural images in this review. We also thank Drs. Matthew Young and Rajesh Kasiviswanathan for the comments and suggestions from their critical reading of this manuscript. This work was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ES 065078). NR 122 TC 52 Z9 53 U1 0 U2 11 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD JAN PY 2011 VL 68 IS 2 BP 219 EP 233 DI 10.1007/s00018-010-0530-4 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 703IA UT WOS:000285970400005 PM 20927567 ER PT B AU Kasprzak, KS AF Kasprzak, Kazimierz S. BE Banfalvi, G TI Role of Oxidative Damage in Metal-Induced Carcinogenesis SO CELLULAR EFFECTS OF HEAVY METALS LA English DT Article; Book Chapter ID DNA-BASE DAMAGE; LIPID-PEROXIDATION PRODUCT; N-TERMINAL SEQUENCE; IN-VITRO INHIBITION; PROTEIN CROSS-LINKS; HUMAN PROTAMINE HP2; HYDROGEN-PEROXIDE; FERRIC NITRILOTRIACETATE; NICKEL SUBSULFIDE; MAMMALIAN-CELLS AB This chapter presents and discusses evidence of possible mechanistic involvement of oxidative DNA and protein damage in metal-induced carcinogenesis. Carcinogenic metals, e.g., Be, Cd, Cr, Co, Ni, and the metalloid As, are capable of generating various kinds of active oxygen and other reactive species in direct redox reactions with O-2, O-2(-center dot), H2O2, organic peroxides, and other cellular or tissue substrates, and/or indirectly by inducing inflammation or unleashing physiological redox-active metals, Fe and Cu. The reactive species may damage all cell components, including DNA, RNA, free triphosphonucleosides, proteins, and lipids, and exhaust cellular antioxidant defenses, e.g., deplete ascorbate. The damage may be aggravated by metal-assisted inhibition of DNA repair and histone demethylation systems. The association of oxidative damage with carcinogenesis is strongly supported by mutagenicity of DNA base products, strand breaks, apurinic sites, cross-links, and adducts typical for the attacking reactive species (oxygen-, carbon-, or sulfur-centered radicals), originating from oxidized amino acids and proteins, and 4-hydroxynonenal, a lipid oxidation product. Oxidative damage to nuclear proteins affects chromatin structure and gene expression, whereas such damage to regulatory proteins disturbs cell cycle and apoptosis. Thus, oxidative DNA damage may assist in the initiation while RNA and protein damage may facilitate the promotion and progression of cancer. C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Kasprzak, KS (reprint author), NCI, Comparat Carcinogenesis Lab, Bldg 538,Room 205E, Frederick, MD 21702 USA. EM kasprzak@mail.nih.gov NR 133 TC 3 Z9 3 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-94-007-0427-5 PY 2011 BP 237 EP 259 DI 10.1007/978-94-007-0428-2_11 D2 10.1007/978-94-007-0428-2 PG 23 WC Biochemistry & Molecular Biology; Cell Biology; Toxicology SC Biochemistry & Molecular Biology; Cell Biology; Toxicology GA BUF64 UT WOS:000289171800011 ER PT J AU Tan, CY Ramaswamy, M Shi, GP Vistica, BP Siegel, RM Gery, I AF Tan, Cuiyan Ramaswamy, Madhu Shi, Guangpu Vistica, Barbara P. Siegel, Richard M. Gery, Igal TI Inflammation-inducing Th1 and Th17 cells differ in their expression patterns of apoptosis-related molecules SO CELLULAR IMMUNOLOGY LA English DT Article DE Apoptosis; Apoptosis-related molecules; Activation-induced cell death; Eye; Inflammation; Th1; Th17 ID T-CELL; PD-1 PATHWAY; AUTOIMMUNITY; DEATH; ACTIVATION; HOMEOSTASIS; TOLERANCE; PHENOTYPE; PROTEINS; SYSTEM AB Th1 cells are remarkably more susceptible to activation induced cell death than Th17. Here, we compared cultures of these two cell subpopulations for their expression of apoptosis-related molecules when re-exposed to their specific antigen. We also compared the expression of apoptosis-related molecules in the mouse eye with inflammation induced by Th1 or Th17 cells. Using qPCR we found that the mRNA transcript levels of the majority of tested apoptosis-related molecules were higher in the Th1 cultures, and in eyes with Th1-induced inflammation. Apoptotic intrinsic pathway molecules played minor roles in the processes in vitro or in vivo, whereas extrinsic pathway molecules, as well as PD-1, its ligands and Tim3, were heavily involved. Published by Elsevier Inc. C1 [Tan, Cuiyan; Shi, Guangpu; Vistica, Barbara P.; Gery, Igal] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Ramaswamy, Madhu; Siegel, Richard M.] NIAMSD, Autoimmun Branch, 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 This research was supported by the Intramural Research Program of the National Eye Institute, NIH. NR 24 TC 9 Z9 11 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PY 2011 VL 271 IS 2 BP 210 EP 213 DI 10.1016/j.cellimm.2011.08.006 PG 4 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 837RC UT WOS:000296219900002 PM 21903206 ER PT J AU Martina, JA Wu, XFS Catalfamo, M Sakamoto, T Yi, C Hammer, JA AF Martina, Jose A. Wu, Xufeng S. Catalfamo, Marta Sakamoto, Takeshi Yi, Chang Hammer, John A., III TI Imaging of lytic granule exocytosis in CD8(+) cytotoxic T lymphocytes reveals a modified form of full fusion SO CELLULAR IMMUNOLOGY LA English DT Article DE Lytic granule; Granzyme; Serglycin; Exocytosis; TIRF imaging; Cytotoxic T lymphocyte ID GRANZYME-B; MEDIATED APOPTOSIS; PLASMA-MEMBRANE; FLUORESCENT PROTEIN; PORE FORMATION; CELL-DEATH; PERFORIN; INFLAMMATION; MECHANISMS; SERGLYCIN AB Here we imaged the exocytosis of lytic granules from human CD8(+) cytotoxic T lymphocytes using rapid total internal reflection microscopy, Lamp-1 tagged with mGFP to follow the fate of the lytic granule membrane, and granzyme A, granzyme B or serglycin tagged with mRFP to follow the fate of lytic granule cargo. Lytic granules were released by full fusion with the plasma membrane, such that the entire granule content for all three cargos visualized was released on a subsecond time scale. The behavior of GFP-Lamp-1 was, however, more complex. While it entered the plasma membrane in all cases, the extent to which it then diffused away from the site of exocytosis varied from nearly complete to highly restricted. Finally, the diffusion properties upon release of the three cargos examined put an upper limit on the size of the macromolecular complex of granzyme and serglycin that is presented to the target cell. Published by Elsevier Inc. C1 [Martina, Jose A.; Wu, Xufeng S.; Yi, Chang; Hammer, John A., III] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Catalfamo, Marta] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Sakamoto, Takeshi] Wayne State Univ, Dept Phys, Detroit, MI 48202 USA. RP Hammer, JA (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 50,Room 2306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hammerj@nhlbi.nih.gov FU Intramural NIH HHS [Z01 HL000514-24] NR 39 TC 7 Z9 7 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PY 2011 VL 271 IS 2 BP 267 EP 279 DI 10.1016/j.cellimm.2011.07.004 PG 13 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 837RC UT WOS:000296219900008 PM 21843881 ER PT J AU Mkrtichyan, M Ghochikyan, A Davtyan, H Movsesyan, N Loukinov, D Lobanenkov, V Cribbs, DH Laust, AK Nelson, EL Agadjanyan, MG AF Mkrtichyan, Mikayel Ghochikyan, Anahit Davtyan, Hayk Movsesyan, Nina Loukinov, Dmitry Lobanenkov, Victor Cribbs, David H. Laust, Amanda K. Nelson, Edward L. Agadjanyan, Michael G. TI Cancer-testis antigen, BORIS based vaccine delivered by dendritic cells is extremely effective against a very aggressive and highly metastatic mouse mammary carcinoma SO CELLULAR IMMUNOLOGY LA English DT Article DE Immunotherapy of breast cancer; Myeloid derived suppressor cells (MDSC); Cancer-testis antigen (CTA); Dendritic cell (DC)-based vaccine; Brother of regulator of imprinted sites (BORIS); Tumor promoting transcription factor; 4T1 mammary carcinoma ID REGULATORY T-CELLS; COMPLEX CLASS-II; BREAST-CANCER; SUPPRESSOR-CELLS; ANTITUMOR IMMUNITY; TRANSCRIPTION FACTOR; TUMOR VACCINES; IMMUNOTHERAPY; PROTEIN; GENE AB Here, we analyze for the first time the immunological and therapeutic efficacy of a dendritic cell (DC) vaccine based on a cancer-testis antigen, Brother of regulator of imprinted sites (BORIS), an epigenetically acting tumor-promoting transcription factor. Vaccination of mice with DC loaded with truncated form of BORIS (DC/mBORIS) after 4T1 mammary tumor implantation induced strong anti-cancer immunity, inhibited tumor growth (18.75% of mice remained tumor-free), and dramatically lowered the number of spontaneous clonogenic metastases (50% of mice remained metastases-free). Higher numbers of immune effector CD4 and CD8 T cells infiltrated the tumors of vaccinated mice vs. control animals. Vaccination significantly decreased the number of myeloid-derived suppressor cells (MDSCs) infiltrating the tumor sites, but not MDSCs in the spleens of vaccinated animals. These data suggest that DC-based mBORIS vaccination strategies have significant anti-tumor activity in a therapeutic setting and will be more effective when combined with agents to attenuate tumor-associated immune suppression. (C) 2011 Elsevier Inc. All rights reserved. C1 [Mkrtichyan, Mikayel; Ghochikyan, Anahit; Davtyan, Hayk; Agadjanyan, Michael G.] Inst Mol Med, Dept Mol Immunol, Huntington Beach, CA 92647 USA. [Movsesyan, Nina; Cribbs, David H.; Agadjanyan, Michael G.] Univ Calif Irvine, Inst Memory Impairments & Neurol Disorders, Irvine, CA 92697 USA. [Loukinov, Dmitry; Lobanenkov, Victor] NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA. [Cribbs, David H.] Univ Calif Irvine, Dept Neurol, Irvine, CA 92697 USA. [Laust, Amanda K.; Nelson, Edward L.] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. [Nelson, Edward L.] Univ Calif Irvine, Div Hematol & Oncol, Dept Med, Irvine, CA 92697 USA. RP Agadjanyan, MG (reprint author), Inst Mol Med, Dept Mol Immunol, 16371 Gothard St,Suite H, Huntington Beach, CA 92647 USA. EM mikayel.mkrtichyan@nih.gov; aghochikya-n@immed.org; hayk.davtyan@immed.org; nmovse-sy@uci.edu; DLOUKINOV@niaid.nih.gov; VLOBANENKOV@niaid.nih.gov; cribbs@uci.edu; alaust@uci.edu; enelson@uci.edu; magadjanyan@imme-d.org OI Lobanenkov, Victor/0000-0001-6665-3635; Ghochikyan, Anahit/0000-0001-5436-0616 FU Susan Komen Foundation [BCTR0707720]; NIH [AG-20241]; National Institute of Allergy and Infectious Diseases, NIH [NS-50895, NS57395] FX We would like to thank students Mr. M. Shugay, Mr. J. Khlghatyan, Mr. Tiraturyan, Ms. A. Davtyan, and Ms. A. Hovakimyan for technical help and Dr. I. Petrushina for valuable comments. This work was supported by Susan Komen Foundation BCTR0707720 for ELN and NIH AG-20241 for DHC and MGA; NS-50895 for DHC and MGA; NS57395 for MGA grants and in part by Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH. NR 63 TC 12 Z9 13 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 J9 CELL IMMUNOL JI Cell. Immunol. PY 2011 VL 270 IS 2 BP 188 EP 197 DI 10.1016/j.cellimm.2011.05.007 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 812UV UT WOS:000294319300011 PM 21641588 ER PT J AU Ito, T Choi, BY King, KA Zalewski, CK Muskett, J Chattaraj, P Shawker, T Reynolds, JC Butman, JA Brewer, CC Wangemann, P Alper, SL Griffith, AJ AF Ito, Taku Choi, Byung Yoon King, Kelly A. Zalewski, Christopher K. Muskett, Julie Chattaraj, Parna Shawker, Thomas Reynolds, James C. Butman, John A. Brewer, Carmen C. Wangemann, Philine Alper, Seth L. Griffith, Andrew J. TI SLC26A4 Genotypes and Phenotypes Associated with Enlargement of the Vestibular Aqueduct SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Review DE SLC26A4; Pendred syndrome; Hearing; Deafness; Inner ear; Genotype-phenotype correlation ID NONSYNDROMIC HEARING IMPAIRMENT; THAN C VARIANT; PENDRED-SYNDROME; CONGENITAL DEAFNESS; COINCIDENTAL POLYMORPHISM; PATHOGENIC MUTATION; RECESSIVE DEAFNESS; TEMPORAL BONE; PDS MUTATIONS; GENE AB Enlargement of the vestibular aqueduct (EVA) is the most common inner ear anomaly detected in ears of children with sensorineural hearing loss. Pendred syndrome (PS) is an autosomal recessive disorder characterized by bilateral sensorineural hearing loss with EVA and an iodine organification defect that can lead to thyroid goiter. Pendred syndrome is caused by mutations of the SLC26A4 gene. SLC26A4 mutations may also be identified in some patients with nonsyndromic EVA (NSEVA). The presence of two mutant alleles of SLC26A4 is correlated with bilateral EVA and Pendred syndrome, whereas unilateral EVA and NSEVA are correlated with one (M1) or zero (M0) mutant alleles of SLC26A4. Thyroid gland enlargement (goiter) appears to be primarily dependent on the presence of two mutant alleles of SLC26A4 in pediatric patients, but not in older patients. In M1 families, EVA may be associated with a second, undetected SLC26A4 mutation or epigenetic modifications. In M0 families, there is probably etiologic heterogeneity that includes causes other than, or in addition to, monogenic inheritance. Copyright (C) 2011 S. Karger AG, Basel C1 [Ito, Taku; King, Kelly A.; Zalewski, Christopher K.; Muskett, Julie; Chattaraj, Parna; Brewer, Carmen C.; Griffith, Andrew J.] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Rockville, MD 20850 USA. [Choi, Byung Yoon] Natl Inst Deafness & Other Commun Disorders, Genet Mol Lab, NIH, Rockville, MD 20850 USA. [Shawker, Thomas; Butman, John A.] NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Reynolds, James C.] NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. [Wangemann, Philine] Kansas State Univ, Dept Anat & Physiol, Manhattan, KS 66506 USA. [Alper, Seth L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Griffith, AJ (reprint author), Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, 5 Res Court, Rockville, MD 20850 USA. EM griffita@nidcd.nih.gov RI Wangemann, Philine/N-2826-2013; Butman, John/J-2780-2013 OI Butman, John/0000-0002-1547-9195 FU NIH [Z01-DC-000039, Z01-DC-000060, Z01-DC-000064, R01-DK43495, P30-DK34854]; Kansas State University CVM-SMILE; Kansas City Area Life Science Institute FX We thank Dennis Drayna and Thomas B. Friedman for critical review of this manuscript. Work in the authors' laboratories was supported by NIH intramural research funds Z01-DC-000039, Z01-DC-000060 and Z01-DC-000064, NIH grants R01-DK43495 and P30-DK34854, Kansas State University CVM-SMILE and the Kansas City Area Life Science Institute. NR 56 TC 33 Z9 40 U1 1 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2011 VL 28 IS 3 BP 545 EP 552 DI 10.1159/000335119 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 861IA UT WOS:000298011400018 PM 22116369 ER PT J AU Bortner, CD Cidlowski, JA AF Bortner, Carl D. Cidlowski, John A. TI Life and Death of Lymphocytes: A Volume Regulation Affair SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Review DE Cell Volume Regulation; Apoptotic Resistance; Osmotic stress; RVI ID PLASMA-MEMBRANE DEPOLARIZATION; PROGRAMMED CELL-DEATH; INDUCED APOPTOSIS; PHYSIOLOGICAL CONCENTRATIONS; DEOXYRIBONUCLEIC-ACID; GLUTATHIONE DEPLETION; THYMOCYTE APOPTOSIS; SHRINKAGE NECROSIS; CHLORIDE CHANNELS; FLOW-CYTOMETRY AB The loss of cell volume, termed apoptotic volume decrease (AVD) has been a hallmark feature of apoptosis. However the role of this characteristic attribute of programmed cell death has always been questioned as to whether it plays an active or passive factor during apoptosis. Here we review studies that suggest that AVD plays an active role during apoptosis and the underlying flux of ions that results in this morphological event regulates the programmed cell death process. Copyright (C) 2011 S. Karger AG, Basel C1 [Bortner, Carl D.; Cidlowski, John A.] NIEHS, Lab Signal Transduct, NIH, US Dept HHS,NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, US Dept HHS,NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cidlowski@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 51 TC 14 Z9 14 U1 3 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2011 VL 28 IS 6 BP 1079 EP 1088 DI 10.1159/000335864 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 867YH UT WOS:000298490200003 PM 22178997 ER PT J AU Bortner, CD Scoltock, AB Cidlowski, JA AF Bortner, Carl D. Scoltock, Alyson B. Cidlowski, John A. TI OSMOTIC STRESS RESPONSE MECHANISMS IMPART INTRINSIC APOPTOTIC PATHWAY RESISTANCE IN LYMPHOCYTES SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Meeting Abstract CT Cell Volume Regulation Meeting CY SEP 04-07, 2011 CL Tuebingen, GERMANY C1 [Bortner, Carl D.; Scoltock, Alyson B.; Cidlowski, John A.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2011 VL 28 IS 6 BP 1326 EP 1327 PG 2 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 867YH UT WOS:000298490200089 ER PT J AU Cidlowski, JA Duma, D Bortner, CD AF Cidlowski, John A. Duma, Danielle Bortner, Carl D. TI GENOME WIDE MOLECULAR ANALYSIS OF GENES AND STRESS SIGNALING PATHWAYS ASSOCIATED WITH APOPTOTIC RESISTANCE IN LYMPHOID CELLS SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Meeting Abstract CT Cell Volume Regulation Meeting CY SEP 04-07, 2011 CL Tuebingen, GERMANY C1 [Cidlowski, John A.; Duma, Danielle; Bortner, Carl D.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2011 VL 28 IS 6 BP 1327 EP 1327 PG 1 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 867YH UT WOS:000298490200090 ER PT J AU Peterlin, BL Rosso, AL Sheftell, FD Libon, DJ Mossey, JM Merikangas, KR AF Peterlin, B. Lee Rosso, Andrea L. Sheftell, Fred D. Libon, David J. Mossey, Jana M. Merikangas, Kathleen R. TI Post-traumatic stress disorder, drug abuse and migraine: New findings from the National Comorbidity Survey Replication (NCS-R) SO CEPHALALGIA LA English DT Article DE Anxiety; chronic daily headache; depression; drug abuse; migraine; post-traumatic stress disorder; smoking ID TENSION-TYPE HEADACHE; CORTISOL; PTSD; TRAUMA; WOMEN AB Background: Post-traumatic stress disorder (PTSD) has been shown to be associated with migraine and drug abuse. Methods: This was an analysis of data from the National Comorbidity Survey Replication (NCS-R) to evaluate the association of PTSD in those with episodic migraine (EM) and chronic daily headache (CDH). Results: Our sample consisted of 5,692 participants. Lifetime and 12-month prevalence rates of PTSD were increased in those with EM and CDH. After adjustments, the lifetime odds ratio (OR) of PTSD was greater in those with EM (OR 3.07 confidence interval [CI]: 2.12, 4.46) compared to those without headache; was greater in men than women with EM (men: OR 6.86; CI: 3.11, 15.11; women: OR 2.77; CI: 1.83, 4.21); and was comparable or greater than the association between migraine with depression or anxiety. The lifetime OR of PTSD was also increased in CDH sufferers. The OR of illicit drug abuse was not increased in those with EM or CDH unless co-occurring with PTSD or depression. Conclusion: The lifetime and 12-month OR of PTSD is increased in those with migraine or CDH, and is greater in men than women with migraine. The lifetime and 12-month OR of illicit drug abuse is not increased in those with migraine or CDH unless co-occurring with PTSD or depression. C1 [Peterlin, B. Lee] Johns Hopkins Univ, Bayview Med Ctr, Baltimore, MD 21224 USA. [Rosso, Andrea L.; Libon, David J.] Drexel Univ, Coll Med, Philadelphia, PA USA. [Rosso, Andrea L.; Mossey, Jana M.] Drexel Univ, Sch Publ Hlth, Philadelphia, PA USA. [Sheftell, Fred D.] Albert Einstein Coll Med, Bronx, NY USA. [Merikangas, Kathleen R.] NIMH, NIH, Bethesda, MD USA. RP Peterlin, BL (reprint author), Johns Hopkins Univ, Bayview Med Ctr, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM lpeterlin@jhmi.edu OI Rosso, Andrea/0000-0001-5890-9856 FU US National Institute of Mental Health (NIMH) [U01-MH60220]; National Institute of Drug Abuse; Substance Abuse and Mental Health Services Administration; Robert Wood Johnson Foundation [044780]; John W. Alden Trust; GSK; Pfizer FX The National Comorbidity Survey Replication (NCS-R) is supported by the US National Institute of Mental Health (NIMH; U01-MH60220) with supplemental support from the National Institute of Drug Abuse, the Substance Abuse and Mental Health Services Administration, the Robert Wood Johnson Foundation (Grant #044780) and the John W. Alden Trust. Collaborating NCS-R investigators include Kathleen Merikangas (co-principal investigator, NIMH). 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 organizations, agencies or the US government. Dr. Peterlin had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.; Dr. Peterlin has been a consultant for OrthoMcNeil and Pfizer, is on the speakers' bureaus for GlaxoSmithKline (GSK), Endo and Merck, has grant support from GSK, has an intellectual property patent for the use of adiponectin-modulating drugs for migraine and is an associate editor for the journal Headache. Dr. Sheftell has served on advisory boards for GSK, Merck, MAP, NuPath, Optinose, and Novartis, is on the speaker's bureaus for Merck and GSK, has received grant support from Pfizer and has an intellectual property patent for montelukast and leukotriene modifiers for migraine and neuroinflammatory disorders. He is an associate editor for the journal Headache Currents. Dr. Mossey is an associate editor for the journal Pain Medicine. A. Rosso, Dr. Libon and Dr. Merikangas have no conflicts of interest or disclosures. NR 30 TC 30 Z9 30 U1 1 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD JAN PY 2011 VL 31 IS 2 BP 235 EP 244 DI 10.1177/0333102410378051 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 711SO UT WOS:000286611900013 PM 20813779 ER PT J AU Nahab, FB Kundu, P Gallea, C Kakareka, J Pursley, R Pohida, T Miletta, N Friedman, J Hallett, M AF Nahab, Fatta B. Kundu, Prantik Gallea, Cecile Kakareka, John Pursley, Randy Pohida, Tom Miletta, Nathaniel Friedman, Jason Hallett, Mark TI The Neural Processes Underlying Self-Agency SO CEREBRAL CORTEX LA English DT Article DE efference copy; fMRI; ownership; sense of agency; voluntary movement ID PARIETAL CORTEX; AWARENESS; OWN; MOVEMENTS; HAND; CONSEQUENCES; STIMULATION; PERCEPTION; PREDICTION; EXPERIENCE AB Self-agency (SA) is the individual's perception that an action is the consequence of his/her own intention. The neural networks underlying SA are not well understood. We carried out a novel, ecologically valid, virtual-reality experiment using blood oxygen level-dependent functional magnetic resonance imaging (fMRI) where SA could be modulated in real-time while subjects performed voluntary finger movements. Behavioral testing was also performed to assess the explicit judgment of SA. Twenty healthy volunteers completed the experiment. Results of the behavioral testing demonstrated paradigm validity along with the identification of a bias that led subjects to over- or underestimate the amount of control they had. The fMRI experiment identified 2 discrete networks. These leading and lagging networks likely represent a spatial and temporal flow of information, with the leading network serving the role of mismatch detection and the lagging network receiving this information and mediating its elevation to conscious awareness, giving rise to SA. C1 [Nahab, Fatta B.; Kundu, Prantik] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Nahab, Fatta B.; Kundu, Prantik; Gallea, Cecile; Miletta, Nathaniel; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, Bethesda, MD 20892 USA. [Kakareka, John; Pursley, Randy; Pohida, Tom] NIH, Signal Proc & Instrumentat Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Friedman, Jason] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel. RP Nahab, FB (reprint author), Univ Miami, Miller Sch Med, Dept Neurol, Clin Res Bldg C-215,1120 NW 14th St,Suite 1347, Miami, FL 33136 USA. EM fnahab@med.miami.edu RI Friedman, Jason/B-4690-2008; OI Friedman, Jason/0000-0001-8845-5082; Kundu, Prantik/0000-0001-9367-3068; Kakareka, John/0000-0003-0072-0035 FU National Institute of Neurological Disorders and Stroke FX Intramural program of the National Institute of Neurological Disorders and Stroke. NR 33 TC 52 Z9 52 U1 1 U2 22 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JAN PY 2011 VL 21 IS 1 BP 48 EP 55 DI 10.1093/cercor/bhq059 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 692ZZ UT WOS:000285195700005 PM 20378581 ER PT B AU Goldman, D AF Goldman, David BE Maheu, L MacDonald, RA TI Gene x Stress Interactions: An Integrative Perspective SO CHALLENGING GENETIC DETERMINISM: NEW PERSPECTIVES ON THE GENE IN ITS MULTIPLE ENVIRONMENTS LA English DT Proceedings Paper CT Fall Symposium of the Royal-Society-of-Canada - Social Sciences Facing Modern Genetics Challenges CY NOV 16, 2007 CL Univ Alberta, Edmonton, CANADA SP Royal Soc Canada, Royal Soc Canada, Social Sci Acad (Acad II) HO Univ Alberta ID ANTISOCIAL PERSONALITY-DISORDER; CHILDHOOD SEXUAL-ABUSE; SEROTONIN-TRANSPORTER; NEUROPEPTIDE-Y; FUNCTIONAL POLYMORPHISM; NALTREXONE RESPONSE; ALCOHOL DEPENDENCE; PROTEIN EXPRESSION; MONOAMINE-OXIDASE; SIGNAL PEPTIDE C1 [Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. EM davidgoldman@mail.nih.gov NR 64 TC 0 Z9 0 U1 4 U2 4 PU MCGILL-QUEENS UNIV PR PI MONTREAL PA 3430 MCTAVISH ST, MONTREAL, PQ H3A 1X9, CANADA BN 978-0-7735-8654-3; 978-0-7735-3780-4 PY 2011 BP 99 EP 125 PG 27 WC Psychology, Biological; Behavioral Sciences; Genetics & Heredity; Medical Ethics; Social Sciences, Biomedical SC Psychology; Behavioral Sciences; Genetics & Heredity; Medical Ethics; Biomedical Social Sciences GA BHI22 UT WOS:000325485400005 ER PT J AU Milac, AL Anishkin, A Fatakia, SN Chow, CC Sukharev, S Guy, HR AF Milac, Adina L. Anishkin, Andriy Fatakia, Sarosh N. Chow, Carson C. Sukharev, Sergei Guy, H. Robert TI Structural models of TREK channels and their gating mechanism SO CHANNELS LA English DT Article DE mechanosensitive ion channels; structure prediction; gating mechanism; proline hinge; mutual information; mutual information graph ID DOMAIN K+ CHANNELS; SECONDARY STRUCTURE PREDICTION; MOLECULAR-DYNAMICS SIMULATION; 2-PORE-DOMAIN POTASSIUM CHANNELS; POLYUNSATURATED FATTY-ACIDS; PROTEIN-STRUCTURE; CRYSTAL-STRUCTURE; K-2P CHANNELS; FAMILY; MSCL AB Mechanosensitive TREK channels belong to the family of K2P channels, a family of widely distributed, well-modulated channels that uniquely have two similar or identical subunits, each with two TM1-P-TM2 motifs. Our goal is to build viable structural models of TREK channels, as representatives of K2P channels family. The structures available to be used as templates belong to the 2TM channels superfamily. These have low sequence similarity and different structural features: four symmetrically arranged subunits, each having one TM1-P-TM2 motif. Our model building strategy used two subunits of the template (KcsA) to build one subunit of the target (TREK-1). Our models of the closed channel were adjusted to differ substantially from those of the template, e. g., TM2 of the second repeat is near the axis of the pore whereas TM2 of the first repeat is far from the axis. Segments linking the two repeats and immediately following the last TM segment were modeled ab initio as alpha-helices based on helical periodicities of hydrophobic and hydrophilic residues, highly conserved and poorly conserved residues and statistically related positions from multiple sequence alignments. The models were further refined by 2-fold symmetry-constrained MD simulations using a protocol we developed previously. We also built models of the open state and suggest a possible tension-activated gating mechanism characterized by helical motion with 2-fold symmetry. Our models are consistent with deletion/truncation mutagenesis and thermodynamic analysis of gating described in the accompanying paper. C1 [Anishkin, Andriy; Sukharev, Sergei] Univ Maryland, Dept Biol, Bethesda, MD USA. [Milac, Adina L.; Guy, H. Robert] NCI, Cell Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Fatakia, Sarosh N.; Chow, Carson C.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. [Milac, Adina L.] Acad Romana, Inst Biochem, Bucharest, Romania. RP Sukharev, S (reprint author), Univ Maryland, Dept Biol, Bethesda, MD USA. EM sukharev@umd.edu RI Milac, Adina/C-1070-2011; Chow, Carson/A-7970-2009; OI Milac, Adina/0000-0003-1845-4281; Fatakia, Sarosh/0000-0003-0430-3191 FU NIH, National Cancer Institute, Center for Cancer Research FX This work was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health (NIH), Bethesda, MD. The authors thank Drs. Stewart Durell, Yinon Shafrir, Sijung Yun (LCB, NCI) for fruitful discussions. NR 75 TC 11 Z9 12 U1 0 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6950 J9 CHANNELS JI Channels PD JAN-FEB PY 2011 VL 5 IS 1 BP 23 EP 33 DI 10.4161/chan.5.1.13905 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 713IC UT WOS:000286730000005 PM 21084863 ER PT J AU Maksaev, G Milac, A Anishkin, A Guy, HR Sukharev, S AF Maksaev, Grigory Milac, Adina Anishkin, Andriy Guy, H. Robert Sukharev, Sergei TI Analyses of gating thermodynamics and effects of deletions in the mechanosensitive channel TREK-1 Comparisons with structural models SO CHANNELS LA English DT Article DE membrane tension; gating transition; channel domains; protein expansion ID ALTERNATIVE TRANSLATION INITIATION; K+ CHANNEL; POTASSIUM CHANNEL; K-2P CHANNELS; MOLECULAR-DYNAMICS; GENERAL-ANESTHESIA; DOMAIN; NEUROPROTECTION; MECHANISM; RESISTANT AB TREK-1, a mechanosensitive K channel from the two-pore family (K(2)P), is involved in protective regulation of the resting potential in CNS neurons and other tissues. The structure of TREK-1 and the basis of its sensitivity to stretch and variety of lipid-soluble factors remain unknown. Using existing K channel structures as modeling templates, TREK-1 was envisioned as a 2-fold symmetrical complex with the gate formed primarily by the centrally positioned TM2b helices of the second homologous repeat. Opening was modeled as a conical expansion of the barrel separating TM2b's accompanied by extension of TM2a helices with the cytoplasmic TM2a-TM1b connector. Seeking first experimental support to the models we have accomplished thermodynamic analysis of mouse TREK-1 gating and functional testing of several deletion mutants. The predicted increase of the channel in-plane area (Delta A) of similar to 5 nm(2) in models was supported by the experimental Delta A of similar to 4 nm(2) derived from the slope of open probability versus membrane tension in HE K-293T cells and their cytoskeleton-depleted blebs. In response to steps of suction, wild-type channel produced transient currents in cell-attached patches and mostly sustained currents upon patch excision. TREK-1 motifs not present in canonical K channels include divergent cytoplasmic N- and C-termini, and a characteristic 50-residue extracellular loop in the first homologous repeat. Deletion of the extracellular loop (Delta 76-124) reduced the average current density in patches, increased spontaneous activity and generated a larger sub-population of high-conductance channels, while activation by tension augmented by arachidonic acid was fully retained. Further deletion of the C-terminal end (Delta 76-124/Delta 334-411) removed voltage dependency but otherwise produced no additional effect. In an attempt to generate a cysteine-free version of the channel, we mutated two remaining cysteines 159 and 219 in the transmembrane region. C219A did not compromise channel activity, whereas the C159A/S mutants were essentially inactive. Treatment with beta-mercaptoethanol suggested that none of these cysteines form functionally-important disulfides. C1 [Maksaev, Grigory; Anishkin, Andriy; Sukharev, Sergei] Univ Maryland, Dept Biol, Bethesda, MD USA. [Milac, Adina; Guy, H. Robert] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Milac, Adina] Acad Romana, Inst Biochem, Bucharest, Romania. RP Sukharev, S (reprint author), Univ Maryland, Dept Biol, Bethesda, MD USA. EM sukharev@umd.edu RI Milac, Adina/C-1070-2011; OI Milac, Adina/0000-0003-1845-4281; Sukharev, Sergei/0000-0002-4807-9665 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX The authors thank Mrs. Naili Liu for technical assistance with cell cultures and DNA isolation. This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. The authors also thank Drs. Amanda Patel and Eric Honore (Centre National de la Recherche Scientifique) for discussions and intellectual support. NR 43 TC 5 Z9 5 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6950 J9 CHANNELS JI Channels PD JAN-FEB PY 2011 VL 5 IS 1 BP 34 EP 42 DI 10.4161/chan.5.1.13906 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 713IC UT WOS:000286730000006 PM 21057213 ER PT S AU McNeil, SE AF McNeil, Scott E. BE McNeil, SE TI Unique Benefits of Nanotechnology to Drug Delivery and Diagnostics SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Nanoparticles; nanomedicine; active and passive targeting; efficacy; toxicity ID PACLITAXEL AB Nanotechnology offers many potential benefits to medical research by making pharmaceuticals more efficacious and by decreasing their adverse side-effects. Preclinical characterization of nanoparticles intended for medical applications is complicated due to the variety of materials used, their unique surface properties and multifunctional nature. This chapter serves as an introduction to the volume, giving a broad overview of applications of nanotechnology to medicine, and describes some of the beneficial aspects of nanotechnology-based drug delivery. We define nanotechnology and provide brief descriptions of the major classes of nanomaterials used for medical applications. The following two chapters discuss scientific and regulatory hurdles involved in the use of nanotechnology in medicine. The remaining bulk of the volume provides the reader with protocols that have been tested against clinically relevant nanoparticles and describes some of the nuances of nanoparticle types and necessary controls. C1 [McNeil, Scott E.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP McNeil, SE (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 10 TC 18 Z9 18 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 3 EP 8 DI 10.1007/978-1-60327-198-1_1 D2 10.1007/978-1-60327-198-1 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400001 PM 21116949 ER PT S AU McNeil, SE AF McNeil, Scott E. BE McNeil, SE TI Challenges for Nanoparticle Characterization SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Nanoparticles; nanomedicine; active and passive targeting; efficacy; toxicity ID POLYSTYRENE MICROSPHERES; ULTRAFINE PARTICLES; HEPATIC-UPTAKE; RATS; SIZES AB The Food and Drug Administration (FDA) and pharmaceutical industry have used standards to assess material biocompatibility, immunotoxicity, purity, and sterility (as well as many other properties) for several decades. Nanoparticle developers and manufacturers leverage well-established methods as much as possible. However, the unique properties of nanomaterials often interfere with standardized protocols, giving Use-positive or false-negative results. This chapter provides details of some of the problems which can arise during the characterization of nanoparticle samples. Additionally, we discuss ways to identify, avoid, and resolve such interference, with emphasis on the use of inhibition and enhancement controls. C1 NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP McNeil, SE (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 9 TC 10 Z9 10 U1 2 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 9 EP 15 DI 10.1007/978-1-60327-198-1_2 D2 10.1007/978-1-60327-198-1 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400002 PM 21116950 ER PT S AU Hackley, VA Clogston, JD AF Hackley, Vincent A. Clogston, Jeffrey D. BE McNeil, SE TI Measuring the Hydrodynamic Size of Nanoparticles in Aqueous Media Using Batch-Mode Dynamic Light Scattering SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Hydrodynamic size; dynamic light scattering; photon correlation spectroscopy; quasi-elastic light scattering; DLS; PCS; QELS; diffusion; diffusion coefficient ID DENDRIMER CORES; CONTRAST AGENTS AB Particle size characterization is of particular importance to nanomedicine. The size similarity of nanoparticles to biological moieties is believed to impart many of their unique medical properties. Here we present a method for sample preparation and the determination of mean nanoparticle size (hydrodynamic diameter) using batch-mode dynamic light scattering (DLS) in dilute aqueous suspensions. We then demonstrate this method for 30 nm colloidal gold. C1 [Hackley, Vincent A.] NIST, Div Ceram, Gaithersburg, MD 20899 USA. [Clogston, Jeffrey D.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Hackley, VA (reprint author), NIST, Div Ceram, Gaithersburg, MD 20899 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012; OI Hackley, Vincent/0000-0003-4166-2724 FU NCI NIH HHS [N01-CO-12400] NR 16 TC 15 Z9 15 U1 0 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 35 EP 52 DI 10.1007/978-1-60327-198-1_4 D2 10.1007/978-1-60327-198-1 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400004 PM 21116952 ER PT S AU Ramalinga, U Clogston, JD Patri, AK Simpson, JT AF Ramalinga, Uma Clogston, Jeffrey D. Patri, Anil K. Simpson, John T. BE McNeil, SE TI Characterization of Nanoparticles by Matrix Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE mass spectrometry; MALDI; electrospray; nanotechnology; dendrimers ID POLY(AMIDOAMINE) DENDRIMERS AB Determining the molecular weight of nanoparticles can be challenging. The molecular weight characterization of dendrimers, for example, with varying covalent and noncovalent modifications is critical to their use as therapeutics. As such, we describe in this chapter a protocol for the analysis of these molecules by matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). C1 [Ramalinga, Uma; Clogston, Jeffrey D.; Patri, Anil K.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Simpson, John T.] NCI, Prot Chem Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Ramalinga, U (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 12 TC 0 Z9 0 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 53 EP 61 DI 10.1007/978-1-60327-198-1_5 D2 10.1007/978-1-60327-198-1 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400005 PM 21116953 ER PT S AU Clogston, JD Patri, AK AF Clogston, Jeffrey D. Patri, Anil K. BE McNeil, SE TI Zeta Potential Measurement SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Zeta potential; surface charge; nanoparticles AB This chapter describes a method for the measurement of the electrostatic potential at the electrical double layer surrounding a nanoparticle in solution. This is referred to as the zeta potential. Nanoparticles with a zeta potential between -10 and +10 mV are considered approximately neutral, while nanoparticles with zeta potentials of greater than +30 mV or less than -30 mV are considered strongly cationic and strongly anionic, respectively. Since most cellular membranes are negatively charged, zeta potential can affect a nanoparticle's tendency to permeate membranes, with cationic particles generally displaying more toxicity associated with cell wall disruption. This technique is demonstrated for two types of nanoparticles commonly used in biological applications: colloidal gold (strongly anionic) and amine-terminated PAMAM dendrimer (strongly cationic). C1 [Clogston, Jeffrey D.; Patri, Anil K.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Clogston, JD (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 1 TC 87 Z9 87 U1 9 U2 29 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 63 EP 70 DI 10.1007/978-1-60327-198-1_6 D2 10.1007/978-1-60327-198-1 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400006 PM 21116954 ER PT S AU Nagashima, K Zheng, JW Parmiter, D Patri, AK AF Nagashima, Kunio Zheng, Jiwen Parmiter, David Patri, Anil K. BE McNeil, SE TI Biological Tissue and Cell Culture Specimen Preparation for TEM Nanoparticle Characterization SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Nanoparticles; electron microscopy; transmission electron microscopy (TEM) AB This chapter outlines the procedures for ex vivo TEM preparation of nanoparticle-containing tissue or cell culture samples using an epoxy resin embedding method. The purpose of this procedure is to preserve the structure of tissue in a hardened epoxy block with minimal disruption of cellular structures, to aid in the meaningful analysis of in vivo or cell culture experiments. The process begins with hydrated tissue and ends with tissue that is virtually water-free and preserved in a static state within a plastic resin matrix. The resin mixture permeates the dehydrated tissue, making the sample firm enough to cut. Procedures are also given for fixing nanoparticle-containing cell culture samples. C1 [Nagashima, Kunio] NCI, Elect Microscopy Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Zheng, Jiwen; Parmiter, David; Patri, Anil K.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Nagashima, K (reprint author), NCI, Elect Microscopy Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 2 TC 7 Z9 7 U1 0 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 83 EP 91 DI 10.1007/978-1-60327-198-1_8 D2 10.1007/978-1-60327-198-1 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400008 PM 21116956 ER PT S AU Zheng, JW Nagashima, K Parmiter, D de la Cruz, J Patri, AK AF Zheng, Jiwen Nagashima, Kunio Parmiter, David de la Cruz, Jason Patri, Anil K. BE McNeil, SE TI SEM X-Ray Microanalysis of Nanoparticles Present in Tissue or Cultured Cell Thin Sections SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Nanoparticles; electron microscopy; energy dispersive X-ray spectroscopy (EDX) AB Energy Dispersive X-ray (EDX) microanalysis is a technique used for identification of the elemental composition of a specimen. The detection of nanoparticles in tissue is a common problem of biodistribution and toxicity studies. High-resolution transmission electron microscopy (TEM) can be employed to detect nanoparticles based on morphology; however, TEM alone cannot conclusively identify nanoparticles. Indeed, micrographs are often ambiguous due to particle aggregation, contamination, or morphology change after cellular uptake. EDX can be used to confirm the composition and distribution of the nanoparticles through spectrum and elemental mapping. This protocol outlines the procedures for compositional identification of nanoparticles using an EDX spectrometer incorporated into a scanning electron microscopy (SEM) system. This protocol outlines sample preparation, EDX spectrum acquisition, elemental peak analysis and spectral mapping acquisition. C1 [Zheng, Jiwen; Parmiter, David; Patri, Anil K.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Nagashima, Kunio; de la Cruz, Jason] NCI, Elect Microscopy Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Zheng, JW (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 4 TC 9 Z9 9 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 93 EP 99 DI 10.1007/978-1-60327-198-1_9 D2 10.1007/978-1-60327-198-1 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400009 PM 21116957 ER PT S AU Clogston, JD Patri, AK AF Clogston, Jeffrey D. Patri, Anil K. BE McNeil, SE TI Detecting and Measuring Free Gadolinium in Nanoparticles for MRI Imaging SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE gadolinium; chelate; magnetic resonance imaging (MRI); Arsenazo; contrast agents AB This chapter describes a method for the measurement of free gadolinium in nanoparticle samples. Conjugation of a gadolinium-chelate to a nanoparticle allows the particle's distribution to be imaged via magnetic resonance imaging (MRI). Free (unchelated) gadolinium is a known toxin, being a heavy metal, and may contribute towards total gadolinium concentration. Determining the amount of free gadolinium is therefore an important aspect of the preclinical characterization of gadolinium-chelate MRI imaging agent nanoparticles. C1 [Clogston, Jeffrey D.; Patri, Anil K.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Clogston, JD (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 1 TC 2 Z9 2 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 101 EP 108 DI 10.1007/978-1-60327-198-1_10 D2 10.1007/978-1-60327-198-1 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400010 PM 21116958 ER PT S AU Clogston, JD Patri, AK AF Clogston, Jeffrey D. Patri, Anil K. BE McNeil, SE TI Lipid Component Quantitation by Thin Layer Chromatography SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE TLC; lipids; nanoemulsions; liposomes; ceramide AB This chapter describes a thin layer chromatography (TLC) method for the quantitation of various lipids (such as phospholipids, sphingolipids, acylglycerols, and fatty acids) in lipid-based nanoparticle formulations such as liposomes and nanoemulsions. We illustrate this technique to quantify C6-ceramide (N-hexanoyl-d-erythro-sphingosine) in a nanoemulsion formulation. C6-ceramide is a powerful chemotherapeutic that is poorly soluble in aqueous buffers. C1 [Clogston, Jeffrey D.; Patri, Anil K.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Clogston, JD (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 1 TC 5 Z9 5 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 109 EP 117 DI 10.1007/978-1-60327-198-1_11 D2 10.1007/978-1-60327-198-1 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400011 PM 21116959 ER PT S AU Neun, BW Dobrovolskaia, MA AF Neun, Barry W. Dobrovolskaia, Marina A. BE McNeil, SE TI Detection and Quantitative Evaluation of Endotoxin Contamination in Nanoparticle Formulations by LAL-Based Assays SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE endotoxin; lipopolysaccharide; Limulus amoebocyte lysate (LAL) ID LIPOPOLYSACCHARIDE AB Bacterial endotoxin or lipopolysaccharide (LPS) is a membrane component of all Gram-negative bacteria. The administration of products contaminated with bacterial endotoxin can cause fever, shock, and even death. Accordingly, the FDA sets limits on the number of endotoxin units (EU) that may be present in a drug or device product. Limulus amoebocyte lysate (LAL) is the extract from amoebocytes of the horseshoe crab Limulus polyphemus, which reacts with bacterial endotoxin. Detection of the products of this reaction is an effective means of quantifying the EU present in a drug formulation. However, nanoparticles frequently interfere with the reactivity of endotoxin, the LAL reaction, or the detection of the reaction products. This interference can be manifested as either an enhancement or an inhibition, causing a respective overestimation or underestimation of the EU in the sample. Here, we present two methods for the detection and quantification of endotoxin in nanoparticle preparations: one is based on an end-point chromogenic LAL assay, and the second approach is based on measuring the turbidity of the LAL extract. C1 [Neun, Barry W.; Dobrovolskaia, Marina A.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Neun, BW (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 8 TC 25 Z9 25 U1 1 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 121 EP 130 DI 10.1007/978-1-60327-198-1_12 D2 10.1007/978-1-60327-198-1 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400012 PM 21116960 ER PT S AU Potter, TM Dobrovolskaia, MA AF Potter, Timothy M. Dobrovolskaia, Marina A. BE McNeil, SE TI Analysis of Microbial Contamination in Nanoparticle Formulations SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Nanoparticles; contamination; bacteria; yeast; mold AB This chapter describes a procedure for quantitative determination of microbial contamination of a nanoparticle formulation. The protocol includes tests for yeast, mold, and bacteria using Millipore sampler devices. This approach is primarily intended to avoid contamination of cell cultures and transmitting potential microbial contaminants to animals in preclinical studies of efficacy, biodistribution, and toxicity. Other methods common to microbiology will likely work equally well. C1 [Potter, Timothy M.; Dobrovolskaia, Marina A.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD USA. RP Potter, TM (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 4 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 131 EP 134 DI 10.1007/978-1-60327-198-1_13 D2 10.1007/978-1-60327-198-1 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400013 PM 21116961 ER PT S AU Aggarwal, P Dobrovolskaia, MA AF Aggarwal, Parag Dobrovolskaia, Marina A. BE McNeil, SE TI Gold Nanoparticle Quantitation via Fluorescence in Solution and Cell Culture SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE fluorescence; gold; nanoparticles AB This chapter provides a protocol for quantitative analysis of gold in solution as well as gold uptake by macrophages. A 96-well fluorescence assay was developed to be able to determine gold concentrations for a given gold nanoparticle as well as quantify the degree of gold nanoparticle uptake by macrophages. This assay detects a decrease in the fluorescence of a dye upon forming a complex with gold and a ligand. The decrease in fluorescence is proportional to the amount of gold. This protocol provides a preliminary and qualitative first-step alternative for the determination of gold nanoparticle concentration without requiring expensive, time-consuming methods such as inductively coupled plasma mass spectroscopy. This protocol can be used to support the uptake studies by the light microscopy method described in Chapter 23. This assay requires 200 mu L of each test nanoparticle at a concentration of the users choosing. Up to 32 variations of test nanoparticles can be evaluated in duplicate in one assay run. C1 [Aggarwal, Parag; Dobrovolskaia, Marina A.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Aggarwal, P (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 3 TC 4 Z9 4 U1 1 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 137 EP 143 DI 10.1007/978-1-60327-198-1_14 D2 10.1007/978-1-60327-198-1 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400014 PM 21116962 ER PT S AU Chan, KC Veenstra, TD Issaq, HJ AF Chan, King C. Veenstra, Timothy D. Issaq, Haleem J. BE McNeil, SE TI Quantitation of Nanoparticles in Serum Matrix by Capillary Electrophoresis SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE carboxyfullerene; nanoparticle; serum; capillary electrophoresis ID POLY(AMIDOAMINE) DENDRIMERS; ZONE-ELECTROPHORESIS; AU NANOPARTICLES; CARBOXYFULLERENE; CE; CHROMATOGRAPHY; NANODEVICES; COMPLEX; ACID AB Sensitive and fast analytical techniques are needed to determine the concentration of nanoparticles in biological samples (e.g., blood and tissues) for biodistribution and toxicity studies. This chapter describes a method for the use of capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography (MEKC) for the quantitation of fullerene nanoparticles in human serum matrix. Data on the fullerene-based nanoparticle carboxyfullerene (C3 fullerene) in human serum is presented as an example. C1 [Chan, King C.; Veenstra, Timothy D.; Issaq, Haleem J.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Chan, KC (reprint author), NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. FU NCI NIH HHS [N01-CO-12400] NR 25 TC 0 Z9 1 U1 1 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 145 EP 153 DI 10.1007/978-1-60327-198-1_15 D2 10.1007/978-1-60327-198-1 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400015 PM 21116963 ER PT S AU Potter, TM Stern, ST AF Potter, Timothy M. Stern, Stephan T. BE McNeil, SE TI Evaluation of Cytotoxicity of Nanoparticulate Materials in Porcine Kidney Cells and Human Hepatocarcinoma Cells SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Nanoparticles; cytotoxicity; MTT; LDH ID CYTO-TOXICITY; REDUCTION; RELEASE; ASSAY AB This chapter describes method for evaluation of nanomaterial cytotoxicity by examining effects on porcine kidney (LLC-PK1) and human cancerous liver cells (Hep G2). Several studies indicate that many nanoparticles are cleared from the body through the kidney or liver, making these organs good choices for target organ toxicity evaluation. In this standard, two separate metrics (MTT and LDH) provide complementary data, that can be used to identify interference. C1 [Potter, Timothy M.; Stern, Stephan T.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Potter, TM (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 7 TC 3 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 157 EP 165 DI 10.1007/978-1-60327-198-1_16 D2 10.1007/978-1-60327-198-1 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400016 PM 21116964 ER PT S AU Potter, TM Stern, ST AF Potter, Timothy M. Stern, Stephan T. BE McNeil, SE TI Monitoring Nanoparticle-Treated Hepatocarcinoma Cells for Apoptosis SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Apoptosis; cell death; nanoparticles; hepatocarcinoma AB This chapter describes a method for monitoring nanoparticle treated human hepatocarcinoma cells (Hep G2) for apoptosis. The protocol utilizes a fluorescent method to determine the degree of caspase-3 activation. C1 [Potter, Timothy M.; Stern, Stephan T.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Potter, TM (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 3 TC 1 Z9 1 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 167 EP 172 DI 10.1007/978-1-60327-198-1_17 D2 10.1007/978-1-60327-198-1 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400017 PM 21116965 ER PT S AU Zolnik, B Potter, TM Stern, ST AF Zolnik, Banu Potter, Timothy M. Stern, Stephan T. BE McNeil, SE TI Detecting Reactive Oxygen Species in Primary Hepatocytes Treated with Nanoparticles SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Reactive oxygen species; oxidative stress; hepatocytes; nanoparticles ID ULTRAFINE PARTICLES; IN-VIVO; SIZE; C-60 AB This chapter describes a protocol for testing nanoparticle formulations for reactive oxygen species generation in male Sprague-Dawley (SD) primary hepatocytes. The protocol utilizes the fluorescent redox active probe, dichlorofluorescein diacetate (DCFH-DA). Primary hepatocytes were chosen for this assay since they have greater metabolic activity than hepatocyte cell lines. This method extends previous standardized cytotoxicity methods for particulates by evaluating mechanisms of toxicity in potential target organ cells. Oxidative stress has been identified as a likely mechanism of nanoparticle toxicity, and cell-based in vitro systems for evaluation of nanoparticle-induced oxidative stress are widely considered an important component of biocompatibility screens. C1 [Potter, Timothy M.; Stern, Stephan T.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 10 TC 3 Z9 3 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 173 EP 179 DI 10.1007/978-1-60327-198-1_18 D2 10.1007/978-1-60327-198-1 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400018 PM 21116966 ER PT S AU Potter, TM Neun, BW Stern, ST AF Potter, Timothy M. Neun, Barry W. Stern, Stephan T. BE McNeil, SE TI Assay to Detect Lipid Peroxidation upon Exposure to Nanoparticles SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Lipid peroxidation; oxidative stress; hepatocytes; nanoparticles AB This chapter describes a method for the analysis of human hepatocarcinoma cells (HEP G2) for lipid peroxidation products, such as malondialdehyde (MDA), following treatment with nanoparticle formulations. Oxidative stress has been identified as a likely mechanism of nanoparticle toxicity, and cell-based in vitro systems for evaluation of nanoparticle-induced oxidative stress are widely considered to be an important component of biocompatibility screens. The products of lipid peroxidation, lipid hydroperoxides, and aldehydes, such as MDA, can be measured via a thiobarbituric acid reactive substances (TBARS) assay. In this assay, which can be performed in cell culture or in cell lysate, MDA combines with thiobarbituric acid (TBA) to form a fluorescent adduct that can be detected at an excitation wavelength of 530 nm and an emission wavelength of 550 nm. The results are then expressed as MDA equivalents, normalized to total cellular protein (determined by Bradford assay). C1 [Potter, Timothy M.; Neun, Barry W.; Stern, Stephan T.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Potter, TM (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 5 TC 8 Z9 8 U1 0 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 181 EP 189 DI 10.1007/978-1-60327-198-1_19 D2 10.1007/978-1-60327-198-1 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400019 PM 21116967 ER PT S AU Potter, TM Neun, BW Stern, ST AF Potter, Timothy M. Neun, Barry W. Stern, Stephan T. BE McNeil, SE TI Monitoring Glutathione Homeostasis in Nanoparticle-Treated Hepatocytes SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Glutathione; oxidative stress; hepatocarcinoma; nanoparticles ID PARTICULATE MATTER; OXIDATIVE STRESS; TOXICITY AB This chapter describes a method for the analysis of human hepatocarcinoma cells (Hep G2 cells) for reduced and oxidized glutathione, following treatment with nanoparticle formulations. Glutathione is a tripeptide (L-gamma-glutamyl-L-cysteinyl-glycine) present intracellularly in millimolar concentrations and one of the primary cellular antioxidant defenses against oxidative stress. An increase in the relative amount of oxidized to reduced glutathione may be indicative of oxidative stress, while a decrease in the overall glutathione pool may be indicative of conjugative metabolism or impaired synthesis. The method presented in this chapter utilizes a colorimetric method for detection of reduced and oxidized glutathione. C1 [Potter, Timothy M.; Neun, Barry W.; Stern, Stephan T.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Potter, TM (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 7 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 191 EP 198 DI 10.1007/978-1-60327-198-1_20 D2 10.1007/978-1-60327-198-1 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400020 PM 21116968 ER PT S AU McLeland, CB Rodriguez, J Stern, ST AF McLeland, Christopher B. Rodriguez, Jamie Stern, Stephan T. BE McNeil, SE TI Autophagy Monitoring Assay: Qualitative Analysis of MAP LC3-I to II Conversion by Immunoblot SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Autophagy; lysosomal dysfunction; nanoparticles ID NANOPARTICLES AB Lysosomal dysfunction is a recognized toxic mechanism for xenobiotics, which can result in various pathological states. There is concern that nanoparticles, in particular, may cause lysosomal pathologies, since they are likely to accumulate within lysosomes. Dysregulation of the autophagy-lysosomal degradation pathway is an example of lysosomal dysfunction associated with exposure to some nanomaterials. Here, we present a method to monitor autophagy by measurement the autophagosome marker LC3-II, a phosphatidylethanolamine (PE)-conjugated form of microtubule-associated protein 1 light chain 3-I (MAP LC3-I). As other conditions could potentially result in LC3-II expression, treatment-related changes in expression should be further evaluated by morphological assessment, using techniques such as electron microscopy, to confirm autophagosome involvement. C1 [McLeland, Christopher B.; Rodriguez, Jamie; Stern, Stephan T.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP McLeland, CB (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 NR 5 TC 21 Z9 24 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 199 EP 206 DI 10.1007/978-1-60327-198-1_21 D2 10.1007/978-1-60327-198-1 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400021 PM 21116969 ER PT S AU Neun, BW Stern, ST AF Neun, Barry W. Stern, Stephan T. BE McNeil, SE TI Monitoring Lysosomal Activity in Nanoparticle-Treated Cells SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Nanoparticles; lysosomal activity; lysosome; nanoparticle autophagy; lysotracker ID AUTOPHAGY AB Certain nanoparticles have been shown to accumulate within lysosome and hence may cause lysosomal pathologies such as phospholipidosis, lysosomal overload, and autophagy. This chapter describes a method for evaluation of lysosomal activity in porcine kidney cells (LLC-PK1) after exposure to nanoparticles. This method uses the accumulation of a cationic fluorescent dye (LysoTracker Red) in acidic cellular compartments as an indicator of total lysosome content. The lysotracker signal is normalized to the signal from a thiol-reactive dye which is proportional to the total number of viable cells. C1 [Neun, Barry W.; Stern, Stephan T.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Neun, BW (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 6 TC 12 Z9 13 U1 0 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 207 EP 212 DI 10.1007/978-1-60327-198-1_22 D2 10.1007/978-1-60327-198-1 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400022 PM 21116970 ER PT S AU Neun, BW Dobrovolskaia, MA AF Neun, Barry W. Dobrovolskaia, Marina A. BE McNeil, SE TI Method for Analysis of Nanoparticle Hemolytic Properties In Vitro SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE nanoparticles; hemolysis; hemoglobin; red blood cells (RBC) AB Hemolysis is damage to red blood cells (RBCs), which results in the release of the iron-containing protein hemoglobin into plasma. Here we describe an in vitro assay specifically developed for the analysis of nanoparticle hemolytic properties (see Fig. 1). In this assay, analyte nanoparticles arc incubated in blood, and hemoglobin is released by damaged cells and converted to red-colored cyanmethemoglobin by reagents. The nanoparticles and undamaged RBCs arc then removed by centrifugation, and the amount of cyanmethemoglobin in the supernatant is measured by spectrophotometry. This measured absorbance is compared to a standard curve to determine the concentration of hemoglobin in the supernatant. This hemoglobin concentration is then compared to that in the supernatant of a blood sample treated with a negative control to obtain the percentage of nanoparticle-induced hemolysis. C1 [Neun, Barry W.; Dobrovolskaia, Marina A.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Neun, BW (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 3 TC 10 Z9 10 U1 1 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 215 EP 224 DI 10.1007/978-1-60327-198-1_23 D2 10.1007/978-1-60327-198-1 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400023 PM 21116971 ER PT S AU Neun, BW Dobrovolskaia, MA AF Neun, Barry W. Dobrovolskaia, Marina A. BE McNeil, SE TI Method for In Vitro Analysis of Nanoparticle Thrombogenic Properties SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Nanoparticles; thrombogenicity; platelet aggregation; platelet; blood; plasma coagulation AB Thrombus formation is complex process involving both cellular and molecular (protein) components. Platelets are responsible for maintaining hemostasis and for preventing excessive bleeding. These cells aggregate along with other plasma components and blood cells to form blood clots. Undesirable platelet aggregation may lead to life-threatening conditions such as stroke. Thrombogenicity is the property of a material to induce the formation of a thrombus, which results in partial or complete occlusion of a blood vessel. The tendency to cause platelet aggregation and perturb plasma coagulation can serve as an in vitro measure of a nanomaterial's likelihood to be thrombogenic in vivo. This chapter describes a procedure for in vitro analyses of platelet aggregation and plasma coagulation time. Platelet-rich plasma (PRP) is obtained from freshly derived human whole blood and incubated with nanoparticles. Then the plasma is examined using a particle count and size analyzer to determine the number of active platelets. The percent aggregation is calculated by comparing the number of active platelets in the nanoparticle-exposed sample to control plasma. To measure the plasma coagulation time, platelet-poor plasma from human whole blood is exposed to nanoparticles in vitro and analyzed in prothrombin (PT), activated partial thromboplastin (APTT), and thrombin time assays. C1 [Neun, Barry W.; Dobrovolskaia, Marina A.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD USA. RP Neun, BW (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 4 TC 19 Z9 19 U1 1 U2 10 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 225 EP 235 DI 10.1007/978-1-60327-198-1_24 D2 10.1007/978-1-60327-198-1 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400024 PM 21116972 ER PT S AU Neun, BW Dobrovolskaia, MA AF Neun, Barry W. Dobrovolskaia, Marina A. BE McNeil, SE TI Qualitative Analysis of Total Complement Activation by Nanoparticles SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Nanoparticles; complement; anaphylaxis; C3; western blot AB This chapter describes a method for qualitative detection of complement activation by western blot. This method uses the cleavage product of the C3 component as a marker for complement activation by any pathway. In this protocol, human plasma is exposed to nanoparticles and then analyzed by polyacrylamide gel electrophoresis (PAGE) followed by western blot with anti-C3-specific antibodies. These antibodies recognize both the native C3 component of complement and its cleavage products. The amounts of C3 and the C3 cleavage products are compared to the amounts in control (untreated) plasma and to plasma treated with a positive control to provide a quick and inexpensive qualitative assessment of complement activation. C1 [Neun, Barry W.; Dobrovolskaia, Marina A.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD USA. RP Neun, BW (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 8 TC 15 Z9 15 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 237 EP 245 DI 10.1007/978-1-60327-198-1_25 D2 10.1007/978-1-60327-198-1 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400025 PM 21116973 ER PT S AU Skoczen, SL Potter, TM Dobrovolskaia, MA AF Skoczen, Sarah L. Potter, Timothy M. Dobrovolskaia, Marina A. BE McNeil, SE TI Method for Analysis of Nanoparticle Effects on Cellular Chemotaxis SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Nanoparticles; chemotaxis; chemoattractant; immune response AB Chemotaxis is the phenomenon in which cells direct their movements in the presence of certain chemicals (chemoattractants or chemorepellents). Leukocyte recruitment (via chemotaxis) is an important component of the inflammatory response, both in physiological host defense and in a range of prevalent disorders that include an inflammatory component. Circulating leukocytes in the bloodstream migrate towards the site of inflammation in response to a complex network of proinflammatory signaling molecules (including cytokines, chemokines and prostaglandins). This chapter describes a method for rapid measure of the chemoattractant capacity of nanoparticulate materials. This method is an in vitro model for chemotaxis, in which promyelocytic leukemia cell migration through a filter is monitored using a fluorescent dye. C1 [Skoczen, Sarah L.; Potter, Timothy M.; Dobrovolskaia, Marina A.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Skoczen, SL (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 4 TC 2 Z9 2 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 247 EP 253 DI 10.1007/978-1-60327-198-1_26 D2 10.1007/978-1-60327-198-1 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400026 PM 21116974 ER PT S AU Skoczen, SL Potter, TM Dobrovolskaia, MA AF Skoczen, Sarah L. Potter, Timothy M. Dobrovolskaia, Marina A. BE McNeil, SE TI In Vitro Analysis of Nanoparticle Uptake by Macrophages Using Chemiluminescence SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Nanoparticles; phagocytosis; macrophage uptake ID GOLD NANOPARTICLES; PHAGOCYTOSIS; CELLS AB This chapter provides a protocol for qualitative evaluation of nanoparticle internalization by phagocytic cells such as macrophages. This protocol uses luminol chemiluminescence to detect nanoparticle uptake. This protocol provides a preliminary qualitative look at phagocytosis which should be confirmed by other techniques such as electron microscopy, confocal microscopy, or as applicable to a given nanoparticle sample. C1 [Skoczen, Sarah L.; Potter, Timothy M.; Dobrovolskaia, Marina A.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Skoczen, SL (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 8 TC 5 Z9 5 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 255 EP 261 DI 10.1007/978-1-60327-198-1_27 D2 10.1007/978-1-60327-198-1 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400027 PM 21116975 ER PT J AU Nandurdikar, RS Keefer, LK Saavedra, JE AF Nandurdikar, Rahul S. Keefer, Larry K. Saavedra, Joseph E. TI Novel protection-deprotection strategies in diazeniumdiolate chemistry: synthesis of V-IPA/NO SO CHEMICAL COMMUNICATIONS LA English DT Article ID NITRIC-OXIDE PRODRUG; INDUCED HEPATOTOXICITY; CHEMICAL SYNTHESIS; PYRRO/NO; LIVER; DONOR; HNO; NO; APOPTOSIS; TOXICITY AB Synthesis of previously inaccessible, potentially liver selective HNO donor V-IPA/NO ([iPrHN(3)-N(1)(O(1))=N(2)-O(2)-R], where R = vinyl) is reported here. A novel fluoride-labile TOM group at O-2 in conjunction with MOM protection at N-3 in IPA/NO is employed. The strategy developed is also extended to synthesis of other NO-releasing prodrugs and has applications in diversity-oriented synthesis of HNO- and NO-prodrugs. C1 [Nandurdikar, Rahul S.; Keefer, Larry K.] Natl Canc Inst, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. [Saavedra, Joseph E.] Natl Canc Inst, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Nandurdikar, RS (reprint author), Natl Canc Inst, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. EM nandurdikarr@mail.nih.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded with Federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 22 TC 11 Z9 11 U1 0 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2011 VL 47 IS 23 BP 6710 EP 6712 DI 10.1039/c1cc12130h PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 770UC UT WOS:000291113000059 PM 21556407 ER PT J AU Xing, RJ Liu, G Quan, QM Bhirde, A Zhang, GF Jin, A Bryant, LH Zhang, A Liang, A Eden, HS Hou, YL Chen, XY AF Xing, Ruijun Liu, Gang Quan, Qimeng Bhirde, Ashwinkumar Zhang, Guofeng Jin, Albert Bryant, L. Henry Zhang, Angela Liang, Amy Eden, Henry S. Hou, Yanglong Chen, Xiaoyuan TI Functional MnO nanoclusters for efficient siRNA delivery SO CHEMICAL COMMUNICATIONS LA English DT Article ID MESENCHYMAL STEM-CELLS; NANOPARTICLES; COMPLEXES; CANCER AB A non-viral gene delivery nanovehicle based on Alkyl-PEI2k capped MnO nanoclusters was synthesized via a simple, facile method and used for efficient siRNA delivery and magnetic resonance imaging. C1 [Xing, Ruijun; Hou, Yanglong] Peking Univ, Dept Mat Sci & Engn, Coll Engn, Beijing 100871, Peoples R China. [Xing, Ruijun; Liu, Gang; Quan, Qimeng; Bhirde, Ashwinkumar; Zhang, Angela; Liang, Amy; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Liu, Gang] N Sichuan Med Coll, Affiliated Hosp, Dept Radiol, Sichuan Key Lab Med Imaging, Nanchong 63700, Peoples R China. [Zhang, Guofeng; Jin, Albert; Eden, Henry S.] NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. [Bryant, L. Henry] NIH, Lab Diagnost Radiol Res CC, Bethesda, MD 20892 USA. RP Hou, YL (reprint author), Peking Univ, Dept Mat Sci & Engn, Coll Engn, Beijing 100871, Peoples R China. EM hou@pku.edu.cn; shawn.chen@nih.gov RI Hou, Yanglong/B-8241-2012; Hou, Yanglong/B-8688-2012; OI Jin, Albert/0000-0003-3826-1081 FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH); National Science Foundation of China (NSFC) [81028009, 51172005]; Chinese Scholarship Council (CSC); National Basic Research Program of China [2010CB934602]; China [81101101, 2011JQ0032] FX This work was supported in part by the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) and the International Cooperative Program of the National Science Foundation of China (NSFC) (81028009). R. X. was partially supported by the Chinese Scholarship Council (CSC) and NSFC (51172005), the National Basic Research Program of China (2010CB934602). G.L. was partially supported by projects from China (81101101 & 2011JQ0032). NR 21 TC 25 Z9 26 U1 0 U2 25 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2011 VL 47 IS 44 BP 12152 EP 12154 DI 10.1039/c1cc15408g PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 839CR UT WOS:000296342800035 PM 21991584 ER PT J AU Kobayashi, H Longmire, MR Ogawa, M Choyke, PL AF Kobayashi, Hisataka Longmire, Michelle R. Ogawa, Mikako Choyke, Peter L. TI Rational chemical design of the next generation of molecular imaging probes based on physics and biology: mixing modalities, colors and signals SO CHEMICAL SOCIETY REVIEWS LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; GROWTH-FACTOR RECEPTOR; IRON-OXIDE NANOPARTICLES; MRI CONTRAST AGENTS; PHOTOINDUCED ELECTRON-TRANSFER; CELL-PENETRATING PEPTIDES; DUAL-ENERGY CT; BIOTINYLATED MONOCLONAL-ANTIBODY; ACTIVATABLE FLUORESCENCE PROBES; NEPHROGENIC SYSTEMIC FIBROSIS AB In recent years, numerous in vivo molecular imaging probes have been developed. As a consequence, much has been published on the design and synthesis of molecular imaging probes focusing on each modality, each type of material, or each target disease. More recently, second generation molecular imaging probes with unique, multi-functional, or multiplexed characteristics have been designed. This critical review focuses on (i) molecular imaging using combinations of modalities and signals that employ the full range of the electromagnetic spectra, (ii) optimized chemical design of molecular imaging probes for in vivo kinetics based on biology and physiology across a range of physical sizes, (iii) practical examples of second generation molecular imaging probes designed to extract complementary data from targets using multiple modalities, color, and comprehensive signals (277 references). C1 [Kobayashi, Hisataka; Longmire, Michelle R.; Ogawa, Mikako; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, NIH, Bldg 10,Room B3B69,MSC 1088,10 Ctr Dr, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 277 TC 105 Z9 106 U1 11 U2 97 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0306-0012 J9 CHEM SOC REV JI Chem. Soc. Rev. PY 2011 VL 40 IS 9 BP 4626 EP 4648 DI 10.1039/c1cs15077d PG 23 WC Chemistry, Multidisciplinary SC Chemistry GA 806ZY UT WOS:000293858500013 PM 21607237 ER PT B AU Klein, HG AF Klein, Harvey G. BE Mozzarelli, A Bettati, S TI Red-cell Transfusion in Clinical Practice SO CHEMISTRY AND BIOCHEMISTRY OF OXYGEN THERAPEUTICS: FROM TRANSFUSION TO ARTIFICIAL BLOOD LA English DT Article; Book Chapter ID BLOOD-TRANSFUSION; CRITICALLY-ILL; WHOLE-BLOOD; MORTALITY; SURVIVAL; MEDICINE; STORAGE; DISEASE; ANEMIA; CARE C1 NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Klein, HG (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. NR 32 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-119-97543-4; 978-0-470-68668-3 PY 2011 BP 213 EP 220 D2 10.1002/9781119975427 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA5XQ UT WOS:000337054800016 ER PT S AU Guha, R AF Guha, Rajarshi BE Bajorath, J TI The Ups and Downs of Structure-Activity Landscapes SO CHEMOINFORMATICS AND COMPUTATIONAL CHEMICAL BIOLOGY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE QSAR; Glucocorticoid; Melanocortin; Activity cliff ID HUMAN MELANOCORTIN-4 RECEPTOR; MOLECULAR COMPLEXITY; ACTIVITY CLIFFS; INDEX; SAR; DIHYDROQUINOLINE; DISCOVERY; AGONISTS; QSAR AB In this chapter we discuss the landscape view of structure activity relationships (SARs) The motivation for such a view is that SARs come in a variety of forms, such as those where small changes in structure lead to small changes in activity or where small structural lead to significant changes in activity (also termed activity cliffs) Thus, an SAR dataset is viewed as a landscape comprised of smooth plains, rolling hills, and jagged gorges We review the history of this view and early quantitative approaches that attempted to encode the landscape We then discuss some recent developments that directly characterize structure activity landscapes, in one case with the goal of highlighting activity cliffs while the other allows one to resolve different types of SAR that may be present in a dataset We highlight sonic applications of these approaches, such as predictive model development and SAR elucidation, to SAR datasets obtained from the literature Finally, we conclude with a summary of the landscape approach and why it provides an intuitive and rigorous alternative to standard views of structure activity data C1 NIH Chem Genom Ctr, Rockville, MD USA. RP Guha, R (reprint author), NIH Chem Genom Ctr, Rockville, MD USA. FU Intramural NIH HHS [ZIB HG200319-07] NR 20 TC 10 Z9 10 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-838-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 672 BP 101 EP 117 DI 10.1007/978-1-60761-839-3_3 D2 10.1007/978-1-60761-839-3 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BRE04 UT WOS:000282464300003 PM 20838965 ER PT J AU Yerys, BE Wallace, GL Jankowski, KF Bollich, A Kenworthy, L AF Yerys, Benjamin E. Wallace, Gregory L. Jankowski, Kathryn F. Bollich, Angela Kenworthy, Lauren TI Impaired Consonant Trigrams Test (CTT) performance relates to everyday working memory difficulties in children with Autism Spectrum Disorders SO CHILD NEUROPSYCHOLOGY LA English DT Article DE Autism Spectrum Disorder; Divided attention; Executive function; Asperger's Syndrome; Working memory ID EXECUTIVE FUNCTION; DIVIDED ATTENTION; DEVELOPMENTAL DISORDERS; DIAGNOSTIC INTERVIEW; VARIABILITY; PROFILES; SYMPTOMS; CAPACITY; BEHAVIOR; DEFICITS AB Individuals with Autism Spectrum Disorders (ASD) often struggle with complex tasks, such as those requiring divided attention (simultaneously completing two independent tasks) that also place high demands on working memory. Prior research shows that divided attention is impaired in adults and children with ASD and is related to ASD and comorbid attention deficit/hyperactivity disorder (ADHD) symptoms, but the impact on everyday functioning is unclear. Because ADHD symptoms are associated with poor divided attention and working memory performance in children with ASD, we also examined ADHD symptoms as moderators of divided attention performance. We examined performance on the Consonant Trigrams Test (CTT) between high-functioning 8- to 13-year-olds with ASD (n=28) and typically developing controls (n=18) matched on age and IQ. In the ASD group, we also correlated performance with ADHD symptoms and behavior ratings of everyday working memory. CTT performance in children with ASD was significantly worse than in matched controls. A significant correlation between CTT performance and everyday working memory was observed, but CTT performance was not related to comorbid ADHD symptoms in the ASD group. Divided attention with high working-memory demands is a relative weakness in children with high-functioning ASD; this weakness relates to everyday functioning, and it is independent from ADHD symptoms. That ADHD symptoms are not associated with divided attention performance is inconsistent with one prior investigation, which likely results from using different divided attention tasks in the two studies. C1 [Yerys, Benjamin E.; Jankowski, Kathryn F.; Bollich, Angela; Kenworthy, Lauren] Childrens Natl Med Ctr, Childrens Res Inst, Ctr Neurosci, Washington, DC 20010 USA. [Yerys, Benjamin E.; Jankowski, Kathryn F.; Bollich, Angela; Kenworthy, Lauren] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Washington, DC 20010 USA. [Yerys, Benjamin E.; Bollich, Angela; Kenworthy, Lauren] George Washington Univ, Sch Med & Hlth Sci, Dept Psychiat & Behav Sci, Washington, DC 20052 USA. [Wallace, Gregory L.; Kenworthy, Lauren] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Yerys, BE (reprint author), Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, 15245 Shady Grove Rd,Suite 350, Rockville, MD 20850 USA. EM byerys@cnmc.org OI Wallace, Gregory/0000-0003-0329-5054 FU BRIEF; Frederick and Elizabeth Singer Foundation; Gudelsky Foundation; Studies for the Advancement of Autism Research and Treatment (STAART: NIMH) [U54 MH066417]; Intellectual and Developmental Disabilities Research Center at Children's National Medical Center (NIH IDDRC) [P30HD40677]; General Clinic Research Center (NIH GCRC) [M01-RR13297]; NIH, National Institute of Mental Health FX We thank the children and families that offered their time and energy for the current study. One author (LK) receives financial compensation from the BRIEF. There are no conflicts of interest, financial or otherwise, for the remaining authors involved directly or indirectly with this article. This work was supported by the Frederick and Elizabeth Singer Foundation, the Gudelsky Foundation, and the Studies for the Advancement of Autism Research and Treatment (STAART: NIMH U54 MH066417) for supporting data collection. BEY, and in part this work, was supported by the Intellectual and Developmental Disabilities Research Center at Children's National Medical Center (NIH IDDRC P30HD40677) and the General Clinic Research Center (NIH GCRC M01-RR13297). GLW was supported by the Intramural Program of the NIH, National Institute of Mental Health. NR 31 TC 5 Z9 6 U1 2 U2 8 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0929-7049 J9 CHILD NEUROPSYCHOL JI Child Neuropsychol. PY 2011 VL 17 IS 4 BP 391 EP 399 DI 10.1080/09297049.2010.547462 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 885OG UT WOS:000299787900005 PM 21390918 ER PT J AU McNally, JG AF McNally, James G. TI Foreword. Biophysics in chromatin structure and nuclear dynamics SO CHROMOSOME RESEARCH LA English DT Editorial Material C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP McNally, JG (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, 41 Lib Dr, Bethesda, MD 20892 USA. EM mcnallyj@mail.nih.gov NR 0 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 EI 1573-6849 J9 CHROMOSOME RES JI Chromosome Res. PD JAN PY 2011 VL 19 IS 1 BP 1 EP 3 DI 10.1007/s10577-010-9173-4 PG 3 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 749DW UT WOS:000289443700001 PM 21190131 ER PT S AU Gardner, EL AF Gardner, Eliot L. BE Clark, MR Treisman, GJ TI Addiction and Brain Reward and Antireward Pathways SO CHRONIC PAIN AND ADDICTION SE Advances in Psychosomatic Medicine LA English DT Article; Book Chapter ID GAMMA-VINYL-GABA; CONDITIONED PLACE PREFERENCE; CORTICOTROPIN-RELEASING-FACTOR; NUCLEUS-ACCUMBENS DOPAMINE; OPPONENT-PROCESS THEORY; DRUG-SEEKING BEHAVIOR; LONG-TERM DEPRESSION; INTRACRANIAL SELF-STIMULATION; COCAINE-INDUCED REINSTATEMENT; SUBSTANCE USE DISORDERS AB Addictive drugs have in common that they are voluntarily self-administered by laboratory animals (usually avidly), and that they enhance the functioning of the reward circuitry of the brain (producing the 'high' that the drug user seeks) The core reward circuitry consists of an 'in-series' circuit linking the ventral tegmental area, nucleus accumbens and ventral pallidum via the medial forebrain bundle Although originally believed to simply encode the set point of hedonic tone, these circuits are now believed to be functionally far more complex, also encoding attention, expectancy of reward, disconfirmation of reward expectancy, and incentive motivation. 'Hedonic dysregulation' within these circuits may lead to addiction The 'second-stage' dopaminergic component in this reward circuitry is the crucial addictive-drug-sensitive component All addictive drugs have in common that they enhance (directly or indirectly or even transsynaptically) dopaminergic reward synaptic function in the nucleus accumbens Drug self-administration is regulated by nucleus accumbens dopamine levels, and is done to keep nucleus accumbens dopamine within a specific elevated range (to maintain a desired hedonic level) For some classes of addictive drugs (e g opiates), tolerance to the euphoric effects develops with chronic use. Postuse dysphoria then comes to dominate reward circuit hedonic tone, and addicts no longer use drugs to get high, but simply to get back to normal ('get straight'). The brain circuits mediating the pleasurable effects of addictive drugs are anatomically, neurophysiologically and neurochemically different from those mediating physical dependence, and from those mediating craving and relapse There are important genetic variations in vulnerability to drug addiction, yet environmental factors such as stress and social defeat also alter brain-reward mechanisms in such a manner as to impart vulnerability to addiction In short, the 'bio-psycho-social' model of etiology holds very well for addiction. Addiction appears to correlate with a hypodopaminergic dysfunctional state within the reward circuitry of the brain. Neuroimaging studies in humans add credence to this hypothesis Credible evidence also implicates serotonergic, opioid, endocannabinoid, GABAergic and glutamatergic mechanisms in addiction Critically, drug addiction progresses from occasional recreational use to impulsive use to habitual compulsive use This correlates with a progression from reward-driven to habit-driven drug-seeking behavior. This behavioral progression correlates with a neuroanatomical progression from ventral striatal (nucleus accumbens) to dorsal striatal control over drug-seeking behavior The three classical sets of craving and relapse triggers are (a) reexposure to addictive drugs, (b) stress, and (c) reexposure to environmental cues (people, places, things) previously associated with drug-taking behavior. Drug-triggered relapse involves the nucleus accumbens and the neurotransmitter dopamine. Stress-triggered relapse involves (a) the central nucleus of the amygdala, the bed nucleus of the stria terminal's, and the neurotransmitter corticotrophin-releasing factor, and (b) the lateral tegmental noradrenergic nuclei of the brain stem and the neurotransmitter norepinephrine. Cue-triggered relapse involves the basolateral nucleus of the amygdala, the hippocampus and the neurotransmitter glutamate Knowledge of the neuroanatomy, neurophysiology, neurochemistry and neuropharmacology of addictive drug action in the brain is currently producing a variety of strategies for harmacotherapeutic treatment of drug addiction, some of which appear promising. Copyright (C) 2011 S Karger AG, Basel C1 NIDA, Neuropsychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Gardner, EL (reprint author), NIDA, Neuropsychopharmacol Sect, Intramural Res Program, NIH, BRC Bldg,Room 05-A707,251 Bayview, Baltimore, MD 21224 USA. FU Intramural NIH HHS [Z99 DA999999] NR 278 TC 84 Z9 87 U1 12 U2 61 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3268 BN 978-3-8055-9725-8 J9 ADV PSYCHOSOM MED JI Adv.Psychosom.Med. PY 2011 VL 30 BP 22 EP 60 PG 39 WC Anesthesiology; Substance Abuse; Clinical Neurology; Psychiatry SC Anesthesiology; Substance Abuse; Neurosciences & Neurology; Psychiatry GA BUX72 UT WOS:000290637800003 PM 21508625 ER PT J AU Jain, A McClelland, RL Polak, JF Shea, S Burke, GL Bild, DE Watson, KE Budoff, MJ Liu, KA Post, WS Folsom, AR Lima, JAC Bluemke, DA AF Jain, Aditya McClelland, Robyn L. Polak, Joseph F. Shea, Steven Burke, Gregory L. Bild, Diane E. Watson, Karol E. Budoff, Matthew J. Liu, Kiang Post, Wendy S. Folsom, Aaron R. Lima, Joao A. C. Bluemke, David A. TI Cardiovascular Imaging for Assessing Cardiovascular Risk in Asymptomatic Men Versus Women The Multi-Ethnic Study of Atherosclerosis (MESA) SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE imaging; cardiovascular diseases; sex ID CORONARY-ARTERY CALCIUM; LEFT-VENTRICULAR HYPERTROPHY; AMERICAN-HEART-ASSOCIATION; INTIMA-MEDIA THICKNESS; COMPUTED-TOMOGRAPHY; ISCHEMIC-STROKE; DISEASE; PREDICTION; SEX; CALCIFICATION AB Background-Coronary artery calcium (CAC), carotid intima-media thickness, and left ventricular (LV) mass and geometry offer the potential to characterize incident cardiovascular disease (CVD) risk in clinically asymptomatic individuals. The objective of the study was to compare these cardiovascular imaging measures for their overall and sex-specific ability to predict CVD. Methods and Results-The study sample consisted of 4965 Multi-Ethnic Study of Atherosclerosis participants (48% men; mean age, 62+/-10 years). They were free of CVD at baseline and were followed for a median of 5.8 years. There were 297 CVD events, including 187 coronary heart disease (CHD) events, 65 strokes, and 91 heart failure (HF) events. CAC was most strongly associated with CHD (hazard ratio [HR], 2.3 per 1 SD; 95% CI, 1.9 to 2.8) and all CVD events (HR, 1.7; 95% CI, 1.5 to 1.9). Most strongly associated with stroke were LV mass (HR, 1.3; 95% CI, 1.1 to 1.7) and LV mass/volume ratio (HR, 1.3; 95% CI, 1.1 to 1.6). LV mass showed the strongest association with HF (HR, 1.8; 95% CI, 1.6 to 2.1). There were no significant interactions for imaging measures with sex and ethnicity for any CVD outcome. Compared with traditional risk factors alone, overall risk prediction (C statistic) for future CHD, HF, and all CVD was significantly improved by adding CAC, LV mass, and CAC, respectively (all P<0.05). Conclusions-There was no evidence that imaging measures differed in association with incident CVD by sex. CAC was most strongly associated with CHD and CVD; LV mass and LV concentric remodeling best predicted stroke; and LV mass best predicted HF. (Circ Cardiovasc Imaging. 2011;4:8-15.) C1 [Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Jain, Aditya] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [McClelland, Robyn L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Polak, Joseph F.] Tufts Univ New England Med Ctr, Dept Radiol, Boston, MA USA. [Shea, Steven] Columbia Univ, Dept Med, Sch Med, New York, NY USA. [Shea, Steven] Columbia Univ, Dept Epidemiol, Sch Med, New York, NY USA. [Shea, Steven] Columbia Univ, Dept Med, Sch Publ Hlth, New York, NY USA. [Shea, Steven] Columbia Univ, Dept Epidemiol, Sch Publ Hlth, New York, NY USA. [Burke, Gregory L.] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. [Bild, Diane E.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Watson, Karol E.] Univ Calif Los Angeles, Sch Med, Div Cardiol, Los Angeles, CA 90024 USA. [Budoff, Matthew J.] Harbor UCLA Med Ctr, Div Cardiol, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Liu, Kiang] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Post, Wendy S.; Lima, Joao A. C.] Johns Hopkins Univ, Div Cardiol, Baltimore, MD USA. [Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. RP Bluemke, DA (reprint author), NIH, Ctr Clin, 10 Ctr Dr,Rm 10-1C355, Bethesda, MD 20892 USA. EM bluemked@nih.gov OI Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute [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-95167, N01-HC-95168, N01-HC-95169] FX This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute. NR 26 TC 40 Z9 40 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD JAN PY 2011 VL 4 IS 1 BP 8 EP 15 DI 10.1161/CIRCIMAGING.110.959403 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 707XE UT WOS:000286323700003 PM 21068189 ER PT J AU Qiao, H Zhang, HL Yamanaka, S Patel, VV Petrenko, NB Huang, B Muenz, LR Ferrari, VA Boheler, KR Zhou, R AF Qiao, Hui Zhang, Hualei Yamanaka, Satoshi Patel, Vickas V. Petrenko, Nataliya B. Huang, Bin Muenz, Larry R. Ferrari, Victor A. Boheler, Kenneth R. Zhou, Rong TI Long-Term Improvement in Postinfarct Left Ventricular Global and Regional Contractile Function Is Mediated by Embryonic Stem Cell-Derived Cardiomyocytes SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE cardiac MRI; embryonic stem cells; left ventricular remodeling; left ventricular wall motion; myocardial infarction ID MYOCARDIAL TISSUE TRACKING; RAT HEARTS; INFARCTED MYOCARDIUM; SPATIAL MODULATION; TRANSPLANTATION; CINE; DIFFERENTIATION; MOTION; GENE; MRI AB Background-Pluripotent stem cells represent one promising source for cellular cardiomyoplasty. In this study, we used cardiac magnetic resonance to examine the ability of highly enriched cardiomyocytes (CMs) derived from murine embryonic stem cells (ESC) to form grafts and improve contractile function of infarcted rat hearts. Methods and Results-Highly enriched ESC-CMs were obtained by inducing cardiac differentiation of ESCs stably expressing a cardiac-restricted puromycin resistance gene. At the time of transplantation, enriched ESC-CMs expressed cardiac-specific markers and markers of developing CMs, but only 6% of them were proliferating. A growth factor-containing vehicle solution or ESC-CMs (5 to 10 million) suspended in the same solution was injected into athymic rat hearts 1 week after myocardial infarction. Initial infarct size was measured by cardiac magnetic resonance 1 day after myocardial infarction. Compared with vehicle treatment, treatment with ESC-CMs improved global systolic function 1 and 2 months after injection and significantly increased contractile function in initially infarcted areas and border zones. Immunohistochemistry confirmed successful engraftment and the persistence of alpha-actinin-positive ESC-CMs that also expressed alpha-smooth muscle actin. Connexin-43-positive sites were observed between grafted ESC-CMs but only rarely between grafted and host CMs. No teratomas were observed in any of the animals. Conclusions-Highly enriched and early-stage ESC-CMs were safe, formed stable grafts, and mediated a long-term recovery of global and regional myocardial contractile function after infarction. (Circ Cardiovasc Imaging. 2011;4:33-41.) C1 [Qiao, Hui; Zhang, Hualei; Huang, Bin; Zhou, Rong] Univ Penn, Labs Mol Imaging, Dept Radiol, Philadelphia, PA 19104 USA. [Zhang, Hualei; Zhou, Rong] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [Patel, Vickas V.; Petrenko, Nataliya B.; Ferrari, Victor A.] Univ Penn, Dept Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA. [Qiao, Hui; Zhang, Hualei; Patel, Vickas V.; Petrenko, Nataliya B.; Huang, Bin; Ferrari, Victor A.; Zhou, Rong] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Muenz, Larry R.] Larry R Muenz & Associates Biostat Consulting Stu, Gaithersburg, MD USA. [Yamanaka, Satoshi; Boheler, Kenneth R.] NIA, NIH, Baltimore, MD 21224 USA. RP Zhou, R (reprint author), Univ Penn, Labs Mol Imaging, Dept Radiol, B6 Blockley Hall,422 Curie Blvd, Philadelphia, PA 19104 USA. EM zhou@rad.upenn.edu FU National Institutes of Health [R21EB-2473, R01-HL081185]; National Institutes of Health, National Institute on Aging FX This study was supported by National Institutes of Health grants R21EB-2473 and R01-HL081185 (to R.Z.) and the Intramural Research Program of the National Institutes of Health, National Institute on Aging (to K.R.B.). NR 40 TC 13 Z9 15 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD JAN PY 2011 VL 4 IS 1 BP 33 EP U53 DI 10.1161/CIRCIMAGING.110.957431 PG 12 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 707XE UT WOS:000286323700006 PM 21059858 ER PT J AU Hsich, E Gorodeski, EZ Blackstone, EH Ishwaran, H Lauer, MS AF Hsich, Eileen Gorodeski, Eiran Z. Blackstone, Eugene H. Ishwaran, Hemant Lauer, Michael S. TI Identifying Important Risk Factors for Survival in Patient With Systolic Heart Failure Using Random Survival Forests SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE heart failure; prognosis; statistics; survival analyses ID AMBULATORY PATIENTS; PREDICT SURVIVAL; CLINICAL INDEX; MORTALITY; MODEL; SCORE; CLASSIFICATION; ASSOCIATION; DYSFUNCTION; SELECTION AB Background-Heart failure survival models typically are constructed using Cox proportional hazards regression. Regression modeling suffers from a number of limitations, including bias introduced by commonly used variable selection methods. We illustrate the value of an intuitive, robust approach to variable selection, random survival forests (RSF), in a large clinical cohort. RSF are a potentially powerful extensions of classification and regression trees, with lower variance and bias. Methods and Results-We studied 2231 adult patients with systolic heart failure who underwent cardiopulmonary stress testing. During a mean follow-up of 5 years, 742 patients died. Thirty-nine demographic, cardiac and noncardiac comorbidity, and stress testing variables were analyzed as potential predictors of all-cause mortality. An RSF of 2000 trees was constructed, with each tree constructed on a bootstrap sample from the original cohort. The most predictive variables were defined as those near the tree trunks (averaged over the forest). The RSF identified peak oxygen consumption, serum urea nitrogen, and treadmill exercise time as the 3 most important predictors of survival. The RSF predicted survival similarly to a conventional Cox proportional hazards model (out-of-bag C-index of 0.705 for RSF versus 0.698 for Cox proportional hazards model). Conclusions-An RSF model in a cohort of patients with heart failure performed as well as a traditional Cox proportional hazard model and may serve as a more intuitive approach for clinicians to identify important risk factors for all-cause mortality. (Circ Cardiovasc Qual Outcomes. 2011;4:39-45.) C1 [Lauer, Michael S.] NHLBI, Div Cardiovasc Sci, NIH, Rockledge Ctr 2, Bethesda, MD 20892 USA. [Hsich, Eileen; Gorodeski, Eiran Z.; Blackstone, Eugene H.] Inst Heart & Vasc, Cleveland, OH USA. [Blackstone, Eugene H.; Ishwaran, Hemant] Dept Quantitat Hlth Sci, Cleveland, OH USA. [Hsich, Eileen; Blackstone, Eugene H.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. RP Lauer, MS (reprint author), NHLBI, Div Cardiovasc Sci, NIH, Rockledge Ctr 2, 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA. EM lauerm@nhlbi.nih.gov RI Lauer, Michael/L-9656-2013; OI Lauer, Michael/0000-0002-9217-8177; Gorodeski, Eiran/0000-0003-3756-8831 FU Health Resources and Services Administration [234-2005-370011C]; American Heart Association (AHA) [0730307N]; National Heart, Lung, and Blood Institute (NHLBI) [8324207, HHSN268200800026C] FX This work was supported in part by the Health Resources and Services Administration contract 234-2005-370011C; American Heart Association (AHA) Scientist Development Grant 0730307N; and the National Heart, Lung, and Blood Institute (NHLBI) CAN #8324207 and contract HHSN268200800026C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the AHA, NHLBI, or Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. government. NR 30 TC 23 Z9 23 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2011 VL 4 IS 1 BP 39 EP 45 DI 10.1161/CIRCOUTCOMES.110.939371 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 707TS UT WOS:000286311700009 PM 21098782 ER PT J AU Lee, DS Gona, P Albano, I Larson, MG Benjamin, EJ Levy, D Kannel, WB Vasan, RS AF Lee, Douglas S. Gona, Philimon Albano, Irene Larson, Martin G. Benjamin, Emelia J. Levy, Daniel Kannel, William B. Vasan, Ramachandran S. TI A Systematic Assessment of Causes of Death After Heart Failure Onset in the Community Impact of Age at Death, Time Period, and Left Ventricular Systolic Dysfunction SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; death; cause of death; cardiovascular diseases; epidemiology ID EJECTION FRACTION; ELDERLY-PATIENTS; DISEASE; FRAMINGHAM; MORTALITY; TRIAL; DIE; MORBIDITY; OUTCOMES; HEALTH AB Background-The high mortality rate in patients with heart failure (HF) is influenced by presence of multiple comorbidities. Data are limited on the relative contributions of cardiovascular versus noncardiovascular diseases to death in individuals with HF in the community. Methods and Results-We examined the incidence and predictors of cardiovascular versus noncardiovascular death in participants with HF in the Framingham Heart Study. Underlying, immediate, and contributing causes of death (3 key elements of the World Health Organization classification) were adjudicated by a 3-physician review panel. During 1971 to 2004, 1025 participants with HF died (499 men, mean [SD] age at death 79 [11] years), including 463 participants with left ventricular ejection fraction (LVEF) data. Cardiovascular disease was the cause of death in 66.1% overall. Stratified by LVEF, cardiovascular deaths occurred in 44.5% and 69.9% of those with preserved and reduced LVEF, respectively. Presence of reduced LVEF increased the risk of cardiovascular death, with odds ratios of 3.16 (95% confidence interval [CI], 1.73 to 5.78) in men and 2.39 (95% CI, 1.39 to 4.08) in women. Prior myocardial infarction was associated with increased cardiovascular death in women with HF (odds ratio, 1.87; 95% CI, 1.10 to 3.16) but not in men. The risk of cardiovascular disease death decreased in women (odds ratio after 1980, 0.41; 95% CI, 0.24 to 0.69) and men (odds ratio, 0.66; 95% CI, 0.41 to 1.07, P = 0.095) with HF over time. Infections and kidney disease emerged as key immediate and contributing causes of death, respectively. Conclusions-Individuals with HF in the community often experience cardiovascular death, but noncardiovascular disease also contributes significantly especially among those with preserved LVEF. (Circ Heart Fail. 2011;4:36-43.) C1 [Gona, Philimon; Larson, Martin G.; Benjamin, Emelia J.; Levy, Daniel; Kannel, William B.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Lee, Douglas S.] Univ Toronto, Inst Clin Evaluat Sci, Toronto, ON, Canada. [Lee, Douglas S.] Univ Toronto, Toronto Gen Hosp, Toronto, ON M5G 1L7, Canada. [Albano, Irene] Univ Padua, Dept Med & Surg Sci, Padua, Italy. [Gona, Philimon; Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiovasc Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu RI Lee, Douglas/J-4315-2014; OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Institutes of Health/National Heart, Lung, and Blood Institute [N01-HC-25195, 2K24HL04334]; Canadian Institutes of Health Research [MOP 86718] FX This study was supported by the National Institutes of Health/National Heart, Lung, and Blood Institute Contract N01-HC-25195 and 2K24HL04334 (Dr Vasan) and grant MOP 86718 from the Canadian Institutes of Health Research. Dr Lee was supported by a clinician-scientist award from the Canadian Institutes of Health Research. NR 31 TC 35 Z9 37 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2011 VL 4 IS 1 BP 36 EP U85 DI 10.1161/CIRCHEARTFAILURE.110.957480 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 707UC UT WOS:000286312900010 PM 21071547 ER PT S AU Van Itallie, CM Anderson, JM AF Van Itallie, Christina M. Anderson, James M. BE Turksen, K TI Measuring Size-Dependent Permeability of the Tight Junction Using PEG Profiling SO CLAUDINS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Tight junction; Claudin; Paracellular permeability; Apparent permeability (P-app); Polyethylene glycol (PEG) profiling; Epithelial transport ID BARRIER; TRANSPORT AB Tight junctions restrict the paracellular movement of ions, solutes, drugs, and larger material across epithelia and endothelia. For practical purposes, the barrier can be modeled as having two components. The first is a system of small 4 angstrom radius pores lined or created by claudins. The pores show variable ionic charge selectivity and electrical resistance based on the pattern of claudin proteins expressed in a particular junction. Transport of compounds that are larger than 4 angstrom arc not subject to discrimination based on size or charge; they arc likely passing through transient breaks in the tight junction barrier. The magnitude of the first and second pathways varies among epithelia and is altered in response to physiological and pathological stimuli. Unfortunately, most studies of permeability use few tracer sizes and thus provide limited information on size-dependent changes in permeability. Here we describe a method for simultaneously measuring the size-dependence of apparent permeability using a continuous series of polyethylene polymers which allows quantification of both the pore and leak pathways. C1 [Van Itallie, Christina M.; Anderson, James M.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Van Itallie, CM (reprint author), NHLBI, NIH, South Dr, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 OD999999] NR 13 TC 8 Z9 8 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-184-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 762 BP 1 EP 11 DI 10.1007/978-1-61779-185-7_1 D2 10.1007/978-1-61779-185-7 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BVV48 UT WOS:000292894300001 PM 21717345 ER PT J AU O'Grady, NP Chertow, DS AF O'Grady, Naomi P. Chertow, Daniel S. TI Managing bloodstream infections in patients who have short-term central venous catheters SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Review ID STAPHYLOCOCCUS-AUREUS BACTEREMIA; ENTEROCOCCAL BACTEREMIA; RISK-FACTORS; CLINICAL-FEATURES; AMPHOTERICIN-B; BACTERICIDAL ACTIVITY; HOSPITALIZED-PATIENTS; INVASIVE CANDIDIASIS; VANCOMYCIN-RESISTANT; RANDOMIZED-TRIAL AB Catheter-related bloodstream infections can be complicated to manage, but a growing body of evidence supports specific recommendations. In 2009, the Infectious Diseases Society of America published updated guidelines for the diagnosis and management of all intravascular catheter-related infections. Here we provide a focused review on the management of bloodstream infections in adult patients with short-term (not surgically implanted and not tunneled) central venous catheters, including peripherally inserted central catheters. This review should serve as a ready reference for providers (eg, hospitalists, surgeons, physician assistants, nurse practitioners, intensivists) managing adult patients with short-term central venous catheters in place. C1 [O'Grady, Naomi P.; Chertow, Daniel S.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [O'Grady, Naomi P.] NIH, Procedures Serv, Bethesda, MD 20892 USA. [O'Grady, Naomi P.] NIH, Vasc Access Serv, Bethesda, MD 20892 USA. [O'Grady, Naomi P.] NIH, Conscious Sedat Serv, Bethesda, MD 20892 USA. RP O'Grady, NP (reprint author), NIH, Dept Crit Care Med, Bldg 10,Room 2C142,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. EM nogrady@mail.cc.nih.gov NR 59 TC 9 Z9 11 U1 1 U2 2 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD JAN PY 2011 VL 78 IS 1 BP 10 EP 17 DI 10.3949/ccjm.77a.10015 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 718GA UT WOS:000287107900002 PM 21199902 ER PT J AU Fisher, RW Reed, JL Snoy, PJ Mikolajczyk, MG Bray, M Scott, DE Kennedy, MC AF Fisher, R. W. Reed, J. L. Snoy, P. J. Mikolajczyk, M. G. Bray, M. Scott, D. E. Kennedy, M. C. TI Postexposure Prevention of Progressive Vaccinia in SCID Mice Treated with Vaccinia Immune Globulin SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID VIRUS-INFECTION; ECZEMA VACCINATUM; SMALLPOX VACCINEE; MAST-CELLS; CIDOFOVIR; PROTECTION; EFFICACY; RECEPTOR; MODEL; IGG AB A recently reported case of progressive vaccinia (PV) in an immunocompromised patient has refocused attention on this condition. Uniformly fatal prior to the licensure of vaccinia immune globulin (VIG) in 1978, PV was still fatal in about half of VIG-treated patients overall, with a greater mortality rate in infants and children. Additional therapies would be needed in the setting of a smallpox bioterror event, since mass vaccination following any variola virus release would inevitably result in exposure of immunocompromised people through vaccination or contact with vaccinees. Well-characterized animal models of disease can support the licensure of new products when human studies are not ethical or feasible, as in the case of PV. We chose vaccinia virus-scarified SCID mice to model PV. As in immunocompromised humans, vaccinia virus-scarified SCID animals develop enlarging primary lesions with minimal or no inflammation, eventual distal virus spread, and lethal outcomes if left untreated. Postexposure treatment with VIG slowed disease progression, caused local lesion regression, and resulted in the healthy survival of most of the mice for more than 120 days. Combination treatment with VIG and topical cidofovir also resulted in long-term disease-free survival of most of the animals, even when initiated 7 days postinfection. These results support the possibility that combination treatments may be effective in humans and support using this SCID model of PV to test new antibody therapies and combination therapies and to provide further insights into the pathogenesis and treatment of PV. C1 [Fisher, R. W.; Reed, J. L.; Mikolajczyk, M. G.; Scott, D. E.; Kennedy, M. C.] US FDA, Lab Plasma Derivat, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Snoy, P. J.] US FDA, Div Vet Serv, Off Management, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Bray, M.] NIAID, Integrated Res Facil, NIH, Ft Detrick, MD USA. RP Fisher, RW (reprint author), US FDA, Lab Plasma Derivat, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, HFM-345,1401 Rockville Pike, Rockville, MD 20852 USA. EM Robert.Fisher@fda.hhs.gov FU NIAID for biodefense research FX This work was supported in part by an interagency agreement with NIAID for biodefense research. NR 42 TC 9 Z9 9 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD JAN PY 2011 VL 18 IS 1 BP 67 EP 74 DI 10.1128/CVI.00280-10 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 702BK UT WOS:000285869400006 PM 21106779 ER PT S AU Dunn, BK Jegalian, K Greenwald, P AF Dunn, Barbara K. Jegalian, Karin Greenwald, Peter BE Senn, HJ Otto, F TI Biomarkers for Early Detection and as Surrogate Endpoints in Cancer Prevention Trials: Issues and Opportunities SO CLINICAL CANCER PREVENTION SE Recent Results in Cancer Research LA English DT Proceedings Paper CT 6th International Conference on Clinical Cancer Prevention (SG-CAP 2010) CY MAR 18-20, 2010 CL St Gallen, SWITZERLAND SP Novartis Schweiz AG ID NEGATIVE BREAST-CANCER; SURGICAL ADJUVANT BREAST; SPORADIC COLORECTAL ADENOMAS; BOWEL PROJECT P-1; PROSTATE-CANCER; LUNG-CANCER; PROMOTER HYPERMETHYLATION; MAMMOGRAPHIC DENSITY; POSTMENOPAUSAL WOMEN; RISK-ASSESSMENT AB In orders to improve the early detection and diagnosis of cancer, give more accurate prognoses, stratify individuals by risk, predict response to treatment, and help the transition of basic research into clinical application, biomarkers are needed that accurately represent or predict clinical outcomes. To be useful in trails for chemopreventive agent development, biomarkers must be subject to modulation, easy to obtain and quantify, and have biological meaning, ideally representing steps in well-understood carcinogenic pathways. Though difficult to validate fully, wisely chosen biomarkers in early-phase trails can inform the prioritization of large-scale, long-term trails that measure clinical outcomes. When well-designed, smaller trails using biomarkers as surrogate endpoints should promote faster decisions regarding which targeted preventive agents to pursue, promising greater progress in the personalization of medicine. Biomarkers could become useful in distinguishing indolent from aggressive forms of ductal carcinoma in situ as well as localized invasive breast and prostate cancer, lesions that are often overtreated. Chemopreventive strategies that reduce the progression of early forms of premalignancy can benefit patients not only by reducing their risk of cancer and death from cancer but also by reducing their need for invasive interventions. Genomic and proteomic methods offer the possibility of revealing new potential markers, especially for diseases whose biology is complex or not well understood. Panels of markers may be used to accommodate the molecular heterogencity of cancers. Biomarkers in phase 2 prevention trails of combinations of chemopreventive drugs have been used to demonstrate synergistic action of multiple agents, allowing use of lower doses, with less toxicity, a critical feature of interventions intended for cancer prevention. C1 [Dunn, Barbara K.; Greenwald, Peter] NCI, Basic Prevent Sci Res Grp, Canc Prevent Div, 6130 Execut Boulevard,Room 2056, Bethesda, MD 20892 USA. RP Dunn, BK (reprint author), NCI, Basic Prevent Sci Res Grp, Canc Prevent Div, 6130 Execut Boulevard,Room 2056, Bethesda, MD 20892 USA. EM dunnb@mail.nih.gov; karinjeg@verizon.net; greenwap@mail.nih.gov NR 90 TC 17 Z9 18 U1 0 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 978-3-642-10856-3 J9 RECENT RESULTS CANC JI Rec. Res. Camcer Res. PY 2011 VL 188 BP 21 EP 47 DI 10.1007/978-3-642-10858-7_3 PG 27 WC Oncology SC Oncology GA BWD37 UT WOS:000293617100003 PM 21253787 ER PT J AU Gril, B Palmieri, D Qian, Y Smart, D Ileva, L Liewehr, DJ Steinberg, SM Steeg, PS AF Gril, Brunilde Palmieri, Diane Qian, Yong Smart, DeeDee Ileva, Lilia Liewehr, David J. Steinberg, Seth M. Steeg, Patricia S. TI Pazopanib Reveals a Role for Tumor Cell B-Raf in the Prevention of HER2(+) Breast Cancer Brain Metastasis SO CLINICAL CANCER RESEARCH LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; KINASE; INHIBITOR; MELANOMA; GROWTH; ANGIOGENESIS; PROGRESSION; TRASTUZUMAB; MUTATIONS; THERAPY AB Purpose: Brain metastases of breast cancer contribute significantly to patient morbidity and mortality. We have tested pazopanib, a recently approved antiangiogenic drug that targets VEGFR1, VEGFR2, VEGFR3, PDGFR beta, PDGFR alpha, and c-kit, for prevention of experimental brain metastases and mechanism of action. Experimental Design: In vitro assays included B-Raf enzymatic assays, Western blots, and angiogenesis assays. For in vivo assays, HER2 transfectants of the brain seeking sublines of MDA-MB-231 cells (231-BRHER2) and MCF7 cells (MCF7-HER2-BR3, derived herein) were injected into the left cardiac ventricle of mice and treated with vehicle or pazopanib beginning on day 3 postinjection. Brain metastases were counted histologically, imaged, and immunostained. Results: Treatment with 100 mg/kg of pazopanib resulted in a 73% decline in large 231-BR-HER2 metastases (P < 0.0001) and a 39% decline in micrometastases (P = 0.004). In vitro, pazopanib was directly antiproliferative to 231-BR-HER2 breast cancer cells and inhibited MEK and ERK activation in vitro despite B-Raf and Ras mutations. Enzymatic assays demonstrated that pazopanib directly inhibited the wild type and exon 11 oncogenic mutant, but not the V600E mutant forms of B-Raf. Activation of the B-Raf targets pERK1/2 and pMEK1/2 was decreased in pazopanib-treated brain metastases whereas blood vessel density was unaltered. In the MCF7-HER2-BR3 experimental brain metastasis model, pazopanib reduced overall brain metastasis volume upon magnetic resonance imaging (MRI) by 55% (P = 0.067), without affecting brain metastasis vascular density. Conclusions: The data identify a new activity for pazopanib directly on tumor cells as a pan-Raf inhibitor and suggest its potential for prevention of brain metastatic colonization of HER2(+) breast cancer. Clin Cancer Res; 17(1); 142-53. (C) 2010 AACR. C1 [Gril, Brunilde; Palmieri, Diane; Qian, Yong; Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Smart, DeeDee] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Ileva, Lilia] NCI, Small Anim Imaging Program, Frederick, MD 21701 USA. [Liewehr, David J.; Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Rockville, MD USA. RP Gril, B (reprint author), NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bldg 37,Room 1126, Bethesda, MD 20892 USA. EM grilbrun@mail.nih.gov RI Palmieri, Diane/B-4258-2015 FU National Cancer Institute (NCI); Department of Defense Breast Cancer [W81XWH-062-0033]; GlaxoSmithKline FX P.S.S. receives research support from the Intramural program of the National Cancer Institute (NCI) and by grant W81XWH-062-0033 from the Department of Defense Breast Cancer Research Program. This work was supported by the Intramural program of the National Cancer Institute (NCI), by Grant W81XWH-062-0033 from the Department of Defense Breast Cancer Research Program, and by funding from GlaxoSmithKline. NR 42 TC 38 Z9 38 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2011 VL 17 IS 1 BP 142 EP 153 DI 10.1158/1078-0432.CCR-10-1603 PG 12 WC Oncology SC Oncology GA 702RV UT WOS:000285913600016 PM 21081656 ER PT J AU Karschner, EL Darwin, WD Goodwin, RS Wright, S Huestis, MA AF Karschner, Erin L. Darwin, W. David Goodwin, Robert S. Wright, Stephen Huestis, Marilyn A. TI Plasma Cannabinoid Pharmacokinetics following Controlled Oral Delta(9)-Tetrahydrocannabinol and Oromucosal Cannabis Extract Administration SO CLINICAL CHEMISTRY LA English DT Article ID SINGLE-DOSE KINETICS; MULTIPLE-SCLEROSIS; NEUROPATHIC PAIN; DELTA-9-TETRAHYDROCANNABINOL; EFFICACY; MEDICINE; SMOKING; TOLERABILITY; MARIJUANA; SYMPTOMS AB BACKGROUND: Sativex(R), a cannabis extract oromucosal spray containing Delta(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), is currently in phase III trials as an adjunct to opioids for cancer pain treatment, and recently received United Kingdom approval for treatment of spasticity. There are indications that CBD modulates THC's effects, but it is unclear if this is due to a pharmacokinetic and/or pharmacodynamic interaction. METHODS: Cannabis smokers provided written informed consent to participate in this randomized, controlled, double-blind, double-dummy institutional review board-approved study. Participants received 5 and 15 mg synthetic oral THC, low-dose (5.4 mg THC and 5.0 mg CBD) and high-dose (16.2 mg THC and 15.0 mg CBD) Sativex, and placebo over 5 sessions. CBD, THC, 11-hydroxy-THC, and 11-nor-9-carboxy-THC were quantified in plasma by 2-dimensional GC-MS. Lower limits of quantification were <= 0.25 mu g/L. RESULTS: Nine cannabis smokers completed all 5 dosing sessions. Significant differences (P < 0.05) in maximum plasma concentrations (C-max) and areas under the curve from 0-10.5 h postdose (AUC(0 -> 10.5)) for all analytes were found between low and high doses of synthetic THC and Sativex. There were no statistically significant differences in C-max, time to maximum concentration or in the AUC(0 -> 10.5) between similar oral THC and Sativex doses. Relative bioavailability was calculated to determine the relative rate and extent of THC absorption; 5 and 15 mg oral THC bioavailability was 92.6% (13.1%) and 98.8% (11.0%) of low- and high-dose Sativex, respectively. CONCLUSION: These data suggest that CBD modulation of THC's effects is not due to a pharmacokinetic interaction at these therapeutic doses. (C) 2010 American Association for Clinical Chemistry C1 [Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. [Wright, Stephen] GW Pharma, Salisbury, Wilts, England. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Biomed Res Ctr, 251 Bayview Blvd,Rm 05A721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU National Institute on Drug Abuse, National Institutes of Health FX E.L. Karschner, W.D. Darwin, R.S. Goodwin, and M. A. Huestis, Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. NR 27 TC 45 Z9 45 U1 0 U2 26 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2011 VL 57 IS 1 BP 66 EP 75 DI 10.1373/clinchem.2010.152439 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 699TQ UT WOS:000285686100013 PM 21078841 ER PT J AU van Deventer, HE Mendu, DR Remaley, AT Soldin, SJ AF van Deventer, Hendrick E. Mendu, Damodara R. Remaley, Alan T. Soldin, Steven J. TI Inverse Log-Linear Relationship between Thyroid-Stimulating Hormone and Free Thyroxine Measured by Direct Analog Immunoassay and Tandem Mass Spectrometry SO CLINICAL CHEMISTRY LA English DT Article ID ANALYTE ASSAY FUNCTION; IFCC WORKING GROUP; FREE TRIIODOTHYRONINE; FUNCTION TESTS; NONTHYROIDAL ILLNESS; ILLEGITIMATE TESTS; SERUM; STANDARDIZATION; POPULATIONS; LEGITIMATE AB BACKGROUND: Accurate measurement of free thyroxine (FT(4)) is important for diagnosing and managing thyroid disorders. Most laboratories measure FT(4) by direct analogue immunoassay methods. The validity of these methods have recently been questioned. The inverse log-linear relationship between FT(4) and thyroid-stimulating hormone (TSH) is well described and provides a physiological rationale on which to base an evaluation of FT(4) assays. METHODS: The study included 109 participants for whom FT(4) measurement was requested by their clinician. Samples were selected for inclusion to reflect a wide spectrum of TSH and albumin results. FT(4) and TSH were measured by use of the Siemens Immulite immunoassay (IA). FT(4) was also measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) (MS-FT(4)). RESULTS: The inverse log-linear correlation coefficient between TSH and FT(4) was significantly better (P < 0.0001) for MS-FT(4) (0.84, 95% CI, 0.77-0.88) than for IA-FT(4) (0.45, 95% CI, 0.29-0.59). IA-FT(4) showed a significant correlation with albumin (Spearman correlation coefficient 0.45, 95% CI, 0.29-0.5, P < 0.0001) and thyroxine-binding globulin (TBG) (Spearman correlation coefficient 0.23, 95% CI, 0.05-0.41, P = 0.02). In contrast, FT(4) measurement by LC-MS/MS did not show a significant correlation with albumin or TBG. CONCLUSIONS: The inverse log-linear relationship between FT(4) and TSH was significantly better for FT(4) measured by LC-MS/MS than by IA. The MS-FT(4) method therefore provides FT(4) results that agree clinically with those obtained for TSH. Additionally, the significant correlation between IA-FT(4) with albumin and TBG suggests that this FT(4) method depends on binding protein concentrations and consequently does not accurately reflect FT(4). (C) 2010 American Association for Clinical Chemistry C1 [Mendu, Damodara R.; Soldin, Steven J.] Georgetown Univ, Med Ctr, Gen Clin Res Ctr, Bioanalyt Core Lab, Washington, DC 20007 USA. [van Deventer, Hendrick E.; Remaley, Alan T.; Soldin, Steven J.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Mendu, Damodara R.; Soldin, Steven J.] Georgetown Univ, Dept Pharmacol, Washington, DC USA. [Mendu, Damodara R.; Soldin, Steven J.] Georgetown Univ, Dept Med, Washington, DC USA. [Mendu, Damodara R.; Soldin, Steven J.] George Washington Univ, Sch Med, Dept Pediat, Washington, DC 20052 USA. [Mendu, Damodara R.; Soldin, Steven J.] George Washington Univ, Sch Med, Dept Pathol, Washington, DC 20052 USA. [Soldin, Steven J.] NMS Labs, Clin Endocrinol Lab, Willow Grove, PA USA. RP Soldin, SJ (reprint author), Georgetown Univ, Med Ctr, Gen Clin Res Ctr, Bioanalyt Core Lab, Room GM12A,Preclin Sci Bldg, Washington, DC 20007 USA. EM sjs44@georgetown.edu FU NIH [1UL1RR031975-01]; NIH, Warren Grant Magnuson Clinical Center FX Tests performed at NIH (FT4 by immunoassay and the TBG, albumin, and TSH tests) were supported in part by the Intramural Research Program of the NIH, Warren Grant Magnuson Clinical Center. S.J. Soldin is partially supported by NIH Clinical and Translational Science Awards grant 1UL1RR031975-01. NR 27 TC 40 Z9 40 U1 0 U2 13 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2011 VL 57 IS 1 BP 122 EP 127 DI 10.1373/clinchem.2010.154088 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 699TQ UT WOS:000285686100019 PM 21097676 ER PT J AU Semple, PL Watkins, M Davids, V Krensky, AM Hanekom, WA Kaplan, G Ress, S AF Semple, Patricia L. Watkins, Marcia Davids, Virginia Krensky, Alan M. Hanekom, Willem A. Kaplan, Gilla Ress, Stanley TI Induction of Granulysin and Perforin Cytolytic Mediator Expression in 10-Week-Old Infants Vaccinated with BCG at Birth SO CLINICAL & DEVELOPMENTAL IMMUNOLOGY LA English DT Article ID MYCOBACTERIUM-BOVIS BCG; CD8(+) T-CELLS; CALMETTE-GUERIN VACCINATION; INTERFERON-GAMMA PRODUCTION; CORD-BLOOD; IMMUNE-RESPONSES; ANTIMYCOBACTERIAL ACTIVITY; CRYPTOCOCCUS-NEOFORMANS; ANTIMICROBIAL ACTIVITY; TUBERCULOSIS VACCINE AB Background. While vaccination at birth with Mycobacterium bovis Bacilli Calmette-Guerin (BCG) protects against severe childhood tuberculosis, there is no consensus as to which components of the BCG-induced immune response mediate this protection. However, granulysin and perforin, found in the granules of cytotoxic T lymphocytes and Natural Killer (NK) cells, can kill intracellular mycobacteria and are implicated in protection against Mycobacterium tuberculosis. Methods. We compared the cellular expression of granulysin and perforin cytolytic molecules in cord blood and peripheral blood from 10-week-old infants vaccinated at birth with either Japanese or Danish BCG, administered either intradermally or percutaneously. Results. In cord blood, only CD56(+) NK cells expressed granulysin and perforin constitutively. These cytolytic mediators were upregulated in CD4(+) and CD8(+) cord blood cells by ex vivo stimulation with BCG but not with PPD. Following BCG vaccination of neonates, both BCG and PPD induced increased expression of granulysin and perforin by CD4(+) and CD8(+) T cells. There was no difference in expression of cytolytic molecules according to vaccination route or strain. Conclusions. Constitutive expression of perforin and granulysin by cord blood NK-cells likely provides innate immunity, while BCG vaccination-induced expression of these cytolytic mediators may contribute towards protection of the neonate against tuberculosis. C1 [Semple, Patricia L.; Watkins, Marcia; Ress, Stanley] Univ Cape Town, Dept Med, Div Clin Immunol, ZA-7925 Cape Town, South Africa. [Watkins, Marcia] Natl Hlth Lab Serv, ZA-8000 Cape Town, South Africa. [Davids, Virginia; Hanekom, Willem A.] Univ Cape Town, Inst Infect Dis & Mol Med, S African TB Vaccine Initiat, ZA-7700 Cape Town, South Africa. [Krensky, Alan M.] NCI, NIH, Bethesda, MD 20892 USA. [Hanekom, Willem A.] Univ Cape Town, Sch Child & Adolescent Med, ZA-7925 Cape Town, South Africa. [Kaplan, Gilla] Univ Med & Dent New Jersey, Lab Mycobacterial Immun & Pathogenesis, Publ Hlth Res Inst, Newark, NJ 07103 USA. [Ress, Stanley] Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. RP Ress, S (reprint author), Univ Cape Town, Dept Med, Div Clin Immunol, ZA-7925 Cape Town, South Africa. EM stan.ress@uct.ac.za FU Medical Research Council Tuberculosis Vaccine Initiative; National Research Foundation (Thuthuka); AERAS Global Tuberculosis Vaccine Foundation FX S. Ress was supported by a grant from the Medical Research Council Tuberculosis Vaccine Initiative. P. L. Semple was supported by National Research Foundation (Thuthuka). G. Kaplan and W. A. Hanekom were supported by the AERAS Global Tuberculosis Vaccine Foundation. NR 53 TC 11 Z9 11 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1740-2522 J9 CLIN DEV IMMUNOL JI Clin. Dev. Immunol. PY 2011 AR 438463 DI 10.1155/2011/438463 PG 10 WC Immunology SC Immunology GA 706WL UT WOS:000286248400001 ER PT J AU Yu, JE De Ravin, SS Uzel, G Landers, C Targan, S Malech, HL Holland, SM Cao, WQ Harpaz, N Mayer, L Cunningham-Rundles, C AF Yu, Joyce E. De Ravin, Suk See Uzel, Gulbu Landers, Carol Targan, Stephan Malech, Harry L. Holland, Steven M. Cao, Wenqing Harpaz, Noam Mayer, Lloyd Cunningham-Rundles, Charlotte TI High levels of Crohn's disease-associated anti-microbial antibodies are present and independent of colitis in chronic granulomatous disease SO CLINICAL IMMUNOLOGY LA English DT Article DE Chronic granulomatous disease; Hyper IgE Syndrome; Inflammatory bowel disease; Serum antimicrobial antibodies; Colitis; Innate immunity ID INFLAMMATORY-BOWEL-DISEASE; LEUKOCYTE ADHESION DEFICIENCY; HYPER-IGE SYNDROME; MICROBIAL ANTIGENS; ULCERATIVE-COLITIS; RESPONSES; IMMUNITY; INNATE; COMPLICATIONS; BIOMARKERS AB Chronic granulomatous disease (CGD) and inflammatory bowel disease (IBD) have overlapping gastrointestinal manifestations. Serum antibodies to intestinal microbial antigens in IBD are thought to reflect a loss of tolerance in the setting of genetically encoded innate immune defects. CGD subjects studied here, with or without colitis, had considerably higher levels of ASCA IgA, ASCA IgG, anti-OmpC, anti-I2, and anti-CBir1, but absent to low pANCA, compared to IBD-predictive cutoffs. Higher antibody levels were not associated with a history of colitis. Except for higher ASCA IgG in subjects <18 years, antibody levels were not age-dependent. In comparison, 7 HIES subjects expressed negative to low antibody levels to all of these antigens; none had colitis. Our results suggest that markedly elevated levels of antimicrobial antibodies in CGD do not correlate with a history of colitis but may reflect a specific defect in innate immunity in the face of chronic antigenic stimulation. (C) 2010 Elsevier Inc. All rights reserved. C1 [Cunningham-Rundles, Charlotte] Mt Sinai Sch Med, Inst Immunol, Dept Med, Div Clin Immunol, New York, NY 10029 USA. [De Ravin, Suk See; Malech, Harry L.] NIAID, Host Def Lab, Bethesda, MD 20892 USA. [Uzel, Gulbu; Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Landers, Carol; Targan, Stephan] Univ Calif Los Angeles, Sch Med, Cedars Sinai Div Gastroenterol, Los Angeles, CA USA. [Cao, Wenqing; Harpaz, Noam] Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA. RP Cunningham-Rundles, C (reprint author), Mt Sinai Sch Med, Inst Immunol, Dept Med, Div Clin Immunol, 1425 Madison Ave, New York, NY 10029 USA. EM Charlotte.Cunningham-Rundles@mssm.edu OI Malech, Harry/0000-0001-5874-5775; Cao, Wenqing/0000-0002-2761-3355 FU National Institutes of Health [AI-101093, AI-467320, AI-48693, T32 AI007605-07]; National Institute of Allergy and Infectious Diseases [03-22]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Institutes of Health/National Institute of Allergy and Infectious Diseases; Baxter Therapeutics FX Supported by the National Institutes of Health AI-101093, AI-467320, AI-48693 and National Institute of Allergy and Infectious Diseases Contract 03-22 (CCR), National Institutes of Health T32 AI007605-07 (JEY), and the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.; C.C.R. has received research support from the National Institutes of Health/National Institute of Allergy and Infectious Diseases, has served on the medical advisory boards of Talecris Corporation and Baxter Therapeutics, and has received a research grant from Baxter Therapeutics. NR 63 TC 22 Z9 22 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JAN PY 2011 VL 138 IS 1 BP 14 EP 22 DI 10.1016/j.clim.2010.08.003 PG 9 WC Immunology SC Immunology GA 713DA UT WOS:000286714000004 PM 20956091 ER PT J AU Greenbaum, LA Munoz, A Schneider, MF Kaskel, FJ Askenazi, DJ Jenkins, R Hotchkiss, H Moxey-Mims, M Furth, SL Warady, BA AF Greenbaum, Larry A. Munoz, Alvaro Schneider, Michael F. Kaskel, Frederick J. Askenazi, David J. Jenkins, Randall Hotchkiss, Hilary Moxey-Mims, Marva Furth, Susan L. Warady, Bradley A. TI The Association between Abnormal Birth History and Growth in Children with CKD SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; CHRONIC-RENAL-FAILURE; FOR-GESTATIONAL-AGE; NEURODEVELOPMENTAL OUTCOMES; HORMONE TREATMENT; RISK-FACTORS; WEIGHT; INFANTS; HEIGHT AB Background and objectives Poor linear growth is a well described complication of chronic kidney disease (CKD). This study evaluated whether abnormal birth history defined by low birth weight (LBW; <2500 g), prematurity (gestational age <36 weeks), small for gestational age (SGA; birth weight <10th percentile for gestational age), or intensive care unit (ICU) at birth were risk factors for poor growth outcomes in children with CKD. Design, setting, participants, & measurements Growth outcomes were quantified by age-sex-specific height and weight z-scores during 1393 visits from 426 participants of the Chronic Kidney Disease in Children Study, an observational cohort of children with CKD. Median baseline GFR was 42.9 ml/min per 1.73 m(2), 21% had a glomerular diagnosis, and 52% had CKD for >= 90% of their lifetime. Results A high prevalence of LBW (17%), SGA (14%), prematurity (12%), and ICU after delivery (40%) was observed. Multivariate analyses demonstrated a negative effect of LBW (-0.43 +/- 0.14; P < 0.01 for height and 0.37 +/- 0.16; P = 0.02 for weight) and of SGA (-0.29 +/- 0.16; P = 0.07 for height and 0.41 +/- 0.19; P = 0.03 for weight) on current height and weight. In children with glomerular versus nonglomerular diagnoses, the effect of SGA (-1.08 versus -0.18; P = 0.029) on attained weight was more pronounced in children with a glomerular diagnosis. Conclusions LBW and SGA are novel risk factors for short stature and lower weight percentiles in children with mild to moderate CKD independent of kidney function. Clin J Am Soc Nephrol 6: 14-21, 2011. doi: 10.2215/CJN.08481109 C1 [Greenbaum, Larry A.] Emory Univ, Div Pediat Nephrol, Dept Pediat, Atlanta, GA 30322 USA. [Greenbaum, Larry A.] Childrens Healthcare Atlanta, Atlanta, GA USA. [Munoz, Alvaro; Schneider, Michael F.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Kaskel, Frederick J.] Albert Einstein Coll Med, Dept Pediat, New York, NY USA. [Askenazi, David J.] Univ Alabama, Dept Pediat, Birmingham, AL USA. [Jenkins, Randall] Emanuel Childrens Hosp, Portland, OR USA. [Hotchkiss, Hilary] Mt Sinai Sch Med, Dept Pediat, New York, NY USA. [Moxey-Mims, Marva] NIDDKD, NIH, Bethesda, MD 20892 USA. [Furth, Susan L.] Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA. [Warady, Bradley A.] Childrens Mercy Hosp, Kansas City, MO 64108 USA. RP Greenbaum, LA (reprint author), Emory Univ, Div Pediat Nephrol, Dept Pediat, 2015 Uppergate Dr NE, Atlanta, GA 30322 USA. EM lgreen6@emory.edu FU National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Child Health and Human Development; National Institute of Neurologic Disorders and Stroke; participating institutional General Clinical Research Centers; Clinical Translational Research Centers; Clinical and Translational Science Award [UL1 RR025008]; General Clinical Research Center [M01 RR0039]; National Institutes of Health; National Center for Research Resources FX The CKiD prospective cohort study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the National Heart, Lung, and Blood Institute, the National Institute of Child Health and Human Development, and the National Institute of Neurologic Disorders and Stroke. The CKiD study has been supported by participating institutional General Clinical Research Centers and Clinical Translational Research Centers. Research at Emory is supported in part by PHS Grant UL1 RR025008 from the Clinical and Translational Science Award program and PHS Grant M01 RR0039 from the General Clinical Research Center program, National Institutes of Health, and the National Center for Research Resources. The CKiD prospective cohort study has clinical coordinating centers (principal investigators) at Children's Mercy Hospital and the University of Missouri-Kansas City (Bradley Warady, MD; U01-DK-66143) and at Johns Hopkins School of Medicine (Susan Furth, MD, Ph.D.; U01-DK-66174), a data coordinating center at Johns Hopkins Bloomberg School of Public Health (Alvaro Munoz, Ph.D.; U01-DK-66116), and the Central Biochemistry Laboratory at the University of Rochester Medical Center (George J. Schwartz, MD; U01-DK82194). NR 27 TC 30 Z9 32 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JAN PY 2011 VL 6 IS 1 BP 14 EP 21 DI 10.2215/CJN.08481109 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 709PP UT WOS:000286452900005 PM 21030583 ER PT J AU Lara, PN Longmate, J Reckamp, K Gitlitz, B Argiris, A Ramalingam, S Belani, CP Mack, PC Lau, DHM Koczywas, M Wright, JJ Shepherd, FA Leighl, N Gandara, DR AF Lara, Primo N., Jr. Longmate, Jeff Reckamp, Karen Gitlitz, Barbara Argiris, Athanassios Ramalingam, Suresh Belani, Chandra P. Mack, Philip C. Lau, Derick H. M. Koczywas, Mariana Wright, John J. Shepherd, Frances A. Leighl, Natasha Gandara, David R. TI Randomized Phase II Trial of Concurrent Versus Sequential Bortezomib Plus Docetaxel in Advanced Non-Small-Cell Lung Cancer: A California Cancer Consortium Trial SO CLINICAL LUNG CANCER LA English DT Article DE Bortezomib; Docetaxel; Proteasome inhibition ID PROTEASOME INHIBITOR BORTEZOMIB; SOLID TUMORS; PS-341; CHEMOTHERAPY; COMBINATION; APOPTOSIS; XENOGRAFTS; ARREST; MECHANISMS; THERAPY AB Background: The proteasome inhibitor bortezomib sensitizes tumor cells to chemotherapy-induced apoptosis. In preclinical non-small-cell lung cancer (NSCLC) models, p53-dependent growth arrest after bortezomib treatment resulted in reduced cytotoxicity if bortezomib preceded docetaxel. The reverse sequence of docetaxel before bortezomib was associated with increased apoptosis, cleavage of caspase-3 and PARP (poly [ADP-ribose] polymerase), and reduction in Bcl-2. A prospective randomized phase II trial of concurrent versus sequential docetaxel and bortezomib was conducted to assess whether administration sequence resulted in measurable clinical differences. Patients and Methods: Previously treated patients with advanced NSCLC were randomized to concurrent (CON) or sequential (SEQ) docetaxel (75 mg/m(2) intravenous [I.V.]) followed by bortezomib, every 3 weeks. In the CON arm, bortezomib (1.6 mg/m(2) I.V.) was given on days 1 and 8, and in the SEQ arm, it was given on days 2 and 8. Previous erlotinib as well as treated or controlled brain metastases were allowed. The primary endpoint was objective response rate (RR); progression-free (PFS) and overall survival (OS) were secondary endpoints. Results: Eighty-one patients were randomized (40 CON and 41 SEQ). Grade 3+ toxicities were mostly due to myelosuppression. One patient each had grade 4 hyponatremia and syncope. Toxicities were similar between the arms. There was 1 treatment-related death in the SEQ arm. There were 8 partial responders, 4 in each arm, for an overall RR of 10%. Disease control rate was similar in both arms (50% vs. 49%). Median PFS was 12 weeks in the CON arm and 11 weeks in the SEQ arm. Median OS times in the CON and SEQ arms were 13.3 and 10.5 months, respectively. Conclusion: Docetaxel plus bortezomib given sequentially or concurrently has similar RR and PFS. Median survival in the SEQ arm exceeds published survival estimates for either agent alone or in combination. Any further studies in this population would require molecular characterization of a phenotype most likely to benefit from proteasome inhibitor therapy. C1 [Lara, Primo N., Jr.; Mack, Philip C.; Lau, Derick H. M.; Gandara, David R.] Univ Calif Davis, Davis Canc Ctr, Sacramento, CA 95817 USA. [Lara, Primo N., Jr.; Lau, Derick H. M.] VANCHCS, Martinez, CA USA. [Longmate, Jeff; Reckamp, Karen; Koczywas, Mariana] City Hope Med Grp, Pasadena, CA USA. [Longmate, Jeff; Reckamp, Karen; Koczywas, Mariana] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Gitlitz, Barbara] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Argiris, Athanassios] Univ Pittsburgh, Med Ctr, Inst Canc, Pittsburgh, PA USA. [Ramalingam, Suresh] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Belani, Chandra P.] Penn State Hershey Canc Inst, Hershey, PA USA. [Wright, John J.] Natl Canc Inst, Canc Therapy Evaluat Program, Bethesda, MD USA. [Shepherd, Frances A.; Leighl, Natasha] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. RP Lara, PN (reprint author), Univ Calif Davis, Davis Canc Ctr, 4501 X St, Sacramento, CA 95817 USA. EM primo.lara@ucdmc.ucdavis.edu OI Belani, Chandra/0000-0001-5049-5329; Longmate, Jeffrey/0000-0002-0869-7928; Reckamp, Karen/0000-0002-9213-0325 FU National Cancer Institute [NO1 CM-62209]; Millennium Pharmaceuticals; Millennium Pharmaceuticals, Inc.; National Cancer Institute/National Institutes of Health; sanofi-aventis FX Supported by the National Cancer Institute through an N01 Early Therapeutics contract (NO1 CM-62209) to the California Cancer Consortium.; Athanassios Argiris has received research support from Millennium Pharmaceuticals. Mariana Koczywas is a member of the Speaker's Bureau for Genentech, Inc. Primo N. Lara, Jr. has received research support from Millennium Pharmaceuticals, Inc., National Cancer Institute/National Institutes of Health, and sanofi-aventis U.S. Primo N. Lara, Jr. has also served as a paid consultant or has been on the Advisory Board of Millennium Pharmaceuticals and sanofi-aventis U.S. Karen Reckamp is a member of the Speaker's Bureau for Eli Lilly and Company and Genentech, Inc. Frances A. Shepherd has served as a consultant or been on an advisory board for Millennium Pharmaceuticals and sanofi-aventis U.S. All other authors have no relevant relationships to disclose. NR 25 TC 12 Z9 13 U1 2 U2 6 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1525-7304 J9 CLIN LUNG CANCER JI Clin. Lung Cancer PD JAN PY 2011 VL 12 IS 1 BP 33 EP 37 DI 10.3816/CLC.2011.n.004 PG 5 WC Oncology SC Oncology GA 712GP UT WOS:000286654500004 PM 21273177 ER PT J AU Cook, NL Romashkan, S AF Cook, N. L. Romashkan, S. TI Why Do We Need a Trial on the Effects of Testosterone Therapy in Older Men? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material AB Decreases in levels of sex hormones occur with aging. Observational studies have found associations of low testosterone concentrations in older men with adverse symptoms; however, these associations do not prove causality. Therefore, the question arises whether to treat older men whose serum testosterone is low. In 2009, the Testosterone Trial (T Trial) was funded to examine the efficacy of therapy in 800 elderly men with low testosterone levels; potentially associated symptoms; and abnormalities in physical, sexual, or cognitive function or vitality. C1 [Romashkan, S.] NIA, Div Geriatr & Clin Gerontol, NIH, Bethesda, MD 20892 USA. [Cook, N. L.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. RP Romashkan, S (reprint author), NIA, Div Geriatr & Clin Gerontol, NIH, Bethesda, MD 20892 USA. EM romashks@nia.nih.gov NR 9 TC 4 Z9 4 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2011 VL 89 IS 1 BP 29 EP 31 DI 10.1038/clpt.2010.217 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 697UI UT WOS:000285543900013 PM 21170069 ER PT J AU Drayna, D AF Drayna, Dennis BE Ward, D Scott, KS TI Possible genetic factors in cluttering SO CLUTTERING: A HANDBOOK OF RESEARCH, INTERVENTION AND EDUCATION LA English DT Article; Book Chapter ID SPEECH C1 Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. RP Drayna, D (reprint author), Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-1-84872-029-9 PY 2011 BP 29 EP 33 PG 5 WC Language & Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA BUK60 UT WOS:000289669500003 ER PT J AU Mazzone, L Reale, L Mannino, V Cocuzza, M Vitiello, B AF Mazzone, Luigi Reale, Laura Mannino, Valeria Cocuzza, Mariadonatella Vitiello, Benedetto TI Lower IQ is Associated with Decreased Clinical Response to Atomoxetine in Children and Adolescents with Attention-Deficit Hyperactivity Disorder SO CNS DRUGS LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; DEFICIT/HYPERACTIVITY DISORDER; MENTAL-RETARDATION; PREFRONTAL CORTEX; METHYLPHENIDATE; SYMPTOMS; EFFICACY; DOPAMINE; VALIDITY; AUTISM AB Objectives: Atomoxetine is commonly used to treat attention-deficit hyperactivity disorder (ADHD) in children with a broad range of cognitive abilities. We examined the association between level of cognitive functioning as determined by IQ and clinical response during treatment with atomoxetine. Methods: The records of all the children and adolescents treated with atomoxetine at a university clinic in Catania, Italy, over a 3-year period were examined. A total of 55 clinically referred children and adolescents (aged 5-15 years, 53 males) with ADHD were treated with atomoxetine (10-110 mg/day; mean: 1.28 mg/kg/day) for a period ranging from 2 to 168 weeks (mean: 57.3 +/- SD 39.4, median: 56). The IQ was assessed as part of the diagnostic evaluation prior to starting treatment. During treatment, clinical outcome was rated on the Clinical Global Impression-Improvement (CGI-I) and CGI-Severity (CGI-S) scales. Results: The IQ ranged from 43 to 117 (mean: 80.6 +/- SD 18.6, median: 84). The IQ and final CGI-I scores were negatively correlated (r = -0.68; p < 0.01). Children and adolescents with an IQ <85 were less likely to be responders (defined as a final CGI-I score of 1 or 2) than children and adolescents with an IQ >= 85 (20.71% vs 76.9%; p < 0.001). None of the patients discontinued atomoxetine due to adverse effects, while treatment was discontinued in 20 subjects due to a lack of efficacy or ambivalence of parents about pharmacological treatment. Conclusions: Atomoxetine appears to be less effective in children and adolescents with an IQ <85 than in children and adolescents in the average range of cognitive functioning. This difference is not accounted for by differences in the severity of ADHD symptoms, co-morbidity or reduced tolerability to the medication. These findings suggest that, in order to be fully informative, clinical trials of medications for ADHD should also include children and adolescents functioning in the borderline and cognitive disability range. C1 [Mazzone, Luigi; Reale, Laura; Mannino, Valeria; Cocuzza, Mariadonatella] Univ Catania, Div Child Neurol & Psychiat, Dept Pediat, I-95100 Catania, Italy. [Vitiello, Benedetto] NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD 20892 USA. RP Mazzone, L (reprint author), Univ Catania, Div Child Neurol & Psychiat, Dept Pediat, Via S Sofia 78, I-95100 Catania, Italy. EM gigimazzone@yahoo.it FU Division of Child Neurology and Psychiatry of the University of Catania, Catania, Italy; Eli Lilly FX Luigi Mazzone and Laura Reale contributed equally to this work in terms of realization of the study, data analysis and paper writing. Valeria Mannino and Mariadonatella Cocuzza collected the data, and Benedetto Vitiello contributed to the design of the study, supervised statistical analysis and helped in the theoretical interpretation of the results. This study was funded by the Division of Child Neurology and Psychiatry of the University of Catania, Catania, Italy. Dr Mannino received educational travel funds by Eli Lilly. The other authors (LM, LR, BV) have no relevant financial disclosures. NR 21 TC 13 Z9 13 U1 2 U2 7 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2011 VL 25 IS 6 BP 503 EP 509 PG 7 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 789QN UT WOS:000292531500005 PM 21649450 ER PT J AU Post, RM Weiss, SRB AF Post, Robert M. Weiss, Susan R. B. TI Tolerance to the Prophylactic Effects of Carbamazepine and Related Mood Stabilizers in the Treatment of Bipolar Disorders SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Review DE Anticonvulsants; Depression; Lithium; Mania; Seizures; Treatment resistance ID AMYGDALA-KINDLED SEIZURES; CONTINGENT TOLERANCE; LITHIUM-DISCONTINUATION; TRIGEMINAL NEURALGIA; CROSS-TOLERANCE; AFFECTIVE-ILLNESS; LAMOTRIGINE; RATS; REFRACTORINESS; IMPROVEMENT AB Tolerance development after successful long-term treatment of bipolar disorder is under recognized, as are ways to prevent or show its occurrence or reverse it once it has occurred. We review the clinical literature which suggests that tolerance can develop to most treatment approaches in bipolar illness and present an animal model of tolerance development to anticonvulsant effects of carbamazepine or lamotrigine on amgydala-kindled seizures. In this model tolerance does not have a pharmacokinetic basis, but is contingent upon the drug being present in the brain at the time of amygdala stimulation. The occurrence of seizures in the absence of drug is sufficient to reverse tolerance and re-establish anticonvulsant efficacy. Based on the model, we hypothesize that some episode-induced compensatory adaptive changes in gene expression fail to occur in tolerant subjects and that episodes off medication re-induce these changes and renew drug effectiveness. Approaches that slow or reverse tolerance development in the animal model are reviewed so that they can be tested for their applicability in the clinic. Criteria for assessing tolerance development are offered in the hope that this will facilitate a more systemic literature about its prevalence, prevention, and reversal. Careful longitudinal monitoring of episode occurrence is essential to understanding tolerance development in the affective disorder and its treatment. C1 [Post, Robert M.] Bipolar Collaborat Network, Bethesda, MD 20814 USA. [Post, Robert M.] George Washington Univ, Dept Psychiat, Washington, DC USA. [Weiss, Susan R. B.] Natl Inst Drug Abuse, Sci Policy Branch, Off Sci Policy & Commun, Bethesda, MD USA. RP Post, RM (reprint author), Bipolar Collaborat Network, 5415 W Cedar Lane,Suite 201-B, Bethesda, MD 20814 USA. EM robert.post@speakeasy.net NR 56 TC 5 Z9 5 U1 2 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2011 VL 17 IS 6 BP 649 EP 660 DI 10.1111/j.1755-5949.2010.00215.x PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 852AT UT WOS:000297316900011 PM 21159150 ER PT J AU Machado-Vieira, R Ibrahim, L Zarate, CA AF Machado-Vieira, Rodrigo Ibrahim, Lobna Zarate, Carlos A., Jr. TI Histone Deacetylases and Mood Disorders: Epigenetic Programming in Gene-Environment Interactions SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Review DE Bipolar disorder; Depression; Epigenetics; Histones; Pathophysiology; Treatment; Valproate ID BIPOLAR-DISORDER; VALPROIC ACID; MOUSE MODEL; HUNTINGTONS-DISEASE; DOPAMINERGIC-NEURONS; SYNAPTIC PLASTICITY; EARLY INTERVENTION; FRIEDREICH ATAXIA; SODIUM-BUTYRATE; HDAC INHIBITION AB Epigenetics involves molecular mechanisms related to gene expression independent of DNA sequence, mostly mediated by modification of chromatin histones. It has recently been suggested that these transcriptional changes may be implicated in the pathophysiology of mood disorders. In addition, histone deacetylase (HDAC) inhibitors have been shown to control epigenetic programming associated with the regulation of cognition and behavior, and may reverse dysfunctional epigenetic regulation associated with early life events in preclinical models. In this context, the active and continuous adaptation of chromatin, and the access of gene promoters to transcription factor mechanisms may represent a potential therapeutic target in the treatment of mood disorders such as bipolar disorder (BD) and major depressive disorder (MDD). Notably, the standard mood stabilizer valproate (VPA) has been shown to modulate the epigenome by inhibiting HDACs. However, several potential limitations are associated with this class of agents, including lack of selectivity for specific HDAC isoforms as well as risk of potentially serious side effects. Further studies regarding the potential role of chromatin remodeling in the mechanism of action of antidepressants and mood stabilizers are necessary to clarify the potential role of this class of agents as therapeutics for mood disorders. C1 [Machado-Vieira, Rodrigo; Ibrahim, Lobna; Zarate, Carlos A., Jr.] NIMH, Intramural Res Program, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Machado-Vieira, Rodrigo; Ibrahim, Lobna; Zarate, Carlos A., Jr.] US Dept HHS, Bethesda, MD USA. [Machado-Vieira, Rodrigo] Univ Sao Paulo, Inst & Dept Psychiat, BR-05508 Sao Paulo, Brazil. RP Zarate, CA (reprint author), 10 Ctr Dr CRC,7 SE Unit,Rm 7-3465, Bethesda, MD 20892 USA. EM zaratec@intra.nimh.nih.gov RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services (NIMH-NIH-DHHS) FX Ioline Henter provided invaluable editorial assistance. Funding for this work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services (IRP-NIMH-NIH-DHHS). NR 77 TC 28 Z9 28 U1 1 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2011 VL 17 IS 6 BP 699 EP 704 DI 10.1111/j.1755-5949.2010.00203.x PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 852AT UT WOS:000297316900016 PM 20961400 ER PT J AU Kallmes, DF Buchbinder, R Miller, FG AF Kallmes, David F. Buchbinder, Rachelle Miller, Franklin G. TI VIEWPOINT: Randomised controlled trials using invasive control interventions should be included in Cochrane Reviews SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Editorial Material DE Placebo; Study methodology C1 [Kallmes, David F.] Mayo Clin, Dept Diagnost Radiol, Rochester, MN 55905 USA. [Buchbinder, Rachelle] Cabrini Hosp, Monash Dept Clin Epidemiol, Malvern, Vic 3144, Australia. [Buchbinder, Rachelle] Monash Univ, Sch Publ Hlth & Prevent Med, Dept Epidemiol & Prevent Med, Malvern, Vic 3144, Australia. [Buchbinder, Rachelle] Cabrini Med Ctr, Cochrane Musculoskeletal Grp, Malvern, Vic 3144, Australia. [Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Kallmes, DF (reprint author), Mayo Clin, Dept Diagnost Radiol, 200 First St SW, Rochester, MN 55905 USA. EM kallmes.david@mayo.edu; rachelle.buchbinder@med.monash.edu.au; fmiller@nih.gov FU CareFusion; eV3; MicroVention; Cook Austrlia; Cook; Athrocare; Penumbra; NFocus; Micrus FX The authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available upon request) and declare (1) no receipt of payment or support in kind for any aspect of the article; (2) that D Kallmes' institution has received grants from CareFusion, Cook, Athrocare, eV3, MicroVention, Penumbra, NFocus and Micrus; has received payment for development of educational programmes from CareFusion and eV3; and has received travel/accommodation/meeting expenses from MicroVention; that R Buchbinder's institution received funding from Cook Austrlia to support the vertebroplasty trials; and that F Miller has no financial relationships with any entities that have an interest related to the submitted work; (3) that the spouses/partners/children have no financial relationships with entities that have an interest in the content of the article; and (4) that there are no other relationships or activities that could be perceived as having influenced, or giving the appearance of potentially influencing, what was written in the submitted work. NR 9 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2011 IS 7 AR ED000030 DI 10.1002/14651858.ED000030 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA V34NX UT WOS:000209094200001 PM 21833988 ER PT J AU Haddad, ADM Lissek, S Pine, DS Lau, JYF AF Haddad, Anneke D. M. Lissek, Shmuel Pine, Daniel S. Lau, Jennifer Y. F. TI How do social fears in adolescence develop? Fear conditioning shapes attention orienting to social threat cues SO COGNITION & EMOTION LA English DT Article DE Adolescence; Social anxiety; Attentional biases; Fear conditioning ID EMOTIONAL DISORDERS; ANXIETY; BIAS; STIMULI; EXTINCTION AB Social fears emerging in adolescence can have negative effects on emotional well-being. Yet the mechanisms by which these risks occur are unknown. One possibility is that associative learning results in fears to previously neutral social stimuli. Such conditioned responses may alter subsequent processing of social stimuli. We used a novel conditioning task to examine how associative processes influence social fear and attention orienting in adolescents. Neutral photographs were paired with socially rewarding or aversive stimuli during conditioning; a dot-probe task then assessed biases in attention orienting. The social conditioning task modified subjective ratings of the neutral stimuli. Moreover, for the neutral stimulus that was paired with the aversive stimulus, the strength of conditioning showed a relationship with subsequent attentional vigilance. The findings elucidate mechanisms by which negative peer experiences during adolescence may affect emotional processing. C1 [Haddad, Anneke D. M.; Lau, Jennifer Y. F.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. [Lissek, Shmuel; Pine, Daniel S.] NIMH, NIH, Bethesda, MD 20892 USA. RP Haddad, ADM (reprint author), Univ Oxford, Dept Expt Psychol, S Parks Rd, Oxford OX1 3UD, England. EM anneke.haddad@psy.ox.ac.uk RI Haddad, Anneke/A-9674-2012; OI Haddad, Anneke/0000-0003-3429-0475 FU Intramural NIH HHS [ZIA MH002782-11, ZIA MH002780-11, ZIA MH002781-11] NR 25 TC 14 Z9 15 U1 3 U2 20 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0269-9931 J9 COGNITION EMOTION JI Cogn. Emot. PY 2011 VL 25 IS 6 BP 1139 EP 1147 DI 10.1080/02699931.2010.524193 PG 9 WC Psychology, Experimental SC Psychology GA 882KX UT WOS:000299563600013 PM 21895575 ER PT J AU Chan, AWY Baker, CI AF Chan, Annie W. -Y. Baker, Chris I. TI Differential contributions of occipitotemporal regions to person perception SO COGNITIVE NEUROSCIENCE LA English DT Editorial Material AB Downing and Peelen have produced an excellent review synthesizing the current literature on the processing of body stimuli in visual cortex. However, while they consider the extrastriate body area (EBA) and fusiform body area (FBA) together, these regions are physically separate in cortex and likely contribute differentially to person perception. Here, we evaluate the hierarchical view of processing in EBA and FBA and highlight the visual field biases in these regions, which may provide insight into their origin and functional roles. C1 [Chan, Annie W. -Y.; Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Chan, AWY (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. EM chanannie@mail.nih.gov OI Baker, Chris/0000-0001-6861-8964 FU Intramural NIH HHS [ZIA MH002909-03] NR 0 TC 5 Z9 5 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1758-8928 J9 COGN NEUROSCI-UK JI Cogn. Neurosci PY 2011 VL 2 IS 3-4 SI SI BP 210 EP 211 DI 10.1080/17588928.2011.604723 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 878RJ UT WOS:000299273900014 PM 22383904 ER PT J AU Belluscio, BA Tinaz, S Hallett, M AF Belluscio, Beth A. Tinaz, Sule Hallett, Mark TI Similarities and differences between normal urges and the urge to tic SO COGNITIVE NEUROSCIENCE LA English DT Editorial Material AB Investigations into the neurobiological substrates underlying urge are important for developing better understanding and treatment for impulse-control disorders. We characterize the phenomenon based on normal bodily (interoceptive) urges. Features include the following: a preceding awareness of an uncomfortable bodily sensation, a sense of urgency that action must be taken, rising distress when action is delayed, a temporary (e. g., a few minutes in length) ability to suppress or manifest the action voluntarily, subsequent relief once action is taken, association with an action that is necessary to survival. We compare and contrast these characteristics with those described by Tourette syndrome patients as the urge to tic, and highlight several unknowns which merit further investigation. C1 [Belluscio, Beth A.; Tinaz, Sule; Hallett, Mark] NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA. RP Belluscio, BA (reprint author), NINDS, Human Motor Control Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM belluscb@ninds.nih.gov NR 0 TC 3 Z9 3 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1758-8928 J9 COGN NEUROSCI-UK JI Cogn. Neurosci PY 2011 VL 2 IS 3-4 SI SI BP 245 EP 246 DI 10.1080/17588928.2011.618630 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 878RJ UT WOS:000299273900021 PM 24168545 ER PT B AU Freedman, BA Nesti, LJ AF Freedman, Brett A. Nesti, Leon J. BE Owens, BD Belmont, PJ TI MANAGEMENT OF COMPLEX COMBAT-RELATED SOFT TISSUE WOUNDS/NEGATIVE PRESSURE WOUND THERAPY SO COMBAT ORTHOPEDIC SURGERY: LESSONS LEARNED IN IRAQ AND AFGHANISTAN LA English DT Article; Book Chapter ID OPERATION-ENDURING-FREEDOM; IRAQI-FREEDOM; EXTREMITY WOUNDS; IRRIGATION; INFECTION; DRESSINGS; TRAUMA; MODEL; COMPLICATIONS; COLONIZATION C1 [Freedman, Brett A.] Landstuhl Reg Med Ctr, Spine & Neurosurg Serv, Landstuhl, Germany. [Nesti, Leon J.] McDonald Army Hlth Clin, Ft Eustis, VA USA. [Nesti, Leon J.] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Freedman, BA (reprint author), Landstuhl Reg Med Ctr, Spine & Neurosurg Serv, Landstuhl, Germany. NR 41 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-55642-965-1 PY 2011 BP 65 EP 75 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA BTZ12 UT WOS:000288484200008 ER PT J AU Morrell, CH Sheng, SL Brant, LJ AF Morrell, Christopher H. Sheng, Shan L. Brant, Larry J. TI A Comparative Study of Approaches for Predicting Prostate Cancer from Longitudinal Data SO COMMUNICATIONS IN STATISTICS-SIMULATION AND COMPUTATION LA English DT Article DE Classification; Cross Validation; Linear mixed-effects models; Sensitivity; Specificity ID MIXED-EFFECTS MODEL; PROPORTIONAL HAZARDS MODEL; EVENT TIME DATA; MAXIMUM-LIKELIHOOD; JOINT ANALYSIS; DISEASE; ANTIGEN; SURVIVAL; MIXTURE; ERROR AB Disease prediction based on longitudinal data can be done using various modeling approaches. Alternative approaches are compared using data from a longitudinal study to predict the onset of disease. The data are modeled using linear mixed-effects models. Posterior probabilities of group membership are computed starting with the first observation and sequentially adding observations until the subject is classified as developing the disease or until the last measurement is used. Individuals are classified by computing posterior probabilities using the marginal distributions of the mixed-effects models, the conditional distributions (conditional on the group-specific random effects), and the distributions of the random effects. C1 [Morrell, Christopher H.] Loyola Univ Maryland, Dept Math & Stat, Baltimore, MD 21210 USA. [Morrell, Christopher H.; Sheng, Shan L.; Brant, Larry J.] NIA, Baltimore, MD 21224 USA. RP Morrell, CH (reprint author), Loyola Univ Maryland, Dept Math & Stat, 4501 N Charles St, Baltimore, MD 21210 USA. EM chm@loyola.edu FU NIH, National Institute on Aging FX We thank Dr. Dan L. Longo for encouraging us to pursue the comparison of different prediction approaches using the mixed model. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. We also thank the anonymous referees whose comments led to a great improvement of this article. NR 43 TC 0 Z9 0 U1 1 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-0918 J9 COMMUN STAT-SIMUL C JI Commun. Stat.-Simul. Comput. PY 2011 VL 40 IS 9 BP 1494 EP 1513 DI 10.1080/03610918.2011.575510 PG 20 WC Statistics & Probability SC Mathematics GA 869XF UT WOS:000298631900001 ER PT J AU Takagi, Y Sellers, JR AF Takagi, Y. Sellers, J. R. BE Egelman, EH TI Single Molecule Fluorescence Techniques for Myosin SO COMPREHENSIVE BIOPHYSICS, VOL 4: MOLECULAR MOTORS AND MOTILITY LA English DT Article; Book Chapter ID HAND-OVER-HAND; REGULATORY LIGHT-CHAIN; SKELETAL-MUSCLE FIBERS; ENERGY-TRANSFER MEASUREMENTS; COILED-COIL DOMAIN; ACTIN-BASED MOTOR; LEVER ARM; STRUCTURAL DYNAMICS; UNCONVENTIONAL MYOSIN; ORIENTATION CHANGES C1 [Takagi, Y.; Sellers, J. R.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Takagi, Y (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 112 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-095718-0 PY 2011 BP 170 EP 190 DI 10.1016/B978-0-12-374920-8.00412-4 PG 21 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BA2VE UT WOS:000333926700010 ER PT J AU Buchanan, SK Yamashita, S Fleming, KG AF Buchanan, S. K. Yamashita, S. Fleming, K. G. BE Egelman, EH TI Structure and Folding of Outer Membrane Proteins SO COMPREHENSIVE BIOPHYSICS, VOL 5: MEMBRANES LA English DT Article; Book Chapter ID PEPTIDYL-PROLYL-ISOMERASE; GRAM-NEGATIVE BACTERIA; PERIPLASMIC CHAPERONE SKP; DEPENDENT ANION CHANNEL; 1.8 ANGSTROM RESOLUTION; A TRANSMEMBRANE DOMAIN; MULTIDRUG EFFLUX PUMP; BETA-BARREL PROTEINS; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE C1 [Buchanan, S. K.; Yamashita, S.] NIDDKD, NIH, Bethesda, MD 20892 USA. [Fleming, K. G.] Johns Hopkins Univ, Baltimore, MD USA. RP Buchanan, SK (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. NR 192 TC 1 Z9 1 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-095718-0 PY 2011 BP 139 EP 163 DI 10.1016/B978-0-12-374920-8.00514-2 PG 25 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA BA2US UT WOS:000333923100008 ER PT J AU Collins, RN Holz, RW Zimmerberg, J AF Collins, R. N. Holz, R. W. Zimmerberg, J. BE Egelman, EH TI The Biophysics of Membrane Fusion SO COMPREHENSIVE BIOPHYSICS, VOL 5: MEMBRANES LA English DT Article; Book Chapter ID INFLUENZA-VIRUS HEMAGGLUTININ; PLANAR BILAYER-MEMBRANES; SYNAPTIC VESICLE FUSION; SNARE-COMPLEX; SINGLE-MOLECULE; CONFORMATIONAL-CHANGE; PLASMA-MEMBRANE; CA2+-TRIGGERED EXOCYTOSIS; NEUROTRANSMITTER RELEASE; REGULATED EXOCYTOSIS C1 [Collins, R. N.] Cornell Univ, Ithaca, NY 14850 USA. [Holz, R. W.] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. [Zimmerberg, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Collins, RN (reprint author), Cornell Univ, Ithaca, NY 14850 USA. NR 139 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-095718-0 PY 2011 BP 273 EP 289 DI 10.1016/B978-0-12-374920-8.00523-3 PG 17 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA BA2US UT WOS:000333923100014 ER PT J AU Hassan, SA Mehler, EL AF Hassan, S. A. Mehler, E. L. BE Egelman, EH TI Molecular Electrostatics and Solvent Effects SO COMPREHENSIVE BIOPHYSICS, VOL 9: SIMULATION AND MODELLING LA English DT Article; Book Chapter ID OVOMUCOID 3RD DOMAIN; SOLVATION FREE-ENERGIES; SCALED-PARTICLE THEORY; AQUEOUS-ELECTROLYTE SOLUTIONS; SCREENED COULOMB POTENTIALS; DIPOLE-QUADRUPOLE-OCTUPOLE; PROTEIN PK(A) CALCULATIONS; SIDE-CHAIN INTERACTIONS; LIQUID-STRUCTURE FORCES; CAVITY SURFACE-AREA C1 [Hassan, S. A.] NIH, US DHHS, Bethesda, MD 20892 USA. [Mehler, E. L.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. RP Hassan, SA (reprint author), NIH, US DHHS, Bldg 10, Bethesda, MD 20892 USA. NR 323 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-095718-0 PY 2011 BP 190 EP 228 DI 10.1016/B978-0-12-374920-8.00916-4 PG 39 WC Biophysics; Mathematical & Computational Biology SC Biophysics; Mathematical & Computational Biology GA BA2QL UT WOS:000333766900011 ER PT B AU Sauerwald, TM Lewis, A Dorai, H Betenbaugh, MJ AF Sauerwald, T. M. Lewis, A. Dorai, H. Betenbaugh, M. J. BE MooYoung, M TI Apoptosis: The Signaling Pathways and Their Control SO COMPREHENSIVE BIOTECHNOLOGY, VOL 1: SCIENTIFIC FUNDAMENTALS OF BIOTECHNOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID HAMSTER OVARY CELLS; ENDOPLASMIC-RETICULUM STRESS; MONOCLONAL-ANTIBODY PRODUCTION; TRANSIENT GENE-EXPRESSION; UNFOLDED-PROTEIN RESPONSE; FED-BATCH CULTURE; MAMMALIAN-CELLS; SODIUM-BUTYRATE; CHO-CELLS; CYTOCHROME-C C1 [Sauerwald, T. M.; Dorai, H.] Centocor R&D Inc, Radnor, PA 19087 USA. [Lewis, A.] NIDA, IRP, NIH, DHHS, Baltimore, MD USA. [Lewis, A.; Betenbaugh, M. J.] Johns Hopkins Univ, Baltimore, MD USA. RP Sauerwald, TM (reprint author), Centocor R&D Inc, Radnor, PA 19087 USA. NR 117 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-088504-9; 978-0-44-453352-4 PY 2011 BP 483 EP 494 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA BA3SL UT WOS:000334724000036 ER PT J AU Caban, JJ Rheingans, P Yoo, T AF Caban, J. J. Rheingans, P. Yoo, T. TI An Evaluation of Visualization Techniques to Illustrate Statistical Deformation Models SO COMPUTER GRAPHICS FORUM LA English DT Article ID UNCERTAINTY; MORPHOMETRY; USER AB As collections of 2D/3D images continue to grow, interest in effective ways to visualize and explore the statistical morphological properties of a group of images has surged. Recently, deformation models have emerged as simple methods to capture the variability and statistical properties of a collection of images. Such models have proven to be effective in tasks such as image classification, generation, registration, segmentation, and analysis of modes of variation. A crucial element missing from most statistical models has been an effective way to summarize and visualize the statistical morphological properties of a group of images. This paper evaluates different visualization techniques that can be extended and used to illustrate the information captured by such statistical models. First, four illustration techniques are described as methods to summarize the statistical morphological properties as captured by deformation models. Second, results of a user study conducted to compare the effectiveness of each visualization technique are presented. After comparing the performance of 40 subjects, we found that statistical annotation techniques present significant benefits when analyzing the structural properties of a group of images. C1 [Caban, J. J.; Yoo, T.] NIH, Natl Lib Med, Bethesda, MD 20892 USA. [Rheingans, P.] Univ Maryland, Baltimore Cty UMBC, Baltimore, MD USA. RP Caban, JJ (reprint author), NIH, Natl Lib Med, Bethesda, MD 20892 USA. NR 27 TC 6 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0167-7055 J9 COMPUT GRAPH FORUM JI Comput. Graph. Forum PY 2011 VL 30 IS 3 BP 821 EP 830 DI 10.1111/j.1467-8659.2011.01931.x PG 10 WC Computer Science, Software Engineering SC Computer Science GA 784NP UT WOS:000292164300020 ER PT J AU Martin, S Gillespie, A Wolters, PL Widemann, BC AF Martin, Staci Gillespie, Andrea Wolters, Pamela L. Widemann, Brigitte C. TI Experiences of families with a child, adolescent, or young adult with neurofibromatosis type 1 and plexiform neurofibroma evaluated for clinical trials participation at the National Cancer Institute SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Clinical trials; Research participation; Neurofibromatosis type 1; Children; Families ID IMPROVING INFORMED-CONSENT; ATTITUDES; LEUKEMIA; REASONS; NF1 AB Background: With increasing knowledge of the molecular pathways contributing to the progression of neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN), the number of clinical trials for PNs has increased. However, little is known about the experiences of families with children with NF1 participating in clinical trials. Method: A 47-item anonymous survey, designed to assess experiences in research, was sent to parents with a child with NF1 and PNs who was evaluated at the National Cancer Institute (NCI) for a clinical trial. Results: Sixty-four (85%) parents completed the paper or online questionnaire. Fifty-nine percent of the children were male; 44% were 11 years or older upon enrollment. Most parents reported understanding the purpose of the study, possible side effects, and their right to withdraw. Of respondents whose child had participated in a placebo-controlled trial, 100% said they understood the reason for the placebo at least somewhat. Seventy-four percent felt that study participation helped their child; most would "definitely" or "probably" participate in a future study, including a placebo-controlled trial, and particularly those assessing cognitive functioning or pain. Overall satisfaction with participation was high and correlated with fewer transportation problems, fewer study-related financial difficulties, and fewer school problems for the child (ps<.05). Conclusions: Most parents of children with NF1 who participated in research at the NCI reported a positive impact and would participate in future studies. Respondents identified several areas for improvement. This report may help plan future studies to optimize experiences of children and their families enrolled in clinical trials. Published by Elsevier Inc. C1 [Martin, Staci; Gillespie, Andrea; Wolters, Pamela L.; Widemann, Brigitte C.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Martin, S (reprint author), 9030 Old Georgetown Rd,Rm 107, Bethesda, MD 20892 USA. EM martins@mail.nih.gov; gillesan@mail.nih.gov; woltersp@mail.nih.gov; widemanb@mail.nih.gov FU National Institutes of Health, National Cancer Institute; federal contract [HHSN261200477004C] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and by federal contract HHSN261200477004C. The authors are grateful to the families who responded to this survey. We also thank Jonathan Wiest, Ph.D. for his help with the development of the online version of the survey, and Sally Hunsberger, Ph.D. for her role as statistical consultant NR 21 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2011 VL 32 IS 1 BP 10 EP 15 DI 10.1016/j.cct.2010.10.004 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 710YI UT WOS:000286552500002 PM 20951236 ER PT J AU Kosaka, N Mitsunaga, M Bhattacharyya, S Miller, SC Choyke, PL Kobayashi, H AF Kosaka, Nobuyuki Mitsunaga, Makoto Bhattacharyya, Sukanta Miller, Steven C. Choyke, Peter L. Kobayashi, Hisataka TI Self-illuminating in vivo lymphatic imaging using a bioluminescence resonance energy transfer quantum dot nano-particle SO CONTRAST MEDIA & MOLECULAR IMAGING LA English DT Article DE quantum dot; nanotechnology; fluorescence; bioluminescence; lymphatic imaging; bioluminescence resonance energy transfer (BRET) ID REAL-TIME; MULTICOLOR; TUMORS AB Autofluorescence arising from normal tissues can compromise the sensitivity and specificity of in vivo fluorescence imaging by lowering the target-to-background signal ratio. Since bioluminescence resonance energy transfer quantum dot (BRET-QDot) nano-particles can self-illuminate in near-infrared in the presence of the substrate, coelenterazine, without irradiating excitation lights, imaging using BRET-QDots does not produce any autofluorescence. In this study, we applied this BRET-QDot nano-particle to the in vivo lymphatic imaging in mice in order to compare with BRET, fluorescence or bioluminescence lymphatic imaging. BRET-QDot655, in which QDot655 is contained as a core, was injected at different sites (e. g. chin, ear, forepaws and hind paws) in mice followed by the intravenous coelenterazine injection, and then bioluminescence and fluorescence imaging were serially performed. In all mice, each lymphatic basin was clearly visualized in the BRET imaging with minimal background signals. The BRET signal in the lymph nodes lasted at least 30 min after coelenterazine injections. Furthermore, the BRET signal demonstrated better quantification than the fluorescence signal emitting from QDot655, the core of this BRET particle. These advantages of BRET-QDot allowed us to perform real-time, quantitative lymphatic imaging without image processing. BRET-Qdots have the potential to be a robust nano-material platform for developing optical molecular imaging probes. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Kosaka, Nobuyuki; Mitsunaga, Makoto; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Bhattacharyya, Sukanta; Miller, Steven C.] Zymera Inc, San Jose, CA 95138 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room 1B40,MSC 1088, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 16 TC 17 Z9 17 U1 3 U2 24 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1555-4309 J9 CONTRAST MEDIA MOL I JI Contrast Media Mol. Imaging PD JAN-FEB PY 2011 VL 6 IS 1 BP 55 EP 59 DI 10.1002/cmmi.395 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 729HK UT WOS:000287939100007 PM 21351373 ER PT S AU Solomon, BD Muenke, M AF Solomon, B. D. Muenke, M. BE Muenke, M Kress, W Collmann, H Solomon, BD TI Muenke Syndrome SO CRANIOSYNOSTOSES: MOLECULAR GENETICS, PRINCIPLES OF DIAGNOSIS, AND TREATMENT SE Monographs in Human Genetics LA English DT Article; Book Chapter ID GROWTH-FACTOR RECEPTOR-3; CORONAL SYNOSTOSIS SYNDROME; FGFR3 P250R MUTATION; CRANIOSYNOSTOSIS SYNDROMES; PRO250ARG MUTATION; GENE; DIFFERENTIATION; PREVALENCE; EXPRESSION; PFEIFFER AB Muenke syndrome is defined by the presence of the p.P250R mutation in FGFR3, and is an autosomal dominant disorder with incomplete penetrance and variable expressivity. Typical manifestations of Muenke syndrome include coronal craniosynostosis, hearing loss, developmental delay/cognitive impairment, and relatively minor hand and foot anomalies. Clinical diagnosis is difficult because of phenotypic overlap and diagnosis is always made by molecular testing. Optimal management of patients involves a coordinated, multidisciplinary team familiar with the condition. Copyright (C) 2011 S. Karger AG, Basel C1 [Solomon, B. D.; Muenke, M.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mamuenke@mail.nih.gov; mamuenke@mail.nih.gov NR 37 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0077-0876 BN 978-3-8055-9595-7 J9 MONOGR HUM GENET JI Monogr. Hum. Genet. PY 2011 VL 19 BP 89 EP 97 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA BUD41 UT WOS:000288923200008 ER PT S AU Raam, MS Muenke, M AF Raam, M. S. Muenke, M. BE Muenke, M Kress, W Collmann, H Solomon, BD TI Uncommon Craniosynostosis Syndromes: A Review of Thirteen Conditions SO CRANIOSYNOSTOSES: MOLECULAR GENETICS, PRINCIPLES OF DIAGNOSIS, AND TREATMENT SE Monographs in Human Genetics LA English DT Article; Book Chapter ID ANTLEY-BIXLER-SYNDROME; BALLER-GEROLD-SYNDROME; SHPRINTZEN-GOLDBERG-SYNDROME; BEARE-STEVENSON-SYNDROME; JACKSON-WEISS-SYNDROME; CUTIS-GYRATA-SYNDROME; GROWTH-FACTOR RECEPTOR-2; ACROCEPHALOPOLYSYNDACTYLY TYPE-II; OPITZ-TRIGONOCEPHALY SYNDROME; ROTHMUND-THOMSON-SYNDROME AB Uncommon craniosynostosis syndromes, while individually less well characterized than more common conditions such as Apert, Crouzon, Pfeiffer, Muenke, and Saethre-Chotzen syndromes, comprise a significant proportion of craniosynostosis cases when considered in sum. Thirteen of these rare syndromes are covered here with respect to nosology, associated clinical characteristics, and molecular genetics. They were selected for discussion in this chapter due to recent molecular advances therein that can significantly enhance clinicians' ability to diagnose and counsel patients with these syndromes. The syndromes discussed here include Antley-Bixler syndrome, Baller-Gerold syndrome, Beare-Stevenson cutis gyrata syndrome, Bohring-Opitz syndrome, C (Opitz trigonocephaly) syndrome, Carpenter syndrome, Crouzon syndrome with acanthosis nigricans, Jackson-Weiss syndrome, Jacobsen syndrome, Loeys-Dietz syndrome type I, osteoglophonic dysplasia, P450 oxidoreductase deficiency, and Shprintzen-Goldberg syndrome. Copyright (C) 2011 S. Karger AG, Basel C1 [Raam, M. S.; Muenke, M.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Raam, M. S.] Howard Hughes Med Inst, HHMI NIH Res Scholars Program, Chevy Chase, MD USA. RP Muenke, M (reprint author), Bldg 35,Room 1B203,35 Convent Dr,MSC 3717, Bethesda, MD 20892 USA. EM muenke@nih.gov; muenke@nih.gov NR 148 TC 1 Z9 1 U1 1 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0077-0876 BN 978-3-8055-9595-7 J9 MONOGR HUM GENET JI Monogr. Hum. Genet. PY 2011 VL 19 BP 119 EP 142 PG 24 WC Genetics & Heredity SC Genetics & Heredity GA BUD41 UT WOS:000288923200011 ER PT J AU Franic, T Dodig, G Kardum, G Marcinko, D Ujevic, A Bilusic, M AF Franic, Tomislav Dodig, Goran Kardum, Goran Marcinko, Darko Ujevic, Ante Bilusic, Marijo TI Early Adolescence and Suicidal Ideations in Croatia Sociodemographic, Behavioral, and Psychometric Correlates SO CRISIS-THE JOURNAL OF CRISIS INTERVENTION AND SUICIDE PREVENTION LA English DT Article DE adolescents; gender; suicidal ideations; war; Croatia ID CHILDRENS-DEPRESSION-INVENTORY; GENDER DIFFERENCES; YOUNG ADOLESCENTS; COMMUNITY SAMPLE; SCHOOL-STUDENTS; SOCIAL SUPPORT; RISK-FACTORS; PSYCHOPATHOLOGY; WAR; AGE AB Background/Aims: Suicidal ideations (SI) indicate and predict psychological distress. We examined the prevalence of SI among early adolescents and its association with parental war participation, personal, behavioral, and sociodemographic characteristics. Methods: We performed a cross-sectional questionnaire study on 803 12-year-old adolescents. Data were collected using a sociodemographic questionnaire, the Junior Eysenck Personality Questionnaire and Children Depression Inventory. Unintentional injuries, physical fighting, and involvement in bullying behavior were assessed using questions from the World Health Organization (WHO) survey Health Behavior in School-aged Children. Suicidal ideations were assessed with three dichotomous items. Results: There were no gender differences in SI prevalence. SI in males were associated with lower maternal education, crowded families, birth order, parental war participation, physical fighting, being bullied, and substance use. In females, we found associations with lower parental educational level, number of brothers, lower perception of the relationship with parents, parental relationship, family cohesion and parental control, negative attitude toward school, rare church attendance, fighting, and being bully or bullied. Depressive symptoms and SI were associated in both genders. Conclusions: SI showed gender-specific associations that may partially be explained with parental war involvement. These findings may have potentially important clinical and preventive implications. C1 [Franic, Tomislav; Dodig, Goran] Univ Split, Sch Med, Sect Child & Adolescent Psychiat, Univ Hosp Split, Split 21000, Croatia. [Kardum, Goran] Univ Split, Sch Med, Dept Sci Methodol, Split 21000, Croatia. [Marcinko, Darko] Univ Zagreb, Sch Med, Univ Hosp Zagreb, Dept Psychiat, Zagreb 41000, Croatia. [Ujevic, Ante] Open Univ Split, Split, Croatia. [Bilusic, Marijo] Natl Canc Inst Bethesda, Med Oncol Branch, Bethesda, MD USA. RP Franic, T (reprint author), Univ Split, Sch Med, Sect Child & Adolescent Psychiat, Spinciceva 1, Split 21000, Croatia. EM tomislav.franic@mefst.hr OI Franic, Tomislav/0000-0002-5240-7166 NR 67 TC 6 Z9 6 U1 5 U2 11 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0227-5910 J9 CRISIS JI Crisis PY 2011 VL 32 IS 6 BP 334 EP 345 DI 10.1027/0227-5910/a000107 PG 12 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 866FU UT WOS:000298366700005 PM 21945838 ER PT S AU Rudebeck, PH Murray, EA AF Rudebeck, Peter H. Murray, Elisabeth A. BE Schoenbaum, G Gottfried, JA Murray, EA Ramus, SJ TI Balkanizing the primate orbitofrontal cortex: distinct subregions for comparing and contrasting values SO CRITICAL CONTRIBUTIONS OF THE ORBITOFRONTAL CORTEX TO BEHAVIOR SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Critical Contributions of the Orbitofrontal Cortex to Behavior CY MAR 30-APR 01, 2011 CL New York Acad Sci, New York, NY HO New York Acad Sci DE orbitofrontal cortex; macaque; reward; reversal learning ID MEDIAL PREFRONTAL CORTEX; HIPPOCAMPAL-FORMATION LESIONS; ORBITAL FRONTAL-CORTEX; MACAQUE MONKEYS; NEURONAL-ACTIVITY; REWARD VALUE; DECISION-MAKING; RHESUS-MONKEYS; ARCHITECTONIC SUBDIVISION; SELECTIVE AMYGDALA AB The primate orbitofrontal cortex (OFC) is often treated as a single entity, but architectonic and connectional neuroanatomy indicate that it has distinguishable parts. Nevertheless, few studies have attempted to dissociate the functions of its subregions. Here we review findings from recent neuropsychological and neurophysiological studies that do so. The lateral OFC seems to be important for learning, representing, and updating specific object-reward associations. The medial OFC seems to be important for value comparisons and choosing among objects on that basis. Rather than viewing this dissociation of function in terms of learning versus choosing, however, we suggest that it reflects the distinction between contrasts and comparisons: differences versus similarities. Making use of high-dimensional representations that arise from the convergence of several sensory modalities, the lateral OFC encodes contrasts among outcomes. The medial OFC reduces these contrasting representations of value to a single dimension, a common currency, in order to compare alternative choices. C1 [Rudebeck, Peter H.; Murray, Elisabeth A.] NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Rudebeck, PH (reprint author), NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, Bldg 49,Suite 1B80,49 Convent Dr, Bethesda, MD 20892 USA. EM rudebeckp@mail.nih.gov RI Rudebeck, Peter/G-7931-2012; OI Rudebeck, Peter/0000-0002-1411-7555; Murray, Elisabeth/0000-0003-1450-1642 FU National Institute of Mental Health FX This work was supported by the Intramural Research Program of the National Institute of Mental Health. We thank Steve Kennerley and Steve Wise for thoughtful comments on an earlier version of the manuscript. NR 65 TC 31 Z9 31 U1 0 U2 4 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-822-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2011 VL 1239 BP 1 EP 13 DI 10.1111/j.1749-6632.2011.06267.x PG 13 WC Behavioral Sciences; Multidisciplinary Sciences; Neurosciences; Psychology SC Behavioral Sciences; Science & Technology - Other Topics; Neurosciences & Neurology; Psychology GA BYL19 UT WOS:000299228800001 PM 22145870 ER PT B AU Kwon-Chung, KJ Boekhout, T Wickes, BL Fell, JW AF Kwon-Chung, Kyung J. Boekhout, Teun Wickes, Brian L. Fell, Jack W. BE Heitman, J Kozel, TR KwonChung, KJ Perfect, JR Casadevall, A TI Systematics of the Genus Cryptococcus and Its Type Species C. neoformans SO CRYPTOCOCCUS: FROM HUMAN PATHOGEN TO MODEL YEAST LA English DT Article; Book Chapter ID FILOBASIDIELLA-NEOFORMANS; RIBOSOMAL-RNA; 2 VARIETIES; BASIDIOMYCETOUS YEASTS; INTRASPECIES DIVERSITY; DEOXYRIBONUCLEIC-ACID; MOLECULAR ANALYSIS; ALBIDUS INFECTION; BRITISH-COLUMBIA; SPACER REGIONS C1 [Kwon-Chung, Kyung J.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Boekhout, Teun] CBS Fungal Divers Ctr, NL-3584 CT Utrecht, Netherlands. [Wickes, Brian L.] Univ Texas San Antonio, Univ Texas Hlth Ctr, Dept Microbiol, San Antonio, TX 78284 USA. [Fell, Jack W.] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Key Biscayne, FL 33149 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 131 TC 13 Z9 13 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-501-1 PY 2011 BP 3 EP 15 PG 13 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA BSJ71 UT WOS:000284727500001 ER PT B AU Dolan, G DiMichele, DM Rodriguez-Merchan, EC AF Dolan, Gerard DiMichele, Donna M. Rodriguez-Merchan, Emerito-Carlos BE RodriguezMerchan, EC Valentino, LA TI Perioperative Thromboprophylaxis for Persons with Hemophilia Undergoing Orthopedic Surgery SO CURRENT AND FUTURE ISSUES IN HEMOPHILIA CARE LA English DT Article; Book Chapter ID FACTOR-V-LEIDEN; HEREDITARY BLEEDING DISORDERS; DEEP VENOUS THROMBOSIS; ACTIVATED FACTOR-VII; INHIBITORS; THROMBOEMBOLISM; COMPLICATIONS; HIP; MUTATION; THROMBOPHILIA C1 [Dolan, Gerard] Univ Nottingham Hosp, Nottingham NG7 2UH, England. [DiMichele, Donna M.] Weill Cornell Med Coll, New York, NY USA. [DiMichele, Donna M.] NHLBI, Div Blood Dis & Resources, New York, NY USA. [Rodriguez-Merchan, Emerito-Carlos] La Paz Univ Hosp, Dept Orthoped Surg, Madrid, Spain. [Rodriguez-Merchan, Emerito-Carlos] La Paz Univ Hosp, Hemophilia Unit, Madrid, Spain. [Rodriguez-Merchan, Emerito-Carlos] Autonomous Univ, Sch Med, Madrid, Spain. RP Dolan, G (reprint author), Univ Nottingham Hosp, Nottingham NG7 2UH, England. NR 40 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-119-97937-1; 978-0-470-67057-6 PY 2011 BP 133 EP 137 D2 10.1002/9781119979401 PG 5 WC Hematology SC Hematology GA BA6FM UT WOS:000337127500027 ER PT J AU Sancho, V Di Florio, A Moody, TW Jensen, RT AF Sancho, Veronica Di Florio, Alessia Moody, Terry W. Jensen, Robert T. TI Bombesin Receptor-Mediated Imaging and Cytotoxicity: Review and Current Status SO CURRENT DRUG DELIVERY LA English DT Review DE Bombesin; gastrin-releasing peptide; neuromedin B; BRS-3; receptor-mediated imaging; tumor cytotoxicity; DOTA; DTPA; NOTA ID GASTRIN-RELEASING-PEPTIDE; IN-VIVO EVALUATION; LUNG-CANCER CELLS; POSITRON-EMISSION-TOMOGRAPHY; HUMAN ORPHAN RECEPTOR; HUMAN PROSTATE ADENOCARCINOMA; NEUROMEDIN-B RECEPTOR; GRP-R AGONIST; HIGH-AFFINITY; POSITIVE TUMORS AB The three mammalian bombesin (Bn) receptors (gastrin-releasing peptide [GRP] receptor, neuromedin B [NMB] receptor, BRS-3) are one of the classes of G protein-coupled receptors that are most frequently overexpress/ectopically expressed by common, important malignancies. Because of the clinical success of somatostatin receptor-mediated imaging and cytotoxicity with neuroendocrine tumors, there is now increasing interest in pursuing a similar approach with Bn receptors. In the last few years then have been more than 200 studies in this area. In the present paper, the in vitro and in vivo results, as well as results of human studies from many of these studies are reviewed and the current state of Bn receptor-mediated imaging or cytotoxicity is discussed. Both Bn receptor-mediated imaging studies as well as Bn receptor-mediated tumoral cytotoxic studies using radioactive and non-radioactive Bn-based ligands are covered. C1 [Sancho, Veronica; Di Florio, Alessia; Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. [Moody, Terry W.] NCI, US Dept HHS, Off Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Room 9C-103, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov FU NIDDK; NCI; NIH FX This work was partially supported by intramural research funds of NIDDK and NCI, NIH. NR 188 TC 61 Z9 62 U1 0 U2 20 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2018 EI 1875-5704 J9 CURR DRUG DELIV JI Curr. Drug Deliv. PD JAN PY 2011 VL 8 IS 1 BP 79 EP 134 DI 10.2174/156720111793663624 PG 56 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 768AQ UT WOS:000290903700008 PM 21034419 ER PT J AU Brewer, LC Michos, ED Reis, JP AF Brewer, LaPrincess C. Michos, Erin D. Reis, Jared P. TI Vitamin D in Atherosclerosis, Vascular Disease, and Endothelial Function SO CURRENT DRUG TARGETS LA English DT Review DE Atherosclerosis; calcification; calcitriol; cardiovascular disease; heart disease; vitamin D ID PERIPHERAL ARTERIAL-DISEASE; NUTRITION EXAMINATION SURVEY; CARDIOVASCULAR RISK-FACTORS; BEAM COMPUTED-TOMOGRAPHY; RENIN-ANGIOTENSIN SYSTEM; SMOOTH-MUSCLE-CELLS; 3RD NATIONAL-HEALTH; RANDOMIZED CONTROLLED-TRIAL; PARATHYROID-HORMONE LEVELS; 25-HYDROXYVITAMIN D LEVELS AB Vitamin D deficiency has been linked to an increased risk of hypertension, diabetes, congestive heart failure, peripheral arterial disease, myocardial infarction, stroke, and related mortality, even after adjustment for traditional cardiovascular risk factors. Accumulating evidence from experimental, clinical, and epidemiological studies suggests that vitamin D may also be associated with several indices of vascular function, including the development and progression of atherosclerotic cardiovascular disease. These findings may provide at least a partial explanation for several recent epidemiologic studies implicating low vitamin D status in the pathogenesis of cardiovascular disease. However, many questions still remain. Only a handful of studies are currently available, and the results of these studies have generally been mixed. Additionally, it is unknown whether findings differ across varied subpopulations, including minority subgroups in the United States, younger adults, and those residing in areas with varying amounts of regular sunlight. Furthermore, the exact mechanism by which vitamin D may influence the atherosclerotic disease process has not yet been completely elucidated. In addition, if vitamin D is important in the etiology of atherosclerosis, it is unclear at what stage(s) in the atherosclerotic disease process vitamin D may exert its effects. Large-scale, well-conducted, placebo controlled clinical trials testing the efficacy of vitamin D supplementation in delaying, slowing, or reverting the atherosclerotic disease process have not yet been conducted. Until the results of these studies are available, we believe it is premature to recommend vitamin D as a therapeutic option in atherosclerosis. C1 [Reis, Jared P.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Brewer, LaPrincess C.] Johns Hopkins Univ, Sch Med, Dept Med, Johns Hopkins Bayview Med Ctr, Baltimore, MD 21205 USA. [Michos, Erin D.] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21205 USA. RP Reis, JP (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Suite 10197, Bethesda, MD 20892 USA. EM reisjp@nhlbi.nih.gov OI Brewer, LaPrincess/0000-0002-6468-9324 NR 113 TC 55 Z9 58 U1 0 U2 11 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD JAN PY 2011 VL 12 IS 1 BP 54 EP 60 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 692WJ UT WOS:000285186300006 PM 20795937 ER PT J AU Grant, C Wilson, WH Dunleavy, K AF Grant, Cliona Wilson, Wyndham H. Dunleavy, Kieron TI Neutropenia associated with rituximab therapy SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE B-cell recovery; lymphoma; neutropenia; rituximab; SDF-1 ID NON-HODGKINS-LYMPHOMA; LATE-ONSET NEUTROPENIA; MONOCLONAL-ANTIBODY THERAPY; B-CELL LYMPHOMA; CHEMOKINE RECEPTOR CXCR4; BONE-MARROW; FACTOR-I; LEUKEMIA; TRANSPLANTATION; CHEMOTHERAPY AB Purpose of review Several recent studies have reported the occurrence of late-onset neutropenia (LON) following the use of rituximab or rituximab-based therapies. While this phenomenon is typically self-limiting and of no clinical significance, recognizing its existence is important given the expanding use of rituximab in both hematologic and nonhematologic disorders. This review discusses the incidence of LON and explores several hypotheses that have been proposed to explain its occurrence. Recent findings While the etiology of LON is uncertain and poorly understood, mechanisms that have been suggested include the production of antineutrophil antibodies following rituximab, the expansion of large granular lymphocyte (LGL) populations that may induce neutrophil apoptosis through Fas and Fas-ligand interactions, and aberrant B-cell reconstitution following rituximab leading to immune dyscrasias and the development of neutropenia. We explored an alternative hypothesis that LON following rituximab is caused by perturbations of granulocyte homeostasis, mediated by a complex interaction between B-cell recovery and the chemokine stromal-derived factor-1 (SDF-1). Summary While rituximab has been associated with both early and late neutropenia, LON occurring several weeks to several months after the administration of rituximab is a distinct biologic phenomenon that appears to be related to B-cell recovery. Though it occurs frequently, it is a self-limiting process and is rarely associated with significant clinical sequelae. C1 [Dunleavy, Kieron] NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. RP Dunleavy, K (reprint author), NCI, Ctr Canc Res, Metab Branch, Bldg 10,Room 4-N-115, Bethesda, MD 20892 USA. EM dunleavk@mail.nih.gov FU National Institutes of Health FX Some of the research that is discussed in this review was funded by the National Institutes of Health. NR 34 TC 8 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JAN PY 2011 VL 18 IS 1 BP 49 EP 54 DI 10.1097/MOH.0b013e3283414edf PG 6 WC Hematology SC Hematology GA 692FH UT WOS:000285137900008 PM 21102324 ER PT J AU Maldarelli, F AF Maldarelli, Frank TI Targeting viral reservoirs: ability of antiretroviral therapy to stop viral replication SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE active cycles of replication; drug intensification; HIV infection ID IMMUNODEFICIENCY-VIRUS TYPE-1; INTEGRASE INHIBITOR RALTEGRAVIR; TERMINAL REPEAT CIRCLES; LOW-LEVEL VIREMIA; DYNAMICS IN-VIVO; REVERSE-TRANSCRIPTASE; PROTEASE INHIBITORS; HIV-1 INFECTION; ANTIVIRAL THERAPY; RESIDUAL VIREMIA AB Purpose of review HIV infection is controlled but not cured by combination antiretroviral therapy. HIV may persist for a number of reasons, including ongoing cycles of HIV infection or viral persistence as latent, or HIV replication in long-lived cells containing HIV proviruses. Therapeutic consequences of these alternative mechanisms are significant and distinct. If ongoing replication remains during current antiretroviral therapy, then improvements in potency will be useful in eradication strategies. Alternatively, long-lived cells with integrated proviruses will not be affected by improvements in therapy directed against active infection, and new strategies will be necessary for HIV eradication. Technologic advances have made it possible to carry out a series of drug intensification protocols in well suppressed patients; these and other analyses for HIV replication have been useful to elucidate the nature of HIV persistence on therapy. Recent findings A number of clinical studies intensifying antiretroviral therapy carried out in the last several years have yielded new findings regarding the ability to detect the presence of ongoing replication. Decreases in persistent viremia have not been consistently detected in individuals on potent combination antiretroviral therapy. Evidence for persistent replication has been reported in patients using sensitive assays of cell-associated HIV. Summary HIV viremia persists despite combination antiretroviral therapy. Antiretroviral drug intensification does not lower the level of HIV measured in plasma, suggesting current therapy arrests active virus replication. HIV eradication will most likely require therapy in addition to potent antiretroviral therapy. C1 NCI, HIV Drug Resistance Program, NIH, Bethesda, MD 20892 USA. RP Maldarelli, F (reprint author), NCI, HIV Drug Resistance Program, NIH, Bldg 10,Rm 5A06,10 Ctr Dr, Bethesda, MD 20892 USA. EM fmalli@mail.nih.gov FU National Cancer Institute, National Institutes of Health FX The study received funds from National Cancer Institute, National Institutes of Health. NR 62 TC 20 Z9 20 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD JAN PY 2011 VL 6 IS 1 BP 49 EP 56 DI 10.1097/COH.0b013e32834134ea PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 828OH UT WOS:000295511000009 PM 21228755 ER PT J AU Berger, EA AF Berger, Edward A. TI Targeted cytotoxic therapy: adapting a rapidly progressing anticancer paradigm for depletion of persistent HIV-infected cell reservoirs SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE adoptive cell therapy; antibody-drug conjugates; chimeric antigen receptor; immunotoxin; oncolytic virotherapy; radioimmunotherapy; targeted liposome ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; ZINC-FINGER NUCLEASES; T-CELLS; IN-VIVO; ANTITUMOR-ACTIVITY; VIRAL RESERVOIRS; MAGIC BULLET; RECEPTOR; IMMUNOTOXIN AB Purpose of review HIV-infected cells persisting in the face of highly active antiretroviral therapy are arguably the greatest hurdle to eradication of the virus from the body. Complementary strategies aimed at selective killing of infected cells are described. Recent findings Pioneered by research in the cancer field, various approaches are under development for selective killing of HIV-infected cells. These include targeted cytotoxic proteins, adoptive cell therapy, cytocidal virotherapy, and targeted nonbiological drug carriers. Summary These developmental efforts may provide a critical complement to antiretroviral therapy in efforts to achieve HIV eradication, or a 'functional cure' whereby therapy can be stopped without viral rebound. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Berger, EA (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 33,Room 3W20, Bethesda, MD 20892 USA. EM edward_berger@nih.gov FU National Institute of Allergy and Infectious Diseases, NIH; NIH FX This work was supported in part by the Intramural Program of the National Institute of Allergy and Infectious Diseases, NIH, including the NIH Intramural AIDS Targeted Antiviral Program. E. A. Berger is a co-inventor on NIH-owned patents and patent applications on sCD4-PE40 and 3B3-PE38. NR 50 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD JAN PY 2011 VL 6 IS 1 BP 80 EP 85 DI 10.1097/COH.0b013e3283412515 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 828OH UT WOS:000295511000014 PM 21242898 ER PT J AU Matta, JA Ahern, GP AF Matta, Jose A. Ahern, Gerard P. TI TRPV1 and Synaptic Transmission SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Review DE Brain; CNS; pain; presynaptic; spinal cord; TRPV1 ID PROTEIN-KINASE-C; DORSOLATERAL PERIAQUEDUCTAL GRAY; CAPSAICIN RECEPTOR TRPV1; DORSAL-ROOT GANGLION; NR2B-CONTAINING NMDA RECEPTORS; VANILLOID TYPE-1 RECEPTORS; LONG-TERM POTENTIATION; NEURONS IN-VITRO; SENSORY NEURONS; GLUTAMATE RELEASE AB Transient Receptor Potential Vanilloid Type 1 is a prominent "pain" receptor expressed in sensory afferent neurons. TRPV1 on peripheral nerve terminals detects a variety of noxious stimuli generated at sites of injury and inflammation, and in turn, drives the excitation and sensitization of C-fiber neurons. Significantly, TRPV1 is also located on the central terminals of sensory neurons projecting to the spinal cord and brainstem. These TRPV1 channels appear to stimulate the secretion of glutamate. Further, TRPV1 is expressed diffusely in the brain and there is emerging evidence for TRPV1 modulating transmission at various brain synapses. Here we discuss our current understanding of the potential roles for TRPV1 in synaptic transmission. C1 [Ahern, Gerard P.] Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. [Matta, Jose A.] NIGMS, Bethesda, MD 20892 USA. RP Ahern, GP (reprint author), Georgetown Univ, Med Ctr, Dept Pharmacol, MedDent SW401,3900 Reservoir Rd NW, Washington, DC 20007 USA. EM gpa3@georgetown.edu NR 84 TC 19 Z9 20 U1 1 U2 8 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2010 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PD JAN PY 2011 VL 12 IS 1 BP 95 EP 101 PG 7 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 711KI UT WOS:000286589900011 PM 20932254 ER PT S AU Sartorelli, V Juan, AH AF Sartorelli, Vittorio Juan, Aster H. BE Pavlath, GK TI SCULPTING CHROMATIN BEYOND THE DOUBLE HELIX: EPIGENETIC CONTROL OF SKELETAL MYOGENESIS SO CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY: MYOGENESIS SE Current Topics in Developmental Biology LA English DT Review; Book Chapter ID EMBRYONIC STEM-CELLS; HISTONE METHYLTRANSFERASE ACTIVITY; MUSCLE SATELLITE CELLS; METHYL-TRANSFERASE SUV39H1; MEF2 TRANSCRIPTION FACTOR; POLYCOMB TARGET GENES; SWI/SNF ATPASE BRG1; GROUP PROTEIN EED; POSTNATAL MYOGENESIS; P38 MAPK AB Satellite cells (SCs) are the main source of adult skeletal muscle stem cells responsible for muscle growth and regeneration. By interpreting extracellular cues, developmental regulators control quiescence, proliferation, and differentiation of SCs by influencing coordinate gene expression. The scope of this review is limited to the description and discussion of protein complexes that introduce and decode heritable histone and chromatin modifications and how these modifications are relevant for SC biology. C1 [Sartorelli, Vittorio; Juan, Aster H.] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Lab Muscle Stem Cell & Gene Regulat, NIH, Bethesda, MD USA. RP Sartorelli, V (reprint author), Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Lab Muscle Stem Cell & Gene Regulat, NIH, Bethesda, MD USA. FU Intramural NIH HHS [ZIA AR041126-11] NR 190 TC 22 Z9 22 U1 0 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 BN 978-0-12385-940-2 J9 CURR TOP DEV BIOL JI Curr. Top. Dev. Biol. PY 2011 VL 96 BP 57 EP 83 DI 10.1016/B978-0-12-385940-2.00003-6 PG 27 WC Developmental Biology SC Developmental Biology GA BVN82 UT WOS:000292007000003 PM 21621067 ER PT S AU Nieman, LK AF Nieman, Lynnette K. BE Swearingen, B Biller, BMK TI The Diagnosis of Cushing's Syndrome SO CUSHING'S DISEASE SE Endocrine Updates LA English DT Article; Book Chapter DE Glucocorticoids; Adrenocorticotropic hormone; Cortisol; Biochemical screening ID DEXAMETHASONE-SUPPRESSION TEST; HORMONE STIMULATION TEST; SALIVARY CORTISOL-LEVELS; DIFFERENTIAL-DIAGNOSIS; TESTS; DISEASE; STATES; HYPERCORTISOLISM; POPULATION; MORTALITY AB Cushing's syndrome is characterized by exposure to excess glucocorticoid. It can be caused by exogenous administration of these compounds, usually in supraphysiologic treatment doses. Endogenous Cushing's syndrome is caused either by excessive ACTH production from a pituitary or other tumor, or by autonomous adrenal cortisol production. Clinical features suggestive of the disorder should prompt biochemical screening. Case detection of this rare disorder is justified by the high standardized mortality rate, which is normalized after successful treatment. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, CRC, Bethesda, MD 20892 USA. RP Nieman, LK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, CRC, Bldg 10,1 East,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM NiemanL@nih.gov NR 29 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1566-0729 BN 978-1-4614-0010-3 J9 ENDOCR UPDAT PY 2011 BP 45 EP 55 DI 10.1007/978-1-4614-0011-0_4 D2 10.1007/978-1-4614-0011-0 PG 11 WC Endocrinology & Metabolism; Medicine, General & Internal SC Endocrinology & Metabolism; General & Internal Medicine GA BYU39 UT WOS:000300384400004 ER PT B AU Stratakis, C AF Stratakis, Constantine BE Bronstein, MD TI ACTH-Independent Cushing's Syndrome: Primary Pigmented Nodular Adrenal Disease in the Context of Carney's Complex SO CUSHINGS SYNDROME: PATHOPHYSIOLOGY, DIAGNOSIS AND TREATMENT, FIRST EDITION SE Contemporary Endocrinology LA English DT Article; Book Chapter DE Adrenocortical tumors; cAMP signaling; phosphodiesterases; PKA ID PROTEIN-KINASE-A; PHOSPHODIESTERASE 11A4 PDE11A; FAMILIAL CARDIAC MYXOMAS; SUBUNIT TYPE 1A; REGULATORY SUBUNIT; ADRENOCORTICAL DISEASE; ENDOCRINE OVERACTIVITY; SPOTTY PIGMENTATION; PRKAR1A MUTATIONS; GENE AB In this chapter, we discuss clinical and molecular findings of micronodular adrenal hyperplasias (MAHs) that lead to ACTH-independent Cushing syndrome. We focus on the role of genetic defects in cyclic AMP (cAMP) signaling-related molecules, namely PRKAR1A, GNAS, PDE11A, and PDE8B; molecular defects in the phosphodiesterases (PDE) family are the most recently discovered genetic defects predisposing to adrenocortical tumor formation. The prototype of these disorders was Carney complex (CNC) in the context of which the first MAH was described: primary pigmented nodular adrenocortical disease or PPNAD. PPNAD is due to defects in PRKAR1A, the gene that functions as a receptor for the cAMP. In contrast to GNAS and PRKAR1A, defects in PDE genes are associated more frequently with incomplete penetrance. Identifying low-penetrance mutations in more than one PDE in patients with MAHs is suggestive for a complementary role of the different PDEs in the adrenal gland, and possible involvement of other members of this gene family in adrenocortical tumors and ACTH-independent Cushing syndrome. C1 NICHD, Endocrinol Sect, Genet SEGEN, PDEGEN,NIH, Bethesda, MD USA. RP Stratakis, C (reprint author), NICHD, Endocrinol Sect, Genet SEGEN, PDEGEN,NIH, Bethesda, MD USA. NR 54 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-448-7 J9 CONTEMP ENDOCRINOL S PY 2011 BP 225 EP 234 DI 10.1007/978-1-60327-449-4_18 D2 10.1007/978-1-60327-449-4 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BRP51 UT WOS:000283332000018 ER PT S AU Sojka, D Francischetti, IMB Calvo, E Kotsyfakis, M AF Sojka, Daniel Francischetti, Ivo M. B. Calvo, Eric Kotsyfakis, Michalis BE Robinson, MW Dalton, JP TI CYSTEINE PROTEASES FROM BLOODFEEDING ARTHROPOD ECTOPARASITES SO CYSTEINE PROTEASES OF PATHOGENIC ORGANISMS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID TICK HAEMAPHYSALIS-LONGICORNIS; PROLIXUS STAL HEMIPTERA; YELLOW-FEVER MOSQUITO; BLOOD-MEAL DIGESTION; L-LIKE ENZYME; BOOPHILUS-MICROPLUS; RHODNIUS-PROLIXUS; CATHEPSIN-B; ASPARAGINYL ENDOPEPTIDASES/LEGUMAINS; PROTEOLYTIC ACTIVATION AB Cysteine proteases have been discovered in various bloodfeeding ectoparasites. Here, we assemble the available information about the function of these peptidases and reveal their role in hematophagy and parasite development. While most of the data shed light on key proteolytic events that play a role in arthropod physiology, we also report on the association of cysteine proteases with arthropod vectorial capacity. With emphasis on ticks, specifically Ixodes ricinus, we finally propose a model about the contribution of cysteine peptidases to blood digestion and how their concerted action with other tick midgut proteases leads to the absorbance of nutrients by the midgut epithelial cells. C1 [Kotsyfakis, Michalis] Acad Sci Czech Republic, Ctr Biol, Inst Parasitol, Lab Genom & Prote Dis Vectors, Prague, Czech Republic. [Sojka, Daniel] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, Lab Vector Immunol, CR-37005 Ceske Budejovice, Czech Republic. [Francischetti, Ivo M. B.; Calvo, Eric] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RP Kotsyfakis, M (reprint author), Acad Sci Czech Republic, Ctr Biol, Inst Parasitol, Lab Genom & Prote Dis Vectors, Prague, Czech Republic. EM kotsyfakis@paru.cas.cz RI Sojka, Daniel/G-8354-2014; Kotsyfakis, Michail/G-9525-2014 OI Kotsyfakis, Michail/0000-0002-7526-1876 FU Intramural NIH HHS [Z99 AI999999, ZIA AI001012-04] NR 58 TC 11 Z9 11 U1 0 U2 8 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-8413-5 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2011 VL 712 BP 177 EP 191 D2 10.1007/978-1-4419-8414-2 PG 15 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BUH77 UT WOS:000289378600011 PM 21660665 ER PT J AU Zarkowsky, D Lamoreaux, L Chattopadhyay, P Koup, RA Perfetto, SP Roederer, M AF Zarkowsky, David Lamoreaux, Laurie Chattopadhyay, Pratip Koup, Richard A. Perfetto, Stephen P. Roederer, Mario TI Heavy Metal Contaminants Can Eliminate Quantum Dot Fluorescence SO CYTOMETRY PART A LA English DT Article DE immunophenotyping; formalin; fluorescence intensity; quality control ID POLYMER NANOPARTICLES; SENSOR AB Quantum dots (QD) are fluorescent nanocrystals that are highly useful in imaging and flow cytometric analyses. During routine use of monoclonal antibody conjugates of QD, we have occasionally seen partial or total loss of fluorescence when using certain lots of fixative solutions. We hypothesized that a low level contamination with heavy metal cations was responsible, since low level metal contaminants are not uncommon in formalin solutions. By titrating known concentrations of heavy metal cations into staining solutions, we found that millimolar concentrations of ferrous and zinc ions, and as low as 50 nanomolar cupric ions, completely eliminated QD fluorescence. By mass spectroscopic quantification of metals in commercial fixative solutions previously shown to perform poorly or well with regard to QD fluorescence, we confirmed that the presence of copper in solution was correlated with poor performance. Notably, prior addition of EDTA to chelate the divalent cations in these solutions prevented the inhibition of QD fluorescence. Finally, the copper-induced loss of QD fluorescence is irreversible: cells labeled with QD are highly fluorescent and can be rendered nonfluorescent by the addition of cupric sulfate, even after washing extensively. Indeed, these cells can then be successfully stained with other QD reagents, providing a method for immunofluorescence restaining of cells without contaminating fluorescence from the first stain. Published 2010 Wiley-Liss, Inc.* C1 [Chattopadhyay, Pratip; Perfetto, Stephen P.; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Zarkowsky, David; Lamoreaux, Laurie; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Roederer, M (reprint author), NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 5509, Bethesda, MD 20892 USA. EM Roederer@nih.gov RI Chattopadhyay, Pratip/B-9227-2008; OI Chattopadhyay, Pratip/0000-0002-5457-9666 FU National Institute for Allergy and Infectious Diseases of the National Institutes of Health FX Grant sponsor: Intramural Research Program of the National Institute for Allergy and Infectious Diseases of the National Institutes of Health. NR 6 TC 14 Z9 14 U1 2 U2 22 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD JAN PY 2011 VL 79A IS 1 BP 84 EP 89 DI 10.1002/cyto.a.20986 PG 6 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 703LZ UT WOS:000285980700011 PM 21182185 ER PT J AU Wang, L Abbasi, F Jasper, GA Kreitman, RJ Liewehr, DJ Marti, GE Stetler-Stevenson, M AF Wang, Lili Abbasi, Fatima Jasper, Gregory A. Kreitman, Robert J. Liewehr, David J. Marti, Gerald E. Stetler-Stevenson, Maryalice TI Variables in the Quantification of CD4 in Normals and Hairy Cell Leukemia Patients SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE quantitative flow cytometry; CD4 quantification; anti-CD4 PE unimolar conjugate; sample preparation method ID FLOW CYTOMETRIC ANALYSIS; T-LYMPHOCYTES; EXPRESSION; QUANTITATION; SPECIMENS; BEADS AB Background: Quantitative flow cytometry (QFCM) is being applied in the clinical flow cytometry laboratory. Quantitative normal T-cell CD4 expression represents a biologic standard and quality control agent. However, low levels of CD4 expression were detected in normal T-cells in Hairy Cell Leukemia (HCL) samples. Methods: The QuantiBrite System (R) was used to determine the level of CD4 expression (mean antibody bound per cell, ABC) in fresh and shipped HCL blood and fresh normal donor blood (NDB). The effects of shipping, lysing reagent, cell preparation method, and antibody lot were evaluated. Results: Shipped HCL specimens (n = 69) had a significantly lower mean CD4 ABC of 38,788 (CV = 9.1%) compared to fresh specimens (n = 105) CD4 value of 40,330 (CV = 8.4%) (P < 0.05). In NDB, significant differences were seen for fresh versus shipped specimens using the stain/lyse method but not for lyse/stain method. Consistent differences in CD4 ABC based upon antibody lot were observed in fresh HCL and NDB samples. Stain/lyse and lyse/stain methods using NH(4)Cl lyse were compared in NDB using identical samples and antibodies. The NDB CD4 ABC values obtained with the lyse (NH(4)Cl)/stain method (45,562, 3.7% CV) were lower than those obtained with the stain/lyse (NH(4)Cl) method (49,955, 3.3% CV) with P < 0.001. Conclusions: CD4 expression in HCL patient samples is not inherently different from that observed in NDB and therefore may serve as a biological control in clinical QFCM. Technical variables impact significantly on QFCM of CD4. Published 2010 Wiley-Liss, Inc.(dagger) C1 [Jasper, Gregory A.; Stetler-Stevenson, Maryalice] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Wang, Lili] NIST, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. [Abbasi, Fatima] CBER FDA, Div Cell & Gene Therapies, Lab Stem Cell Biol, Cellular & Tissue Therapy Branch,Off Cellular Tis, Bethesda, MD 20892 USA. [Kreitman, Robert J.] NCI, Clin Immunotherapy Sect, NIH, Bethesda, MD 20892 USA. [Liewehr, David J.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Stetler-Stevenson, M (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A-33,Mail Stop 1500, Bethesda, MD 20892 USA. EM stetler@mail.nih.gov FU NIH; NCI; CBER; FDA FX Grant sponsors: NIH, NCI, CBER, FDA. NR 20 TC 7 Z9 7 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JAN PY 2011 VL 80B IS 1 BP 51 EP 56 DI 10.1002/cyto.b.20541 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 703MC UT WOS:000285981000008 PM 20687201 ER PT S AU Rudrabhatla, P Pant, HC AF Rudrabhatla, Parvathi Pant, Harish C. BE Nixon, RA Yuan, A TI Topographic Regulation of Neuronal Intermediate Filament Proteins by Phosphorylation: In Health and Disease SO CYTOSKELETON OF THE NERVOUS SYSTEM SE Advances in Neurobiology LA English DT Article; Book Chapter DE ALS; Alzheimer's disease; Axonal transport; Neurofilament; Proline-directed kinases ID AMYOTROPHIC-LATERAL-SCLEROSIS; MARIE-TOOTH-DISEASE; CASEIN KINASE-I; CYCLIN-DEPENDENT KINASE-5; NEUROFILAMENT NF-L; MYELIN-ASSOCIATED GLYCOPROTEIN; MICROTUBULE-ASSOCIATED PROTEIN; SQUID STELLATE GANGLION; SLOW AXONAL-TRANSPORT; HELICAL HEAD DOMAIN AB Neurofilaments (NFs) belong to type 1 V family of intermediate filaments and are the most abundant proteins of the nervous system. Mammalian NF triplet proteins constitute three subunits, low molecular weight (NF-L), medium molecular weight (NF-M), and high molecular weight (NF-H) subunit proteins. The NF-M/H carboxy terminal tail domain has multiple KSP repeats (40 >= 100) depending upon species, the phosphorylation of which regulates axonal caliber and axonal transport. The NF tail domain contains phosphorylation sites for proline directed kinases such as mitogen activated protein kinases (MAPKs), cyclin dependent protein kinase 5 (Cdk5), c-Jun amino terminal kinase (JNKs), and glycogen synthase kinase-3 (GSK-3). The signaling cascades involved in NF phosphorylation like MAPKs and Cdk5 can also be affected by myelin associated glycoprotein (MAG). MAG activates the Erk1/2 and Cdk5 activities due to the glial/axon interaction and increases the proline directed Ser/Thr phosphorylation of C-terminal domain of NF-M/H. The NF phosphorylation is topographically regulated. In normal neurons, NFs are phosphorylated only in the axonal compartment. However, in degenerative neurons such as Alzheimer's disease (AD), spinal cord motor neuron inclusions of amyotrophic lateral sclerosis (ALS), Lewy bodies of Parkinson's disease (PD), and Pick's disease neurofilament proteins are aberrantly phosphorylated in the cell bodies. Aberrant phosphorylation of NFs in neurodegeneration is either due to the deregulation of proline directed kinases such as MAPKs and Cdk5 or the downregulation of protein phosphatases such as protein phosphatase 2A (PP2A), calcineurin (PP2B), or both. Recently, studies from our laboratory have shown that peptidyl prolyl isomerase 1 (Pin I) stabilizes the NF phosphorylation in normal and stressed neurons. Pin I selectively binds to the phosphorylated Ser/Thr-Pro residues and converts the cis isomers to the more stable trans isomers. The multiple SP repeats of NF-M/H are stabilized by Pin 1 in a phosphorylation specific manner. Pin I modulates the excitotoxic and oxidative stress induced perikaryal phosphorylation of NF-M/H. Here, we have discussed the factors regulating the topographic phosphorylation of NFs in health and disease. C1 [Rudrabhatla, Parvathi; Pant, Harish C.] NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Pant, HC (reprint author), NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. EM parvathir@ninds.nih.gov; panth@ninds.nih.gov NR 142 TC 2 Z9 2 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2190-5215 BN 978-1-4419-6786-2 J9 ADV NEUROBIOL JI Adv. Neurobiol. PY 2011 VL 3 BP 627 EP 656 DI 10.1007/978-1-4419-6787-9_26 D2 10.1007/978-1-4419-6787-9 PG 30 WC Biology; Neurosciences SC Life Sciences & Biomedicine - Other Topics; Neurosciences & Neurology GA BTS28 UT WOS:000287955100026 ER PT J AU Melenhorst, JJ Barrett, AJ AF Melenhorst, Jan Joseph Barrett, Austin John TI Tumor vaccines and beyond SO CYTOTHERAPY LA English DT Review DE cancer vaccines; gene therapy; genes; stem cell transplantation; T-cell receptor ID T-CELL RESPONSES; MINOR HISTOCOMPATIBILITY ANTIGEN; ACUTE-MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; ALLOGENEIC BONE-MARROW; EXPRESSING INDOLEAMINE 2,3-DIOXYGENASE; ACUTE NONLYMPHOCYTIC LEUKEMIA; PERIPHERAL-BLOOD LYMPHOCYTES; ENHANCED ANTITUMOR-ACTIVITY; MINIMAL RESIDUAL DISEASE AB For the last two decades the immunotherapy of patients with solid and hematopoietic tumors has met with variable success. We have reviewed the field of tumor vaccines to examine what has worked and what has not, why this has been the case, how the anti-tumor responses were examined, and how we can make tumor immunity successful for the majority of individuals rather than for the exceptional patients who currently show successful immune responses against their tumors. C1 [Melenhorst, Jan Joseph; Barrett, Austin John] NHLBI, Stem Cell Allogene Transplant Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Melenhorst, JJ (reprint author), NHLBI, Stem Cell Allogene Transplant Sect, Hematol Branch, NIH, Bldg 10-CRC,10 Ctr Dr,Rm 3-5320, Bethesda, MD 20892 USA. EM melenhoj@nhlbi.nih.gov FU National Institutes of Health, National Heart, Lung, and Blood Institute FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute. NR 164 TC 6 Z9 6 U1 1 U2 5 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD JAN PY 2011 VL 13 IS 1 BP 8 EP 18 DI 10.3109/14653249.2010.530649 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 693SX UT WOS:000285246800002 PM 21067312 ER PT J AU Liu, DL Glaser, AP Patibandla, S Blum, A Munson, PJ Mccoy, JP Raghavachari, N Cannon, RO AF Liu, Delong Glaser, Alexander P. Patibandla, Sushmitha Blum, Arnon Munson, Peter J. Mccoy, J. Philip Raghavachari, Nalini Cannon, Richard O., III TI Transcriptional profiling of CD133(+) cells in coronary artery disease and effects of exercise on gene expression SO CYTOTHERAPY LA English DT Article DE coronary artery disease; exercise; gene expression; progenitor cells; vascular repair ID ENDOTHELIAL PROGENITOR CELLS; HISTONE ACETYLATION MODIFIERS; CARDIOVASCULAR-DISEASE; TRAINING INCREASES; REDUCED NUMBER; NITRIC-OXIDE; STEM; MOBILIZATION; HOXA9; LYMPHOCYTES AB Background aims. Bone marrow (BM)-derived progenitor cells are under investigation for cardiovascular repair but may be altered by disease. Our aim was to identify differences in gene expression in CD133(+) cells of patients with coronary artery disease (CAD) and healthy controls, and determine whether exercise modifies gene expression. Methods. CD133(+) cells were flow-sorted from 10 CAD patients and four controls, and total RNA was isolated for microarray-based gene expression profiling. Genes that were found to be differentially regulated in patients were analyzed further to investigate whether exercise had any normalizing effect on CD 133(+) cells in CAD patients following 3 months of an exercise program. Results. Improvement in effort tolerance and increases in the number of CD133(+) cells were observed in CAD patients after 3 months of exercise. Gene expression analysis of the CD133(+) cells identified 82 differentially expressed genes (2-fold cut-off, 25% false-discovery rate and % present calls) in patients compared with controls, of which 59 were found to be up-regulated and 23 down-regulated. These genes were found to be involved in carbohydrate metabolism, cell cycle, cellular development and signaling, and molecular transport. Following completion of the exercise program, gene expression patterns resembled those of controls in seven of 10 patients. Conclusions. Alterations in gene expression of BM-derived CD133(+) progenitor cells were found in CAD patients, which in part may be normalized by exercise. C1 [Glaser, Alexander P.; Patibandla, Sushmitha; Blum, Arnon; Cannon, Richard O., III] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Liu, Delong; Munson, Peter J.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10-CRC Room 5-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM cannonr@nih.gov OI Glaser, Alexander/0000-0003-1781-9023 FU NIH, National Heart, Lung and Blood Institute FX This research was supported by the Intramural Research Program of the NIH, National Heart, Lung and Blood Institute. We would like to acknowledge Ms Kimberly Woodhouse for her technical assistance in performing the QPCR assays. NR 37 TC 5 Z9 5 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2011 VL 13 IS 2 BP 227 EP 236 DI 10.3109/14653249.2010.491611 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 716HD UT WOS:000286958800010 PM 21235297 ER PT J AU Yong, K Brechbiel, MW AF Yong, Kwon Brechbiel, Martin W. TI Towards translation of Pb-212 as a clinical therapeutic; getting the lead in! SO DALTON TRANSACTIONS LA English DT Article ID DISSEMINATED PERITONEAL DISEASE; ALPHA-PARTICLE EMITTERS; BIFUNCTIONAL CHELATING-AGENT; LINEAR-ENERGY-TRANSFER; IN-VIVO; MONOCLONAL-ANTIBODIES; MAMMALIAN-CELLS; BIOLOGICAL EFFECTIVENESS; EMITTING RADIONUCLIDES; TARGETED RADIOTHERAPY AB Targeted alpha-particle therapy offers the potential for more specific tumor cell killing with less damage to surrounding normal tissue than beta-emitters because of the combination of short path length (50-80 mu m) with the high linear energy transfer (100 keV mu m(-1)) of this emission. These physical properties offer the real possibility of targeted (pre-targeted) alpha-therapy suitable for the elimination of minimal residual or micrometastatic disease. Targeted and pre-targeted radioimmunotherapy (RIT) using alpha-emitters such as Bi-212 (T-1/2 = 1.01 h) and Pb-212 (T-1/2 = 10.6 h) has demonstrated significant utility in both in vitro and in vivo model systems. Pb-212, a promising alpha-particle emitting source, is the longer-lived parent nuclide of Bi-212, and serves as an in vivo generator of Bi-212. The radionuclide has been successfully used in RIT and pre-targeted RIT and demonstrated an enhanced therapeutic efficacy in combination with chemotherapeutics, such as gemcitabine and paclitaxel. The following perspective addresses the modes of radionuclide production, radiolabelling and chelation chemistry, as well as the application of Pb-212 to targeted and pre-targeted radiation therapy. C1 [Yong, Kwon; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bldg 10,Room 1B40,10 Ctr Dr, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 80 TC 29 Z9 29 U1 1 U2 16 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-9226 J9 DALTON T JI Dalton Trans. PY 2011 VL 40 IS 23 BP 6068 EP 6076 DI 10.1039/c0dt01387k PG 9 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 772TQ UT WOS:000291260000002 PM 21380408 ER PT J AU Bhattacharyya, S Dixit, M AF Bhattacharyya, Sibaprasad Dixit, Manish TI Metallic radionuclides in the development of diagnostic and therapeutic radiopharmaceuticals SO DALTON TRANSACTIONS LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; LABELED MONOCLONAL-ANTIBODY; NORMAL TISSUE CONCENTRATIONS; RENAL RADIOACTIVITY LEVELS; IN-VIVO; GA-68-DOTA-TYR(3)-OCTREOTIDE PET; NUCLEAR-MEDICINE; BONE METASTASES; SR-82/RB-82 GENERATOR; BIOLOGICAL EVALUATION AB Metallic radionuclides are the mainstay of both diagnostic and therapeutic radiopharmaceuticals. Therapeutic nuclear medicine is less advanced but has tremendous potential if the radionuclide is accurately targeted. Great interest exists in the field of inorganic chemistry for developing target specific radiopharmaceuticals based on radiometals for non-invasive disease detection and cancer radiotherapy. This perspective will focus on the nuclear properties of a few important radiometals and their recent applications to developing radiopharmaceuticals for imaging and therapy. Other topics for discussion will include imaging techniques, radiotherapy, analytical techniques, and radiation safety. The ultimate goal of this perspective is to introduce inorganic chemists to the field of nuclear medicine and radiopharmaceutical development, where many applications of fundamental inorganic chemistry can be found. C1 [Bhattacharyya, Sibaprasad; Dixit, Manish] NCI, ADRD, SAIC Frederick, NIH, Frederick, MD 21701 USA. RP Bhattacharyya, S (reprint author), NCI, ADRD, SAIC Frederick, NIH, 1050 Boyles St,Bldg 376, Frederick, MD 21701 USA. EM bhattacharyyas2@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This article is dedicated to Professor Animesh Chakravorty in celebration of his 75th birthday.88 The authors are grateful to all the talented researchers cited amongst the references for their significant contributions in this field of research. 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 Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. NR 158 TC 45 Z9 45 U1 5 U2 25 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-9226 J9 DALTON T JI Dalton Trans. PY 2011 VL 40 IS 23 BP 6112 EP 6128 DI 10.1039/c1dt10379b PG 17 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 772TQ UT WOS:000291260000006 PM 21541393 ER PT J AU Gaudet, P Bairoch, A Field, D Sansone, SA Taylor, C Attwood, TK Bateman, A Blake, JA Bult, CJ Cherry, JM Chisholm, RL Cochrane, G Cook, CE Eppig, JT Galperin, MY Gentleman, R Goble, CA Gojobori, T Hancock, JM Howe, DG Imanishi, T Kelso, J Landsman, D Lewis, SE Mizrachi, IK Orchard, S Ouellette, BFF Ranganathan, S Richardson, L Rocca-Serra, P Schofield, PN Smedley, D Southan, C Tan, TW Tatusova, T Whetzel, PL White, O Yamasaki, C AF Gaudet, Pascale Bairoch, Amos Field, Dawn Sansone, Susanna-Assunta Taylor, Chris Attwood, Teresa K. Bateman, Alex Blake, Judith A. Bult, Carol J. Cherry, J. Michael Chisholm, Rex L. Cochrane, Guy Cook, Charles E. Eppig, Janan T. Galperin, Michael Y. Gentleman, Robert Goble, Carole A. Gojobori, Takashi Hancock, John M. Howe, Douglas G. Imanishi, Tadashi Kelso, Janet Landsman, David Lewis, Suzanna E. Mizrachi, Ilene Karsch Orchard, Sandra Ouellette, B. F. Francis Ranganathan, Shoba Richardson, Lorna Rocca-Serra, Philippe Schofield, Paul N. Smedley, Damian Southan, Christopher Tan, Tin W. Tatusova, Tatiana Whetzel, Patricia L. White, Owen Yamasaki, Chisato CA BioDBCore Working Grp TI Towards BioDBcore: a community-defined information specification for biological databases SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Editorial Material ID BIOINFORMATICS; RESOURCES C1 [Gaudet, Pascale; Bairoch, Amos] Swiss Inst Bioinformat, CMU, CH-1211 Geneva 4, Switzerland. [Gaudet, Pascale; Chisholm, Rex L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Field, Dawn] NERC Ctr Ecol & Hydrol, Oxford OX1 3SR, England. [Sansone, Susanna-Assunta; Cook, Charles E.; Rocca-Serra, Philippe] Univ Oxford, Oxford E Res Ctr, Oxford OX1 3QG, England. [Taylor, Chris; Cochrane, Guy; Orchard, Sandra; Smedley, Damian] European Bioinformat Inst EBI, European Mol Biol Lab EMBL Outstn, Cambridge CB10 1SD, England. [Attwood, Teresa K.] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England. [Attwood, Teresa K.; Goble, Carole A.] Univ Manchester, Sch Comp Sci, Manchester M13 9PT, Lancs, England. [Bateman, Alex] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Blake, Judith A.; Bult, Carol J.; Eppig, Janan T.] Jackson Lab, Bar Harbor, ME 04609 USA. [Cherry, J. Michael] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Galperin, Michael Y.; Mizrachi, Ilene Karsch; Tatusova, Tatiana] NIH, NCBI, Natl Lib Med, Bethesda, MD 20894 USA. [Gentleman, Robert] Genentech Inc, San Francisco, CA 94080 USA. [Gojobori, Takashi; Imanishi, Tadashi] Natl Inst Adv Ind Sci & Technol, Biomed Informat Res Ctr, Tokyo 1350064, Japan. [Gojobori, Takashi; Yamasaki, Chisato] DNA Data Bank Japan, Natl Inst Genet, Mishima, Shizuoka 4118540, Japan. [Gojobori, Takashi; Yamasaki, Chisato] Res Org Informat & Syst, Ctr Informat Biol, Mishima, Shizuoka 4118540, Japan. [Hancock, John M.] MRC Harwell, Mammalian Genet Unit, Didcot OX11 0RD, Oxon, England. [Howe, Douglas G.] 5291 Univ Oregon, Eugene, OR 97401 USA. [Kelso, Janet] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, Leipzig, Germany. [Landsman, David] Oxford Univ Press, DATABASE, Oxford OX2 6DP, England. [Lewis, Suzanna E.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA. [Ouellette, B. F. Francis] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada. [Ranganathan, Shoba] Macquarie Univ, Dept Chem & Biomol Sci, Sydney, NSW 2109, Australia. [Ranganathan, Shoba; Tan, Tin W.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117595, Singapore. [Richardson, Lorna] Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland. [Schofield, Paul N.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England. [Southan, Christopher] ChrisDS Consulting, Gothenburg, Sweden. [Whetzel, Patricia L.] Stanford Univ, Stanford Ctr Biomed Informat Res, Natl Ctr Biomed Ontol, Stanford, CA 94305 USA. [White, Owen] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. RP Gaudet, P (reprint author), Swiss Inst Bioinformat, CMU, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland. EM pascale.gaudet@isb-sib.ch RI Galperin, Michael/B-5859-2013; Tan, Tin Wee/B-8963-2009; OI Landsman, David/0000-0002-9819-6675; Orchard, Sandra/0000-0002-8878-3972; Southan, Christopher/0000-0001-9580-0446; Galperin, Michael/0000-0002-2265-5572; Tan, Tin Wee/0000-0002-4062-2854; Cherry, J. Michael/0000-0001-9163-5180; Ouellette, B. F. Francis/0000-0003-4676-675X; Ranganathan, Shoba/0000-0002-8290-813X; Cochrane, Guy/0000-0001-7954-7057; Howe, Douglas/0000-0001-5831-7439; Richardson, Lorna/0000-0002-3655-5660; Lewis, Suzanna/0000-0002-8343-612X; Goble, Carole/0000-0003-1219-2137; Bairoch, Amos/0000-0003-2826-6444 NR 12 TC 7 Z9 7 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PY 2011 AR baq027 DI 10.1093/database/baq027 PG 6 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 883JQ UT WOS:000299630600001 ER PT J AU Lu, ZY AF Lu, Zhiyong TI PubMed and beyond: a survey of web tools for searching biomedical literature SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Review ID INFORMATION-RETRIEVAL; BIOCREATIVE II; MEDLINE; NORMALIZATION; EXTRACTION; PUBCRAWLER; INTERFACE; CITATIONS; ABSTRACTS; BIOLOGIST AB The past decade has witnessed the modern advances of high-throughput technology and rapid growth of research capacity in producing large-scale biological data, both of which were concomitant with an exponential growth of biomedical literature. This wealth of scholarly knowledge is of significant importance for researchers in making scientific discoveries and healthcare professionals in managing health-related matters. However, the acquisition of such information is becoming increasingly difficult due to its large volume and rapid growth. In response, the National Center for Biotechnology Information (NCBI) is continuously making changes to its PubMed Web service for improvement. Meanwhile, different entities have devoted themselves to developing Web tools for helping users quickly and efficiently search and retrieve relevant publications. These practices, together with maturity in the field of text mining, have led to an increase in the number and quality of various Web tools that provide comparable literature search service to PubMed. In this study, we review 28 such tools, highlight their respective innovations, compare them to the PubMed system and one another, and discuss directions for future development. Furthermore, we have built a website dedicated to tracking existing systems and future advances in the field of biomedical literature search. Taken together, our work serves information seekers in choosing tools for their needs and service providers and developers in keeping current in the field. C1 Natl Lib Med, NCBI, Bethesda, MD 20894 USA. RP Lu, ZY (reprint author), Natl Lib Med, NCBI, Bethesda, MD 20894 USA. EM zhiyong.lu@nih.gov FU National Institutes of Health, National Library of Medicine FX Funding for this work and open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 64 TC 18 Z9 18 U1 1 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PY 2011 AR baq036 DI 10.1093/database/baq036 PG 13 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 883JQ UT WOS:000299630600003 ER PT J AU Marino-Ramirez, L Levine, KM Morales, M Zhang, SY Moreland, RT Baxevanis, AD Landsman, D AF Marino-Ramirez, Leonardo Levine, Kevin M. Morales, Mario Zhang, Suiyuan Moreland, R. Travis Baxevanis, Andreas D. Landsman, David TI The Histone Database: an integrated resource for histones and histone fold-containing proteins SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Article ID NUCLEOSOME CORE PARTICLE; CRYSTAL-STRUCTURE; CHROMATIN MODIFICATIONS; ANGSTROM RESOLUTION; VARIANTS; ORIGIN; TRANSCRIPTION; DYNAMICS; OCTAMER AB Eukaryotic chromatin is composed of DNA and protein components-core histones-that act to compactly pack the DNA into nucleosomes, the fundamental building blocks of chromatin. These nucleosomes are connected to adjacent nucleosomes by linker histones. Nucleosomes are highly dynamic and, through various core histone post-translational modifications and incorporation of diverse histone variants, can serve as epigenetic marks to control processes such as gene expression and recombination. The Histone Sequence Database is a curated collection of sequences and structures of histones and non-histone proteins containing histone folds, assembled from major public databases. Here, we report a substantial increase in the number of sequences and taxonomic coverage for histone and histone fold-containing proteins available in the database. Additionally, the database now contains an expanded dataset that includes archaeal histone sequences. The database also provides comprehensive multiple sequence alignments for each of the four core histones (H2A, H2B, H3 and H4), the linker histones (H1/H5) and the archaeal histones. The database also includes current information on solved histone fold-containing structures. The Histone Sequence Database is an inclusive resource for the analysis of chromatin structure and function focused on histones and histone fold-containing proteins. Database URL: The Histone Sequence Database is freely available and can be accessed at http://research.nhgri.nih.gov/histones/. C1 [Marino-Ramirez, Leonardo; Levine, Kevin M.; Landsman, David] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Morales, Mario] NYU, Polytech Inst, MetroTech Ctr 6, Brooklyn, NY 11201 USA. [Zhang, Suiyuan; Moreland, R. Travis; Baxevanis, Andreas D.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Marino-Ramirez, L (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike,MSC 6075, Bethesda, MD 20894 USA. EM marino@ncbi.nlm.nih.gov RI Marino-Ramirez, Leonardo/I-5759-2013 OI Landsman, David/0000-0002-9819-6675; Marino-Ramirez, Leonardo/0000-0002-5716-8512 FU National Center for Biotechnology Information, National Library of Medicine at National Institutes of Health; National Human Genome Research Institute at National Institutes of Health FX Funding for open access charge: The Intramural Research Programs of the National Center for Biotechnology Information, National Library of Medicine and the National Human Genome Research Institute, both at the National Institutes of Health. NR 50 TC 20 Z9 20 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PY 2011 AR bar048 DI 10.1093/database/bar048 PG 7 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 883JQ UT WOS:000299630600050 ER PT J AU Sridhara, V Marchler-Bauer, A Bryant, SH Geer, LY AF Sridhara, Viswanadham Marchler-Bauer, Aron Bryant, Stephen H. Geer, Lewis Y. TI Automatic annotation of experimentally derived, evolutionarily conserved post-translational modifications onto multiple genomes SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Article ID TANDEM MASS-SPECTRA; PROTEIN-PHOSPHORYLATION SITES; AMINO-ACID-SEQUENCES; SACCHAROMYCES-CEREVISIAE; PHOSPHOPROTEOME ANALYSIS; REVEALS EVOLUTIONARY; MODIFIED PEPTIDES; DOMAIN DATABASE; MOUSE-LIVER; IDENTIFICATION AB New generation sequencing technologies have resulted in significant increases in the number of complete genomes. Functional characterization of these genomes, such as by high-throughput proteomics, is an important but challenging task due to the difficulty of scaling up existing experimental techniques. By use of comparative genomics techniques, experimental results can be transferred from one genome to another, while at the same time minimizing errors by requiring discovery in multiple genomes. In this study, protein phosphorylation, an essential component of many cellular processes, is studied using data from large-scale proteomics analyses of the phosphoproteome. Phosphorylation sites from Homo sapiens, Mus musculus and Drosophila melanogaster phosphopeptide data sets were mapped onto conserved domains in NCBI's manually curated portion of Conserved Domain Database (CDD). In this subset, 25 phosphorylation sites are found to be evolutionarily conserved between the three species studied. Transfer of phosphorylation annotation of these conserved sites onto sequences sharing the same conserved domains yield 3253 phosphosite annotations for proteins from coelomata, the taxonomic division that spans H. sapiens, M. musculus and D. melanogaster. The method scales automatically, so as the amount of experimental phosphoproteomics data increases, more conserved phosphorylation sites may be revealed. C1 [Sridhara, Viswanadham; Marchler-Bauer, Aron; Bryant, Stephen H.; Geer, Lewis Y.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Geer, LY (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. EM lewis.geer@nih.gov RI Geer, Lewis/H-2714-2014; OI Marchler-Bauer, Aron/0000-0003-1516-0712 FU NIH, National Library of Medicine FX Intramural Research Program of the NIH, National Library of Medicine. Funding included open access charge. NR 64 TC 2 Z9 2 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PY 2011 AR bar019 DI 10.1093/database/bar019 PG 10 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 883JQ UT WOS:000299630600021 ER PT J AU Stojmirovic, A Yu, YK AF Stojmirovic, Aleksandar Yu, Yi-Kuo TI ppiTrim: constructing non-redundant and up-to-date interactomes SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Article ID PROTEIN-INTERACTION DATABASE; SACCHAROMYCES-CEREVISIAE; INTERACTION NETWORK; UPDATE; INTEGRATION; COMPLEXES AB Robust advances in interactome analysis demand comprehensive, non-redundant and consistently annotated data sets. By non-redundant, we mean that the accounting of evidence for every interaction should be faithful: each independent experimental support is counted exactly once, no more, no less. While many interactions are shared among public repositories, none of them contains the complete known interactome for any model organism. In addition, the annotations of the same experimental result by different repositories often disagree. This brings up the issue of which annotation to keep while consolidating evidences that are the same. The iRefIndex database, including interactions from most popular repositories with a standardized protein nomenclature, represents a significant advance in all aspects, especially in comprehensiveness. However, iRefIndex aims to maintain all information/annotation from original sources and requires users to perform additional processing to fully achieve the aforementioned goals. Another issue has to do with protein complexes. Some databases represent experimentally observed complexes as interactions with more than two participants, while others expand them into binary interactions using spoke or matrix model. To avoid untested interaction information buildup, it is preferable to replace the expanded protein complexes, either from spoke or matrix models, with a flat list of complex members. To address these issues and to achieve our goals, we have developed ppiTrim, a script that processes iRefIndex to produce non-redundant, consistently annotated data sets of physical interactions. Our script proceeds in three stages: mapping all interactants to gene identifiers and removing all undesired raw interactions, deflating potentially expanded complexes, and reconciling for each interaction the annotation labels among different source databases. As an illustration, we have processed the three largest organismal data sets: yeast, human and fruitfly. While ppiTrim can resolve most apparent conflicts between different labelings, we also discovered some unresolvable disagreements mostly resulting from different annotation policies among repositories. Database URL: http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/downloads/ppiTrim.html C1 [Stojmirovic, Aleksandar; Yu, Yi-Kuo] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Yu, YK (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM yyu@ncbi.nlm.nih.gov OI Stojmirovic, Aleksandar/0000-0003-0957-6893 FU National Library of Medicine at the National Institutes of Health; National Institutes of Health FX This work was supported by the Intramural Research Program of the National Library of Medicine at the National Institutes of Health. Funding for open access charge: the National Institutes of Health. NR 37 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PY 2011 AR bar036 DI 10.1093/database/bar036 PG 11 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 883JQ UT WOS:000299630600038 ER PT J AU Turner, CF Pan, HQ Silk, GW Ardini, MA Bakalov, V Bryant, S Cantor, S Chang, KY DeLatte, M Eggers, P Ganapathi, L Lakshmikanthan, S Levy, J Li, SP Pratt, J Pugh, N Qin, Y Rasooly, R Ray, H Richardson, JE Riley, AF Rogers, SM Scheper, C Tan, S White, S Cooley, PC AF Turner, Charles F. Pan, Huaqin Silk, Gregg W. Ardini, Mary-Anne Bakalov, Vesselina Bryant, Stephanie Cantor, Susanna Chang, Kung-yen DeLatte, Michael Eggers, Paul Ganapathi, Laxminarayana Lakshmikanthan, Sujatha Levy, Joshua Li, Sheping Pratt, Joseph Pugh, Norma Qin, Ying Rasooly, Rebekah Ray, Helen Richardson, Jean E. Riley, Amanda Flynn Rogers, Susan M. Scheper, Charlotte Tan, Sylvia White, Stacie Cooley, Philip C. TI The NIDDK Central Repository at 8 years-Ambition, Revision, Use and Impact SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Article ID GENOME-WIDE ASSOCIATION; MEAN BLOOD-GLUCOSE; DIABETIC-NEPHROPATHY; MICROVASCULAR COMPLICATIONS; GLYCEMIC CONTROL; RISK; VARIABILITY; TRIAL; LOCI; GENETICS AB The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repository makes data and biospecimens from NIDDK-funded research available to the broader scientific community. It thereby facilitates: the testing of new hypotheses without new data or biospecimen collection; pooling data across several studies to increase statistical power; and informative genetic analyses using the Repository's well-curated phenotypic data. This article describes the initial database plan for the Repository and its revision using a simpler model. Among the lessons learned were the trade-offs between the complexity of a database design and the costs in time and money of implementation; the importance of integrating consent documents into the basic design; the crucial need for linkage files that associate biospecimen IDs with the masked subject IDs used in deposited data sets; and the importance of standardized procedures to test the integrity data sets prior to distribution. The Repository is currently tracking 111 ongoing NIDDK-funded studies many of which include genotype data, and it houses over 5 million biospecimens of more than 25 types including serum, plasma, stool, urine, DNA, red blood cells, buffy coat and tissue. Repository resources have supported a range of biochemical, clinical, statistical and genetic research (188 external requests for clinical data and 31 for biospecimens have been approved or are pending). Genetic research has included GWAS, validation studies, development of methods to improve statistical power of GWAS and testing of new statistical methods for genetic research. We anticipate that the future impact of the Repository's resources on biomedical research will be enhanced by (i) cross-listing of Repository biospecimens in additional searchable databases and biobank catalogs; (ii) ongoing deployment of new applications for querying the contents of the Repository; and (iii) increased harmonization of procedures, data collection strategies, questionnaires etc. across both research studies and within the vocabularies used by different repositories. Database URL: http://www.niddkrepository.org C1 [Turner, Charles F.; Pan, Huaqin; Ardini, Mary-Anne; Bakalov, Vesselina; Bryant, Stephanie; Cantor, Susanna; DeLatte, Michael; Ganapathi, Laxminarayana; Lakshmikanthan, Sujatha; Levy, Joshua; Li, Sheping; Pratt, Joseph; Pugh, Norma; Qin, Ying; Ray, Helen; Richardson, Jean E.; Riley, Amanda Flynn; Rogers, Susan M.; Scheper, Charlotte; Tan, Sylvia; White, Stacie; Cooley, Philip C.] RTI Int, Res Triangle Pk, NC 27709 USA. [Turner, Charles F.] CUNY, Queens Coll, Flushing, NY 11367 USA. [Turner, Charles F.] CUNY, Grad Ctr, Flushing, NY 11367 USA. [Silk, Gregg W.] N Carolina State Univ, Poole Coll Management, Raleigh, NC 27695 USA. [Chang, Kung-yen] N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27695 USA. [Eggers, Paul; Rasooly, Rebekah] NIDDK, Bethesda, MD 20892 USA. RP Cooley, PC (reprint author), RTI Int, POB 12194, Res Triangle Pk, NC 27709 USA. EM pcc@rtii.org OI Qin, Ying/0000-0002-6099-2190; Rasooly, Rebekah/0000-0002-6357-5528 FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health, Department of Health and Human Services [HHSN: 267200800015C, 267200800016C, 267200800018C]; [RFP NIH-NIDDK-02-04]; [RFP NIH-NIDDK-07-07]; [HHSN267200800016C] FX This article draws upon material included in (i) RTI International's Technical Proposals for the Contracts for Initial Award (RFP NIH-NIDDK-02-04) and Continuation of Funding (RFP NIH-NIDDK-07-07) for the NIDDK Central Repository; (ii) an RTI contract modification proposal submitted in February of 2009; (iii) descriptions of Repository content and procedures posted on current and previous versions of the Repository Website (www.niddkrepository.org/niddk/jsp/public/dataset.jsp), and (iv) a presentation on the Repository by Rasooly, Eggers, et al. (1) at the 2011 meetings of the International Society for Biological and Environmental Repositories. With the exception of this note, we do not identify text that excerpts or draws upon these sources.; National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health, Department of Health and Human Services, under Contracts (HHSN: 267200800015C, 267200800016C and 267200800018C). Funding for open access charge: HHSN267200800016C. NR 35 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PY 2011 AR bar043 DI 10.1093/database/bar043 PG 16 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 883JQ UT WOS:000299630600045 ER PT J AU Deng, XH Wagner, HJ Popper, AN AF Deng, Xiaohong Wagner, Hans-Joachim Popper, Arthur N. TI The inner ear and its coupling to the swim bladder in the deep-sea fish Antimora rostrata (Teleostei: Moridae) SO DEEP-SEA RESEARCH PART I-OCEANOGRAPHIC RESEARCH PAPERS LA English DT Article DE Antimora rostrata; Inner ear; Swim bladder; Deep-sea fish; Saccule; Lagena; Utricle ID MERLUCCIUS-MERLUCCIUS; OTOLITHIC ORGANS; AUDITORY-SYSTEM; EUROPEAN HAKE; HAIR-CELLS; BIOLOGY; GADIFORMES; MORPHOLOGY; ATLANTIC; SACCULUS AB The inner ear structure of Antimora rostrata and its coupling to the swim bladder were analyzed and compared with the inner ears of several shallow-water species that also have similar coupling. The inner ear of Antimora has a long saccular otolith and sensory epithelium as compared to many other fishes. Some parts of the membranous labyrinth are thick and rigid, while other parts are thinner but attached tightly to the bony capsule. The partially rigid membranous labyrinth, along with its intimate connection to the swim bladder, may help the inner ear follow the sound oscillations from the swim bladder with better precision than would occur in a less rigid inner ear. In addition, the saccular sensory epithelium has an elaborate structure and an anterior enlargement that may be correlated with increased hearing sensitivity. Some of the features in the inner ear of Antimora may reflect the functional specialization of deep-water living and support the hypothesis that there is enhanced inner ear sensitivity in some deep-sea fishes. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Deng, Xiaohong; Popper, Arthur N.] Univ Maryland, Dept Biol, Ctr Comparat & Evolutionary Biol Hearing, College Pk, MD 20742 USA. [Deng, Xiaohong; Popper, Arthur N.] Univ Maryland, Neurosci & Cognit Sci Program, College Pk, MD 20742 USA. [Wagner, Hans-Joachim] Univ Tubingen, Anatom Inst, D-72074 Tubingen, Germany. RP Deng, XH (reprint author), NIDCD, NIH, 5 Res Ct, Rockville, MD 20850 USA. EM dengx2@nidcd.nih.gov FU NERC; University of Aberdeen [GR3/12789]; National Institute on Deafness and Other Communication Disorders (NIDCD) of the National Institutes of Health [2 P30 DC004664] FX Thanks to Professor Imants Priede for inviting Deng and Wagner to the RRS Discovery cruises D252, D255 and D260. These cruises were funded by an NERC Grant awarded to Priede. Collins, and Bagley from the University of Aberdeen (GR3/12789). Also thanks to the Masters and crews of RRS Discovery for expert nautical work. Thanks to T. Maugel for his training and expert advices on SEM work. We thank Drs. W. Hodos, C. Platt, A. Coffin, and B. Casper for reading and commenting on earlier versions of this paper. Portions of the microscopy work were supported by P-30 Grant 2 P30 DC004664 from the National Institute on Deafness and Other Communication Disorders (NIDCD) of the National Institutes of Health. NR 71 TC 13 Z9 13 U1 0 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0967-0637 J9 DEEP-SEA RES PT I JI Deep-Sea Res. Part I-Oceanogr. Res. Pap. PD JAN PY 2011 VL 58 IS 1 BP 27 EP 37 DI 10.1016/j.dsr.2010.11.001 PG 11 WC Oceanography SC Oceanography GA 724HE UT WOS:000287565900003 PM 21532967 ER PT J AU Britton, JC Lissek, S Grillon, C Norcross, MA Pine, DS AF Britton, Jennifer C. Lissek, Shmuel Grillon, Christian Norcross, Maxine A. Pine, Daniel S. TI DEVELOPMENT OF ANXIETY: THE ROLE OF THREAT APPRAISAL AND FEAR LEARNING SO DEPRESSION AND ANXIETY LA English DT Review DE fear conditioning; generalization; attention; amygdala; ventromedial prefrontal cortex ID POSTTRAUMATIC-STRESS-DISORDER; VENTROMEDIAL PREFRONTAL CORTEX; CONDITIONED FEAR; POTENTIATED STARTLE; AMYGDALA RESPONSE; FACIAL EXPRESSIONS; SOCIAL PHOBIA; D-CYCLOSERINE; EMOTIONAL REACTIVITY; COGNITIVE REGULATION AB Anxious individuals exhibit threat biases at multiple levels of information processing. From a developmental perspective, abnormal safety learning in childhood may establish threat-related appraisal biases early, which may contribute to chronic disorders in adulthood. This review illustrates how the interface among attention, threat appraisal, and fear learning can generate novel insights for outcome prediction. This review summarizes data on amygdala function, as it relates to learning and attention, highlights the importance of examining threat appraisal, and introduces a novel imaging paradigm to investigate the neural correlates of threat appraisal and threat-sensitivity during extinction recall. This novel paradigm can be used to investigate key questions relevant to prognosis and treatment. Depression and Anxiety 28:5-17, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Britton, Jennifer C.; Lissek, Shmuel; Grillon, Christian; Norcross, Maxine A.; Pine, Daniel S.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Britton, JC (reprint author), NIMH, Mood & Anxiety Disorders Program, 9000 Rockville Pike,Bldg 15K, Bethesda, MD 20892 USA. EM brittonjen@mail.nih.gov RI Britton, Jennifer/J-4501-2013 FU National Institutes of Health; National Institute of Mental Health FX This research was supported in part by the Intramural Research Program of the National Institutes of Health and the National Institute of Mental Health (J.C.B., S.L., C.G., M.A.N., D.S.P.). An earlier version of this work has been presented at the Anxiety Disorders Association of American annual conference in March 2010. NR 128 TC 74 Z9 77 U1 5 U2 51 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JAN PY 2011 VL 28 IS 1 BP 5 EP 17 DI 10.1002/da.20733 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 708HW UT WOS:000286353900002 PM 20734364 ER PT J AU Kessler, RC Cox, BJ Green, JG Ormel, J McLaughlin, KA Merikangas, KR Petukhova, M Pine, DS Russo, LJ Swendsen, J Wittchen, HU Zaslavsky, AM AF Kessler, Ronald C. Cox, Brian J. Green, Jennifer Greif Ormel, Johan McLaughlin, Katie A. Merikangas, Kathleen Ries Petukhova, Maria Pine, Daniel S. Russo, Leo J. Swendsen, Joel Wittchen, Hans-Ulrich Zaslavsky, Alan M. TI THE EFFECTS OF LATENT VARIABLES IN THE DEVELOPMENT OF COMORBIDITY AMONG COMMON MENTAL DISORDERS SO DEPRESSION AND ANXIETY LA English DT Article DE anxiety disorders; comorbidity; epidemiology; epidemiologic methods ID WORLD-HEALTH-ORGANIZATION; SUPPLEMENT NCS-A; DIAGNOSTIC INTERVIEW CIDI; SOCIAL-ANXIETY-DISORDER; DSM-IV DISORDERS; AGE-OF-ONSET; SURVEY REPLICATION; PSYCHIATRIC-DISORDERS; YOUNG-ADULTS; PROSPECTIVE COMMUNITY AB Background: Although numerous studies have examined the role of latent predispositions to internalizing and externalizing disorders in the structure of comorbidity among common mental disorders, none examined latent predispositions in predicting development of comorbidity. Methods: A novel method was used to study the role of latent variables in the development of comorbidity among lifetime DSM-IV disorders in the National Comorbidity Surveys. Broad preliminary findings are briefly presented to describe the method. The method used survival analysis to estimate time-lagged associations among 18 lifetime DSM-IV anxiety, mood, behavior, and substance disorders. A novel estimation approach examined the extent to which these predictive associations could be explained by latent canonical variables representing internalizing and externalizing disorders. Results: Consistently significant positive associations were found between temporally primary and secondary disorders. Within-domain time-lagged associations were generally stronger than between-domain associations. The vast majority of associations were explained by a model that assumed mediating effects of latent internalizing and externalizing variables, although the complexity of this model differed across samples. A number intriguing residual associations emerged that warrant further investigation. Conclusions: The good fit of the canonical model suggests that common causal pathways account for most comorbidity among the disorders considered. These common pathways should be the focus of future research on the development of comorbidity. However, the existence of several important residual associations shows that more is involved than simple mediation. The method developed to carry out these analyses provides a unique way to pinpoint these significant residual associations for subsequent focused study. Depression and Anxiety 28:29-39, 2011. 2011 (C) Wiley-Liss, Inc. C1 [Kessler, Ronald C.; McLaughlin, Katie A.; Petukhova, Maria; Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Cox, Brian J.] Univ Manitoba, Dept Psychiat, Winnipeg, MB R3T 2N2, Canada. [Cox, Brian J.] Univ Manitoba, Dept Psychol, Winnipeg, MB R3T 2N2, Canada. [Cox, Brian J.] Univ Manitoba, Dept Community Hlth Sci, Winnipeg, MB R3T 2N2, Canada. [Green, Jennifer Greif] Boston Univ, Special Educ Program, Sch Educ, Boston, MA 02215 USA. [Ormel, Johan] Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands. [Ormel, Johan] Univ Groningen, Grad Sch Behav & Cognit Neurosci, Groningen, Netherlands. [Ormel, Johan] Univ Groningen, Grad Sch Expt Psychopathol, Groningen, Netherlands. [Merikangas, Kathleen Ries] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. [Russo, Leo J.] Shire Pharmaceut Res & Dev, Chester, PA USA. [Swendsen, Joel] Natl Ctr Sci Res, Bordeaux, France. [Wittchen, Hans-Ulrich] Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, Dresden, Germany. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM kessler@hcp.med.harvard.edu RI Ormel, Johan/C-6094-2013; Wittchen, Hans-Ulrich/A-8507-2014; OI McLaughlin, Katie/0000-0002-1362-2410; Wittchen, Hans-Ulrich/0000-0002-6311-7711 FU National Institute of Mental Health (NIMH) [R01MH46376, R01-MH070884, R13-MH066849, R01-MH069864, R01-MH077883, U01-MH60220, R01-MH66627, U01MH060220-0951]; National Institute on Drug Abuse (NIDA) [R01DA012058, R01-DA016558]; Robert Wood Johnson Foundation (RWJF) [044780]; National Institutes of Health [FIRCA R03-TW006481]; Substance Abuse and Mental Health Services Administration (SAMHSA); John W. Alden Trust; Shire Pharmaceuticals; Canadian Research Chair; Canadian Institutes of Health Research; John D. and Catherine T. MacArthur Foundation; Pfizer Foundation; Pan American Health Organization; Astra Zeneca; BristolMyersSquibb; Eli Lilly and Company; GlaxoSmithKline; Ortho-McNeil; Pfizer; Sanofi-Aventis; Shire, and Wyeth FX The authors disclose the following financial relationships within the past 3 years: Contract grant sponsor: National Institute of Mental Health (NIMH); Contract grant numbers: R01MH46376; R01-MH070884; R13-MH066849; R01-MH069864; R01-MH077883; U01-MH60220; R01-MH66627; U01MH060220-0951; Contract grant sponsor: National Institute on Drug Abuse (NIDA); Contract grant numbers: R01DA012058; R01-DA016558; Contract grant sponsor: The Robert Wood Johnson Foundation (RWJF); Contract grant number: 044780; Contract grant sponsor: National Institutes of Health; Contract grant number: FIRCA R03-TW006481; Contract grant sponsors: The Substance Abuse and Mental Health Services Administration (SAMHSA), and the John W. Alden Trust; Shire Pharmaceuticals; NIMH Intramural Research Program; Canadian Research Chair; Canadian Institutes of Health Research, the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, and the Pan American Health Organization, Astra Zeneca, BristolMyersSquibb, Eli Lilly and Company, GlaxoSmithKline, Ortho-McNeil, Pfizer, Sanofi-Aventis, Shire, and Wyeth. NR 61 TC 29 Z9 29 U1 4 U2 17 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JAN PY 2011 VL 28 IS 1 BP 29 EP 39 DI 10.1002/da.20760 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 708HW UT WOS:000286353900004 PM 21225850 ER PT J AU Pao, M Bosk, A AF Pao, Maryland Bosk, Abigail TI ANXIETY IN MEDICALLY ILL CHILDREN/ADOLESCENTS SO DEPRESSION AND ANXIETY LA English DT Review DE chronic illness; pain; c stress disorder; psychopharmacology; cognitive behavior therapy ID INFLAMMATORY-BOWEL-DISEASE; POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; PEDIATRIC-CANCER-SURVIVORS; LIFE-THREATENING ILLNESSES; RANDOMIZED CLINICAL-TRIAL; VULNERABLE CHILD SYNDROME; MOOD DISORDERS; RISK-FACTORS; DEPRESSION AB Anxiety disorders are thought to be one of the most common psychiatric diagnoses in children/adolescents. Chronic medical illness is a significant risk factor for the development of an anxiety disorder, and the prevalence rate of anxiety disorders among youths with chronic medical illnesses is higher compared to their healthy counterparts. Anxiety disorders may develop secondary to predisposing biological mechanisms related to a child's specific medical illness, as a response to being ill or in the hospital, a threatening environment, as a result of other genetic and psychological factors, or as a combination of all these factors. Additionally, exposure to physical pain early in one's life and/or frequent painful medical procedures are correlated with fear and anxiety during subsequent procedures and treatments, and may lead to medical nonadherence and other comorbidities. Anxiety disorders can have serious consequences in children/adolescents with chronic and/or life-limiting medical illnesses. Therefore, proper identification and treatment of anxiety disorders is necessary and may improve not only psychiatric symptoms but also physical symptoms. Behavioral and cognitive methods as well as psychotropic medications are used to treat anxiety disorders in pediatric patients. We will review current treatments for anxiety in children/adolescents with medical illnesses and propose future research directions. Depression and Anxiety 28:40-49, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Pao, Maryland] NIMH, Clin Res Ctr, Off Clin Director, NIH, Bethesda, MD 20892 USA. RP Pao, M (reprint author), NIMH, Clin Res Ctr, Off Clin Director, NIH, Bethesda, MD 20892 USA. EM paom@mail.nih.gov FU National Institutes of Health; National Institutes of Mental Health FX This research was supported by the Intramural Research Program of the National Institutes of Health and the National Institutes of Mental Health. NR 73 TC 24 Z9 24 U1 3 U2 23 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JAN PY 2011 VL 28 IS 1 BP 40 EP 49 DI 10.1002/da.20727 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 708HW UT WOS:000286353900005 PM 20721908 ER PT J AU Chavez, M Cuthbert, B AF Chavez, Mark Cuthbert, Bruce BE StriegelMoore, RH Wonderlich, SA Walsh, BT Mitchell, JE TI DEVELOPING AN EVIDENCE-BASED CLASSIFICATION OF EATING DISORDERS Scientific Findings for DSM-5 FOREWORD SO DEVELOPING AN EVIDENCE-BASED CLASSIFICATION OF EATING DISORDERS: SCIENTIFIC FINDINGS FOR DSM-5 LA English DT Editorial Material; Book Chapter C1 [Chavez, Mark] NIMH, Eating Disorders Program, Rockville, MD 20857 USA. [Chavez, Mark] NIMH, Side Effects Psychiat Therapeut Program, Rockville, MD 20857 USA. [Chavez, Mark] NIMH, Div Adult Translat Res & Treatment Dev, Rockville, MD 20857 USA. [Cuthbert, Bruce] NIMH, Div Adult Translat Res, Rockville, MD 20857 USA. RP Chavez, M (reprint author), NIMH, Eating Disorders Program, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-0-89042-666-1 PY 2011 BP XXI EP XXII PG 2 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BWM09 UT WOS:000294220100001 ER PT J AU Insel, TR AF Insel, Thomas R. TI Foreword SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE LA English DT Editorial Material C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, NIH, 6001 Execut Blvd Room 8235, Bethesda, MD 20892 USA. EM insel@mail.nih.gov NR 4 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1878-9293 J9 DEV COGN NEUROS-NETH JI Dev. Cogn. Neurosci. PD JAN PY 2011 VL 1 IS 1 BP 1 EP 2 DI 10.1016/j.dcn.2010.08.002 PG 2 WC Neurosciences SC Neurosciences & Neurology GA V28AI UT WOS:000208653300001 PM 22436414 ER PT J AU Blakemore, SJ Dahl, RE Frith, U Pine, DS AF Blakemore, Sarah-Jayne Dahl, R. E. Frith, U. Pine, D. S. TI Developmental cognitive neuroscience SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE LA English DT Editorial Material C1 [Blakemore, Sarah-Jayne; Frith, U.] UCL, Inst Cognit Neurosci, London WC1N 3AR, England. [Dahl, R. E.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Pine, D. S.] NIMH, Bethesda, MD 20892 USA. RP Blakemore, SJ (reprint author), UCL, Inst Cognit Neurosci, 17 Queen Sq, London WC1N 3AR, England. EM s.blakemore@ucl.ac.uk RI Frith, Uta/C-1757-2008 OI Frith, Uta/0000-0002-9063-4466 NR 4 TC 6 Z9 6 U1 0 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1878-9293 J9 DEV COGN NEUROS-NETH JI Dev. Cogn. Neurosci. PD JAN PY 2011 VL 1 IS 1 BP 3 EP 6 DI 10.1016/j.dcn.2010.08.003 PG 4 WC Neurosciences SC Neurosciences & Neurology GA V28AI UT WOS:000208653300002 PM 22436415 ER PT J AU Vasa, RA Pine, DS Thorn, JM Nelson, TE Spinelli, S Nelson, E Maheu, FS Ernst, M Bruck, M Mostofsky, SH AF Vasa, Roma A. Pine, Daniel S. Thorn, Julia M. Nelson, Tess E. Spinelli, Simona Nelson, Eric Maheu, Francoise S. Ernst, Monique Bruck, Maggie Mostofsky, Stewart H. TI Enhanced right amygdala activity in adolescents during encoding of positively valenced pictures SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE LA English DT Article DE Adolescents; Adults; Encoding; Positive stimuli; Amygdala; Hippocampus AB While studies among adults implicate the amygdala and interconnecting brain regions in encoding emotional stimuli, few studies have examined whether developmental changes occur within this emotional-memory network during adolescence. The present study examined whether adolescents and adults differentially engaged the amygdala and hippocampus during successful encoding of emotional pictures, with either positive or negative valence. Eighteen adults and twelve adolescents underwent event-related fMRI while encoding emotional pictures. Approximately 30 min later, outside the scanner, subjects were asked to recall the pictures seen during the scan. Age group differences in brain activity in the amygdala and hippocampus during encoding of the pictures that were later successfully and unsuccessfully recalled were separately compared for the positive and negative pictures. Adolescents, relative to adults, demonstrated enhanced activity in the right amygdala during encoding of positive pictures that were later recalled compared to not recalled. There were no age group differences in amygdala or hippocampal activity during successful encoding of negative pictures. The findings of preferential activity within the adolescent right amygdala during successful encoding of positive pictures may have implications for the increased reward and novelty seeking behavior, as well as elevated rates of psychopathology, observed during this distinct developmental period. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Vasa, Roma A.; Thorn, Julia M.; Nelson, Tess E.; Spinelli, Simona; Mostofsky, Stewart H.] Kennedy Krieger Inst, Baltimore, MD 21205 USA. [Vasa, Roma A.; Bruck, Maggie; Mostofsky, Stewart H.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Pine, Daniel S.; Nelson, Eric; Ernst, Monique] NIMH, Bethesda, MD 20892 USA. [Maheu, Francoise S.] Univ Montreal, Montreal, PQ, Canada. RP Vasa, RA (reprint author), Kennedy Krieger Inst, Dept Psychiat, 716 North Broadway, Baltimore, MD 21205 USA. EM vasa@kennedykrieger.org OI Nelson, Eric/0000-0002-3376-2453 FU Intramural NIH HHS [ZIA MH002781-08, ZIA MH002780-08] NR 115 TC 12 Z9 12 U1 5 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1878-9293 J9 DEV COGN NEUROS-NETH JI Dev. Cogn. Neurosci. PD JAN PY 2011 VL 1 IS 1 BP 88 EP 99 DI 10.1016/j.dcn.2010.08.004 PG 12 WC Neurosciences SC Neurosciences & Neurology GA V28AI UT WOS:000208653300009 PM 21127721 ER PT J AU McClure-Tone, EB Nawa, NE Nelson, EE Detloff, AM Fromm, SJ Pine, DS Ernst, M AF McClure-Tone, Erin B. Nawa, Norberto E. Nelson, Eric E. Detloff, Allison M. Fromm, Stephen J. Pine, Daniel S. Ernst, Monique TI Preliminary Findings: Neural Responses to Feedback Regarding Betrayal and Cooperation in Adolescent Anxiety Disorders SO DEVELOPMENTAL NEUROPSYCHOLOGY LA English DT Article ID BORDERLINE PERSONALITY-DISORDER; POSTTRAUMATIC-STRESS-DISORDER; CORTICAL MIDLINE STRUCTURES; GENERALIZED SOCIAL PHOBIA; MEDIAL PREFRONTAL CORTEX; EMOTIONAL INFORMATION; AMYGDALA ACTIVATION; BRAIN ENGAGEMENT; FEARFUL FACES; ANGRY FACES AB We compared neural and behavioral responses to feedback received during interpersonal interactions within the Prisoner's Dilemma game between adolescents with anxiety disorders (n = 12) and healthy peers (n = 17). Groups differed significantly in neural activation in the medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), precuneus, insula, and temporoparietal junction (TPJ). Anxious adolescents were also more likely than controls to cooperate after co-player betrayal. Our findings provide evidence that social behavior and related neural activity differs between anxious and healthy adolescents. These findings constitute a step toward elucidating neural correlates of social impairment in anxious youths. C1 [McClure-Tone, Erin B.] Georgia State Univ, Dept Psychol, Atlanta, GA 30302 USA. [Nawa, Norberto E.] Universal Media Res Ctr, Natl Inst Informat & Commun Technol, Kyoto, Japan. [Nelson, Eric E.; Detloff, Allison M.; Fromm, Stephen J.; Pine, Daniel S.; Ernst, Monique] NIMH, Bethesda, MD 20892 USA. RP McClure-Tone, EB (reprint author), Georgia State Univ, Dept Psychol, POB 5010, Atlanta, GA 30302 USA. EM etone@gsu.edu OI Nelson, Eric/0000-0002-3376-2453 FU National Institute of Mental Health FX This work was supported by the Intramural Research Program of the National Institute of Mental Health. NR 70 TC 7 Z9 7 U1 6 U2 15 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 8756-5641 J9 DEV NEUROPSYCHOL JI Dev. Neuropsychol. PY 2011 VL 36 IS 4 SI SI BP 453 EP 472 AR PII 936795781 DI 10.1080/87565641.2010.549876 PG 20 WC Psychology, Developmental; Psychology; Psychology, Experimental SC Psychology GA 753VN UT WOS:000289807900004 PM 21516543 ER PT J AU Mazzone, L Mueller, SC Maheu, F VanRyzin, C Merke, DP Ernst, M AF Mazzone, Luigi Mueller, Sven C. Maheu, Francoise VanRyzin, Carol Merke, Deborah P. Ernst, Monique TI Emotional Memory in Early Steroid Abnormalities: An fMRI Study of Adolescents With Congenital Adrenal Hyperplasia SO DEVELOPMENTAL NEUROPSYCHOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; PREFRONTAL CORTEX; MAJOR DEPRESSION; CUSHINGS-SYNDROME; COGNITIVE FUNCTION; STRESS HORMONES; LONG-TERM; RECEPTOR EXPRESSION; FACIAL EXPRESSIONS; SALIVARY CORTISOL AB Hormonal imbalances during development may have long-lasting effects. Using functional magnetic resonance imaging (fMRI), we compared 14 youths with Congenital Adrenal Hyperplasia (CAH), a genetic disorder of hormonal dysfunction, with 22 healthy controls on memory encoding of emotional faces. Patients remembered fewer faces than controls, particularly fearful faces. FMRI data to successfully encoded fearful faces revealed that males with CAH showed significant activations in amygdala, hippocampus, and anterior cingulate relative to unaffected males, while females with CAH demonstrated deactivations relative to unaffected females in these regions. Findings indicate that steroid abnormalities during development can have important effects on neural correlates of emotional memory. C1 [Ernst, Monique] NIH DHSS, Bethesda, MD 20892 USA. [Mazzone, Luigi] Univ Catania, Div Child Neurol & Psychiat, Catania, Italy. [Mueller, Sven C.] NIH DHHS, Bethesda, MD USA. [Maheu, Francoise] Univ Montreal, CHU Ste Justine, Res Ctr, Montreal, PQ, Canada. [VanRyzin, Carol; Merke, Deborah P.] NICHHD DHSS, Ctr Clin, Bethesda, MD USA. RP Ernst, M (reprint author), NIH DHSS, Bethesda, MD 20892 USA. EM ernstm@mail.nih.gov FU Fonds de la recherche en sante du Quebec (FRSQ); NICHD; NIMH, NIH FX We thank the staff of the NIH MR Center for making this study possible. FSM was supported by a postdoctoral fellowship from the Fonds de la recherche en sante du Quebec (FRSQ). This work was supported in part by the intramural program of NICHD and NIMH, NIH. NR 90 TC 8 Z9 8 U1 2 U2 5 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 8756-5641 J9 DEV NEUROPSYCHOL JI Dev. Neuropsychol. PY 2011 VL 36 IS 4 SI SI BP 473 EP 492 AR PII 936796099 DI 10.1080/87565641.2010.549866 PG 20 WC Psychology, Developmental; Psychology; Psychology, Experimental SC Psychology GA 753VN UT WOS:000289807900005 PM 21516544 ER PT J AU Kannan, S Saadani-Makki, F Balakrishnan, B Chakraborty, P Janisse, J Lu, X Muzik, O Romero, R Chugani, DC AF Kannan, Sujatha Saadani-Makki, Fadoua Balakrishnan, Bindu Chakraborty, Pulak Janisse, James Lu, Xin Muzik, Otto Romero, Roberto Chugani, Diane C. TI Magnitude of [C-11]PK11195 Binding Is Related to Severity of Motor Deficits in a Rabbit Model of Cerebral Palsy Induced by Intrauterine Endotoxin Exposure SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Microglia; Positron emission tomography; Neuroinflammation; Cerebral palsy; Maternal inflammation ID POSITRON-EMISSION-TOMOGRAPHY; CENTRAL-NERVOUS-SYSTEM; BENZODIAZEPINE-RECEPTOR; IN-VIVO; MICROGLIAL ACTIVATION; WHITE-MATTER; NITRIC-OXIDE; RAT-BRAIN; OLIGODENDROCYTES; DISEASE AB Intrauterine inflammation is known to be a risk factor for the development of periventricular leukomalacia (PVL) and cerebral palsy. In recent years, activated microglial cells have been implicated in the pathogenesis of PVL and in the development of white matter injury. Clinical studies have shown the increased presence of activated microglial cells diffusely throughout the white matter in brains of patients with PVL. In vitro studies have reported that activated microglial cells induce oligodendrocyte damage and white matter injury by release of inflammatory cytokines, reactive nitrogen and oxygen species and the production of excitotoxic metabolites. PK11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide] is a ligand that is selective for the 18-kDa translocator protein expressed on the outer mitochondrial membrane of activated microglia and macrophages. When labeled with carbon-11, [C-11]PK11195 can effectively be used as a ligand in positron emission tomography (PET) studies for the detection of activated microglial cells in various neuroinflammatory and neurodegenerative conditions. In this study, we hypothesized that the magnitude of [C-11]-(R)-PK11195 uptake in the newborn rabbit brain, as measured using a small-animal PET scanner, would match the severity of motor deficits resulting from intrauterine inflammation-induced perinatal brain injury. Pregnant New Zealand white rabbits were intrauterinely injected with endotoxin or saline at 28 days of gestation. Kits were born spontaneously at 31 days and underwent neurobehavioral testing and PET imaging following intravenous injection of the tracer [C-11]-(R)-PK11195 on the day of birth. The neurobehavioral scores were compared with the change in [C-11]PK11195 uptake over the time of scanning, for each of the kits. Upon analysis using receiver operating characteristic curves, an optimal combined sensitivity and specificity for detecting abnormal neurobehavioral scores suggestive of cerebral palsy in the neonatal rabbit was noted for a positive change in [C-11]PK11195 uptake in the brain over time on PET imaging (sensitivity of 100% and area under the curve of >0.82 for all parameters tested). The strongest agreements were noted between a positive uptake slope - indicating increased [C-11]PK11195 uptake over time - and worsening scores for measures of locomotion (indicated by hindlimb movement, forelimb movement, circular motion and straightline motion; Cohen's kappa >0.75 for each) and feeding (indicated by ability to suck and swallow and turn the head during feeding; Cohen's kappa >0.85 for each). This was also associated with increased numbers of activated microglia (mean ratio 8 +/- SD of activated to total microglia: 0.96 +/- 0.16 in the endotoxin group vs. 0.13 +/- 0.08 in controls; p < 0.001) in the internal capsule and corona radiata. Our findings indicate that the magnitude of [C-11]PK11195 binding measured in vivo by PET imaging matches the severity of motor deficits in the neonatal rabbit. Molecular imaging of ongoing neuroinflammation in the neonatal period may be helpful as a screening biomarker for detecting patients at risk of developing cerebral palsy due to a perinatal insult. Copyright (C) 2011 S. Karger AG, Basel C1 [Kannan, Sujatha; Saadani-Makki, Fadoua; Balakrishnan, Bindu; Lu, Xin; Muzik, Otto; Chugani, Diane C.] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. [Chakraborty, Pulak; Muzik, Otto; Chugani, Diane C.] Wayne State Univ, Dept Radiol, Detroit, MI 48202 USA. [Janisse, James] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI 48202 USA. [Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept Hlth & Human Serv, Detroit, MI USA. RP Kannan, S (reprint author), Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, 600N Wolfe St,904 Blalock, Baltimore, MD 21287 USA. EM skannan.wsu@gmail.com FU National Institute of Child Health and Human Development, NIH [1K08HD050652]; Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, United States Department of Health and Human Services FX This study was funded in part by the National Institute of Child Health and Human Development, NIH (1K08HD050652), and the Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, United States Department of Health and Human Services. We would like to thank Dr. Amar Jyoti for his help with the immunohistochemistry. NR 54 TC 18 Z9 21 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2011 VL 33 IS 3-4 BP 231 EP 240 DI 10.1159/000328125 PG 10 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 842OK UT WOS:000296608600005 PM 21791891 ER PT J AU Thomas, LA Hall, JM Skup, M Jenkins, SE Pine, DS Leibenluft, E AF Thomas, Laura A. Hall, Julie M. Skup, Martha Jenkins, Sarah E. Pine, Daniel S. Leibenluft, Ellen TI A developmental neuroimaging investigation of the change paradigm SO DEVELOPMENTAL SCIENCE LA English DT Article ID EVENT-RELATED FMRI; INFERIOR PREFRONTAL CORTEX; COGNITIVE CONTROL; STOP-SIGNAL; RESPONSE-INHIBITION; ANTERIOR CINGULATE; BRAIN-DEVELOPMENT; DIFFERENTIAL RESPONSES; EXECUTIVE FUNCTIONS; WORKING-MEMORY AB This neuroimaging study examines the development of cognitive flexibility using the Change task in a sample of youths and adults. The Change task requires subjects to inhibit a prepotent response and substitute an alternative response, and the task incorporates an algorithm that adjusts task difficulty in response to subject performance. Data from both groups combined show a network of prefrontal and parietal areas that are active during the task. For adults vs. youths, a distributed network was more active for successful change trials versus go, baseline, or unsuccessful change trials. This network included areas involved in rule representation, retrieval (lateral PFC), and switching (medial PFC and parietal regions). These results are consistent with data from previous task-switching experiments and inform developmental understandings of cognitive flexibility. C1 [Thomas, Laura A.] NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, Mood & Anxiety Program,NIH,Dept Hlth Human Serv, Bethesda, MD 20892 USA. [Hall, Julie M.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Hall, Julie M.] Howard Hughes Med Inst, Natl Inst Hlth Res Scholars Program, Bethesda, MD 20817 USA. [Skup, Martha] Yale Univ, Sch Publ Hlth, New Haven, CT USA. RP Thomas, LA (reprint author), NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, Mood & Anxiety Program,NIH,Dept Hlth Human Serv, 15K N Dr,MSC 2670, Bethesda, MD 20892 USA. EM tlaura@mail.nih.gov OI Thomas, Laura/0000-0002-4106-1358 FU Intramural NIH HHS [Z99 MH999999] NR 79 TC 5 Z9 5 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1363-755X J9 DEVELOPMENTAL SCI JI Dev. Sci. PD JAN PY 2011 VL 14 IS 1 BP 148 EP 161 DI 10.1111/j.1467-7687.2010.00967.x PG 14 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 693TP UT WOS:000285248600015 PM 21159096 ER PT J AU Bornstein, MH Arterberry, ME Mash, C AF Bornstein, Marc H. Arterberry, Martha E. Mash, Clay BE Bornstein, MH Lamb, ME TI PERCEPTUAL DEVELOPMENT SO DEVELOPMENTAL SCIENCE: AN ADVANCED TEXTBOOK, SIXTH EDITION LA English DT Article; Book Chapter ID LANGUAGE SPEECH-PERCEPTION; QUANTITATIVE DENDRITIC ANALYSIS; NONNATIVE CONSONANT CONTRASTS; EARLY VISUAL DEPRIVATION; FACE PROCESSING SKILLS; HUMAN INFANTS; 5-MONTH-OLD INFANTS; YOUNG INFANTS; LIFE-SPAN; PRESCHOOL-CHILDREN C1 [Bornstein, Marc H.; Mash, Clay] NICHHD, Bethesda, MD 20892 USA. [Arterberry, Martha E.] Gettysburg Coll, Gettysburg, PA USA. RP Bornstein, MH (reprint author), NICHHD, Bethesda, MD 20892 USA. NR 359 TC 1 Z9 1 U1 1 U2 3 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-203-84676-6 PY 2011 BP 303 EP 351 PG 49 WC Psychology, Developmental SC Psychology GA BUF20 UT WOS:000289073000009 ER PT J AU Kang, HS Okamoto, K Kim, YS Takeda, Y Bortner, CD Dang, HX Wada, T Xie, W Yang, XP Liao, G Jetten, AM AF Kang, Hong Soon Okamoto, Kyoko Kim, Yong-Sik Takeda, Yukimasa Bortner, Carl D. Dang, Huaixin Wada, Taira Xie, Wen Yang, Xiao-Ping Liao, Grace Jetten, Anton M. TI Nuclear Orphan Receptor TAK1/TR4-Deficient Mice Are Protected Against Obesity-Linked Inflammation, Hepatic Steatosis, and Insulin Resistance SO DIABETES LA English DT Article ID DIET-INDUCED OBESITY; LIPID DROPLETS; ADIPOSE-TISSUE; DEFICIENT MICE; METABOLIC-DISORDERS; MOLECULAR-CLONING; STEROID-RECEPTOR; CD36 EXPRESSION; PPAR-GAMMA; FAT MASS AB OBJECTIVE The nuclear receptor TAK1/TR4/NR2C2 is expressed in several tissues that are important in the control of energy homeostasis. In this study, we investigate whether TAK1 functions as a regulator of lipid and energy homeostasis and has a role in metabolic syndrome. RESEARCH DESIGN AND METHODS We generated TAK1-deficient (TAK1(-/-)) mice to study the function of TAK1 in the development of metabolic syndrome in aged mice and mice fed a high-fat diet (HFD). (Immuno)histochemical, biochemical, and gene expression profile analyses were performed to determine the effect of the loss of TAK1 expression on lipid homeostasis in liver and adipose tissues. In addition, insulin sensitivity, energy expenditure, and adipose-associated inflammation were compared in wild-type (WT) and TAK1(-/-) mice fed a HFD. RESULTS TAK1-deficient (TAK1(-/-)) mice are resistant to the development of age- and HFD-induced metabolic syndrome. Histo- and biochemical analyses showed significantly lower hepatic triglyceride levels and reduced lipid accumulation in adipose tissue in TAK1(-/-) mice compared with WT mice. Gene expression profiling analysis revealed that the expression of several genes encoding proteins involved in lipid uptake and triglyceride synthesis and storage, including Cidea, Cidec, Mogatl, and CD36, was greatly decreased in the liver and primary hepatocytes of TAK1(-/-) mice. Restoration of TAK1 expression in TAK1(-/-) hepatocytes induced expression of several lipogenic genes. Moreover, TAK1(-/-) mice exhibited reduced infiltration of inflammatory cells and expression of inflammatory genes in white adipose tissue, and were resistant to the development of glucose intolerance and insulin resistance. TAK1(-/-) mice consume more oxygen and produce more carbon dioxide than WT mice, suggesting increased energy expenditure. CONCLUSIONS Our data reveal that TAK1 plays a critical role in the regulation of energy and lipid homeostasis, and promotes the development of metabolic syndrome. TAK1 may provide a new therapeutic target in the management of obesity, diabetes, and liver steatosis. Diabetes 60:177-188, 2011 C1 [Kang, Hong Soon; Okamoto, Kyoko; Kim, Yong-Sik; Takeda, Yukimasa; Dang, Huaixin; Yang, Xiao-Ping; Liao, Grace; Jetten, Anton M.] NIEHS, Cell Biol Sect, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. [Bortner, Carl D.] NIEHS, Lab Signal Transduct, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. [Wada, Taira; Xie, Wen] Univ Pittsburgh, Ctr Phannacogenet, Pittsburgh, PA USA. [Wada, Taira; Xie, Wen] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA USA. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Lab Resp Biol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov RI Xie, Wen/M-1768-2016; OI Jetten, Anton/0000-0003-0954-4445 FU National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health [Z01-ES-101586] FX This research was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (Z01-ES-101586). NR 46 TC 46 Z9 50 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2011 VL 60 IS 1 BP 177 EP 188 DI 10.2337/db10-0628 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 703YG UT WOS:000286017300023 PM 20864514 ER PT J AU Song, YQ Xu, Q Park, Y Hollenbeck, A Schatzkin, A Chen, HL AF Song, Yiqing Xu, Qun Park, Yikyung Hollenbeck, Albert Schatzkin, Arthur Chen, Honglei TI Multivitamins, Individual Vitamin and Mineral Supplements, and Risk of Diabetes Among Older US Adults SO DIABETES CARE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; NATIONAL-INSTITUTES; DIETARY CALCIUM; HEALTH; WOMEN; ASSOCIATION; ANTIOXIDANT; POPULATION AB OBJECTIVE- Understanding the relationship between multivitamin use and diabetes risk is important given the wide use of multivitamin supplements among U.S. adults. RESEARCH DESIGN AND METHODS- We prospectively examined supplemental use of multivitamins and individual vitamins and minerals assessed in 1995-1996 in relation to self-reported diabetes diagnosed after 2000 among 232,007 participants in the National Institutes of Health American Association of Retired Persons Diet and Health Study. Multivitamin use was assessed by a food-frequency questionnaire at baseline. Odds ratios (ORs) and 95% CIs were calculated by logistic regression models, adjusted for potential confounders. In total, 14,130 cases of diabetes diagnosed after 2000 were included in the analysis. RESULTS- Frequent use of any multivitamins was not associated with risk of diabetes after adjustment for potential confounders and uses of individual supplements. Compared with nonusers of any multivitamins, the multivariate ORs among users were 1.07 (95% CI 0.94-1.21) for taking vitamins less than once per week, 0.97 (0.88-1.06) for one to three times per week, 0.92 (0.84-1.00) for four to six times per week, and 1.02 (0.98-1.06) for seven or more times per week (P for trend = 0.64). Significantly lower risk of diabetes was associated with the use of vitamin C or calcium supplements. The multivariate ORs comparing daily users with nonusers were 0.91 (0.86-0.97) for vitamin C supplements and 0.85 (0.80-0.90) for calcium supplements. Use of vitamin E or other individual vitamin and mineral supplements were not associated with diabetes risk. CONCLUSIONS- In this large cohort of U.S. older adults, multivitamin use was not associated with diabetes risk. The findings of lower diabetes risk among frequent users of vitamin C or calcium supplements warrant further evaluations. C1 [Xu, Qun; Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. [Xu, Qun] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Epidemiol & Hlth Stat, Beijing 100730, Peoples R China. [Song, Yiqing] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. [Park, Yikyung; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Rockville, MD USA. [Hollenbeck, Albert] Amer Assoc Retired Persons, Washington, DC USA. RP Chen, HL (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. EM chenh2@niehs.nih.gov OI Chen, Honglei/0000-0003-3446-7779; Park, Yikyung/0000-0002-6281-489X FU NIH, the National Institute of Environmental Health Sciences [Z01-ES-101986]; National Cancer Institute [Z01 CP010196-02]; National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland [K01-DK078846] FX This study was supported by the intramural research program of the NIH, the National Institute of Environmental Health Sciences (Z01-ES-101986), and the National Cancer Institute (Z01 CP010196-02). Y.S. is supported by a grant (K01-DK078846) from the National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland. NR 25 TC 12 Z9 13 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2011 VL 34 IS 1 BP 108 EP 114 DI 10.2337/dc10-1260 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 710FT UT WOS:000286497000022 PM 20978095 ER PT J AU de Miguel-Yanes, JM Shrader, P Pencina, MJ Fox, CS Manning, AK Grant, RW Dupuis, J Florez, JC D'Agostino, RB Cupples, LA Meigs, JB AF de Miguel-Yanes, Jose M. Shrader, Peter Pencina, Michael J. Fox, Caroline S. Manning, Alisa K. Grant, Richard W. Dupuis, Josee Florez, Jose C. D'Agostino, Ralph B., Sr. Cupples, L. Adrienne Meigs, James B. CA MAGIC Investigators DIAGRAM Investigators TI Genetic Risk Reclassification for Type 2 Diabetes by Age Below or Above 50 Years Using 40 Type 2 Diabetes Risk Single Nucleotide Polymorphisms SO DIABETES CARE LA English DT Article ID ASSOCIATION ANALYSIS; SUSCEPTIBILITY LOCI; VARIANTS; MELLITUS AB OBJECTIVE- To test if knowledge of type 2 diabetes genetic variants improves disease prediction. RESEARCH DESIGN AND METHODS- We tested 40 single nucleotide polymorphisms (SNPs) associated with diabetes in 3,471 Framingham Offspring Study subjects followed over 34 years using pooled logistic regression models stratified by age (<50 years, diabetes cases = 144; or >= 50 years, diabetes cases = 302). Models included clinical risk factors and a 40-SNP weighted genetic risk score. RESULTS- In people <50 years of age, the clinical risk factors model C-statistic was 0.908; the 40-SNP score increased it to 0.911 (P = 0.3; net reclassification improvement (NRI): 10.2%, P = 0.001). In people >= 50 years of age, the C-statistics without and with the score were 0.883 and 0.884 (P = 0.2; NRI: 0.4%). The risk per risk allele was higher in people <50 than >= 50 years of age (24 vs. 11%; P value for age interaction = 0.02). CONCLUSIONS- Knowledge of common genetic variation appropriately reclassifies younger people for type 2 diabetes risk beyond clinical risk factors but not older people. C1 [de Miguel-Yanes, Jose M.; Shrader, Peter; Grant, Richard W.; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [de Miguel-Yanes, Jose M.; Fox, Caroline S.; Grant, Richard W.; Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [de Miguel-Yanes, Jose M.] Hosp Gen Univ Gregorio Maranon, Dept Med Interna, Madrid, Spain. [Pencina, Michael J.; D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Fox, Caroline S.; Dupuis, Josee; D'Agostino, Ralph B., Sr.; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA. [Manning, Alisa K.; Dupuis, Josee; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM jmeigs@partners.org OI Griffin, Simon/0000-0002-2157-4797; Cupples, L. Adrienne/0000-0003-0273-7965; Dupuis, Josee/0000-0003-2871-3603; Grant, Richard/0000-0002-6164-8025 FU National Heart, Lung, and Blood Institute [N01-HC- 25195]; National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK078616, K24 DK080140, K23 DK65978, R21 DK084527]; "Instituto de Salud Carlos III", Madrid, Spain [2009/90071]; National Institutes of Health National Center for Research Resources [1S10RR163736-01A1] FX This study was supported by the by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract no. N01-HC- 25195), the National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) grants R01 DK078616 and K24 DK080140 (to J.B.M.), NIDDK Research Career Award K23 DK65978 (to J.C.F.), NIDDK Grant R21 DK084527 (to R.W.G.), "Bolsa de Ampliacion de Estudios" from the "Instituto de Salud Carlos III", Madrid, Spain (2009/90071) (to J.M.D.M.Y.), and the Boston University Linux Cluster for Genetic Analysis (LinGA) funded by the National Institutes of Health National Center for Research Resources Shared Instrumentation Grant (1S10RR163736-01A1). NR 15 TC 90 Z9 91 U1 1 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2011 VL 34 IS 1 BP 121 EP 125 DI 10.2337/dc10-1265 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 710FT UT WOS:000286497000025 PM 20889853 ER PT J AU Tobias, DK Zhang, CL van Dam, RM Bowers, K Hu, FB AF Tobias, Deirdre K. Zhang, Cuilin van Dam, Rob M. Bowers, Katherine Hu, Frank B. TI Physical Activity Before and During Pregnancy and Risk of Gestational Diabetes Mellitus A meta-analysis SO DIABETES CARE LA English DT Article ID GLYCEMIC CONTROL; GLUCOSE-UPTAKE; EXERCISE; INSULIN; WOMEN; HETEROGENEITY; MUSCLE; BIAS AB OBJECTIVE- Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy and is associated with a substantially elevated risk of adverse health outcomes for both mothers and offspring. Physical activity may contribute to the prevention of GDM and thus is crucial for dissecting the vicious circle involving GDM, childhood obesity, and adulthood obesity, and diabetes. Therefore, we aimed to systematically review and synthesize the current evidence on the relation between physical activity and the development of GDM. RESEARCH DESIGN AND METHODS- Medline, EMBASE, and Cochrane Reviews were searched from inception to 31 March 2010. Studies assessing the relationship between physical activity and subsequent development of GDM were included. Characteristics including study design, country, GDM diagnostic criteria, ascertainment of physical activity, timing of exposure (prepregnancy or early pregnancy), adjusted relative risks, CIs, and statistical methods were extracted independently by two reviewers. RESULTS- Our search identified seven prepregnancy and five early pregnancy studies, including five prospective cohorts, two retrospective case-control studies, and two cross-sectional study designs. Prepregnancy physical activity was assessed in 34,929 total participants, which included 2,813 cases of GDM, giving a pooled odds ratio (OR) of 0.45 (95% CI 0.28-0.75) when the highest versus lowest categories were compared. Exercise in early pregnancy was assessed in 4,401 total participants, which included 361 cases of GDM, and was also significantly protective (0.76 [95% CI 0.70-0.83]). CONCLUSIONS Higher levels of physical activity before pregnancy or in early pregnancy are associated with a significantly lower risk of developing GDM. C1 [Tobias, Deirdre K.; van Dam, Rob M.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Tobias, Deirdre K.; van Dam, Rob M.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Zhang, Cuilin; Bowers, Katherine] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, Bethesda, MD USA. [van Dam, Rob M.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Epidemiol, Singapore 117595, Singapore. [Hu, Frank B.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Publ Hlth & Med, Singapore 117595, Singapore. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Tobias, DK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. EM dbanel@hsph.harvard.edu RI van Dam, Rob/F-9674-2010; Bowers, Katherine/N-5226-2015 OI van Dam, Rob/0000-0002-7354-8734; FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health FX C.Z. and K.B. were supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. No potential conflicts of interest relevant to this article were reported. NR 38 TC 108 Z9 122 U1 6 U2 36 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2011 VL 34 IS 1 BP 223 EP 229 DI 10.2337/dc10-1368 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 710FT UT WOS:000286497000046 PM 20876206 ER PT J AU Dabelea, D D'Agostino, RB Mason, CC West, N Hamman, RF Mayer-Davis, EJ Maahs, D Klingensmith, G Knowler, WC Nadeau, K AF Dabelea, D. D'Agostino, R. B., Jr. Mason, C. C. West, N. Hamman, R. F. Mayer-Davis, E. J. Maahs, D. Klingensmith, G. Knowler, W. C. Nadeau, K. TI Development, validation and use of an insulin sensitivity score in youths with diabetes: the SEARCH for Diabetes in Youth study SO DIABETOLOGIA LA English DT Article DE Development; Diabetes; Insulin sensitivity; Validation; Youth ID CLINICAL CHARACTERISTICS; WAIST CIRCUMFERENCE; SYNDROME-X; RESISTANCE; TYPE-1; ADOLESCENTS; MELLITUS; QUANTIFICATION; PREVALENCE; SECRETION AB Aims/hypothesis The ability to measure insulin sensitivity across the phenotypic spectrum of diabetes may contribute to a more accurate characterisation of diabetes type. Our goal was to develop and validate an insulin sensitivity (IS) score using the euglycaemic-hyperinsulinaemic clamp in a subset (n = 85) of 12- to 19-year-old youths with diabetes participating in the SEARCH study in Colorado, USA. Methods Youths with a diagnosis of type 1 (n = 60) or type 2 diabetes (n = 25) underwent a 3 h clamp to measure glucose disposal rate (GDR, mg kg(-1) min(-1)). Demographic (age, sex, race), clinical (BMI, waist, Tanner stage) and metabolic characteristics (HbA(1c), lipids, blood pressure, urine albumin: creatinine) were used to estimate log(e)IS score via stepwise linear regression on a model-development set (n = 53). Estimated IS score was evaluated for reproducibility on two validation sets: youths with diabetes (n = 33) and healthy control youths (n = 22). Results The best model included waist, triacylglycerol (TG) and HbA(1c) levels (R-2 = 0.74). Diabetes type did not enter the model and there were no significant interactions between diabetes type and other predictors. Estimated IS score correlated well (r = 0.65, p < 0.0001; r = 0.62, p = 0.002) with GDR on the two validation sets. Based on this analysis, we propose the following formula to estimate insulin sensitivity in youths with diabetes: logeIS 4: 64725 = 0: 02032 (waist; cm) = 0: 09779 (HbA(1c), %) - 0: 00235 (TG; mg/dl; to convert TG values from mmol/l to mg/dl; divide by 0.0113). Conclusions/interpretation Insulin sensitivity can be estimated in adolescents with diabetes using routinely collected measures. This score can be applied to epidemiological studies of youths with diabetes to characterise relationships between dimensions of diabetes type. C1 [Dabelea, D.; West, N.; Hamman, R. F.] Univ Colorado Denver, Dept Epidemiol, Colorado Sch Publ Hlth, Aurora, CO 80045 USA. [D'Agostino, R. B., Jr.] Wake Forest Univ, Sch Med, Dept Biostat Sci, Winston Salem, NC 27109 USA. [Mason, C. C.; Knowler, W. C.] NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. [Mayer-Davis, E. J.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Maahs, D.; Klingensmith, G.; Nadeau, K.] Univ Colorado Denver, Sch Med, Barbara Davis Ctr, Aurora, CO USA. [Maahs, D.; Klingensmith, G.; Nadeau, K.] Univ Colorado Denver, Sch Med, Dept Pediat, Aurora, CO USA. RP Dabelea, D (reprint author), Univ Colorado Denver, Dept Epidemiol, Colorado Sch Publ Hlth, 13001 E 17th Ave,Box B119,Room W3110, Aurora, CO 80045 USA. EM Dana.Dabelea@ucdenver.edu RI Dagostino Jr, Ralph/C-4060-2017 OI Dagostino Jr, Ralph/0000-0002-3550-8395 FU Pediatric General Clinical Research Center; University of Colorado, Denver, CO, USA; National Institute of Diabetes and Digestive and Kidney Diseases; Centers for Disease Control and Prevention [00097, DP-05-069]; Kaiser Permanente Southern California [U01 DP000246]; University of Colorado, Denver, CO, USA [U01 DP000247]; Pacific Health Research Institute [U01 DP000245]; Children's Hospital Medical Center (Cincinnati) [U01 DP000248]; University of North Carolina at Chapel Hill [U01 DP000254]; University of Washington School of Medicine [U01 DP000244]; Wake Forest University School of Medicine [U01 DP000250]; [R01 DK059184]; [RR020038]; [JDRF5-2008-291] FX This study was supported by R01 DK059184 (D. Dabelea); K23 RR020038 and JDRF5-2008-291 (K. Nadeau), the Pediatric General Clinical Research Center, the University of Colorado, Denver, CO, USA and the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (C. C. Mason and W. C. Knowler). SEARCH for Diabetes in Youth is funded by the Centers for Disease Control and Prevention (PA number 00097 and DP-05-069), Kaiser Permanente Southern California (U01 DP000246), University of Colorado, Denver, CO, USA (U01 DP000247), Pacific Health Research Institute (U01 DP000245), Children's Hospital Medical Center (Cincinnati) (U01 DP000248), University of North Carolina at Chapel Hill (U01 DP000254), University of Washington School of Medicine (U01 DP000244) and Wake Forest University School of Medicine (U01 DP000250). NR 33 TC 35 Z9 38 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2011 VL 54 IS 1 BP 78 EP 86 DI 10.1007/s00125-010-1911-9 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 688ZQ UT WOS:000284896900014 PM 20886205 ER PT J AU Jafar-Mohammadi, B Groves, CJ Gjesing, AP Herrera, BM Winckler, W Stringham, HM Morris, AP Lauritzen, T Doney, ASF Morris, AD Weedon, MN Swift, AJ Kuusisto, J Laakso, M Altshuler, D Hattersley, AT Collins, FS Boehnke, M Hansen, T Pedersen, O Palmer, CNA Frayling, TM Gloyn, AL McCarthy, MI AF Jafar-Mohammadi, B. Groves, C. J. Gjesing, A. P. Herrera, B. M. Winckler, W. Stringham, H. M. Morris, A. P. Lauritzen, T. Doney, A. S. F. Morris, A. D. Weedon, M. N. Swift, A. J. Kuusisto, J. Laakso, M. Altshuler, D. Hattersley, A. T. Collins, F. S. Boehnke, M. Hansen, T. Pedersen, O. Palmer, C. N. A. Frayling, T. M. Gloyn, A. L. McCarthy, M. I. CA DIAGRAM Consortium TI A role for coding functional variants in HNF4A in type 2 diabetes susceptibility SO DIABETOLOGIA LA English DT Article DE HNF4A; Low-frequency variants; T130I; Type 2 diabetes; V255M ID GENOME-WIDE ASSOCIATION; NUCLEAR FACTOR 4-ALPHA; CHROMOSOME 20Q; FACTOR-4-ALPHA GENE; COMMON VARIANTS; T130I MUTATION; UK POPULATION; LOCI; RISK; REPLICATION AB Aims/hypothesis Rare mutations in the gene HNF4A, encoding the transcription factor hepatocyte nuclear factor 4 alpha (HNF-4A), account for similar to 5% of cases of MODY and more frequent variants in this gene may be involved in multifactorial forms of diabetes. Two low-frequency, non-synonymous variants in HNF4A (V255M, minor allele frequency [MAF] similar to 0.1%; T130I, MAF similar to 3.0%)-known to influence downstream HNF-4A target gene expression-are of interest, but previous type 2 diabetes association reports were inconclusive. We aimed to evaluate the contribution of these variants to type 2 diabetes susceptibility through large-scale association analysis. Methods We genotyped both variants in at least 5,745 cases and 14,756 population controls from the UK and Denmark. We also undertook an expanded association analysis that included previously reported and novel genotype data obtained in Danish, Finnish, Canadian and Swedish samples. A meta-analysis incorporating all published association studies of the T130I variant was subsequently carried out in a maximum sample size of 14,279 cases and 26,835 controls. Results We found no association between V255M and type 2 diabetes in either the initial (p = 0.28) or the expanded analysis (p = 0.44). However, T130I demonstrated a modest association with type 2 diabetes in the UK and Danish samples (additive per allele OR 1.17 [95% CI 1.08-1.28]; p = 1.5 x 10(-4)), which was strengthened in the meta-analysis (OR 1.20 [95% CI 1.10-1.30]; p = 2.1 x 10(-5)). Conclusions Our data are consistent with T130I as a low-frequency variant influencing type 2 diabetes risk, but are not conclusive when judged against stringent standards for genome-wide significance. This study exemplifies the difficulties encountered in association testing of low-frequency variants. C1 [Jafar-Mohammadi, B.; Groves, C. J.; Herrera, B. M.; Gloyn, A. L.; McCarthy, M. I.] Univ Oxford, Churchill Hosp, OCDEM, Oxford OX3 7LJ, England. [Jafar-Mohammadi, B.; Groves, C. J.; Gloyn, A. L.; McCarthy, M. I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Gjesing, A. P.; Hansen, T.; Pedersen, O.] Steno Diabet Ctr, Copenhagen, Denmark. [Gjesing, A. P.; Hansen, T.; Pedersen, O.] Hagedorn Res Inst, Copenhagen, Denmark. [Herrera, B. M.; Morris, A. P.; McCarthy, M. I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Winckler, W.; Altshuler, D.] Broad Inst Harvard, Cambridge, MA USA. [Winckler, W.; Altshuler, D.] MIT, Cambridge, MA 02139 USA. [Stringham, H. M.; Boehnke, M.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Lauritzen, T.] Univ Aarhus, Dept Gen Practice, Aarhus, Denmark. [Doney, A. S. F.; Morris, A. D.] Univ Dundee, Ninewells Hosp & Med Sch, Diabet Res Grp, Dundee DD1 9SY, Scotland. [Weedon, M. N.; Hattersley, A. T.; Frayling, T. M.] Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England. [Weedon, M. N.; Hattersley, A. T.; Frayling, T. M.] Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England. [Swift, A. J.] NHGRI, NIH, Bethesda, MD 20892 USA. [Kuusisto, J.; Laakso, M.] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Kuusisto, J.; Laakso, M.] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Altshuler, D.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, D.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Altshuler, D.] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA USA. [Altshuler, D.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, D.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Hansen, T.] Univ So Denmark, Fac Hlth Sci, Odense, Denmark. [Pedersen, O.] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. [Pedersen, O.] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark. [Palmer, C. N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Ctr, Dundee DD1 9SY, Scotland. RP McCarthy, MI (reprint author), Univ Oxford, Churchill Hosp, OCDEM, Old Rd, Oxford OX3 7LJ, England. EM mark.mccarthy@drl.ox.ac.uk RI Altshuler, David/A-4476-2009; Palmer, Colin/C-7053-2008; Boehm, Bernhard/F-8750-2015; Study, GoDARTS/K-9448-2016 OI Altshuler, David/0000-0002-7250-4107; Palmer, Colin/0000-0002-6415-6560; FU Medical Research Council (MRC) [G0000934, 81696]; Wellcome Trust [068545/Z/02, GR072960]; Oxford NIHR Biomedical Research Centre; Danish Agency for Science Technology and Innovation [271-06-0539]; National Health Services in the counties of Copenhagen, Aarhus, Ringkobing, Ribe and South Jutland; Danish Research Foundation for General Practice, Danish Centre for Evaluation and Health Technology Assessment; National Board of Health; Danish Medical Research Council; Aarhus University Research Foundation; Novo Nordisk Foundation; Novo Nordisk; Novo Nordisk Scandinavia; Astra Denmark; Pfizer Denmark; GlaxoSmithKline Pharma Denmark; Servier Denmark; HemoCue Denmark; US National Institutes of Health [DK062370, DK072193, HL084729, HG002651, U54 DA021519]; National Human Genome Research Institute [1 Z01 HG000024]; Academy of Finland; EVO [5263]; Sigrid Juselius Foundation; Finnish Diabetes Research Foundation; Folkhalsan Research Foundation; EC [BM4-CT95-0662]; Swedish Medical Research Council; JDF Wallenberg Foundation FX We acknowledge use of genotype data from the British 1958 Birth Cohort DNA collection, funded by the Medical Research Council (MRC) grant G0000934 and the Wellcome Trust grant 068545/Z/02. We acknowledge Diabetes UK for funding the collection of the Warren 2 resource and would also like to thank G. Hitman, Barts and The London School of Medicine and Dentistry, UK, and M. Walker, Newcastle University, UK. We thank the staff and senior management of the UK Blood Services responsible for the UK Blood Services Collection. The UK Type 2 Diabetes Genetics Consortium collection was supported by the Wellcome Trust (Biomedical Collections Grant GR072960). B. Jafar-Mohammadi is a Diabetes UK Clinical Training Fellow. A. L. Gloyn is an MRC New Investigator (Grant Reference 81696). This work was part funded in Oxford by the Oxford NIHR Biomedical Research Centre Programme. The Danish studies were supported by the Danish Agency for Science Technology and Innovation (grant no. 271-06-0539). The ADDITION study was initiated by: K. Borch-Johnsen, Steno Diabetes Centre, Gentofte, Denmark (principal investigator), T. Lauritzen, University of Aarhus, Denmark (principal investigator) and A. Sandbaek, University of Aarhus, Aarhus, Denmark. The study was supported by the National Health Services in the counties of Copenhagen, Aarhus, Ringkobing, Ribe and South Jutland, together with the Danish Research Foundation for General Practice, Danish Centre for Evaluation and Health Technology Assessment, the diabetes fund of the National Board of Health, the Danish Medical Research Council, the Aarhus University Research Foundation and the Novo Nordisk Foundation. The study received unrestricted grants from Novo Nordisk, Novo Nordisk Scandinavia, Astra Denmark, Pfizer Denmark, GlaxoSmithKline Pharma Denmark, Servier Denmark and HemoCue Denmark. We acknowledge use of the FUSION genotyping data. Support for this study was provided by US National Institutes of Health grants (DK062370, DK072193, HL084729, HG002651 and U54 DA021519) as well as National Human Genome Research Institute intramural project number 1 Z01 HG000024. The METSIM study was supported by the Academy of Finland and the EVO grant (no. 5263). The Broad study would like to acknowledge the many clinical researchers involved with these sample collections. The Scandinavian collections are part of the Botnia Study, and are principally supported by the Sigrid Juselius Foundation, the Academy of Finland, the Finnish Diabetes Research Foundation, the Folkhalsan Research Foundation, EC (BM4-CT95-0662, GIFT), the Swedish Medical Research Council, the JDF Wallenberg Foundation, and the Novo Nordisk Foundation. We thank other members of the DIAGRAM consortium (see the ESM for a full listing) for sharing data. Funding sources for the DIAGRAM consortium are included in Voight et al. [8]. D. Altshuler is a Burroughs Wellcome Fund Clinical Scholar in Translational Research, which supported this work. NR 33 TC 14 Z9 15 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2011 VL 54 IS 1 BP 111 EP 119 DI 10.1007/s00125-010-1916-4 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 688ZQ UT WOS:000284896900018 PM 20878384 ER PT J AU Cotsapas, C Prokunina-Olsson, L Welch, C Saxena, R Weaver, C Usher, N Guiducci, C Bonakdar, S Turner, N LaCroix, B Hall, JL AF Cotsapas, C. Prokunina-Olsson, L. Welch, C. Saxena, R. Weaver, C. Usher, N. Guiducci, C. Bonakdar, S. Turner, N. LaCroix, B. Hall, J. L. TI Expression analysis of loci associated with type 2 diabetes in human tissues (vol 53, pg 2334, 2010) SO DIABETOLOGIA LA English DT Correction C1 [Welch, C.; Weaver, C.; Usher, N.; Turner, N.; LaCroix, B.; Hall, J. L.] Lillehei Heart Inst, Dept Med, Minneapolis, MN 55455 USA. [Prokunina-Olsson, L.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Cotsapas, C.; Saxena, R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hall, J. L.] Univ Minnesota, Ctr Dev Biol, Minneapolis, MN USA. [Cotsapas, C.; Saxena, R.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Saxena, R.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Cotsapas, C.; Saxena, R.; Guiducci, C.; Bonakdar, S.] Broad Inst, Cambridge, MA USA. RP Hall, JL (reprint author), Lillehei Heart Inst, Dept Med, 4-280 NHH,312 Church St SE, Minneapolis, MN 55455 USA. EM jlhall@umn.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2011 VL 54 IS 1 BP 209 EP 209 DI 10.1007/s00125-010-1939-x PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 688ZQ UT WOS:000284896900031 ER PT J AU Ojeaburu, JV Ito, T Crafa, P Bordi, C Jensen, RT AF Ojeaburu, Jeremiah V. Ito, Tetsuhide Crafa, Pellegrino Bordi, Cesare Jensen, Robert T. TI Mechanism of Acid Hypersecretion Post Curative Gastrinoma Resection SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Zollinger-Ellison syndrome; Gastrinoma; Acid secretion; Proton pump inhibitors; ECL cells ID ZOLLINGER-ELLISON-SYNDROME; ENDOCRINE NEOPLASIA TYPE-1; PUMP INHIBITOR THERAPY; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; INSTITUTES-OF-HEALTH; SERUM CHROMOGRANIN-A; LONG-TERM TREATMENT; HELICOBACTER-PYLORI; SUPPRESSIVE THERAPY; REFLUX ESOPHAGITIS AB Background Some patients with Zollinger-Ellison syndrome post curative gastrinoma resection continue to show gastric acid hypersecretion; however, the mechanism is unknown. Aim The aim of this study was to prospectively study acid secretion following curative gastrinoma resection and analyze factors contributing in patients with Zollinger-Ellison syndrome. Methods Fifty patients cured post gastrinoma resection were studied with serial assessments of acid secretory status, cure status and ECL-cell status/activity (with serial biopsies, CgA, urinary N-MIAA). Correlative analysis was performed to determine predictive factors. Results Hypersecretion occurred in 31 patients (62%) and 14 had extreme-hypersecretion. There was an initial decline (3-6 months) in BAO/MAO, which then remained stable for eight years. Preoperative BAO correlated with the postoperative secretion, but not other clinical, tumoral, laboratory variables, the degree of postoperative acid suppression or type of antisecretory drug needed. Hypersecretors had greater postoperative ECL changes (P = 0.005), serum CGA (P = 0.009) and 24-h urinary N-MIAA (P = 0.0038). Conclusions Post curative resection, gastric hypersecretion persists long term (mean 8 years) in 62% of patients and in 28% it is extreme, despite normogastrinemia. No preoperative variable except BAO correlates with postresection hypersecretion. The persistent increased ECL-cell extent post curative resection suggests prolonged hypergastrinemia can lead to changes in ECL-cells that are either irreversible in humans or sustained by unknown mechanisms not involving fasting hypergastrinemia and which can result in hypersecretion, in a proportion of which it can be extreme. Whether similar findings may occur in patients with idiopathic GERD treated for prolonged periods (>10 years) with PPIs, at present, is unknown. C1 [Ojeaburu, Jeremiah V.; Jensen, Robert T.] NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. [Ito, Tetsuhide] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Fukuoka 812, Japan. [Crafa, Pellegrino; Bordi, Cesare] Univ Parma, Dept Pathol & Lab Med, Sect Pathol Anat, I-43100 Parma, Italy. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Rm 9C-103,10 Ctr DR MSC 1804, Bethesda, MD 20892 USA. EM ojeaburu@hotmail.com; itopapa@intmed3.med.kyushu-u.ac.jp; rcrafa@ao.pr.it; cesare.bordi@unipr.it; RobertJ@bdg10.niddk.nih.gov FU NIDDK, NIH; Italian Association for Cancer Research (AIRC), Milan; Italian Ministry for University, Scientific and Technological Research (MURST); Italian Ministry of Health [ICS060.2/RF00-57] FX This study was partially supported by intramural funds of NIDDK, NIH and by grants from the Italian Association for Cancer Research (AIRC), Milan; the Italian Ministry for University, Scientific and Technological Research (MURST); the Italian Ministry of Health (grant number ICS060.2/RF00-57). NR 73 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JAN PY 2011 VL 56 IS 1 BP 139 EP 154 DI 10.1007/s10620-010-1234-1 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 703UD UT WOS:000286005900019 PM 20725788 ER PT J AU Reznick, JS AF Reznick, Jeffrey S. TI History at the intersection of disability and public health: The case of John Galsworthy and disabled soldiers of the First World War SO DISABILITY AND HEALTH JOURNAL LA English DT Article DE History; War; Rehabilitation; Disabled veterans AB The author presented an earlier version of this historical article to the Disability Section of the American Public Health Association (November 2009). It is part of his ongoing research in the social and cultural history of medicine as the field intersects with the history of disability, veterans, and public health, as well as current issues that touch all of these areas. This article introduces readers to perspectives on disability held by the British novelist John Galsworthy (1867-1933), which he developed primarily through his philanthropic support for and his compositions about rehabilitation programs for British and American soldiers disabled in the First World War (1914-1918). Readers will learn that Galsworthy's perspectives are as much about his identity as an individual with disabilities as they are about men disabled in the "war to end all wars." The rediscovery of Galsworthy's experiences and words more than 90 years after the end of World War I reveals how history is present today at the intersection of disability and public health. Indeed, the story of Galsworthy ultimately seeking to forget his own experiences during the "Great War," as well as the very physical and psychological disability caused by that conflict, can inspire public health professionals and disability rights advocates today to remember-indeed, to advocate for-men and women who served in battle and have returned home to realize renewed health and social participation despite permanent physical and psychological wounds. Readers will note that language used throughout this article to describe disability is period-specific and therefore not keeping with current conventions. Published by Elsevier Inc. C1 NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20894 USA. RP Reznick, JS (reprint author), NIH, Hist Med Div, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM jeffrey.reznick@nih.gov NR 11 TC 1 Z9 1 U1 4 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-6574 J9 DISABIL HEALTH J JI Disabil. Health J. PD JAN PY 2011 VL 4 IS 1 BP 24 EP 27 DI 10.1016/j.dhjo.2010.07.008 PG 4 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health; Rehabilitation SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Rehabilitation GA 710WG UT WOS:000286547100005 PM 21168804 ER PT J AU Cui, C Chatterjee, B Francis, D Yu, Q SanAgustin, JT Francis, R Tansey, T Henry, C Wang, BL Lemley, B Pazour, GJ Lo, CW AF Cui, Cheng Chatterjee, Bishwanath Francis, Deanne Yu, Qing SanAgustin, Jovenal T. Francis, Richard Tansey, Terry Henry, Charisse Wang, Baolin Lemley, Bethan Pazour, Gregory J. Lo, Cecilia W. TI Disruption of Mks1 localization to the mother centriole causes cilia defects and developmental malformations in Meckel-Gruber syndrome SO DISEASE MODELS & MECHANISMS LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; PLANAR CELL POLARITY; LEFT-RIGHT ASYMMETRY; RIGHT AXIS DETERMINATION; BASAL BODY PROTEIN; INTRAFLAGELLAR TRANSPORT; JOUBERT-SYNDROME; MUTANT MICE; FLOOR PLATE; NODAL FLOW AB Meckel-Gruber syndrome (MKS) is a recessive disorder resulting in multiple birth defects that are associated with mutations affecting ciliogenesis. We recovered a mouse mutant with a mutation in the Mks1 gene (Mks1(del64-323)) that caused a 260-amino-acid deletion spanning nine amino acids in the B9 domain, a protein motif with unknown function conserved in two other basal body proteins. We showed that, in wild-type cells, Mks1 was localized to the mother centriole from which the cilium was generated. However, in mutant Mks1(del64-323) cells, Mks1 was not localized to the centriole, even though it maintained a punctate distribution. Resembling MKS patients, Mks1 mutants had craniofacial defects, polydactyly, congenital heart defects, polycystic kidneys and randomized left-right patterning. These defects reflected disturbance of functions subserved by motile and nonmotile cilia. In the kidney, glomerular and tubule cysts were observed along with short cilia, and cilia were reduced in number to a near-complete loss. Underlying the left-right patterning defects were fewer and shorter nodal cilia, and analysis with fluorescent beads showed no directional flow at the embryonic node. In the cochlea, the stereocilia were mal-patterned, with the kinocilia being abnormally positioned. Together, these defects suggested disruption of planar cell polarity, which is known to regulate node, kidney and cochlea development. In addition, we also showed that Shh signaling was disrupted. Thus, in the neural tube, the floor plate was not specified posteriorly even as expression of the Shh mediator Gli2 increased. By contrast, the Shh signaling domain was expanded in the anterior neural tube and anterior limb bud, consistent with reduced Gli3-repressor (Gli3R) function. The latter probably accounted for the preaxial digit duplication exhibited by the Mks1(del64-323) mutants. Overall, these findings indicate that centriole localization of Mks1 is required for ciliogenesis of motile and non-motile cilia, but not for centriole assembly. On the basis of these results, we hypothesize a role for the B9 domain in mother centriole targeting, a possibility that warrants further future investigations. C1 [Cui, Cheng; Francis, Richard; Lo, Cecilia W.] Univ Pittsburgh, Dept Dev Biol, Rangos Res Ctr 8111, Pittsburgh, PA 15201 USA. [Chatterjee, Bishwanath; Francis, Deanne; Yu, Qing; Tansey, Terry; Henry, Charisse; Lemley, Bethan] NHLBI, NIH, Bethesda, MD 20892 USA. [SanAgustin, Jovenal T.; Pazour, Gregory J.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. [Wang, Baolin] Cornell Univ, Weill Med Coll, Dept Med Genet, New York, NY 10021 USA. RP Lo, CW (reprint author), Univ Pittsburgh, Dept Dev Biol, Rangos Res Ctr 8111, 530 45th St, Pittsburgh, PA 15201 USA. EM cel36@pitt.edu RI Francis, Richard/P-2524-2015; OI Francis, Deanne/0000-0002-4158-1521; Pazour, Gregory/0000-0002-6285-8796 FU NIH [GM060992, GM070820, ZO1-HL005701, U01-HL098180]; Diabetes Endocrinology Research Center [DK32520] FX RNA in-situ probe plasmids were generously provided by Lee Niswander (Fgf4), Gail Martin (Fgf8), Richard M. Harland (gremlin), Marian A. Rot (dHand), Richard R. Behringer (Sox9) and Chi-chung Hui (Gli1). We thank Chi-chung Hui at The Hospital for Sick Children, Toronto, Canada for generously providing reagents and for helpful discussions, Matthew Kelley and Chandrakala Puligilla at NIDCD for help with cochlea dissection, Yingfan Zhang at National Heart, Lung and Blood Institute and Alex Bao at National Cancer Institute for assistance with western blotting, Susan Mackem at NCI for helpful discussions on Gli processing and roles in neural tube and limb patterning, Xiaoyan Ding at Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China for assistance with immunostaining, and Mathew P. Daniels and the NHLBI Electron Microscopy Core Facility for help with scanning electron microscopy. The antibodies (Shh, FoxA2, Pax6, Pax7, Nkx2.2, Nkx6.1) were obtained from the NICE-ID Developmental Studies Hybridoma Bank, maintained by The University of Iowa, Iowa City, IA. Anti-Olig2 antibody was a kind gift of Bennett Novitch (UCLA), and anti-Gli3 antibody was a kind gift of Susan (Mackem (NCI). This work is supported in the Pazour laboratory by NIH GM060992 and core resources funded by the Diabetes Endocrinology Research Center (grant DK32520), in the Wang laboratory by NIH GM070820, and in the Lo laboratory by NIH funding ZO1-HL005701 and U01-HL098180. NR 75 TC 37 Z9 37 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD JAN PY 2011 VL 4 IS 1 BP 43 EP 56 DI 10.1242/dmm.006262 PG 14 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 725WO UT WOS:000287677800008 PM 21045211 ER PT S AU Redon, CE Nakamura, AJ Sordet, O Dickey, JS Gouliaeva, K Tabb, B Lawrence, S Kinders, RJ Bonner, WM Sedelnikova, OA AF Redon, Christophe E. Nakamura, Asako J. Sordet, Olivier Dickey, Jennifer S. Gouliaeva, Ksenia Tabb, Brian Lawrence, Scott Kinders, Robert J. Bonner, William M. Sedelnikova, Olga A. BE Didenko, VV TI gamma-H2AX Detection in Peripheral Blood Lymphocytes, Splenocytes, Bone Marrow, Xenografts, and Skin SO DNA DAMAGE DETECTION IN SITU, EX VIVO, AND IN VIVO: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE gamma-H2AX; DNA damage; Immunofluorescence; Immunoblotting; Flow cytometry; Lymphocytes; Splenocytes; Bone marrow; Xenografts; Skin ID DOUBLE-STRAND BREAKS; HISTONE H2AX PHOSPHORYLATION; DNA-DAMAGE; REPAIR; CELLS; CANCER; RADIATION AB Measurement of DNA double-strand break (DSB) levels in cells is useful in many research areas, including those related to DNA damage and repair, tumorigenesis, anti-cancer drug development, apoptosis, radiobiology, environmental effects, and aging, as well as in the clinic. DSBs can be detected in the nuclei of cultured cells and tissues with an antibody to H2AX phosphorylated on serine residue 139 (gamma-H2AX). DSB levels can be obtained either by measuring overall gamma-H2AX protein levels in a cell population or by counting gamma-H2AX foci in individual nuclei. Total levels can be obtained in extracts of cell populations by immunoblot analysis, and in cell populations by flow cytometry. Furthermore, with flow cytometry, the cell cycle distribution of a population can be obtained in addition to DSB levels, which is an advantage when studying anti-cancer drugs targeting replicating tumor cells. These described methods are used in genotoxicity assays of compounds of interest or in analyzing DSB repair after exposure to drugs or radiation. Immunocyto/immunohistochemical analysis can detect gamma-H2AX foci in individual cells and is very sensitive (a single DSB can be visualized), permitting the use of extremely small samples. Measurements of gamma-H2AX focal numbers can reveal subtle changes found in the radiation-induced tissue bystander response, low dose radiation exposure, and in cells with mutations in genomic stability maintenance pathways. In addition, marking DNA DSBs in a nucleus with gamma-H2AX is a powerful tool to identify novel DNA repair proteins by their abilities to co-localize with gamma-H2AX foci at the DSB site. This chapter presents techniques for gamma-H2AX detection in a variety of human and mouse samples. C1 [Redon, Christophe E.; Nakamura, Asako J.; Sordet, Olivier; Dickey, Jennifer S.; Gouliaeva, Ksenia; Bonner, William M.; Sedelnikova, Olga A.] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Tabb, Brian; Lawrence, Scott] NCI, Pathol & Histol Lab PHL, SAIC Frederick Inc, Frederick, MD 21701 USA. [Kinders, Robert J.] NCI, SAIC Frederick Inc, PADIS, Lab Human Toxicol & Pharmacol, Frederick, MD 21701 USA. RP Redon, CE (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 20 TC 34 Z9 35 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-408-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 682 BP 249 EP 270 DI 10.1007/978-1-60327-409-8_18 D2 10.1007/978-1-60327-409-8 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BSJ64 UT WOS:000284724100018 PM 21057933 ER PT S AU Ma, WJ Westmoreland, J Nakai, W Malkova, A Resnick, MA AF Ma, Wenjian Westmoreland, Jim Nakai, Wataru Malkova, Anna Resnick, Michael A. BE Tsubouchi, H TI Characterizing Resection at Random and Unique Chromosome Double-Strand Breaks and Telomere Ends SO DNA RECOMBINATION: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE DNA; double-strand break repair; resection; pulsed-field gel electrophoresis (PFGE); ionizing radiation; HO endonuclease; I-SceI; mung bean nuclease; telomere ID DNA-DAMAGE RESPONSE; BUDDING YEAST; HOMOLOGOUS RECOMBINATION; IN-VIVO; REPAIR; CHECKPOINT; SITE; ACCUMULATION; RECOGNITION; PROTEINS AB Resection of DNA double-strand break (DSB) ends, which results in 3' single-stranded tails, is an early event of DSB repair and can be a critical determinant in choice of repair pathways and eventual genome stability. Current techniques for examining resection are restricted to model in vivo systems with defined substrates (i.e., HO-endonuclease targets). We present here a robust assay that can analyze not only the resection of site-specific DSBs which typically have "clean" double-strand ends but also random "dirty-ended" DSBs such as those generated by ionizing radiation and chemotherapeutic agents. The assay is based on our finding that yeast chromosomes with single-stranded DNA tails caused by resection are less mobile during pulsed-field gel electrophoresis (PFGE) than those without a tail. In combination with the use of a circular chromosome and enzymatic trimming of single-stranded DNA, resection of random DSBs can be easily detected and analyzed. This mobility-shift assay provides a unique opportunity to examine the mechanisms of resection, early events in DSB repair, as well as factors involved in pathway regulation. C1 [Ma, Wenjian; Westmoreland, Jim; Nakai, Wataru; Resnick, Michael A.] NIEHS, Chromosome Stabil Sect, NIH, Res Triangle Pk, NC 27709 USA. [Malkova, Anna] Indiana Univ Purdue Univ, Dept Biol, Indianapolis, IN 46205 USA. RP Ma, WJ (reprint author), NIEHS, Chromosome Stabil Sect, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES065073]; NIGMS NIH HHS [R01 GM084242] NR 25 TC 3 Z9 3 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-128-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 745 BP 15 EP 31 DI 10.1007/978-1-61779-129-1_2 D2 10.1007/978-1-61779-129-1 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BVR27 UT WOS:000292530400002 PM 21660686 ER PT J AU Mason, JM Reddy, HM Frydrychova, RC AF Mason, James M. Reddy, Hemakumar M. Frydrychova, Radmila Capkova BE Seligmann, H TI Telomere Maintenance in Organisms without Telomerase SO DNA REPLICATION - CURRENT ADVANCES LA English DT Article; Book Chapter ID DROSOPHILA-MELANOGASTER TELOMERES; RETROTRANSPOSON GAG PROTEINS; PROTECTING CHROMOSOME ENDS; TERMINAL-GENE-CONVERSION; HET-A; DNA-SEQUENCES; BOMBYX-MORI; ALLIUM-CEPA; HETEROCHROMATIN PROTEIN-1; TRANSPOSABLE ELEMENTS C1 [Mason, James M.; Reddy, Hemakumar M.] NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. [Frydrychova, Radmila Capkova] Inst Entomol, Branisovska, Czech Republic. RP Mason, JM (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 114 TC 4 Z9 4 U1 1 U2 1 PU INTECH EUROPE PI RIJEKA PA JANEZA TRDINE9, RIJEKA, 51000, CROATIA BN 978-953-307-593-8 PY 2011 BP 323 EP 346 D2 10.5772/791 PG 24 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BF9TM UT WOS:000385876400016 ER PT J AU Cadet, JL Brannock, C Ladenheim, B McCoy, MT Beauvais, G Hodges, AB Lehrmann, E Wood, WH Becker, KG Krasnova, IN AF Cadet, Jean Lud Brannock, Christie Ladenheim, Bruce McCoy, Michael T. Beauvais, Genevieve Hodges, Amber B. Lehrmann, Elin Wood, William H., III Becker, Kevin G. Krasnova, Irina N. TI METHAMPHETAMINE PRECONDITIONING CAUSES DIFFERENTIAL CHANGES IN STRIATAL TRANSCRIPTIONAL RESPONSES TO LARGE DOSES OF THE DRUG SO DOSE-RESPONSE LA English DT Article DE methamphetamine; preconditioning; striatum; BDNF; heat shock proteins ID INDUCED NEUROTOXICITY; ISCHEMIC TOLERANCE; HEME OXYGENASE-1; MICROGLIAL ACTIVATION; ENDOPLASMIC-RETICULUM; PSYCHIATRIC-SYMPTOMS; GENE-EXPRESSION; TRANSGENIC MICE; NULL MUTATION; RAT STRIATUM AB Methamphetamine (METH) is a toxic drug of abuse, which can cause significant decreases in the levels of monoamines in various brain regions. However, animals treated with progressively increasing doses of METH over several weeks are protected against the toxic effects of the drug. In the present study, we tested the possibility that this pattern of METH injections might be associated with transcriptional changes in the rat striatum, an area of the brain which is known to be very sensitive to METH toxicity and which is protected by METH preconditioning. We found that the presence and absence of preconditioning followed by injection of large doses of METH caused differential expression in different sets of striatal genes. Quantitative PCR confirmed METH-induced changes in some genes of interest. These include small heat shock 27 kD proteins 1 and 2 (HspB1 and HspB2), brain derived neurotrophic factor (BDNF), and heme oxygenase-1 (Hmox-1). Our observations are consistent with previous studies which have reported that ischemic or pharmacological preconditioning can cause reprogramming of gene expression after lethal ischemic insults. These studies add to the growing literature on the effects of preconditioning on the brain transcriptome. RP Cadet, JL (reprint author), Natl Inst Drug Abuse, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH,DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov OI Lehrmann, Elin/0000-0002-9869-9475; Becker, Kevin/0000-0002-6794-6656 FU National Institute on Drug Abuse, NIH, DHHS FX The study is supported by Intramural Research Program of the National Institute on Drug Abuse, NIH, DHHS. NR 60 TC 8 Z9 8 U1 1 U2 2 PU INT DOSE-RESPONSE SOC PI AMHERST PA UNIV MASSACHUSETTS SPH, MORRILL SCI CTR 1, N344, 639 N PLEASANT ST, AMHERST, MA 01003-9298 USA SN 1559-3258 J9 DOSE-RESPONSE JI Dose-Response PY 2011 VL 9 IS 2 BP 165 EP 181 DI 10.2203/dose-response.10-011.Cadet PG 17 WC Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging; Toxicology SC Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging; Toxicology GA 775EZ UT WOS:000291442800003 PM 21731535 ER PT J AU Kapetanovic, IM AF Kapetanovic, Izet M. BE Kapetanovic, IM TI Overview of Current Drug Discovery and Development with an Eye Towards the Future Introductory Chapter SO DRUG DISCOVERY AND DEVELOPMENT - PRESENT AND FUTURE LA English DT Editorial Material; Book Chapter ID COMPUTATIONAL TOXICOLOGY; NETWORK; BIOMARKERS; INNOVATION; MEDICINE; BIOLOGY C1 [Kapetanovic, Izet M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Kapetanovic, IM (reprint author), NCI, Canc Prevent Div, Bethesda, MD 20892 USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU INTECH EUROPE PI RIJEKA PA JANEZA TRDINE9, RIJEKA, 51000, CROATIA BN 978-953-307-615-7 PY 2011 BP 1 EP 6 D2 10.5772/1179 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BF9TO UT WOS:000385879400002 ER PT J AU Kapetanovic, IM AF Kapetanovic, Izet M. BE Kapetanovic, IM TI DRUG DISCOVERY AND DEVELOPMENT - PRESENT AND FUTURE Preface SO DRUG DISCOVERY AND DEVELOPMENT - PRESENT AND FUTURE LA English DT Editorial Material; Book Chapter C1 [Kapetanovic, Izet M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Kapetanovic, IM (reprint author), NCI, Canc Prevent Div, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INTECH EUROPE PI RIJEKA PA JANEZA TRDINE9, RIJEKA, 51000, CROATIA BN 978-953-307-615-7 PY 2011 BP IX EP X D2 10.5772/1179 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BF9TO UT WOS:000385879400001 ER PT J AU Alcoser, SY Hollingshead, MG AF Alcoser, Sergio Y. Hollingshead, Melinda G. BE Kapetanovic, IM TI Genetically Engineered Mouse Models in Preclinical Anti-Cancer Drug Development SO DRUG DISCOVERY AND DEVELOPMENT - PRESENT AND FUTURE LA English DT Article; Book Chapter ID CELL LUNG-CANCER; TUMOR-SUPPRESSOR GENE; PROTEIN TRANSFERASE INHIBITOR; TYROSINE KINASE INHIBITORS; METASTATIC BREAST-CANCER; ONCOGENIC K-RAS; T-ANTIGEN GENES; TRANSGENIC MICE; EGFR MUTATIONS; MAMMARY-TUMORS C1 [Alcoser, Sergio Y.; Hollingshead, Melinda G.] NCI, Biol Testing Branch, Dev Therapeut Program, Bethesda, MD 20892 USA. RP Alcoser, SY (reprint author), NCI, Biol Testing Branch, Dev Therapeut Program, Bethesda, MD 20892 USA. NR 106 TC 0 Z9 0 U1 0 U2 0 PU INTECH EUROPE PI RIJEKA PA JANEZA TRDINE9, RIJEKA, 51000, CROATIA BN 978-953-307-615-7 PY 2011 BP 99 EP 124 D2 10.5772/1179 PG 26 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BF9TO UT WOS:000385879400007 ER PT B AU Penzak, SR AF Penzak, Scott R. BE Piscitelli, SC Rodvold, KA Pai, MP TI Interactions Between Herbs and Antiinfective Medications SO DRUG INTERACTIONS IN INFECTIOUS DISEASES, THIRD EDITION SE Infectious Disease LA English DT Article; Book Chapter ID ST-JOHNS-WORT; GINKGO-BILOBA EXTRACT; IN-VITRO EVALUATION; HUMAN CYTOCHROME-P450 3A4; ALTERNATIVE MEDICINE USE; HIV-INFECTED PATIENTS; COHOSH CIMICIFUGA-RACEMOSA; DRUG-METABOLIZING-ENZYMES; THISTLE SILYBUM-MARIANUM; TEA CAMELLIA-SINENSIS AB Over 15 million people in the United States report using complementary and alternative medications (CAM). Patients with HIV infection represent an important segment of this population. Because of their ability to modulate a variety of cytochrome P450 (CYP) enzymes and drug transport proteins such as P-glycoprotein (P-gp), a number of herbs have been shown to interact with coadministered medications. Unfortunately, in vitro microsomal studies often fail to predict results obtained in humans. The herb associated with the greatest number of drug interactions in humans is St. John's wort (Hypericum perforatum). As a potent inducer of CYP and P-gp, St. John's wort has been shown to reduce the plasma concentrations of certain coadministered medications by >50%. Other herbs have been shown to induce the metabolism of coadministered medications as well. However, the magnitude of these interactions is markedly less than that produced by St. John's wort. Nonetheless, even mild herb-drug interactions may be clinically relevant for coadministered medications with narrow therapeutic indices. To this end, the need for rigorous studies to identify potentially significant herb-drug interactions continues. Clinicians caring for patients taking CAM therapy should maintain a high degree of suspicion for herb-drug interactions in the face of unexplained toxicity or loss of efficacy, and be familiar with resources that can help manage or avoid herb-drug interactions. C1 NIH, Clin Pharmacokinet Res Lab, Clin Res Ctr, Dept Pharm, Bethesda, MD 20879 USA. RP Penzak, SR (reprint author), NIH, Clin Pharmacokinet Res Lab, Clin Res Ctr, Dept Pharm, Bethesda, MD 20879 USA. EM spenzak@mail.cc.nih.gov NR 149 TC 0 Z9 0 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-61779-212-0 J9 INFECT DIS PY 2011 BP 131 EP 165 DI 10.1007/978-1-61779-213-7_5 D2 10.1007/978-1-61779-213-7 PG 35 WC Infectious Diseases; Medicine, General & Internal; Pharmacology & Pharmacy SC Infectious Diseases; General & Internal Medicine; Pharmacology & Pharmacy GA BYU08 UT WOS:000300328700005 ER PT J AU Shukla, SJ Sakamuru, S Huang, RL Moeller, TA Shinn, P VanLeer, D Auld, DS Austin, CP Xia, MH AF Shukla, Sunita J. Sakamuru, Srilatha Huang, Ruili Moeller, Timothy A. Shinn, Paul VanLeer, Danielle Auld, Douglas S. Austin, Christopher P. Xia, Menghang TI Identification of Clinically Used Drugs That Activate Pregnane X Receptors SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID REPORTER GENE ASSAY; ORPHAN NUCLEAR RECEPTORS; XENOBIOTIC RECEPTOR; HUMAN HEPATOCYTES; PRIMARY CULTURES; CYP3A INDUCTION; ADULT-RAT; IN-VITRO; PXR; EXPRESSION AB The pregnane X receptor (PXR) binds xenobiotics and regulates the expression of several drug-metabolizing enzymes and transporters. Human PXR (hPXR) activation and CYP3A4 induction can be involved in drug-drug interactions, resulting in reduced efficacy or increased toxicity. However, there are known species-specific differences with regard to PXR activation that should be taken into account when animal PXR data are extrapolated to humans. We profiled 2816 clinically used drugs from the National Institutes of Health Chemical Genomics Center Pharmaceutical Collection for their ability to activate hPXR and rat PXR (rPXR) at the cellular level, induce human CYP3A4 at the cellular level, and bind human PXR at the protein level. From 6 to 11% of drugs were identified as active across the four assays, which included assay-specific and pan-active compounds. The lowest concordance was observed between the hPXR and rPXR assays, and many compounds active in both assays nonetheless demonstrated significant potency differences between species. Analysis based on clustering potency values demonstrated the greatest activity correlation between the hPXR activation and CYP3A4 induction assays. Structure-activity relationship analysis identified chemical scaffolds that were pan-active (e.g., dihydropyridine calcium channel blockers) and others that were uniquely active in individual assays (e.g., steroids and fatty acids). These results provide important information on PXR activation by clinically used drugs, highlight the species specificity of PXR activation by xenobiotics, and provide a means of prioritizing compounds for follow-up studies and optimization efforts. C1 [Shukla, Sunita J.; Sakamuru, Srilatha; Huang, Ruili; Shinn, Paul; VanLeer, Danielle; Auld, Douglas S.; Austin, Christopher P.; Xia, Menghang] NHGRI, Natl Inst Hlth Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. [Moeller, Timothy A.] Celsis Vitro Technol, Halethorpe, MD USA. RP Xia, MH (reprint author), NIH, 9800 Med Ctr Dr, Rockville, MD 20850 USA. EM mxia@mail.nih.gov FU National Institutes of Health National Human Genome Research Institute FX This research was supported in part by the Intramural Research Program of the National Institutes of Health National Human Genome Research Institute. NR 40 TC 37 Z9 38 U1 1 U2 9 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JAN PY 2011 VL 39 IS 1 BP 151 EP 159 DI 10.1124/dmd.110.035105 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 694WR UT WOS:000285332100021 PM 20966043 ER PT S AU Pluta, RM AF Pluta, Ryszard M. BE Feng, H Mao, Y Zhang, JH TI New Regulatory, Signaling Pathways, and Sources of Nitric Oxide SO EARLY BRAIN INJURY OR CEREBRAL VASOSPASM, VOL 1: PATHOPHYSIOLOGY SE Acta Neurochirurgica Supplementum LA English DT Proceedings Paper CT 10th International Conference on Cerebral Vasospasm CY OCT 09-11, 2009 CL Chongqing, PEOPLES R CHINA DE Hemoglobin; Neuroglobin; Nitric oxide; SAH; Vasospasm ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; DELAYED CEREBRAL VASOSPASM; CANINE BASILAR ARTERY; BLOOD-FLOW; ENDOTHELIAL-CELLS; PRIMATE MODEL; L-ARGININE; IN-VIVO; SYNTHASE; MECHANISMS AB Discovered in 1980 by the late Robert F. Furchgott, endothelium-derived relaxing factor, nitric oxide (NO), has been in the forefront of vascular research for several decades. What was originally a narrow approach, has been significantly widened due to major advances in understanding the chemical and biological properties of NO as well as its signaling pathways and discovering new sources of this notorious free radical gas. In this review, recent discoveries regarding NO and their implications on therapy for delayed cerebral vasospasm are presented. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Pluta, RM (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Room 3D20, Bethesda, MD 20892 USA. EM Ryszard.Pluta@jama-archives.org FU Intramural NIH HHS NR 42 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 978-3-7091-0352-4 J9 ACTA NEUROCHIR SUPPL JI Acta Neurochir. Suppl. PY 2011 VL 110 BP 7 EP 12 DI 10.1007/978-3-7091-0353-1_2 PN 1 PG 6 WC Clinical Neurology; Surgery; Peripheral Vascular Disease SC Neurosciences & Neurology; Surgery; Cardiovascular System & Cardiology GA BUT00 UT WOS:000290247600002 PM 21116907 ER PT S AU Fathi, AR Bakhtian, KD Pluta, RM AF Fathi, Ali R. Bakhtian, Kamran D. Pluta, Ryszard M. BE Feng, H Mao, Y Zhang, JH TI The Role of Nitric Oxide Donors in Treating Cerebral Vasospasm After Subarachnoid Hemorrhage SO EARLY BRAIN INJURY OR CEREBRAL VASOSPASM, VOL 1: PATHOPHYSIOLOGY SE Acta Neurochirurgica Supplementum LA English DT Proceedings Paper CT 10th International Conference on Cerebral Vasospasm CY OCT 09-11, 2009 CL Chongqing, PEOPLES R CHINA DE Cerebral vasospasm; DIND; Nitric oxide; NO Donors; Subarachnoid hemorrhage ID INTRATHECAL SODIUM-NITROPRUSSIDE; PRIMATE MODEL; CEREBROSPINAL-FLUID; PREVENTION; ERYTHROPOIETIN; NITROGLYCERIN; SYNTHASE; INFUSIONS; REVERSAL; ARTERIES AB Reduced intra- and perivascular availability of nitric oxide (NO) significantly contributes to the multifactorial pathophysiology of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). The short half-life of NO demands its therapeutic substitution via NO donors. Classic NO donors such as sodium nitroprusside and nitroglycerin cannot be used as routine therapeutics because of serious side effects. Thus, a new generation of NO donors has been the subject of experimental investigations to avoid the drawbacks of the classic drugs. The purpose of this paper is to review the characteristics of different NO donors with regard to their promise and potential consequences in treating cerebral vasospasm. Additional novel concepts to increase NO concentrations, such as the activation of endothelial nitric oxide synthase (eNOS), are discussed. C1 [Fathi, Ali R.; Bakhtian, Kamran D.; Pluta, Ryszard M.] NINDS, Surg Neurol Branch, NIH, SNB NINDS NIH, Bethesda, MD USA. RP Pluta, RM (reprint author), NINDS, Surg Neurol Branch, NIH, SNB NINDS NIH, 10 Ctr Dr,Bldg 10,Room 3D20, Bethesda, MD USA. EM rysiek@ninds.nih.gov FU Intramural NIH HHS NR 46 TC 8 Z9 10 U1 0 U2 5 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 978-3-7091-0352-4 J9 ACTA NEUROCHIR SUPPL JI Acta Neurochir. Suppl. PY 2011 VL 110 BP 93 EP 97 DI 10.1007/978-3-7091-0353-1_17 PN 1 PG 5 WC Clinical Neurology; Surgery; Peripheral Vascular Disease SC Neurosciences & Neurology; Surgery; Cardiovascular System & Cardiology GA BUT00 UT WOS:000290247600017 PM 21116922 ER PT J AU Wolkoff, LE Tanofsky-Kraff, M Shomaker, LB Kozlosky, M Columbo, KM Elliott, CA Ranzenhofer, LM Osborn, RL Yanovski, SZ Yanovski, JA AF Wolkoff, Laura E. Tanofsky-Kraff, Marian Shomaker, Lauren B. Kozlosky, Merel Columbo, Kelli M. Elliott, Camden A. Ranzenhofer, Lisa M. Osborn, Robyn L. Yanovski, Susan Z. Yanovski, Jack A. TI Self-reported vs. actual energy intake in youth with and without loss of control eating SO EATING BEHAVIORS LA English DT Article DE Child; Adolescent; Binge eating; Loss of control eating; Reporting accuracy; Obesity ID AFRICAN-AMERICAN; DIET HISTORY; CHILDREN; OVERWEIGHT; ADOLESCENTS; DISORDER; ALEXITHYMIA; PREVALENCE; BEHAVIORS; BULIMIA AB Episodes of loss of control overeating (LOC) in children and adolescents - often characterized by the consumption of highly palatable dessert and snack-type foods - have been associated with a lack of awareness while eating that could lead to under- or over-estimation of how much food is consumed. However, little is known about the reporting accuracy of food intake in youth with and without LOC eating. One hundred fifty-six girls and boys were administered the Eating Disorder Examination to assess for the presence of LOC eating. Youth were queried regarding the amounts of foods consumed directly following a multi-item, laboratory buffet test meal. Children with LOC (n = 42) did not differ significantly from youth without LOC (n = 114) in reporting accuracy of total food intake (reported minus actual energy intake: 153.0 +/- 59.6 vs. 96.9 +/- 36.0 kcal; p = 0.42). However, compared to those without LOC, children with LOC were less accurate at reporting percentage of energy intake from carbohydrate (p = 0.01). Youth with LOC were also less accurate at reporting their intake of desserts (p = 0.04). Findings point to the possibility that youth with LOC may have poorer recall of sweet food consumption. Future research is required to examine whether poorer recall reflects a lack of awareness while eating palatable, sweet foods. Published by Elsevier Ltd. C1 [Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol MPS, Bethesda, MD 20814 USA. [Wolkoff, Laura E.; Tanofsky-Kraff, Marian; Shomaker, Lauren B.; Columbo, Kelli M.; Elliott, Camden A.; Ranzenhofer, Lisa M.; Yanovski, Susan Z.; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, Bethesda, MD USA. [Kozlosky, Merel] NIH, Dept Nutr, Ctr Clin, DHHS, Bethesda, MD USA. [Yanovski, Susan Z.] NIDDK, Div Digest Dis & Nutr, NIH, DHHS, Bethesda, MD 20892 USA. RP Tanofsky-Kraff, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol MPS, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM mtanofsky@usuhs.mil OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z99 HD999999]; NICHD NIH HHS [Z01 HD000641]; NIDDK NIH HHS [1R01DK080906-01A1, R01 DK080906, R01 DK080906-01A1] NR 47 TC 12 Z9 12 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1471-0153 J9 EAT BEHAV JI Eat. Behav. PD JAN PY 2011 VL 12 IS 1 BP 15 EP 20 DI 10.1016/j.eatbeh.2010.09.001 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 714XT UT WOS:000286845700003 PM 21184968 ER PT J AU Feldmann, H AF Feldmann, Heinrich TI Emergency Vaccines Against Viral Hemorrhagic Fevers SO ECOHEALTH LA English DT Meeting Abstract C1 [Feldmann, Heinrich] NIAID, Virol Lab, Rocky Mt Labs, Div Intramural Res,NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1612-9202 J9 ECOHEALTH JI EcoHealth PY 2011 VL 7 SU 1 BP S62 EP S62 PG 1 WC Biodiversity Conservation; Ecology; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 728VB UT WOS:000287901500103 ER PT J AU Wong, KJ Baidoo, KE Nayak, TK Garmestani, K Brechbiel, MW Milenic, DE AF Wong, Karen J. Baidoo, Kwamena E. Nayak, Tapan K. Garmestani, Kayhan Brechbiel, Martin W. Milenic, Diane E. TI In vitro and in vivo pre-clinical analysis of a F(ab')(2) fragment of panitumumab for molecular imaging and therapy of HER1-positive cancers SO EJNMMI RESEARCH LA English DT Article AB Background: The objective of this study was to characterize the in vitro and in vivo properties of the F(ab')(2) fragment of panitumumab and to investigate its potential for imaging and radioimmunotherapy. Methods: The panitumumab F(ab')(2) was generated by enzymatic pepsin digestion. After the integrity and immunoreactivity of the F(ab')(2) was evaluated, the fragment was radiolabeled. In vivo studies included direct quantitation of tumor targeting and normal organ distribution of the radiolabeled panitumumab F(ab')(2) as well as planar gamma-scintigraphy and PET imaging. Results: The panitumumab F(ab')(2) was successfully produced by peptic digest. The F(ab')(2) was modified with the CHX-A"-DTPA chelate and efficiently radiolabeled with either In-111 or Y-86. In vivo tumor targeting was achieved with acceptable uptake of radioactivity in the normal organs. The tumor targeting was validated by both imaging modalities with good visualization of the tumor at 24 h. Conclusions: The panitumumab F(ab')(2) fragment is a promising candidate for imaging of HER1-positive cancers. C1 [Wong, Karen J.] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Baidoo, Kwamena E.; Nayak, Tapan K.; Garmestani, Kayhan; Brechbiel, Martin W.; Milenic, Diane E.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Milenic, DE (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Ctr Canc Res,NIH, 10 Ctr Dr MSC 1002, Bethesda, MD 20892 USA. EM milenicd@mail.nih.gov OI Nayak, Tapan/0000-0002-3706-6092 FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The authors are grateful for the support and encouragement so kindly provided by Mr. Elwood P. Dowd during the course of these studies. NR 54 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 2191-219X J9 EJNMMI RES JI EJNMMI Res. PY 2011 VL 1 AR 1 DI 10.1186/2191-219X-1-1 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V39UJ UT WOS:000209435600001 ER PT J AU Park, HJ Gusarova, G Wang, ZB Carr, JR Li, J Kim, KH Qiu, J Park, YD Williamson, PF Hay, N Tyner, AL Lau, LF Costa, RH Raychaudhuri, P AF Park, Hyun Jung Gusarova, Galina Wang, Zebin Carr, Janai R. Li, Jing Kim, Ki-Hyun Qiu, Jin Park, Yoon-Dong Williamson, Peter F. Hay, Nissim Tyner, Angela L. Lau, Lester F. Costa, Robert H. Raychaudhuri, Pradip TI Deregulation of FoxM1b leads to tumour metastasis SO EMBO MOLECULAR MEDICINE LA English DT Article DE Arf; FoxM1; metastasis ID EPITHELIAL-MESENCHYMAL TRANSITION; HEPATOCELLULAR-CARCINOMA; TRANSCRIPTION FACTOR; LYSYL OXIDASE; GLIOMA-CELLS; PROMOTES; EXPRESSION; PROGRESSION; PATHWAY; CANCER AB The forkhead box M1b (FoxM1b) transcription factor is over-expressed in human cancers, and its expression often correlates with poor prognosis. Previously, using conditional knockout strains, we showed that FoxM1b is essential for hepatocellular carcinoma (HCC) development. However, over-expression of FoxM1b had only marginal effects on HCC progression. Here we investigated the effect of FoxM1b expression in the absence of its inhibitor Arf. We show that transgenic expression of FoxM1b in an Atf-null background drives hepatic fibrosis and metastasis of HCC. We identify novel mechanisms of FoxM1b that are involved in epithelial-mesenchymal transition, cell motility, invasion and a pre-metastatic niche formation. FoxM1b activates the Akt-Snail1 pathway and stimulates expression of Stathmin, lysyl oxidase, lysyl oxidase like-2 and several other genes involved in metastasis. Furthermore, we show that an Arf-derived peptide, which inhibits FoxM1b, impedes metastasis of the FoxM1b-expressing HCC cells. The observations indicate that FoxM1b is a potent activator of tumour metastasis and that the Arf-mediated inhibition of FoxM1b is a critical mechanism for suppression of tumour metastasis. C1 [Park, Hyun Jung; Gusarova, Galina; Wang, Zebin; Carr, Janai R.; Li, Jing; Kim, Ki-Hyun; Hay, Nissim; Tyner, Angela L.; Lau, Lester F.; Costa, Robert H.; Raychaudhuri, Pradip] Univ Illinois, Coll Med, Dept Biochem & Mol Genet, UIC Canc Ctr, Chicago, IL USA. [Qiu, Jin; Park, Yoon-Dong; Williamson, Peter F.] NIAID, Sect Translat Mycol, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Williamson, Peter F.] Univ Illinois, Infect Dis Sect, Chicago, IL USA. [Raychaudhuri, Pradip] Jesse Brown VA Med Ctr, Chicago, IL USA. RP Raychaudhuri, P (reprint author), Univ Illinois, Coll Med, Dept Biochem & Mol Genet, UIC Canc Ctr, Chicago, IL USA. EM pradip@uic.edu OI Tyner, Angela/0000-0001-7448-8625 FU US Public Health Service (PHS) [CA 124488, CA 100035, AG02438]; Veteran's Administration [IO1BX000131]; PHS [AG021842, DK44525, DK068503, CA090764, AG016927, AG025953] FX We dedicate this work to the memory of Dr Robert H. Costa. Also, we thank Dr G. Adami (UIC-College of Dentistry) for the FoxM1b adenovirus. This work was supported by US Public Health Service (PHS) Grants CA 124488, CA 100035 and AG02438 to PR, and by a Merit Review Grant (IO1BX000131) from the Veteran's Administration to PR. LFL is supported by PHS grant AG021842. ALT is supported by the PHS grants DK44525 and DK068503 to ALT. NH is supported by the PHS grants CA090764, AG016927 and AG025953. NR 52 TC 63 Z9 68 U1 1 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1757-4676 J9 EMBO MOL MED JI EMBO Mol. Med. PD JAN PY 2011 VL 3 IS 1 BP 21 EP 34 DI 10.1002/emmm.201000107 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 716JD UT WOS:000286964000003 PM 21204266 ER PT J AU Blair, RJR AF Blair, R. J. R. TI Should Affective Arousal be Grounded in Perception-Action Coupling? SO EMOTION REVIEW LA English DT Editorial Material DE empathy; perception-action coupling ID OTHERS AB Decety (2011) considers the cognitive neuroscience of empathy and, in particular, his three-component model of empathic responding. His position is highly influential with its emotional awareness/understanding and emotional regulation components representing clear extensions of previous theorizing on empathy. In this brief commentary, I will critically consider the third of his components: affective arousal. In particular, I will consider the implications of the literature to the proposed computations, based on perception-action coupling, that underlie this component of his model. I will suggest that perception-action coupling does not underlie affective arousal but rather that this is mediated by far more simple mechanisms of emotional arousal based on conditioning. C1 NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, 15K North Dr,MSC 2670, Bethesda, MD 20892 USA. EM JamesBlair@mail.nih.gov NR 5 TC 8 Z9 8 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1754-0739 J9 EMOT REV JI Emot. Rev. PD JAN PY 2011 VL 3 IS 1 BP 109 EP 110 DI 10.1177/1754073910384157 PG 2 WC Psychology, Multidisciplinary SC Psychology GA 972IT UT WOS:000306271500012 ER PT J AU Kashimada, K Pelosi, E Chen, HJ Schlessinger, D Wilhelm, D Koopman, P AF Kashimada, Kenichi Pelosi, Emanuele Chen, Huijun Schlessinger, David Wilhelm, Dagmar Koopman, Peter TI FOXL2 and BMP2 Act Cooperatively to Regulate Follistatin Gene Expression during Ovarian Development SO ENDOCRINOLOGY LA English DT Article ID TRANSCRIPTION FACTOR FOXL2; GRANULOSA-CELL LINES; SEX DETERMINATION; MICE DEFICIENT; FEMALE; DIFFERENTIATION; DEFECTS; WNT4; DELETION; ACTIVIN AB Follistatin is a secreted glycoprotein required for female sex determination and early ovarian development, but the precise mechanisms regulating follistatin (Fst) gene expression are not known. Here, we investigate the roles of bone morphogenetic protein 2 (BMP2) and forkhead-domain transcription factor L2 (FOXL2) in the regulation of Fst expression in the developing mouse ovary. Bmp2 and Fst showed similar temporal profiles of mRNA expression, whereas FOXL2 protein and Fst mRNA were coexpressed in the same ovarian cells. In a cell culture model, both FOXL2 and BMP2 up-regulated Fst expression. In ex vivo mouse fetal gonad culture, exogenous BMP2 increased Fst expression, but this effect was counteracted by the BMP antagonist Noggin. Moreover, in Foxl2-null mice, Fst expression was reduced throughout fetal ovarian development, and Bmp2 expression was also reduced. Our data support a model in which FOXL2 and BMP2 cooperate to ensure correct expression of Fst in the developing ovary. Further, Wnt4-knockout mice showed reduced expression of Fst limited to early ovarian development, suggesting a role for WNT4 in the initiation, but not the maintenance, of Fst expression. (Endocrinology 152: 272-280, 2011) C1 [Kashimada, Kenichi; Chen, Huijun; Wilhelm, Dagmar; Koopman, Peter] Univ Queensland, Inst Mol Biosci, Div Mol Genet & Dev, Brisbane, Qld 4072, Australia. [Pelosi, Emanuele; Schlessinger, David] NIA, NIH, Biomed Res Ctr, Intramural Res Program,Lab Genet, Baltimore, MD 21224 USA. RP Koopman, P (reprint author), Univ Queensland, Inst Mol Biosci, Div Mol Genet & Dev, Brisbane, Qld 4072, Australia. EM p.koopman@uq.edu.au RI Koopman, Peter /C-9416-2009; Wilhelm, Dagmar/B-6915-2009; OI Koopman, Peter /0000-0001-6939-0914; Wilhelm, Dagmar/0000-0002-7757-4075; Pelosi, Emanuele/0000-0003-1890-9821; Kashimada, Kenichi/0000-0003-2505-5932 FU Australian Research Council; National Health and Medical Research Council of Australia; National Health and Medical Research Council; National Institutes of Health, National Institute on Aging FX This work was supported by research grants from the Australian Research Council and National Health and Medical Research Council of Australia. D.W. is a Career Development Award II Fellow of the National Health and Medical Research Council. P.K. is a Federation Fellow of the Australian Research Council. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 39 TC 39 Z9 41 U1 2 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2011 VL 152 IS 1 BP 272 EP 280 DI 10.1210/en.2010-0636 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 698DT UT WOS:000285573000028 PM 21084449 ER PT J AU Pratt, MM King, LC Adams, LD John, K Sirajuddin, P Olivero, OA Manchester, DK Sram, RJ DeMarini, DM Poirieri, MC AF Pratt, M. Margaret King, Leon C. Adams, Linda D. John, Kaarthik Sirajuddin, Paul Olivero, Ofelia A. Manchester, David K. Sram, Radim J. DeMarini, David M. Poirieri, Miriam C. TI Assessment of Multiple Types of DNA Damage in Human Placentas From Smoking and Nonsmoking Women in the Czech Republic SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE automated cellular imaging system; immunohistochemistry; BPDE-DNA antiserum; abasic sites; (32)P-Postlabeling; Teplice Program ID POLYCYCLIC AROMATIC-HYDROCARBONS; WHITE BLOOD-CELLS; ADDUCT FORMATION; RISK-ASSESSMENT; AIR-POLLUTION; AMBIENT AIR; EXPOSURE; IMMUNOHISTOCHEMISTRY; PREGNANCY; CANCER AB Three classes of DNA damage were assessed in human placentas collected (2000-2004) from 51 women living in the Teplice region of the Czech Republic, a mining area considered to have some of the worst environmental pollution in Europe in the 1980s. Polycyclic aromatic hydrocarbon (PAH)-DNA adducts were localized and semiquantified using immunohistochemistry (IHC) and the Automated Cellular Imaging System (ACIS). More generalized DNA damage was measured both by (32)P-postlabeling and by abasic (AB) site analysis. Placenta stained with antiserum elicited against DNA modified with 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE) revealed PAH-DNA adduct localization in nuclei of the cytotrophoblast (CT) cells and syncytiotrophoblast (ST) knots lining the chorionic villi. The highest levels of DNA damage, 49-312 PAH-DNA adducts/10(8) nucleotides, were found by IHC/ACIS in 14 immediately fixed placenta samples. An additional 37 placenta samples were stored frozen before fixation and embedding, and because PAH-DNA adducts were largely undetectable in these samples, freezing was implicated in the loss of IHC signal. The same placentas (n = 37) contained 1.7-8.6 stable/bulky DNA adducts/10(8) nucleotides and 0.6-47.2 AB sites/10(5) nucleotides. For all methods, there was no correlation among types of DNA damage and no difference in extent of DNA damage between smokers and nonsmokers. Therefore, the data show that DNA from placentas obtained in Teplice contained multiple types of DNA damage, which likely arose from various environmental exposures. In addition, PAH-DNA adducts were present at high concentrations in the CT cells and ST knots of the chorionic villi. Environ. Mol. Mutagen. 52:58-68, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Pratt, M. Margaret; John, Kaarthik; Sirajuddin, Paul; Olivero, Ofelia A.; Poirieri, Miriam C.] NCI, Carcinogen DNA Interact Sect, LCBG, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [King, Leon C.; Adams, Linda D.; DeMarini, David M.] US EPA, Integrated Syst Toxicol Div, Res Triangle Pk, NC 27711 USA. [Manchester, David K.] Univ Colorado Denver, Sch Med, Childrens Hosp, Aurora, CO USA. [Sram, Radim J.] Acad Sci Czech Republic, Inst Expt Med, Prague, Czech Republic. RP Pratt, MM (reprint author), NCI, Carcinogen DNA Interact Sect, LCBG, Ctr Canc Res,NIH, 37 Convent Dr,Bldg 37,Room 4032, Bethesda, MD 20892 USA. EM m2pratt@yahoo.com RI Sram, Radim/H-2455-2014 OI Sram, Radim/0000-0003-4256-3816 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; United States Environmental Protection Agency; Czech Ministry of Environment [SP/1b3/8/8/08] FX Grant sponsor: Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; Grant sponsor: The United States Environmental Protection Agency; Grant sponsor: The Czech Ministry of Environment; Grant number: SP/1b3/8/8/08. Margaret Pratt and Leon C. King contributed equally to this study. NR 38 TC 9 Z9 9 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JAN PY 2011 VL 52 IS 1 BP 58 EP 68 DI 10.1002/em.20581 PG 11 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 714CG UT WOS:000286784500008 PM 20839217 ER PT J AU Ela, WP Sedlak, DL Barlaz, MA Henry, HF Muir, DCG Swackhamer, DL Weber, EJ Arnold, RG Ferguson, PL Field, JA Furlong, ET Giesy, JP Halden, RU Henry, T Hites, RA Hornbuckle, KC Howard, PH Luthy, RG Meyer, AK Saez, AE vom Saal, FS Vulpe, CD Wiesner, MR AF Ela, Wendell P. Sedlak, David L. Barlaz, Morton A. Henry, Heather F. Muir, Derek C. G. Swackhamer, Deborah L. Weber, Eric J. Arnold, Robert G. Ferguson, P. Lee Field, Jennifer A. Furlong, Edward T. Giesy, John P. Halden, Rolf U. Henry, Tala Hites, Ronald A. Hornbuckle, Keri C. Howard, Philip H. Luthy, Richard G. Meyer, Anita K. Saez, A. Eduardo vom Saal, Frederick S. Vulpe, Chris D. Wiesner, Mark R. TI Toward Identifying the Next Generation of Superfund and Hazardous Waste Site Contaminants SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE contaminants of emerging concern; emerging contaminant; hazardous waste site; Superfund ID POLYBROMINATED DIPHENYL ETHERS; PERSISTENT ORGANIC POLLUTANTS; BROMINATED FLAME RETARDANTS; WATER TREATMENT; DRINKING-WATER; QUANTITATIVE-DETERMINATION; EMERGING CONTAMINANTS; ESTROGENIC ACTIVITY; GREAT-LAKES; HOUSE-DUST AB BACKGROUND: This commentary evolved from a workshop sponsored by the National Institute of Environmental Health Sciences titled "Superfund Contaminants: The Next Generation" held in Tucson, Arizona, in August 2009. All the authors were workshop participants. OBJECTIVES: Our aim was to initiate a dynamic, adaptable process for identifying contaminants of emerging concern (CECs) that are likely to be found in future hazardous waste sites, and to identify the gaps in primary research that cause uncertainty in determining future hazardous waste site contaminants. DISCUSSION: Superfund-relevant CECs can be characterized by specific attributes: They are persistent, bioaccumulative, toxic, occur in large quantities, and have localized accumulation with a likelihood of exposure. Although still under development and incompletely applied, methods to quantify these attributes can assist in winnowing down the list of candidates from the universe of potential CECs. Unfortunately, significant research gaps exist in detection and quantification, environmental fate and transport, health and risk assessment, and site exploration and remediation for CECs. Addressing these gaps is prerequisite to a preventive approach to generating and managing hazardous waste sites. CONCLUSIONS: A need exists for a carefully considered and orchestrated expansion of programmatic and research efforts to identify, evaluate, and manage CECs of hazardous waste site relevance, including developing an evolving list of priority CECs, intensifying the identification and monitoring of likely sites of present or future accumulation of CECs, and implementing efforts that focus on a holistic approach to prevention. C1 [Ela, Wendell P.; Arnold, Robert G.; Saez, A. Eduardo] Univ Arizona, Tucson, AZ 85721 USA. [Sedlak, David L.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Barlaz, Morton A.] N Carolina State Univ, Raleigh, NC 27695 USA. [Henry, Heather F.] NIEHS, Superfund Res Program, Res Triangle Pk, NC 27709 USA. [Muir, Derek C. G.] Environm Canada, Aquat Ecosyst Protect Res Div, Burlington, ON L7R 4A6, Canada. [Swackhamer, Deborah L.] Univ Minnesota, Environm Hlth Sci Water Res Ctr, St Paul, MN 55108 USA. [Weber, Eric J.] US EPA, Natl Exposure Res Lab, Athens, GA USA. [Ferguson, P. Lee; Wiesner, Mark R.] Duke Univ, Durham, NC USA. [Field, Jennifer A.] Oregon State Univ, Corvallis, OR 97331 USA. [Furlong, Edward T.] US Geol Survey, Natl Water Qual Lab, Denver, CO 80225 USA. [Giesy, John P.] Univ Saskatchewan, Saskatoon, SK, Canada. [Halden, Rolf U.] Arizona State Univ, Sch Sustainable Engn & Built Environm, Tempe, AZ USA. [Halden, Rolf U.] Johns Hopkins Univ, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. [Henry, Tala] US EPA, Natl Program Chem Div, Washington, DC 20460 USA. [Hites, Ronald A.] Indiana Univ, Bloomington, IN USA. [Hornbuckle, Keri C.] Univ Iowa, Iowa City, IA USA. [Howard, Philip H.] Syracuse Res Corp, Syracuse, NY USA. [Luthy, Richard G.] Stanford Univ, Stanford, CA 94305 USA. [Meyer, Anita K.] USA, Environm & Munit Ctr Expertise, Corps Engineers, Omaha, NE USA. [vom Saal, Frederick S.] Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA. [Vulpe, Chris D.] Univ Calif Berkeley, Berkeley, CA 94720 USA. RP Ela, WP (reprint author), Univ Arizona, 1133 E James E Rogers Way,POB 210011, Tucson, AZ 85721 USA. EM wela@engr.arizona.edu RI Furlong, Edward/C-3999-2011; Hornbuckle, Keri/A-8155-2008; Ferguson, Lee/A-5501-2013; Halden, Rolf/F-9562-2010; Saez, Avelino/K-1136-2016; OI Furlong, Edward/0000-0002-7305-4603; Hornbuckle, Keri/0000-0002-3478-3221; Halden, Rolf/0000-0001-5232-7361; Saez, Avelino/0000-0002-3548-6325; Muir, Derek/0000-0001-6631-9776 FU National Institute of Environmental Health Sciences [P42-ES04940] FX Support for the workshop, from which this article evolved, was provided by the National Institute of Environmental Health Sciences Superfund Research Program (P42-ES04940). NR 55 TC 9 Z9 9 U1 2 U2 66 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2011 VL 119 IS 1 BP 6 EP 10 DI 10.1289/ehp.1002497 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 701BI UT WOS:000285788900017 PM 21205582 ER PT J AU Zhao, R Hou, YY Xue, P Woods, CG Fu, JQ Feng, B Guan, DW Sun, GF Chan, JY Waalkes, MP Andersen, ME Pi, JB AF Zhao, Rui Hou, Yongyong Xue, Peng Woods, Courtney G. Fu, Jingqi Feng, Bo Guan, Dawei Sun, Guifan Chan, Jefferson Y. Waalkes, Michael P. Andersen, Melvin E. Pi, Jingbo TI Long Isoforms of NRF1 Contribute to Arsenic-Induced Antioxidant Response in Human Keratinocytes SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE apoptosis; arsenic; cytotoxicity; KEAP1; keratinocyte; NRF1; NRF2; oxidative stress ID ENDOPLASMIC-RETICULUM STRESS; ELEMENT-MEDIATED EXPRESSION; BZIP TRANSCRIPTION FACTOR; OXIDATIVE DNA-DAMAGE; ADAPTIVE RESPONSE; EMBRYONIC LETHALITY; MOLECULAR-CLONING; DRINKING-WATER; LOW-LEVEL; ACTIVATION AB BACKGROUND: Human exposure to inorganic arsenic (iAs), a potent oxidative stressor, causes various dermal disorders, including hyperkeratosis and skin cancer. Nuclear factor-erythroid 2-related factor 1 (NRF1, also called NFE2L1) plays a critical role in regulating the expression of many antioxidant response element (ARE)-dependent genes. OBJECTIVES: We investigated the role of NRF1 in arsenic-induced antioxidant response and cytotoxicity in human keratinocytes. RESULTS: In cultured human keratinocyte HaCaT cells, inorganic arsenite (iAs(3+)) enhanced the protein accumulation of long isoforms (120-140 kDa) of NRF1 in a dose-and time-dependent fashion. These isoforms accumulated mainly in the nuclei of HaCaT cells. Selective deficiency of NRF1 by lentiviral short-hairpin RNAs in HaCaT cells [NRF1-knockdown (KD)] led to decreased expression of gamma-glutamate cysteine ligase catalytic subunit (GCLC) and regulatory subunit (GCLM) and a reduced level of intra-cellular glutathione. In response to acute iAs(3+) exposure, induction of some ARE-dependent genes, including NAD(P)H:quinone oxidoreductase 1 (NQO1), GCLC, and GCLM, was significantly attenuated in NRF1-KD cells. However, the iAs(3)-induced expression of heme oxygenase 1 (HMOX-1) was unaltered by silencing NRF1, suggesting that HMOX-1 is not regulated by NRF1. In addition, the lack of NRF1 in HaCaT cells did not disturb iAs(3+)-induced NRF2 accumulation but noticeably decreased Kelch-like ECH-associated protein 1 (KEAP1) levels under basal and iAs(3+)-exposed conditions, suggesting a potential interaction between NRF1 and KEAP1. Consistent with the critical role of NRF1 in the transcriptional regulation of some ARE-bearing genes, knockdown of NRF1 significantly increased iAs(3+)-induced cytotoxicity and apoptosis. CONCLUSIONS: Here, we demonstrate for the first time that long isoforms of NRF1 contribute to arsenic-induced antioxidant response in human keratinocytes and protect the cells from acute arsenic cytotoxicity. C1 [Pi, Jingbo] Hamner Inst Hlth Sci, Div Translat Biol, Res Triangle Pk, NC 27709 USA. [Zhao, Rui; Guan, Dawei] China Med Univ, Sch Forens Med, Shenyang, Peoples R China. [Hou, Yongyong; Xue, Peng; Fu, Jingqi; Sun, Guifan] China Med Univ, Sch Publ Hlth, Shenyang, Peoples R China. [Feng, Bo] China Med Univ, Clin Coll 1, Shenyang, Peoples R China. [Chan, Jefferson Y.] Univ Calif Irvine, Dept Lab Med & Pathol, Irvine, CA USA. [Waalkes, Michael P.] NIEHS, Natl Toxicol Program, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Pi, JB (reprint author), Hamner Inst Hlth Sci, Div Translat Biol, 6 Davis Dr, Res Triangle Pk, NC 27709 USA. EM jpi@thehamner.org RI xue, peng/K-4159-2015; OI Andersen, Melvin/0000-0002-3894-4811 FU National Institutes of Health [ES016005]; American Chemistry Council Long Range Research Initiative; Dow Chemical Company; National Institute of Environmental Health Sciences; American Chemistry Council FX This research was supported in part by National Institutes of Health grant ES016005 (J.P.), the American Chemistry Council Long Range Research Initiative (M.E.A.), the Dow Chemical Company (M.E.A.), and the Intramural Research program of the National Institute of Environmental Health Sciences (M.P.W.).; R.Z., Y.H., P.X., C.G.W, J.F. M.E.A., and J.P. are employees of the Hamner Institutes for Health Sciences, a 501(c) 3 not-for-profit organization that has a diverse research portfolio that includes funding from the American Chemistry Council, a trade association that represents chemical manufacturers. The remaining authors declare they have no actual or potential competing financial interests. NR 54 TC 35 Z9 36 U1 1 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 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2011 VL 119 IS 1 BP 56 EP 62 DI 10.1289/ehp.1002304 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 701BI UT WOS:000285788900024 PM 20805060 ER PT J AU Hewitt, SC Korach, KS AF Hewitt, Sylvia C. Korach, Kenneth S. TI Estrogenic Activity of Bisphenol A and 2,2-bis(p-Hydroxyphenyl)-1,1,1-trichloroethane (HPTE) Demonstrated in Mouse Uterine Gene Profiles SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE BPA; ER alpha; estrogen; HPTE; microarray; uterus ID RECEPTOR-ALPHA; ENVIRONMENTAL ESTROGENS; BREAST-CANCER; ER-ALPHA; IN-VIVO; METHOXYCHLOR; EXPRESSION; BINDING; TRANSCRIPTION; UTERUS AB BACKGROUND: Interest and concern regarding potentially estrogenic substances have resulted in development of model systems to evaluate mechanisms of such chemicals. Microarray studies have indicated that estradiol (E(2))-stimulated uterine responses can be divided into early and late phases. Comparison of E(2) uterine transcript profiles and those of other estrogenic chemicals of interest in vivo indicates mechanisms and activities of test compounds. OBJECTIVES: We compared transcript responses and mechanisms of response using mouse reproductive tracts after treatment with E(2), estriol (E(3)), bisphenol A (BPA), and 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE). METHODS: Uterine RNA from ovariectomized wild-type mice, estrogen receptor alpha (ER alpha) knockout (alpha ERKO) mice, and mice expressing a DNA-binding-deficient ER alpha (KIKO) treated with E(2), E(3), BPA, or HPTE for 2 or 24 hr was analyzed by microarray. Resulting regulated transcripts were compared by hierarchical clustering and correlation analysis, and response patterns were verified by reverse-transcription real-time polymerase chain reaction (RT-PCR). RESULTS: Both xenoestrogens, BPA and HPTE, showed profiles highly correlated to that of E(2) in the early response phase (2 hr), but the correlation diminished in the later response phase (24 hr), similar to the known weak estrogen E(3). Both xenoestrogens also mimicked E(2) in samples from KIKO mice, indicating that they are able to utilize the indirect tethering mode of ER alpha signaling. No response was detected in ER alpha-null uteri, indicating that ER alpha mediates the responses. CONCLUSION: Our study forms a basis on which patterns of response and molecular mechanisms of potentially estrogenic chemicals can be assessed. C1 [Hewitt, Sylvia C.; Korach, Kenneth S.] NIEHS, Receptor Biol Sect, Lab Reprod & Dev Toxicol, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Hewitt, SC (reprint author), NIEHS, Receptor Biol Sect, Lab Reprod & Dev Toxicol, NIH,Dept Hlth & Human Serv, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM curtiss@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X FU NIEHS [Z01ES70065] FX This work was supported by NIEHS project Z01ES70065. NR 47 TC 21 Z9 21 U1 0 U2 9 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2011 VL 119 IS 1 BP 63 EP 70 DI 10.1289/ehp.1002347 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 701BI UT WOS:000285788900025 PM 20826375 ER PT J AU Nicolle-Mir, L AF Nicolle-Mir, Laurence TI Plombenia and amyotrophic lateral sclerosis risk SO ENVIRONNEMENT RISQUES & SANTE LA French DT News Item C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Nicolle-Mir, L (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1635-0421 J9 ENVIRON RISQUE SANTE JI Environ. Risque Sante PD JAN-FEB PY 2011 VL 10 IS 1 BP 15 EP 16 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 735KS UT WOS:000288413800009 ER PT J AU Baird, D Wise, LA AF Baird, Donna Wise, Lauren A. TI Childhood Abuse and Fibroids SO EPIDEMIOLOGY LA English DT Editorial Material ID UNITED-STATES; UTERINE LEIOMYOMATA; DIAGNOSIS; STRESS; MYOMAS; HEALTH; HYSTERECTOMY; ASSOCIATION; EXPERIENCES; DISORDERS C1 [Baird, Donna] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Wise, Lauren A.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. RP Baird, D (reprint author), NIEHS, Epidemiol Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM baird@niehs.nih.gov OI Wise, Lauren/0000-0003-2138-3752; Baird, Donna/0000-0002-5544-2653 FU Intramural NIH HHS [ZIA ES049013-16] NR 27 TC 6 Z9 6 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2011 VL 22 IS 1 BP 15 EP 17 DI 10.1097/EDE.0b013e3181fe1fbe PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 692WT UT WOS:000285187300003 PM 21150350 ER PT J AU Costello, S Friesen, MC Christiani, DC Eisena, EA AF Costello, Sadie Friesen, Melissa C. Christiani, David C. Eisena, Ellen A. TI Metalworking Fluids and Malignant Melanoma in Autoworkers SO EPIDEMIOLOGY LA English DT Article ID AUTOMOBILE-INDUSTRY; CANCER INCIDENCE; CUTTING OILS; MINERAL-OILS; EXPOSURE; MORTALITY; WORKERS; COHORT; SKIN; DERMATITIS AB Background: Occupational exposure to mineral oil-based metalworking fluids has been consistently linked with skin conditions such as contact dermatitis and squamous cell skin cancer, especially of the scrotum. We examined the incidence of malignant melanoma in a study of autoworkers. Methods: We followed a cohort of autoworkers from 1985 through 2004 for cancer incidence. Hazard ratios (HRs) were estimated in Cox models for cumulative exposure to total particulate of straight fluid (neat oil), soluble fluid (oil emulsified in water), and synthetic fluid (no oil). Exposure was partitioned into time windows by latency and by calendar periods defined by changes in the content of polycyclic aromatic hydrocarbon in the refined oils. The population was restricted to workers born after 1935. We examined the date-of-birth restriction in a sensitivity analysis. Results: On the basis of 76 incident cases of malignant melanoma in the cohort of 14,139 white males, the HR was 1.99 (95% confidence interval = 1.00-3.96) for the highest category of straight fluid. Risk was greatest in the most recent time window. Penalized splines suggested a linear exposure-response over the full range of exposure. The change in HR for malignant melanoma per mg/m(3)-year of straight fluid increased monotonically from 1.01 to 1.04, when the date-of-birth restriction increased from 1925 to 1945 in 5-year intervals. Results for soluble fluid were more modest. There was no association with synthetic fluid. Conclusions: Results provide evidence, based on quantitative measures of metalworking fluid, that oil-based fluid, particularly straight mineral oils, are associated with the incidence of malignant melanoma. C1 [Costello, Sadie; Friesen, Melissa C.; Eisena, Ellen A.] Univ Calif Berkeley, Sch Publ Hlth, Dept Environm Hlth Sci, Berkeley, CA 94720 USA. [Friesen, Melissa C.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Christiani, David C.; Eisena, Ellen A.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Eisena, EA (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Dept Environm Hlth Sci, 50 Univ Hall 7360, Berkeley, CA 94720 USA. EM eeisen@berkeley.edu RI Friesen, Melissa/A-5362-2009 FU Department of Health and Human Services, Centers for Disease Control/National Institute for Occupational Safety and Health [R01 OH008927] FX Supported by the Department of Health and Human Services, Centers for Disease Control/National Institute for Occupational Safety and Health (R01 OH008927). NR 37 TC 11 Z9 12 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2011 VL 22 IS 1 BP 90 EP 97 DI 10.1097/EDE.0b013e3181fce4b8 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 692WT UT WOS:000285187300014 PM 20975563 ER PT J AU Kilfoy, B Heltshe, S Nuckols, J Sabra, M Shuldiner, A Mitchell, B Holford, T Zhang, YW Ward, M AF Kilfoy, Briseis Heltshe, Sonya Nuckols, John Sabra, Mona Shuldiner, Alan Mitchell, Braxton Holford, Theodore Zhang, Yawei Ward, Mary TI Nitrate From Drinking Water and Prevalence of Abnormal Thyroid Conditions Among the Old Order Amish in Pennsylvania SO EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Conference of International-Society-of-Exposure-Science/International-Society-for-Envi ronmental-Epidemiology CY AUG 28-SEP 01, 2010 CL Seoul, SOUTH KOREA SP Int Soc Exposure Sci, Int Soc Environm Epidemiol C1 [Kilfoy, Briseis; Heltshe, Sonya; Ward, Mary] NCI, Rockville, MD USA. [Kilfoy, Briseis; Holford, Theodore; Zhang, Yawei] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Nuckols, John] Colorado State Univ, Dept Environm & Radiol Hlth, Ft Collins, CO 80523 USA. [Sabra, Mona; Shuldiner, Alan; Mitchell, Braxton] Univ Maryland, Sch Med, Dept Endocrinol, Baltimore, MD 21201 USA. RI Aschebrook-Kilfoy, Briseis/A-2537-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1044-3983 EI 1531-5487 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2011 VL 22 IS 1 SU S BP S295 EP S296 DI 10.1097/01.ede.0000392609.10543.43 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 695VN UT WOS:000285400800917 ER PT J AU Ward, MH Kilfoy, B Sinha, R Hollenbeck, AR Schatzkin, A Cross, A AF Ward, Mary H. Kilfoy, Briseis Sinha, Rashmi Hollenbeck, A. R. Schatzkin, Arthur Cross, Amanda TI Ingestion of Nitrate and Nitrite and Risk of Stomach Cancer in the NIH-AARP Diet and Health Study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Conference of International-Society-of-Exposure-Science/International-Society-for-Envi ronmental-Epidemiology CY AUG 28-SEP 01, 2010 CL Seoul, SOUTH KOREA SP Int Soc Exposure Sci, Int Soc Environm Epidemiol C1 [Ward, Mary H.; Kilfoy, Briseis; Sinha, Rashmi; Schatzkin, Arthur; Cross, Amanda] NCI, Bethesda, MD 20892 USA. [Hollenbeck, A. R.] AARP, Washington, DC USA. RI Aschebrook-Kilfoy, Briseis/A-2537-2012 NR 0 TC 2 Z9 2 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1044-3983 EI 1531-5487 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2011 VL 22 IS 1 SU S BP S107 EP S108 DI 10.1097/01.ede.0000391997.79108.fb PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 695VN UT WOS:000285400800305 ER PT S AU Miller, FW AF Miller, Frederick W. BE Ballestar, E TI ENVIRONMENTAL AGENTS AND AUTOIMMUNE DISEASES SO EPIGENETIC CONTRIBUTIONS IN AUTOIMMUNE DISEASE SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TYPE-1 DIABETES-MELLITUS; ULTRAVIOLET-RADIATION INTENSITY; SILICONE BREAST IMPLANTS; RHEUMATOID-ARTHRITIS; RISK-FACTORS; OCCUPATIONAL-EXPOSURE; CIGARETTE-SMOKING; PARVOVIRUS B19; ONSET AB Autoimmune diseases, which comprise over 80 clinically distinct conditions, are characterized by the presence of autoantibodies or autoreactive T cells directed against self structures (autoantigens). While these often incurable disorders appear to be rapidly increasing in recognition throughout the world, their rarity, heterogeneity and complex etiologies have limited our understanding of their pathogeneses. The precise mechanisms for the development of autoimmune diseases are not known, however, evidence from many complementary lines of investigation suggests that autoimmune diseases result from the interactions of both environmental and genetic risk factors. While considerable progress has been made in understanding multiple genetic risk factors for many autoimmune diseases, relatively little information is now available regarding the role of the environment in the development of these illnesses. This chapter examines the limited but growing evidence for the role of the environment in the development and progression of autoimmune diseases, the specific exposures that have been suspected of being involved, the possible mechanisms by which these agents may induce and sustain autoimmune processes and the approaches needed to better understand these issues in the future. Identifying the necessary and sufficient genetic and environmental risk factors for disease holds the promise of allowing for the prevention of some illnesses through avoidance of environmental risk factors by genetically susceptible individuals or via gene or other therapies to correct the effects of deleterious genetic risk factors in the case of unavoidable environmental agents. C1 NIEHS, Environm Autoimmun Grp, NIH, HHS, Bethesda, MD USA. RP Miller, FW (reprint author), NIEHS, Environm Autoimmun Grp, NIH, HHS, Bethesda, MD USA. EM millerf@mail.nih.gov OI Miller, Frederick/0000-0003-2831-9593 FU Intramural NIH HHS NR 93 TC 14 Z9 14 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-8215-5 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2011 VL 711 BP 61 EP 81 D2 10.1007/978-1-4419-8216-2 PG 21 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BTS53 UT WOS:000287980700006 PM 21627043 ER PT J AU Pradhan, AK Divekar, G Masserang, K Romoser, M Zafian, T Blomberg, RD Thomas, FD Reagan, I Knodler, M Pollatsek, A Fisher, DL AF Pradhan, A. K. Divekar, G. Masserang, K. Romoser, M. Zafian, T. Blomberg, R. D. Thomas, F. D. Reagan, I. Knodler, M. Pollatsek, A. Fisher, D. L. TI The effects of focused attention training on the duration of novice drivers' glances inside the vehicle SO ERGONOMICS LA English DT Article DE novice drivers; attention; training; distraction; eye movements; field driving study ID DRIVING SIMULATION; PERCEPTION; EXPERIENCE; TASKS AB Several studies have documented that the failure of drivers to attend to the forward roadway for a period lasting longer than 2-3 s is a major cause of highway crashes. Moreover, several studies have demonstrated that novice drivers are more likely to glance away from the roadway than the experienced drivers for extended periods when attempting to do a task inside the vehicle. The present study examines the efficacy of a PC-based training programme (FOrward Concentration and Attention Learning, FOCAL) designed to teach novice drivers not to glance away for these extended periods of time. A FOCAL-trained group was compared with a placebo-trained group in an on-road test, and the FOCAL-trained group made significantly fewer glances away from the roadway that were more than 2 s than the placebo-trained group. Other measures indicated an advantage for the FOCAL-trained group as well. Statement of relevance: Distracted driving is increasingly a problem, as cell phones, navigation systems, and other in-vehicle devices are introduced into the cabin of the automobile. A training programme is described that has been tested on the open road and can reduce the behaviours that lead to crashes caused by the distracted driving. C1 [Pradhan, A. K.; Divekar, G.; Romoser, M.; Zafian, T.] Univ Massachusetts, Dept Mech & Ind Engn, Elab 110, Amherst, MA 01003 USA. [Masserang, K.; Pollatsek, A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Blomberg, R. D.] Dunlap & Associates Inc, Stamford, CT 06906 USA. [Reagan, I.] Natl Highway Traff Safety Adm US, Washington, DC 20590 USA. [Knodler, M.] Univ Massachusetts, Dept Civil & Environm Engn, Amherst, MA 01003 USA. RP Pradhan, AK (reprint author), Kennedy Shriver Natl Inst Child Hlth & Human Dev, NIH, Bethesda, MD 20892 USA. EM anuj.pradhan@nih.gov OI Pradhan, Anuj/0000-0002-7612-4208 FU National Highway Traffic Safety Administration; National Institutes of Health [1R01HD057153] FX The authors would like to thank the following persons for their assistance with various aspects of the study: Bill Ryan for his help in the programming of the FOCAL interface, Joe Usowski for help with video data reduction, and Don-Tre Driving School, Milburn, NJ, for their help in recruiting participants and data collection. The research was funded by the grants from the National Highway Traffic Safety Administration and the National Institutes of Health grant number 1R01HD057153. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NHTSA or NIH. NR 47 TC 21 Z9 21 U1 4 U2 22 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0014-0139 J9 ERGONOMICS JI Ergonomics PY 2011 VL 54 IS 10 BP 917 EP 931 DI 10.1080/00140139.2011.607245 PG 15 WC Engineering, Industrial; Ergonomics; Psychology, Applied; Psychology SC Engineering; Psychology GA 887KA UT WOS:000299924800004 PM 21973003 ER PT S AU Tamaki, A Ierano, C Szakacs, G Robey, RW Bates, SE AF Tamaki, Akina Ierano, Caterina Szakacs, Gergely Robey, Robert W. Bates, Susan E. BE Sharom, FJ TI The controversial role of ABC transporters in clinical oncology SO ESSAYS IN BIOCHEMISTRY: ABC TRANSPORTERS SE Essays in Biochemistry LA English DT Review; Book Chapter ID ACUTE-MYELOID-LEUKEMIA; CANCER RESISTANCE PROTEIN; CELL LUNG-CANCER; BLOOD-BRAIN-BARRIER; REFRACTORY MULTIPLE-MYELOMA; P-GLYCOPROTEIN EXPRESSION; PHASE-I TRIAL; MULTIDRUG-RESISTANCE; BREAST-CANCER; DRUG EFFLUX AB The phenomenon of multidrug resistance in cancer is often associated with the overexpression of the ABC (ATP-binding cassette) transporters Pgp (P-glycoprotein) (ABCB1), MRP1 (multidrug resistance-associated protein 1) (ABCC1) and ABCG2 [BCRP (breast cancer resistance protein)]. Since the discovery of Pgp over 35 years ago, studies have convincingly linked ABC transporter expression to poor outcome in several cancer types, leading to the development of transporter inhibitors. Three generations of inhibitors later, we are still no closer to validating the 'Pgp hypothesis', the idea that increased chemotherapy efficacy can be achieved by inhibition of transporter-mediated efflux. In this chapter, we highlight the difficulties and past failures encountered in the development of clinical inhibitors of ABC transporters. We discuss the challenges that remain in our effort to exploit decades of work on ABC transporters in oncology. In learning from past mistakes, it is hoped that ABC transporters can be developed as targets for clinical intervention. C1 [Tamaki, Akina; Ierano, Caterina; Robey, Robert W.; Bates, Susan E.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Szakacs, Gergely] Hungarian Acad Sci, Inst Enzymol, Budapest, Hungary. RP Bates, SE (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 13N240, Bethesda, MD 20892 USA. EM sebates@helix.nih.gov RI Szakacs, Gergely/A-2580-2009; Ierano, Caterina/K-1676-2016 OI Szakacs, Gergely/0000-0002-9311-7827; Ierano, Caterina/0000-0003-3138-1873 NR 99 TC 62 Z9 65 U1 0 U2 25 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON W1N 3AJ, ENGLAND SN 0071-1365 BN 978-1-85578-181-8 J9 ESSAYS BIOCHEM JI Essays Biochem. PY 2011 VL 50 BP 209 EP 232 DI 10.1042/BSE0500209 PG 24 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BXA76 UT WOS:000295553500011 PM 21967059 ER PT J AU Lochhead, P Ng, MTH Hold, GL Rabkin, CS Vaughan, TL Gammon, MD Risch, HA Lissowska, J Mukhopadhya, I Chow, WH El-Omar, EM AF Lochhead, Paul Ng, Michael T. H. Hold, Georgina L. Rabkin, Charles S. Vaughan, Thomas L. Gammon, Marilie D. Risch, Harvey A. Lissowska, Jolanta Mukhopadhya, Indrani Chow, Wong-Ho El-Omar, Emad M. TI Possible association between a genetic polymorphism at 8q24 and risk of upper gastrointestinal cancer SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article DE cancer susceptibility; gastric cancer; genetic polymorphism; oesophageal cancer ID GENOME-WIDE ASSOCIATION; LONG-RANGE INTERACTION; PROSTATE-CANCER; COLORECTAL-CANCER; CHROMOSOME 8Q24; STOMACH-CANCER; SUSCEPTIBILITY LOCUS; GASTRIC CARDIA; POPULATION; VARIANT AB Over recent years, genome-wide association studies have contributed to our understanding of genetic susceptibility to sporadic cancer. In this study, we assessed the association between upper gastrointestinal cancer risk and four genome-wide association studies-identified single nucleotide polymorphisms (SNPs), implicated earlier in prostate and colorectal cancer susceptibility. Genotyping for each SNP was performed in two independent Caucasian population-based case-control studies. The first study comprised 290 gastric cancer cases and 374 controls. The second study included 185 noncardia gastric cancers, 123 cardia cancers, 158 oesophageal cancers and 209 controls. Odds ratios (ORs) were computed from logistic models and adjusted for potential confounding variables. An inverse association was observed between the SNP rs1447295, located at 8q24, and gastric cancer risk in the first study population (OR = 0.63; 95% confidence interval: 0.41-0.97). A positive association was observed for the same SNP and oesophageal squamous cell carcinoma in the second study population (OR = 7.43; 95% confidence interval: 1.37-49.98). No significant associations were detected in either study for the three remaining SNPs (rs6983297, rs10505477 and rs719725). Our data represent novel findings on heritable susceptibility to gastric and oesophageal cancer and warrant validation in additional populations. European Journal of Cancer Prevention 20: 54-57 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [El-Omar, Emad M.] Univ Aberdeen, Div Appl Med, Sch Med & Dent, Inst Med Sci,Gastrointestinal Res Grp, Aberdeen AB25 2ZD, Scotland. [Rabkin, Charles S.; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Vaughan, Thomas L.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. [Vaughan, Thomas L.] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA. [Gammon, Marilie D.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Risch, Harvey A.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Div Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. RP El-Omar, EM (reprint author), Univ Aberdeen, Div Appl Med, Sch Med & Dent, Inst Med Sci,Gastrointestinal Res Grp, Foresterhill, Aberdeen AB25 2ZD, Scotland. EM e.el-omar@abdn.ac.uk OI Lissowska, Jolanta/0000-0003-2695-5799 FU NHS; Scottish Government Chief Scientist Office; United States Public Health Service [U01-CA57983, U01-CA57949, U01-CA57923, P30ES10126]; National Cancer Institute; National Institutes of Health; Department of Health and Human Services [N02-CP40501, N01-CN05230] FX This study was supported by a grant from the NHS Grampian endowments. P.L. is funded by a fellowship from the Scottish Government Chief Scientist Office. The US multicentre oesophageal and gastric cancer study was supported by the United States Public Health Service (U01-CA57983, U01-CA57949, U01-CA57923, P30ES10126) and by the National Cancer Institute, the National Institutes of Health, the Department of Health and Human Services (N02-CP40501, N01-CN05230). NR 31 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD JAN PY 2011 VL 20 IS 1 BP 54 EP 57 DI 10.1097/CEJ.0b013e328341e320 PG 4 WC Oncology SC Oncology GA 688AZ UT WOS:000284821800008 PM 21102338 ER PT J AU Lam, CSP Donal, E Kraigher-Krainer, E Vasan, RS AF Lam, Carolyn S. P. Donal, Erwan Kraigher-Krainer, Elisabeth Vasan, Ramachandran S. TI Epidemiology and clinical course of heart failure with preserved ejection fraction SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Review DE Heart failure with preserved ejection fraction; Epidemiology ID VENTRICULAR SYSTOLIC FUNCTION; LONG-TERM; EUROPEAN-SOCIETY; PULMONARY-HYPERTENSION; DIASTOLIC DYSFUNCTION; DIAGNOSTIC-CRITERIA; HONG-KONG; COMMUNITY; PREVALENCE; OUTCOMES AB Heart failure with preserved ejection fraction (HFPEF) is increasingly recognized as a major public health problem worldwide. Significant advances have been made in our understanding of the epidemiology of HFPEF over the past two decades, with the publication of numerous population-based epidemiological studies, large heart failure registries, and randomized clinical trials. These recent studies have provided detailed characterization of larger numbers of patients with HFPEF than ever before. This review summarizes the state of current knowledge with regards to the disease burden, patient characteristics, clinical course, and outcomes of HFPEF. Despite the wealth of available data, substantive gaps in knowledge were identified. These gaps represent opportunities for further research in HFPEF, a syndrome that is clearly a rising societal burden and that is associated with substantial morbidity and mortality. C1 [Lam, Carolyn S. P.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Donal, Erwan] Rennes Univ Hosp, Dept Cardiol, Rennes, France. [Kraigher-Krainer, Elisabeth] Med Univ Graz, Dept Cardiol, Graz, Austria. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM vasan@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute's Framingham Heart Study [NO1-HC-25195] FX This work was supported in part by National Heart, Lung, and Blood Institute's Framingham Heart Study (Contract No. NO1-HC-25195). NR 78 TC 174 Z9 187 U1 4 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD JAN PY 2011 VL 13 IS 1 BP 18 EP 28 DI 10.1093/eurjhf/hfq121 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 696BG UT WOS:000285416300004 PM 20685685 ER PT J AU Dubourg, C David, V Gropman, A Mercier, S Muenke, M Odent, S Pineda-Alvarez, DE Roessler, E AF Dubourg, Christele David, Veronique Gropman, Andrea Mercier, Sandra Muenke, Maximilian Odent, Sylvie Pineda-Alvarez, Daniel E. Roessler, Erich TI Clinical utility gene card for: Holoprosencephaly SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Editorial Material C1 [Dubourg, Christele; David, Veronique; Mercier, Sandra; Odent, Sylvie] Univ Rennes, CHU Pontchaillou, UMR CNRS IGDR 6061, Rennes, France. [Gropman, Andrea] CNMC Ctr Neurosci Res, Washington, DC USA. [Muenke, Maximilian; Pineda-Alvarez, Daniel E.; Roessler, Erich] NHGRI, NIH, Bethesda, MD 20892 USA. RP Dubourg, C (reprint author), CHU Rennes, CNRS, UMR 6061, 2 Rue Henri Le Guilloux, F-35033 Rennes, France. EM christele.dubourg@chu-rennes.fr NR 6 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD JAN PY 2011 VL 19 IS 1 DI 10.1038/ejhg.2010.110 PG 3 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 692FV UT WOS:000285139600023 ER PT J AU Raam, MS Pineda-Alvarez, DE Hadley, DW Solomon, BD AF Raam, Manu S. Pineda-Alvarez, Daniel E. Hadley, Donald W. Solomon, Benjamin D. TI Long-term outcomes of adults with features of VACTERL association SO EUROPEAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE VACTERL; VACTERL association; VATER; VATER association ID QUALITY-OF-LIFE; AND/OR TRACHEOESOPHAGEAL FISTULA; ESOPHAGEAL ATRESIA; VATER-ASSOCIATION; IMPERFORATE ANUS; ANORECTAL-MALFORMATIONS; MUTATION; POPULATION; DEFINITION; EXPERIENCE AB VACTERL association involves the presence of specific congenital, multi-organ malformations that tend to co-occur. Clinical and research efforts typically center on pediatric patients, and there is a scarcity of information in the literature regarding VACTERL-related issues and outcomes in adulthood. We describe here 11 adults with features of VACTERL association ascertained through our research study on the condition. In our cohort of adult patients, approximately 25% of medically significant malformations that are component features of VACTERL association, including 40% of vertebral, 50% of cardiac, and 50% of renal anomalies, were not identified during childhood. Additionally, medical sequelae of many of the primary malformations identified in infancy or early childhood persist or are first reported in adulthood. These sequelae can involve challenging medical and surgical management in adulthood. As most adults with VACTERL association are not specifically followed for VACTERL-related issues, a more uniform diagnostic work-up and a low threshold for investigation of medical sequelae of the primary disorder may enhance the quality of clinical management in these patients. Published by Elsevier Masson SAS. C1 [Raam, Manu S.; Pineda-Alvarez, Daniel E.; Solomon, Benjamin D.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Raam, Manu S.] Howard Hughes Med Inst, HHMI NIH Res Scholars Program, Chevy Chase, MD 20815 USA. [Hadley, Donald W.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP Solomon, BD (reprint author), NHGRI, Med Genet Branch, NIH, Bldg 35,Room 1B207,35 Convent Dr MSC 3717, Bethesda, MD 20892 USA. EM raamm@ccf.org; pinedaad@mail.nih.gov; dhadley@nhgri.nih.gov; solomonb@mail.nih.gov FU Howard Hughes Medical Institute; Division of Intramural Research at the National Human Genome Research Institute (National Institutes of Health, Department of Health and Human Services, United States of America) FX We would like to express our gratitude to the patients described in this article for their willingness to take part in this study. This research was supported in part by the Howard Hughes Medical Institute and by the Division of Intramural Research at the National Human Genome Research Institute (National Institutes of Health, Department of Health and Human Services, United States of America). NR 42 TC 9 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1769-7212 J9 EUR J MED GENET JI Eur. J. Med. Genet. PD JAN-FEB PY 2011 VL 54 IS 1 BP 34 EP 41 DI 10.1016/j.ejmg.2010.09.007 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 805QH UT WOS:000293743600007 PM 20888933 ER PT J AU Sibley, D Hazelwood, L Roof, R Free, RB Han, Y Javitch, J AF Sibley, D. Hazelwood, L. Roof, R. Free, R. B. Han, Y. Javitch, J. TI MEMBRANE LIPID RAFTS ARE REQUIRED FOR D2 DOPAMINE RECEPTOR SIGNALING SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Sibley, D.; Hazelwood, L.; Roof, R.; Free, R. B.] NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA. [Han, Y.; Javitch, J.] Columbia Univ, Ctr Mol Recognit, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2011 VL 26 SU 1 MA P02-314 PG 1 WC Psychiatry SC Psychiatry GA V27VS UT WOS:000208641301011 ER PT J AU O'Gorman, RL Shmueli, K Ashkan, K Samuel, M Lythgoe, DJ Shahidiani, A Wastling, SJ Footman, M Selway, RP Jarosz, J AF O'Gorman, Ruth L. Shmueli, Karin Ashkan, Keyoumars Samuel, Michael Lythgoe, David J. Shahidiani, Asal Wastling, Stephen J. Footman, Michelle Selway, Richard P. Jarosz, Jozef TI Optimal MRI methods for direct stereotactic targeting of the subthalamic nucleus and globus pallidus SO EUROPEAN RADIOLOGY LA English DT Article DE MRI; Deep brain stimulation; Direct stereotactic targeting; Subthalamic nucleus; Globus pallidus ID DEEP BRAIN-STIMULATION; INVERSION-RECOVERY SEQUENCE; PARKINSONS-DISEASE; IRON; LOCALIZATION; IMPLANTATION; VARIABILITY; DYSTONIA; LOCATION; CONTRAST AB Reliable identification of the subthalamic nucleus (STN) and globus pallidus interna (GPi) is critical for deep brain stimulation (DBS) of these structures. The purpose of this study was to compare the visibility of the STN and GPi with various MRI techniques and to assess the suitability of each technique for direct stereotactic targeting. MR images were acquired from nine volunteers with T2- and proton density-weighted (PD-W) fast spin echo, susceptibility-weighted imaging (SWI), phase-sensitive inversion recovery and quantitative T1, T2 and T2* mapping sequences. Contrast-to-noise ratios (CNR) for the STN and GPi were calculated for all sequences. Targeting errors on SWI were evaluated on magnetic susceptibility maps. The sequences demonstrating the best conspicuity of DBS target structures (SWI and T2*) were then applied to ten patients with movement disorders, and the CNRs for these techniques were assessed. SWI offers the highest CNR for the STN, but standard PD-W images provide the best CNR for the pallidum. Susceptibility maps indicated that the GPi margins may be shifted slightly on SWI, although no shifts were seen for the STN. SWI may improve the visibility of the STN on pre-operative MRI, potentially improving the accuracy of direct stereotactic targeting. C1 [O'Gorman, Ruth L.] Univ Childrens Hosp, Kinderspital, MR Zentrum, CH-8032 Zurich, Switzerland. [O'Gorman, Ruth L.; Jarosz, Jozef] Kings Coll Hosp London, Dept Neuroradiol, London SE5 9RS, England. [Samuel, Michael] NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Ashkan, Keyoumars; Selway, Richard P.] Kings Coll Hosp London, Dept Neurosurg, London SE5 9RS, England. [Samuel, Michael] Kings Coll Hosp London, Dept Neurol, London SE5 9RS, England. [Lythgoe, David J.; Shahidiani, Asal; Wastling, Stephen J.] Inst Psychiat, Dept Clin Neurosci, London SE5 8AF, England. [Wastling, Stephen J.; Footman, Michelle] Kings Coll Hosp London, Dept Med Engn & Phys, London SE5 9RS, England. RP O'Gorman, RL (reprint author), Univ Childrens Hosp, Kinderspital, MR Zentrum, Steinwiesstr 75, CH-8032 Zurich, Switzerland. EM ruth.ogorman@kcl.ac.uk RI Shmueli, Karin/B-9432-2017; OI O'Gorman, Ruth/0000-0001-5932-7786 NR 27 TC 25 Z9 25 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD JAN PY 2011 VL 21 IS 1 BP 130 EP 136 DI 10.1007/s00330-010-1885-5 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 689AO UT WOS:000284899700016 PM 20652256 ER PT S AU Lynch, SK Liu, C Assoufid, L Morgan, NY Mazilu, D Bennett, E Kemble, CK Wen, HH AF Lynch, Susanna K. Liu, Chian Assoufid, Lahsen Morgan, Nicole Y. Mazilu, Dumitru Bennett, Eric Kemble, Camille K. Wen, Han Harold BE Hudec, R Pina, L TI Multilayer-Coated Micro-Grating Array for X-Ray Phase-Contrast Imaging SO EUV AND X-RAY OPTICS: SYNERGY BETWEEN LABORATORY AND SPACE II SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on EUV and X-Ray Optics - Synergy between Laboratory and Space II CY APR 20-21, 2011 CL Prague, CZECH REPUBLIC SP SPIE DE x-ray; grating; multilayer; phase-contrast; dark-field; imaging; CT; interferometer ID SHEARING INTERFEROMETER; FABRICATION; SCATTERING; BEAM AB X-ray imaging techniques based on grating interferometers rely on transmission gratings to detect x-ray refraction and scattering in a sample. Gratings periods below 2 microns are challenging to realize due to the high aspect ratio of the structures. We propose a method to fabricate transmission gratings with sub-micron periods over centimeter areas by multilayer coating of a staircase (echelle) substrate. The advantage of this approach is the high aspect ratio of multilayer coating and the large area of the echelle substrate. The staircase pattern is etched on the surface of a silicon wafer through anisotropic etching. Multiple layers are deposited on the horizontal surfaces of the stairs by magnetron sputtering in a single run. The layers alternate between two materials of different absorption coefficients or refractive indices. The layer thickness d is designed to be (stair height)/2N, where 2N is the total number of layers. The incident x-ray beam is parallel to the layers and oblique to the wafer surface. Each stair of the echelle substrate forms a micro grating of period 2d, and the array of micro gratings together act as a single grating over a large area given the right continuity conditions. The grating period potentially can be below 100 nm. We present theoretical description of wave diffraction by the grating array, and results of the first fabrication test with magnetron sputtering deposition. C1 [Lynch, Susanna K.; Mazilu, Dumitru; Bennett, Eric; Kemble, Camille K.; Wen, Han Harold] NHLBI, Lab Imaging Phys, Biophys & Biochem Ctr, NIH, Bethesda, MD 20892 USA. RP Lynch, SK (reprint author), NHLBI, Lab Imaging Phys, Biophys & Biochem Ctr, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. RI Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 NR 16 TC 0 Z9 0 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-81948-666-0 J9 PROC SPIE PY 2011 VL 8076 AR 80760F DI 10.1117/12.888939 PG 10 WC Optics; Physics, Applied SC Optics; Physics GA BXY15 UT WOS:000297594500014 ER PT B AU Fowler, DH AF Fowler, Daniel H. BE Medin, J Fowler, D TI Allogeneic and Autologous Transplantation Therapy of Cancer: Converging Themes SO EXPERIMENTAL AND APPLIED IMMUNOTHERAPY LA English DT Article; Book Chapter DE GVHD; JAK/STAT pathway; Pentostatin; Rapamycin; Th1/Th2 ID VERSUS-HOST-DISEASE; STEM-CELL TRANSPLANTATION; CD8(+) T-CELLS; ANTIGEN-PRESENTING CELLS; I CLINICAL-TRIAL; DONOR TH2 CELLS; GRAFT-REJECTION; ADOPTIVE TRANSFER; GENE-THERAPY; ANTITUMOR IMMUNITY AB Effective adoptive T-cell therapy of cancer occurs after allogeneic bone marrow transplantation, and is now increasingly observed after autologous transplantation. As the clinical practice of each field evolves and the biologic underpinnings of these two seemingly disparate approaches are elucidated, four converging themes have emerged. (1) T-cell antigen specificity. The alloreactive T-cell graft-versus-tumor response is difficult to dissociate from potentially lethal graft-versus-host disease (GVHD); as such, efforts are underway to enhance antigen-specificity after allogeneic transplantation. By comparison, the field of autologous T-cell therapy has now largely redefined itself by use of highly specific T-cell receptor reactivities, which may ultimately prove limiting in terms of tumor escape mechanisms; efforts are therefore underway to broaden antigenic reactivities after autologous transplantation. (2) Host conditioning. Myeloablative conditioning used in allogeneic transplantation causes significant morbidity and mortality even in young and healthy patients, thereby limiting broader application to the majority of cancer patients; in response, less intensive and better tolerated nonmyeloablative regimens are being developed. By comparison, autologous T-cell therapy has been primarily limited by lack of efficacy, and in response, investigators have increased host conditioning to myeloablative levels to create immune space that facilitates T-cell expansion and effectiveness in vivo. (3) T-cell function. The evolving discipline of T-cell biology will continue to enhance the efficacy of both autologous and allogeneic transplantation therapy. The quality of the T-cell response is of paramount importance, and is determined by T-cell differentiation status, apoptotic tendency, and cytokine phenotype vis-a-vis Th1, Th2, Treg, and Th17 balance; modulation of this balance for therapeutic gain will depend upon an ability to understand and control an emerging phenomenon termed T-cell plasticity. (4) T-cell-mediated immune pathology. GVHD after allogeneic transplantation has been an instrumental model system for understanding T-cell pathology; importantly, cellular and molecular mechanisms underlying GVHD may also contribute to toxicities observed after effective autologous T-cell therapy. As such, both allogeneic and autologous immunotherapies are now confronted with an overall goal of maximizing T-cell efficacy while limiting T-cell toxicity. Attainment of such enhanced therapeutic windows may be facilitated by recent developments in immune cell modulation, including use of cell fate control genes and use of inhibitors of the mammalian target of rapamycin (mTOR) and JAK/STAT pathways. In conclusion, converging themes in autologous and allogeneic transplantation therapy indicate that a bright future will emerge for T-cell therapies, the success of which will be realized through advances in T-cell biology and T-cell engineering. C1 NCI, NIH, Expt Transplatat & Immunol Branch, Bethesda, MD 20892 USA. RP Fowler, DH (reprint author), NCI, NIH, Expt Transplatat & Immunol Branch, Bethesda, MD 20892 USA. EM dhfowler@helix.nih.gov NR 95 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-60761-979-6 PY 2011 BP 411 EP 430 DI 10.1007/978-1-60761-980-2_19 D2 10.1007/978-1-60761-980-2 PG 20 WC Oncology; Immunology; Medicine, Research & Experimental; Pathology SC Oncology; Immunology; Research & Experimental Medicine; Pathology GA BSY36 UT WOS:000286130400019 ER PT J AU Kautz-Neu, K Kostka, SL Dinges, S Iwakura, Y Udey, MC von Stebut, E AF Kautz-Neu, Kordula Kostka, Susanna L. Dinges, Stephanie Iwakura, Yoichiro Udey, Mark C. von Stebut, Esther TI IL-1 signalling is dispensable for protective immunity in Leishmania-resistant mice SO EXPERIMENTAL DERMATOLOGY LA English DT Letter DE IL-1; dendritic cells; L; major ID DENDRITIC CELLS; C57BL/6 MICE; BALB/C MICE; INTERLEUKIN-1; RECEPTOR; SUSCEPTIBILITY; DISEASE AB Leishmaniasis is a parasitic disease affecting similar to 12 million people. Control of infection (e.g. in C57BL/6 mice) results from IL-12-dependent production of IFN gamma by Th1/Tc1 cells. In contrast, BALB/c mice succumb to infection because of preferential Th2-type cytokine induction. Infected dendritic cells (DC) represent important sources of IL-12. Genetically determined differences in DC IL-1 alpha/beta production contribute to disease outcome. Whereas the course of disease was not dramatically altered in IL-1RI-/- mice, local administration of IL-1 alpha to infected C57BL/6 mice improved disease outcome. To definitively elucidate the involvement of IL-1 in immunity against leishmaniasis, we now utilized IL-1 alpha/beta-double-deficient C57BL/6 mice. C57BL/6 mice are believed to be a good surrogate model for human, self limited cutaneous leishmaniasis (CL). Leishmania major-infected IL-1 alpha/beta-/- mice were resistant to experimental CL comparable to controls. In addition, DC-based vaccination against leishmaniasis in C57BL/6 mice was independent of IL-1. Thus, in Leishmania-resistant C57BL/6 mice, IL-1 signalling is dispensable for protection. C1 [Kautz-Neu, Kordula; Kostka, Susanna L.; Dinges, Stephanie; von Stebut, Esther] Johannes Gutenberg Univ Mainz, Dept Dermatol, D-55131 Mainz, Germany. [Iwakura, Yoichiro] Univ Tokyo, Inst Med Sci, Ctr Expt Med & Syst Biol, Tokyo, Japan. [Iwakura, Yoichiro] Japan Sci & Technol Agcy, CREST, Saitama, Japan. [Udey, Mark C.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP von Stebut, E (reprint author), Johannes Gutenberg Univ Mainz, Dept Dermatol, Langenbeckstr 1, D-55131 Mainz, Germany. EM vonstebu@uni-mainz.de RI Iwakura, Yoichiro/E-5457-2011 OI Iwakura, Yoichiro/0000-0002-9934-5775 NR 17 TC 16 Z9 16 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD JAN PY 2011 VL 20 IS 1 BP 77 EP 78 DI 10.1111/j.1600-0625.2010.01172.x PG 2 WC Dermatology SC Dermatology GA 695QY UT WOS:000285388900016 PM 20955202 ER PT J AU Bohlhalter, S Abela, E Hallett, M AF Bohlhalter, S. Abela, E. Hallett, M. TI Functional MRI of impaired finger dexterity in Parkinson's disease SO EXPERIMENTAL NEUROLOGY LA English DT Editorial Material ID LIMB-KINETIC APRAXIA; MOVEMENTS; FMRI; ACTIVATION; FREQUENCY; PET C1 [Bohlhalter, S.] Univ Hosp Bern, Inselspital, Div Cognit & Restorat Neurol, Dept Neurol, CH-3010 Bern, Switzerland. [Abela, E.] Kantonsspital St Gallen, Dept Neurol, St Gallen, Switzerland. [Hallett, M.] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Bohlhalter, S (reprint author), Univ Hosp Bern, Inselspital, Div Cognit & Restorat Neurol, Dept Neurol, Anna Seiler Haus, CH-3010 Bern, Switzerland. EM stephan.bohlhalter@insel.ch; hallettm@ninds.nih.gov NR 16 TC 1 Z9 1 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JAN PY 2011 VL 227 IS 1 BP 24 EP 25 DI 10.1016/j.expneurol.2010.11.006 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 708NF UT WOS:000286367800005 PM 21075105 ER PT J AU Ostera, G Tokumasu, F Teixeira, C Collin, N Sa, J Hume, J Kumar, S Ribeiro, J Lukat-Rodgers, GS Rodgers, KR AF Ostera, Graciela Tokumasu, Fuyuki Teixeira, Clarissa Collin, Nicolas Sa, Juliana Hume, Jennifer Kumar, Sanjai Ribeiro, Jose Lukat-Rodgers, Gudrun S. Rodgers, Kenton R. TI Plasmodium falciparum: Nitric oxide modulates heme speciation in isolated food vacuoles SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Protozoa; Plasmodium falciparum; Malaria; Nitric oxide; Heme; Hemozoin; Antimalarials; Food vacuole ID REDUCTIVE NITROSYLATION; SCHISTOSOMA-MANSONI; MALARIA PARASITE; BETA-HEMATIN; HEMOZOIN; COMPLEXES; CRYSTALLIZATION; ADDUCTS; INSECT; NO AB Nitric oxide (NO) and NO-derived reactive nitrogen species (RNS) are present in the food vacuole (FV) of Plasmodium falciparum trophozoites. The product of PFL1555w, a putative cytochrome 65, localizes in the FV membrane, similar to what was previously observed for the product of PF13_0353, a putative cytochrome 65 reductase. These two gene products may contribute to NO generation by denitrification chemistry from nitrate and/or nitrite present in the erythrocyte cytosol. The possible coordination of NO to heme species present in the food vacuole was probed by resonance Raman spectroscopy. The spectroscopic data revealed that in situ generated NO interacts with heme inside the intact FVs to form ferrous heme nitrosyl complexes that influence intra-vacuolar heme solubility. The formation of heme nitrosyl complexes within the FV is a previously unrecognized factor that could affect the equilibrium between soluble and crystallized heme within the FV in vivo. (C) 2010 Elsevier Inc. All rights reserved. C1 [Ostera, Graciela; Tokumasu, Fuyuki; Teixeira, Clarissa; Sa, Juliana; Hume, Jennifer; Ribeiro, Jose] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Collin, Nicolas] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. [Kumar, Sanjai] US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Lukat-Rodgers, Gudrun S.; Rodgers, Kenton R.] N Dakota State U, Dept Chem & Biochem, Fargo, ND 58108 USA. RP Ostera, G (reprint author), Georgetown Univ, Dept Biochem, Washington, DC 20057 USA. EM osterag@georgetown.edu; kent.rodgers@ndsu.edu OI Tokumasu, Fuyuki/0000-0003-2790-1071; Ribeiro, Jose/0000-0002-9107-0818 FU NIH-NIAID [AI072719] FX The authors would like to thank Drs. Thomas Wellems, Jesus Valenzuela, Alan Schechter and F. Ann Walker for their helpful discussions and contributions to this project. This research was supported by the Intramural Research Program of the NIAID, NIH and by NIH-NIAID (AI072719 to K.R.R.). NR 31 TC 8 Z9 8 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD JAN PY 2011 VL 127 IS 1 BP 1 EP 8 DI 10.1016/j.exppara.2010.05.006 PG 8 WC Parasitology SC Parasitology GA 710BV UT WOS:000286486800001 PM 20493843 ER PT J AU Lea, WA Simeonov, A AF Lea, Wendy A. Simeonov, Anton TI Fluorescence polarization assays in small molecule screening SO EXPERT OPINION ON DRUG DISCOVERY LA English DT Review DE competitive-binding assay; drug discovery; enzyme assay; fluorescence anisotropy; fluorescence polarization; high-throughput screening; ligand displacement ID PROTEIN-PROTEIN INTERACTIONS; FUTURE ANTIADHESION DRUGS; POLO-BOX DOMAIN; COUPLED RECEPTORS; BINDING ASSAY; KINASE ASSAY; COMPOUND INTERFERENCE; ANISOTROPY ASSAY; LIGAND-BINDING; INHIBITORS AB Importance of the field: Fluorescence polarization (FP) is a homogeneous method that allows rapid and quantitative analysis of diverse molecular interactions and enzyme activities. This technique has been widely utilized in clinical and biomedical settings, including the diagnosis of certain diseases and monitoring therapeutic drug levels in body fluids. Recent developments in the field have been symbolized by the facile adoption of FP in high-throughput screening and small molecule drug discovery of an increasing range of target classes. Areas covered in this review: The article provides a brief overview of the theoretical foundation of FP, followed by updates on recent advancements in its application for various drug target classes, including GPCRs, enzymes and protein-protein interactions. The strengths and weaknesses of this method, practical considerations in assay design, novel applications and future directions are also discussed. What the reader will gain: The reader is informed of the most recent advancements and future directions of FP application to small molecule screening. Take home message: In addition to its continued utilization in high-throughput screening, FP has expanded into new disease and target areas and has been marked by increased use of labeled small molecule ligands for receptor-binding studies. C1 [Lea, Wendy A.; Simeonov, Anton] NHGRI, NIH, NIH Chem Genom Ctr, Bethesda, MD 20892 USA. RP Simeonov, A (reprint author), NHGRI, NIH, NIH Chem Genom Ctr, Bethesda, MD 20892 USA. EM asimeono@mail.nih.gov FU Molecular Libraries Initiative of the NIH Roadmap for Medical Research; NHGRI, US National Institutes of Health; US Government FX This work was supported, in part, by the Molecular Libraries Initiative of the NIH Roadmap for Medical Research and the Intramural Research Program of NHGRI, US National Institutes of Health. A Simeonov is an employee of, and is supported by the US Government. WA Lea is a US Government Post-doctoral fellow and is also supported by the US Government. NR 113 TC 92 Z9 94 U1 16 U2 96 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1746-0441 J9 EXPERT OPIN DRUG DIS JI Expert. Opin. Drug Discov. PD JAN PY 2011 VL 6 IS 1 BP 17 EP 32 DI 10.1517/17460441.2011.537322 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 697XG UT WOS:000285552500003 PM 22328899 ER PT J AU Freudlsperger, C Burnett, JR Friedman, JA Kannabiran, VR Chen, Z Van Waes, C AF Freudlsperger, Christian Burnett, Jeffrey R. Friedman, Jay A. Kannabiran, Vishnu R. Chen, Zhong Van Waes, Carter TI EGFR-PI3K-AKT-mTOR signaling in head and neck squamous cell carcinomas: attractive targets for molecular-oriented therapy SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE Akt; EGFR; head and neck squamous cell carcinoma; mTOR; PI3K; targeted therapy ID GROWTH-FACTOR RECEPTOR; PROTEIN-KINASE CK2; MULTICENTER PHASE-II; ANTITUMOR-ACTIVITY; PHOSPHOINOSITIDE 3-KINASE; INHIBITOR 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; HEAT-SHOCK-PROTEIN-90 INHIBITOR; REPEAT POLYMORPHISM; MAMMALIAN TARGET; PIK3CA MUTATIONS AB Importance of the field: Recent advances in the understanding of the oncogenesis of head and neck squamous cell carcinomas (HNSCC) have revealed multiple dysregulated signaling pathways. One frequently altered axis is the EGFR-PI3K-Akt-mTOR pathway. This pathway plays a central role in numerous cellular processes including metabolism, cell growth, apoptosis, survival and differentiation, which ultimately contributes to HNSCC progression. Areas covered in this review: Books, journals, databases and websites have been searched to provide a current review on the subject. What the reader will gain: This article reviews the current understanding of EGFR-PI3K-Akt-mTOR signaling in HNSCC, including the impact of both genetic and epigenetic alterations. This review further highlights the potential of targeting this signaling cascade as a promising therapeutic approach in the treatment of HNSCC. Take home message: Genetic alterations of several nodes within this pathway, including both genetic and epigenetic changes, leading to either oncogene activation or inactivation of tumor suppressors have frequently been implicated in HNSCC. Consequently, drugs that target the central nodes of this pathway have become attractive for molecular oriented cancer therapies. Numerous preclinical and clinical studies are being performed in HNSCC; however, more studies are still needed to better understand the biology of this pathway. C1 [Freudlsperger, Christian; Burnett, Jeffrey R.; Friedman, Jay A.; Kannabiran, Vishnu R.; Chen, Zhong; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. [Freudlsperger, Christian] Univ Heidelberg Hosp, Dept Oral & Maxillofacial Surg, Heidelnberg, Germany. RP Van Waes, C (reprint author), Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bldg 10,CRC Rm 4-2732, Bethesda, MD 20892 USA. EM vanwaesc@nidcd.nih.gov FU NIDCD [ZIA-DC-000073] FX Gefitinib (Astra Zeneca) and PI3K-mTOR inhibitors (Pfizer) have been provided for research and clinical trials through material transfer and clinical trials agreements between these companies and the National Cancer Institute or National Institute on Deafness and Other Communication Disorders. This work was supported by NIDCD Intramural Research Project ZIA-DC-000073. C Van Waes and the other authors declare no financial conflict of interest and have received no payment in preparation of this manuscript. NR 115 TC 54 Z9 55 U1 1 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD JAN PY 2011 VL 15 IS 1 BP 63 EP 74 DI 10.1517/14728222.2011.541440 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 693AW UT WOS:000285198000007 PM 21110697 ER PT J AU Uckun, FM Pitt, J Qazi, S AF Uckun, Fatih M. Pitt, Jason Qazi, Sanjive TI JAK3 pathway is constitutively active in B-lineage acute lymphoblastic leukemia SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE Janus kinase 3; leukemia; leukemic B-cell precursors; lymphoma; nanomedicines ID LARGE-CELL LYMPHOMA; ACUTE MEGAKARYOBLASTIC LEUKEMIA; FUNCTIONAL-ANALYSIS; GAMMA-CHAIN; BONE-MARROW; C-MYC; ACTIVATION; RECEPTOR; KINASES; INTERLEUKIN-7 AB In this article, we report that primary leukemic B-cell precursors from B-lineage acute lymphoblastic leukemia (ALL) patients overexpress multiple JAK3-activating cytokines as well as their receptors. We also show that amplified expression of JAK3 pathway genes in B-lineage ALL is associated with steroid resistance and relapse. Our findings further demonstrate that several different diagnostic classes of B-lineage lymphoid malignancies exhibit upregulated expression of JAK3 pathway genes, which are associated with an overexpression of genes for JAK3-stimulatory cytokines with concomitant deficiency of JAK3-inhibitory signaling molecules. Thus, despite the rare occurrence of activating JAK3 mutations, JAK3 appears to be constitutively active and represents a viable molecular target in the treatment of a broad range of B-lineage lymphoid malignancies, including B-lineage ALL. C1 [Uckun, Fatih M.] Univ So Calif, Keck Sch Med, Div Hematol Oncol, Dept Pediat,Childrens Ctr Canc & Blood Dis, Los Angeles, CA 90027 USA. [Uckun, Fatih M.] Childrens Hosp Los Angeles, Inst Pediat Clin Res, Dev Therapeut Program, Los Angeles, CA 90027 USA. [Pitt, Jason] NCI, Gene Silencing Sect, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Qazi, Sanjive] Gustavus Adolphus Coll, Dept Biol, St Peter, MN 56082 USA. [Qazi, Sanjive] Gustavus Adolphus Coll, Bioinformat Program, St Peter, MN 56082 USA. RP Uckun, FM (reprint author), Univ So Calif, Keck Sch Med, Div Hematol Oncol, Dept Pediat,Childrens Ctr Canc & Blood Dis, Los Angeles, CA 90027 USA. EM fmuckun@chla.usc.edu NR 62 TC 5 Z9 6 U1 1 U2 3 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD JAN PY 2011 VL 11 IS 1 BP 37 EP 48 DI 10.1586/ERA.10.203 PG 12 WC Oncology SC Oncology GA 742IM UT WOS:000288935400012 PM 21070101 ER PT J AU Finley, DS Pouliot, F Shuch, B Chin, A Pantuck, A Dekernion, JB Belldegrun, AS AF Finley, David S. Pouliot, Frederic Shuch, Brian Chin, Arnold Pantuck, Alan Dekernion, Jean B. Belldegrun, Arie S. TI Ultrasound-based combination therapy: potential in urologic cancer SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE high-intensity focused ultrasound; immunotherapy; kidney cancer; LOFU; low-intensity focused ultrasound; prostate cancer; pulsed HIFU ID INTENSITY FOCUSED ULTRASOUND; ANTITUMOR IMMUNE-RESPONSES; SQUAMOUS-CELL CARCINOMA; HUMAN DENDRITIC CELLS; SPONTANEOUS REGRESSION; PROSTATE-CANCER; TUMOR-CELLS; T-CELLS; BREAST-CANCER; IMMUNOGENICITY AB Immune-sensitive urologic malignancies include prostate, kidney and bladder cancers. To date, most immunotherapeutic treatments have been applied to advanced metastatic disease. Limited efficacy in this setting is likely due to an excessive disease burden, which overwhelms the capacity of the immune system. Immunotherapy has not been widely utilized in a low-disease-burden state - a setting in which the immune system may be best suited to effectively mount a clinically meaningful response. The emergence of high-intensity focused ultrasound, and more recently, low-intensity focused ultrasound technologies, have demonstrated not only immune-stimulatory effects but also an interesting capacity to alter tissue architecture and cell membrane properties, which may be exploited to increase tumoral uptake of drugs and vaccines. In this article, we review the literature supporting the novel use of ultrasound combination therapy with adjunctive agents in the treatment of urologic malignancy. C1 [Finley, David S.; Chin, Arnold; Pantuck, Alan; Dekernion, Jean B.; Belldegrun, Arie S.] Univ Calif Los Angeles, David Geffen Sch Med, Inst Urol Oncol, Los Angeles, CA 90095 USA. [Pouliot, Frederic] Univ Laval, Serv Urol, Dept Chirurg, Quebec City, PQ, Canada. [Shuch, Brian] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Finley, DS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Inst Urol Oncol, Los Angeles, CA 90095 USA. EM dfinley@mednet.ucla.edu FU US HIFU FX Arie Belldegrun is a member of the US HIFU Board of Directors. US HIFU provided an education grant to the UCLA Institute of Urologic Oncology. 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 59 TC 5 Z9 6 U1 2 U2 5 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD JAN PY 2011 VL 11 IS 1 BP 107 EP 113 DI 10.1586/ERA.10.174 PG 7 WC Oncology SC Oncology GA 742IM UT WOS:000288935400018 PM 21166515 ER PT J AU Vyas, NS Patel, NH Nijran, KS Al-Nahhas, A Puri, BK AF Vyas, Nora S. Patel, Neva H. Nijran, Kuldip S. Al-Nahhas, Adil Puri, Basant K. TI The use of PET imaging in studying cognition, genetics and pharmacotherapeutic interventions in schizophrenia SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE antipsychotics; cognition; COMT; dopamine receptors; memory; PET; prefrontal cortex; schizophrenia; serotonin ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL GLUCOSE-UTILIZATION; ANTERIOR CINGULATE CORTEX; EARLY-ONSET SCHIZOPHRENIA; 5-HT2 RECEPTOR OCCUPANCY; BRAIN TRANSFER CONSTANTS; TIME UPTAKE DATA; WORKING-MEMORY; DOPAMINE RELEASE; BIPOLAR DISORDER AB Positron emission tomography (PET) offers a strategic imaging platform to provide a map of functional neural correlates associated with the underlying cognitive deficits in schizophrenia. It enables regional cerebral glucose metabolism and dopaminergic and serotonergic receptor function to be studied. PET neuroimaging can therefore be used in drug development and to study putative treatments. Recent PET studies of the first-generation antipsychotics flupentixol and haloperidol, and of the second-generation antipsychotics risperidone, aripiprazole, quetiapine, sertindole, ziprasidone, paliperidone and olanzapine, have been carried out; modulation of limbic circuitry has been found to be a predictor of treatment response. PET can also be used to predict and monitor likely extrapyramidal side effects from antipsychotic treatment. PET and neuropsychological testing can together also allow the study of putative molecular genetic changes associated with schizophrenia. Advances in the imaging, cognition and molecular genetics are likely to lead to the development of future diagnostics, treatments and novel pharmacological agents. C1 [Vyas, Nora S.] Kings Coll London, Inst Psychiat, Div Psychol Med & Psychiat, London SE5 8AF, England. [Vyas, Nora S.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Vyas, Nora S.; Patel, Neva H.; Nijran, Kuldip S.; Al-Nahhas, Adil; Puri, Basant K.] Imperial Coll Healthcare NHS Trust, London, England. [Puri, Basant K.] Univ Limerick, Limerick, Ireland. RP Vyas, NS (reprint author), Kings Coll London, Inst Psychiat, Div Psychol Med & Psychiat, Box PO66,De Crespigny Pk, London SE5 8AF, England. EM nora.vyas@kcl.ac.uk RI Vyas, Nora/C-3570-2011 NR 96 TC 11 Z9 11 U1 0 U2 8 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD JAN PY 2011 VL 11 IS 1 BP 37 EP 51 DI 10.1586/ERN.10.160 PG 15 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 737PX UT WOS:000288581800011 PM 21158554 ER PT J AU Falzarano, D Geisbert, TW Feldmann, H AF Falzarano, Darryl Geisbert, Thomas W. Feldmann, Heinz TI Progress in filovirus vaccine development: evaluating the potential for clinical use SO EXPERT REVIEW OF VACCINES LA English DT Review DE Ebola virus; filovirus; Marburg virus; postexposure; prophylactic; vaccine ID EBOLA-VIRUS-INFECTION; VESICULAR-STOMATITIS-VIRUS; EQUINE ENCEPHALITIS-VIRUS; PROTECTS NONHUMAN-PRIMATES; ATTENUATED RECOMBINANT VACCINE; HUMAN-PAPILLOMAVIRUS VACCINES; HEMORRHAGIC-FEVER; MARBURG VIRUS; GUINEA-PIGS; REPLICATION-COMPETENT AB Marburg and Ebola viruses cause severe hemorrhagic fever in humans and nonhuman primates. Currently, there are no effective treatments and no licensed vaccines; although a number of vaccine platforms have proven successful in animal models. The ideal filovirus vaccine candidate should be able to provide rapid protection following a single immunization, have the potential to work postexposure and be cross-reactive or multivalent against all Marburg virus strains and all relevant Ebola virus species and strains. Currently, there are multiple platforms that have provided prophylactic protection in nonhuman primates, including DNA, recombinant adenovirus serotype 5, recombinant human parainfluenza virus 3 and virus-like particles. In addition, a single platform, recombinant vesicular stomatitis virus, has demonstrated both prophylactic and postexposure protection in nonhuman primates. These results demonstrate that achieving a vaccine that is protective against filoviruses is possible; the challenge now is to prove its safety and efficacy in order to obtain a vaccine that is ready for human use. C1 [Falzarano, Darryl; Feldmann, Heinz] NIAID, Virol Lab, Rocky Mt Labs, Div Intramural Res,NIH, Hamilton, MT 59840 USA. [Geisbert, Thomas W.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX USA. [Geisbert, Thomas W.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX USA. [Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. RP Feldmann, H (reprint author), NIAID, Virol Lab, Rocky Mt Labs, Div Intramural Res,NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM heinrich.feldmann@nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH) FX The authors would like to thank the many people in the field for their contributions and helpful discussions. They would also like to thank Anita Mora (Rocky Mountain Laboratories, NIAID) for assistance with production of FIGURE 1. Research on filoviruses is supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH). NR 127 TC 53 Z9 54 U1 3 U2 21 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD JAN PY 2011 VL 10 IS 1 BP 63 EP 77 DI 10.1586/ERV.10.152 PG 15 WC Immunology SC Immunology GA 742IN UT WOS:000288935500014 PM 21162622 ER PT B AU Bugge, TH Behrendt, N AF Bugge, Thomas H. Behrendt, Niels BE Parks, WC Mecham, RP TI Cooperation Between Proteolysis and Endocytosis in Collagen Turnover SO EXTRACELLULAR MATRIX DEGRADATION SE Biology of Extracellular Matrix LA English DT Article; Book Chapter ID RECEPTOR-ASSOCIATED PROTEIN/ENDO180; PLASMINOGEN-ACTIVATOR RECEPTOR; 3-DIMENSIONAL EXTRACELLULAR-MATRIX; MACROPHAGE MANNOSE RECEPTOR; CATHEPSIN-K DEFICIENCY; NATIVE TYPE-I; INTRACELLULAR COLLAGEN; BONE-RESORPTION; METALLOPROTEINASE ACTIVITY; DENATURED COLLAGEN AB Studies conducted as of today collectively suggest that the degradation of collagen in mammals is carried out in equal parts within the extracellular environment, via the action of a limited number of secreted or plasma membrane proteases with the unique ability to cleave native collagen, and intracellularly, via an assortment of lysosomal cathepsins that degrade collagen made available through its uptake by specific collagen endocytic receptors. Emerging evidence indicates that these two principal mechanisms for collagen degradation cooperate to form a single pathway that executes the sequential and complete degradation of collagen during both physiological tissue remodeling and pathological remodeling, including tumor progression. The chapter summarizes the prevailing paradigms regarding the turnover of this abundant extracellular matrix molecule. C1 [Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. [Behrendt, Niels] Rigshosp, Finsen Lab, Sect 3735, Copenhagen Bioctr, DK-2200 Copenhagen N, Denmark. RP Bugge, TH (reprint author), Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. EM thomas.bugge@nih.gov; niels.behrendt@finsenlab.dk NR 101 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-642-16860-4 J9 BIOL EXTRACELL MATR PY 2011 BP 53 EP 74 DI 10.1007/978-3-642-16861-1_3 D2 10.1007/978-3-642-16861-1 PG 22 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA BVE59 UT WOS:000291321500003 ER PT J AU Catherino, WH Parrott, E Segars, J AF Catherino, William H. Parrott, Estella Segars, James TI Proceedings from the National Institute of Child Health and Human Development Conference on the Uterine Fibroid Research Update Workshop SO FERTILITY AND STERILITY LA English DT Editorial Material DE Leiomyoma; myometrium; epidemiology; etiology; therapy; clinical trials ID SMOOTH-MUSCLE-CELLS; LEIOMYOMA CELLS; EXTRACELLULAR-MATRIX; EXPRESSION; PROLIFERATION; WOMEN AB The purpose of the National Institutes of Health conference Fibroid Research Workshop in September 2007 was to bring Eunice Kennedy Shriver National Institute of Child Health and Human Development-funded fibroid investigators together to discuss basic science and clinical research advances on uterine leiomyomata. General topics included advances in epidemiology, etiology, therapeutic approaches, and clinical trial challenges; suggestions for advancement of basic understanding, clinical intervention, clinical trials, and future directions were highlighted. (Fertil Steril (R) 2011; 95: 9-12. (C)2011 by American Society for Reproductive Medicine.) C1 [Catherino, William H.; Segars, James] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. [Catherino, William H.; Segars, James] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, US Dept HHS, Bethesda, MD USA. [Parrott, Estella] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Med Gynecol Program, NIH, US Dept HHS, Bethesda, MD USA. RP Catherino, WH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bldg A,Room 3078,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM catheriw@mail.nih.gov FU Intramural NIH HHS [ZIA HD008737-10] NR 27 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2011 VL 95 IS 1 BP 9 EP 12 DI 10.1016/j.fertnstert.2010.08.049 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 695ZL UT WOS:000285411600008 PM 20883986 ER PT J AU Csokmay, JM Hill, MJ Maguire, M Payson, MD Fujimoto, VY Armstrong, AY AF Csokmay, John M. Hill, Micah J. Maguire, Marcy Payson, Mark D. Fujimoto, Victor Y. Armstrong, Alicia Y. TI Are there ethnic differences in pregnancy rates in African-American versus white women undergoing frozen blastocyst transfers? SO FERTILITY AND STERILITY LA English DT Article DE Ethnicity; racial; disparities; live birth rate; infertility; IVF; ART ID ASSISTED REPRODUCTIVE TECHNOLOGY; BLACK-WOMEN; OUTCOMES; CARE AB Objective: To determine whether frozen-thawed blastocyst transfer pregnancy rates (PR) are lower in African-American compared with white women. Design: Retrospective review of frozen blastocyst cycles. Setting: University-based assisted reproductive technology (ART) program. Patient(s): All patients who underwent a frozen blastocyst transfer between 2003 and 2008. Intervention: None. Main Outcome Measure(s): Live birth rate. Result(s): One hundred sixty-nine patients underwent transfer of a frozen-thawed blastocyst. African-American women had a higher incidence of leiomyoma (40% vs. 10%) and tubal and uterine factor infertility. There was no difference in the live birth rate for African-American patients (28.0%) compared with white patients (30.2%). Of the patients who underwent a frozen-thawed blastocyst transfer, 58% (n = 98) had their fresh, autologous IVF cycle, which produced the cryopreserved blastocyst, at Walter Reed Medical Center. A higher peak serum E(2) level was noted in African-American patients (5,355 pg/mL) compared with white patients (4,541 pg/mL). During the fresh cycle, the live birth rates between African-American and white patients were significantly different at 16.7% versus 39.7%, respectively. Conclusion(s): Live birth rates after frozen blastocyst transfer are not different between African-American and white women despite a fourfold higher incidence of leiomyomas in African-American women. (Fertil Steril (R) 2011; 95: 89-93. (C)2011 by American Society for Reproductive Medicine.) C1 [Csokmay, John M.; Hill, Micah J.; Maguire, Marcy; Payson, Mark D.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Csokmay, John M.; Hill, Micah J.; Maguire, Marcy; Armstrong, Alicia Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. [Fujimoto, Victor Y.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. RP Armstrong, AY (reprint author), NICHD, NIH, 10 Ctr Dr,Bldg 10,CRC 1E-3140, Bethesda, MD 20892 USA. EM armstroa@mail.nih.gov FU National Institute of Child Health and Human Development-Uniformed Services University of the Health Sciences FX The authors acknowledge Jacques Cohen, Ph.D., Aidita James, Ph.D., Sasha Hennessey, B. S., Frederick Larsen, M. D., Donna Hoover, R.N., Darshana Naik, R.N., and fellows in the Reproductive Endocrine Fellowship at National Institute of Child Health and Human Development-Uniformed Services University of the Health Sciences for their support and contributions. NR 17 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2011 VL 95 IS 1 BP 89 EP 93 DI 10.1016/j.fertnstert.2010.03.050 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 695ZL UT WOS:000285411600023 PM 20451186 ER PT J AU Whitcomb, BW Turzanski-Fortner, R Richter, KS Kipersztok, S Stillman, RJ Levy, MJ Levens, ED AF Whitcomb, Brian W. Turzanski-Fortner, Renee Richter, Kevin S. Kipersztok, Simon Stillman, Robert J. Levy, Michael J. Levens, Eric D. TI Contribution of male age to outcomes in assisted reproductive technologies SO FERTILITY AND STERILITY LA English DT Article DE Male age; IVF; donor oocyte; live birth rates ID OOCYTE DONATION; PATERNAL AGE; SEMEN QUALITY; MATERNAL AGE; INFERTILITY; FERTILITY; RISK; RATES AB Objective: To evaluate the relationship between male age and pregnancy outcome in donor oocyte assisted reproductive technology cycles. Design: Retrospective cohort. Setting: Private IVF center. Patient(s): A total of 1,392 donor cycles from 1,083 female recipients and their male partners. Intervention(s): Oocyte donor cycles. Main Outcome Measure(s): Live birth. Result(s): Increasing male age was associated with semen parameters including volume and motility; however, male age was not observed to have a statistically significant association with likelihood of live birth in donor cycles after adjustment for female recipient age. Conclusion(s): When treatment cycle number and female recipient age were taken into account, male age had no significant association with pregnancy outcomes in assisted reproductive technology donor cycles in this study population. (Fertil Steril(R) 2011;95:147-51. (C) 2011 by American Society for Reproductive Medicine.) C1 [Levens, Eric D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, CRC, Bethesda, MD 20892 USA. [Whitcomb, Brian W.; Turzanski-Fortner, Renee] Univ Massachusetts, Div Biostat & Epidemiol, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. [Richter, Kevin S.; Kipersztok, Simon; Stillman, Robert J.; Levy, Michael J.; Levens, Eric D.] Shady Grove Reprod Sci Ctr, Rockville, MD USA. RP Levens, ED (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, CRC, Bldg 10,Room E1-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM eric.levens@integramed.com FU Program in Reproductive and Adult Endocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland FX This research was supported in part by the Program in Reproductive and Adult Endocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of Health and Human Services. NR 21 TC 21 Z9 26 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2011 VL 95 IS 1 BP 147 EP 151 DI 10.1016/j.fertnstert.2010.06.039 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 695ZL UT WOS:000285411600033 PM 20663496 ER PT J AU Naka, KK Kalantaridou, SN Kravariti, M Bechlioulis, A Kazakos, N Calis, KA Makrigiannakis, A Katsouras, CS Chrousos, GP Tsatsoulis, A Michalis, LK AF Naka, Katerina K. Kalantaridou, Sophia N. Kravariti, Maria Bechlioulis, Aris Kazakos, Nikolaos Calis, Karim A. Makrigiannakis, Antonis Katsouras, Christos S. Chrousos, George P. Tsatsoulis, Agathocles Michalis, Lampros K. TI Effect of the insulin sensitizers metformin and pioglitazone on endothelial function in young women with polycystic ovary syndrome: a prospective randomized study SO FERTILITY AND STERILITY LA English DT Article DE Polycystic ovary syndrome; endothelial function; metformin; pioglitazone; atherosclerosis ID NORMAL-WEIGHT WOMEN; POSTMENOPAUSAL WOMEN; DYSFUNCTION; RESISTANCE; RISK; ATHEROSCLEROSIS; OBESE; ROSIGLITAZONE; IMPROVEMENT; PREDICTORS AB Objective: To compare the effect of two different insulin sensitizers, metformin and pioglitazone, on endothelial function in women with polycystic ovary syndrome (PCOS). Design: Prospective randomized study. Setting: University Hospital endocrinology outpatient clinic. Patient(s): Young women with PCOS (aged 23.3 +/- 4.9 years). Intervention(s): Patients were assigned randomly to no treatment (n = 14), metformin 850 mg two times per day (n = 15), and pioglitazone 30 mg daily (n = 14) for 6 months. Healthy age-and body mass index-matched women served as controls (n = 14). Main Outcome Measure(s): Brachial artery flow-mediated dilation was studied at baseline and 6 months. Result(s): Women with PCOS had higher insulin resistance and hyperandrogenism indices and lower flow-mediated dilation compared with controls. The three groups of women with PCOS did not differ at baseline. No differences were observed at follow-up in women who received no treatment. Metformin and pioglitazone improved flow-mediated dilation to a similar extent, restoring it to normal values at 6 months. Both insulin sensitizers induced favorable changes in insulin resistance and hyperandrogenism indices in women with PCOS. Independent predictors of flow-mediated dilation improvement at 6 months were treatment with insulin sensitizers and reduction in insulin resistance. Conclusion(s): In young women with PCOS, treatment with metformin or pioglitazone for 6 months induces a similar beneficial effect on endothelial function; this may be partially attributed to an improvement in insulin resistance. Further research is needed to investigate whether treatment with insulin sensitizers in women with PCOS also reduces cardiovascular risk. (Fertil Steril(R) 2011;95:203-9. (C) 2011 by American Society for Reproductive Medicine.) C1 [Kravariti, Maria; Tsatsoulis, Agathocles] Univ Ioannina, Dept Endocrinol, GR-45110 Ioannina, Greece. [Naka, Katerina K.; Bechlioulis, Aris; Kazakos, Nikolaos; Katsouras, Christos S.; Michalis, Lampros K.] Univ Ioannina, Michaelid Cardiac Ctr, GR-45110 Ioannina, Greece. [Naka, Katerina K.; Katsouras, Christos S.; Michalis, Lampros K.] Univ Ioannina, Dept Cardiol, GR-45110 Ioannina, Greece. [Kalantaridou, Sophia N.] Univ Ioannina, Dept Obstet & Gynecol, GR-45110 Ioannina, Greece. [Calis, Karim A.] NIH, Dept Pharm, Clin Res Ctr, Bethesda, MD 20892 USA. [Makrigiannakis, Antonis] Univ Crete, Dept Obstet & Gynecol, Crete, NE USA. [Makrigiannakis, Antonis] Univ Athens, Dept Pediat 1, Athens, Greece. RP Tsatsoulis, A (reprint author), Univ Ioannina, Dept Endocrinol, GR-45110 Ioannina, Greece. EM atsatsou@uoi.gr RI Bechlioulis, Aris/D-4814-2011 NR 32 TC 26 Z9 28 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2011 VL 95 IS 1 BP 203 EP 209 DI 10.1016/j.fertnstert.2010.06.058 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 695ZL UT WOS:000285411600042 PM 20684955 ER PT J AU Baird, DD Garrett, TA Laughlin, SK Davis, B Semelka, RC Peddada, SD AF Baird, Donna Day Garrett, Tiana A. Laughlin, Shannon K. Davis, Barbara Semelka, Richard C. Peddada, Shyamal D. TI Short-term change in growth of uterine leiomyoma: tumor growth spurts SO FERTILITY AND STERILITY LA English DT Article DE Uterine leiomyoma; tumor growth; fibroid size; ethnic disparity; magnetic resonance imaging; longitudinal study; short-term variability ID NATURAL-HISTORY; UNITED-STATES; RENAL MASSES; HYSTERECTOMY AB Objective: To describe the short-term changes in growth of uterine leiomyomas (fibroids). Design: Prospective observational study. Setting: University research center. Patient(s): Premenopausal women with fibroids (18 blacks and 18 whites) recruited through a physician network and community outreach. Intervention(s): Not applicable. Main Outcome Measure(s): The volumes of 101 fibroids were measured at enrollment, 3, 6, and 12 months with magnetic resonance imaging, resulting in three interval-specific growth rates. Growth spurts were defined by interval growth rates >= 30% per 3 months and substantially greater than during other intervals of observation. An overall measure of short-term change in fibroid growth was calculated as the variance of the three interval-specific growth rates. Result(s): Growth spurts were observed in 37 of the 101 fibroids, a prevalence nearly tenfold higher than that attributable to potential measurement error. Fibroids from the same woman did not have similar short-term growth, nor were woman-specific factors (age, race/ethnicity, parity, body mass) or the fibroid position in the uterus important. However, large fibroids (>5 cm diameter) had less short-term change than smaller fibroids. Conclusion(s): Short spurts of growth are common for fibroids, suggesting that tumor biology may change rapidly. (Fertil Steril(R) 2011;95:242-6. (C) 2011 by American Society for Reproductive Medicine.) C1 [Baird, Donna Day; Laughlin, Shannon K.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Davis, Barbara] Natl Inst Environm Hlth Sci, Lab Womens Hlth, Res Triangle Pk, NC 27709 USA. [Peddada, Shyamal D.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Garrett, Tiana A.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Semelka, Richard C.] Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. RP Baird, DD (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, MD A3-05, Res Triangle Pk, NC 27709 USA. EM baird@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012; Baird, Donna/D-5214-2017 OI Baird, Donna/0000-0002-5544-2653 FU National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health [Z01ES 101663-05]; National Center on Minority Health and Health Disparities [MO1RR00046]; NIEHS [N01-ES-95446, 273-01-C-0157] FX Supported by the Intramural Research Program of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (Z01ES 101663-05), with partial funding from the National Center on Minority Health and Health Disparities grant no. MO1RR00046 and NIEHS contract nos. N01-ES-95446 and 273-01-C-0157. NR 17 TC 20 Z9 20 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2011 VL 95 IS 1 BP 242 EP 246 DI 10.1016/j.fertnstert.2010.05.011 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 695ZL UT WOS:000285411600049 PM 21168581 ER PT J AU Maguire, M Csokmay, J Segars, J Payson, M Armstrong, A AF Maguire, Marcy Csokmay, John Segars, James Payson, Mark Armstrong, Alicia TI Enough is enough! Patients who do not conceive on 600 IU/d of gonadotropins show no improvement from an additional 150 IU of LH activity SO FERTILITY AND STERILITY LA English DT Editorial Material DE Luteinizing hormone; gonadotropin dose; pregnancy rate; miscarriage rate; cancellation rate ID IN-VITRO FERTILIZATION; POOR RESPONDERS; HORMONE; DOSAGE; FSH AB Studies have suggested that supplemental LH improves outcomes in assisted reproductive technology (ART) cycles. In this retrospective review, an additional 150 IU of LH activity did not improve ART outcomes in women undergoing a second round of IVF/ intracytoplasmic sperm injection (ICSI) after an initial failed cycle using 600 IU of gonadotropins. (Fertil Steril (R) 2011; 95:372-3. (c) 2011 by American Society for Reproductive Medicine.) C1 [Maguire, Marcy] NICHD, Program Reprod & Adult Endocrinol, NIH, Walter Reed Army Med Ctr,Natl Naval Med Ctr,CRC, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Maguire, M (reprint author), NICHD, Program Reprod & Adult Endocrinol, NIH, Walter Reed Army Med Ctr,Natl Naval Med Ctr,CRC, Bldg 10,Room 1E-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM maguiremf@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 8 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2011 VL 95 IS 1 BP 372 EP 373 DI 10.1016/j.fertnstert.2010.08.020 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 695ZL UT WOS:000285411600098 PM 20850732 ER PT J AU Nagrani, SR Levens, ED Baxendale, V Boucheron, C Chan, WY Rennert, OM AF Nagrani, Sohan R. Levens, Eric D. Baxendale, Vanessa Boucheron, Catherine Chan, Wai Yee Rennert, Owen M. TI Methylation patterns of Brahma during spermatogenesis and oogenesis: potential implications SO FERTILITY AND STERILITY LA English DT Editorial Material DE Smarca2; Sma2; Brahma; Brm; methylation; CpG island; gametogenesis; chromatin remodeling; SWI/SNF complex; ART ID MALE GERM-CELLS; DNA METHYLATION; SERIAL ANALYSIS; CANCER; COMPLEX; GENOME; LINE; BRM AB To compare methylation profiles and expression levels of Brahma at different stages of spermatogenesis, and to identify the methylation pattern during oogenesis, we analyzed gene expression and methylation patterns in murine germ cells at various developmental stages. The methylation levels of CpG islands within Brahma increased during spermatogenesis and decreased during oogenesis. This change in methylation pattern correlates with the change in expression of Brahma during spermatogenesis. As the degree of methylation increases, the expression decreases. The change in methylation is opposite during oogenesis, which suggests opposite expression levels. (Fertil Steril (R) 2011;95:382-4. (C) 2011 by American Society for Reproductive Medicine.) C1 [Nagrani, Sohan R.] NICHHD, Lab Clin & Dev Genom, NIH, Bethesda, MD 20814 USA. [Levens, Eric D.; Baxendale, Vanessa; Boucheron, Catherine; Chan, Wai Yee; Rennert, Owen M.] NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20814 USA. RP Nagrani, SR (reprint author), NICHHD, Lab Clin & Dev Genom, NIH, 49 Convent Dr,Room 2C08, Bethesda, MD 20814 USA. EM nagranisr@mail.nih.gov FU Intramural NIH HHS [NIH0014330077, ]; PHS HHS [NIH0014330077] NR 19 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2011 VL 95 IS 1 BP 382 EP 384 DI 10.1016/j.fertnstert.2010.05.064 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 695ZL UT WOS:000285411600101 PM 20719309 ER PT J AU Coates, PM Meyers, CM AF Coates, Paul M. Meyers, Catherine M. TI The National Institutes of Health investment in research on botanicals SO FITOTERAPIA LA English DT Review DE National Institutes of Health; Herbs; Botanicals; Federal funding for research ID REFERENCE MATERIALS PROGRAM; DIETARY-SUPPLEMENTS AB The Office of Dietary Supplements (ODS) and the National Center for Complementary and Alternative Medicine (NCCAM) were both established by Congress in the 1990s. ODS aims to strengthen knowledge and understanding of dietary supplements (DS). NCCAM promotes exploration of complementary and alternative medicine in the context of rigorous science. Together, they developed the Botanical Research Centers Program to promote interdisciplinary study of botanicals, particularly those found in DS, by supporting research activities ranging from plant and characterization to preclinical and early-phase clinical studies. These Centers are part of the coordinated efforts of ODS and NCCAM to enhance botanical research. Published by Elsevier B.V. C1 [Coates, Paul M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Meyers, Catherine M.] NIH, Natl Ctr Complementary & Alternat Med, Off Clin & Regulatory Affairs, Bethesda, MD 20892 USA. RP Coates, PM (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Suite 3B01, Bethesda, MD 20892 USA. EM coatesp@od.nih.gov FU Intramural NIH HHS [Z99 OD999999] NR 5 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0367-326X J9 FITOTERAPIA JI Fitoterapia PD JAN PY 2011 VL 82 IS 1 SI SI BP 11 EP 13 DI 10.1016/j.fitote.2010.11.013 PG 3 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 724HS UT WOS:000287567300003 PM 21075178 ER PT J AU Betz, JM Brown, PN Roman, MC AF Betz, Joseph M. Brown, Paula N. Roman, Mark C. TI Accuracy, precision, and reliability of chemical measurements in natural products research SO FITOTERAPIA LA English DT Review DE Accuracy; Precision; Validation; Analytical methods; Natural products; Herbals ID EPHEDRINE-TYPE ALKALOIDS; DIETARY-SUPPLEMENTS AB Natural products chemistry is the discipline that lies at the heart of modern pharmacognosy. The field encompasses qualitative and quantitative analytical tools that range from spectroscopy and spectrometry to chromatography. Among other things, modern research on crude botanicals is engaged in the discovery of the phytochemical constituents necessary for therapeutic efficacy, including the synergistic effects of components of complex mixtures in the botanical matrix. In the phytomedicine field, these botanicals and their contained mixtures are considered the active pharmaceutical ingredient (API), and pharmacognosists are increasingly called upon to supplement their molecular discovery work by assisting in the development and utilization of analytical tools for assessing the quality and safety of these products. Unlike single-chemical entity APIs, botanical raw materials and their derived products are highly variable because their chemistry and morphology depend on the genotypic and phenotypic variation, geographical origin and weather exposure, harvesting practices, and processing conditions of the source material. Unless controlled, this inherent variability in the raw material stream can result in inconsistent finished products that are under-potent, over-potent, and/or contaminated. Over the decades, natural product chemists have routinely developed quantitative analytical methods for phytochemicals of interest. Quantitative methods for the determination of product quality bear the weight of regulatory scrutiny. These methods must be accurate, precise, and reproducible. Accordingly, this review discusses the principles of accuracy (relationship between experimental and true value), precision (distribution of data values), and reliability in the quantitation of phytochemicals in natural products. Published by Elsevier B.V. C1 [Betz, Joseph M.] US Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD 20892 USA. [Brown, Paula N.] British Columbia Inst Technol, Ctr Appl Res & Innovat, Burnaby, BC V5G 3H2, Canada. [Roman, Mark C.] Tampa Bay Analyt Res Inc, Largo, FL 33777 USA. RP Betz, JM (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Suite 3B01, Bethesda, MD 20892 USA. EM betzj@od.nih.gov FU Intramural NIH HHS [Z99 OD999999] NR 35 TC 33 Z9 34 U1 1 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0367-326X J9 FITOTERAPIA JI Fitoterapia PD JAN PY 2011 VL 82 IS 1 SI SI BP 44 EP 52 DI 10.1016/j.fitote.2010.09.011 PG 9 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 724HS UT WOS:000287567300008 PM 20884340 ER PT B AU Stetler-Stevenson, M AF Stetler-Stevenson, Maryalice BA Ortolani, C BF Ortolani, C TI Antigens SO FLOW CYTOMETRY OF HEMATOLOGICAL MALIGNANCIES LA English DT Article; Book Chapter ID CHRONIC-LYMPHOCYTIC-LEUKEMIA; ACUTE-LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; T-CELL LYMPHOMA; NATURAL-KILLER-CELL; FLOW-CYTOMETRIC ANALYSIS; ACUTE PROMYELOCYTIC LEUKEMIA; HUMAN-BONE-MARROW; TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE; HUMAN PERIPHERAL-BLOOD C1 NCI, Flow Cytometry Lab, NIH, Bethesda, MD 20892 USA. RP Stetler-Stevenson, M (reprint author), NCI, Flow Cytometry Lab, NIH, Bethesda, MD 20892 USA. NR 1744 TC 0 Z9 0 U1 2 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-4443-9804-5; 978-1-4443-3588-0 PY 2011 BP 1 EP 157 D2 10.1002/9781444398069 PG 157 WC Oncology; Hematology SC Oncology; Hematology GA BA6IY UT WOS:000337155100004 ER PT B AU Stetler-Stevenson, M AF Stetler-Stevenson, Maryalice BA Ortolani, C BF Ortolani, C TI Flow Cytometry of Hematological Malignancies Foreword SO FLOW CYTOMETRY OF HEMATOLOGICAL MALIGNANCIES LA English DT Editorial Material; Book Chapter C1 NCI, Flow Cytometry Lab, NIH, Bethesda, MD 20892 USA. RP Stetler-Stevenson, M (reprint author), NCI, Flow Cytometry Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-4443-9804-5; 978-1-4443-3588-0 PY 2011 BP VII EP VII D2 10.1002/9781444398069 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA BA6IY UT WOS:000337155100001 ER PT B AU Stetler-Stevenson, M AF Stetler-Stevenson, Maryalice BA Ortolani, C BF Ortolani, C TI Flow Cytometry of Hematological Malignancies Foreword SO FLOW CYTOMETRY OF HEMATOLOGICAL MALIGNANCIES LA English DT Editorial Material; Book Chapter C1 NCI, Flow Cytometry Lab, NIH, Bethesda, MD 20892 USA. RP Stetler-Stevenson, M (reprint author), NCI, Flow Cytometry Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-4443-9804-5; 978-1-4443-3588-0 PY 2011 BP IX EP IX D2 10.1002/9781444398069 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA BA6IY UT WOS:000337155100002 ER PT B AU Stetler-Stevenson, M AF Stetler-Stevenson, Maryalice BA Ortolani, C BF Ortolani, C TI Flow Cytometry of Hematological Malignancies Preface and acknowledgments SO FLOW CYTOMETRY OF HEMATOLOGICAL MALIGNANCIES LA English DT Editorial Material; Book Chapter C1 NCI, Flow Cytometry Lab, NIH, Bethesda, MD 20892 USA. RP Stetler-Stevenson, M (reprint author), NCI, Flow Cytometry Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-4443-9804-5; 978-1-4443-3588-0 PY 2011 BP XI EP XI D2 10.1002/9781444398069 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA BA6IY UT WOS:000337155100003 ER PT B AU Stetler-Stevenson, M AF Stetler-Stevenson, Maryalice BA Ortolani, C BF Ortolani, C TI Diseases SO FLOW CYTOMETRY OF HEMATOLOGICAL MALIGNANCIES LA English DT Article; Book Chapter ID CHRONIC-LYMPHOCYTIC-LEUKEMIA; T-CELL-LYMPHOMA; ACUTE-LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; OF-THE-LITERATURE; MARGINAL ZONE LYMPHOMA; CHRONIC MYELOGENOUS LEUKEMIA; FLOW-CYTOMETRIC ANALYSIS; NON-HODGKINS-LYMPHOMAS C1 NCI, Flow Cytometry Lab, NIH, Bethesda, MD 20892 USA. RP Stetler-Stevenson, M (reprint author), NCI, Flow Cytometry Lab, NIH, Bethesda, MD 20892 USA. NR 1489 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-4443-9804-5; 978-1-4443-3588-0 PY 2011 BP 159 EP 300 D2 10.1002/9781444398069 PG 142 WC Oncology; Hematology SC Oncology; Hematology GA BA6IY UT WOS:000337155100005 ER PT S AU Telford, WG Komoriya, A Packard, BZ Bagwell, CB AF Telford, William G. Komoriya, Akira Packard, Beverly Z. Bagwell, C. Bruce BE Hawley, TS Hawley, RG TI Multiparametric Analysis of Apoptosis by Flow Cytometry SO FLOW CYTOMETRY PROTOCOLS, THIRD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Apoptosis; Caspasc; Flow cytometry; Annexin V; 7-Aminoactinomycin D; Propidium iodide; Pacific Blue; Hoechst 33258 ID LASER-SCANNING CYTOMETRY; FLUOROCHROME-LABELED INHIBITORS; CELL-DEATH; CASPASE ACTIVITY; ACTIVATION; THYMOCYTES; BINDING; ICE AB Flow cytometry is the most widely used technology for analyzing apoptosis. The multiparametric nature of flow cytometry allows several apoptotic characteristics to be combined in a single sample, making it a powerful tool for analyzing the complex progression of apoptotic death. This chapter provides guidelines for combining caspase detection, annexin V binding, DNA dye exclusion, and other single apoptotic assays into multiparametric assays. This approach to analyzing apoptosis provides far more information than single parameter assays that provide only an ambiguous "percent apoptotic" result, given that multiple early, intermediate and late apoptotic stages can be visualized simultaneously. This multiparametric approach is also amenable to a variety of flow cytometric instrumentation, both old and new. C1 [Telford, William G.] NCI, FAGS Core Facilty, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Komoriya, Akira; Packard, Beverly Z.] OncoImmunin Inc, Gaithersburg, MD USA. [Bagwell, C. Bruce] Ver Software House, Topsham, ME USA. RP Telford, WG (reprint author), NCI, FAGS Core Facilty, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 22 TC 11 Z9 11 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61737-949-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 699 SI 3rd BP 203 EP 227 DI 10.1007/978-1-61737-950-5_10 D2 10.1007/978-1-61737-950-5 PG 25 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BSR17 UT WOS:000285531800010 PM 21116985 ER PT S AU Calvo, KR Mccoy, CS Stetler-Stevenson, M AF Calvo, Katherine R. McCoy, Catharine S. Stetler-Stevenson, Maryalice BE Hawley, TS Hawley, RG TI Flow Cytometry Immunophenotyping of Hematolymphoid Neoplasia SO FLOW CYTOMETRY PROTOCOLS, THIRD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Leukemia; Lymphoma; Myelodysplastic syndrome; Immunophenotype; Prognosis ID CONSENSUS RECOMMENDATIONS; T-CELL; EXPRESSION; LEUKEMIA AB Flow cytometry immunophenotyping (FCI) of hematolymphoid specimens is a powerful tool in clinical medicine aiding in the accurate diagnosis and subclassification of acute and chronic leukemias, non-Hodgkin lymphomas, myelodysplasia, and other hematolymphoid neoplastic processes. Multiple flow cytometric strategies arc used to evaluate hematolymphoid populations, including identification of neoplastic populations with aberrant immunophenotypes, abnormal maturation patterns, monotypic kappa/lambda light chain expression, restricted V-beta expression, and abnormal light scatter properties. In this chapter, we present a general approach to analyze hematolymphoid populations. Specimen handling, gating strategies, and appropriate antibody panels for flow cytometric detection of abnormal hematologic populations are presented. C1 [Calvo, Katherine R.] NIH, Dept Lab Med, Hematol Sect, Ctr Clin, Bethesda, MD 20892 USA. [McCoy, Catharine S.] NCI, Flow Cytometry Lab, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Stetler-Stevenson, Maryalice] NCI, Flow Cytometry Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Calvo, KR (reprint author), NIH, Dept Lab Med, Hematol Sect, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. OI Calvo, Katherine/0000-0002-0771-4191 NR 15 TC 6 Z9 7 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61737-949-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 699 SI 3rd BP 295 EP 316 DI 10.1007/978-1-61737-950-5_14 D2 10.1007/978-1-61737-950-5 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BSR17 UT WOS:000285531800014 PM 21116989 ER PT S AU Zaidi, MR Day, CP Merlino, G AF Zaidi, M. Raza Day, Chi-Ping Merlino, Glenn BE Hawley, TS Hawley, RG TI Fluorescent Protein-Assisted Purification for Gene Expression Profiling SO FLOW CYTOMETRY PROTOCOLS, THIRD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Tetracycline-induced system; Green fluorescent protein; Luciferase; Skin stem cells; Label-retaining cells; Pol2 promoter; Syngeneic mice; Lung metastases ID IN-VIVO; CELLS; SKIN AB Cell type-specific expression of fluorescent proteins allows the purification of rare cells from complex tissues by flow cytometry. This strategy is especially useful for molecular analysis of cancer cells because these cells can be effectively purified away from the noncancerous tumor stroma. Coexpression of bioluminescence with fluorescence makes further allows in vivo tracking of cancer cells, which can then be purified at specific tumorigenic stages. Here, we describe protocols for purifying rare skin stem cells, and for in vivo monitoring and purification of cancer cells from lung metastases. Also described is a protocol for the isolation of total RNA from the purified cells for the purpose of performing gene expression profiling. C1 [Zaidi, M. Raza; Day, Chi-Ping; Merlino, Glenn] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Zaidi, MR (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RI Zaidi, M. Raza/H-1386-2016 OI Zaidi, M. Raza/0000-0003-0480-3188 NR 11 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61737-949-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 699 SI 3rd BP 393 EP 405 DI 10.1007/978-1-61737-950-5_19 D2 10.1007/978-1-61737-950-5 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BSR17 UT WOS:000285531800019 PM 21116994 ER PT S AU Perfetto, SP Ambrozak, DR Nguyen, R Roederer, M Koup, RA Holmes, KL AF Perfetto, Stephen P. Ambrozak, David R. Nguyen, Richard Roederer, Mario Koup, Richard A. Holmes, Kevin L. BE Hawley, TS Hawley, RG TI Standard Practice for Cell Sorting in a BSL-3 Facility SO FLOW CYTOMETRY PROTOCOLS, THIRD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Flow cytometry; High speed sorting; Biosafety; Biohazard; Safety in flow cytometry ID UNFIXED CELLS; BIOSAFETY GUIDELINES AB Over the past decade, there has been a rapid growth in the number of BSL-3 and BSL-4 laboratories in the USA and an increase in demand for infectious cell sorting in BSL-3 laboratories. In 2007, the International Society for Advancement of Cytometry (ISAC) Biosafety Committee published standards for the sorting of unfixed cells and is an important resource for biosafety procedures when performing infectious cell sorting. Following a careful risk assessment, if it is determined that a cell sorter must be located within a BSL-3 laboratory, there are a variety of factors to be considered prior to the establishment of the laboratory. This chapter outlines procedures for infectious cell sorting in a BSL-3 environment to facilitate the establishment and safe operation of a BSL-3 cell sorting laboratory. Subjects covered include containment verification, remote operation, disinfection, personal protective equipment (PPE), and instrument-specific modifications for enhanced aerosol evacuation. C1 [Perfetto, Stephen P.; Ambrozak, David R.; Nguyen, Richard; Roederer, Mario; Koup, Richard A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Holmes, Kevin L.] NIAID, Flow Cytometry Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA. RP Perfetto, SP (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS [Z99 AI999999]; NCI NIH HHS [HHSN261200800001E] NR 9 TC 2 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61737-949-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 699 SI 3rd BP 449 EP 469 DI 10.1007/978-1-61737-950-5_22 D2 10.1007/978-1-61737-950-5 PG 21 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BSR17 UT WOS:000285531800022 PM 21116997 ER PT J AU Turner, PC Ji, BT Shu, XO Zheng, W Chow, WH Gao, YT Hardie, LJ AF Turner, P. C. Ji, B. T. Shu, X. O. Zheng, W. Chow, W. H. Gao, Y. T. Hardie, L. J. TI A biomarker survey of urinary deoxynivalenol in China: the Shanghai Women's Health Study SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE LC/MS; exposure; mycotoxins; trichothecenes ID UK ADULTS; NATURAL OCCURRENCE; ESOPHAGEAL CANCER; HIGH-RISK; ZEARALENONE; MYCOTOXINS; TOXICOLOGY; METABOLITE; WHEAT; CORN AB Deoxynivalenol (DON) is a trichothecene mycotoxin found on wheat, maize and barley. In ecological surveys in China, DON and other trichothecenes have been implicated in acute poisoning episodes and linked with the incidence of esophageal cancer. In order to better understand exposure patterns, this pilot survey provided a combined measure of urinary un-metabolised or free DON (fD) and its glucuronide metabolite (DG) in a subset of 60 samples taken from the Shanghai Women's Health Study cohort, China. Samples were collected in 1997/1998 from women age 40-70 years. Urinary fD+DG combined was detected in 58/60 (96.7%) samples (mean 5.9 ng DON/mg creatinine; range nd - 30.5); a similar frequency, and a mean level approximately half, of that previously observed for women in the UK. Wheat consumption was approximately 25% of that consumed by western diets; thus DON contamination of wheat may be higher in Shanghai than the UK. The de-epoxy metabolite of DON, a detoxification product observed in animals, was not detected, suggesting that humans may be particularly sensitive to DON due to a more restricted detoxification capacity. C1 [Turner, P. C.; Hardie, L. J.] Univ Leeds, Mol Epidemiol Unit, Leeds Inst Genet Hlth & Therapeut, Leeds LS2 9JT, W Yorkshire, England. [Ji, B. T.; Chow, W. H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Shu, X. O.; Zheng, W.] Vanderbilt Epidemiol Ctr, Inst Med & Publ Hlth, Nashville, TN 37203 USA. [Gao, Y. T.] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. RP Turner, PC (reprint author), Univ Leeds, Mol Epidemiol Unit, Leeds Inst Genet Hlth & Therapeut, Leeds LS2 9JT, W Yorkshire, England. EM p.c.turner@leeds.ac.uk RI Turner, Paul/B-8131-2013 FU US National Institutes of Health [R37 CA070867]; National Institutes of Health, Division of Cancer Epidemiology and Genetics [NO2-CP-11010-66] FX This study was supported by the US National Institutes of Health (grant R37 CA070867) and the Intramural Research Program of the National Institutes of Health, Division of Cancer Epidemiology and Genetics (contact NO2-CP-11010-66). Authors also thank Kay White for technical assistance in LC-MS analysis. NR 26 TC 14 Z9 14 U1 0 U2 18 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1944-0049 J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PY 2011 VL 28 IS 9 BP 1220 EP 1223 DI 10.1080/19440049.2011.584070 PG 4 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 830XW UT WOS:000295693800009 PM 21774617 ER PT J AU Nagpal, R Behare, P Rana, R Kumar, A Kumar, M Arora, S Morotta, F Jain, S Yadav, H AF Nagpal, Ravinder Behare, Pradip Rana, Rajiv Kumar, Ashwani Kumar, Manoj Arora, Sanu Morotta, Fransesco Jain, Shalini Yadav, Hariom TI Bioactive peptides derived from milk proteins and their health beneficial potentials: an update SO FOOD & FUNCTION LA English DT Review ID I-CONVERTING-ENZYME; VAL-PRO-PRO; N-TERMINAL REGION; ACE-INHIBITORY-ACTIVITY; BOVINE WHEY PROTEINS; AMINO-ACID SEQUENCE; BETA-LACTOGLOBULIN; LACTOFERRICIN-B; OPIOID-PEPTIDES; CHEMICAL CHARACTERIZATION AB It has been well recognized that dietary proteins provide a rich source of biologically active peptides. Today, milk proteins are considered the most important source of bioactive peptides and an increasing number of bioactive peptides have been identified in milk protein hydrolysates and fermented dairy products. Bioactive peptides derived from milk proteins offer a promising approach for the promotion of health by means of a tailored diet and provide interesting opportunities to the dairy industry for expansion of its field of operation. The potential health benefits of milk protein-derived peptides have been a subject of growing commercial interest in the context of health-promoting functional foods. Hence, these peptides are being incorporated in the form of ingredients in functional and novel foods, dietary supplements and even pharmaceuticals with the purpose of delivering specific health benefits. C1 [Nagpal, Ravinder; Kumar, Ashwani] JMIT Inst Engn & Technol, Dept Biotechnol, Radaur 135133, Haryana, India. [Behare, Pradip] Coll Dairy Technol, Latur 413517, Maharashtra, India. [Rana, Rajiv] Lovely Profess Univ, Dept Biotechnol, Jalandhar, Punjab, India. [Kumar, Manoj] Natl Dairy Res Inst, Dairy Microbiol Div, Karnal 132001, Haryana, India. [Arora, Sanu] Punjab Agr Univ, Dept Biotechnol, Ludhiana, Punjab, India. [Morotta, Fransesco] S Giuseppe Hosp, Hepato GI Dept, Milan, Italy. [Jain, Shalini; Yadav, Hariom] NIDDK, NIH, Clin Res Ctr, Diabet Branch, Bethesda, MD 20892 USA. RP Nagpal, R (reprint author), JMIT Inst Engn & Technol, Dept Biotechnol, Radaur 135133, Haryana, India. EM yadavh@mail.nih.gov OI Yadav, Hariom/0000-0003-4504-1597 NR 122 TC 83 Z9 88 U1 7 U2 75 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2042-6496 EI 2042-650X J9 FOOD FUNCT JI Food Funct. PD JAN PY 2011 VL 2 IS 1 BP 18 EP 27 DI 10.1039/c0fo00016g PG 10 WC Biochemistry & Molecular Biology; Food Science & Technology SC Biochemistry & Molecular Biology; Food Science & Technology GA 758RD UT WOS:000290181900003 PM 21773582 ER PT J AU Hancock, CN Stockwin, LH Han, BN Divelbiss, RD Jun, JH Malhotra, SV Hollingshead, MG Newton, DL AF Hancock, Chad N. Stockwin, Luke H. Han, Bingnan Divelbiss, Raymond D. Jun, Jung Ho Malhotra, Sanjay V. Hollingshead, Melinda G. Newton, Dianne L. TI A copper chelate of thiosemicarbazone NSC 689534 induces oxidative/ER stress and inhibits tumor growth in vitro and in vivo SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Thiosemicarbazone; Copper; ER stress; UPR; Macroautophagy; Oxidative stress; Free radicals ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; PERFORMANCE LIQUID-CHROMATOGRAPHY; HUMAN RIBONUCLEOTIDE REDUCTASE; AUTOPHAGIC CELL-DEATH; ARSENIC TRIOXIDE; 3-AMINOPYRIDINE-2-CARBOXALDEHYDE THIOSEMICARBAZONE; CANCER-CELLS; CERVICAL-CANCER; IRON CHELATORS AB In this study, a Cu2+ chelate of the novel thiosemicarbazone NSC 689534 was evaluated for in vitro and in vivo anti-cancer activity. Results demonstrated that NSC 689534 activity (low micromolar range) was enhanced four- to fivefold by copper chelation and completely attenuated by iron. Importantly, once formed, the NSC 689534/Cu2+ complex retained activity in the presence of additional iron or iron-containing biomolecules. NSC 689534/Cu2+ mediated its effects primarily through the induction of ROS, with depletion of cellular glutathione and protein thiols. Pretreatment of cells with the antioxidant N-acetyl-l-cysteine impaired activity, whereas NSC 689534/Cu2+ effectively synergized with the glutathione biosynthesis inhibitor buthionine sulfoximine. Microarray analysis of NSC 689534/Cu2+-treated cells highlighted activation of pathways involved in oxidative and ER stress/UPR, autophagy, and metal metabolism. Further scrutiny of the role of ER stress and autophagy indicated that NSC 689534/Cu2+-induced cell death was ER-stress dependent and autophagy independent. Last, NSC 689534/Cu2+ was shown to have activity in an HL60 xenograft model. These data suggest that NSC 689534/Cu2+ is a potent oxidative stress inducer worthy of further preclinical investigation. (C) 2010 Elsevier Inc. All rights reserved. C1 [Hancock, Chad N.; Stockwin, Luke H.; Han, Bingnan; Divelbiss, Raymond D.; Newton, Dianne L.] SAIC Frederick, Biol Testing Branch, Dev Therapeut Program, Frederick, MD 21702 USA. [Jun, Jung Ho; Malhotra, Sanjay V.] SAIC Frederick Inc, Lab Synthet Chem, Frederick, MD 21702 USA. [Hollingshead, Melinda G.] NCI, Biol Testing Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Newton, DL (reprint author), SAIC Frederick, Biol Testing Branch, Dev Therapeut Program, Frederick, MD 21702 USA. EM newtondianne@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Division of Cancer Treatment and Diagnosis of the National Cancer Institute FX We gratefully acknowledge the excellent technical assistance of Ms. Sherry Yu. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract 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 U.S. government. This research was supported (in part) by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute. NCI-Frederick is accredited by AAALACi and follows the Public Health Service Policy on the Care and Use of Laboratory Animals. All animals used in this research project were cared for and used humanely according to the following policies: the U.S. Public Health Service Policy on Humane Care and Use of Animals (1996), the Guide for the Care and Use of Laboratory Animals (1996), and the U.S. government Principles for Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training (1985). NR 59 TC 58 Z9 62 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JAN 1 PY 2011 VL 50 IS 1 BP 110 EP 121 DI 10.1016/j.freeradbiomed.2010.10.696 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 709AO UT WOS:000286407700012 PM 20971185 ER PT J AU Mukhopadhyay, P Horvath, B Rajesh, M Matsumoto, S Saito, K Batkai, S Patel, V Tanchian, G Gao, RY Cravatt, BF Hasko, G Pacher, P AF Mukhopadhyay, Partha Horvath, Bela Rajesh, Mohanraj Matsumoto, Shingo Saito, Keita Batkai, Sandor Patel, Vivek Tanchian, Galin Gao, Rachel Y. Cravatt, Benjamin F. Hasko, Gyoergy Pacher, Pal TI Fatty acid amide hydrolase is a key regulator of endocannabinoid-induced myocardial tissue injury SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Cardiomyopathy; Endocannabinoids; Cannabinoid receptors; Cell death; Oxidative stress; Nitrosative stress; Free radicals ID CB1 CANNABINOID RECEPTORS; DOXORUBICIN-INDUCED CARDIOTOXICITY; ISCHEMIA-REPERFUSION INJURY; APOPTOSIS IN-VITRO; INDUCED CELL-DEATH; REACTIVE OXYGEN; ENDOTHELIAL-CELLS; NITRIC-OXIDE; CARDIOVASCULAR-DISEASE; INDUCED CARDIOMYOPATHY AB Previous studies have suggested that increased levels of endocannabinoids in various cardiovascular disorders (e.g., various forms of shock, cardiomyopathies, atherosclerosis) through the activation of CB(1) cannabinoid receptors may promote cardiovascular dysfunction and tissue injury. We have investigated the role of the main endocannabinoid anandamide-metabolizing enzyme (fatty acid amide hydrolase; FAAH) in myocardial injury induced by an important chemotherapeutic drug, doxorubicin (DOX; known for it cardiotoxicity mediated by increased reactive oxygen and nitrogen species generation), using well-established acute and chronic cardiomyopathy models in mice. The DOX-induced myocardial oxidative/nitrative stress (increased 4-hydroxynonenal, protein carbonyl, and nitrotyrosine levels and decreased glutathione content) correlated with multiple cell death markers, which were enhanced in FAAH knockout mice exhibiting significantly increased DOX-induced mortality and cardiac dysfunction compared to their wild type. The effects of DOX in FAAH knockouts were attenuated by CB(1) receptor antagonists. Furthermore, anandamide induced enhanced cell death in human cardiomyocytes pretreated with FAAH inhibitor and enhanced sensitivity to ROS generation in inflammatory cells of FAAH knockouts. These results suggest that in pathological conditions associated with acute oxidative/nitrative stress FAAH plays a key role in controlling the tissue injury that is, at least in part, mediated by the activation of CB(1) receptors by endocannabinoids. Published by Elsevier Inc. C1 [Mukhopadhyay, Partha; Horvath, Bela; Rajesh, Mohanraj; Batkai, Sandor; Patel, Vivek; Tanchian, Galin; Gao, Rachel Y.; Pacher, Pal] NCI, Lab Physiol Studies, NIAAA, NIH, Bethesda, MD 20892 USA. [Matsumoto, Shingo; Saito, Keita] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. [Cravatt, Benjamin F.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Cravatt, Benjamin F.] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. [Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. [Horvath, Bela] Semmelweis Univ, Inst Human Physiol & Clin Expt Res, Budapest, Hungary. RP Pacher, P (reprint author), NCI, Lab Physiol Studies, NIAAA, NIH, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Horvath, Bela/A-7368-2009; Batkai, Sandor/G-3889-2010; MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; FU National Institutes of Health/NIAAA; NKTH-OTKA-EU [MB08-A 80238] FX This study was supported by the Intramural Research Program of the National Institutes of Health/NIAAA (to P.P.). Dr. Horvath was supported by an NKTH-OTKA-EU 7FW fellowship (MB08-A 80238). The authors are indebted to Dr. Murali C. Krishna for generously providing his resources and expertise with EPR measurements and Dr. George Kunos for providing support and resources for the completion of this study. Dr. Pacher dedicates this study to his beloved mother Iren Bolfert, who died from the cardiovascular complications of chemotherapy. NR 75 TC 41 Z9 41 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JAN 1 PY 2011 VL 50 IS 1 BP 179 EP 195 DI 10.1016/j.freeradbiomed.2010.11.002 PG 17 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 709AO UT WOS:000286407700019 PM 21070851 ER PT J AU Park, S Yoon, SJ Tae, HJ Shim, CY AF Park, Sungha Yoon, Se-Jung Tae, Hyun-Jin Shim, Chi Young TI RAGE and cardiovascular disease SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE RAGE; Inflammation; Cardiovascular disease; Atherosclerosis; sRAGE; Review ID GLYCATION END-PRODUCTS; CORONARY-ARTERY-DISEASE; INFLAMMATORY CELL RECRUITMENT; MYOCARDIAL ISCHEMIC-INJURY; CROSS-LINK BREAKER; C-REACTIVE PROTEIN; SOLUBLE RECEPTOR; MAILLARD REACTION; SERUM-LEVELS; ENDOTHELIAL DYSFUNCTION AB RAGE is pattern recognizing receptors for diverse endogenous ligands. RAGE activation by RAGE ligands is known to be associated with reactive oxygen species generation, activation of NF kappa B, as well as recruitment of proinflammatory cells. Activated endothelial cells, vascular smooth muscle cells in atherosclerotic plaques and activated inflammatory cells all have increased expression of RAGE, which with its interaction with RAGE ligands increases the secretion of proinflammatory cytokines and cell adhesion molecules. Furthermore, RAGE may have a significant role in leukocyte recruitment into the intima of the atherosclerosis. Initial insults resulting in endothelial dysfunction will result in leukocyte infiltration, oxidative stress and vascular inflammation that is amplified by RAGE activation. RAGE and its interaction with RAGE ligands may be important for initializing and maintaining the pathological processes that result in various entities of cardiovascular disease. Soluble RAGE competitively inhibits the binding of RAGE ligands to RAGE and attenuates the development of atherosclerosis in vivo. Thus RAGE may be a promising target for treatment of cardiovascular disease in the future. C1 [Park, Sungha; Shim, Chi Young] Yonsei Univ, Coll Med, Div Cardiol, Seoul, South Korea. [Tae, Hyun-Jin] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. [Yoon, Se-Jung] Natl Hlth Insurance Corp Ilsan Hosp, Div Cardiol, Seoul, South Korea. RP Park, S (reprint author), Yonsei Univ Hlth Syst, Div Cardiol, Seoul, South Korea. EM shpark0530@yuhs.ac FU Korea Research Foundation [KRF-013-2009-01-E00008]; National Research Foundation [NRF-2010-0003855] FX This work was supported by the Korea Research Foundation Grant (KRF-013-2009-01-E00008) and the National Research Foundation Grant (NRF-2010-0003855). NR 104 TC 41 Z9 42 U1 1 U2 10 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN 1 PY 2011 VL 16 BP 486 EP 497 DI 10.2741/3700 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 757MZ UT WOS:000290092700007 PM 21196183 ER PT J AU Bishayee, A Ahmed, S Brankov, N Perloff, M AF Bishayee, Anupam Ahmed, Shamima Brankov, Nikoleta Perloff, Marjorie TI Triterpenoids as potential agents for the chemoprevention and therapy of breast cancer SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE Apoptosis; Breast Cancer; Chemoprevention; Review; Treatment; Triterpenoids; Tumor Cells ID MEDICINALLY IMPORTANT COMPOUNDS; CDDO-METHYL ESTER; CELLS IN-VITRO; ANTITUMOR-ACTIVITY; OLEANOLIC ACID; BETULINIC ACID; GROWTH ARREST; CYTOTOXIC TRITERPENOIDS; DEPENDENT APOPTOSIS; MOLECULAR TARGETS AB Breast cancer remains a major cause of death in the United States as well as the rest of the world. In view of the limited treatment options for patients with advanced breast cancer, preventive and novel therapeutic approaches play an important role in combating this disease. The plant-derived triterpenoids, commonly used for medicinal purposes in many Asian countries, posses various pharmacological properties. A large number of triterpenoids are known to exhibit cytotoxicity against a variety of tumor cells as well as anticancer efficacy in preclinical animal models. Numerous triterpenoids have been synthesized by structural modification of natural compounds. Some of these analogs are considered to be the most potent antiinflammatory and anticarcinogenic triterpenoids known. This review examines the potential role of natural triterpenoids and their derivatives in the chemoprevention and treatment of mammary tumors. Both in vitro and in vivo effects of these agents and related molecular mechanisms are presented. Potential challenges and future directions involved in the advancement of these promising compounds in the prevention and therapy of human breast cancer are also identified. C1 [Bishayee, Anupam; Ahmed, Shamima; Brankov, Nikoleta] Northeastern Ohio Univ Coll Med & Pharm, Dept Pharmaceut Sci, Coll Med, Canc Therapeut & Chemoprevent Grp, Rootstown, OH 44272 USA. [Bishayee, Anupam; Ahmed, Shamima; Brankov, Nikoleta] Northeastern Ohio Univ Coll Med & Pharm, Dept Pharmaceut Sci, Coll Pharm, Canc Therapeut & Chemoprevent Grp, Rootstown, OH 44272 USA. [Perloff, Marjorie] NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Bishayee, A (reprint author), Northeastern Ohio Univ Coll Med & Pharm, Dept Pharmaceut Sci, Coll Med, Canc Therapeut & Chemoprevent Grp, 4209 State Route 44, Rootstown, OH 44272 USA. EM abishayee@neoucom.edu FU National Cancer Institute [R03CA13614] FX The research on triterpenoid and breast cancer chemoprevention at the corresponding author's laboratory is supported by the award R03CA13614 from the National Cancer Institute. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The authors thank Altaf S. Darvesh, Ph.D., for carefully editing the manuscript and providing valuable comments and Werner J. Geldenhuys, Ph.D., for assistance with the chemical structures. NR 113 TC 95 Z9 98 U1 4 U2 31 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN 1 PY 2011 VL 16 BP 980 EP 996 DI 10.2741/3730 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 757NC UT WOS:000290093100010 PM 21196213 ER PT J AU Keller, MD Petersen, M Ong, P Church, J Risma, K Burham, J Jain, A Stiehm, ER Hanson, EP Uzel, G Deardorff, MA Orange, JS AF Keller, Michael D. Petersen, Maureen Ong, Peck Church, Joseph Risma, Kimberly Burham, Jon Jain, Ashish Stiehm, E. Richard Hanson, Eric P. Uzel, Gulbu Deardorff, Matthew A. Orange, Jordan S. TI Hypohidrotic ectodermal dysplasia and immunodeficiency with coincident NEMO and EDA mutations SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE NEMO; EDA; ectodermal dysplasia; immunodeficiency AB Ectodermal dysplasias (ED) are uncommon genetic disorders resulting in abnormalities in ectodermally derived structures. Many ED-associated genes have been described, of which ectodysplasin-A (FDA) is one of the more common. The NE-03 essential modulator (NEMO encoded by the IKBKG gene) is unique in that mutations result in severe humoral and cellular immunologic defects in addition to ED. We describe three unrelated kindreds with defects in both FDA and IKBKG resulting from X-chromosome crossover. This demonstrates the importance of thorough immunologic consideration of patients with ED even when an FDA etiology is confirmed, and raises the possibility of a specific phenotype arising from coincident mutations in FDA and IKBKG. C1 [Keller, Michael D.; Orange, Jordan S.] Childrens Hosp Philadelphia, Div Immunol, Philadelphia, PA 19104 USA. [Petersen, Maureen] Walter Reed Natl Mil Med Ctr, Div Allergy & Immunol, Bethesda, MD USA. [Ong, Peck; Church, Joseph] Childrens Hosp Los Angeles, Div Clin Immunol & Allergy, Los Angeles, CA 90027 USA. [Risma, Kimberly] Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH 45229 USA. [Burham, Jon] Childrens Hosp Philadelphia, Div Rheumatol, Philadelphia, PA 19104 USA. [Jain, Ashish] NIAID, Host Def Lab, Clin Immunol Unit, Bethesda, MD 20892 USA. [Stiehm, E. Richard] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Allergy Immunol & Rheumatol, Los Angeles, CA 90095 USA. [Hanson, Eric P.] NIAMSD, Immunoregulatory Sect, NIH, Bethesda, MD 20892 USA. [Uzel, Gulbu] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, Bethesda, MD USA. [Deardorff, Matthew A.] Childrens Hosp Philadelphia, Div Genet, Philadelphia, PA 19104 USA. RP Orange, JS (reprint author), Childrens Hosp Philadelphia, Abramson Res Bldg Room 909, Philadelphia, PA 19104 USA. EM orange@mail.med.upenn.edu OI orange, jordan/0000-0001-7117-7725; Risma, Kimberly/0000-0003-0671-4859 FU National Institutes of Health (NIH) [AI079731] FX The authors would like to thank Linda Monaco-Shawver, Pinaki Banerjee, Sherry Bale, David Adams, Raquel Deering, and Veronique Weinstein for their assistance in this study. Supported by National Institutes of Health (NIH) AI079731 (Jordan S. Orange). NR 27 TC 7 Z9 8 U1 0 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2011 VL 2 AR 61 DI 10.3389/fimmu.2011.00061 PG 8 WC Immunology SC Immunology GA V40TR UT WOS:000209501400061 PM 22566850 ER PT J AU Pandiyan, P Zheng, LX Lenardo, MJ AF Pandiyan, Pushpa Zheng, Lixin Lenardo, Michael J. TI The molecular mechanisms of regulatory T cell immunosuppression SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE tregs; Th17; immune suppression mechanism; BIM cytokine deprivation death; apoptosis; regulatory T cells; Foxp3; cytokine consumption AB CD4(+)CD25(+)Foxp3(+) T lymphocytes, known as regulatory T cells or T-regs, have been proposed to be a lineage of professional immune suppressive cells that exclusively counteract the effects of the immunoprotective "helper" and "cytotoxic" lineages of T lymphocytes. Here we discuss new concepts on the mechanisms and functions of Tregs. There are several key points we emphasize: 1. Tregs exert suppressive effects both directly on effector T cells and indirectly through antigen-presenting cells; 2. Regulation can occur through a novel mechanism of cytokine consumption to regulate as opposed to the usual mechanism of cytokine/chemokine production; 3. In cases where CD4(+) effectorT cells are directly inhibited by T-regs, it is chiefly through a mechanism of lymphokine withdrawal apoptosis leading to polyclonal deletion; and 4. Contrary to the current view, we discuss new evidence that T-regs, similar to otherT-cells lineages, can promote protective immune responses in certain infectious contexts (Chen et al., 2011; Pandiyan et al., 2011). Although these points are at variance to varying degrees with the standard model of Treg behavior, we will recount developing findings that support these new concepts. C1 [Pandiyan, Pushpa; Zheng, Lixin; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Pandiyan, P (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM ppandiyan@niaid.nih.gov FU National Research Council (NRC), National Academy of Sciences; National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) FX Pushpa Pandiyan was partially supported by a fellowship from the National Research Council (NRC), National Academy of Sciences, This work was supported by the intramural research program of National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). NR 116 TC 11 Z9 12 U1 2 U2 4 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2011 VL 2 AR 60 DI 10.3389/fimmu.2011.00060 PG 11 WC Immunology SC Immunology GA V40TR UT WOS:000209501400060 PM 22566849 ER PT J AU Beare, PA Sandoz, KM Omsland, A Rockey, DD Heinzen, RA AF Beare, Paul A. Sandoz, Kelsi M. Omsland, Anders Rockey, Daniel D. Heinzen, Robert A. TI Advances in genetic manipulation of obligate intracellular bacterial pathogens SO FRONTIERS IN MICROBIOLOGY LA English DT Review DE transposon mutagenesis; electroporation; antibiotic selection; allelic exchange; genetic transformation; virulence factor; shuttle vector; complementation AB Infections by obligate intracellular bacterial pathogens result in significant morbidity and mortality worldwide. These bacteria include Chlamydia spp., which causes millions of cases of sexually transmitted disease and blinding trachoma annually, and members of the alpha-proteobacterial genera Anaplasma, Ehrlichia, Orientia, and Rickettsia, agents of serious human illnesses including epidemic typhus. Coxiella burnetii, the agent of human Q fever, has also been considered a prototypical obligate intracellular bacterium, but recent host cell-free (axenic) growth has rescued it from obligatism. The historic genetic intractability of obligate intracellular bacteria has severely limited molecular dissection of their unique lifestyles and virulence factors involved in pathogenesis. Host cell restricted growth is a significant barrier to genetic transformation that can make simple procedures for free-living bacteria, such as cloning, exceedingly difficult. Low transformation efficiency requiring long-term culture in host cells to expand small transformant populations is another obstacle. Despite numerous technical limitations, the last decade has witnessed significant gains in genetic manipulation of obligate intracellular bacteria including allelic exchange. Continued development of genetic tools should soon enable routine mutation and complementation strategies for virulence factor discovery and stimulate renewed interest in these refractory pathogens. In this review, we discuss the technical challenges associated with genetic transformation of obligate intracellular bacteria and highlight advances made with individual genera. C1 [Beare, Paul A.; Omsland, Anders; Heinzen, Robert A.] NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Coxiella Pathogenesis Sect, Hamilton, MT 59840 USA. [Sandoz, Kelsi M.; Rockey, Daniel D.] Oregon State Univ, Dept Biomed Sci, Corvallis, OR 97331 USA. RP Heinzen, RA (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, 903 South Fourth St, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases FX We thank Shelly Robertson for critical reading of the manuscript and Anita Mora for graphic support. This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases. NR 82 TC 41 Z9 41 U1 1 U2 13 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-302X J9 FRONT MICROBIOL JI Front. Microbiol. PY 2011 VL 2 AR 97 DI 10.3389/fmicb.2011.00097 PG 13 WC Microbiology SC Microbiology GA V31DE UT WOS:000208863500107 PM 21833334 ER PT J AU Bensaci, MF Gurnev, PA Bezrukov, SM Takemoto, JY AF Bensaci, Mekki F. Gurnev, Philip A. Bezrukov, Sergey M. Takemoto, Jon Y. TI Fungicidal activities and mechanisms of action of Pseudomonas syringae pv. syringae lipodepsipeptide syringopeptins 22A and 25A SO FRONTIERS IN MICROBIOLOGY LA English DT Article DE syringopeptin; fungicide; syringomycin; yeast; Pseudomonas syringae; ion channel AB The plant-associated bacterium Pseudomonas syringae pv. syringae simultaneously produces two classes of metabolites: the small cyclic lipodepsinonapeptides such as the syringomycins and the larger cyclic lipodepsipeptide syringopeptins SP22 or SP25. The syringomycins inhibit a broad spectrum of fungi (but particularly yeasts) by lipid-dependent membrane interaction. The syringopeptins are phytotoxic and inhibitory to Gram-positive bacteria. In this study, the fungicidal activities of two major syringopeptins, SP22A and SP25A, and their mechanisms of action were investigated and compared to those of syringomycin E. SP22A and SP25A were observed to inhibit the fungal yeasts Saccharomyces cerevisiae and Candida albicans although less effectively than syringomycin E. S. cerevisiae mutants defective in ergosterol and sphingolipid biosyntheses were less susceptible to SP22A and SP25A but the relative inhibitory capabilities of SRE vs. SP22A and SP25A were maintained. Similar differences were observed for capabilities to cause cellular K+ and Ca2+ fluxes in S. cerevisiae. Interestingly, in phospholipid bilayers the syringopeptins are found to induce larger macroscopic ionic conductances than syringomycin E but form single channels with similar properties. These findings suggest that the syringopeptins target the yeast plasma membrane, and, like syringomycin E, employ a lipid-dependent channel-forming mechanism of action. The differing degrees of growth inhibition by these lipodepsipeptides may be explained by differences in their hydrophobicities. The more hydrophobic 5P22A and 5P25A might interact more strongly with the yeast cell wall that would create a selective barrier for their incorporation into the plasma membrane. C1 [Bensaci, Mekki F.; Takemoto, Jon Y.] Utah State Univ, Dept Biol, Logan, UT 84322 USA. [Gurnev, Philip A.; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA. RP Takemoto, JY (reprint author), Utah State Univ, Dept Biol, 5305 Old Main Hill, Logan, UT 84322 USA. EM jon@biology.usu.edu RI Takemoto, Jon/A-5309-2011 OI Takemoto, Jon/0000-0001-9919-9168 FU National Science Foundation [9003393]; Utah Agricultural Experiment Station (UTA) [569]; Intramural Research Program of the NHL Eunice Kennedy hriver National Institute of Child Health and Human Development; N. R Gandhi Graduate Research Fellowship FX This research was supported by the National Science Foundation (9003393), the Utah Agricultural Experiment Station (UTA 569; approved as journal paper no 7972), the Intramural Research Program of the NHL Eunice Kennedy hriver National Institute of Child Health and Human Development, and an N. R Gandhi Graduate Research Fellowship to Mekki F. Bensaci. We thank Dr. Joanne E. Hughes (Utah State University) for conducting 45Ca2+ flux measure merits. NR 34 TC 7 Z9 7 U1 1 U2 8 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-302X J9 FRONT MICROBIOL JI Front. Microbiol. PY 2011 VL 2 AR 216 DI 10.3389/fmicb.2011.00216 PG 7 WC Microbiology SC Microbiology GA V31DE UT WOS:000208863500224 PM 22046175 ER PT J AU Bosio, CM AF Bosio, Catharine M. TI The subversion of the immune system by Francisella tularensis SO FRONTIERS IN MICROBIOLOGY LA English DT Review DE Francisella tularensis; antibody; complement; oxidative burst; macrophage; dendritic cell; inflammation; suppression AB Francisella tularensis is a highly virulent bacterial pathogen and the causative agent of tularemia. Perhaps the most impressive feature of this bacterium is its ability to cause lethal disease following inoculation of as few as 15 organisms. This remarkable virulence is, in part, attributed to the ability of this microorganism to evade, disrupt, and modulate host immune responses. The objective of this review is to discuss the mechanisms utilized by F. tularensis to evade and inhibit innate and adaptive immune responses. The capability of F. tularensis to interfere with developing immunity in the host was appreciated decades ago. Early studies in humans were the first to demonstrate the ability of F. tularensis to suppress innate immunity. This work noted that humans suffering from tularemia failed to respond to a secondary challenge of endotoxin isolated from unrelated bacteria. Further, anecdotal observations of individuals becoming repeatedly infected with virulent strains of F. tularensis suggests that this bacterium also interferes with the generation of adequate adaptive immunity. Recent advances utilizing the mouse model for in vivo studies and human cells for in vitro work have identified specific bacterial and host compounds that play a role in mediating ubiquitous suppression of the host immune response. Compilation of this work will undoubtedly aid in enhancing our understanding of the myriad of mechanisms utilized by virulent F. tularensis for successful infection, colonization, and pathogenesis in the mammalian host. C1 [Bosio, Catharine M.] NIAID, Immun Pulm Pathogens Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Bosio, CM (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM bosioc@niaid.nih.gov RI Bosio, Catharine/D-7456-2015 NR 46 TC 20 Z9 20 U1 1 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-302X J9 FRONT MICROBIOL JI Front. Microbiol. PY 2011 VL 2 AR 9 DI 10.3389/fmicb.2011.00009 PG 5 WC Microbiology SC Microbiology GA V31DE UT WOS:000208863500019 PM 21687406 ER PT J AU Fields, KA Heinzen, RA Carabeo, R AF Fields, Kenneth A. Heinzen, Robert A. Carabeo, Rey TI The obligate intracellular lifestyle SO FRONTIERS IN MICROBIOLOGY LA English DT Editorial Material C1 [Fields, Kenneth A.] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. [Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Rocky Mt Labs, NIH, Hamilton, MT USA. [Carabeo, Rey] Univ London Imperial Coll Sci Technol & Med, Ctr Mol Microbiol & Infect, Div Cell & Mol Biol, London, England. RP Fields, KA (reprint author), Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. EM kfields@med.miami.edu FU Medical Research Council [G0900213]; NIAID NIH HHS [R01 AI065545-05, R01 AI065545] NR 12 TC 0 Z9 0 U1 1 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-302X J9 FRONT MICROBIOL JI Front. Microbiol. PY 2011 VL 2 AR 99 DI 10.3389/fmicb.2011.00099 PG 2 WC Microbiology SC Microbiology GA V31DE UT WOS:000208863500109 PM 21747803 ER PT J AU Garduno, RA Chong, A Nasrallah, GK Allan, DS AF Garduno, Rafael A. Chong, Audrey Nasrallah, Gheyath K. Allan, David S. TI The Legionella pneumophila chaperonin - an unusual multifunctional protein in unusual locations SO FRONTIERS IN MICROBIOLOGY LA English DT Review DE HtpB; Hsp60; GroEL; pathogenesis; mitochondria; microfilaments; polyamines AB The Legionella pneumophila chaperonin, high temperature protein B (HtpB), was discovered as a highly immunogenic antigen, only a few years after the identification of L. pneumophila as the causative agent of Legionnaires' disease. As its counterparts in other bacterial pathogens, HtpB did not initially receive further attention, particularly because research was focused on a few model chaperonins that were used to demonstrate that chaperonins are essential stress proteins, present in all cellular forms of life and involved in helping other proteins to fold. However, chaperonins have recently attracted increasing interest, particularly after several reports confirmed their multifunctional nature and the presence of multiple chaperonin genes in numerous bacterial species. It is now accepted that bacterial chaperonins are capable of playing a variety of protein folding-independent roles. HtpB is clearly a multifunctional chaperonin that according to its location in the bacterial cell, or in the L. pneumophila-infected cell, plays different roles. HtpB exposed on the bacterial cell surface can act as an invasion factor for non-phagocytic cells, whereas the HtpB released in the host cell can act as an effector capable of altering organelle trafficking, the organization of actin microfilaments and cell signaling pathways. The road to discover the multifunctional nature of HtpB has been exciting and here we provide a historical perspective of the key findings linked to such discovery, as well as a summary of the experimental work (old and new) performed in our laboratory. Our current understanding has led us to propose that HtpB is an ancient protein that L. pneumophila uses as a key molecular tool important to the intracellular establishment of this fascinating pathogen. C1 [Garduno, Rafael A.; Nasrallah, Gheyath K.; Allan, David S.] Dalhousie Univ, Dept Microbiol & Immunol, Halifax, NS, Canada. [Garduno, Rafael A.] Dalhousie Univ, Dept Med, Div Infect Dis, Halifax, NS, Canada. [Chong, Audrey] NIAID, Intracellular Parasites Lab, NIH, Rocky Mt Labs, Hamilton, MT USA. RP Garduno, RA (reprint author), Dept Microbiol & Immunol, Sir Charles Tupper Med Bldg,7th Floor, Halifax, NS B3H 1X5, Canada. EM rafael.garduno@dal.ca OI Nasrallah, Gheyath/0000-0001-9252-1038 FU Canadian Natural Sciences and Engineering Research Council (NSERC) FX The work performed in the Garduno lab, has been funded by the Canadian Natural Sciences and Engineering Research Council (NSERC), Rafael A. Garduno holds a Canada Research Chair, Tier II, in Foodborne and Waterborne Bacterial Pathogens. We acknowledge the valuable suggestions received from the anonymous reviewers of our original manuscript, which resulted in a much improved revised version. NR 94 TC 10 Z9 10 U1 0 U2 5 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-302X J9 FRONT MICROBIOL JI Front. Microbiol. PY 2011 VL 2 AR 122 DI 10.3389/fmicb.2011.00122 PG 12 WC Microbiology SC Microbiology GA V31DE UT WOS:000208863500132 PM 21713066 ER PT J AU Hobbs, MM Sparling, PF Cohen, MS Shafer, WM Deal, CD Jerse, AE AF Hobbs, Marcia M. Sparling, P. Frederick Cohen, Myron S. Shafer, William M. Deal, Carolyn D. Jerse, Ann E. TI Experimental gonococcal infection in male volunteers: cumulative experience with Neisseria gonorrhoeae strains FA1090 and MS11mkC SO FRONTIERS IN MICROBIOLOGY LA English DT Review DE gonorrhea; pathogenesis; infection; urethritis AB Experimental infection of male volunteers with Neisseria gonorrhoeae is safe and reproduces the clinical features of naturally acquired gonococcal urethritis. Human inoculation studies have helped define the natural history of experimental infection with two well-characterized strains of N. gonorrhoeae, FA1090 and MS11 mkC. The human model has proved useful for testing the importance of putative gonococcal virulence factors for urethral infection in men. Studies with isogenic mutants have improved our understanding of the requirements for gonococcal LOS structures, pill, opacity proteins, IgA1 protease, and the ability of infecting organisms to obtain iron from human transferrin and lactoferrin during uncomplicated urethritis. The model also presents opportunities to examine innate host immune responses that may be exploited or improved in development and testing of gonococcal vaccines. Here we review results to date with human experimental gonorrhea. C1 [Hobbs, Marcia M.; Sparling, P. Frederick; Cohen, Myron S.] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. [Hobbs, Marcia M.; Sparling, P. Frederick; Cohen, Myron S.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. [Shafer, William M.] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Shafer, William M.] Vet Affairs Med Ctr Atlanta, Labs Bacterial Pathogenesis, Decatur, GA USA. [Deal, Carolyn D.] NIAID, NIH, Bethesda, MD 20892 USA. [Jerse, Ann E.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. RP Hobbs, MM (reprint author), Univ N Carolina, Dept Med, CB 7031, Chapel Hill, NC 27599 USA. EM mmhobbs@med.unc.edu FU Sexually Transmitted Infections Cooperative Research Center of the US National Institutes of Health [U1 9-AI03 1496]; Medical Research Service of the Department of Veterans Affairs FX We are grateful to Janne G. Cannon for sharing previously unpublished data and for critically reviewing the manuscript. We thank Christopher E. Thomas for sharing data in advance of publication. Experimental gonococcal infection studies at the University of North Carolina at Chapel Hill were supported by the Sexually Transmitted Infections Cooperative Research Center of the US National Institutes of Health (U19-AI031496). William M. Shafer was supported in part by a Senior Research Career Scientist Award from the Medical Research Service of the Department of Veterans Affairs. NR 72 TC 33 Z9 33 U1 2 U2 4 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-302X J9 FRONT MICROBIOL JI Front. Microbiol. PY 2011 VL 2 AR 123 DI 10.3389/fmicb.2011.00123 PG 12 WC Microbiology SC Microbiology GA V31DE UT WOS:000208863500133 PM 21734909 ER PT J AU Malik-Kale, P Jolly, CE Lathrop, S Winfree, S Luterbach, C Steele-Mortimer, O AF Malik-Kale, Preeti Jolly, Carrie E. Lathrop, Stephanie Winfree, Seth Luterbach, Courtney Steele-Mortimer, Olivia TI Salmonella - at home in the host cell SO FRONTIERS IN MICROBIOLOGY LA English DT Review DE effectors; invasion; membrane tubules; phagosome; type III secretion system; vacuole AB The Gram-negative bacterium Salmonella enterica has developed an array of sophisticated tools to manipulate the host cell and establish an intracellular niche, for successful propagation as a facultative intracellular pathogen. While Salmonella exerts diverse effects on its host cell, only the cell biology of the classic "trigger"-mediated invasion process and the subsequent development of the Salmonella-containing vacuole have been investigated extensively. These processes are dependent on cohorts of effector proteins translocated into host cells by two type Ill secretion systems (T3SS), although T3SS-independent mechanisms of entry may be important for invasion of certain host cell types. Recent studies into the intracellular lifestyle of Salmonella have provided new insights into the mechanisms used by this pathogen to modulate its intracellular environment. Here we discuss current knowledge of Salmonella-host interactions including invasion and establishment of an intracellular niche within the host. C1 [Malik-Kale, Preeti; Jolly, Carrie E.; Lathrop, Stephanie; Winfree, Seth; Luterbach, Courtney; Steele-Mortimer, Olivia] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Steele-Mortimer, O (reprint author), NIAID, Rocky Mt Labs, NIH, 903 South 4th St, Hamilton, MT 59840 USA. EM omortimer@niaid.nih.gov FU Intramural Research Program (DIR) of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH) FX Work in the author's laboratory is funded by the Intramural Research Program (DIR) of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH). NR 121 TC 32 Z9 33 U1 5 U2 9 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-302X J9 FRONT MICROBIOL JI Front. Microbiol. PY 2011 VL 2 AR 125 DI 10.3389/fmicb.2011.00125 PG 9 WC Microbiology SC Microbiology GA V31DE UT WOS:000208863500135 PM 21687432 ER PT J AU Warawa, JM Long, D Rosenke, R Gardner, D Gherardini, FC AF Warawa, Jonathan M. Long, Dan Rosenke, Rebecca Gardner, Don Gherardini, Frank C. TI Bioluminescent diagnostic imaging to characterize altered respiratory tract colonization by the Burkholderia pseudomallei capsule mutant SO FRONTIERS IN MICROBIOLOGY LA English DT Article DE bioluminescent diagnostic imaging; hairless mouse model; upper respiratory tract infection; pulmonary disease; Burkholderia pseudomallei; melioidosis; capsular polysaccharide; intranasal infection AB Pneumonia is a common manifestation of the potentially fatal disease melioidosis, caused by the select agent bacteria Burkholderia pseudomaller In this study we describe a new model system to investigate pulmonary melioidosis in vivo using bioluminescent-engineered bacteria in a murine respiratory disease model. Studies were performed to validate that the stable, light producing B. pseudomallei strain JW280 constitutively produced light in biologically relevant host pathogen interactions. Hairless outbred SKH1 mice were used to enhance the ability to monitor B. pseudomallei respiratory disease, and were found to be similarly susceptible to respiratory melioidosis as BALB/c mice. This represents the first demonstration of in vivo diagnostic imaging of pulmonary melioidosis permitting the detection of B. pseudomallei less than 24 h post-infection. Diagnostic imaging of pulmonary melioidosis revealed distinct temporal patterns of bacterial colonization unique to both BALB/c and SKH1 mice. Validation of these model systems included the use of the previously characterized capsule mutant, which was found to colonize the upper respiratory tract at significantly higher levels than the wild type strain. These model systems allow for high resolution detection of bacterial pulmonary disease which will facilitate studies of therapeutics and basic science evaluation of melioidosis. C1 [Warawa, Jonathan M.; Gherardini, Frank C.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Warawa, Jonathan M.] Univ Louisville, Dept Microbiol & Immunol, Ctr Predict Med, Louisville, KY 40202 USA. [Long, Dan; Rosenke, Rebecca; Gardner, Don] NIAID, Rocky Mt Vet Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Warawa, JM (reprint author), Univ Louisville, Dept Microbiol & Immunol, Ctr Predict Med, 505 South Hancock St,CTRB 619, Louisville, KY 40202 USA. EM jonathan.warawa@louisville.edu FU Intramural Research Program of the NIH NIAID FX This research was supported by Intramural Research Program of the NIH NIAID. We thank D Matthew Lawrenz for his critical evaluation of this manuscript. NR 32 TC 15 Z9 15 U1 0 U2 0 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-302X J9 FRONT MICROBIOL JI Front. Microbiol. PY 2011 VL 2 AR 133 DI 10.3389/fmicb.2011.00133 PG 12 WC Microbiology SC Microbiology GA V31DE UT WOS:000208863500143 PM 21720539 ER PT J AU Yoshida, T Kao, S Strebel, K AF Yoshida, Takeshi Kao, Sandra Strebel, Klaus TI Identification of residues in the BST-2 TM domain important for antagonism by HIV-1 Vpu using a gain-of-function approach SO FRONTIERS IN MICROBIOLOGY LA English DT Article DE BST-2; tetherin; Vpu; restriction factor; HIV-1 AB The HIV-1 Vpu protein enhances the release of viral particles from the cell-surface in a cell-type specific manner. In the absence of Vpu, nascent virions remain tethered to the cell-surface in restricted cell-types. Recently, the human host factor BST-2/CD317/tetherin was found to be responsible for the inhibition of virus release. It was also reported that HIV-1 Vpu can target human BST-2 but is unable to interfere with the function of murine or simian BST-2. We performed a gain-of-function study to determine which of the differences between human and rhesus BST-2 account for the differential sensitivity to Vpu. We transferred human BST-2 sequences into rhesus BST-2 and assessed the resulting chimeras for inhibition of HIV-1 virus release and sensitivity to Vpu. We found that rhesus BST-2 carrying the transmembrane (TM) domain of human BST-2 is susceptible to HIV-1 Vpu. Finally, a single-amino-acid change in the rhesus BST-2 TM domain was sufficient to confer Vpu sensitivity. C1 [Yoshida, Takeshi; Kao, Sandra; Strebel, Klaus] NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Strebel, K (reprint author), NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, Bldg 4,Room 310,4 Ctr Dr MSC 0460, Bethesda, MD 20892 USA. EM kstrebel@nih.gov FU NIH; Intramural Research Program of the NIH, NIAID FX We would like to thank Masashi Shingai for helpful discussion and for generously providing pooled rhesus macaque RNA for cloning of rhesus BST-2. We are grateful to Eri Miyagi, Amy Andrew, Robert C. Walker, Jr., and Sarah Welbourn for valuable suggestions and for critical comments on the manuscript. Thanks also to the members of the LMM core facility for sequence analysis and oligonucleotide synthesis. Pooled HIV-1 positive patient serum was obtained from the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: HIV-IG from NABI and NHLBI (Cat # 3957). This work was supported in part by a Grant from the NIH Intramural AIDS Targeted Antiviral Program to Klaus Strebel and by the Intramural Research Program of the NIH, NIAID. NR 60 TC 10 Z9 10 U1 0 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-302X J9 FRONT MICROBIOL JI Front. Microbiol. PY 2011 VL 2 AR 35 DI 10.3389/fmicb.2011.00035 PG 11 WC Microbiology SC Microbiology GA V31DE UT WOS:000208863500045 PM 21687426 ER PT J AU Chuang, DM Wang, ZF Chiu, CT AF Chuang, De-Maw Wang, Zhifei Chiu, Chi-Tso TI GSK-3 as a target for lithium-induced neuroprotection against excitotoxicity in neuronal cultures and animal models of ischemic stroke SO FRONTIERS IN MOLECULAR NEUROSCIENCE LA English DT Review DE lithium; glycogen synthase kinase-3; excitotoxicity; cerebral ischemia; mesenchymal stem cells AB The mood stabilizer lithium inhibits glycogen synthase kinase-3 (GSK-3) directly or indirectly by enhancing serine phosphorylation of both alpha and beta isoforms. Lithium robustly protected primary brain neurons from glutamate-induced excitotoxicity; these actions were mimicked by other GSK-3 inhibitors or silencing/inhibiting GSK-3 alpha and/or beta isoforms. Lithium rapidly activated Akt to enhance GSK-3 serine phosphorylation and to block glutamate-induced Akt inactivation. Lithium also up-regulated Bcl-2 and suppressed glutamate-induced p53 and Bax. Induction of brain-derived neurotrophic factor (BDNF) was required for lithium's neuroprotection to occur. BDNF promoter IV was activated by GSK-3 inhibition using lithium or other drugs, or through gene silencing/inactivation of either isoform. Further, lithium's neuroprotective effects were associated with inhibition of NMDA receptor-mediated calcium influx and down-stream signaling. In rodent ischemic models, post-insult treatment with lithium decreased infarct volume, ameliorated neurological deficits, and improved functional recovery. Up-regulation of heat-shock protein 70 and Bcl-2 as well as down-regulation of p53 likely contributed to lithium's protective effects. Delayed treatment with lithium improved functional MRI responses, which was accompanied by enhanced angiogenesis. Two GSK-3-regulated pro-angiogenic factors, matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor were induced by lithium. Finally, lithium promoted migration of mesenchymal stem cells (MSCs) by up-regulation of MMP-9 through GSK-3 beta inhibition. Notably, transplantation of lithium-primed MSCs into ischemic rats enhanced MSC migration to the injured brain regions and improved the neurological performance. Several other GSK-3 inhibitors have also been reported to be beneficial in rodent ischemic models. Together, GSK-3 inhibition is a rational strategy to combat ischemic stroke and other excitotoxicity-related brain disorders. C1 [Chuang, De-Maw; Wang, Zhifei; Chiu, Chi-Tso] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, Bldg 10,Room 3D38,10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov RI Wang, Zhifei/I-2787-2013 FU Intramural Research Program of the National Institute of Mental Health (NIMH); National Institutes of Health; Hsu family gift fund FX This work was supported by the Intramural Research Program of the National Institute of Mental Health (NIMH), National Institutes of Health, and the Hsu family gift fund. The authors would like to thank Dr. Elizabeth Sherman, Peter Leeds, and Fairouz Chibane of the NIMH for their editorial assistance. NR 105 TC 50 Z9 51 U1 0 U2 11 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5099 J9 FRONT MOL NEUROSCI JI Front. Molec. Neurosci. PY 2011 VL 4 AR 15 DI 10.3389/fnmol.2011.00015 PG 12 WC Neurosciences SC Neurosciences & Neurology GA V38VE UT WOS:000209370100013 PM 21886605 ER PT J AU Diamond, JS AF Diamond, Jeffrey S. TI Calcium-permeable AMPA receptors in the retina SO FRONTIERS IN MOLECULAR NEUROSCIENCE LA English DT Review DE apoptosis; TARP; vision; polyamine; review; ganglion cell; receptor trafficking; feedback AB The retina transforms light entering the eye into a sophisticated neural representation of our visual world. Specialized synapses, cells, and circuits in the retina have evolved to encode luminance, contrast, motion, and other complex visual features. Although a great deal has been learned about the cellular morphology and circuitry that underlies this image processing, many of the synapses in the retina remain incompletely understood. For example, excitatory synapses in the retina feature the full panoply of glutamate receptors, but in most cases specific roles for different receptor subtypes are unclear. In this brief review, I will discuss recent progress toward understanding how Ca2+-permeable AMPA receptors (CP-GluARs) contribute to synaptic transmission and newly discovered forms of synaptic plasticity in the retina. C1 NINDS, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Diamond, JS (reprint author), NINDS, Synapt Physiol Sect, NIH, 35 Convent Dr,Bldg 35,Room 3C-1000, Bethesda, MD 20892 USA. EM diamondj@ninds.nih.gov FU NINDS Intramural Research Program FX This work was supported by the NINDS Intramural Research Program. NR 59 TC 11 Z9 11 U1 0 U2 0 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5099 J9 FRONT MOL NEUROSCI JI Front. Molec. Neurosci. PY 2011 VL 4 AR 27 DI 10.3389/fnmol.2011.00027 PG 5 WC Neurosciences SC Neurosciences & Neurology GA V38VE UT WOS:000209370100024 PM 21991245 ER PT J AU Gorospe, M Tominaga, K Wu, X Fahling, M Ivan, M AF Gorospe, Myriam Tominaga, Kumiko Wu, Xue Faehling, Michael Ivan, Mircea TI Post-transcriptional control of the hypoxic response by RNA-binding proteins and microRNAs SO FRONTIERS IN MOLECULAR NEUROSCIENCE LA English DT Review DE hypoxia; post-transcriptional gene regulation; microRNAs; RNA-binding proteins; mRNA turnover; translational control; ribonucleoprotein complex; untranslated regions AB Mammalian gene expression patterns change profoundly in response to low oxygen levels. These changes in gene expression programs are strongly influenced by post-transcriptional mechanisms mediated by mRNA-binding factors: RNA-binding proteins (RBPs) and microRNAs (miRNAs). Here, we review the RBPs and miRNAs that modulate mRNA turnover and translation in response to hypoxic challenge. RBPs such as HuR (human antigen R), RIB (polypyrimidine tract-binding protein), heterogeneous nuclear ribonucleoproteins (hnRNPs), tristetraprolin, nucleolin, iron-response element-binding proteins (IRPs), and cytoplasmic polyadenylation-element-binding proteins (CPEBs), selectively bind to numerous hypoxia-regulated transcripts and play a major role in establishing hypoxic gene expression patterns. MiRNAs including miR-210, miR-373, and miR-21 associate with hypoxia-regulated transcripts and further modulate the levels of the encoded proteins to implement the hypoxic gene expression profile. We discuss the potent regulation of hypoxic gene expression by RBPs and miRNAs and their integrated actions in the cellular hypoxic response. C1 [Gorospe, Myriam; Tominaga, Kumiko] NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Wu, Xue; Ivan, Mircea] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. [Faehling, Michael] Charite, Inst Vegetat Physiol, D-13353 Berlin, Germany. RP Gorospe, M (reprint author), NIA, RNA Regulat Sect, Lab Mol Biol & Immunol, Intramural Res Program,NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov; michael.faehling@charite.de RI Ivan, Mircea/A-8109-2012 FU Intramural Research Program of the National Institute on Aging, National Institutes of Health; American Cancer Society Research Scholar Grant; Deutsche Forschungsgemeinschaft (DFG) [FA845/2-2] FX Myriam Gorospe and Kumiko Tominaga were supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. Mircea. Ivan and Xue Wu are supported by an American Cancer Society Research Scholar Grant. Michael Fahling is supported by the Deutsche Forschungsgemeinschaft (DFG, grant FA845/2-2). NR 161 TC 48 Z9 49 U1 2 U2 9 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5099 J9 FRONT MOL NEUROSCI JI Front. Molec. Neurosci. PY 2011 VL 4 AR 7 DI 10.3389/fnmol.2011.00007 PG 14 WC Neurosciences SC Neurosciences & Neurology GA V38VE UT WOS:000209370100005 PM 21747757 ER PT J AU Hansen, KA Hillenbrand, SF Ungerleider, LG AF Hansen, Kathleen A. Hillenbrand, Sarah F. Ungerleider, Leslie G. TI Persistency of priors-induced bias in decision behavior and the fMRI signal SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE choice; experience; expectation AB It is well known that people take advantage of prior knowledge to bias decisions. To investigate this phenomenon behaviorally and in the brain, we acquired fMRI data while human subjects viewed ambiguous abstract shapes and decided whether a shape was of Category A (smoother) or B (bumpier). The decision was made in the context of one of two prior knowledge cues, 80/20 and 50/50. The 80/20 cue indicated that upcoming shapes had an 80% probability of being of one category, e.g., B, and a 20% probability of being of the other. The 50/50 cue indicated that upcoming shapes had an equal probability of being of either category. The ideal observer would bias decisions in favor of the indicated alternative at 80/20 and show zero bias at 50/50. We found that subjects did bias their decisions in the predicted direction at 80/20 but did not show zero bias at 50/50. Instead, at 50/50 the subjects retained biases of the same sign as their 80/20 biases, though of diminished magnitude. The signature of a persistent though diminished bias at 50/50 was also evident in fMRI data from frontal and parietal regions previously implicated in decision-making. As a control, we acquired fMRI data from naive subjects who experienced only the 50/50 stimulus distributions during both the pre-scan training and the fMRI experiment. The behavioral and fMRI data from the naive subjects reflected decision biases closer to those of the ideal observer than those of the prior knowledge subjects at 50/50. The results indicate that practice making decisions in the context of non-equal prior probabilities biases decisions made later when prior probabilities are equal. This finding may be related to the "anchoring and adjustment" strategy described in the psychology, economics, and marketing literatures, in which subjects adjust a first approximation response - the "anchor" - based on additional information, typically applying insufficient adjustment relative to the ideal observer. C1 [Hansen, Kathleen A.; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Hillenbrand, Sarah F.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. RP Hansen, KA (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. EM hansenka@mail.nih.gov NR 31 TC 4 Z9 4 U1 0 U2 0 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PY 2011 VL 5 AR UNSP 29 DI 10.3389/fnins.2011.00029 PG 9 WC Neurosciences SC Neurosciences & Neurology GA V36GI UT WOS:000209200600027 PM 21647208 ER PT J AU Kiselycznyk, C Holmes, A AF Kiselycznyk, Carly Holmes, Andrew TI All (C57BL/6) mice are not created equal SO FRONTIERS IN NEUROSCIENCE LA English DT Article C1 [Kiselycznyk, Carly; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, Rockville, MD 20852 USA. RP Kiselycznyk, C (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, Rockville, MD 20852 USA. EM kiselycznykc@mail.nih.gov FU National Institute on Alcohol Abuse and Alcoholism Intramural Research Program FX Thanks to John Crabbe and Valerie Bolivar for valuable comments. The authors are supported by the National Institute on Alcohol Abuse and Alcoholism Intramural Research Program. NR 23 TC 18 Z9 18 U1 1 U2 4 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PY 2011 VL 5 AR 10 DI 10.3389/fnins.2011.00010 PG 3 WC Neurosciences SC Neurosciences & Neurology GA V36GI UT WOS:000209200600009 PM 21390289 ER PT J AU Heim, S Wirth, N Keil, A AF Heim, Sabine Wirth, Nadine Keil, Andreas TI Competition for cognitive resources during rapid serial processing: changes across childhood SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE attention; development; children; rapid serial visual processing; attentional blink AB The ability to direct cognitive resources to target objects despite distraction by competing information plays an important role for the development of mental aptitudes and skills. We examined developmental changes of this ability in a cross-sectional design, using the "attentional blink" (AB) paradigm. The AB is a pronounced impairment of T2 report, which occurs when a first (T1) and second target (T2) embedded in a rapid stimulus sequence are separated by at least one distractor and occur within 500 ms of each other. Two groups of children (6- to 7-year-olds and 10- to 11-year-olds; ns = 21 and 24, respectively) were asked to identify green targets in two AB tasks: one using non-linguistic symbols and the other letters or words. The temporal distance or stimulus-onset asynchrony (SOA) between T1 and T2 varied between no intervening distractor (Lag 1, 116-ms SOA) and up to 7 intervening distractors (Lag 8, 928-ms SOA). In the symbol task, younger children linearly increased T2 identification with increasing lag. Older children, however, displayed a hook-shaped pattern as typically seen in adults, with lowest identification reports in T2 symbols at the critical blink interval (Lag 2, 232-ms SOA), and a slight performance gain for the Lag 1 condition. In the verbal task, the older group again exhibited a prominent drop in T2 identification at Lag 2, whereas the younger group showed a more alleviated and temporally diffuse AB impairment. Taken together, this pattern of results suggests that the control of attention allocation and/or working memory consolidation of targets among distractors represents a cognitive skill that emerges during primary school age. C1 [Heim, Sabine] German Inst Int Educ Res, Ctr Res Individual Dev & Adapt Educ, D-60486 Frankfurt, Germany. [Heim, Sabine; Wirth, Nadine] Univ Konstanz, Dept Psychol, Constance, Germany. [Keil, Andreas] Univ Florida, Dept Psychol, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32611 USA. RP Heim, S (reprint author), German Inst Int Educ Res, Ctr Res Individual Dev & Adapt Educ, Solmsstr 73-75, D-60486 Frankfurt, Germany. EM heim@dipf.de RI Keil, Andreas/F-9427-2011 OI Keil, Andreas/0000-0002-4064-1924 FU NIMH NIH HHS [R01 MH084932] NR 45 TC 5 Z9 5 U1 2 U2 7 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PY 2011 VL 2 AR 9 DI 10.3389/fpsyg.2011.00009 PG 10 WC Psychology, Multidisciplinary SC Psychology GA V31DG UT WOS:000208863700021 PM 21713183 ER PT J AU Rong, F Holroyd, T Husain, FT Contreras-Vidal, JL Horwitz, B AF Rong, Feng Holroyd, Tom Husain, Fatima T. Contreras-Vidal, Jose L. Horwitz, Barry TI Task-specific modulation of human auditory evoked response in a delayed-match-to-sample task SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE task-specificity; cognitive modulation; auditory evoked response; MEG; functional interaction AB In this study, we focus our investigation on task-specific cognitive modulation of early cortical auditory processing in human cerebral cortex. During the experiments, we acquired whole-head magnetoencephalography data while participants were performing an auditory delayed-match-to-sample (DMS) task and associated control tasks. Using a spatial filtering beamformer technique to simultaneously estimate multiple source activities inside the human brain, we observed a significant DMS-specific suppression of the auditory evoked response to the second stimulus in a sound pair, with the center of the effect being located in the vicinity of the left auditory cortex. For the right auditory cortex, a non-invariant suppression effect was observed in both DMS and control tasks. Furthermore, analysis of coherence revealed a beta band (12 similar to 20 Hz) DMS-specific enhanced functional interaction between the sources in left auditory cortex and those in left inferior frontal gyrus, which has been shown to be involved in short-term memory processing during the delay period of DMS task. Our findings support the view that early evoked cortical responses to incoming acoustic stimuli can be modulated by task-specific cognitive functions by means of frontal-temporal functional interactions. C1 [Rong, Feng; Husain, Fatima T.; Horwitz, Barry] Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. [Rong, Feng; Contreras-Vidal, Jose L.] Univ Maryland, Dept Kinesiol, Grad Program Neurosci, College Pk, MD 20742 USA. [Rong, Feng; Contreras-Vidal, Jose L.] Univ Maryland, Dept Kinesiol, Grad Program Cognit Sci, College Pk, MD 20742 USA. [Holroyd, Tom] NIMH, MEG Core Facil, NIH, Bethesda, MD 20892 USA. RP Horwitz, B (reprint author), Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bldg 10,Room 5D39 10 Ctr Dr, Bethesda, MD 20892 USA. EM horwitzb@nidcd.nih.gov NR 90 TC 4 Z9 4 U1 0 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PY 2011 VL 2 AR 85 DI 10.3389/fpsyg.2011.00085 PG 15 WC Psychology, Multidisciplinary SC Psychology GA V31DG UT WOS:000208863700097 PM 21687454 ER PT B AU Pandiri, AR Lahousse, SA Sills, RC AF Pandiri, Arun R. Lahousse, Stephanie A. Sills, Robert C. BE Bolon, B Butt, MT TI MOLECULAR TECHNIQUES IN TOXICOLOGICAL NEUROPATHOLOGY SO FUNDAMENTAL NEUROPATHOLOGY FOR PATHOLOGISTS AND TOXICOLOGISTS: PRINCIPLES AND TECHNIQUES LA English DT Article; Book Chapter ID LASER-CAPTURE MICRODISSECTION; MESSENGER-RNA AMPLIFICATION; CDNA MICROARRAY EXPERIMENTS; IMAGING MASS-SPECTROMETRY; CONTROL MAQC PROJECT; ADULT-MOUSE BRAIN; GENE-EXPRESSION; PROTEOMIC ANALYSIS; POSTMORTEM BRAIN; ALZHEIMERS-DISEASE C1 [Pandiri, Arun R.; Lahousse, Stephanie A.; Sills, Robert C.] NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Pandiri, AR (reprint author), NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 137 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-93994-9; 978-0-470-22733-6 PY 2011 BP 285 EP 318 D2 10.1002/9780470939956 PG 34 WC Clinical Neurology; Toxicology SC Neurosciences & Neurology; Toxicology GA BA6JJ UT WOS:000337159300023 ER PT J AU Park, EM Liu, BG Xia, XJ Zhu, F Jami, WB Hu, YL AF Park, Eunmi Liu, Bigang Xia, Xiaojun Zhu, Feng Jami, Willette-Brown Hu, Yinling TI Role of IKK alpha in skin squamous cell carcinomas SO FUTURE ONCOLOGY LA English DT Review DE carcinogenesis; EGFR; gene mutations; IKK alpha; keratinocyte differentiation and proliferation; squamous cell carcinoma; TGF beta ID NF-KAPPA-B; SEVERE LIVER DEGENERATION; GROWTH-FACTOR RECEPTOR; GAMMA-DEFICIENT MICE; HARVEY-RAS ONCOGENE; KINASE-ALPHA; TERMINAL DIFFERENTIATION; INCONTINENTIA PIGMENTI; TGF-BETA; HA-RAS AB Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are two major types of skin cancer derived from keratinocytes. SCC is a more aggressive type of cancer than BCC in humans. One significant difference between SCC and BCC is that SCC development is generally associated with cell dedifferentiation and morphological changes. When SCC is converted to spindle cell carcinoma, the latest stage of cancer, the tumor cells change to a fibroblastic cell morphology (epithelial-to-mesenchymal transition) and lose their differentiation markers. Recently, several laboratories have reported altered I kappa B kinase alpha (IKK alpha) protein localization, downregulated IKK alpha, and IKK alpha gene deletions and mutations in human SCCs of the skin, lung, esophagus, and neck and head. In addition, IKK alpha reduction promotes chemical carcinogen- and ultraviolet B-induced skin carcinogenesis, and IKK alpha deletion in keratinocytes causes spontaneous skin SCCs, but not BCCs, in mice. Thus, IKK alpha emerges as a bona fide skin tumor suppressor. In this article, we will discuss the role of IKK alpha in skin SCC development. C1 [Jami, Willette-Brown; Hu, Yinling] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA. [Park, Eunmi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Liu, Bigang; Zhu, Feng] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX 78957 USA. [Xia, Xiaojun] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. RP Hu, YL (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA. EM huy2@mail.nih.gov FU National Cancer Institute [CA102510, CA117314, CA105345] FX National Cancer Institute grants CA102510 and CA117314 (to Yinling Hu), CA105345 (to Susan M Fischer), and the National Cancer Institute intramural budget supported the work. 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 79 TC 6 Z9 6 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 J9 FUTURE ONCOL JI Future Oncol. PD JAN PY 2011 VL 7 IS 1 BP 123 EP 134 DI 10.2217/FON.10.166 PG 12 WC Oncology SC Oncology GA 719BJ UT WOS:000287173900014 PM 21174543 ER PT S AU Costanzi, S AF Costanzi, Stefano BE Giraldo, J Pin, JP TI Structure-based Virtual Screening for Ligands of G Protein-coupled Receptors SO G PROTEIN-COUPLED RECEPTORS: FROM STRUCTURE TO FUNCTION SE RSC Drug Discovery Series LA English DT Article; Book Chapter ID STRUCTURE-BASED DISCOVERY; BETA(2)-ADRENERGIC RECEPTOR; CRYSTAL-STRUCTURE; HOMOLOGY MODELS; DRUG DISCOVERY; BINDING; ANTAGONISTS; RHODOPSIN; PREDICTION; MODULATORS C1 NIDDK, Lab Biol Modeling, NIH, DHHS, Bethesda, MD 20892 USA. RP Costanzi, S (reprint author), NIDDK, Lab Biol Modeling, NIH, DHHS, Bethesda, MD 20892 USA. NR 40 TC 5 Z9 5 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 2041-3203 BN 978-1-84973-183-6; 978-1-84973-344-1 J9 RSC DRUG DISCOV JI RSC Drug Discov. PY 2011 IS 8 BP 359 EP 374 DI 10.1039/9781849733441-00359 D2 10.1039/9781849733441 PG 16 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BIE27 UT WOS:000327871700020 ER PT J AU Wininger, M AF Wininger, Michael TI A regressed phase analysis for coupled joint systems SO GAIT & POSTURE LA English DT Article DE Joint coupling; Kinematics; Gait; Phase analysis; Cerebral palsy ID INTERJOINT COORDINATION; GAIT AB This study aims to address shortcomings of the relative phase analysis, a widely used method for assessment of coupling among joints of the lower limb. Goniometric data from 15 individuals with spastic diplegic cerebral palsy were recorded from the hip and knee joints during ambulation on a flat surface, and from a single healthy individual with no known motor impairment, over at least 10 gait cycles. The minimum relative phase (MRP) revealed substantial disparity in the timing and severity of the instance of maximum coupling, depending on which reference frame was selected: MRP(knee-hip) differed from MRP(hip-knee) by 16.1 +/- 14% of gait cycle and 50.6 +/- 77% difference in scale. Additionally, several relative phase portraits contained discontinuities which may contribute to error in phase feature extraction. These vagaries can be attributed to the predication of relative phase analysis on a transformation into the velocity-position phase plane, and the extraction of phase angle by the discontinuous arctangent operator. Here, an alternative phase analysis is proposed, wherein kinematic data is transformed into a profile of joint coupling across the entire gait cycle. By comparing joint velocities directly via a standard linear regression in the velocity-velocity phase plane, this regressed phase analysis provides several key advantages over relative phase analysis including continuity, commutativity between reference frames, and generalizability to many-joint systems. (C) 2010 Elsevier B.V. All rights reserved. C1 [Wininger, Michael] NIMH, Clin Brain Disorders Branch, NIH, IRP,CBDB,GCAP, Bethesda, MD 20892 USA. [Wininger, Michael] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. RP Wininger, M (reprint author), NIMH, Clin Brain Disorders Branch, NIH, IRP,CBDB,GCAP, Bldg 10,Room 4N313D, Bethesda, MD 20892 USA. EM michael.wininger@nih.gov FU NIDRR RERC FX The author gratefully acknowledges Eileen Fowler Ph.D., PT, and Evan Goldberg M.S. for furnishing the data on which this report is based. William Craelius Ph.D., Nam-Hun Kim Ph.D., are acknowledged for technical assistance, Troy Shinbrot Ph.D., and Don Yungher Ph.D., for their helpful contributions, and Catherine-Anne Nash A.S., C.V.T., for assistance in writing and editing. Work funded in part by a NIDRR RERC grant to W.C. NR 14 TC 1 Z9 1 U1 2 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD JAN PY 2011 VL 33 IS 1 BP 136 EP 139 DI 10.1016/j.gaitpost.2010.09.011 PG 4 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 724FI UT WOS:000287561100026 PM 20971643 ER PT J AU Parkman, HP Yates, K Hasler, WL Nguyen, L Pasricha, PJ Snape, WJ Farrugia, G Koch, KL Abell, TL McCallum, RW Lee, L Unalp-Arida, A Tonascia, J Hamilton, F AF Parkman, Henry P. Yates, Katherine Hasler, William L. Nguyen, Linda Pasricha, Pankaj J. Snape, William J. Farrugia, Gianrico Koch, Kenneth L. Abell, Thomas L. McCallum, Richard W. Lee, Linda Unalp-Arida, Aynur Tonascia, James Hamilton, Frank CA Natl Inst Diabet Digestive Kidney TI Clinical Features of Idiopathic Gastroparesis Vary With Sex, Body Mass, Symptom Onset, Delay in Gastric Emptying, and Gastroparesis Severity SO GASTROENTEROLOGY LA English DT Article DE Gastroparesis; Gastric Emptying; Nausea; Vomiting; Functional Dyspepsia ID UPPER GASTROINTESTINAL DISORDERS; BECK DEPRESSION INVENTORY; FUNCTIONAL DYSPEPSIA; SOLIDS; INDEX; DYSFUNCTION; VALIDATION AB BACKGROUND & AIMS: Idiopathic gastroparesis (IG) is a common but poorly understood condition with significant morbidity. We studied characteristics of patients with IG enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Registry. METHODS: Data from medical histories, symptom questionnaires, and 4-hour gastric emptying scintigraphy studies were obtained from patients with IG. RESULTS: The mean age of 243 patients with IG studied was 41 years; 88% were female, 46% were overweight, 50% had acute onset of symptoms, and 19% reported an initial infectious prodrome. Severe delay in gastric emptying (>35% retention at 4 hours) was present in 28% of patients. Predominant presenting symptoms were nausea (34%), vomiting (19%), an abdominal pain (23%). Women had more severe nausea, satiety, constipation, and overall gastroparesis symptoms. Patients who experienced acute-onset IG had worse nausea than those with insidious onset. Overweight patients had more bloating and gastric retention at 2 hours but less severe loss of appetite. Patients with severely delayed gastric emptying had worse vomiting and more severe loss of appetite and overall gastroparesis symptoms. Severe anxiety and depression were present in 36% and 18%, respectively. A total of 86% met criteria for functional dyspepsia, primarily postprandial distress syndrome. CONCLUSIONS: IG is a disorder that primarily affects young women, beginning acutely in 50% of cases; unexpectedly, many patients are overweight. Severe delay in gastric emptying was associated with more severe symptoms of vomiting and loss of appetite. IG is a diverse syndrome that varies by sex, body mass, symptom onset, and delay in gastric emptying. C1 [Parkman, Henry P.] Temple Univ, Sch Med, Gastroenterol Sect, Philadelphia, PA 19140 USA. [Yates, Katherine; Lee, Linda; Unalp-Arida, Aynur; Tonascia, James] Johns Hopkins Univ, Baltimore, MD USA. [Hasler, William L.] Univ Michigan, Ann Arbor, MI 48109 USA. [Nguyen, Linda; Pasricha, Pankaj J.] Stanford Univ, Palo Alto, CA 94304 USA. [Snape, William J.] Calif Pacific Med Ctr, San Francisco, CA USA. [Farrugia, Gianrico] Mayo Clin, Rochester, MN USA. [Koch, Kenneth L.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Abell, Thomas L.] Univ Mississippi, Jackson, MS 39216 USA. [McCallum, Richard W.] Texas Tech Univ, Dept Med, El Paso, TX USA. [Hamilton, Frank] NIDDKD, Bethesda, MD 20892 USA. RP Parkman, HP (reprint author), Temple Univ, Sch Med, Gastroenterol Sect, 8th Floor,3401 N Broad St, Philadelphia, PA 19140 USA. EM henry.parkman@temple.edu RI Vaughn, Ivana/B-6138-2016 OI Vaughn, Ivana/0000-0002-7201-0289 FU National Institute of Diabetes and Digestive and Kidney Diseases [U01DK073983, U01DK073975, U01DK073985, U01DK074007, U01DK073974, U01DK074008] FX The Gastroparesis Clinical Research Consortium is supported by National Institute of Diabetes and Digestive and Kidney Diseases grants U01DK073983, U01DK073975, U01DK073985, U01DK074007, U01DK073974, and U01DK074008. NR 36 TC 99 Z9 102 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2011 VL 140 IS 1 BP 101 EP + DI 10.1053/j.gastro.2010.10.015 PG 25 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 697HF UT WOS:000285503200026 PM 20965184 ER PT J AU Wilson, MS Ramalingam, TR Rivollier, A Shenderov, K Mentink-Kane, MM Madala, SK Cheever, AW Artis, D Kelsall, BL Wynn, TA AF Wilson, Mark S. Ramalingam, Thirumalai R. Rivollier, Aymeric Shenderov, Kevin Mentink-Kane, Margaret M. Madala, Satish K. Cheever, Allen W. Artis, David Kelsall, Brian L. Wynn, Thomas A. TI Colitis and Intestinal Inflammation in IL10(-/-) Mice Results From IL-13R alpha 2-Mediated Attenuation of IL-13 Activity SO GASTROENTEROLOGY LA English DT Article DE Colitis; Helminth; IBD; Th17 ID NK-T-CELLS; BOWEL-DISEASE; ULCERATIVE-COLITIS; NEMATODE INFECTION; CROHNS-DISEASE; INTERLEUKIN-10-DEFICIENT MICE; AIRWAY INFLAMMATION; CYTOKINE PRODUCTION; TH17 CELLS; RECEPTOR AB BACKGROUND & AIMS: The cytokine interleukin (IL)-10 is required to maintain immune homeostasis in the gastrointestinal tract. IL-10 null mice spontaneously develop colitis or are more susceptible to induction of colitis by infections, drugs, and autoimmune reactions. IL-13 regulates inflammatory conditions; its activity might be compromised by the IL-13 decoy receptor (IL-13R alpha 2). METHODS: We examined the roles of IL-13 and IL-13R alpha 2 in intestinal inflammation in mice. To study the function of IL-13R alpha 2, il10(-/-) mice were crossed with il13r alpha 2(-/-) to generate il10(-/-) il13r alpha 2(-/-) double knockout (dKO) mice. Colitis was induced with the gastrointestinal toxin piroxicam or Trichuris muris infection. RESULTS: Induction of colitis by interferon (IFN)-gamma or IL-17 in IL-10 null mice requires IL-13R alpha 2. Following exposure of il10(-/-) mice to piroxicam or infection with T muris, production of IL-13R alpha 2 increased, resulting in decreased IL-13 bioactivity and increased inflammation in response to IFN-gamma or IL-17A. In contrast to il10(-/-) mice, dKO mice were resistant to piroxicam-induced colitis; they also developed less severe colitis during chronic infection with T muris infection. In both models, resistance to IFN-gamma and IL-17-mediated intestinal inflammation was associated with increased IL-13 activity. Susceptibility to colitis was restored when the dKO mice were injected with monoclonal antibodies against IL-13, confirming its protective role. CONCLUSIONS: Colitis and intestinal inflammation in IL10(-/-) mice results from IL-13R alpha 2-mediated attenuation of IL-13 activity. In the absence of IL-13R alpha 2, IL-13 suppresses proinflammatory Th1 and Th17 responses. Reagents that block the IL-13 decoy receptor IL-13R alpha 2 might be developed for inflammatory bowel disease associated with increased levels of IFN-gamma and IL-17. C1 [Wilson, Mark S.; Ramalingam, Thirumalai R.; Mentink-Kane, Margaret M.; Madala, Satish K.; Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Shenderov, Kevin] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Rivollier, Aymeric; Kelsall, Brian L.] NIAID, Lab Mucosal Immunol, NIH, Bethesda, MD 20892 USA. [Cheever, Allen W.] Biomed Res Inst, Rockville, MD 20852 USA. [Artis, David] Univ Penn, Dept Pathobiol, Philadelphia, PA 19104 USA. RP Wynn, TA (reprint author), 50 South Dr,Rm 6154,MSC 8003, Bethesda, MD 20892 USA. EM twynn@niaid.nih.gov RI Wynn, Thomas/C-2797-2011 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Institutes of Health [AI61570]; William and Shelby Modell Family Foundation FX Supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. David Artis is funded by National Institutes of Health grant nos. AI61570 and Crohn's and Colitis Foundation of America's William and Shelby Modell Family Foundation Research Award. NR 52 TC 44 Z9 46 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2011 VL 140 IS 1 BP 254 EP + DI 10.1053/j.gastro.2010.09.047 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 697HF UT WOS:000285503200041 PM 20951137 ER PT J AU Bruno, RD Smith, GH AF Bruno, Robert D. Smith, Gilbert H. TI Role of Epithelial Stem/Progenitor Cells in Mammary Cancer SO GENE EXPRESSION LA English DT Article DE Breast cancer; Mammary biology; Stem cells; Progenitor cells; Tumorigenesis ID BRCA1-RELATED BREAST-CANCER; ADULT HUMAN BREAST; STEM-CELL; IN-VIVO; TGF-BETA-1 EXPRESSION; PROGENITOR CELLS; TUMOR-CELLS; MOUSE; GLAND; PHENOTYPE AB Both mouse and human mammary glands contain stem/progenitor functional hierarchies that are maintained through the entire life span of the animal. Cells with such functional capacities are potential candidates for tumorigenesis as they are long lived, multipotent, and self-renewing. Using the mouse as a model, this review will discuss what is known about the mammary stem/progenitor hierarchy, the evidence that particular progenitor functions are susceptible to tumorigenic stimuli, how these findings in mice are relevant to the disease in humans, and the role of the local microenvironment in controlling tumorigenesis. C1 [Bruno, Robert D.; Smith, Gilbert H.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Smith, GH (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, Bldg 37,Room 1112B,37 Convent Dr, Bethesda, MD 20892 USA. EM smithg@mail.nih.gov OI Bruno, Robert/0000-0003-3329-9478 NR 43 TC 4 Z9 4 U1 1 U2 6 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 1052-2166 J9 GENE EXPRESSION JI Gene Expr. PY 2011 VL 15 IS 3 SI SI BP 133 EP 140 DI 10.3727/105221611X13176664479368 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 862BQ UT WOS:000298065200004 PM 22268295 ER PT J AU Gao, R Yan, X Zheng, C Goldsmith, CM Afione, S Hai, B Xu, J Zhou, J Zhang, C Chiorini, JA Baum, BJ Wang, S AF Gao, R. Yan, X. Zheng, C. Goldsmith, C. M. Afione, S. Hai, B. Xu, J. Zhou, J. Zhang, C. Chiorini, J. A. Baum, B. J. Wang, S. TI AAV2-mediated transfer of the human aquaporin-1 cDNA restores fluid secretion from irradiated miniature pig parotid glands SO GENE THERAPY LA English DT Article DE salivary gland; irradiation; aquaporin-1; AAV2 ID ADENOVIRAL-MEDIATED TRANSFER; MOUSE SALIVARY-GLANDS; GENE-TRANSFER; IN-VIVO; NONHUMAN-PRIMATES; NECK RADIOTHERAPY; TRANSDUCTION; TOXICITY; VECTORS; HEAD AB Previously (Shan et al, 2005), we reported that adenoviral vector-mediated transfer of the human aquaporin-1 (hAQP1) cDNA to minipig parotid glands following irradiation (IR) transiently restored salivary flow to near normal levels. This study evaluated a serotype 2, adeno-associated viral (AAV2) vector for extended correction of IR (single dose; 20 Gy)-induced, parotid salivary hypofunction in minipigs. At 16 weeks following the IR parotid salivary flow decreased by 85-90%. AAV2hAQP1 administration at week 17 transduced only duct cells and resulted in a dose-dependent increase in salivary flow to similar to 35% of pre-IR levels (to similar to 1ml per 10 min) after 8 weeks (peak response). Administration of a control AAV2 vector or saline was without effect. Little change was observed in clinical chemistry and hematology values after AAV2hAQP1 delivery. Vector-treated animals generated high anti-AAV2 neutralizing antibody titers by week 4 (similar to 1:1600) and significant elevations in salivary (similar to 15%), but not serum, granulocyte macrophage colony-stimulating factor levels. Following vector administration, salivary [Na+] was dramatically increased, from similar to 10 to similar to 55 mM (at 4 weeks) and finally to 39 mM (8 weeks). The findings demonstrate that localized delivery of AAV2hAQP1 to IR-damaged parotid glands leads to increased fluid secretion from surviving duct cells, and may be useful in providing extended relief of salivary hypofunction in previously irradiated patients. Gene Therapy (2011) 18, 38-42; doi:10.1038/gt.2010.128; published online 30 September 2010 C1 [Gao, R.; Yan, X.; Hai, B.; Xu, J.; Zhou, J.; Zhang, C.; Wang, S.] Capital Med Univ, Sch Stomatol, Salivary Gland Dis Ctr, Beijing 100050, Peoples R China. [Gao, R.; Yan, X.; Hai, B.; Xu, J.; Zhou, J.; Zhang, C.; Wang, S.] Capital Med Univ, Sch Stomatol, Mol Lab Gene Therapy, Beijing 100050, Peoples R China. [Zheng, C.; Goldsmith, C. M.; Afione, S.; Chiorini, J. A.; Baum, B. J.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Wang, S.] Capital Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100050, Peoples R China. RP Wang, S (reprint author), Capital Med Univ, Sch Stomatol, Salivary Gland Dis Ctr, Tian Tan Xi Li 4, Beijing 100050, Peoples R China. EM slwang@ccmu.edu.cn FU National Basic Research Program of China [2007CB947304, 2010CB944801]; Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the jurisdiction of Beijing Municipality [PHR20090510, 2006 ID 0301200094, KM200510025002]; Ministry of Education, China [200778]; National Institute of Dental and Craniofacial Research FX This work was supported by grants from the National Basic Research Program of China (2007CB947304 and 2010CB944801), the Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the jurisdiction of Beijing Municipality (PHR20090510, 2006 ID 0301200094 and KM200510025002), National Excellent PhD Theses Award grant from Ministry of Education, China (200778) and the Intramural Research Program of the National Institute of Dental and Craniofacial Research. NR 32 TC 25 Z9 26 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 EI 1476-5462 J9 GENE THER JI Gene Ther. PD JAN PY 2011 VL 18 IS 1 BP 38 EP 42 DI 10.1038/gt.2010.128 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 703EU UT WOS:000285960500005 PM 20882054 ER PT B AU Briest, W Talan, MI AF Briest, Wilfried Talan, Mark I. BE Ostadal, B Nagano, M Dhalla, NS TI Vascular Ehlers-Danlos Syndrome: A Good Experimental Model Is Needed for Development of Treatment Strategies SO GENES AND CARDIOVASCULAR FUNCTION LA English DT Article; Book Chapter DE Aorta; Aortic wall strength; Beta-blocker therapy; Collagen; Connective tissue; Ehlers-Danlos syndrome; Extracellular matrix; MMP inhibition; Treatment strategies ID ABDOMINAL AORTIC-ANEURYSMS; SYNDROME TYPE-IV; MARFAN-SYNDROME; III COLLAGEN; RNA INTERFERENCE; MATRIX METALLOPROTEINASES; GENETIC FEATURES; MESSENGER-RNAS; CLINICAL-TRIAL; DOXYCYCLINE AB The vascular form of the Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder. Patients have a reduced life span (under 50) due to spontaneous and often fatal rupture of blood vessels and hollow organs. Until very recently no evidence-based treatment had been available. VEDS results from mutations in the COL3A1 gene that encodes the chains of collagen type III and alters the sequence in the triple-helical domain. A mouse model of vEDS created by inactivation of the Col3a1 gene has been of limited use as only 5% of homozygous animals survived to adulthood. The haploinsufficiency for one COL3A1 allele is one of the genotypes resulting in vEDS. In this review we provide evidence that haploinsufficiency for Col3a1 in mice recapitulates features of vEDS in humans and might be used as an experimental model. There was a reduced level of aortic collagen and correspondingly reduced aortic wall strength. A spectrum of lesions was detected in the aorta similar to those observed in human patients. Lesions increased in number and age and were more common in male than in female mice. Furthermore, potential treatment strategies are discussed including the already tested beta-adrenergic receptor (AR)-blocker therapy, the inhibition of extracellular matrix degrading enzymes, and the only causative approach of selective silencing of the mutant form of COL3A1 by allele-specific RNA interference. C1 [Briest, Wilfried] Fritz Lipmann Inst, Leibniz Inst Age Res, Jena, Germany. [Talan, Mark I.] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Briest, W (reprint author), Fritz Lipmann Inst, Leibniz Inst Age Res, Jena, Germany. EM wilfried.briest@arcor.de NR 71 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7206-4 PY 2011 BP 241 EP 251 DI 10.1007/978-1-4419-7207-1_23 D2 10.1007/978-1-4419-7207-1 PG 11 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA BWM92 UT WOS:000294269500023 ER PT J AU Zhong, F Savage, SA Shkreli, M Giri, N Jessop, L Myers, T Chen, R Alter, BP Artandi, SE AF Zhong, Franklin Savage, Sharon A. Shkreli, Marina Giri, Neelam Jessop, Lea Myers, Timothy Chen, Renee Alter, Blanche P. Artandi, Steven E. TI Disruption of telomerase trafficking by TCAB1 mutation causes dyskeratosis congenita SO GENES & DEVELOPMENT LA English DT Article DE telomerase trafficking; telomerase RNP; dyskeratosis congenita ID CAJAL BODY LOCALIZATION; BONE-MARROW FAILURE; HUMAN CANCER-CELLS; REVERSE-TRANSCRIPTASE; PULMONARY-FIBROSIS; RNA; COMPONENT; BODIES; ANTICIPATION; RECRUITMENT AB Dyskeratosis congenita (DC) is a genetic disorder of defective tissue maintenance and cancer predisposition caused by short telomeres and impaired stem cell function. Telomerase mutations are thought to precipitate DC by reducing either the catalytic activity or the overall levels of the telomerase complex. However, the underlying genetic mutations and the mechanisms of telomere shortening remain unknown for as many as 50% of DC patients, who lack mutations in genes controlling telomere homeostasis. Here, we show that disruption of telomerase trafficking accounts for unknown cases of DC. We identify DC patients with missense mutations in TCAB1, a telomerase holoenzyme protein that facilitates trafficking of telomerase to Cajal bodies. Compound heterozygous mutations in TCAB1 disrupt telomerase localization to Cajal bodies, resulting in misdirection of telomerase RNA to nucleoli, which prevents telomerase from elongating telomeres. Our findings establish telomerase mislocalization as a novel cause of DC, and suggest that telomerase trafficking defects may contribute more broadly to the pathogenesis of telomere-related disease. C1 [Zhong, Franklin; Shkreli, Marina; Artandi, Steven E.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Zhong, Franklin; Artandi, Steven E.] Stanford Univ, Canc Biol Program, Sch Med, Stanford, CA 94305 USA. [Savage, Sharon A.; Giri, Neelam; Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Jessop, Lea; Chen, Renee] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Myers, Timothy] NCI Frederick, Core Genotyping Facil, SAIC Frederick Inc, NIH, Bethesda, MD 20892 USA. RP Artandi, SE (reprint author), Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. EM savagesh@mail.nih.gov; sartandi@stanford.edu RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU Agency for Science, Technology, and Research (A*STAR), Singapore; National Cancer Institute, National Institutes of Health; NIH [AG033747, CA125453, CA111691]; Leukemia and Lymphoma Society FX We are grateful to the patients and families for their valuable contributions to this study. Lisa Leathwood, RN, and Laura Harney, RN, of Westat, Inc., provided outstanding study support. We thank Dr. Jerry Hsu for assistance in acquiring control tumor samples, and Dr. Stephen Chanock (NCI) for helpful advice. F.Z. was supported by a fellowship from the Agency for Science, Technology, and Research (A*STAR), Singapore. This work was supported, in part, by the intramural research program of the National Cancer Institute, National Institutes of Health; by NIH grants AG033747, CA125453, and CA111691; and by a SCOR grant from the Leukemia and Lymphoma Society. NR 30 TC 100 Z9 107 U1 1 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 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 1 PY 2011 VL 25 IS 1 BP 11 EP 16 DI 10.1101/gad.2006411 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 702BT UT WOS:000285870300002 PM 21205863 ER PT J AU Horibata, K Saijo, M Bay, MN Lan, L Kuraoka, I Brooks, PJ Honma, M Nohmi, T Yasui, A Tanaka, K AF Horibata, Katsuyoshi Saijo, Masafumi Bay, Mui N. Lan, Li Kuraoka, Isao Brooks, Philip J. Honma, Masamitsu Nohmi, Takehiko Yasui, Akira Tanaka, Kiyoji TI Mutant Cockayne syndrome group B protein inhibits repair of DNA topoisomerase I-DNA covalent complex SO GENES TO CELLS LA English DT Article ID UV-SENSITIVE SYNDROME; CSB GENE; XERODERMA-PIGMENTOSUM; CLEAVAGE COMPLEXES; OXIDATIVE STRESS; SYNDROME CELLS; DAMAGE; DEGRADATION; DEFECT; CAMPTOTHECIN AB Two UV-sensitive syndrome patients who have mild photosensitivity without detectable somatic abnormalities lack detectable Cockayne syndrome group B (CSB) protein because of a homozygous null mutation in the CSB gene. In contrast, mutant CSB proteins are produced in CS-B patients with the severe somatic abnormalities of Cockayne syndrome and photosensitivity. It is known that the piggyBac transposable element derived 3 is integrated within the CSB intron 5, and that CSB-piggyBac transposable element derived 3 fusion (CPFP) mRNA is produced by alternative splicing. We found that CPFP or truncated CSB protein derived from CPFP mRNA was stably produced in CS-B patients, and that wild-type CSB, CPFP, and truncated CSB protein interacted with DNA topoisomerase I. We also found that CPFP inhibited repair of a camptothecin-induced topoisomerase I-DNA covalent complex. The inhibition was suppressed by the presence of wild-type CSB, consistent with the autosomal recessive inheritance of Cockayne syndrome. These results suggested that reduced repair of a DNA topoisomerase I-DNA covalent complex because of truncated CSB proteins is involved in the pathogenesis of CS-B. C1 [Horibata, Katsuyoshi; Saijo, Masafumi; Bay, Mui N.; Kuraoka, Isao; Tanaka, Kiyoji] Osaka Univ, Human Cell Biol Grp, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan. [Lan, Li; Yasui, Akira] Tohoku Univ, Inst Dev Aging & Canc, Div Dynam Proteome, Aoba Ku, Sendai, Miyagi 9808575, Japan. [Brooks, Philip J.] NIAAA, Mol Neurobiol Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Honma, Masamitsu; Nohmi, Takehiko] Natl Inst Hlth Sci, Div Genet & Mutagenesis, Setagaya Ku, Tokyo 1588501, Japan. RP Tanaka, K (reprint author), Osaka Univ, Human Cell Biol Grp, Grad Sch Frontier Biosci, 1-3 Yamadaoka, Suita, Osaka 5650871, Japan. EM ktanaka@fbs.osaka-u.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan; Health and Labor Sciences Research Grants; Ishihara Sangyo Kaisha, Ltd FX We thank Drs Takeshi Horio, Errol C. Friedberg, and Miria Stefanini for providing us CS3AM, COFS03MA, Tel-COFS02MA, and CS3PV cells, respectively. We acknowledge Dr Ryuki Hirano and Ms Yuka Iwamoto for their help, and Ms Cheryl Marietta for her assistance in editing the manuscript. This work was supported by a Grant-in-Aid for Scientific Research (S) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and Health and Labor Sciences Research Grants for research on intractable diseases. MNB is a recipient of the Graduate Biomedical Sciences Scholarship sponsored by Ishihara Sangyo Kaisha, Ltd. NR 36 TC 17 Z9 17 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1356-9597 J9 GENES CELLS JI Genes Cells PD JAN PY 2011 VL 16 IS 1 BP 101 EP 114 DI 10.1111/j.1365-2443.2010.01467.x PG 14 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 700RR UT WOS:000285762500010 PM 21143350 ER PT J AU Manning, AK LaValley, M Liu, CT Rice, K An, P Liu, YM Miljkovic, I Rasmussen-Torvik, L Harris, TB Province, MA Borecki, IB Florez, JC Meigs, JB Cupples, LA Dupuis, J AF Manning, Alisa K. LaValley, Michael Liu, Ching-Ti Rice, Kenneth An, Ping Liu, Yongmei Miljkovic, Iva Rasmussen-Torvik, Laura Harris, Tamara B. Province, Michael A. Borecki, Ingrid B. Florez, Jose C. Meigs, James B. Cupples, L. Adrienne Dupuis, Josee TI Meta-Analysis of Gene-Environment Interaction: Joint Estimation of SNP and SNP x Environment Regression Coefficients SO GENETIC EPIDEMIOLOGY LA English DT Article DE 2 degree of freedom meta-analysis; joint meta-analysis; PPARG; gene-environment interaction meta-analysis ID GENOME-WIDE ASSOCIATION; TYPE-2 DIABETES RISK; PRO12ALA POLYMORPHISM; DESIGN; HEART; OBJECTIVES; HEALTH; GAMMA AB Introduction: Genetic discoveries are validated through the meta-analysis of genome-wide association scans in large international consortia. Because environmental variables may interact with genetic factors, investigation of differing genetic effects for distinct levels of an environmental exposure in these large consortia may yield additional susceptibility loci undetected by main effects analysis. We describe a method of joint meta-analysis (JMA) of SNP and SNP by Environment (SNP x E) regression coefficients for use in gene-environment interaction studies. Methods: In testing SNP x E interactions, one approach uses a two degree of freedom test to identify genetic variants that influence the trait of interest. This approach detects both main and interaction effects between the trait and the SNP. We propose a method to jointly meta-analyze the SNP and SNP x E coefficients using multivariate generalized least squares. This approach provides confidence intervals of the two estimates, a joint significance test for SNP and SNP x E terms, and a test of homogeneity across samples. Results: We present a simulation study comparing this method to four other methods of meta-analysis and demonstrate that the JMA performs better than the others when both main and interaction effects are present. Additionally, we implemented our methods in a meta-analysis of the association between SNPs from the type 2 diabetes-associated gene PPARG and log-transformed fasting insulin levels and interaction by body mass index in a combined sample of 19,466 individuals from five cohorts. Genet. Epidemiol. 35:11-18, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Manning, Alisa K.; LaValley, Michael; Liu, Ching-Ti; Cupples, L. Adrienne; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [An, Ping; Province, Michael A.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA. [Liu, Yongmei] Wake Forest Univ, Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. [Miljkovic, Iva] Univ Pittsburgh, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15261 USA. [Rasmussen-Torvik, Laura] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Harris, Tamara B.] NIA, Geriatr Epidemiol Sect, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Cupples, L. Adrienne; Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Manning, AK (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. EM amanning@bu.edu; dupuis@bu.edu RI Rice, Kenneth/A-4150-2013 OI Rice, Kenneth/0000-0001-5779-4495 FU National Heart, Lung and Blood Institute [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Department of Medicine at Boston University School of Medicine and Boston Medical Center; Doris Duke Charitable Foundation; National Institute on Aging; National Institute for Diabetes and Digestive and Kidney Diseases [R01 DK078616, K24 DK080140, K23 DK65978, K01 DK083029]; NIA [N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]; National Institutes of Health [HHSN268200782096C, HHSN268200625226C, 5R01 HL08770003]; National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, U01HG004402, N01-HC- 85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL087652, 5R01 HL08821502]; National Institute of Neurological Disorders and Stroke; National Center for Research Resources [M01RR00069]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491, 5R01 DK07568102, 5R01 DK06833603] FX Contract grant sponsor: National Heart, Lung and Blood Institute's Framingham Heart Study; Contract grant number: N01-HC-25195; Contract grant sponsor: Affymetrix, Inc; Contract grant number: N02-HL-6-4278; Contract grant sponsors: Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center, Massachusetts General Hospital Physician Scientist Development Award and a Doris Duke Charitable Foundation Clinical Scientist Development Award, National Institute on Aging; National Institute for Diabetes and Digestive and Kidney Diseases; Contract grant numbers: R01 DK078616; K24 DK080140; K23 DK65978; K01 DK083029; Contract grant sponsor: NIA; Contract grant numbers: N01AG62101; N01AG62103; N01AG62106; 1R01AG032098-01A1; Contract grant sponsor: National Institutes of Health; Contract grant numbers: HHSN268200782096C; HHSN268200625226C; 5R01 HL08770003; Contract grant sponsor: National Heart, Lung, and Blood Institute; Contract grant numbers: N01-HC-55015; N01-HC-55016; N01-HC-55018; N01-HC-55019; N01-HC-55020; N01-HC-55021; N01-HC-55022; R01HL087641; R01HL59367; R01HL086694; U01HG004402; N01-HC- 85079; N01-HC-85086; N01-HC-35129; N01 HC-15103; N01 HC-55222; N01-HC-75150; N01-HC-45133; U01 HL080295; R01 HL087652; 5R01 HL08821502; Contract grant sponsors: National Institute of Neurological Disorders and Stroke; National Center for Research Resources; Contract grant number: M01RR00069; Contract grant sponsor: National Institute of Diabetes and Digestive and Kidney Diseases; Contract grant numbers: DK063491; 5R01 DK07568102; 5R01 DK06833603. NR 29 TC 54 Z9 54 U1 2 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JAN PY 2011 VL 35 IS 1 BP 11 EP 18 DI 10.1002/gepi.20546 PG 8 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 705RQ UT WOS:000286156000002 PM 21181894 ER PT J AU Bailey-Wilson, JE Brennan, JS Bull, SB Culverhouse, R Kim, Y Jiang, Y Jung, JS Li, Q Lamina, C Liu, Y Magi, R Niu, YS Simpson, CL Wang, LB Yilmaz, YE Zhang, HP Zhang, ZG AF Bailey-Wilson, Joan E. Brennan, Jennifer S. Bull, Shelley B. Culverhouse, Robert Kim, Yoonhee Jiang, Yuan Jung, Jeesun Li, Qing Lamina, Claudia Liu, Ying Maegi, Reedik Niu, Yue S. Simpson, Claire L. Wang, Libo Yilmaz, Yildiz E. Zhang, Heping Zhang, Zhaogong TI Regression and data mining methods for analyses of multiple rare variants in the Genetic Analysis Workshop 17 mini-exome data SO GENETIC EPIDEMIOLOGY LA English DT Article DE rare variants; LASSO; machine learning; random forests; logic regression; binary trees; Poisson regression; ISIS; classification trees; meta-analysis; extreme sampling ID ASSOCIATION AB Group 14 of Genetic Analysis Workshop 17 examined several issues related to analysis of complex traits using DNA sequence data. These issues included novel methods for analyzing rare genetic variants in an aggregated manner (often termed collapsing rare variants), evaluation of various study designs to increase power to detect effects of rare variants, and the use of machine learning approaches to model highly complex heterogeneous traits. Various published and novel methods for analyzing traits with extreme locus and allelic heterogeneity were applied to the simulated quantitative and disease phenotypes. Overall, we conclude that power is (as expected) dependent on locus-specific heritability or contribution to disease risk, large samples will be required to detect rare causal variants with small effect sizes, extreme phenotype sampling designs may increase power for smaller laboratory costs, methods that allow joint analysis of multiple variants per gene or pathway are more powerful in general than analyses of individual rare variants, population-specific analyses can be optimal when different subpopulations harbor private causal mutations, and machine learning methods may be useful for selecting subsets of predictors for follow-up in the presence of extreme locus heterogeneity and large numbers of potential predictors. Genet. Epidemiol. 35:S92S100, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Bailey-Wilson, Joan E.; Kim, Yoonhee; Li, Qing; Simpson, Claire L.] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA. [Brennan, Jennifer S.; Jiang, Yuan; Zhang, Heping] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Bull, Shelley B.; Yilmaz, Yildiz E.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Bull, Shelley B.; Yilmaz, Yildiz E.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. [Culverhouse, Robert] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Jung, Jeesun] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA. [Jung, Jeesun] Indiana Univ Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN USA. [Lamina, Claudia] Innsbruck Med Univ, Dept Med Genet Mol & Clin Pharmacol, Innsbruck, Austria. [Liu, Ying] Columbia Univ, Dept Stat, New York, NY USA. [Maegi, Reedik] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Niu, Yue S.] Univ Arizona, Dept Math, Tucson, AZ 85721 USA. [Wang, Libo] Purdue Univ, Dept Stat, W Lafayette, IN 47907 USA. [Zhang, Zhaogong] Michigan Technol Univ, Dept Math Sci, Houghton, MI 49931 USA. RP Bailey-Wilson, JE (reprint author), NHGRI, Inherited Dis Res Branch, NIH, 333 Cassell Dr,Suite 1200, Baltimore, MD 21224 USA. EM jebw@mail.nih.gov RI Bull, Shelley/A-1920-2013; OI Simpson, Claire/0000-0003-2244-7690; Bailey-Wilson, Joan/0000-0002-9153-2920; Magi, Reedik/0000-0002-2964-6011 FU National Institutes of Health (NIH) [R01 GM031575]; National Human Genome Research Institute, NIH [T32 MH-14235, R21 DA033827] FX The Genetic Analysis Workshops are supported by National Institutes of Health (NIH) grant R01 GM031575. This work was supported in part by the Intramural Research Program of the National Human Genome Research Institute, NIH grant T32 MH-14235 and R21 DA033827. NR 27 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2011 VL 35 SU 1 BP S92 EP S100 DI 10.1002/gepi.20657 PG 9 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 854BF UT WOS:000297468800016 PM 22128066 ER PT J AU Dasgupta, A Sun, YV Konig, IR Bailey-Wilson, JE Malley, JD AF Dasgupta, Abhijit Sun, Yan V. Koenig, Inke R. Bailey-Wilson, Joan E. Malley, James D. TI Brief review of regression-based and machine learning methods in genetic epidemiology: the Genetic Analysis Workshop 17 experience SO GENETIC EPIDEMIOLOGY LA English DT Review DE unsupervised learning; supervised learning; cluster analysis; logistic regression; Poisson regression; logic regression; LASSO; ridge regression; decision trees; random forests; cross-validation; software ID INFLATED POISSON REGRESSION; GENOME-WIDE ASSOCIATION; HIGH-DIMENSIONAL DATA; LOGISTIC-REGRESSION; LOGIC REGRESSION; LASSO; STABILITY; SELECTION AB Genetics Analysis Workshop 17 provided common and rare genetic variants from exome sequencing data and simulated binary and quantitative traits in 200 replicates. We provide a brief review of the machine learning and regression-based methods used in the analyses of these data. Several regression and machine learning methods were used to address different problems inherent in the analyses of these data, which are high-dimension, low-sample-size data typical of many genetic association studies. Unsupervised methods, such as cluster analysis, were used for data segmentation and, subset selection. Supervised learning methods, which include regression-based methods (e.g., generalized linear models, logic regression, and regularized regression) and tree-based methods (e.g., decision trees and random forests), were used for variable selection (selecting genetic and clinical features most associated or predictive of outcome) and prediction (developing models using common and rare genetic variants to accurately predict outcome), with the outcome being case-control status or quantitative trait value. We include a discussion of cross-validation for model selection and assessment, and a description of available software resources for these methods. Genet. Epidemiol. 35:S5S11, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Bailey-Wilson, Joan E.] NHGRI, Stat Genet Sect, NIH, Baltimore, MD 21224 USA. [Dasgupta, Abhijit] NIAMSD, Clin Sci Sect, NIH, Bethesda, MD 20892 USA. [Sun, Yan V.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Koenig, Inke R.] Univ Lubeck, Inst Med Biometrie & Stat, Lubeck, Germany. [Malley, James D.] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Bailey-Wilson, JE (reprint author), NHGRI, Stat Genet Sect, NIH, 333 Cassell Dr,Suite 1200, Baltimore, MD 21224 USA. EM jebw@mail.nih.gov RI Konig, Inke/A-4544-2009; OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU National Institute for Arthritis and Musculoskeletal and Skin Diseases; National Human Genome Research Institute; Center for Information Technology of the National Institutes of Health; National Institutes of Health, National Heart, Lung, and Blood Institute [HL100245] FX This work was supported in part by the Intramural Research Programs of the National Institute for Arthritis and Musculoskeletal and Skin Diseases, the National Human Genome Research Institute, and the Center for Information Technology of the National Institutes of Health. It was also supported in part by National Institutes of Health grant HL100245 from the National Heart, Lung, and Blood Institute (YVS). NR 33 TC 13 Z9 14 U1 3 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2011 VL 35 SU 1 BP S5 EP S11 DI 10.1002/gepi.20642 PG 7 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 854BF UT WOS:000297468800002 PM 22128059 ER PT J AU Hemmelmann, C Daw, EW Wilson, AF AF Hemmelmann, Claudia Daw, E. Warwick Wilson, Alexander F. TI Quality control issues and the identification of rare functional variants with next-generation sequencing data SO GENETIC EPIDEMIOLOGY LA English DT Article DE 1000 Genomes Project; association; collection of rare variants; family data; next-generation sequencing; regression; quality control ID PROTEIN FUNCTION; COMMON DISEASES; ASSOCIATION; GENOTYPE; REGRESSION; MUTATIONS AB Next-generation sequencing of large numbers of individuals presents challenges in data preparation, quality control, and statistical analysis because of the rarity of the variants. The Genetic Analysis Workshop 17 (GAW17) data provide an opportunity to survey existing methods and compare these methods with novel ones. Specifically, the GAW17 Group 2 contributors investigate existing and newly proposed methods and study design strategies to identify rare variants, predict functional variants, and/or examine quality control. We introduce the eight Group 2 papers, summarize their approaches, and discuss their strengths and weaknesses. For these investigations, some groups used only the genotype data, whereas others also used the simulated phenotype data. Although the eight Group 2 contributions covered a wide variety of topics under the general idea of identifying rare variants, they can be grouped into three broad categories according to their common research interests: functionality of variants and quality control issues, family-based analyses, and association analyses of unrelated individuals. The aims of the first subgroup were quite different. These were population structure analyses that used rare variants to predict functionality and examine the accuracy of genotype calls. The aims of the family-based analyses were to select which families should be sequenced and to identify high-risk pedigrees; the aim of the association analyses was to identify variants or genes with regression-based methods. However, power to detect associations was low in all three association studies. Thus this work shows opportunities for incorporating rare variants into the genetic and statistical analyses of common diseases. Genet. Epidemiol. 35:S22S28, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Hemmelmann, Claudia] Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Med Biometrie & Stat, D-23562 Lubeck, Germany. [Daw, E. Warwick] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA. [Wilson, Alexander F.] NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. RP Hemmelmann, C (reprint author), Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Med Biometrie & Stat, Campus Lubeck,Maria Goeppert Str 1, D-23562 Lubeck, Germany. EM hemmelmann@imbs.uni-luebeck.de RI Wilson, Alexander/C-2320-2009 FU National Institute of General Medical Sciences, National Institutes of Health (NIH) [R01 GM031575]; Medical Faculty of the university of Lubeck; Division of Intramural Research, National Human Genome Research Institute, NIH FX The Genetic Analysis Workshops are supported by National Institutes of Health (NIH) grant R01 GM031575 from the National Institute of General Medical Sciences. We thank the Group 2 participants for their contributions and the reviewers for their helpful comments. This summary was supported in part by an intramural grant from the Medical Faculty of the university of Lubeck and by the Division of Intramural Research, National Human Genome Research Institute, NIH. NR 29 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2011 VL 35 SU 1 BP S22 EP S28 DI 10.1002/gepi.20645 PG 7 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 854BF UT WOS:000297468800005 PM 22128054 ER PT J AU Wilson, AF Ziegler, A AF Wilson, Alexander F. Ziegler, Andreas TI Lessons learned from Genetic Analysis Workshop 17: transitioning from genome-wide association studies to whole-genome statistical genetic analysis SO GENETIC EPIDEMIOLOGY LA English DT Article DE linkage; association; next-generation sequencing; computer simulation ID REGRESSION AB Genetic Analysis Workshop 17 (GAW17) focused on the transition from genome-wide association study designs and methods to the study designs and statistical genetic methods that will be required for the analysis of next-generation sequence data including both common and rare sequence variants. In the 166 contributions to GAW17, a wide variety of statistical methods were applied to simulated traits in population- and family-based samples, and results from these analyses were compared to the known generating model. In general, many of the statistical genetic methods used in the population-based sample identified causal sequence variants (SVs) when the estimated locus-specific heritability, as measured in the population-based sample, was greater than about 0.08. However, SVs with locus-specific heritabilities less than 0.03 were rarely identified consistently. In the family-based samples, many of the methods detected SVs that were rarer than those detected in the population-based sample, but the estimated locus-specific heritabilities for these rare SVs, as measured in the family-based samples, were substantially higher (>0.2) than their corresponding heritabilities in the population-based samples. Substantial inflation of the type I error rate was observed across a wide variety of statistical methods. Although many of the contributions found little inflation in type I error for Q4, a trait with no causal SVs, type I error rates for Q1 and Q2 were well above their nominal levels with the inflation for Q1 being higher than that for Q2. It seems likely that this inflation in type I error is due to correlations among SVs. Genet. Epidemiol. 35:S107S114, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Wilson, Alexander F.] NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA. [Ziegler, Andreas] Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Med Biometrie & Stat, Lubeck, Germany. RP Wilson, AF (reprint author), NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, 333 Cassell Dr,Suite 1200, Baltimore, MD 21224 USA. EM afw@mail.nih.gov RI Wilson, Alexander/C-2320-2009; OI Ziegler, Andreas/0000-0002-8386-5397 FU National Institutes of Health [R01 GM031575]; Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health; University of Lubeck, Lubeck, Germany FX The Genetic Analysis Workshops are supported by National Institutes of Health grant R01 GM031575. This summary was supported, in part, by the Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health; and an intramural grant from the University of Lubeck, Lubeck, Germany. We would like to thank Dr. Cristina Justice, Mera Krishnan, and Alexa J. M. Sorant for their efforts in determining the locus-specific heritabilities for the family- and population-based samples, and Drs. Joan Bailey-Wilson, Jean MacCluer, and Laura Almasy for their helpful suggestions and comments. NR 8 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2011 VL 35 SU 1 BP S107 EP S114 DI 10.1002/gepi.20659 PG 8 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 854BF UT WOS:000297468800018 PM 22128050 ER PT J AU Iglesias-Gato, D Martin-Marcos, P Santos, MA Hinnebusch, AG Tamame, M AF Iglesias-Gato, Diego Martin-Marcos, Pilar Santos, Maria A. Hinnebusch, Alan G. Tamame, Mercedes TI Guanine Nucleotide Pool Imbalance Impairs Multiple Steps of Protein Synthesis and Disrupts GCN4 Translational Control in Saccharomyces cerevisiae SO GENETICS LA English DT Article ID ACID BIOSYNTHETIC GENES; METHIONYL-TRANSFER-RNA; TRANSCRIPTIONAL ACTIVATOR; NUCLEAR EXPORT; KINASE GCN2; GCD GENES; YEAST; INITIATION; EXPRESSION; MUTANTS AB Purine nucleotides are structural components of the genetic material, function as phosphate donors, participate in cellular signaling, are cofactors in enzymatic reactions, and constitute the main carriers of cellular energy. Thus, imbalances in A/G nucleotide biosynthesis affect nearly the whole cellular metabolism and must be tightly regulated. We have identified a substitution mutation (G388D) that reduces the activity of the GMP synthase Gua1 in budding yeast and the total G-nucleotide pool, leading to precipitous reductions in the GDP/GTP ratio and ATP level in vivo. gua1-G388D strongly reduces the rate of growth, impairs general protein synthesis, and derepresses translation of GCN4 mRNA, encoding a transcriptional activator of diverse amino acid biosynthetic enzymes. Although processing of pre-tRNAi(Met) and other tRNA precursors, and the aminoacylation of tRNAi(Met) are also strongly impaired in gua1-G388D cells, tRNAi(Met)-containing complexes with the macromolecular composition of the eIF2.tRNAi(Met). GTP complex (TC) and the multifactor complex (MFC) required for translation initiation accumulate similar to 10-fold in gua1-G388D cells and, to a lesser extent, in wild-type (WT) cells treated with 6-azauracil (6AU). Consistently, addition of an external supply of guanine reverts all the phenotypes of gua1-G388D cells, but not those of gua1-G388D Delta hpt1 mutants unable to refill the internal GMP pool through the salvage pathway. These and other findings suggest that a defect in guanine nucleotide biosynthesis evokes a reduction in the rate of general protein synthesis by impairing multiple steps of the process, disrupts the gene-specific reinitiation mechanism for translation of GCN4 mRNA and has far-reaching effects in cell biology and metabolism. C1 [Tamame, Mercedes] Univ Salamanca, CSIC, Inst Biol Func Genom, Edificio Dept, Salamanca 37007, Spain. [Martin-Marcos, Pilar; Hinnebusch, Alan G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Tamame, M (reprint author), Univ Salamanca, CSIC, Inst Biol Func Genom, Edificio Dept, Campus Miguel Unamuno, Salamanca 37007, Spain. EM tamame@usal.es RI Iglesias-Gato, Diego/R-1794-2016; Santos, Maria A./H-2239-2015 OI Iglesias-Gato, Diego/0000-0002-8982-9936; Santos, Maria A./0000-0002-1257-7611 FU Department of Education, Universities, and Research of the Basque government (Spain) [BFI02.95]; Department of Universities and Research of the Junta de Castilla y Leon Government (JCyL) (Spain) [SA098A09]; Spanish Ministerio de Ciencia e Innovacion (MICINN) [PET2008-0283-01]; JCyL [CSI007A10-2]; National Institutes of Health FX We thank D. Martin-Zanca for helpful suggestions regarding this work and J. R. Gutierrez for help with the procedure of yeast metabolite extractions. D. I.-G. was supported by a postgraduate fellowship (BFI02.95), granted by the Department of Education, Universities, and Research of the Basque government (Spain). M. A. S. was supported by Project #SA098A09, granted by the Department of Universities and Research of the Junta de Castilla y Leon Government (JCyL) (Spain). M. Tamame was supported by Projects PET2008-0283-01, granted by the Spanish Ministerio de Ciencia e Innovacion (MICINN), and CSI007A10-2, granted by JCyL. The work was supported partly by the Intramural Research Program of the National Institutes of Health. NR 63 TC 9 Z9 9 U1 0 U2 2 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD JAN PY 2011 VL 187 IS 1 BP 105 EP 122 DI 10.1534/genetics.110.122135 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA 705AU UT WOS:000286100900009 PM 20980241 ER PT J AU Verhagen, JH Munster, VJ Fouchier, RAM AF Verhagen, Josanne H. Munster, Vincent J. Fouchier, Ron A. M. BE Tibayrenc, M TI Ecology and Evolution of Avian Influenza Viruses SO GENETICS AND EVOLUTION OF INFECTIOUS DISEASES LA English DT Article; Book Chapter ID GENE SEGMENT REASSORTMENT; WILD AQUATIC BIRDS; A-VIRUS; MIGRATORY WATERFOWL; NORTH-AMERICA; HONG-KONG; EXPERIMENTAL-INFECTION; HEMAGGLUTININ SUBTYPE; PHYLOGENETIC ANALYSES; ASIAN LINEAGE C1 [Verhagen, Josanne H.; Fouchier, Ron A. M.] Erasmus MC, Dept Virol, Rotterdam, Netherlands. [Verhagen, Josanne H.; Fouchier, Ron A. M.] Erasmus MC, Natl Influenza Ctr, Rotterdam, Netherlands. [Munster, Vincent J.] NIAID, Virol Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Verhagen, JH (reprint author), Erasmus MC, Dept Virol, Rotterdam, Netherlands. EM r.fouchier@erasmusmc.nl OI Munster, Vincent/0000-0002-2288-3196 NR 91 TC 0 Z9 1 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-384891-8 PY 2011 BP 729 EP 749 DI 10.1016/B978-0-12-384890-1.00028-5 PG 21 WC Evolutionary Biology; Infectious Diseases SC Evolutionary Biology; Infectious Diseases GA BER10 UT WOS:000317831700030 ER EF