FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Roetzheim, RG Freund, KM Corle, DK Murray, DM Snyder, FR Kronman, AC Jean-Pierre, P Raich, PC Holden, AEC Darnell, JS Warren-Mears, V Patierno, S AF Roetzheim, Richard G. Freund, Karen M. Corle, Don K. Murray, David M. Snyder, Frederick R. Kronman, Andrea C. Jean-Pierre, Pascal Raich, Peter C. Holden, Alan E. C. Darnell, Julie S. Warren-Mears, Victoria Patierno, Steven CA PNRP Design Anal Comm Patient Nav TI Analysis of combined data from heterogeneous study designs: an applied example from the patient navigation research program SO CLINICAL TRIALS LA English DT Article ID BASE-LINE CHARACTERISTICS; PROSPECTIVE METAANALYSIS; RANDOMIZED-TRIALS; CLINICAL-TRIALS; CHOLESTEROL; COLLABORATION; INTERVENTION; METHODOLOGY; PREVENTION; RATIONALE AB Background The Patient Navigation Research Program (PNRP) is a cooperative effort of nine research projects, with similar clinical criteria but with different study designs. To evaluate projects such as PNRP, it is desirable to perform a pooled analysis to increase power relative to the individual projects. There is no agreed-upon prospective methodology, however, for analyzing combined data arising from different study designs. Expert opinions were thus solicited from the members of the PNRP Design and Analysis Committee. Purpose To review possible methodologies for analyzing combined data arising from heterogeneous study designs. Methods The Design and Analysis Committee critically reviewed the pros and cons of five potential methods for analyzing combined PNRP project data. The conclusions were based on simple consensus. The five approaches reviewed included the following: (1) analyzing and reporting each project separately, (2) combining data from all projects and performing an individual-level analysis, (3) pooling data from projects having similar study designs, (4) analyzing pooled data using a prospective meta-analytic technique, and (5) analyzing pooled data utilizing a novel simulated group-randomized design. Results Methodologies varied in their ability to incorporate data from all PNRP projects, to appropriately account for differing study designs, and to accommodate differing project sample sizes. Limitations The conclusions reached were based on expert opinion and not derived from actual analyses performed. C1 [Roetzheim, Richard G.] Univ S Florida, Dept Family Med, Tampa, FL 33612 USA. [Roetzheim, Richard G.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Freund, Karen M.; Kronman, Andrea C.] Boston Univ, Sch Med, Dept Med, Womens Hlth Unit, Boston, MA 02118 USA. [Corle, Don K.] NCI, Rockville, MD USA. [Murray, David M.] Ohio State Univ, Coll Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA. [Snyder, Frederick R.] NOVA Res Co, Bethesda, MD USA. [Jean-Pierre, Pascal] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Jean-Pierre, Pascal] Sylvester Comprehens Canc Ctr, Miami, FL USA. [Raich, Peter C.] Denver Hlth & Hosp Author, Div Hematol Oncol, Denver, CO USA. [Holden, Alan E. C.] Univ Texas Hlth Sci Ctr San Antonio, Inst Hlth Promot Res, San Antonio, TX 78229 USA. [Darnell, Julie S.] Univ Illinois, Sch Publ Hlth, Div Hlth Policy & Adm, Chicago, IL USA. [Warren-Mears, Victoria] NW Portland Area Indian Hlth Board, NW Tribal Epidemiol Ctr, Portland, OR USA. [Patierno, Steven] George Washington Univ, Med Ctr, George Washington Canc Inst, Washington, DC 20037 USA. RP Roetzheim, RG (reprint author), Univ S Florida, Dept Family Med, 12901 Bruce B Downs Blvd,MDC 13, Tampa, FL 33612 USA. EM rroetzhe@health.usf.edu RI Roetzheim, Richard/J-4696-2012; OI Freund, Karen/0000-0002-9049-5574 FU NIH [U01 CA116892, U01 CA 117281, U01CA116903, U01CA116937, U01CA116924, U01CA116885, U01CA116875, U01CA116925]; American Cancer Society [SIRSG-05-253-01] FX The Patient Navigation Research Program is supported by NIH Grants U01 CA116892, U01 CA 117281, U01CA116903, U01CA116937, U01CA116924, U01CA116885, U01CA116875, U01CA116925, and American Cancer Society No. SIRSG-05-253-01. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the Center to Reduce Cancer Health Disparities, NCI/NIH, or the American Cancer Society. NR 37 TC 7 Z9 7 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD APR PY 2012 VL 9 IS 2 BP 176 EP 187 DI 10.1177/1740774511433284 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 923RN UT WOS:000302636500004 PM 22273587 ER PT J AU Schwartz, RH AF Schwartz, Ronald H. TI Historical Overview of Immunological Tolerance SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID REGULATORY T-CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; FC-GAMMA-RIIB; PLASMACYTOID DENDRITIC CELLS; TRANSCRIPTION FACTOR FOXP3; AUTOREACTIVE B-CELLS; E3 UBIQUITIN LIGASE; TOLL-LIKE RECEPTORS; AUTOIMMUNE-DISEASE; IMMUNE-RESPONSES AB A fundamental property of the immune system is its ability to mediate self-defense with a minimal amount of collateral damage to the host. The system uses several different mechanisms to achieve this goal, which is collectively referred to as the "process of immunological tolerance." This article provides an introductory historical overview to these various mechanisms, which are discussed in greater detail throughout this collection, and then briefly describes what happens when this process fails, a state referred to as "autoimmunity." C1 NIAID, Lab Cellular & Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Schwartz, RH (reprint author), NIAID, Lab Cellular & Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rs34r@nih.gov FU NIAID, NIH FX I thank Dr. Nevil Singh and Dr. Pascal Chappert for constructive suggestions that helped to improve the manuscript. This work was supported by the Intramural Research Program of NIAID, NIH. NR 178 TC 5 Z9 5 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD APR PY 2012 VL 4 IS 4 AR a006908 DI 10.1101/cshperspect.a006908 PG 14 WC Cell Biology SC Cell Biology GA 922ND UT WOS:000302553400005 PM 22395097 ER PT J AU Saha, TD Compton, WM Chou, SP Smith, S Ruan, WJ Huang, B Pickering, RP Grant, BF AF Saha, Tulshi D. Compton, Wilson M. Chou, S. Patricia Smith, Sharon Ruan, W. June Huang, Boji Pickering, Roger P. Grant, Bridget F. TI Analyses related to the development of DSM-5 criteria for substance use related disorders 1. Toward amphetamine, cocaine and prescription drug use disorder continua using Item Response Theory SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Amphetamine use disorder; Cocaine use disorder; Prescription drug use disorder; DSM-5; Item Response Theory ID ALCOHOL-USE DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; MARGINAL MAXIMUM-LIKELIHOOD; INTERVIEW SCHEDULE AUDADIS; EM ALGORITHM; DEPENDENCE; RELIABILITY; CANNABIS; MODULES; ABUSE AB Background: Prior research has demonstrated the dimensionality of alcohol, nicotine and cannabis use disorders criteria. The purpose of this study was to examine the unidimensionality of DSM-IV cocaine, amphetamine and prescription drug abuse and dependence criteria and to determine the impact of elimination of the legal problems criterion on the information value of the aggregate criteria. Methods: Factor analyses and Item Response Theory (IRT) analyses were used to explore the unidimensionality and psychometric properties of the illicit drug use criteria using a large representative sample of the U.S. population. Results: All illicit drug abuse and dependence criteria formed unidimensional latent traits. For amphetamines, cocaine, sedatives, tranquilizers and opioids, IRT models fit better for models without legal problems criterion than models with legal problems criterion and there were no differences in the information value of the IRT models with and without the legal problems criterion, supporting the elimination of that criterion. Conclusion: Consistent with findings for alcohol, nicotine and cannabis, amphetamine, cocaine, sedative, tranquilizer and opioid abuse and dependence criteria reflect underlying unitary dimensions of severity. The legal problems criterion associated with each of these substance use disorders can be eliminated with no loss in informational value and an advantage of parsimony. Taken together, these findings support the changes to substance use disorder diagnoses recommended by the American Psychiatric Association's DSM-5 Substance and Related Disorders Workgroup. Published by Elsevier Ireland Ltd. C1 [Saha, Tulshi D.; Chou, S. Patricia; Smith, Sharon; Ruan, W. June; Huang, Boji; Pickering, Roger P.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. [Compton, Wilson M.] NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA. RP Saha, TD (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Lane,Room 3083, Bethesda, MD 20892 USA. EM sahatd@mail.nih.gov FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute on Drug Abuse (NIDA) FX The National Institute on Alcohol Abuse and Alcoholism (NIAAA) funded the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) with supplemental funding from the National Institute on Drug Abuse (NIDA). NR 40 TC 23 Z9 23 U1 5 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD APR 1 PY 2012 VL 122 IS 1-2 BP 38 EP 46 DI 10.1016/j.drugalcdep.2011.09.004 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 925CW UT WOS:000302739300006 PM 21963414 ER PT J AU MacDonald, C Buchkovich, NJ Stringer, DK Emr, SD Piper, RC AF MacDonald, Chris Buchkovich, Nicholas J. Stringer, Daniel K. Emr, Scott D. Piper, Robert C. TI Cargo ubiquitination is essential for multivesicular body intralumenal vesicle formation SO EMBO REPORTS LA English DT Article DE ubiquitin; lysosome; multivesicular body; endosome; vacuole ID SACCHAROMYCES-CEREVISIAE; MECHANISMS; COOPERATE; ENDOSOME; PROTEINS; BINDING; DOMAINS AB The efficient formation of a variety of transport vesicles is influenced by the presence of cargo, suggesting that cargo itself might have a defining role in vesicle biogenesis. However, definitive in vivo experiments supporting this concept are lacking, as it is difficult to eliminate endogenous cargo. The Endosomal Sorting Complexes Required for Transport (ESCRT) apparatus sorts ubiquitinated membrane proteins into endosomal intralumenal vesicles (ILVs) that accumulate within multivesicular bodies. Here we show that cargo ubiquitination is required for effective recruitment of the ESCRT machinery onto endosomal membranes and for the subsequent formation of ILVs. C1 [Buchkovich, Nicholas J.; Emr, Scott D.] Cornell Univ, Weill Inst Cell & Mol Biol, Ithaca, NY 14853 USA. [MacDonald, Chris; Stringer, Daniel K.; Piper, Robert C.] Univ Iowa, Iowa City, IA 52246 USA. RP Emr, SD (reprint author), NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, Frederick, MD 21702 USA. EM sde26@cornell.edu; robert-piper@uiowa.edu OI MacDonald, Chris/0000-0002-7450-600X FU NIH [R01GM58202]; American Hearth Association FX We thank J. Ross, J. Shao (University of Iowa Central Microscopy Facility), B. Judson and J. Sun for technical assistance, as well as members of the Emr and Piper labs for helpful discussion. This work was supported in part by an American Hearth Association predoctoral fellowship (DKS) and NIH R01GM58202 (RCP). NR 19 TC 30 Z9 30 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD APR PY 2012 VL 13 IS 4 BP 331 EP 338 DI 10.1038/embor.2012.18 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 922QI UT WOS:000302562500016 PM 22370727 ER PT J AU Starks, SE Hoppin, JA Kamel, F Lynch, CF Jones, MP Alavanja, MC Sandler, DP Gerr, F AF Starks, Sarah E. Hoppin, Jane A. Kamel, Freya Lynch, Charles F. Jones, Michael P. Alavanja, Michael C. Sandler, Dale P. Gerr, Fred TI Peripheral Nervous System Function and Organophosphate Pesticide Use among Licensed Pesticide Applicators in the Agricultural Health Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE agricultural workers; neurological testing; occupational exposure; organophosphates; pesticide exposure ID RELIABILITY; EXPOSURES; NEUROTOXICITY AB BACKGROUND: Evidence is limited that long-term human exposure to organophosphate (OP) pesticides, without poisoning, is associated with adverse peripheral nervous system (PNS) function. OBJECTIVE: We investigated associations between OP pesticide use and PNS function by administering PNS tests to 701 male pesticide applicators in the Agricultural Health Study (AHS). METHODS: Participants completed a neurological physical examination (NPx) and electrophysiological tests as well as tests of hand strength, sway speed, and vibrotactile threshold. Self-reported information on lifetime use of 16 OP pesticides was obtained from AHS interviews and a study questionnaire. Associations between pesticide use and measures of PNS function were estimated with linear and logistic regression controlling for age and outcome-specific covariates. RESULTS: Significantly increased odds ratios (ORs) were observed for associations between ever use of 10 of the 16 OP pesticides and one or more of six NPx outcomes. Most notably, abnormal toe proprioception was significantly associated with ever use of 6 OP pesticides, with ORs ranging from 2.03 to 3.06; monotonic increases in strength of association with increasing use was observed for 3 of the 6 pesticides. Mostly null associations were observed between OP pesticide use and electrophysiological tests, hand strength, sway speed, and vibrotactile threshold. CONCLUSIONS: This study provides some evidence that long-term exposure to OP pesticides is associated with signs of impaired PNS function among pesticide applicators. C1 [Starks, Sarah E.; Gerr, Fred] Univ Iowa, Dept Occupat & Environm Hlth, Iowa City, IA 52242 USA. [Hoppin, Jane A.; Kamel, Freya; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. [Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA. [Jones, Michael P.] Univ Iowa, Dept Biostat, Iowa City, IA 52242 USA. [Alavanja, Michael C.] NCI, NIH, US Dept HHS, Rockville, MD USA. RP Gerr, F (reprint author), Univ Iowa, Dept Occupat & Environm Hlth, Univ Iowa Res Pk,140 IREH, Iowa City, IA 52242 USA. EM fred-gerr@uiowa.edu OI Sandler, Dale/0000-0002-6776-0018 FU National Institute of Environmental Health Sciences (NIEHS) [R01-ES013067-03]; National Institutes of Health, NIEHS [Z01ES04903]; National Cancer Institute [Z01CP010119] FX This work was supported by National Institute of Environmental Health Sciences (NIEHS) grant R01-ES013067-03, the Intramural Research Program of the National Institutes of Health, NIEHS grant Z01ES04903, and National Cancer Institute grant Z01CP010119. NR 18 TC 16 Z9 16 U1 1 U2 6 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 APR PY 2012 VL 120 IS 4 BP 515 EP 520 DI 10.1289/ehp.1103944 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 921KJ UT WOS:000302476200019 PM 22262687 ER PT J AU Walker, VR Jefferson, WN Couse, JF Korach, KS AF Walker, Vickie R. Jefferson, Wendy N. Couse, John F. Korach, Kenneth S. TI Estrogen Receptor-alpha Mediates Diethylstilbestrol-Induced Feminization of the Seminal Vesicle in Male Mice SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE development; endocrine disruptor; reproductive tract ID REPRODUCTIVE-TRACT; PRENATAL EXPOSURE; DEVELOPMENTAL EXPOSURE; ANDROGEN RECEPTOR; GENE-EXPRESSION; KNOCKOUT MICE; NULL MICE; PROSTATE; BETA; CARCINOGENICITY AB BACKGROUND: Studies have shown that perinatal exposure to the synthetic estrogen diethylstilbestrol (DES) leads to feminization of the seminal vesicle (SV) in male mice, as illustrated by tissue hyperplasia, ectopic expression of the major estrogen-inducible uterine secretory protein lactoferrin (LF), and reduced expression of SV secretory protein IV (SVS IV). OBJECTIVES: The present study was designed to evaluate the role of the estrogen receptor (ER) in this action by using ER-knockout (ERKO) mice. METHODS: Wild-type (WT), ER alpha-null (alpha ERKO), and ER beta-null (beta ERKO) male mice were treated with either vehicle or DES (2 mu g/day) on neonatal days 1-5. These mice were divided into two groups: In the first group, intact mice were sacrificed at 10 weeks of age; in the second group, mice were castrated at 10 weeks of age, allowed to recover for 10 days, treated with dihydrotestosterone (DHT) or placebo, and sacrificed 2 weeks later. Body weights and SV weights were recorded, and mRNA expression levels of Ltf(lactoferrin), Svs4, and androgen receptor (Ar) were assessed. RESULTS: In DES-treated intact mice, SV weights were reduced in WT and beta ERKO mice but not in alpha ERKO mice. DES-treated WT and beta ERKO males, but not alpha ERKO males, exhibited ectopic expression of LF in the SV. DES treatment resulted in decreased SVS IV protein and mRNA expression in WT males, but no effect was seen in alpha ERKO mice. In addition, DES-treated beta ERKO mice exhibited reduced Svs4 mRNA expression but maintained control levels of SVS IV protein. In DES-treated castrated mice, DHT implants restored SV weights to normal levels in alpha ERKO mice but not in WT mice, suggesting full androgen responsiveness in alpha ERKO mice. CONCLUSIONS: These data suggest that DES-induced SV toxicity and feminization are primarily mediated by ER alpha; however, some aspects of androgen response may require the action of ER beta. C1 [Walker, Vickie R.; Couse, John F.; Korach, Kenneth S.] NIEHS, Receptor Biol Sect, Lab Reprod & Dev Toxicol, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Jefferson, Wendy N.] NIEHS, Reprod Med Grp, Lab Reprod & Dev Toxicol, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Couse, John F.] Taconic Inc, Germantown, NY USA. RP Korach, KS (reprint author), NIEHS, Receptor Biol Sect, Lab Reprod & Dev Toxicol, NIH,Dept Hlth & Human Serv, MD B3-02,POB 12233, Res Triangle Pk, NC 27709 USA. EM korach@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X FU National Institutes of Health, National Institute of Environmental Health Sciences [Z01ES70065] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (Z01ES70065). NR 41 TC 7 Z9 8 U1 2 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 APR PY 2012 VL 120 IS 4 BP 560 EP 565 DI 10.1289/ehp.1103678 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 921KJ UT WOS:000302476200027 PM 22275727 ER PT J AU Schecter, A Malik-Bass, N Calafat, AM Kato, K Colacino, JA Gent, TL Hynan, LS Harris, TR Malla, S Birnbaum, L AF Schecter, Arnold Malik-Bass, Noor Calafat, Antonia M. Kato, Kayoko Colacino, Justin A. Gent, Tyra L. Hynan, Linda S. Harris, T. Robert Malla, Sunitha Birnbaum, Linda TI Polyfluoroalkyl Compounds in Texas Children from Birth through 12 Years of Age SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE blood; children; infants; PFC; PFOA; PFOS; polyfluoroalkyl compounds; United States ID PERFLUOROOCTANOIC ACID PFOA; PERFLUORINATED COMPOUNDS; NATIONAL-HEALTH; SERUM CONCENTRATIONS; NHANES 1999-2000; SULFONATE PFOS; BLOOD-SAMPLES; US POPULATION; HUMAN-MILK; CHEMICALS AB BACKGROUND: For > 50 years, polyfluoroalkyl compounds (PFCs) have been used worldwide, mainly as surfactants and emulsifiers, and human exposure to some PFCs is widespread. OBJECTIVES: Our goal was to report PFC serum concentrations from a convenience sample of Dallas, Texas, children from birth to < 13 years of age, and to examine age and sex differences in PFC concentrations. METHODS: We analyzed 300 serum samples collected in 2009 for eight PFCs by online solid phase extraction-high performance liquid chromatography-isotope dilution-tandem mass spectrometry. RESULTS: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) were detected in > 92% of participants; the other PFCs measured were detected less frequently. Overall median concentrations of PFOS (4.1 ng/mL) were higher than those for PFOA (2.85 ng/mL), PFNA (1.2 ng/mL), and PFHxS (1.2 ng/mL). For PFOS, PFOA, PFNA, and PFHxS, we found no significant differences (p < 0.05) by sex, significantly increasing concentrations for all four chemicals by age, and significantly positive correlations between all four compounds. CONCLUSIONS: We found no significant differences in the serum concentrations of PFOS, PFOA, PFNA, and PFHxS by sex, but increasing concentrations with age. Our results suggest that these 300 Texas children from birth through 12 years of age continued to be exposed to several PFCs in late 2009, years after changes in production of some PFCs in the United States. C1 [Schecter, Arnold; Malik-Bass, Noor; Gent, Tyra L.; Harris, T. Robert; Malla, Sunitha] Univ Texas Sch Publ Hlth, Dallas, TX 75390 USA. [Calafat, Antonia M.; Kato, Kayoko] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA. [Colacino, Justin A.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Hynan, Linda S.] Univ Texas SW Med Ctr Dallas, Dept Clin Sci Biostat, Dallas, TX 75390 USA. [Hynan, Linda S.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Birnbaum, Linda] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Schecter, A (reprint author), Univ Texas Sch Publ Hlth, 6011 Harry Hines Blvd,V8-112, Dallas, TX 75390 USA. EM arnold.schecter@utsouthwestern.edu OI Hynan, Linda/0000-0002-4642-7769 FU CDC; National Institute of Environmental Health Sciences (NIEHS), NIH [T32 ES007062] FX This study was supported primarily by the CDC and involved the CDC, CMC Dallas, the University of Texas Southwestern Medical Center, the University of Texas School of Public Health, Dallas Campus, and the National Institutes of Health (NIH). Support for J. Colacino was provided by an Institutional Training Grant from the National Institute of Environmental Health Sciences (NIEHS), NIH (T32 ES007062). NR 46 TC 25 Z9 25 U1 3 U2 37 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 APR PY 2012 VL 120 IS 4 BP 590 EP 594 DI 10.1289/ehp.1104325 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 921KJ UT WOS:000302476200032 PM 22182702 ER PT J AU Jusko, TA Sonneborn, D Palkovicova, L Kocan, A Drobna, B Trnovec, T Hertz-Picciotto, I AF Jusko, Todd A. Sonneborn, Dean Palkovicova, Lubica Kocan, Anton Drobna, Beata Trnovec, Tomas Hertz-Picciotto, Irva TI Pre- and Postnatal Polychlorinated Biphenyl Concentrations and Longitudinal Measures of Thymus Volume in Infants SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE atrophy; cohort; epidemiology; immune; Roma; T cell ID RECEPTOR-DEFICIENT MICE; ORGANOCHLORINE PESTICIDES; SONOGRAPHIC MEASUREMENT; EASTERN SLOVAKIA; PCB EXPOSURE; HUMAN SERUM; SIZE; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; DIOXINS; BIRTH AB BACKGROUND: Previously, we reported an association between higher maternal polychlorinated biphenyl (PCB) concentrations and smaller thymus volume in newborns in a birth cohort residing in eastern Slovakia. OBJECTIVE: In the present report we address whether thymus volume at later ages is influenced by prenatal and early postnatal PCB exposure. METHODS: At the time of delivery, 1,134 mother-infant pairs were enrolled. Maternal and 6- and 16-month infant blood samples were collected and analyzed for 15 PCB congeners. Thymus volume was measured in infants shortly after birth and at ages 6 and 16 months using ultrasonography. RESULTS: Higher maternal PCB concentration was associated with reduced thymus volume at birth [a 0.21 SD reduction in thymus volume for an increase in total maternal PCB concentration from the 10th to the 90th percentile; 95% confidence interval (CI): -0.37, -0.05], whereas maternal PCB concentration was not predictive of 6- and 16-month thymus volume. Six-month infant PCB concentration was associated with a 0.40 SD decrease in 6-month thymus volume (95% CI: -0.76, -0.04). There was also some suggestion that thymus volume at 16 months was positively associated with concurrent infant PCB concentration. CONCLUSIONS: The potential adverse effects of in utero PCB exposure on thymic development may extend beyond the neonatal period. Results from this highly exposed cohort provide suggestive evidence that postnatal PCB concentrations may be influential, but a smaller set of 6-month PCB measurements limited statistical power at that time point. Implications regarding impaired immunologic maturation or long-term clinical implications remain to be determined. C1 [Jusko, Todd A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Sonneborn, Dean; Hertz-Picciotto, Irva] Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Div Epidemiol, Davis, CA 95616 USA. [Palkovicova, Lubica; Trnovec, Tomas] Slovak Med Univ, Dept Environm Med, Bratislava, Slovakia. [Kocan, Anton; Drobna, Beata] Slovak Med Univ, Dept Tox Organ Pollutants, Bratislava, Slovakia. RP Jusko, TA (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05,111 TW Alexander Dr,Rall Bldg, Durham, NC 27709 USA. EM todd.jusko@nih.gov FU National Institutes of Health [U01-ES016127, R01-CA096525, R03-TW007152, R01-ES015359]; National Institutes of Health, National Institute of Environmental Health Sciences; ENVIRISK of the European Commission [SSPI044232]; U.S. State Department FX This research received support from National Institutes of Health grants U01-ES016127, R01-CA096525, R03-TW007152, and R01-ES015359 and from the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. Funding was also provided by ENVIRISK grant SSPI044232 of the European Commission and by a Fulbright Grant from the U.S. State Department. NR 38 TC 17 Z9 17 U1 1 U2 7 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 APR PY 2012 VL 120 IS 4 BP 595 EP 600 DI 10.1289/ehp.1104229 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 921KJ UT WOS:000302476200033 PM 22275729 ER PT J AU Birnbaum, LS AF Birnbaum, Linda S. TI Environmental Chemicals: Evaluating Low-Dose Effects SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material ID HEALTH; EXPOSURE C1 [Birnbaum, Linda S.] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. [Birnbaum, Linda S.] NIH, NTP, US Dept HHS, Res Triangle Pk, NC USA. RP Birnbaum, LS (reprint author), NIEHS, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM birnbaumls@niehs.nih.gov NR 14 TC 36 Z9 38 U1 0 U2 5 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 APR PY 2012 VL 120 IS 4 BP A143 EP A144 DI 10.1289/ehp.1205179 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 921KJ UT WOS:000302476200002 PM 22470049 ER PT J AU Moriwaki, S Takigawa, M Igarashi, N Nagai, Y Amano, H Ishikawa, O Khan, SG Kraemer, KH AF Moriwaki, Shinichi Takigawa, Masahiro Igarashi, Naoya Nagai, Yayoi Amano, Hiroo Ishikawa, Osamu Khan, Sikandar G. Kraemer, Kenneth H. TI Xeroderma pigmentosum complementation group G patient with a novel homozygous missense mutation and no neurological abnormalities SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE DNA repair; mutation; skin cancer; ultraviolet; xeroderma pigmentosum group G ID COCKAYNE-SYNDROME; DNA-REPAIR; MALIGNANT-MELANOMA; SKIN-CANCER; JAPAN; GENOTYPE; XPG AB We describe an unusual xeroderma pigmentosum (XP) patient with a mutation in XP complementation group G, representing only the third reported Japanese XP-G patient. A 40-year-old men (XP3HM), born from consanguineous parents experienced sun sensitivity and pigmentary changes of sun-exposed skin since childhood. He developed a squamous cell carcinoma on his lower lip at the age of 40. He has neither neurological abnormalities nor Cockayne syndrome. The primary fibroblasts of the patient were hypersensitive to killing by UV (D0 = 0.6 J/m2) and the post-UV unscheduled DNA synthesis was 8% of normal. Host cell reactivation complementation analysis implicated XP complementation group G. We identified a novel homozygous mutation (c.194T>C) in a conserved portion of the XPG(ERCC5) gene, resulting in a predicted amino acid change; p.L65P. We confirmed that this genetic change reduced DNA repair thus linking this mutation to increased skin cancer. C1 [Moriwaki, Shinichi] Osaka Med Coll, Dept Dermatol, Takatsuki, Osaka 5698686, Japan. [Takigawa, Masahiro] Hamamatsu Univ Sch Med, Dept Dermatol, Hamamatsu, Shizuoka 4313192, Japan. [Igarashi, Naoya; Nagai, Yayoi; Amano, Hiroo; Ishikawa, Osamu] Gunma Univ, Grad Sch Med Maebashi, Dept Dermatol, Gunma, Japan. [Khan, Sikandar G.; Kraemer, Kenneth H.] NCI, DNA Repair Sect, Dermatol Branch, Bethesda, MD 20892 USA. RP Moriwaki, S (reprint author), Osaka Med Coll, Dept Dermatol, 2-7 Daigaku Machi, Takatsuki, Osaka 5698686, Japan. EM der002@poh.osaka-med.ac.jp OI Ishikawa, Osamu/0000-0002-7655-0610 FU Intramural NIH HHS [ZIA BC004517-35] NR 23 TC 13 Z9 14 U1 4 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0906-6705 EI 1600-0625 J9 EXP DERMATOL JI Exp. Dermatol. PD APR PY 2012 VL 21 IS 4 BP 304 EP 307 DI 10.1111/j.1600-0625.2012.01446.x PG 4 WC Dermatology SC Dermatology GA 908ZW UT WOS:000301532600013 PM 22417308 ER PT J AU Barrioluengo, V Wang, Y Le Grice, SFJ Menendez-Arias, L AF Barrioluengo, Veronica Wang, Yi Le Grice, Stuart F. J. Menendez-Arias, Luis TI Intrinsic DNA synthesis fidelity of xenotropic murine leukemia virus-related virus reverse transcriptase SO FEBS JOURNAL LA English DT Article DE DNA polymerase; fidelity; retroviruses; reverse transcriptase; XMRV ID MISPAIR EXTENSION FREQUENCIES; CHRONIC-FATIGUE-SYNDROME; RETROVIRUS XMRV; MUTATION-RATE; MOUSE DNA; IN-VITRO; HIV-1; TYPE-1; CONTAMINATION; RESISTANCE AB Although recent reports have provided strong evidence to suggest that xenotropic murine leukemia virus-related virus (XMRV) is unlikely to be the causative agent of prostate cancer and chronic fatigue syndrome, this recombinant retrovirus can nonetheless infect human cells in vitro and induce a chronic infection in macaques. In the present study, we determined the accuracy of DNA synthesis of the reverse transcriptases (RTs) of XMRV and Moloney murine leukemia virus (MoMLV) using a combination of pre-steady-state kinetics of nucleotide incorporation and an M13mp2-based forward mutation assay. The results obtained were compared with those previously reported for the HIV type 1 BH10 strain (HIV-1BH10) RT. MoMLV and XMRV RTs were 13.9 and 110 times less efficient [as determined by the catalytic rate constant of the nucleotide incorporation reaction (kpol)/equilibrium constant (Kd)] than the HIV-1BH10 RT in incorporating correct nucleotides. Misinsertion and mispair extension kinetic studies demonstrated that MoMLV RT was more accurate than the HIV-1BH10 RT. In comparison with the MoMLV RT, the XMRV RT showed decreased mispair extension fidelity and was less faithful when misincorporating C or A opposite A. However, the XMRV RT showed stronger selectivity against G in misinsertion fidelity assays. Forward mutation assays revealed that XMRV and MoMLV RTs had similar accuracy of DNA-dependent DNA synthesis, but were > 13 times more faithful than the HIV-1BH10 enzyme. The mutational spectra of XMRV and MoMLV RTs were similar in having a relatively higher proportion of frameshifts and transversions compared with the HIV-1BH10 RT. However, the XMRV polymerase was less prone to introduce large deletions and one-nucleotide insertions. C1 [Barrioluengo, Veronica; Menendez-Arias, Luis] CSIC UAM, Ctr Biol Mol Severo Ochoa, Madrid 28049, Spain. [Wang, Yi; Le Grice, Stuart F. J.] NCI, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA. RP Menendez-Arias, L (reprint author), CSIC UAM, Ctr Biol Mol Severo Ochoa, C Nicolas Cabrera 1,Campus Cantoblanco, Madrid 28049, Spain. EM lmenendez@cbm.uam.es RI Menendez Arias, Luis /G-2436-2016; Menendez Arias, Luis/N-7447-2016 OI Menendez Arias, Luis/0000-0002-1251-6640 FU Ministery of Science and Innovation of Spain [BIO2010/15532]; Fondo de Investigacion Sanitaria through the 'Red Tematica de Investigacion Cooperativa en SIDA' [RD06/0006]; Fundacion Ramon Areces; National Cancer Institute, National Institutes of Health FX This work was supported, in part, by grants of the Ministery of Science and Innovation of Spain (BIO2010/15532), Fondo de Investigacion Sanitaria (through the 'Red Tematica de Investigacion Cooperativa en SIDA' RD06/0006), and an institutional grant from the Fundacion Ramon Areces. S.F.J. Le G. and Y.W. are supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 42 TC 5 Z9 5 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD APR PY 2012 VL 279 IS 8 BP 1433 EP 1444 DI 10.1111/j.1742-4658.2012.08532.x PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 920IJ UT WOS:000302397200011 PM 22340433 ER PT J AU Senac, JS Chandler, RJ Sysol, JR Li, L Venditti, CP AF Senac, J. S. Chandler, R. J. Sysol, J. R. Li, L. Venditti, C. P. TI Gene therapy in a murine model of methylmalonic acidemia using rAAV9-mediated gene delivery SO GENE THERAPY LA English DT Article DE AAV9; MMA; methylmalonic acidemia; stable isotope; renal disease ID LIVER-KIDNEY TRANSPLANTATION; SKELETAL-MUSCLE TRANSDUCTION; OF-THE-LITERATURE; SYSTEMIC INJECTION; MICE; VECTORS; EXPRESSION; MANAGEMENT; SEROTYPE-9; ACIDURIA AB Methylmalonic acidemia (MMA), an inherited metabolic disorder caused by deficient activity of methylmalonyl-CoA mutase, carries a poor prognosis for long-term survival. While administration of a recombinant adeno-associated virus serotype 8 vector (rAAV8) can rescue Mut(-/-) mice from neonatal lethality and provide sustained phenotypic correction, translation of gene therapy to human subjects will likely require multiple rounds of systemic administration and, ideally, the use of a vector that transduces the kidney. To examine the effectiveness of alternative rAAVs in the treatment of MMA, a serotype 9 rAAV expressing the Mut cDNA was constructed and delivered to newborn Mut(-/-) mice (n=11). rAAV9 gene therapy directed hepatic transgene expression within 24 h and effectively rescued the Mut(-/-) mice from lethality, conferred long-term survival, markedly improved metabolism and resulted in striking preservation of renal function and histology. Systemic readministration of the vector at a dose similar to that used in human clinical trials (2.5 x 10(9) GC of rAAV9 per gram) to older, treated Mut(-/-) mice (n=5) lowered circulating metabolites, increased in vivo propionate oxidative capacity and produced transgene expression in the kidney and liver. Our data support the use of an rAAV9 vector in the acute and chronic treatment of MMA, and highlight the renal tropism afforded by this novel serotype. Gene Therapy (2012) 19, 385-391; doi: 10.1038/gt.2011.108; published online 21 July 2011 C1 [Senac, J. S.; Chandler, R. J.; Sysol, J. R.; Venditti, C. P.] NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Chandler, R. J.] George Washington Univ, Inst Biomed Sci, Washington, DC USA. [Li, L.] NIDDK, Kidney Dis Branch, NIH, Bethesda, MD USA. RP Venditti, CP (reprint author), NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bldg 49 Room 4A18, Bethesda, MD 20892 USA. EM venditti@mail.nih.gov FU National Human Genome Research Institute, National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Angels for Alyssa MMA Research Foundation FX JSS, RJC, JRS and CPV were supported, in part, by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. LL was supported, in part, by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. JRS also received support from the Angels for Alyssa MMA Research Foundation. NR 43 TC 6 Z9 6 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD APR PY 2012 VL 19 IS 4 BP 385 EP 391 DI 10.1038/gt.2011.108 PG 7 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 925OD UT WOS:000302769800004 PM 21776024 ER PT J AU Simons-Morton, B Abraido-Lanza, AF Bernhardt, JM Schoenthaler, A Schnitzer, A Allegrante, JP AF Simons-Morton, B. Abraido-Lanza, A. F. Bernhardt, J. M. Schoenthaler, A. Schnitzer, A. Allegrante, J. P. TI Demystifying peer review (vol 39, pg 3, 2012) SO HEALTH EDUCATION & BEHAVIOR LA English DT Correction AB Simons-Morton, B., Abraido-Lanza, A. F., Bernhardt, J. M., Schoenthaler, A., Schnitzer, A., & Allegrante, J. P. (2012). Demystifying peer review. Health Education & Behavior, 39(1), 3-7. (Original DOI: 10.1177/1090198111433309). C1 [Allegrante, J. P.] NIH, Bethesda, MD 20892 USA. [Allegrante, J. P.] Columbia Univ, New York, NY USA. NR 1 TC 0 Z9 0 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD APR PY 2012 VL 39 IS 2 BP 244 EP 244 DI 10.1177/1090198112442149 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 918XL UT WOS:000302284700014 ER PT J AU Everson, GT Shiffman, ML Hoefs, JC Morgan, TR Sterling, RK Wagner, DA Lauriski, S Curto, TM Stoddard, A Wright, EC AF Everson, Gregory T. Shiffman, Mitchell L. Hoefs, John C. Morgan, Timothy R. Sterling, Richard K. Wagner, David A. Lauriski, Shannon Curto, Teresa M. Stoddard, Anne Wright, Elizabeth C. CA HALT-C Trial Grp TI Quantitative liver function tests improve the prediction of clinical outcomes in chronic hepatitis C: Results from the hepatitis C antiviral long-term treatment against cirrhosis trial SO HEPATOLOGY LA English DT Article ID CHRONIC HCV INFECTION; PROGNOSTIC VALUE; UNITED-STATES; BIOPSY; DISEASE; FIBROSIS; COMPLICATIONS; MODEL; STAGE; THERAPY AB Risk for future clinical outcomes is proportional to the severity of liver disease in patients with chronic hepatitis C virus (HCV). We measured disease severity by quantitative liver function tests (QLFTs) to determine cutoffs for QLFTs that identified patients who were at low and high risk for a clinical outcome. Two hundred and twenty-seven participants in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial underwent baseline QLFTs and were followed for a median of 5.5 years for clinical outcomes. QLFTs were repeated in 196 patients at month 24 and in 165 patients at month 48. Caffeine elimination rate (kelim), antipyrine (AP) clearance (Cl), MEGX concentration, methionine breath test (MBT), galactose elimination capacity (GEC), dual cholate (CA) clearances and shunt, perfused hepatic mass (PHM), and liver and spleen volumes (by single-photon emission computed tomography) were measured. Baseline QLFTs were significantly worse (P = 0.0017 to P < 0.0001) and spleen volumes were larger (P < 0.0001) in the 54 patients who subsequently experienced clinical outcomes. QLFT cutoffs that characterized patients as low and high risk for clinical outcome yielded hazard ratios ranging from 2.21 (95% confidence interval [CI]: 1.29-3.78) for GEC to 6.52 (95% CI: 3.63-11.71) for CA clearance after oral administration (Cloral). QLFTs independently predicted outcome in models with Ishak fibrosis score, platelet count, and standard laboratory tests. In serial studies, patients with high-risk results for CA Cloral or PHM had a nearly 15-fold increase in risk for clinical outcome. Less than 5% of patients with low risk QLFTs experienced a clinical outcome. Conclusion: QLFTs independently predict risk for future clinical outcomes. By improving risk assessment, QLFTs could enhance the noninvasive monitoring, counseling, and management of patients with chronic HCV. (HEPATOLOGY 2012) C1 [Everson, Gregory T.; Lauriski, Shannon] Univ Colorado Denver, Div Gastroenterol & Hepatol, Sect Hepatol, Aurora, CO 80045 USA. [Shiffman, Mitchell L.] Bon Secours Hlth Syst, Liver Inst Virginia, Newport News, VA USA. [Hoefs, John C.; Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Hoefs, John C.; Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Sterling, Richard K.] Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA. [Wagner, David A.] Metab Solut Inc, Nashua, NH USA. [Curto, Teresa M.; Stoddard, Anne] New England Res Inst, Watertown, MA 02172 USA. [Wright, Elizabeth C.] NIDDK, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Everson, GT (reprint author), Univ Colorado Denver, Div Gastroenterol & Hepatol, Sect Hepatol, 1635 N Aurora Court,B-154, Aurora, CO 80045 USA. EM greg.everson@ucdenver.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [N01-DK-9-2327, M01RR-00051, N01-DK-9-2320, M01RR-00827, N01-DK-9-2322, M01RR-00065, N01-DK-9-2328]; National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Center for Minority Health and Health Disparities; General Clinical Research Center from the National Center for Research Resources, National Institutes of Health; Metabolic Solutions, Inc.; Hoffmann-La Roche, Inc. through National Institutes of Health FX This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (Contract N01-DK-9-2327, Grant M01RR-00051; Contract N01-DK-9-2320, Grant M01RR-00827; Contract N01-DK-9-2322, Grant M01RR-00065; Contract N01-DK-9-2328), the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the National Center for Minority Health and Health Disparities, and by General Clinical Research Center grants from the National Center for Research Resources, National Institutes of Health. Additional funding was supplied by Metabolic Solutions, Inc. and by Hoffmann-La Roche, Inc., through Cooperative Research and Development Agreements with the National Institutes of Health. NR 53 TC 23 Z9 23 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2012 VL 55 IS 4 BP 1019 EP 1029 DI 10.1002/hep.24752 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 916AW UT WOS:000302069900005 PM 22030902 ER PT J AU Ishikawa, T Factor, VM Marquardt, JU Raggi, C Seo, D Kitade, M Conner, EA Thorgeirsson, SS AF Ishikawa, Tsuyoshi Factor, Valentina M. Marquardt, Jens U. Raggi, Chiara Seo, Daekwan Kitade, Mitsuteru Conner, Elizabeth A. Thorgeirsson, Snorri S. TI Hepatocyte growth factor/c-met signaling is required for stem-cell-mediated liver regeneration in mice SO HEPATOLOGY LA English DT Article ID OVAL CELLS; MATRIX METALLOPROTEINASES; PROGENITOR CELLS; MOUSE-LIVER; RAT-LIVER; PROLIFERATION; FIBROSIS; INJURY; DIFFERENTIATION; MACROPHAGES AB Hepatocyte growth factor (HGF)/c-Met supports a pleiotrophic signal transduction pathway that controls stem cell homeostasis. Here, we directly addressed the role of c-Met in stem-cellmediated liver regeneration by utilizing mice harboring c-met floxed alleles and Alb-Cre or Mx1-Cre transgenes. To activate oval cells, the hepatic stem cell (HSC) progeny, we used a model of liver injury induced by diet containing the porphyrinogenic agent, 3,5-diethocarbonyl-1,4-dihydrocollidine (DDC). Deletion of c-met in oval cells was confirmed in both models by polymerase chain reaction analysis of fluorescence-activated cell-sorted epithelial cell adhesion molecule (EpCam)-positive cells. Loss of c-Met receptor decreased the sphere-forming capacity of oval cells in vitro as well as reduced oval cell pool, impaired migration, and decreased hepatocytic differentiation in vivo, as demonstrated by double immunofluorescence using oval- (A6 and EpCam) and hepatocyte-specific (i.e. hepatocyte nuclear factor 4-alpha) antibodies. Furthermore, lack of c-Met had a profound effect on tissue remodeling and overall composition of HSC niche, which was associated with greatly reduced matrix metalloproteinase (MMP)9 activity and decreased expression of stromal-cellderived factor 1. Using a combination of double immunofluorescence of cell-typespecific markers with MMP9 and gelatin zymography on the isolated cell populations, we identified macrophages as a major source of MMP9 in DDC-treated livers. The Mx1-Cre-driven c-met deletion caused the greatest phenotypic impact on HSCs response, as compared to the selective inactivation in the epithelial cell lineages achieved in c-Metfl/fl; Alb-Cre+/- mice. However, in both models, genetic loss of c-met triggered a similar cascade of events, leading to the failure of HSC mobilization and death of the mice. Conclusion: These results establish a direct contribution of c-Met in the regulation of HSC response and support a unique role for HGF/c-Met as an essential growth-factorsignaling pathway for regeneration of diseased liver. (HEPATOLOGY 2012) C1 [Ishikawa, Tsuyoshi; Factor, Valentina M.; Marquardt, Jens U.; Raggi, Chiara; Seo, Daekwan; Kitade, Mitsuteru; Conner, Elizabeth A.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bldg 37,Room 4146A,37 Convent Dr, Bethesda, MD 20892 USA. EM Snorri_thorgeirsson@nih.gov OI RAGGI, Chiara/0000-0003-2473-3535 FU National Institutes of Health, National Cancer Institute FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 53 TC 58 Z9 62 U1 1 U2 34 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2012 VL 55 IS 4 BP 1215 EP 1226 DI 10.1002/hep.24796 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 916AW UT WOS:000302069900025 PM 22095660 ER PT J AU Chen, F Du, SY Bian, JH You, ZB Wu, Y AF Chen, Fang Du, Shouyang Bian, Jianghui You, Zhi-Bing Wu, Yan TI Chronic hypoxia exposure during pregnancy is associated with a decreased active nursing activity in mother and an abnormal birth weight and postnatal growth in offspring of rats SO HORMONES AND BEHAVIOR LA English DT Article DE Corticosterone; Gestational hypoxia; Maternal behavior; Offspring development; Rat ID PITUITARY-ADRENAL AXIS; PRENATAL STRESS; MATERNAL-BEHAVIOR; GESTATIONAL STRESS; NORWAY RATS; CARE; CORTICOSTERONE; INSULIN; MICE; HIPPOCAMPUS AB Stress during pregnancy is known to have a significant impact on animal's behavior and offspring development. The effects of gestational hypoxia on maternal behavior have not been studied. In the present study, we investigated the effects of gestational hypoxia exposure on dam's maternal behavior, offspring's growth and plasma corticosterone levels after parturition in rats. Altitude hypoxia (3 and 5 km) was simulated in the hypobaric chambers during the last week of pregnancy and the effects were compared to those found in controls exposed at sea level. We found that gestational hypoxia significantly decreased dam's arched-back nursing activity across the lactation period. The effect was more profound in 5 km group. Gestational hypoxia also altered other maternal behaviors such as blanket and passive nursing. Hypoxia exposure was associated with abnormal birth weight and postnatal growth in pups, with a significantly higher and lower birth weight than control found in 3 and 5 km groups, respectively, and accelerated growth in both stressed groups. Gestational hypoxia exposure significantly elevated plasma corticosterone levels in dams at the time of weaning and in pups across the measurement days. Taken together, the present results indicate that hypoxia, particularly severe hypoxia during the late phase of pregnancy has a significantly adverse impact on animal's behavior, endocrine function and offspring development The higher birth weight found in the offspring of 3 km group suggests a compensatory system counteracting with the inhibitory effects of hypoxia on fetus growth at this altitude. (C) 2012 Elsevier Inc. All rights reserved. C1 [Chen, Fang; Du, Shouyang; Wu, Yan] Hangzhou Normal Univ, Xiasha High Educ Area, Coll Life & Environm Sci, Hangzhou 310036, Zhejiang, Peoples R China. [Bian, Jianghui] Chinese Acad Sci, NW Plateau Inst Biol, Xining 810008, Qinghai, Peoples R China. [You, Zhi-Bing] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Wu, Y (reprint author), Hangzhou Normal Univ, Xiasha High Educ Area, Coll Life & Environm Sci, 16 Xuelin St, Hangzhou 310036, Zhejiang, Peoples R China. EM wuyanqh@163.com FU National Natural Science Foundation of China [30570294, 31170394]; Hangzhou Key Laboratory of Animal Adaptation and Evolution FX This study was supported by the National Natural Science Foundation of China (30570294, 31170394) and Hangzhou Key Laboratory of Animal Adaptation and Evolution. We thank Dr. Stephan Steidl, at Behavioral Neuroscience Branch, NIDA-IRP, for his critical reading and editing the manuscript. NR 60 TC 5 Z9 7 U1 2 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0018-506X J9 HORM BEHAV JI Horm. Behav. PD APR PY 2012 VL 61 IS 4 BP 504 EP 511 DI 10.1016/j.yhbeh.2012.01.009 PG 8 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA 925LW UT WOS:000302763700006 PM 22285933 ER PT J AU Chen, XJ Udupa, JK Bagci, U Ying, ZG Yao, JH AF Chen, Xinjian Udupa, Jayaram K. Bagci, Ulas Ying Zhuge Yao, Jianhua TI Medical Image Segmentation by Combining Graph Cuts and Oriented Active Appearance Models SO IEEE TRANSACTIONS ON IMAGE PROCESSING LA English DT Article DE Active appearance model (AAM); graph cut (GC); live wire (LW); object segmentation ID SHAPE MODELS; ENERGY MINIMIZATION; FUZZY CONNECTEDNESS; LIVER SEGMENTATION; OBJECT DEFINITION; CARDIAC MR; CT IMAGES; ALGORITHMS; ATLAS; CONSTRUCTION AB In this paper, we propose a novel method based on a strategic combination of the active appearance model (AAM), live wire (LW), and graph cuts (GCs) for abdominal 3-D organ segmentation. The proposed method consists of three main parts: model building, object recognition, and delineation. In the model building part, we construct the AAM and train the LW cost function and GC parameters. In the recognition part, a novel algorithm is proposed for improving the conventional AAM matching method, which effectively combines the AAM and LW methods, resulting in the oriented AAM (OAAM). A multiobject strategy is utilized to help in object initialization. We employ a pseudo-3-D initialization strategy and segment the organs slice by slice via a multiobject OAAM method. For the object delineation part, a 3-D shape-constrained GC method is proposed. The object shape generated from the initialization step is integrated into the GC cost computation, and an iterative GC-OAAM method is used for object delineation. The proposed method was tested in segmenting the liver, kidneys, and spleen on a clinical CT data set and also on the MICCAI 2007 Grand Challenge liver data set. The results show the following: 1) The overall segmentation accuracy of true positive volume fraction TPVF > 94.3% and false positive volume fraction FPVF < 0.2% can be achieved; 2) the initialization performance can be improved by combining the AAM and LW; 3) the multiobject strategy greatly facilitates initialization; 4) compared with the traditional 3-D AAM method, the pseudo-3-D OAAM method achieves comparable performance while running 12 times faster; and 5) the performance of the proposed method is comparable to state-of-the-art liver segmentation algorithm. The executable version of the 3-D shape-constrained GC method with a user interface can be downloaded from http://xinjianchen.wordpress.com/research/. C1 [Chen, Xinjian; Bagci, Ulas; Yao, Jianhua] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20814 USA. [Udupa, Jayaram K.] Univ Penn, Dept Radiol, Med Image Proc Grp, Philadelphia, PA 19104 USA. [Ying Zhuge] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20814 USA. RP Chen, XJ (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20814 USA. EM myfuturejian@gmail.com; jay@mail.med.upenn.edu; bagciu@mail.nih.gov; zhugey@mail.nih.gov; jyao@mail.nih.gov RI Bagci, Ulas/A-4225-2012; Chen, Xinjian/E-8592-2016; OI Bagci, Ulas/0000-0001-7379-6829 FU Clinical Center, NIH FX Manuscript received December 27, 2010; revised May 10, 2011, October 03, 2011, and January 04, 2012; accepted January 09, 2012. Date of publication January 31, 2012; date of current version March 21, 2012. This work was supported in part by the Intramural Research Program of the Clinical Center, NIH. The associate editor coordinating the review of this manuscript and approving it for publication was Prof. Margaret Cheney. NR 49 TC 55 Z9 67 U1 5 U2 30 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1057-7149 J9 IEEE T IMAGE PROCESS JI IEEE Trans. Image Process. PD APR PY 2012 VL 21 IS 4 BP 2035 EP 2046 DI 10.1109/TIP.2012.2186306 PG 12 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 917MP UT WOS:000302181800048 PM 22311862 ER PT J AU Paulson, ML Olivier, KN Holland, SM AF Paulson, M. L. Olivier, K. N. Holland, S. M. TI Pulmonary non-tuberculous mycobacterial infection in congenital contractural arachnodactyly SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE atypical mycobacterial; Mycobacterium avium complex; human fibrillin 2 (congenital contracrural arachnodactyly) protein; fibrillin ID EXTRACELLULAR MICROFIBRILS; MARFAN-SYNDROME; DISEASE; MUTATIONS AB Congenital contractural arachnodactyly (CCA) is caused by mutations within the fibrillin-2 gene (FBN2), which is crucial for microfibril structure. Affected individuals may have contractures, chest wall deformities, scoliosis, abnormal ear folding and elongated limbs. We describe a novel FBN2 mutation in a woman with CCA who also had pulmonary non-tuberculous mycobacteria (NTM) infection. The population with pulmonary NTM infections shares phenotypic features with CCA, such as elongated body habitus, scoliosis and pectus deformities. While it is unlikely that FBN2 defects account for susceptibility to NTM infection in the majority of cases, the overlap between these two diseases suggests some shared pathophysiology. C1 [Paulson, M. L.] NCI, Lab Clin Infect Dis, SAIC Frederick Inc, NIH, Bethesda, MD 20892 USA. RP Paulson, ML (reprint author), NCI, Lab Clin Infect Dis, SAIC Frederick Inc, NIH, 9000 Rockville Pike,CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA. EM paulsonm@niaid.nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This research was supported [in part] by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. NR 10 TC 11 Z9 11 U1 0 U2 1 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD APR PY 2012 VL 16 IS 4 BP 561 EP 563 DI 10.5588/ijtld.11.0301 PG 3 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 919OA UT WOS:000302336300025 PM 22325249 ER PT J AU Cabral-Marques, O Schimke, LF Pereira, PVS Falcai, A de Oliveira, JB Hackett, MJ Errante, PR Weber, CW Ferreira, JF Kuntze, G Rosario, NA Ochs, HD Torgerson, TR Carvalho, BTC Condino-Neto, A AF Cabral-Marques, Otavio Schimke, Lena-Friederike Soeiro Pereira, Paulo Vitor Falcai, Angela de Oliveira, Joao Bosco Hackett, Mary J. Errante, Paolo Ruggero Weber, Cristina Worm Ferreira, Janaira Fernandes Kuntze, Gisele Rosario-Filho, Nelson Augusto Ochs, Hans D. Torgerson, Troy R. Costa Carvalho, Beatriz Tavares Condino-Neto, Antonio TI Expanding the Clinical and Genetic Spectrum of Human CD40L Deficiency: The Occurrence of Paracoccidioidomycosis and Other Unusual Infections in Brazilian Patients SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE Paracoccidioides brasiliensis; CD40 ligand; primary immunodeficiency; X-linked hyper-IgM syndrome ID HYPER-IGM SYNDROME; CHRONIC MUCOCUTANEOUS CANDIDIASIS; HUMAN-IMMUNODEFICIENCY-VIRUS; FUNGAL-INFECTIONS; ENDEMIC AREA; LIGAND GENE; T-CELLS; MUTATIONS; DISEASE; SERIES AB CD40 ligand (CD40L) deficiency or X-linked hyper-IgM syndrome (X-HIGM) is a well-described primary immunodeficiency in which Pneumocystis jiroveci pneumonia is a common clinical feature. We have identified an unusual high incidence of fungal infections and other not yet described infections in a cohort of 11 X-HIGM patients from nine unrelated Brazilian families. Among these, we describe the first case of paracoccidioidomycosis (PCM) in X-HIGM. The molecular genetic analysis of CD40L was performed by gene sequencing and evaluation of CD40L protein expression. Nine of these 11 patients (82%) had fungal infections. These included fungal species common to CD40L deficiency (P. jiroveci and Candida albicans) as well as Paracoccidioides brasiliensis. One patient presented with PCM at age 11 years and is now doing well at 18 years of age. Additionally, one patient presented with a simultaneous infection with Klebsiella and Acinetobacter, and one with condyloma caused by human papilloma virus. Molecular analysis revealed four previously described CD40L mutations, two novel missense mutations (c.433 T>G and c.476 G>C) resulting in the absence of CD40L protein expression by activated CD4(+) cells and one novel insertion (c.484_485insAA) within the TNFH domain leading to a frame shift and premature stop codon. These observations demonstrated that the susceptibility to fungal infections in X-HIGM extends beyond those typically associated with X-HIGM (P. jiroveci and C. albicans) and that these patients need to be monitored for those pathogens. C1 [Cabral-Marques, Otavio; Schimke, Lena-Friederike; Soeiro Pereira, Paulo Vitor; Falcai, Angela; Errante, Paolo Ruggero; Condino-Neto, Antonio] Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, BR-05508000 Sao Paulo, Brazil. [Hackett, Mary J.; Ochs, Hans D.; Torgerson, Troy R.] Univ Washington, Dept Pediat, Sch Med & Seattle, Childrens Hosp, Seattle, WA 98195 USA. [de Oliveira, Joao Bosco] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Weber, Cristina Worm] Pediat Allergy & Immunol Clin, Caxias Do Sul, RS, Brazil. [Ferreira, Janaira Fernandes] Albert Sabin Hosp, Fortaleza, Ceara, Brazil. [Kuntze, Gisele] Pequeno Principe Hosp, Curitiba, Parana, Brazil. [Rosario-Filho, Nelson Augusto] Univ Fed Parana, Dept Pediat, Sch Med, BR-80060000 Curitiba, Parana, Brazil. [Costa Carvalho, Beatriz Tavares] Univ Fed Sao Paulo, Div Allergy & Clin Immunol & Rheumatol, Dept Pediat, Sch Med, Sao Paulo, Brazil. RP Condino-Neto, A (reprint author), Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, 1730 Lineu Prestes Ave, BR-05508000 Sao Paulo, Brazil. EM condino@icb.usp.br OI Oliveira, Joao/0000-0001-9388-8173 FU FAPESP [2008/06635-0, 2008/55700-9]; CNPq; Jeffrey Modell Foundation FX The authors thank FAPESP (grant 2008/06635-0 to OCM and grant 2008/55700-9 to ACN), CNPq, and Jeffrey Modell Foundation for financial support and the patients and their families for their participation in this study. NR 55 TC 15 Z9 16 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 212 EP 220 DI 10.1007/s10875-011-9623-6 PG 9 WC Immunology SC Immunology GA 923JI UT WOS:000302615200002 PM 22193914 ER PT J AU Ding, L Mo, A Jutivorakool, K Pancholi, M Holland, SM Browne, SK AF Ding, Li Mo, Allen Jutivorakool, Kamonwan Pancholi, Minjal Holland, Steven M. Browne, Sarah K. TI Determination of Human Anticytokine Autoantibody Profiles Using a Particle-Based Approach SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE Interferon gamma; luminex; thymoma; pulmonary alveolar proteinosis; immunodeficiency ID PEMPHIGUS-VULGARIS; RITUXIMAB; DISEASE; ASSAY; IGG AB Background Anticytokine autoantibodies cause numerous human diseases, ranging from pure red cell aplasia to acquired immunodeficiencies. Rapid, simple, and affordable detection and monitoring of these antibodies is essential. We sought to develop a standardizable assay that is rapid, sensitive, and specific and able to simultaneously detect multiple anticytokine autoantibodies in small volumes (<10 mu l). Methods We conjugated purified human cytokines to commercially available fluorescently labeled microspheres and tested them against sera from well-characterized subjects with at least one high-titer, disease-associated anticytokine autoantibody. Results Cytokine-conjugated microspheres efficiently and rapidly determined plasma concentration and IgG subclass of anticytokine autoantibodies in single or multiplex formats. Conclusion This particle-based multiplex assay can reproducibly characterize anticytokine autoantibodies. This efficient and inexpensive approach to diagnosing and monitoring anticytokine autoantibodies has clinical applications. C1 [Ding, Li; Mo, Allen; Jutivorakool, Kamonwan; Pancholi, Minjal; Holland, Steven M.; Browne, Sarah K.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Mo, Allen] Colgate Univ, Hamilton, NY 13346 USA. RP Browne, SK (reprint author), NIAID, Lab Clin Infect Dis, 9000 Rockville Pike,MSC 1684,Bldg 10-CRC,Rm B3-42, Bethesda, MD 20892 USA. EM brownesa@niaid.nih.gov FU Division of Intramural Research at the National Institute of Allergy and Infectious Diseases; Colgate University FX This work was supported by the Division of Intramural Research at the National Institute of Allergy and Infectious Diseases and Colgate University. NR 17 TC 18 Z9 18 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 238 EP 245 DI 10.1007/s10875-011-9621-8 PG 8 WC Immunology SC Immunology GA 923JI UT WOS:000302615200005 PM 22170314 ER PT J AU Cunha, LAO Figueiredo, BCG Silva, ML Nunes, JBS Cunha, JM Oliveira, JB Pinto, JA AF Cunha, L. A. O. Figueiredo, B. C. G. Silva, M. L. Nunes, J. B. S. Cunha, J. M. Oliveira, Joao Bosco Pinto, J. A. TI Could Maternal T Cell Engraftment Be Good to a SCID Patient? SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Cunha, L. A. O.; Figueiredo, B. C. G.; Silva, M. L.; Nunes, J. B. S.; Pinto, J. A.] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. [Cunha, J. M.] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil. [Oliveira, Joao Bosco] NIH, Dept Lab Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 358 EP 359 PG 2 WC Immunology SC Immunology GA 923JI UT WOS:000302615200038 ER PT J AU Albert, MH Aydin, S Alsum, Z Chatila, T Su, HL Heinz, V Al-Herz, W Keles, S Picard, C Kilic, S Gathmann, B Honig, M Almousa, H Sawalle-Belohradsky, J Gennery, A Geha, RS Renner, E Grimbacher, B Freeman, AF Engelhardt, KR AF Albert, Michael H. Aydin, Susanne Alsum, Zobaida Chatila, Talal Su, Helen Heinz, Valerie Al-Herz, Waleed Keles, Sevgi Picard, Capucine Kilic, Sara Gathmann, Benjamin Hoenig, Manfred Almousa, Hamoud Sawalle-Belohradsky, Julie Gennery, Andrew Geha, Raif S. Renner, Ellen Grimbacher, Bodo Freeman, Alexandra F. Engelhardt, Karin R. TI Clinical Presentation, Long-Term Outcome and Therapeutic Management of DOCK8 Deficiency-an International Survey of 125 Patients SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Albert, Michael H.; Aydin, Susanne; Heinz, Valerie; Sawalle-Belohradsky, Julie; Renner, Ellen] Univ Munich, Dr Von Haunerschen Kinderspital, D-80337 Munich, Germany. [Alsum, Zobaida; Almousa, Hamoud] King Faisal Specialist Hosp & Res Ctr, Ryadh, Saudi Arabia. [Chatila, Talal] Univ Calif Los Angeles, Los Angeles, CA USA. [Chatila, Talal] Childrens Hosp, Boston, MA 02115 USA. [Su, Helen; Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Al-Herz, Waleed] Kuwait Univ, Dept Pediat, Fac Med, Kuwait, Kuwait. [Keles, Sevgi] Konya Univ, Meram Med Fac, Konya, Turkey. [Picard, Capucine] Univ Paris 05, Hop Necker Enfants Malad, Paris, France. [Kilic, Sara] Uludag Univ, Fac Med, Bursa, Turkey. [Gathmann, Benjamin; Grimbacher, Bodo; Engelhardt, Karin R.] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany. [Hoenig, Manfred] Univ Kinderklin, Ulm, Germany. [Gennery, Andrew] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Geha, Raif S.] Harvard Univ, Sch Med, Childrenns Hosp, Div Immunol, Boston, MA USA. [Grimbacher, Bodo; Engelhardt, Karin R.] Royal Free Hosp, Dept Immunol & Mol Pathol, London NW3 2QG, England. [Grimbacher, Bodo; Engelhardt, Karin R.] UCL, London, England. RI Su, Helen/H-9541-2015 OI Su, Helen/0000-0002-5582-9110 NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 359 EP 359 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200039 ER PT J AU Engelhardt, KR Gertz, EM Keles, S Schaffer, AA Ceja, R Sassi, A Graham, L Massaad, MJ Bejaoui, M Barbouche, MR Geha, RS Chatila, TA Grimbacher, B AF Engelhardt, Karin R. Gertz, E. Michael Keles, Sevgi Schaeffer, Alejandro A. Ceja, Ruben Sassi, Atfa Graham, Laura Massaad, Michel J. Bejaoui, Mohamed Barbouche, Mohamed-Ridha Geha, Raif S. Chatila, Talal A. Grimbacher, Bodo CA 38 Referring Phys TI DOCK8 Deficiency and Diagnostic Guidelines for Hyper-IgE Syndromes SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Engelhardt, Karin R.; Graham, Laura] Royal Free Hosp, Dept Immunol & Mol Pathol, London NW3 2QG, England. [Engelhardt, Karin R.; Graham, Laura] UCL, London, England. [Engelhardt, Karin R.; 38 Referring Phys] Univ Med Ctr Freiburg, CCI, Freiburg, Germany. [Gertz, E. Michael; Schaeffer, Alejandro A.] NIH, Dept Hlth & Human Serv, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Keles, Sevgi; Ceja, Ruben] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Immunol Allergy & Rheumatol, Los Angeles, CA 90095 USA. [Keles, Sevgi] Selcuk Univ, Div Pediat Allergy & Immunol, Konya, Turkey. [Sassi, Atfa] Inst Pasteur, Lab Immunopathol Vaccinol & Mol Genet, Tunis, Tunisia. [Bejaoui, Mohamed] Bone Marrow Transplantat Cener, Dept Pediat, Tunis, Tunisia. [Barbouche, Mohamed-Ridha] Inst Pasteur, Dept Immunol, Tunis, Tunisia. [Geha, Raif S.] Harvard Univ, Childrens Hosp, Sch Med, Div Immunol, Boston, MA 02115 USA. [Ceja, Ruben; Massaad, Michel J.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA. RI Schaffer, Alejandro/F-2902-2012; Sassi, Atfa/A-5676-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 361 EP 361 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200045 ER PT J AU Sanchez, LA Cuellar-Rodriguez, J Zerbe, CS Hsu, AP Hickstein, DD Freeman, AF Holland, SM AF Sanchez, Lauren A. Cuellar-Rodriguez, Jennifer Zerbe, Christa S. Hsu, Amy P. Hickstein, Dennis D. Freeman, Alexandra F. Holland, Steven M. TI Thrombotic Complications in GATA2 Deficiency SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Sanchez, Lauren A.; Cuellar-Rodriguez, Jennifer; Zerbe, Christa S.; Hsu, Amy P.; Freeman, Alexandra F.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Hickstein, Dennis D.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 362 EP 362 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200048 ER PT J AU Lopez-Herrera, G Tampella, G Baronio, M Vitali, M Lougaris, V Plebani, A Pan-Hammarstrom, Q Hammarstrom, L Du, LK Hultenby, K Trujillo-Vargas, CM Phadwal, K Simon, AK Moutschen, M Etzioni, A Srugo, AMI Melamed, D Liu, CH Philippet, P Dideberg, V Aghamohammadi, A Rezai, N Enright, V Stauss, H Herholz, P Salzer, U Eibel, H Pfeifer, D Velkeen, H Gertz, EM Schaffer, AA Grimbacher, B AF Lopez-Herrera, Gabriela Tampella, Giacomo Baronio, Manuela Vitali, Massimilaino Lougaris, Vassilious Plebani, Alessandro Pan-Hammarstroem, Qiang Hammarstroem, Lennart Du, Likun Hultenby, Kjell Trujillo-Vargas, Claudia M. Phadwal, Kanchan Simon, Anna Katharina Moutschen, Michel Etzioni, Amos Srugo, Adi Mory Izhak Melamed, Doron Liu, Chonghai Philippet, Pierre Dideberg, Vinciane Aghamohammadi, Asghar Rezai, Nima Enright, Victoria Stauss, Hans Herholz, Peer Salzer, Ulrich Eibel, Hermann Pfeifer, Dietmar Velkeen, Hendrik Gertz, E. Michael Schaeffer, Alejandro A. Grimbacher, Bodo TI Mutations in LRBA are Associated with a Syndrome of Immune Deficiency and Autoimmunity SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Lopez-Herrera, Gabriela; Trujillo-Vargas, Claudia M.; Stauss, Hans; Grimbacher, Bodo] UCL, Dept Immunol, Div Infect & Immun, Royal Free Hosp, London, England. [Lopez-Herrera, Gabriela] Immunodeficiency Res Unit, Mexico City, DF, Mexico. [Lopez-Herrera, Gabriela] Natl Inst Pediat, Mexico City, DF, Mexico. [Plebani, Alessandro] Univ Brescia, Dept Pediat, Brescia, Italy. [Plebani, Alessandro] Univ Brescia, Inst Mol Med A Novicelli, Brescia, Italy. [Hultenby, Kjell; Liu, Chonghai] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Dept Lab Med, Stockholm, Sweden. [Trujillo-Vargas, Claudia M.] Univ Antioquia, Grp Primary Immunodeficiencies, Medellin, Colombia. [Phadwal, Kanchan; Simon, Anna Katharina] Univ Oxford, BRC Translat Immunol Lab, NIHR, Nuffield Dept Med,John Radcliffe Hosp, Oxford OX3 9DS, England. [Simon, Anna Katharina] Univ Oxford, MRC Human Immunol Unit, Weatherall Inst Mol Med, John Radcliffe Hosp, Oxford OX3 9DS, England. [Moutschen, Michel] Univ Liege Ctr Immunol CIL, Lab Immunoendocrinol, Inst Pathol, Liege, Belgium. [Melamed, Doron] Technion Israel Inst Technol, Meyers Children Hosp, Rambam Hlth Care Campus & Rappaport Fac Med, Haifa, Israel. [Liu, Chonghai] Affiliated Hosp, N Sichuan Med Coll, Dept Pediat, Nanchong 637000, Sichuan, Peoples R China. [Philippet, Pierre] CHC Esperance, Dept Pediat, Montegnee, Belgium. [Dideberg, Vinciane] Univ Liege, Ctr Human Genet, Liege, Belgium. [Aghamohammadi, Asghar] Univ Tehran Med Sci, Res Ctr Immunodeficiencies, Childrens Med Ctr, Pediat Ctr Excellence, Tehran, Iran. [Rezai, Nima] Univ Tehran Med Sci, Sch Med, Mol Immunol Res Ctr, Tehran, Iran. [Rezai, Nima] Univ Tehran Med Sci, Sch Med, Dept Immunol, Tehran, Iran. [Eibel, Hermann] Univ Med Ctr Freiburg, CCI, Freiburg, Germany. [Pfeifer, Dietmar] Univ Freiburg, Dept Hematol & Oncol, D-79106 Freiburg, Germany. [Velkeen, Hendrik] Leiden Univ, Med Ctr, Dept Hematol, Leiden, Netherlands. [Gertz, E. Michael; Schaeffer, Alejandro A.] NIH, Department Hlth & Human Serv, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RI Schaffer, Alejandro/F-2902-2012 NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 363 EP 364 PG 2 WC Immunology SC Immunology GA 923JI UT WOS:000302615200053 ER PT J AU Myles, IA Gaidamakova, EK McDaniel, DP Fowler, CJ Valdez, PA Gayen, M Gupta, P Sharma, A Glass, P Maheshwari, RK Daly, MJ Datta, SK AF Myles, Ian A. Gaidamakova, Elena K. McDaniel, Dennis P. Fowler, Cedar J. Valdez, Patricia A. Gayen, Manoshi Gupta, Paridhi Sharma, Anuj Glass, Pamela Maheshwari, Radha K. Daly, Michael J. Datta, Sandip K. TI Sterility Without Loss of Immunogenicity with Irradiated Vaccine Preparations of Viruses and Staphylococcus Aureus SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Myles, Ian A.; Fowler, Cedar J.; Valdez, Patricia A.; Datta, Sandip K.] NIAID, NIH, Bethesda, MD 20892 USA. [Gaidamakova, Elena K.; McDaniel, Dennis P.; Daly, Michael J.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Gayen, Manoshi; Gupta, Paridhi; Sharma, Anuj; Glass, Pamela; Maheshwari, Radha K.] Birla Inst Technol & Sci, Pilani, Rajasthan, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 365 EP 365 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200057 ER PT J AU Browne, SK Rosen, LB Rader, C Holland, SM AF Browne, Sarah K. Rosen, Lindsey B. Rader, Christoph Holland, Steven M. TI Titer, and Not Avidity Determines Degree of Pathogenicity of Anti-IFN gamma Autoantibodies in Mediating Immunodeficiency SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Browne, Sarah K.; Rosen, Lindsey B.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 371 EP 372 PG 2 WC Immunology SC Immunology GA 923JI UT WOS:000302615200077 ER PT J AU Jutivorakool, K Ding, L Hsu, AP Holland, SM Browne, SK AF Jutivorakool, Kamonwan Ding, Li Hsu, Amy P. Holland, Steven M. Browne, Sarah K. TI Epitope Mapping, Isotype and IgG Subclass of Anti-Interferon Gamma Autoantibodies SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Jutivorakool, Kamonwan; Ding, Li; Hsu, Amy P.; Holland, Steven M.; Browne, Sarah K.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Jutivorakool, Kamonwan] Chulalongkorn Univ, Dept Med, Fac Med, Bangkok, Thailand. [Jutivorakool, Kamonwan] King Chulalongkorn Mem Hosp, Thai Red Cross Soc, Bangkok, Thailand. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 371 EP 371 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200075 ER PT J AU Freeman, AF Renner, E Olivier, KN Henderson, C Langenbeck, A Kwong, KF Holland, SM AF Freeman, Alexandra F. Renner, Ellen Olivier, Kenneth N. Henderson, Carolyn Langenbeck, Anne Kwong, King F. Holland, Steven M. TI Lung Surgery Outcomes in Stat3 Mutated Hyper IgE Syndrome SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Freeman, Alexandra F.; Olivier, Kenneth N.; Henderson, Carolyn; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Renner, Ellen] Dr von Haunersches Kinderspital, Munich, Germany. [Kwong, King F.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 372 EP 372 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200079 ER PT J AU Menard, L Tangye, S Church, J Klion, A Cunningham-Rundles, C Nichols, K Meffre, E AF Menard, Laurence Tangye, Stuart Church, Joseph Klion, Amy Cunningham-Rundles, Charlotte Nichols, Kim Meffre, Eric TI Slam-Associated Protein (SAP) is Essential for the Establishment of Human B Cell Tolerance SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Menard, Laurence; Meffre, Eric] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Church, Joseph] Childrens Hosp Los Angeles, Los Angeles, CA USA. [Klion, Amy] NIAID, NIH, Bethesda, MD 20892 USA. [Cunningham-Rundles, Charlotte] Mt Sinai Med Ctr, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 373 EP 373 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200082 ER PT J AU Sowerwine, KJ Nicholas, SK Holland, SM Freeman, AF AF Sowerwine, Kathryn J. Nicholas, Sarah K. Holland, Steven M. Freeman, Alexandra F. TI Adverse Reactions After Administration of 23-Valent Pneumococcal Polysaccharide Vaccine (PPV-23) in STAT3 Deficient Hyper IgE Syndrome (STAT3 HIES) SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Sowerwine, Kathryn J.; Holland, Steven M.; Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Nicholas, Sarah K.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 378 EP 379 PG 2 WC Immunology SC Immunology GA 923JI UT WOS:000302615200098 ER PT J AU Sowerwine, KJ Boris, L Davis, J Welch, P Holland, SM Freeman, AF AF Sowerwine, Kathryn J. Boris, Lisa Davis, Joie Welch, Pamela Holland, Steven M. Freeman, Alexandra F. TI Clinical and Immunologic Findings in Young Children with Early Diagnosis of STAT3 Deficient Hyper IgE Syndrome (STAT3 HIES) SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Sowerwine, Kathryn J.; Holland, Steven M.; Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Boris, Lisa; Davis, Joie; Welch, Pamela] NIAID, DCR, ICMOB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 378 EP 378 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200097 ER PT J AU Siegel, AM Lawrence, MG Freeman, AF Stone, K Barber, J Jung, MY Desai, A Olivera, A Farber, O Gilfillan, AM Rivera, J Milner, J AF Siegel, Andrea M. Lawrence, Monica G. Freeman, Alexandra F. Stone, Kelly Barber, John Jung, Mi-yeon Desai, Avanti Olivera, Ana Farber, Orly Gilfillan, Alasdair M. Rivera, Juan Milner, Joshua TI Impaired Mast Cell Function Leads to Reduced Allergic Disease in Ad-hies Patients SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Barber, John] NIAID, Allerg Inflammat Unit, Lab Allerg Dis, Bethesda, MD 20892 USA. [Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Milner, Joshua] NIAID, Allerg Inflammat Unit, Lab Allerg Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 379 EP 380 PG 2 WC Immunology SC Immunology GA 923JI UT WOS:000302615200101 ER PT J AU Lawrence, MG Barber, J Desai, A O'Brien, M Jones, N Garabedian, E Sokolic, R Candotti, F Stone, K Milner, J AF Lawrence, Monica G. Barber, John Desai, Avanti O'Brien, Michelle Jones, Nina Garabedian, Elizabeth Sokolic, Robert Candotti, Fabio Stone, Kelly Milner, Joshua TI Lymphopenia is Associated with a TH2 Phenotype and Specific Allergen Sensitivity in Patients with ADA-SCID SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Lawrence, Monica G.; Barber, John; Desai, Avanti; O'Brien, Michelle; Jones, Nina; Stone, Kelly; Milner, Joshua] NIAID, Bethesda, MD 20892 USA. [Sokolic, Robert] NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RI Sokolic, Robert/I-6072-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 383 EP 383 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200112 ER PT J AU Barber, J Yokomizo, L Milner, J AF Barber, John Yokomizo, Lauren Milner, Joshua TI A Novel Approach to Activating CD4 T-Cells and Assessing the Diversity of T-Cell Receptors Using Randomized Peptide Pools SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Barber, John; Yokomizo, Lauren; Milner, Joshua] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. [Yokomizo, Lauren] Stanford Univ, Sch Med, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 384 EP 384 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200116 ER PT J AU Dowdell, K Lu, LH Kuehn, H Rao, VK Fleisher, TA Oliveira, JB AF Dowdell, Kennichi Lu, Lianghao Kuehn, Hyesun Rao, V. Koneti Fleisher, Thomas A. Oliveira, Joao Bosco TI The BH3 Mimetic, Small Molecule, ABT-737, was Effective for the Treatment of THE MRL/LPR-/- Mouse Model of Autoimmune Lymphoproliferative Syndrome (ALPS) SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Oliveira, Joao Bosco] NIH, Dept Lab Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 385 EP 385 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200120 ER PT J AU Uzel, G Sampaio, EP Lawrence, MG Hsu, AP Dorsey, M Freeman, AF Gambinieri, E Dat, QT Torgerson, TR Milner, J Holland, SM AF Uzel, Gulbu Sampaio, Elizabeth P. Lawrence, Monica G. Hsu, Amy P. Dorsey, Morna Freeman, Alexandra F. Gambinieri, Eleonora Dat, Q. Tran Torgerson, Troy R. Milner, Joshua Holland, Steven M. TI Dominant Gain-of-Function Mutations in STAT1 and FOXP3+IPEX-Like Disease SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Uzel, Gulbu; Hsu, Amy P.; Freeman, Alexandra F.; Holland, Steven M.] NIAID, NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Dorsey, Morna] Univ S Florida, Dept Allergy Immunol & Rheumatol, St Petersburg, FL 33701 USA. [Gambinieri, Eleonora] Univ Florence, Anna Meyer Childrens Hosp, Haematol Oncol Dept, BMT Unit, Florence, Italy. [Torgerson, Troy R.] Univ Washington, Ctr Immun & Immunotherapies, Seattle Childrens Res Inst, Seattle, WA 98195 USA. [Milner, Joshua] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 386 EP 386 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200121 ER PT J AU Leiding, JW Marciano, BE DeRavin, SS Malech, HL Holland, SM AF Leiding, Jennifer W. Marciano, Beatriz E. DeRavin, Suk See Malech, Harry L. Holland, Steven M. TI Diabetes and Cardiovascular Disease in p47phox-/- Chronic Granulomatous Disease SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Leiding, Jennifer W.; Marciano, Beatriz E.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [DeRavin, Suk See; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 389 EP 389 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200132 ER PT J AU Cunha, LAO Oliveira, JB Guimaraes, TN Figueiredo, BCG Silva, ML Nunes, JBS Miranda, LC Pinto, JA AF Cunha, L. A. O. Oliveira, Joao Bosco Guimaraes, Tiago Nunes Figueiredo, B. C. G. Silva, M. L. Nunes, J. B. S. Miranda, L. C. Pinto, J. A. TI CD3 Delta Deficiency: Finding a Familial Cluster in Minas Gerais, Brazil SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Guimaraes, Tiago Nunes] Univ Fed Minas Gerais, Sch Med, Div Allergy & Immunol, Belo Horizonte, MG, Brazil. [Oliveira, Joao Bosco] NIH, Serv Immunol, Dept Lab Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 391 EP 391 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200137 ER PT J AU Rosenzweig, SD Kuehn, H Fleisher, TA Oliveira, JB AF Rosenzweig, Sergio D. Kuehn, Hyesun Fleisher, Thomas A. Oliveira, Joao Bosco TI Caspase-8 Deficiency Manifesting as Adult-Onset Multi-Organ Granulomatous Disorder with Recurrent Infections SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Oliveira, Joao Bosco] NIH, Dept Lab Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 391 EP 391 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200136 ER PT J AU Matharu, K Zarember, KA Kuhns, DB Spalding, C Garofalo, M Dimaggio, T Holland, SM Malech, HL Gallin, JI AF Matharu, Kabir Zarember, Kol A. Kuhns, Douglas B. Spalding, Chris Garofalo, Mary Dimaggio, Thomas Holland, Steven M. Malech, Harry L. Gallin, John I. TI B-Cell Activating Factor (BAFF/BLYS) in Chronic Granulomatous Disease (CGD) SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Matharu, Kabir] NIAID, Host Def Lab, Howard Hughes Med Inst, Chevy Chase, MD USA. [Matharu, Kabir; Zarember, Kol A.; Garofalo, Mary; Malech, Harry L.; Gallin, John I.] NIAID, Host Def Lab, NIH, Chevy Chase, MD USA. [Kuhns, Douglas B.; Dimaggio, Thomas] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. [Spalding, Chris; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 392 EP 392 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200141 ER PT J AU Falcone, EL Greenberg, DE Tierce, ML de la Morena, MT Chase, JM Church, J Zelazny, AM Holland, SM AF Falcone, Emilia Liana Greenberg, David E. Tierce, Millard Lucien de la Morena, M. Teresa Chase, John M. Church, Joseph Zelazny, Adrian M. Holland, Steven M. TI Methylotrophs: A New Group of Bacteria Affecting Patients with Chronic Granulomatous Disease SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Falcone, Emilia Liana; Zelazny, Adrian M.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Greenberg, David E.] Univ Texas SW Med Ctr Dallas, Div Infect Dis, Dallas, TX 75390 USA. [Tierce, Millard Lucien] Childrens Hosp Michigan, Detroit, MI 48201 USA. [de la Morena, M. Teresa] UT SW Med Ctr, Dept Pediat, Childrens Med Ctr Dallas, Dallas, TX USA. [Chase, John M.; Church, Joseph] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Chase, John M.] Univ So Calif, Div Gen Pediat, Childrens Hosp Los Angeles, Los Angeles, CA USA. [Church, Joseph] Univ So Calif, Div Clin Immunol & Allergy, Childrens Hosp Los Angeles, Los Angeles, CA USA. [Zelazny, Adrian M.] NIH, Microbiol Serv, Dept Lab Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 402 EP 403 PG 2 WC Immunology SC Immunology GA 923JI UT WOS:000302615200173 ER PT J AU Pechacek, JJ Hsu, AP Bax, H Dias, DL Paulson, M Ding, L Uzel, G Rosen, LB Browne, SK Datta, S Milner, J Chandrasekaran, P Zerbe, CS Wiley, H Greenberg, DE Hoover, S Rosenzweig, SD Galgiani, JN Holland, SM Sampaio, EP AF Pechacek, Joseph J. Hsu, Amy P. Bax, Hannalore Dias, Dalton L. Paulson, Michelle Ding, Li Uzel, Gulbu Rosen, Lindsey B. Browne, Sarah K. Datta, Shrimati Milner, Joshua Chandrasekaran, Prabha Zerbe, Christa S. Wiley, Henry Greenberg, David E. Hoover, Susan Rosenzweig, Sergio D. Galgiani, John N. Holland, Steven M. Sampaio, Elizabeth P. TI Dominant STAT1 Mutations Leading to Disseminated Fungal Infections SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Pechacek, Joseph J.; Hsu, Amy P.; Ding, Li; Uzel, Gulbu; Browne, Sarah K.; Zerbe, Christa S.; Holland, Steven M.] NIAID, NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Bax, Hannalore] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Bax, Hannalore] Erasmus MC, Dept Med Microbiol & Infect Dis, Rotterdam, Netherlands. [Paulson, Michelle] SAIC Frederick, Clin Res Directorate, CMRP, Bethesda, MD USA. [Rosen, Lindsey B.] NIAID, LCID, NIH, Bethesda, MD 20892 USA. [Milner, Joshua] NIAID, Allerg Inflammat Unit, Lab Allerg Dis, Bethesda, MD 20892 USA. [Greenberg, David E.] Univ Texas SW Med Ctr Dallas, Div Infect Dis, Dallas, TX 75390 USA. [Hoover, Susan; Galgiani, John N.] Univ Arizona, Valley Fever Ctr Excellence, Coll Med, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 403 EP 403 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200174 ER PT J AU Sokolic, R Muul, L Garabedian, E Shaw, K Hershfield, MS Wayne, AS Kohn, DB Candotti, F AF Sokolic, Robert Muul, Linda Garabedian, Elizabeth Shaw, Kit Hershfield, Michael S. Wayne, Alan S. Kohn, Donald B. Candotti, Fabio TI Systemic Effects of PEG-ADA Withdrawal with or Without Chemotherapy (CHTX) and Cytotherapy (CTX) in Adenosine Deaminase-Deficient Severe Combined Immune Deficiency (ADA-SCID) SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Sokolic, Robert] NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. [Shaw, Kit; Kohn, Donald B.] Univ Calif Los Angeles, Los Angeles, CA USA. [Hershfield, Michael S.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Wayne, Alan S.] NCI, Bethesda, MD 20892 USA. RI Sokolic, Robert/I-6072-2012 NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 404 EP 404 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200176 ER PT J AU Falcao, ACAM Marques, PTL Santos, AR Oliveira, JB AF Augusto Moura Falcao, Ana Carla Lyra Marques, Paula Teixeira Santos, Andreia Rangel Oliveira, Joao Bosco TI Disseminated Histoplasmosis Caused by IL12RB1 Gene Mutations in Two Brazilian Siblings SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Augusto Moura Falcao, Ana Carla; Lyra Marques, Paula Teixeira] Univ Fed Pernambuco, Recife, PE, Brazil. [Oliveira, Joao Bosco] NIH, Serv Immunol, Dept Lab Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 405 EP 405 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200180 ER PT J AU Punwani, D Gonzalez-Espinosa, D Dutra, A Pak, E Puck, J AF Punwani, Divya Gonzalez-Espinosa, Diana Dutra, Amalia Pak, Evgenia Puck, Jennifer TI A Universal Callibrator for TREC Testing Assists Newborn Screening for SCID and Studies of Immunoreconstitution SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American Conference on Primary Immune Deficiency Diseases CY MAY 17-20, 2012 CL Chicago, IL SP Clin Immunol Soc (CIS) C1 [Punwani, Divya; Gonzalez-Espinosa, Diana; Puck, Jennifer] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Dutra, Amalia; Pak, Evgenia] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2012 VL 32 IS 2 BP 409 EP 409 PG 1 WC Immunology SC Immunology GA 923JI UT WOS:000302615200191 ER PT J AU Stojmirovic, A Yu, YK AF Stojmirovic, Aleksandar Yu, Yi-Kuo TI Information Flow in Interaction Networks II: Channels, Path Lengths, and Potentials SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE Markov chains; random walks; matrices; proteins; networks; information theory; pathways; channels ID PROTEIN INTERACTION NETWORK; COLLABORATIVE RECOMMENDATION; INTERACTION DATABASE; MAP; YEAST; RESOURCE; GRAPH; SUM AB In our previous publication, a framework for information flow in interaction networks based on random walks with damping was formulated with two fundamental modes: emitting and absorbing. While many other network analysis methods based on random walks or equivalent notions have been developed before and after our earlier work, one can show that they can all be mapped to one of the two modes. In addition to these two fundamental modes, a major strength of our earlier formalism was its accommodation of context-specific directed information flow that yielded plausible and meaningful biological interpretation of protein functions and pathways. However, the directed flow from origins to destinations was induced via a potential function that was heuristic. Here, with a theoretically sound approach called the channel mode, we extend our earlier work for directed information flow. This is achieved by constructing a potential function facilitating a purely probabilistic interpretation of the channel mode. For each network node, the channel mode combines the solutions of emitting and absorbing modes in the same context, producing what we call a channel tensor. The entries of the channel tensor at each node can be interpreted as the amount of flow passing through that node from an origin to a destination. Similarly to our earlier model, the channel mode encompasses damping as a free parameter that controls the locality of information flow. Through examples involving the yeast pheromone response pathway, we illustrate the versatility and stability of our new framework. 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 FX This work was supported by the Intramural Research Program of the National Library of Medicine at the National Institutes of Health. NR 38 TC 8 Z9 8 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PD APR PY 2012 VL 19 IS 4 BP 379 EP 403 DI 10.1089/cmb.2010.0228 PG 25 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 922NH UT WOS:000302553800004 PM 22409812 ER PT J AU Kendra, R Bell, KM Guimond, JM AF Kendra, Rachel Bell, Kathryn M. Guimond, Jennifer M. TI The Impact of Child Abuse History, PTSD Symptoms, and Anger Arousal on Dating Violence Perpetration Among College Women SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE Dating violence; Anger; PTSD; Child abuse ID POSTTRAUMATIC-STRESS-DISORDER; INTIMATE PARTNER VIOLENCE; FAMILY-OF-ORIGIN; SEXUAL-ABUSE; ADULT VICTIMIZATION; PHYSICAL VIOLENCE; TRAUMA; MALTREATMENT; SYMPTOMATOLOGY; RECOGNITION AB Preliminary research suggests that child abuse is indirectly associated with female-perpetrated intimate partner violence via posttraumatic stress disorder (PTSD) symptoms and anger. To date, however, no known studies have investigated these relationships for physical and psychological dating violence within a female college sample. Therefore, the purpose of the current study was to examine the impact of child abuse history, PTSD symptoms, and anger arousal on female-perpetrated physical and psychological dating violence. Female undergraduates (N = 496) completed measures of child abuse, PTSD symptoms, anger arousal, and dating violence perpetration as part of a larger trauma and violence study. Results indicated that child abuse directly predicted female-perpetrated physical and psychological dating violence and indirectly impacted female-perpetrated physical and psychological dating violence via PTSD symptoms and anger arousal. The direct relationships between PTSD symptoms and female-perpetrated physical and psychological dating violence were nonsignificant after controlling for the effect of anger arousal. C1 [Bell, Kathryn M.] Capital Univ, Dept Psychol, Columbus, OH 43209 USA. [Kendra, Rachel] No Illinois Univ, Dept Psychol, De Kalb, IL 60115 USA. [Guimond, Jennifer M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, DHHS, Bethesda, MD USA. RP Bell, KM (reprint author), Capital Univ, Dept Psychol, Columbus, OH 43209 USA. EM kbell626@capital.edu OI Guimond, Jennifer/0000-0002-8887-5885 NR 81 TC 14 Z9 14 U1 7 U2 24 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD APR PY 2012 VL 27 IS 3 BP 165 EP 175 DI 10.1007/s10896-012-9415-7 PG 11 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 923UN UT WOS:000302645500001 ER PT J AU Liu, S Chen, ZS Zhu, F Hu, YL AF Liu, Shuang Chen, Zhisong Zhu, Feng Hu, Yinling TI I kappa B Kinase Alpha and Cancer SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Review ID SQUAMOUS-CELL CARCINOMAS; SKIN TUMOR-DEVELOPMENT; HELIX-LOOP-HELIX; IKK-ALPHA; TERMINAL DIFFERENTIATION; EPIDERMAL MORPHOGENESIS; EXPRESSION PROMOTES; SIGNALING PATHWAY; SOMATIC MUTATION; GENE-EXPRESSION AB I kappa B kinase alpha (Ikk-alpha) gene mutations and IKK-alpha downregulation have been detected in various human squamous cell carcinomas (SCCs), which are malignancies derived from squamous epithelial cells. These squamous epithelial cells distribute to many organs in the body; however, the epidermis is the only organ mainly composed of stratified squamous epithelial cells, called keratinocytes. SCC is the second most common type of skin cancer. Reducing IKK-alpha expression promotes tumor initiation, and its loss greatly enhances tumor progression from benign papillomas to malignant carcinomas during chemical skin carcinogenesis in mice. Thus, IKK-alpha has emerged as a tumor suppressor for SCCs. Furthermore, inducible deletion of IKK-alpha in the keratinocytes of adult mice causes spontaneous skin papillomas and carcinomas, indicating that IKK-alpha deletion functions as a tumor initiator as well as a tumor promoter. This article discusses IKK-alpha biological activities and associated molecular events in skin tumor development, which may provide insight into the diagnosis, treatment, and prevention of human squamous cell carcinomas (SCCs) in the future. C1 [Liu, Shuang; Chen, Zhisong; Zhu, Feng; Hu, Yinling] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21701 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] FX Our studies were supported by National Cancer Institute grants CA102510 and CA117314 (to Y.H) and National Cancer Institute intramural program. NR 62 TC 4 Z9 4 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD APR PY 2012 VL 32 IS 4 BP 152 EP 158 DI 10.1089/jir.2011.0107 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 925OT UT WOS:000302771400002 PM 22149351 ER PT J AU Goldstein, DS AF Goldstein, David S. TI Cardiac Sympathetic Neuroimaging in Dementia with Lewy Bodies SO JOURNAL OF NEUROIMAGING LA English DT Review DE Power spectral analysis; heart rate variability; sympathetic; parasympathetic; autonomic ID PARKINSONS-DISEASE AB J Neuroimaging 2012;22:109-110. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr MSC 1620,Bldg 10,Room 5N220, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov FU Division of Intramural Research, NINDS, NIH FX Division of Intramural Research, NINDS, NIH. NR 7 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD APR PY 2012 VL 22 IS 2 BP 109 EP 110 DI 10.1111/j.1552-6569.2010.00526.x PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 923PM UT WOS:000302631200006 PM 20977534 ER PT J AU Sancarlo, D Pilotto, A Panza, F Copetti, M Longo, MG D'Ambrosio, P D'Onofrio, G Ferrucci, L Pilotto, A AF Sancarlo, Daniele Pilotto, Andrea Panza, Francesco Copetti, Massimiliano Longo, Maria Grazia D'Ambrosio, Piero D'Onofrio, Grazia Ferrucci, Luigi Pilotto, Alberto TI A Multidimensional Prognostic Index (MPI) based on a comprehensive geriatric assessment predicts short- and long-term all-cause mortality in older hospitalized patients with transient ischemic attack SO JOURNAL OF NEUROLOGY LA English DT Article DE Transient ischemic attack (TIA); All-cause mortality; Risk factor; Multidimensional Prognostic Index (MPI); Aging; Comprehensive geriatric assessment (CGA) ID MAJOR VASCULAR EVENTS; EARLY STROKE RISK; ELDERLY PATIENTS; FOLLOW-UP; VALIDATION; SCORE; SURVIVAL; REFINEMENT; DISEASE; DEFICIT AB A multidimensional impairment may influence the clinical outcome of acute diseases in older patients. The aim of the current study was to evaluate whether a Multidimensional Prognostic Index (MPI) based on a comprehensive geriatric assessment (CGA) predicts short- and long-term all-cause mortality in older patients hospitalized for transient ischemic attack (TIA). In this prospective study with 1-year follow-up, 654 patients aged 65 and older with a diagnosis of TIA according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM 435.x) were enrolled. A standardized CGA that included information on functional (activities of daily living, ADL, and Instrumental ADL), cognitive status (Short Portable Mental Status Questionnaire), nutrition (Mini Nutritional Assessment), risk of pressure sores (Exton-Smith Scale), comorbidities (Cumulative Illness Rating Scale), medications and co-habitation status was used to calculate the MPI for mortality using a previously validated algorithm. Higher MPI values were significantly associated with higher 1-month all-cause mortality (incidence rates: MPI-1 low risk = 0.32%, MPI-2 moderate risk = 5.36%, MPI-3 high risk = 10.42%; p < 0.001), 6-month all-cause mortality (MPI-1 = 1.95%, MPI-2 = 9.77%, MPI-3 = 27.22%; p < 0.001) and 12-month all-cause mortality (MPI-1 = 5.19%, MPI-2 = 16.47%, MPI-3 = 44.32%; p < 0.001). Age- and gender-adjusted Cox regression analyses demonstrated that MPI was a significant predictor of all-cause mortality. MPI showed a significant high discriminatory power with an area under the receiver operating characteristics (ROC) curve of 0.819, 95% CI = 0.749-0.888 for 1-month mortality, 0.799, 95% CI = 0.738-0.861 for 6-month mortality and 0.770, 95% CI = 0.716-0.824 for 12-month mortality. The MPI, calculated from information collected in a standardized CGA, appeared to be effective in estimating short- and long-term all-cause mortality in older patients hospitalized for TIA. C1 [Pilotto, Alberto] S Antonio Hosp, Geriatr Unit, I-35127 Padua, Italy. [Sancarlo, Daniele; Panza, Francesco; Longo, Maria Grazia; D'Ambrosio, Piero; D'Onofrio, Grazia] IRCCS Casa Sollievo Sofferenza, Geriatr Unit, I-71013 Foggia, Italy. [Sancarlo, Daniele; Panza, Francesco; Longo, Maria Grazia; D'Ambrosio, Piero; D'Onofrio, Grazia] IRCCS Casa Sollievo Sofferenza, Gerontol Geriatr Res Lab, Dept Med Sci, I-71013 Foggia, Italy. [Pilotto, Andrea] Univ Brescia, Neurol Unit, Brescia, Italy. [Copetti, Massimiliano] IRCCS Casa Sollievo Sofferenza, Unit Biostat, San Giovanni Rotondo, Italy. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Pilotto, A (reprint author), S Antonio Hosp, Geriatr Unit, Azienda ULSS Padova 16,Via Facciolati 71, I-35127 Padua, Italy. EM alberto.pilotto@sanita.padova.it; alberto.pilotto@sanita.padova.it RI Copetti, Massimiliano/K-3186-2016; D'Onofrio, Grazia/K-9740-2016; Sancarlo, Daniele/C-1056-2017; OI Copetti, Massimiliano/0000-0002-7960-5947; D'Onofrio, Grazia/0000-0002-5905-6063; Sancarlo, Daniele/0000-0001-9541-6364; Panza, Francesco/0000-0002-7220-0656; Pilotto, Andrea/0000-0003-2029-6606 FU Ministero della Salute FX This work was fully supported by grants from Ministero della Salute, IRCCS Research Program 2009-2011, Line 2: "Malattie complesse". NR 39 TC 15 Z9 17 U1 0 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD APR PY 2012 VL 259 IS 4 BP 670 EP 678 DI 10.1007/s00415-011-6241-4 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 921PL UT WOS:000302489400011 PM 21947223 ER PT J AU Ramachandran, R Gravenstein, KS Metter, EJ Egan, JM Ferrucci, L Chia, CW AF Ramachandran, Ramona Gravenstein, Kristofer S. Metter, E. Jeffrey Egan, Josephine M. Ferrucci, Luigi Chia, Chee W. TI Selective Contribution of Regional Adiposity, Skeletal Muscle, and Adipokines to Glucose Disposal in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE low muscle mass; regional adiposity; glucose disposal ID BODY-COMPOSITION; INSULIN-RESISTANCE; LIPID-METABOLISM; FAT DISTRIBUTION; GROWTH-HORMONE; LEPTIN; SARCOPENIA; HEALTHY; RISK; EPIDEMIOLOGY AB OBJECTIVES: To study the relationships between muscle mass, regional adiposity, and adipokines and glucose disposal in an older population. DESIGN: Cross-sectional analysis. SETTING: Community-dwelling volunteers from the Baltimore Longitudinal Study of Aging. PARTICIPANTS: Two hundred eighty men and 259 women with a mean age of 71.1 +/- 0.4 (range 55-96) and complete data on fasting plasma adiponectin and leptin, oral glucose tolerance test (OGTT) (plasma glucose available at 0, 20, 40, 60, 80, 100, and 120 minutes), thigh computed tomography (CT), physical activity levels, and anthropometric measures. MEASUREMENTS: Participants were classified into eight groups according to the presence of global adiposity (body mass index > 27 kg/m(2)), central adiposity (waist circumference > 88 cm for women and > 102 cm for men), and low muscle mass (CT thigh, lowest sex-specific tertile (93.8 cm(2) in women and 110.7 cm(2) in men) of adjusted thigh muscle area). Linear regression models were used to estimate the contribution of these eight groups to early glucose area under the curve (AUC) (t = 0-40 minutes), late glucose AUC (t = 60-120 minutes), and total glucose AUC (t = 0-120 minutes) from the OGTT. RESULTS: Regardless of muscle mass, individuals with a combination of central and global adiposity were more likely to have delayed glucose disposal rates (P < .05). A strong negative association was also found between circulating adiponectin levels and glucose disposal rates (early AUC, beta = -0.14; late AUC, beta = -0.20; and total AUC, beta = -0.20; P < .05 for all three AUCs) after adjusting for regional adiposity, muscle mass, circulating leptin levels, physical activity, age, and sex. CONCLUSION: Older individuals with global and central adiposity may be at risk of glucose intolerance unrelated to low muscle mass. J Am Geriatr Soc 60:707-712, 2012. C1 [Ramachandran, Ramona; Gravenstein, Kristofer S.; Metter, E. Jeffrey; Egan, Josephine M.; Ferrucci, Luigi; Chia, Chee W.] NIA, Clin Res Branch, NIH, Baltimore, MD 21225 USA. [Egan, Josephine M.] NIA, Clin Invest Lab, NIH, Baltimore, MD 21225 USA. RP Chia, CW (reprint author), NIA, Clin Res Branch, NIH, 3001 S Hanover St,NM 533, Baltimore, MD 21225 USA. EM chiac@mail.nih.gov FU National Institutes of Health, National Institute on Aging FX This work was supported entirely by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 26 TC 5 Z9 5 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 IS 4 BP 707 EP 712 DI 10.1111/j.1532-5415.2011.03865.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 923MR UT WOS:000302623900015 PM 22417789 ER PT J AU Crasto, C Semba, RD Sun, K Ferrucci, L AF Crasto, Candace Semba, Richard D. Sun, Kai Ferrucci, Luigi TI Serum Fibroblast Growth Factor 21 Is Associated with Renal Function and Chronic Kidney Disease in Community-Dwelling Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter C1 [Crasto, Candace; Semba, Richard D.; Sun, Kai] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Crasto, C (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. FU NHLBI NIH HHS [R01 HL094507, R01 HL094507-03]; NIA NIH HHS [R01 AG027012, R01 AG027012-06] NR 9 TC 12 Z9 13 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 IS 4 BP 792 EP 793 DI 10.1111/j.1532-5415.2011.03879.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 923MR UT WOS:000302623900031 PM 22494291 ER PT J AU Leandri, M Ghignotti, M Emionite, L AF Leandri, M. Ghignotti, M. Emionite, L. TI NOCICEPTIVE MECHANISMS INVOLVED IN THE TAIL FLICK REFLEX SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Meeting Abstract CT Meeting of the Italian-Association-for-the-Peripheral-Nervous-System and Pain and Neuroscience Group of the Italian-Society-of-Neurology CY APR 12-14, 2012 CL Pisa, ITALY SP Italian Assoc Peripheral Nervous Syst, Italian Soc Neurol C1 [Leandri, M.; Ghignotti, M.] Univ Genoa, Interuniv Ctr Pain Neurophysiol, Genoa, Italy. [Leandri, M.; Ghignotti, M.] Univ Genoa, Dept Neurol Ophthalmol & Genet, Genoa, Italy. [Emionite, L.] Natl Canc Inst, Anim Facil, Genoa, Italy. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1085-9489 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PD APR PY 2012 VL 17 SU 1 BP S31 EP S31 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 921GK UT WOS:000302465900064 ER PT J AU Leandri, M Ghignotti, M Emionite, L AF Leandri, M. Ghignotti, M. Emionite, L. TI COMPOUND ACTION POTENTIAL OF THE CAUDAL NERVE IN A CIPN ANIMAL MODEL SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Meeting Abstract CT Meeting of the Italian-Association-for-the-Peripheral-Nervous-System and Pain and Neuroscience Group of the Italian-Society-of-Neurology CY APR 12-14, 2012 CL Pisa, ITALY SP Italian Assoc Peripheral Nervous Syst, Italian Soc Neurol C1 [Leandri, M.; Ghignotti, M.] Univ Genoa, Interuniv Ctr Pain Neurophysiol, Genoa, Italy. [Leandri, M.; Ghignotti, M.] Univ Genoa, Dept Neurol Ophthalmol & Genet, Genoa, Italy. [Emionite, L.] Natl Canc Inst, Anim Facil, Genoa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1085-9489 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PD APR PY 2012 VL 17 SU 1 BP S30 EP S31 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 921GK UT WOS:000302465900063 ER PT J AU Cardone, G Newcomb, WW Cheng, NQ Wingfield, PT Trus, BL Brown, JC Steven, AC AF Cardone, Giovanni Newcomb, William W. Cheng, Naiqian Wingfield, Paul T. Trus, Benes L. Brown, Jay C. Steven, Alasdair C. TI The UL36 Tegument Protein of Herpes Simplex Virus 1 Has a Composite Binding Site at the Capsid Vertices SO JOURNAL OF VIROLOGY LA English DT Article ID CRYOELECTRON MICROSCOPY; ELECTRON-MICROSCOPY; CELL ENTRY; TYPE-1; DNA; UL25; VP26; VISUALIZATION; MICROTUBULES; MATURATION AB Herpesviruses have an icosahedral nucleocapsid surrounded by an amorphous tegument and a lipoprotein envelope. The tegument comprises at least 20 proteins destined for delivery into the host cell. As the tegument does not have a regular structure, the question arises of how its proteins are recruited. The herpes simplex virus 1 (HSV-1) tegument is known to contact the capsid at its vertices, and two proteins, UL36 and UL37, have been identified as candidates for this interaction. We show that the interaction is mediated exclusively by UL36. HSV-1 nucleocapsids extracted from virions shed their UL37 upon incubation at 37 degrees C. Cryo-electron microscopy (cryo-EM) analysis of capsids with and without UL37 reveals the same penton-capping density in both cases. As no other tegument proteins are retained in significant amounts, it follows that this density feature (similar to 100 kDa) represents the ordered portion of UL36 (336 kDa). It binds between neighboring UL19 protrusions and to an adjacent UL17 molecule. These observations support the hypothesis that UL36 plays a major role in the tegumentation of the virion, providing a flexible scaffold to which other tegument proteins, including UL37, bind. They also indicate how sequential conformational changes in the maturing nucleocapsid control the ordered binding, first of UL25/UL17 and then of UL36. C1 [Cardone, Giovanni; Cheng, Naiqian; Steven, Alasdair C.] NIAMSD, Struct Biol Lab, Bethesda, MD 20892 USA. [Wingfield, Paul T.] NIAMSD, Prot Express Lab, Bethesda, MD 20892 USA. [Trus, Benes L.] NIH, Ctr Informat Technol, Imaging Sci Lab, Bethesda, MD 20892 USA. [Newcomb, William W.; Brown, Jay C.] Univ Virginia Hlth Syst, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA USA. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, Bethesda, MD 20892 USA. EM stevena@mail.nih.gov FU NIAMS; NIH [R01AI041644] FX This study was supported by the Intramural Research Program of NIAMS and by NIH grant R01AI041644 to J.C.B. NR 45 TC 28 Z9 30 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2012 VL 86 IS 8 BP 4058 EP 4064 DI 10.1128/JVI.00012-12 PG 7 WC Virology SC Virology GA 917NU UT WOS:000302185400002 PM 22345483 ER PT J AU Bello, NF Dussupt, V Sette, P Rudd, V Nagashima, K Bibollet-Ruche, F Chen, CP Montelaro, RC Hahn, BH Bouamr, F AF Bello, Nana F. Dussupt, Vincent Sette, Paola Rudd, Victoria Nagashima, Kunio Bibollet-Ruche, Frederic Chen, Chaoping Montelaro, Ronald C. Hahn, Beatrice H. Bouamr, Fadila TI Budding of Retroviruses Utilizing Divergent L Domains Requires Nucleocapsid SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; INFECTIOUS-ANEMIA VIRUS; ROUS-SARCOMA-VIRUS; PROTEIN-SORTING PATHWAY; LATE ASSEMBLY DOMAIN; GAG PROTEIN; IN-VITRO; CAPSID PROTEIN; ZINC FINGERS; BRO1 DOMAIN AB We recently reported that human immunodeficiency virus type 1 (HIV-1) carrying PTAP and LYPXnL L domains ceased budding when the nucleocapsid (NC) domain was mutated, suggesting a role for NC in HIV-1 release. Here we investigated whether NC involvement in virus release is a property specific to HIV-1 or a general requirement of retroviruses. Specifically, we examined a possible role for NC in the budding of retroviruses relying on divergent L domains and structurally homologous NC domains that harbor diverse protein sequences. We found that NC is critical for the release of viruses utilizing the PTAP motif whether it functions within its native Gag in simian immunodeficiency virus cpzGAB2 (SIVcpzGAB2) or SIVsmmE543 or when it is transplanted into the heterologous Gag protein of equine infectious anemia virus (EIAV). In both cases, virus release was severely diminished even though NC mutant Gag proteins retained the ability to assemble spherical particles. Moreover, budding- defective NC mutants, which displayed particles tethered to the plasma membrane, were triggered to release virus when access to the cell endocytic sorting complex required for transport pathway was restored (i. e., in trans expression of Nedd4.2s). We also examined the role of NC in the budding of EIAV, a retrovirus relying exclusively on the (L) YPXnL-type L domain. We found that EIAV late budding defects were rescued by overexpression of the isolated Alix Bro1 domain (Bro1). Bro1-mediated rescue of EIAV release required the wild-type NC. EIAV NC mutants lost interactions with Bro1 and failed to produce viruses despite retaining the ability to self-assemble. Together, our studies establish a role for NC in the budding of retroviruses harboring divergent L domains and evolutionarily diverse NC sequences, suggesting the utilization of a common conserved mechanism and/ or cellular factor rather than a specific motif. C1 [Bello, Nana F.; Dussupt, Vincent; Sette, Paola; Rudd, Victoria] NIAID, Mol Microbiol Lab, Virus Budding Unit, NIH, Bethesda, MD 20892 USA. [Nagashima, Kunio] NCI, Image Anal Lab, Adv Technol Program, SAIC Frederick, Frederick, MD 21701 USA. [Bibollet-Ruche, Frederic; Hahn, Beatrice H.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Bibollet-Ruche, Frederic; Hahn, Beatrice H.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. [Chen, Chaoping] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA. [Montelaro, Ronald C.] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA USA. RP Bouamr, F (reprint author), NIAID, Mol Microbiol Lab, Virus Budding Unit, NIH, Bethesda, MD 20892 USA. EM bouamrf@mail.nih.gov FU NIAID,NIH [R37 AI050529] FX This work was supported in part by R37 AI050529 and the Intramural Research Program of the NIAID,NIH. NR 80 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD APR PY 2012 VL 86 IS 8 BP 4182 EP 4193 DI 10.1128/JVI.07105-11 PG 12 WC Virology SC Virology GA 917NU UT WOS:000302185400014 PM 22345468 ER PT J AU Falkowska, E Ramos, A Feng, Y Zhou, TQ Moquin, S Walker, LM Wu, XL Seaman, MS Wrin, T Kwong, PD Wyatt, RT Mascola, JR Poignard, P Burton, DR AF Falkowska, Emilia Ramos, Alejandra Feng, Yu Zhou, Tongqing Moquin, Stephanie Walker, Laura M. Wu, Xueling Seaman, Michael S. Wrin, Terri Kwong, Peter D. Wyatt, Richard T. Mascola, John R. Poignard, Pascal Burton, Dennis R. TI PGV04, an HIV-1 gp120 CD4 Binding Site Antibody, Is Broad and Potent in Neutralization but Does Not Induce Conformational Changes Characteristic of CD4 SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; RATIONAL DESIGN; IN-VITRO; BREADTH; INDIVIDUALS; MECHANISM; EVOLUTION; INFECTION AB Recently, several broadly neutralizing monoclonal antibodies (bnMAbs) directed to the CD4-binding site (CD4bs) of gp120 have been isolated from HIV-1-positive donors. These include VRC01, 3BNC117, and NIH45-46, all of which are capable of neutralizing about 90% of circulating HIV-1 isolates and all of which induce conformational changes in the HIV-1 gp120 monomer similar to those induced by the CD4 receptor. In this study, we characterize PGV04 (also known as VRC-PG04), a MAb with potency and breadth that rivals those of the prototypic VRC01 and 3BNC117. When screened on a large panel of viruses, the neutralizing profile of PGV04 was distinct from those of CD4, b12, and VRC01. Furthermore, the ability of PGV04 to neutralize pseudovirus containing single alanine substitutions exhibited a pattern distinct from those of the other CD4bs MAbs. In particular, substitutions D279A, I420A, and I423A were found to abrogate PGV04 neutralization. In contrast to VRC01, PGV04 did not enhance the binding of 17b or X5 to their epitopes (the CD4-induced [CD4i] site) in the coreceptor region on the gp120 monomer. Furthermore, in contrast to CD4, none of the anti-CD4bs MAbs induced the expression of the 17b epitope on cell surface-expressed cleaved Env trimers. We conclude that potent CD4bs bnMAbs can display differences in the way they recognize and access the CD4bs and that mimicry of CD4, as assessed by inducing conformational changes in monomeric gp120 that lead to enhanced exposure of the CD4i site, is not uniquely correlated with effective neutralization at the site of CD4 binding on HIV-1. C1 [Falkowska, Emilia; Ramos, Alejandra; Feng, Yu; Walker, Laura M.; Wyatt, Richard T.; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Falkowska, Emilia; Ramos, Alejandra; Feng, Yu; Walker, Laura M.; Wyatt, Richard T.; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Falkowska, Emilia; Burton, Dennis R.] MIT & Harvard, Ragon Inst MGH, Boston, MA USA. [Zhou, Tongqing; Moquin, Stephanie; Wu, Xueling; Kwong, Peter D.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Seaman, Michael S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Wrin, Terri] Monogram Biosci Inc, San Francisco, CA USA. RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. EM burton@scripps.edu RI Zhou, Tongqing/A-6880-2010; Feng, Yu/A-3396-2012; poignard, pascal/N-6678-2013 OI Zhou, Tongqing/0000-0002-3935-4637; FU International AIDS Vaccine Initiative (IAVI); Ragon Institute; United States Agency for International Development (USAID); Bill and Melinda Gates foundation [38619]; NIAID [AI33292, AI084817] FX This work was supported by the International AIDS Vaccine Initiative (IAVI), NIAID (grants AI33292 to D.R.B. and AI084817 to I.A.W.), the Ragon Institute, and the United States Agency for International Development (USAID).; The neutralization experiments on the 97-virus panel were done by Michael Seaman's group (Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA), and this work was funded through the Bill and Melinda Gates foundation (grant no. 38619). NR 34 TC 64 Z9 64 U1 1 U2 18 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2012 VL 86 IS 8 BP 4394 EP 4403 DI 10.1128/JVI.06973-11 PG 10 WC Virology SC Virology GA 917NU UT WOS:000302185400034 PM 22345481 ER PT J AU Prasad, A Lu, M Lukac, DM Zeichner, SL AF Prasad, Alka Lu, Michael Lukac, David M. Zeichner, Steven L. TI An Alternative Kaposi's Sarcoma-Associated Herpesvirus Replication Program Triggered by Host Cell Apoptosis SO JOURNAL OF VIROLOGY LA English DT Article ID LYTIC SWITCH PROTEIN; ACTIVATES GENE-EXPRESSION; RBP-J-KAPPA; COUPLED RECEPTOR; NUCLEAR ANTIGEN; DNA-SEQUENCES; TRANSCRIPTIONAL ACTIVATION; SMALL-MOLECULE; RTA; PROMOTER AB Kaposi's sarcoma-associated herpesvirus (KSHV) is linked to several neoplastic diseases: Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). KSHV replicates actively, via a controlled gene expression program, but can also remain latent. It had been thought that the transition from latent to lytic replication was controlled exclusively by the replication and transcription activator protein RTA (open reading frame 50 [ORF50] gene product). A dominant-negative (DN) ORF50 mutant, ORF50 Delta STAD, blocks gene expression and replication. We produced a PEL cell line derivative containing both latent KSHV genomes and an inducible ORF50 Delta STAD. We unexpectedly found that induction of apoptosis triggered high-level viral replication, even when DN ORF50 Delta STAD was present, suggesting that apoptosis triggers KSHV replication through a distinct RTA-independent pathway. We verified that apoptosis triggers KSHV replication independent of RTA using ORF50 small interfering RNA (siRNA) and also showed that caspase activity is required to trigger KSHV replication. We showed that when apoptosis triggers KSHV replication, the kinetics of late gene expression is accelerated by 12 to 24 h and that virus produced following apoptosis has reduced infectivity. KSHV therefore appears to replicate via two distinct pathways, a conventional pathway requiring RTA, with slower replication kinetics, producing virus with higher infectivity, and an alternative apoptosis-triggered pathway that does not require RTA, has faster replication kinetics, and produces virus with lower infectivity. The existence of a distinct apoptosis-triggered, accelerated replication pathway may have evolutionary advantages for the virus and clinical significance for the treatment of KSHV-associated neoplasms. It also provides further evidence that KSHV can sense and react to its environment. C1 [Prasad, Alka; Zeichner, Steven L.] Childrens Natl Med Ctr, Childrens Res Inst, Ctr Canc & Immunol Res, Washington, DC 20010 USA. [Lu, Michael] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Lukac, David M.] Univ Med & Dent New Jersey, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA. [Zeichner, Steven L.] George Washington Univ, Dept Pediat & Microbiol, Washington, DC USA. [Zeichner, Steven L.] George Washington Univ, Dept Immunol, Washington, DC USA. [Zeichner, Steven L.] George Washington Univ, Dept Trop Med, Washington, DC USA. RP Zeichner, SL (reprint author), Childrens Natl Med Ctr, Childrens Res Inst, Ctr Canc & Immunol Res, Washington, DC 20010 USA. EM zeichner@gwu.edu OI Lukac, David /0000-0003-0380-5990 FU George Washington University AIDS Institute; Children's Research Institute Research Advisory Committee; Conner Family Foundation; District of Columbia Developmental Center for AIDS Research(NIAD,NIH) [P30AI0877714] FX This work was supported in part by a Collaborative Faculty Award for AIDS Research from the George Washington University AIDS Institute, a Children's Research Institute Research Advisory Committee Award, a gift from the Conner Family Foundation, and the District of Columbia Developmental Center for AIDS Research (P30AI087714 from NIAID, NIH). NR 53 TC 9 Z9 9 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2012 VL 86 IS 8 BP 4404 EP 4419 DI 10.1128/JVI.06617-11 PG 16 WC Virology SC Virology GA 917NU UT WOS:000302185400035 PM 22345480 ER PT J AU Xiao, P Patterson, LJ Kuate, S Brocca-Cofano, E Thomas, MA Venzon, D Zhao, J DiPasquale, J Fenizia, C Lee, EM Kalisz, I Kalyanaraman, VS Pal, R Montefiori, D Keele, BF Robert-Guroff, M AF Xiao, Peng Patterson, L. Jean Kuate, Seraphin Brocca-Cofano, Egidio Thomas, Michael A. Venzon, David Zhao, Jun DiPasquale, Janet Fenizia, Claudio Lee, Eun Mi Kalisz, Irene Kalyanaraman, Vaniambadi S. Pal, Ranajit Montefiori, David Keele, Brandon F. Robert-Guroff, Marjorie TI Replicating Adenovirus-Simian Immunodeficiency Virus (SIV) Recombinant Priming and Envelope Protein Boosting Elicits Localized, Mucosal IgA Immunity in Rhesus Macaques Correlated with Delayed Acquisition following a Repeated Low-Dose Rectal SIVmac251 Challenge SO JOURNAL OF VIROLOGY LA English DT Article ID CLASS-I MOLECULE; T-CELLS; PROTECTIVE EFFICACY; HIV-1 INFECTION; NEUTRALIZING ANTIBODIES; SUBLINGUAL IMMUNIZATION; SHIV89.6P CHALLENGE; NONHUMAN-PRIMATES; VACCINE REGIMEN; RESPONSES AB We have shown that sequential replicating adenovirus type 5 host range mutant human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) recombinant priming delivered first intranasally (i.n.) plus orally and then intratracheally (i.t.), followed by envelope protein boosting, elicits broad cellular immunity and functional, envelope-specific serum and mucosal antibodies that correlate with protection from high-dose SIV and simian/human immunodeficiency virus (SHIV) challenges in rhesus macaques. Here we extended these studies to compare the standard i.n./i.t. regimen with additional mucosal administration routes, including sublingual, rectal, and vaginal routes. Similar systemic cellular and humoral immunity was elicited by all immunization routes. Central and effector memory T cell responses were also elicited by the four immunization routes in bronchoalveolar lavage fluid and jejunal, rectal, and vaginal tissue samples. Cellular responses in vaginal tissue were more compartmentalized, being induced primarily by intravaginal administration. In contrast, all immunization routes elicited secretory IgA (sIgA) responses at multiple mucosal sites. Following a repeated low-dose intrarectal (i.r.) challenge with SIVmac251 at a dose transmitting one or two variants, protection against acquisition was not achieved except in one macaque in the i.r. immunized group. All immunized macaques exhibited reduced peak viremia compared to that of controls, correlated inversely with prechallenge serum antienvelope avidity, antibody-dependent cellular cytotoxicity (ADCC) titers, and percent antibody-dependent cell-mediated viral inhibition. Both antibody avidity and ADCC titers were correlated with the number of exposures required for infection. Notably, we show for the first time a significant correlation of vaccine-induced sIgA titers in rectal secretions with delayed acquisition. Further investigation of the characteristics and properties of the sIgA should elucidate the mechanism leading to this protective effect. C1 [Xiao, Peng; Patterson, L. Jean; Kuate, Seraphin; Brocca-Cofano, Egidio; Thomas, Michael A.; Zhao, Jun; DiPasquale, Janet; Fenizia, Claudio; Robert-Guroff, Marjorie] Natl Canc Inst, Vaccine Branch, Bethesda, MD USA. [Venzon, David] Natl Canc Inst, Biostat & Data Management Sect, Bethesda, MD USA. [Lee, Eun Mi; Kalisz, Irene; Kalyanaraman, Vaniambadi S.; Pal, Ranajit] Adv Biosci Lab Inc, Kensington, MD USA. [Montefiori, David] Duke Univ, Med Ctr, Durham, NC USA. [Keele, Brandon F.] SAIC Frederick Inc, AIDS & Canc Virus Program, NCI Frederick, Frederick, MD USA. RP Robert-Guroff, M (reprint author), Natl Canc Inst, Vaccine Branch, Bethesda, MD USA. EM guroffm@mail.nih.gov FU NIH, National Cancer Institute FX This study was supported by the Intramural Research Program of the NIH, National Cancer Institute. NR 55 TC 63 Z9 65 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2012 VL 86 IS 8 BP 4644 EP 4657 DI 10.1128/JVI.06812-11 PG 14 WC Virology SC Virology GA 917NU UT WOS:000302185400058 PM 22345466 ER PT J AU Bonsignori, M Montefiori, DC Wu, XL Chen, X Hwang, KK Tsao, CY Kozink, DM Parks, RJ Tomaras, GD Crump, JA Kapiga, SH Sam, NE Kwong, PD Kepler, TB Liao, HX Mascola, JR Haynesa, BF AF Bonsignori, Mattia Montefiori, David C. Wu, Xueling Chen, Xi Hwang, Kwan-Ki Tsao, Chun-Yen Kozink, Daniel M. Parks, Robert J. Tomaras, Georgia D. Crump, John A. Kapiga, Saidi H. Sam, Noel E. Kwong, Peter D. Kepler, Thomas B. Liao, Hua-Xin Mascola, John R. Haynesa, Barton F. TI Two Distinct Broadly Neutralizing Antibody Specificities of Different Clonal Lineages in a Single HIV-1-Infected Donor: Implications for Vaccine Design SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; HIV-ANTIBODIES; EPITOPE; GLYCOPROTEIN; INDIVIDUALS; BREADTH; REVEAL; GP41; PG16 AB Plasma from a small subset of subjects chronically infected with HIV-1 shows remarkable magnitude and breadth of neutralizing activity. From one of these individuals (CH0219), we isolated two broadly neutralizing antibodies (bnAbs), CH01 and VRC-CH31, from two clonal lineages of memory B cells with distinct specificities (variable loop 1 and 2 [V1V2] conformational specificity and CD4-binding site specificity, respectively) that recapitulate 95% of CH0219 serum neutralization breadth. These data provide proof of concept for an HIV-1 vaccine that aims to elicit bnAbs of multiple specificities. C1 [Bonsignori, Mattia; Montefiori, David C.; Chen, Xi; Hwang, Kwan-Ki; Tsao, Chun-Yen; Kozink, Daniel M.; Parks, Robert J.; Tomaras, Georgia D.; Kepler, Thomas B.; Liao, Hua-Xin; Haynesa, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA. [Crump, John A.] Duke Univ, Med Ctr, Dept Med, Div Infect Dis & Int Hlth, Durham, NC 27710 USA. [Tomaras, Georgia D.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Crump, John A.] Duke Univ, Med Ctr, Duke Global Hlth Inst, Durham, NC 27710 USA. [Kepler, Thomas B.] Duke Univ, Med Ctr, Ctr Computat Immunol, Durham, NC 27710 USA. [Crump, John A.; Sam, Noel E.] Kilimanjaro Christian Med Ctr, Moshi, Tanzania. [Crump, John A.] Kilimanjaro Christian Med Coll, Moshi, Tanzania. [Kapiga, Saidi H.] London Sch Hyg & Trop Med, London WC1, England. [Wu, Xueling; Kwong, Peter D.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Bonsignori, M (reprint author), Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA. EM mattia.bonsignori@duke.edu; barton.haynes@duke.edu RI Tomaras, Georgia/J-5041-2016; OI Kepler, Thomas/0000-0002-1383-6865 FU NIH, NIAID; Division of AIDS; Center for HIV/AIDS Vaccine Immunology (CHAVI) [U19 AI067854]; Vaccine Research Center, NIAID, NIH FX This work was supported by NIH, NIAID, the Division of AIDS with the Center for HIV/AIDS Vaccine Immunology (CHAVI; grant U19 AI067854), and by the Intramural Research Program of the Vaccine Research Center, NIAID, NIH. NR 26 TC 82 Z9 85 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2012 VL 86 IS 8 BP 4688 EP 4692 DI 10.1128/JVI.07163-11 PG 5 WC Virology SC Virology GA 917NU UT WOS:000302185400062 PM 22301150 ER PT J AU Ambrose, Z Lee, K Ndjomou, J Xu, HZ Oztop, I Matous, J Takemura, T Unutmaz, D Engelman, A Hughes, SH KewalRamani, VN AF Ambrose, Zandrea Lee, KyeongEun Ndjomou, Jean Xu, Hongzhan Oztop, Ilker Matous, James Takemura, Taichiro Unutmaz, Derya Engelman, Alan Hughes, Stephen H. KewalRamani, Vineet N. TI Human Immunodeficiency Virus Type 1 Capsid Mutation N74D Alters Cyclophilin A Dependence and Impairs Macrophage Infection SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 INFECTION; DENDRITIC CELLS; NUCLEAR IMPORT; RESTRICTION; COMPLEX; PROTEIN; REPLICATION; RESISTANCE; PARTICLES; SAMHD1 AB The antiviral factor CPSF6-358 interferes with the nuclear entry of human immunodeficiency virus type 1 (HIV-1). HIV-1 acquires resistance to CPSF6-358 through the N74D mutation of the capsid (CA), which alters its nuclear entry pathway. Here we show that compared to wild-type (WT) HIV-1, N74D HIV-1 is more sensitive to cyclosporine, has increased sensitivity to nevirapine, and is impaired in macrophage infection prior to reverse transcription. These phenotypes suggest a difference in the N74D reverse transcription complex that manifests early after infection and prior to interaction with the nuclear pore. Overall, our data indicate that N74D HIV-1 replication in transformed cells requires cyclophilin A but is dependent on other interactions in macrophages. C1 [Ambrose, Zandrea; Ndjomou, Jean; Xu, Hongzhan; Matous, James] Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15260 USA. [Lee, KyeongEun; Takemura, Taichiro; Hughes, Stephen H.; KewalRamani, Vineet N.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Oztop, Ilker; Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Unutmaz, Derya] NYU, Sch Med, Dept Pathol & Microbiol, New York, NY USA. RP Ambrose, Z (reprint author), Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15260 USA. EM zaa4@pitt.edu; vineet@mail.nih.gov FU Pittsburgh Center for HIV Protein Interactions; National Cancer Institute's intramural Center for Cancer Research; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [1 UL1 RR024153]; NIH Roadmap for Medical Research; NIH [GM082251, AI078839, AI052014] FX This work was supported by a contribution from the Pittsburgh Center for HIV Protein Interactions and was supported by the National Cancer Institute's intramural Center for Cancer Research, which supports the HIV Drug Resistance Program (S. H. H. and V.N.K.), grant number 1 UL1 RR024153 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research (Z.A.), and NIH grants GM082251 (Z.A.), AI078839 (D.U.), and AI052014 (A.E.). NR 30 TC 39 Z9 39 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2012 VL 86 IS 8 BP 4708 EP 4714 DI 10.1128/JVI.05887-11 PG 7 WC Virology SC Virology GA 917NU UT WOS:000302185400066 PM 22301145 ER PT J AU Tembhare, P Yuan, C Korde, N Maric, I Landgren, O AF Tembhare, Prashant Yuan, Constance Korde, Neha Maric, Irina Landgren, Ola TI Antigenic drift in relapsed extramedullary multiple myeloma: plasma cells without CD38 expression SO LEUKEMIA & LYMPHOMA LA English DT Letter ID FLOW-CYTOMETRY; IMMUNOPHENOTYPE; DISORDERS; DISEASE C1 [Landgren, Ola] NCI, NIH, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. [Tembhare, Prashant; Yuan, Constance] NCI, Flow Cytometry Unit, Bethesda, MD 20892 USA. [Korde, Neha] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Maric, Irina] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Landgren, O (reprint author), NCI, NIH, Ctr Canc Res, Metab Branch, 9000 Rockville Pike,Bldg 10,Room 13N240, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov NR 16 TC 1 Z9 1 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD APR PY 2012 VL 53 IS 4 BP 721 EP 724 DI 10.3109/10428194.2011.623257 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 915ZV UT WOS:000302067100031 PM 21942285 ER PT J AU George, AK Faranesh, AZ Ratnayaka, K Derbyshire, JA Lederman, RJ Hansen, MS AF George, Ashvin K. Faranesh, Anthony Z. Ratnayaka, Kanishka Derbyshire, J. Andrew Lederman, Robert J. Hansen, Michael S. TI Virtual Dye Angiography: Flow Visualization for MRI-Guided Interventions SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE real-time MRI; interventional MRI; noncontrast; endogenous contrast; visualization ID STATE FREE PRECESSION; PULSE-WAVE VELOCITY; MAGNETIC-RESONANCE; STEADY-STATE; PHASE; EXCITATION; INVERSION; SSFP AB In magnetic resonance imaging-guided cardiovascular interventional procedures, it is valuable to be able to visualize blood flow immediately and interactively in selected regions. In particular, it is useful to assess normal or pathological communications between specific heart chambers and vessels. Phase-contrast velocity mapping is not suitable for this purpose as it requires too much data and is not capable of determining directly if blood originating in one location travels to a nearby location. This article presents a novel flow visualization method called virtual dye angiography that enables visualization of blood flow analogous to selective catheter angiography. The method uses two-dimensional radio frequency pulses to achieve interactive, intermittent, targeted saturation of a localized region of the blood pool. The flow of the saturated spins is observed directly on real-time images or, in an enhanced manner, using ECG synchronized background subtraction. The modular nature of the technique allows for easy and seamless integration into a real-time, interactive imaging system with minimal overhead. We present initial results in animals and in a healthy human volunteer. Magn Reson Med 67:1013-1021, 2012. (c) 2011 Wiley Periodicals, Inc. C1 [George, Ashvin K.; Faranesh, Anthony Z.; Ratnayaka, Kanishka; Derbyshire, J. Andrew; Lederman, Robert J.; Hansen, Michael S.] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Ratnayaka, Kanishka] Childrens Natl Med Ctr, Childrens Natl Heart Inst, Washington, DC 20010 USA. RP Hansen, MS (reprint author), 10 Ctr Dr,Bldg 10,B1D405, Bethesda, MD 20892 USA. EM michael.hansen@nih.gov RI Hansen, Michael/J-5391-2015; OI Hansen, Michael/0000-0002-8087-8731; lederman, robert/0000-0003-1202-6673 FU Division of Intramural Research, National Heart Lung and Blood Institute, National Institutes of Health USA [Z01-HL006039-01, Z01-HL005062-08] FX Grant sponsor: Division of Intramural Research, National Heart Lung and Blood Institute, National Institutes of Health USA; Grant numbers: Z01-HL006039-01 and Z01-HL005062-08. NR 28 TC 5 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD APR PY 2012 VL 67 IS 4 BP 1013 EP 1021 DI 10.1002/mrm.23078 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 909AF UT WOS:000301533500015 PM 21858865 ER PT J AU Chowdhuri, SR Xi, LQ Pham, THT Hanson, J Rodriguez-Canales, J Berman, A Rajan, A Giaccone, G Emmert-Buck, M Raffeld, M Filie, AC AF Chowdhuri, Sinchita Roy Xi, Liqiang Trinh Hoc-Tran Pham Hanson, Jeffrey Rodriguez-Canales, Jaime Berman, Arlene Rajan, Arun Giaccone, Giuseppe Emmert-Buck, Michael Raffeld, Mark Filie, Armando C. TI EGFR and KRAS mutation analysis in cytologic samples of lung adenocarcinoma enabled by laser capture microdissection SO MODERN PATHOLOGY LA English DT Article DE cytology; EGFR; KRAS; laser capture microdissection; lung adenocarcinoma; mutation ID GROWTH-FACTOR RECEPTOR; TRANSBRONCHIAL NEEDLE ASPIRATION; GENE-MUTATIONS; SENSITIVE METHOD; PARADIGM-SHIFT; CANCER; GEFITINIB; SPECIMENS; THERAPY; ERLOTINIB AB The discovery of activating mutations in EGFR and KRAS in a subset of lung adenocarcinomas was a major advance in our understanding of lung adenocarcinoma biology, and has led to groundbreaking studies that have demonstrated the efficacy of tyrosine kinase inhibitor therapy. Fine-needle aspirates and other cytologic procedures have become increasingly popular for obtaining diagnostic material in lung carcinomas. However, frequently the small amount of material or sparseness of tumor cells obtained from cytologic preparations limit the number of specialized studies, such as mutation analysis, that can be performed. In this study we used laser capture microdissection to isolate small numbers of tumor cells to assess for EGFR and KRAS mutations from cell block sections of 19 cytology samples from patients with known lung adenocarcinomas. We compared our results with previous molecular assays that had been performed on either surgical or cytology specimens as part of the patient's initial clinical work-up. Not only were we able to detect the identical EGFR or KRAS mutation that was present in the patient's prior molecular assay in every case, but we were also able to consistently detect the mutation from as few as 50 microdissected tumor cells. Furthermore, isolating a more pure population of tumor cells resulted in increased sensitivity of mutation detection as we were able to detect mutations from laser capture microdissection-enriched cases where the tumor load was low and traditional methods of whole slide scraping failed. Therefore, this method can not only significantly increase the number of lung adenocarcinoma patients that can be screened for EGFR and KRAS mutations, but can also facilitate the use of cytologic samples in the newly emerging field of molecular-based personalized therapies. Modern Pathology (2012) 25, 548-555; doi:10.1038/modpathol.2011.184; published online 9 December 2011 C1 [Filie, Armando C.] NCI, Cytopathol Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Berman, Arlene; Rajan, Arun; Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Filie, AC (reprint author), NCI, Cytopathol Sect, Pathol Lab, Ctr Canc Res, 10 Ctr Dr,Bldg 10,Room 2A19, Bethesda, MD 20892 USA. EM afilie@mail.nih.gov RI Giaccone, Giuseppe/E-8297-2017; OI Giaccone, Giuseppe/0000-0002-5023-7562; Rodriguez-Canales, Jaime/0000-0002-0885-2377 FU NIH, National Cancer Institute; NIH FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute.; Michael Emmert-Buck is an inventor on all NIH-held patents covering laser capture microdissection technology and receives royalty payments through the NIH technology transfer program. NR 42 TC 35 Z9 35 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD APR PY 2012 VL 25 IS 4 BP 548 EP 555 DI 10.1038/modpathol.2011.184 PG 8 WC Pathology SC Pathology GA 922AZ UT WOS:000302520500007 PM 22157931 ER PT J AU Campbell, MC Ranciaro, A Froment, A Hirbo, J Omar, S Bodo, JM Nyambo, T Lema, G Zinshteyn, D Drayna, D Breslin, PAS Tishkoff, SA AF Campbell, Michael C. Ranciaro, Alessia Froment, Alain Hirbo, Jibril Omar, Sabah Bodo, Jean-Marie Nyambo, Thomas Lema, Godfrey Zinshteyn, Daniel Drayna, Dennis Breslin, Paul A. S. Tishkoff, Sarah A. TI Evolution of Functionally Diverse Alleles Associated with PTC Bitter Taste Sensitivity in Africa SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE adaptive evolution; genotype-phenotype association; African genetic diversity; excess of rare mutations ID RECEPTOR GENE; HUMAN GENOME; INDIVIDUAL-DIFFERENCES; SELECTIVE PRESSURES; LACTASE PERSISTENCE; DEMOGRAPHIC HISTORY; NATURAL-SELECTION; HUMAN ORIGINS; PERCEPTION; FOOD AB Although human bitter taste perception is hypothesized to be a dietary adaptation, little is known about genetic signatures of selection and patterns of bitter taste perception variability in ethnically diverse populations with different diets, particularly from Africa. To better understand the genetic basis and evolutionary history of bitter taste sensitivity, we sequenced a 2,975 bp region encompassing TAS2R38, a bitter taste receptor gene, in 611 Africans from 57 populations in West Central and East Africa with diverse subsistence patterns, as well as in a comparative sample of 132 non-Africans. We also examined the association between genetic variability at this locus and threshold levels of phenylthiocarbamide (PTC) bitterness in 463 Africans from the above populations to determine how variation influences bitter taste perception. Here, we report striking patterns of variation at TAS2R38, including a significant excess of novel rare nonsynonymous polymorphisms that recently arose only in Africa, high frequencies of haplotypes in Africa associated with intermediate bitter taste sensitivity, a remarkably similar frequency of common haplotypes across genetically and culturally distinct Africans, and an ancient coalescence time of common variation in global populations. Additionally, several of the rare nonsynonymous substitutions significantly modified levels of PTC bitter taste sensitivity in diverse Africans. While ancient balancing selection likely maintained common haplotype variation across global populations, we suggest that recent selection pressures may have also resulted in the unusually high level of rare nonsynonymous variants in Africa, implying a complex model of selection at the TAS2R38 locus in African populations. Furthermore, the distribution of common haplotypes in Africa is not correlated with diet, raising the possibility that common variation may be under selection due to their role in nondietary biological processes. In addition, our data indicate that novel rare mutations contribute to the phenotypic variance of PTC sensitivity, illustrating the influence of rare variation on a common trait, as well as the relatively recent evolution of functionally diverse alleles at this locus. C1 [Campbell, Michael C.; Ranciaro, Alessia; Hirbo, Jibril; Tishkoff, Sarah A.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. [Froment, Alain] IRD MNHN, Musee Homme, UMR 208, Paris, France. [Omar, Sabah] Ctr Biotechnol Res & Dev, Kenya Med Res Inst, Nairobi, Kenya. [Bodo, Jean-Marie] Minist Sci Res & Innovat, Yaounde, Cameroon. [Nyambo, Thomas; Lema, Godfrey] Muhimbili Univ Hlth & Allied Sci, Dept Biochem, Dar Es Salaam, Tanzania. [Zinshteyn, Daniel; Tishkoff, Sarah A.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. [Drayna, Dennis] Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD USA. [Breslin, Paul A. S.] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. [Breslin, Paul A. S.] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. RP Tishkoff, SA (reprint author), Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. EM tishkoff@mail.med.upenn.edu FU US National Science Foundation (NSF) [BCS-0552486, BCS-0827436]; US National Institutes of Health (NIH) [R01GM076637, DP1-OD-006445, RO1 DC02995]; David and Lucile Packard Career Award FX We thank Fathya Abdo, Eva Aluvalla, Angel Carracedo, Graham Coop, Clara Elbers, Joseph Jarvis, Daniel Kariuki, Wen-Ya Ko, Joseph Lachance, Charla Lambert, Mingyao Li, Trini Miguel, Lilian Alando Nyindodo, Laura Scheinfeldt, Mark Shriver, Shamil Sunyaev, and Stephen Wooding for sample collection, valuable discussions, and/or statistical advice. We also thank the many Africans who generously donated their DNA and time so that we could learn more about the genetic basis and evolutionary history of bitter taste sensitivity in Africa. This study was funded by the US National Science Foundation (NSF) grant BCS-0552486, US NSF grant BCS-0827436, US National Institutes of Health (NIH) grant R01GM076637, US NIH Director's Pioneer Award Program DP1-OD-006445, and a David and Lucile Packard Career Award to S.A.T and a US NIH grant RO1 DC02995 to P.A.S.B. NR 52 TC 29 Z9 29 U1 19 U2 153 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD APR PY 2012 VL 29 IS 4 BP 1141 EP 1153 DI 10.1093/molbev/msr293 PG 13 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 915IQ UT WOS:000302018100005 PM 22130969 ER PT J AU Thomas, JA Weintraub, ST Wu, WM Winkler, DC Cheng, NQ Steven, AC Black, LW AF Thomas, Julie A. Weintraub, Susan T. Wu, Weimin Winkler, Dennis C. Cheng, Naiqian Steven, Alasdair C. Black, Lindsay W. TI Extensive proteolysis of head and inner body proteins by a morphogenetic protease in the giant Pseudomonas aeruginosa phage phi KZ SO MOLECULAR MICROBIOLOGY LA English DT Article ID BACTERIOPHAGE-T4 PREHEAD PROTEINASE; HIDDEN MARKOV-MODELS; PROHEAD PROTEASE; MYOVIRUS 201-PHI-2-1; SEQUENCE-ANALYSIS; DNA; CELLS; TRANSGLYCOSYLASE; IDENTIFICATION; INFECTIONS AB Encased within the 280 kb genome in the capsid of the giant myovirus fKZ is an unusual cylindrical proteinaceous inner body of highly ordered structure. We present here mass spectrometry, bioinformatic and biochemical studies that reveal novel information about the fKZ head and the complex inner body. The identification of 39 cleavage sites in 19 fKZ head proteins indicates cleavage of many prohead proteins forms a major morphogenetic step in fKZ head maturation. The fKZ head protease, gp175, is newly identified here by a bioinformatics approach, as confirmed by a protein expression assay. Gp175 is distantly related to T4 gp21 and recognizes and cleaves head precursors at related but distinct S/A/G-X-E recognition sites. Within the fKZ head there are six high-copy-number proteins that are probable major components of the inner body. The molecular weights of five of these proteins are reduced 3565% by cleavages making their mature form similar (2631 kDa), while their precursors are dissimilar (3688 kDa). Together the six abundant proteins sum to the estimated mass of the inner body (1520 MDa). The identification of these proteins is important for future studies on the composition and function of the inner body. C1 [Thomas, Julie A.; Black, Lindsay W.] Univ Maryland, Baltimore, MD 21201 USA. [Weintraub, Susan T.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Wu, Weimin; Winkler, Dennis C.; Cheng, Naiqian; Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. RP Black, LW (reprint author), Univ Maryland, Baltimore, MD 21201 USA. EM lblack@umaryland.edu FU NIH [AI11676]; NIAMS FX phi KZ and the phi KZ tailless mutant were generously provided by Dr A. Fokine (Purdue University) and Dr K. Miroshnikov (Russian Academy of Sciences) respectively. P. aeruginosa PAO1 was kindly provided by Dr R. Ernst (University of Maryland Baltimore). The pHERD20T vector was provided by Dr Yu (Marshall University). We thank Kevin Hakala and Sam Pardo for the excellent MS analyses that were conducted in the UTHSCSA Institutional Mass Spectrometry Laboratory. We thank Ru-ching Hsia (University of Maryland Baltimore) for her help with TEM and Qin Dan for her technical support. We are extremely grateful to Dr S.C. Hardies for allowing access to his collection of bioinformatics software and the UTHSCSA Bioinformatics Center for assistance with computational aspects of the project. This work was supported by NIH Grant AI11676 to L.W.B. and by the Intramural Research Program of NIAMS. NR 46 TC 13 Z9 13 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD APR PY 2012 VL 84 IS 2 BP 324 EP 339 DI 10.1111/j.1365-2958.2012.08025.x PG 16 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 922IA UT WOS:000302539400009 PM 22429790 ER PT J AU Singleton, AB AF Singleton, Andrew B. TI Rapid genetic diagnosis in single-gene movement disorders SO MOVEMENT DISORDERS LA English DT Editorial Material ID PARKINSON-DISEASE; MUTATIONS; DYSTONIA; ATAXIAS; PLA2G6; VPS35 C1 NIA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Singleton, AB (reprint author), NIA, Neurogenet Lab, Bethesda, MD 20892 USA. EM singleta@mail.nih.gov RI Singleton, Andrew/C-3010-2009 FU Intramural NIH HHS [Z01 AG000957-05]; NIA NIH HHS [Z01 AG000957, Z01 AG000957-09] NR 23 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD APR PY 2012 VL 27 IS 4 BP 467 EP 469 DI 10.1002/mds.24896 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 921HP UT WOS:000302469000039 PM 22488858 ER PT J AU Callahan, DJ Liu, WE Li, XH Dreher, MR Hassouneh, W Kim, M Marszalek, P Chilkoti, A AF Callahan, Daniel J. Liu, Wenge Li, Xinghai Dreher, Matthew R. Hassouneh, Wafa Kim, Minkyu Marszalek, Piotr Chilkoti, Ashutosh TI Triple Stimulus-Responsive Polypeptide Nanoparticles That Enhance Intratumoral Spatial Distribution SO NANO LETTERS LA English DT Article DE Polypeptides; block copolymers; stimulus-responsive; pH responsive; tumor drug delivery ID ELASTIN-LIKE POLYPEPTIDES; PH-SENSITIVE IMMUNOLIPOSOMES; INTRACELLULAR DRUG-DELIVERY; PROTEIN-BASED POLYMERS; SOLID TUMORS; PACLITAXEL DELIVERY; MICELLES; DOXORUBICIN; SYSTEM; DESTABILIZATION AB To address the limited tumor penetration of nanoparticle drug delivery vehicles, we report the first pH-responsive polypeptide micelle that dissociates at the low extracellular pH of solid tumors. This histidine-rich elastin-like polypeptide block copolymer self-assembles at 37 degrees C into spherical micelles that are stabilized by Zn2+ and are disrupted as the pH drops from 7.4 to 6.4. These pH-sensitive micelles demonstrate better in vivo penetration and distribution in tumors than a pH-insensitive control. C1 [Callahan, Daniel J.; Liu, Wenge; Li, Xinghai; Hassouneh, Wafa; Chilkoti, Ashutosh] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. [Callahan, Daniel J.; Hassouneh, Wafa; Kim, Minkyu; Marszalek, Piotr; Chilkoti, Ashutosh] Duke Univ, Ctr Biol Inspired Mat & Mat Syst, Durham, NC 27708 USA. [Dreher, Matthew R.] NCI, Ctr Intervent Oncol, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Kim, Minkyu; Marszalek, Piotr] Duke Univ, Dept Mech Engn & Mat Sci, Durham, NC 27708 USA. RP Chilkoti, A (reprint author), Duke Univ, Dept Biomed Engn, 136 Hudson Hall,Box 90281, Durham, NC 27708 USA. EM chilkoti@duke.edu OI Liu, Wenge/0000-0002-0688-1879; /0000-0002-9476-6351 FU NIH [R01EB007205]; Triangle MRSEC through NSF DMR; NSF [NSF-DGE-02-21632]; Center for Interventional Oncology of NIH FX The authors acknowledge molecular biology assistance from John Andrew Pura and Andrew Sobel. This work was supported by NIH Grant R01EB007205 (A.C.), the Triangle MRSEC through NSF DMR, an NSF-sponsored IGERT fellowship to D.J.C. through Grant NSF-DGE-02-21632, and the Center for Interventional Oncology in the Intramural Research Program of the NIH. NR 43 TC 40 Z9 40 U1 8 U2 81 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 J9 NANO LETT JI Nano Lett. PD APR PY 2012 VL 12 IS 4 BP 2165 EP 2170 DI 10.1021/nl300630c PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 922CO UT WOS:000302524600071 PM 22417133 ER PT J AU Charles, N Dema, B Rivera, J AF Charles, Nicolas Dema, Barbara Rivera, Juan TI Basophils from humans with systemic lupus erythematosus do not express MHC-II reply SO NATURE MEDICINE LA English DT Letter C1 [Charles, Nicolas; Dema, Barbara; Rivera, Juan] Natl Inst Arthrit & Musculoskeletal & Skin Dis, Immunogenet Mol Lab, US Natl Inst Hlth, Bethesda, MD USA. [Charles, Nicolas] Paris Diderot Univ, Inst Natl Sante & Rech Med, UMR 699, Bichat Med Sch, Paris, France. RP Charles, N (reprint author), Natl Inst Arthrit & Musculoskeletal & Skin Dis, Immunogenet Mol Lab, US Natl Inst Hlth, Bethesda, MD USA. EM riveraj@arb.niams.nih.gov RI Charles, Nicolas/P-5430-2014 OI Charles, Nicolas/0000-0002-5416-5834 NR 5 TC 1 Z9 1 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2012 VL 18 IS 4 BP 488 EP 490 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 923KI UT WOS:000302617800018 ER PT J AU Morales, M Bonci, A AF Morales, Marisela Bonci, Antonello TI Hooking CB2 receptor into drug abuse? SO NATURE MEDICINE LA English DT Editorial Material ID CANNABINOID RECEPTOR; BRAIN; EXPRESSION; MICROGLIA; SYSTEM C1 [Morales, Marisela; Bonci, Antonello] NIDA, Intramural Res Program, Baltimore, MD USA. [Bonci, Antonello] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Bonci, Antonello] Johns Hopkins Univ, Sch Med, Solomon H Snyder Neurosci Inst, Baltimore, MD USA. RP Morales, M (reprint author), NIDA, Intramural Res Program, Baltimore, MD USA. EM antonello.bonci@nih.gov NR 14 TC 13 Z9 13 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2012 VL 18 IS 4 BP 504 EP 505 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 923KI UT WOS:000302617800026 PM 22481411 ER PT J AU Sorge, RE Trang, T Dorfman, R Smith, SB Beggs, S Ritchie, J Austin, JS Zaykin, DV Vander Meulen, H Costigan, M Herbert, TA Yarkoni-Abitbul, M Tichauer, D Livneh, J Gershon, E Zheng, M Tan, K John, SL Slade, GD Jordan, J Woolf, CJ Peltz, G Maixner, W Diatchenko, L Seltzer, Z Salter, MW Mogil, JS AF Sorge, Robert E. Trang, Tuan Dorfman, Ruslan Smith, Shad B. Beggs, Simon Ritchie, Jennifer Austin, Jean-Sebastien Zaykin, Dmitri V. Vander Meulen, Heather Costigan, Michael Herbert, Teri A. Yarkoni-Abitbul, Merav Tichauer, David Livneh, Jessica Gershon, Edith Zheng, Ming Tan, Keith John, Sally L. Slade, Gary D. Jordan, Joanne Woolf, Clifford J. Peltz, Gary Maixner, William Diatchenko, Luda Seltzer, Ze'ev Salter, Michael W. Mogil, Jeffrey S. TI Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity SO NATURE MEDICINE LA English DT Article ID SPARED NERVE INJURY; NEUROPATHIC PAIN; SPINAL-CORD; P2X(7); MOUSE; NOCICEPTION; ANTAGONIST; COMPLEX; RAT; INTERLEUKIN-1-BETA AB Chronic pain is highly variable between individuals, as is the response to analgesics. Although much of the variability in chronic pain and analgesic response is heritable, an understanding of the genetic determinants underlying this variability is rudimentary(1). Here we show that variation within the coding sequence of the gene encoding the P2X7 receptor (P2X7R) affects chronic pain sensitivity in both mice and humans. P2X7Rs, which are members of the family of ionotropic ATP-gated receptors, have two distinct modes of function: they can function through their intrinsic cationic channel or by forming nonselective pores that are permeable to molecules with a mass of up to 900 Da(2,3). Using genome-wide linkage analyses, we discovered an association between nerve-injury-induced pain behavior (mechanical allodynia) and the P451L mutation of the mouse P2rx7 gene, such that mice in which P2X7Rs have impaired pore formation as a result of this mutation showed less allodynia than mice with the pore-forming P2rx7 allele. Administration of a peptide corresponding to the P2X7R C-terminal domain, which blocked pore formation but not cation channel activity, selectively reduced nerve injury and inflammatory allodynia only in mice with the pore-forming P2rx7 allele. Moreover, in two independent human chronic pain cohorts, a cohort with pain after mastectomy and a cohort with osteoarthritis, we observed a genetic association between lower pain intensity and the hypofunctional His270 (rs7958311) allele of P2RX7. Our findings suggest that selectively targeting P2X7R pore formation may be a new strategy for individualizing the treatment of chronic pain. C1 [Sorge, Robert E.; Ritchie, Jennifer; Austin, Jean-Sebastien; Mogil, Jeffrey S.] McGill Univ, Dept Psychol, Montreal, PQ, Canada. [Sorge, Robert E.; Ritchie, Jennifer; Austin, Jean-Sebastien; Mogil, Jeffrey S.] McGill Univ, Alan Edwards Ctr Res Pain, Montreal, PQ, Canada. [Trang, Tuan; Dorfman, Ruslan; Beggs, Simon; Vander Meulen, Heather; Salter, Michael W.] Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 1X8, Canada. [Smith, Shad B.; Maixner, William; Diatchenko, Luda] Univ N Carolina, Ctr Neurosensory Disorders, Chapel Hill, NC USA. [Smith, Shad B.; Slade, Gary D.; Maixner, William; Diatchenko, Luda; Mogil, Jeffrey S.] Algynomics Inc, Chapel Hill, NC USA. [Zaykin, Dmitri V.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Costigan, Michael; Herbert, Teri A.; Woolf, Clifford J.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Yarkoni-Abitbul, Merav; Tichauer, David; Seltzer, Ze'ev; Salter, Michael W.] Univ Toronto, Fac Dent, Toronto, ON, Canada. [Yarkoni-Abitbul, Merav; Tichauer, David; Seltzer, Ze'ev; Salter, Michael W.] Univ Toronto, Fac Med, Toronto, ON, Canada. [Livneh, Jessica] Chaim Sheba Med Ctr, Inst Oncol, Ramat Gan, Israel. [Gershon, Edith] Ein Hod, Hof Hacarmel, Israel. [Zheng, Ming; Peltz, Gary] Stanford Univ Sch Med, Dept Anesthesia, Stanford, CA USA. [Tan, Keith; John, Sally L.] Pfizer Global Res & Dev, Sandwich, Kent, England. [Slade, Gary D.] Univ N Carolina, Sch Dent, Dept Dent Ecol, Chapel Hill, NC 27599 USA. [Jordan, Joanne] Univ N Carolina, Thurston Arthrit Ctr, Chapel Hill, NC USA. RP Mogil, JS (reprint author), McGill Univ, Dept Psychol, Montreal, PQ, Canada. EM mike.salter@utoronto.ca; jeffrey.mogil@mcgill.ca OI Vandermeulen, Heather/0000-0003-1885-2298 FU US National Institutes of Health (NIH); Louise and Alan Edwards Foundation; Canada Research Chairs program; Howard Hughes Medical Institute; Canadian Institutes of Health Research; Krembil Foundation; Ontario Research Foundation; Algynomics/Pfizer; AstraZeneca-Alan Edwards Centre for Research on Pain; NIH; NIH (National Institute of Environmental Health Sciences) FX This research was supported by the US National Institutes of Health (NIH) (C.J.W., W.M., L.D., Z.S. and J.S.M.), the Louise and Alan Edwards Foundation (J.S.M.), the Canada Research Chairs program (M.W.S., J.S.M. and Z.S.), the Howard Hughes Medical Institute (M.W.S.), the Canadian Institutes of Health Research (M.W.S. and J.S.M.), the Krembil Foundation (M.W.S. and J.S.M.), the Ontario Research Foundation (M.W.S.) and Algynomics/Pfizer research funds (W.M., L.D.). R.E.S. was supported by an AstraZeneca-Alan Edwards Centre for Research on Pain postdoctoral fellowship. T.T. was supported by a Canadian Institutes of Health Research Fellowship. S.B.S. was supported by a National Research Service Award Fellowship from the NIH. D.V.Z. was supported by the Intramural Research Program of the NIH (National Institute of Environmental Health Sciences). NR 30 TC 130 Z9 139 U1 6 U2 36 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2012 VL 18 IS 4 BP 595 EP 599 DI 10.1038/nm.2710 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 923KI UT WOS:000302617800037 PM 22447075 ER PT J AU Taniguchi, H Jacinto, FV Villanueva, A Fernandez, AF Yamamoto, H Carmona, FJ Puertas, S Marquez, VE Shinomura, Y Imai, K Esteller, M AF Taniguchi, H. Jacinto, F. V. Villanueva, A. Fernandez, A. F. Yamamoto, H. Carmona, F. J. Puertas, S. Marquez, V. E. Shinomura, Y. Imai, K. Esteller, M. TI Silencing of Kruppel-like factor 2 by the histone methyltransferase EZH2 in human cancer SO ONCOGENE LA English DT Article DE epigenetics; histone methyltransferase; EZH2; KLF2 ID GROUP PROTEIN EZH2; PROSTATE-CANCER; TRANSCRIPTION FACTORS; CELL-GROWTH; POLYCOMB; REPRESSION; METHYLATION; PROGRESSION; EXPRESSION; APOPTOSIS AB The Kruppel-like factor (KLF) proteins are multitasked transcriptional regulators with an expanding tumor suppressor function. KLF2 is one of the prominent members of the family because of its diminished expression in malignancies and its growth-inhibitory, pro-apoptotic and anti-angiogenic roles. In this study, we show that epigenetic silencing of KLF2 occurs in cancer cells through direct transcriptional repression mediated by the Polycomb group protein Enhancer of Zeste Homolog 2 (EZH2). Binding of EZH2 to the 5'-end of KLF2 is also associated with a gain of trimethylated lysine 27 histone H3 and a depletion of phosphorylated serine 2 of RNA polymerase. Upon depletion of EZH2 by RNA interference, short hairpin RNA or use of the small molecule 3-Deazaneplanocin A, the expression of KLF2 was restored. The transfection of KLF2 in cells with EZH2-associated silencing showed a significant anti-tumoral effect, both in culture and in xenografted nude mice. In this last setting, KLF2 transfection was also associated with decreased dissemination and lower mortality rate. In EZH2-depleted cells, which characteristically have lower tumorigenicity, the induction of KLF2 depletion 'rescued' partially the oncogenic phenotype, suggesting that KLF2 repression has an important role in EZH2 oncogenesis. Most importantly, the translation of the described results to human primary samples demonstrated that patients with prostate or breast tumors with low levels of KLF2 and high expression of EZH2 had a shorter overall survival. Oncogene (2012) 31, 1988-1994; doi:10.1038/onc.2011.387; published online 5 September 2011 C1 [Taniguchi, H.; Jacinto, F. V.; Fernandez, A. F.; Carmona, F. J.; Esteller, M.] Hosp Duran & Reynals, Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Barcelona 08908, Catalonia, Spain. [Taniguchi, H.; Yamamoto, H.; Shinomura, Y.] Sapporo Med Univ, Sch Med, Dept Internal Med 1, Sapporo, Hokkaido, Japan. [Taniguchi, H.] Sapporo Med Univ, Sch Med, Tumor Med Examinat & Treatment Ctr, Sapporo, Hokkaido, Japan. [Jacinto, F. V.] Salk Inst Biol Studies, Mol & Cell Biol Lab, La Jolla, CA 92037 USA. [Villanueva, A.; Puertas, S.] Bellvitge Biomed Res Inst IDIBELL, ICO, Barcelona, Spain. [Marquez, V. E.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA. [Imai, K.] Univ Tokyo, Inst Med Sci, Tokyo, Japan. [Esteller, M.] Univ Barcelona, Sch Med, Dept Physiol Sci 2, Barcelona, Spain. [Esteller, M.] ICREA, Barcelona, Spain. RP Esteller, M (reprint author), Hosp Duran & Reynals, Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, 3rd Floor,Avda Gran Via LHosp 199-203, Barcelona 08908, Catalonia, Spain. EM mesteller@idibell.cat RI Esteller, Manel/L-5956-2014; Fernandez, Agustin/N-7302-2014; OI Esteller, Manel/0000-0003-4490-6093; Fernandez, Agustin/0000-0002-3792-4085; Carmona Sanz, F Javier/0000-0001-7904-8493 FU Lilly Foundation; Dr Josef Steiner Cancer Research Foundation; NIH, National Cancer Institute and Center for Cancer Research; [SAF2007-00027-65134]; [Consolider CSD2006-49] FX We thank O Dominguez for help with the microarray procedures and analysis, F Setien for technical assistance and Miki Kojiya for the flow cytometry analysis. This work was supported by Grants SAF2007-00027-65134, Consolider CSD2006-49, and Lilly Foundation and Dr Josef Steiner Cancer Research Foundation to ME, and the Intramural Research Program of the NIH, National Cancer Institute and Center for Cancer Research to VEM. HT is supported by the Uehara Memorial Foundation and Pancreas Research Foundation of Japan. ME is an ICREA Research Professor. NR 26 TC 41 Z9 43 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR PY 2012 VL 31 IS 15 BP 1988 EP 1994 DI 10.1038/onc.2011.387 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 926CW UT WOS:000302809900010 PM 21892211 ER PT J AU Fernandez, AB Wong, TY Klein, R Collins, D Burke, G Cotch, MF Klein, B Sadeghi, MM Chen, J AF Fernandez, Antonio B. Wong, Tien Y. Klein, Ronald Collins, Dorothea Burke, Gregory Cotch, Mary Frances Klein, Barbara Sadeghi, Mehran M. Chen, Jersey TI Age-Related Macular Degeneration and Incident Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis SO OPHTHALMOLOGY LA English DT Article ID COMPLEMENT FACTOR-H; ENDOTHELIAL DYSFUNCTION; MYOCARDIAL-INFARCTION; EYE DISEASE; MACULOPATHY; RISK; NEOVASCULARIZATION; ANGIOGENESIS; INFLAMMATION; POLYMORPHISM AB Objective: To determine whether age-related macular degeneration (AMD) is a risk indicator for coronary heart disease (CHD) and cardiovascular disease (CVD) events independent of other known risk factors in a multi-ethnic cohort. Design: Population-based prospective cohort study. Participants: A diverse population sample of 6233 men and women aged 45 to 84 years without known CVD from the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: Participants in the MESA had retinal photographs taken between 2002 and 2003. Photographs were evaluated for AMD. Incident CHD and CVD events were ascertained during clinical follow-up visits for up to 8 years after the retinal images were taken. Main Outcome Measures: Incident CHD and CVD events. Results: Of the 6814 persons at risk of CHD, there were 893 participants with early AMD (13.1%) and 27 patients (0.5%) at baseline. Over a mean follow-up period of 5.4 years, there was no statistically significant difference in incident CHD or CVD between the AMD and non-AMD groups (5.0% vs. 3.9%, P = 0.13 for CHD and 6.6% vs. 5.5%, P = 0.19 for CVD). In Cox regression models adjusting for CVD risk factors, there was no significant relationship between presence of any AMD and any CHD/CVD events (hazard ratio 0.99; 95% confidence interval, 0.74-1.33; P = 0.97). No significant association was found between subgroups of early AMD or late AMD and incident CHD/CVD events. Conclusions: In persons without a history of CVD, AMD was not associated with an increased risk of CHD or CVD. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;119:765-770 (C) 2012 by the American Academy of Ophthalmology. C1 [Fernandez, Antonio B.] Brown Univ, Warren Alpert Sch Med, Div Cardiol, Providence, RI 02903 USA. [Wong, Tien Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore Eye Res Inst, Singapore 117595, Singapore. [Klein, Ronald; Klein, Barbara] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Collins, Dorothea; Sadeghi, Mehran M.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Burke, Gregory] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. [Sadeghi, Mehran M.; Chen, Jersey] Yale Univ, Sch Med, Sect Cardiovasc Med, New Haven, CT USA. RP Fernandez, AB (reprint author), Brown Univ, Sch Med, Rhode Isl Hosp, Dept Cardiol, 593 Eddy St, Providence, RI 02903 USA. EM antoinefernandezt@hotmail.com OI Cotch, Mary Frances/0000-0002-2046-4350; Klein, Ronald/0000-0002-4428-6237 FU National Heart, Lung, and Blood Institute [HL69979-03, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166]; Agency for Healthcare Research and Quality [1K08HS018781-01] FX This research was supported by Grant HL69979-03 to Dr. Klein and Dr. Wong and by contracts N01-HC-95159 to N01-HC-95166 from the National Heart, Lung, and Blood Institute. Dr. Chen is supported by an award from the Agency for Healthcare Research and Quality (1K08HS018781-01). NR 31 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 2012 VL 119 IS 4 BP 765 EP 770 DI 10.1016/j.ophtha.2011.09.044 PG 6 WC Ophthalmology SC Ophthalmology GA 919UQ UT WOS:000302355400015 PM 22197438 ER PT J AU LaGasse, LL Derauf, C Smith, LM Newman, E Shah, R Neal, C Arria, A Huestis, MA DellaGrotta, S Lin, H Dansereau, LM Lester, BM AF LaGasse, Linda L. Derauf, Chris Smith, Lynne M. Newman, Elana Shah, Rizwan Neal, Charles Arria, Amelia Huestis, Marilyn A. DellaGrotta, Sheri Lin, Hai Dansereau, Lynne M. Lester, Barry M. TI Prenatal Methamphetamine Exposure and Childhood Behavior Problems at 3 and 5 Years of Age SO PEDIATRICS LA English DT Article DE amphetamines; behavior disorders/problems; children; methamphetamine; prenatal exposure ID MATERNAL LIFE-STYLE; INFANT DEVELOPMENT; COCAINE EXPOSURE; INTRAUTERINE GROWTH; SUBSTANCE USE; CHILDREN; ENVIRONMENT; AMPHETAMINE; PREGNANCY; IMPACT AB OBJECTIVE: We evaluated behavior problems in children who were prenatally exposed to methamphetamine (MA) at ages 3 and 5 years. METHODS: The Infant Development, Environment, and Lifestyle study, a prospective, longitudinal study of prenatal MA exposure and child outcome, enrolled subjects postpartum in Los Angeles, California; Honolulu, Hawaii; Des Moines, Iowa; and Tulsa, Oklahoma. Prenatal exposure was determined by maternal self-report and/or meconium results. Exposed and comparison groups were matched on race, birth weight, public health insurance, and education. Mothers in the comparison group denied use and had a negative meconium screen for amphetamines. Prenatal exposures to tobacco, alcohol, or marijuana occurred in both groups. At ages 3 and 5 years, 330 children (166 exposed and 164 comparison) were assessed for behavior problems by using the caregiver report on the Child Behavior Checklist. General linear mixed models were used to determine the effects of prenatal MA exposure, including heavy exposure (>= 3 days per week), age, and the interaction of exposure and age on behavior problems with adjustment for other drugs of abuse and environmental risk factors. RESULTS: MA exposure was associated with increased emotional reactivity and anxious/depressed problems at both ages and externalizing and attention-deficit/hyperactivity disorder problems by age 5 years. Heavy exposure was related to attention problems and withdrawn behavior at both ages. There were no effects of MA on the internalizing or total behavior problems scales. CONCLUSIONS: This first report of behavior problems in patients as young as 3 years associated with MA exposure identifies an important public health problem. Continued follow-up can inform the development of preventive intervention programs. Pediatrics 2012;129:681-688 C1 [LaGasse, Linda L.; DellaGrotta, Sheri; Lin, Hai; Dansereau, Lynne M.; Lester, Barry M.] Brown Univ, Warren Alpert Med Sch, Brown Ctr Study Children Risk, Providence, RI 02905 USA. [LaGasse, Linda L.; DellaGrotta, Sheri; Lin, Hai; Dansereau, Lynne M.; Lester, Barry M.] Women & Infants Hosp Rhode Isl, Providence, RI 02905 USA. [Derauf, Chris; Neal, Charles] Univ Hawaii, Dept Pediat, Honolulu, HI 96822 USA. [Smith, Lynne M.] Univ Calif Los Angeles, Dept Pediat, Los Angeles Biomed Res Inst, Harbor UCLA Med Ctr, Los Angeles, CA 90024 USA. [Smith, Lynne M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Newman, Elana] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA. [Shah, Rizwan] Blank Childrens Hosp, Reg Child Protect Ctr, Des Moines, IA USA. [Arria, Amelia] Univ Maryland, Sch Publ Hlth, Ctr Young Adult Hlth & Dev, Family Sci Dept, College Pk, MD 20742 USA. [Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA. RP LaGasse, LL (reprint author), Brown Univ, Warren Alpert Med Sch, Brown Ctr Study Children Risk, 101 Dudley St, Providence, RI 02905 USA. EM linda_lagasse@brown.edu OI Arria, Amelia/0000-0002-6360-9265 FU National Institutes on Drug Abuse [2R01DA014948]; National Center for Research Resources [5P20RR11091, 3M01RR00425]; National Institutes of Health (NIH) FX Funding was provided by the National Institutes on Drug Abuse (2R01DA014948 to Dr Lester) and in part by the National Center for Research Resources (5P20RR11091 and 3M01RR00425). Funded by the National Institutes of Health (NIH). NR 45 TC 33 Z9 34 U1 4 U2 25 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2012 VL 129 IS 4 BP 681 EP 688 DI 10.1542/peds.2011-2209 PG 8 WC Pediatrics SC Pediatrics GA 922IX UT WOS:000302541700046 PM 22430455 ER PT J AU Marcus, MD Foster, GD El Ghormli, L Baranowski, T Goldberg, L Jago, R Linder, B Steckler, A Trevino, R AF Marcus, Marsha D. Foster, Gary D. El Ghormli, Laure Baranowski, Tom Goldberg, Linn Jago, Russell Linder, Barbara Steckler, Allan Trevino, Roberto TI Shifts in BMI Category and Associated Cardiometabolic Risk: Prospective Results From HEALTHY Study SO PEDIATRICS LA English DT Article DE obesity; overweight; obesity trends; BMI; glucose; insulin; blood pressure; lipids ID BODY-MASS INDEX; CORONARY-HEART-DISEASE; PROSPECTIVE COHORT; METABOLIC SYNDROME; CHILDHOOD OBESITY; CHILDREN; ADOLESCENCE; INTERVENTION; PREVALENCE; ADIPOSITY AB OBJECTIVES: To evaluate shifts across BMI categories and associated changes in cardiometabolic risk factors over 2.5 years in an ethnically diverse middle school sample. METHODS: As part of HEALTHY, a multisite school-based study designed to mitigate risk for type 2 diabetes, 3993 children participated in health screenings at the start of sixth and end of eighth grades. Assessments included anthropometric measures, blood pressure, and glucose, insulin, and lipids. Students were classified as underweight, healthy weight, overweight, obese, or severely obese. Mixed models controlling for school intervention status and covariates were used to evaluate shifts in BMI category over time and the relation between these shifts and changes in risk factors. RESULTS: At baseline, students averaged 11.3 (+/- 0.6) years; 47.6% were boys, 59.6% were Hispanic, and 49.8% were overweight or obese. Shifts in BMI category over time were common. For example, 35.7% of youth who were overweight moved to the healthy weight range, but 13% in the healthy weight range became overweight. BMI shifts were not associated with school intervention condition, household education, or youth gender, race/ethnicity, pubertal status, or changes in height. Increases in BMI category were associated with worsening of cardiometabolic risk factors, and decreases were associated with improvements. Boys who increased BMI category were more vulnerable to negative risk factor changes than girls. CONCLUSIONS: There are substantial shifts across BMI categories during middle school that are associated with clinically meaningful changes in cardiometabolic risk factors. Programs to promote decreases in BMI and prevent increases are clearly warranted. Pediatrics 2012;129:e983-e991 C1 [Marcus, Marsha D.] Univ Pittsburgh Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Foster, Gary D.] Temple Univ, Ctr Obes Res & Educ, Philadelphia, PA 19122 USA. [El Ghormli, Laure] George Washington Univ, Ctr Biostat, Washington, DC USA. [Baranowski, Tom] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Goldberg, Linn] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Jago, Russell] Univ Bristol, Sch Policy Studies, Ctr Exercise Nutr & Hlth, Bristol, Avon, England. [Linder, Barbara] NIDDKD, Bethesda, MD 20892 USA. [Steckler, Allan] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Behav, Chapel Hill, NC USA. [Trevino, Roberto] Univ Texas Hlth Sci Ctr San Antonio, Social & Hlth Res Ctr, San Antonio, TX 78229 USA. RP Marcus, MD (reprint author), Univ Pittsburgh Med Ctr, Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. EM marcusmd@upmc.edu OI Jago, Russell/0000-0002-3394-0176; Baranowski, Tom/0000-0002-0653-2222 FU National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health [U01-DK61230, U01-DK61249, U01-DK61231, U01-DK61223]; National Institutes of Health (NIH); American Diabetes Association FX This work was completed with funding from National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health grants U01-DK61230, U01-DK61249, U01-DK61231, and U01-DK61223, with additional support from the American Diabetes Association. Funded by the National Institutes of Health (NIH). NR 23 TC 21 Z9 21 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2012 VL 129 IS 4 BP E983 EP E991 DI 10.1542/peds.2011-2696 PG 9 WC Pediatrics SC Pediatrics GA 922IX UT WOS:000302541700017 PM 22430457 ER PT J AU Nansel, TR Iannotti, RJ Liu, AY AF Nansel, Tonja R. Iannotti, Ronald J. Liu, Aiyi TI Clinic-Integrated Behavioral Intervention for Families of Youth With Type 1 Diabetes: Randomized Clinical Trial SO PEDIATRICS LA English DT Article DE type 1 diabetes; children; adolescents; adherence; behavioral intervention; glycemic control ID PERSONAL TRAINER INTERVENTION; METABOLIC-CONTROL; SELF-MANAGEMENT; GLYCEMIC CONTROL; TREATMENT ADHERENCE; HEALTH OUTCOMES; ADOLESCENTS; CHILDREN; MELLITUS; CARE AB OBJECTIVE: To test the effect on diabetes management outcomes of a low-intensity, clinic-integrated behavioral intervention for families of youth with type 1 diabetes. METHODS: Families (n = 390) obtaining care for type 1 diabetes participated in a 2-year randomized clinical trial of a clinic-integrated behavioral intervention designed to improve family diabetes management practices. Measurement of hemoglobin A1c, the primary outcome, was obtained at each clinic visit and analyzed centrally. Blood glucose meter data were downloaded at each visit. Adherence was assessed by using a semistructured interview at baseline, mid-study, and follow-up. Analyses included 2-sample t tests at predefined time intervals and mixed-effect linear-quadratic models to assess for difference in change in outcomes across the study duration. RESULTS: A significant overall intervention effect on change in glycemic control from baseline was observed at the 24-month interval (P = .03). The mixed-effect model showed a significant intervention by age interaction (P < .001). Among participants aged 12 to 14, a significant effect on glycemic control was observed (P = .009 for change from baseline to 24-month interval; P = .035 for mixed-effect model across study duration), but there was no effect among those aged 9 to 11. There was no intervention effect on child or parent report of adherence; however, associations of change in adherence with change in glycemic control were weak. CONCLUSIONS: This clinic-integrated behavioral intervention was effective in preventing the deterioration in glycemic control evident during adolescence, offering a potential model for integrating medical and behavioral sciences in clinical care. Pediatrics 2012; 129: e866-e873 C1 [Nansel, Tonja R.; Iannotti, Ronald J.; Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Nansel, TR (reprint author), 6100 Execut Blvd,Room 7B13R MSC 7510, Bethesda, MD 20892 USA. EM nanselt@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595; Liu, Aiyi/0000-0002-6618-5082 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [N01-HD-4-3364, N01-HD-4-3361, N01-HD-4-3362, N01-HD-4-3363, N01-HD-3-3360]; National Institutes of Health (NIH) FX Supported by the intramural research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, under the following contracts: N01-HD-4-3364, Joslin Diabetes Center, Boston, Massachusetts; N01-HD-4-3361, Nemours Children's Clinic, Jacksonville, Florida; N01-HD-4-3362, Texas Children's Hospital, Houston, Texas; N01-HD-4-3363, Children's Memorial Hospital, Chicago, Illinois; and N01-HD-3-3360, James Bell Associates, Arlington, Virginia. Funded by the National Institutes of Health (NIH). NR 46 TC 23 Z9 23 U1 8 U2 17 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2012 VL 129 IS 4 BP E866 EP E873 DI 10.1542/peds.2011-2858 PG 8 WC Pediatrics SC Pediatrics GA 922IX UT WOS:000302541700002 PM 22392172 ER PT J AU Shane, AL Hansen, NI Stoll, BJ Bell, EF Sanchez, PJ Shankaran, S Laptook, AR Das, A Walsh, MC Hale, EC Newman, NS Schrag, SJ Higgins, RD AF Shane, Andi L. Hansen, Nellie I. Stoll, Barbara J. Bell, Edward F. Sanchez, Pablo J. Shankaran, Seetha Laptook, Abbot R. Das, Abhik Walsh, Michele C. Hale, Ellen C. Newman, Nancy S. Schrag, Stephanie J. Higgins, Rosemary D. CA Eunice Kennedy Shriver Natl Inst TI Methicillin-Resistant and Susceptible Staphylococcus aureus Bacteremia and Meningitis in Preterm Infants SO PEDIATRICS LA English DT Article DE Staphylococcus aureus; methicillin resistant; infant; newborn ID INTENSIVE-CARE-UNIT; NEONATAL RESEARCH NETWORK; NECROTIZING ENTEROCOLITIS; PREGNANT-WOMEN; ONSET SEPSIS; INFECTIONS; TRANSMISSION; PROPHYLAXIS; EXPERIENCE; HEALTH AB BACKGROUND: Data are limited on the impact of methicillin-resistant Staphylococcus aureus (MRSA) on morbidity and mortality among very low birth weight (VLBW) infants with S aureus (SA) bacteremia and/or meningitis (B/M). METHODS: Neonatal data for VLBW infants (birth weight 401-1500 g) born January 1, 2006, to December 31, 2008, who received care at centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were collected prospectively. Early-onset (<= 72 hours after birth) and late-onset (>72 hours) infections were defined by blood or cerebrospinal fluid cultures and antibiotic treatment of >= 5 days (or death <5 days with intent to treat). Outcomes were compared for infants with MRSA versus methicillin-susceptible S aureus (MSSA) B/M. RESULTS: Of 8444 infants who survived >3 days, 316 (3.7%) had SA B/M. Eighty-eight had MRSA (1% of all infants, 28% of infants with SA); 228 had MSSA (2.7% of all infants, 72% of infants with SA). No infant had both MRSA and MSSA B/M. Ninety-nine percent of MRSA infections were late-onset. The percent of infants with MRSA varied by center (P < .001) with 9 of 20 centers reporting no cases. Need for mechanical ventilation, diagnosis of respiratory distress syndrome, necrotizing enterocolitis, and other morbidities did not differ between infants with MRSA and MSSA. Mortality was high with both MRSA (23 of 88, 26%) and MSSA (55 of 228, 24%). CONCLUSIONS: Few VLBW infants had SA B/M. The 1% with MRSA had morbidity and mortality rates similar to infants with MSSA. Practices should provide equal focus on prevention and management of both MRSA and MSSA infections among VLBW infants. Pediatrics 2012;129:e914-e922 C1 [Shane, Andi L.; Stoll, Barbara J.; Hale, Ellen C.] Emory Univ Sch Med, Dept Pediat, Atlanta, GA 30322 USA. [Shane, Andi L.; Stoll, Barbara J.; Hale, Ellen C.] Childrens Healthcare Atlanta, Atlanta, GA USA. [Hansen, Nellie I.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA. [Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Sanchez, Pablo J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. [Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA. [Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA. [Walsh, Michele C.; Newman, Nancy S.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA. [Schrag, Stephanie J.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Shane, AL (reprint author), Emory Univ Sch Med, Dept Pediat, 2015 Uppergate Dr NE, Atlanta, GA 30322 USA. EM ashane@emory.edu FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) FX The National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) provided grant support for the Neonatal Research Network's (NRN) Generic Database Study. The funding source had no direct involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Funded by the National Institutes of Health (NIH). NR 23 TC 28 Z9 28 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD APR PY 2012 VL 129 IS 4 BP E914 EP E922 DI 10.1542/peds.2011-0966 PG 9 WC Pediatrics SC Pediatrics GA 922IX UT WOS:000302541700008 PM 22412036 ER PT J AU Coiro, MJ Riley, A Broitman, M Miranda, J AF Coiro, Mary Jo Riley, Anne Broitman, Marina Miranda, Jeanne TI Effects on Children of Treating Their Mothers' Depression: Results of a 12-Month Follow-Up SO PSYCHIATRIC SERVICES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ONE-YEAR OUTCOMES; MATERNAL DEPRESSION; MINORITY WOMEN; SINGLE MOTHERS; MENTAL-HEALTH; UNITED-STATES; SYMPTOMS; PARENTS; PREVENTION AB Objective: This study used a controlled research design to examine the effects on children of treating their mothers' depression and of remission of the mothers' depression. Method: The sample consisted of 60 low-income women with major depression, who were predominantly from minority racial-ethnic groups, and their children ages four to 11. Women were randomly assigned to receive one of two active treatments (medication or cognitive-behavioral therapy) or a referral to existing community services. The mothers' depression was assessed by self-report on the Hamilton Depression Rating Scale, and the children's symptoms and adaptive skills were assessed by their mothers at baseline and six-month and 12-month follow-ups with the Behavior Assessment System for Children. Results.: Mixed-effects random intercept and random slope repeated-measures analyses using an intent-to-treat approach indicated that active treatment of mothers did not result in improvement in their children's behavior problems or adaptive skills. However, at both the six- and the 12-month follow-ups, children of mothers whose depression had remitted, regardless of treatment assignment, had significantly fewer behavior problems than children whose mothers remained depressed. Conclusions: The results support the need to expand access to, and support participation in, depression treatment among low-income women from minority racial-ethnic groups. Although treatment alone of this undertreated population was not associated with improvement in children's outcomes, it is a necessary first step to prevent psychopathology among offspring of depressed parents. (Psychiatric Services 63:357-363, 2012; doi: 10.1176/appi.ps.201100126) C1 [Coiro, Mary Jo] Loyola Univ Maryland, Dept Psychol, Baltimore, MD 21212 USA. [Riley, Anne] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD USA. [Broitman, Marina] NIMH, Div Extramural Act, Bethesda, MD 20892 USA. [Miranda, Jeanne] Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. [Miranda, Jeanne] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. RP Coiro, MJ (reprint author), Loyola Univ Maryland, Dept Psychol, 5911 York Rd,Suite 100, Baltimore, MD 21212 USA. EM mcoiro@loyola.edu FU National Institute of Mental Health [MH58384, MH56864] FX This research was supported by grants MH58384 and MH56864 from the National Institute of Mental Health. The authors gratefully acknowledge data analytic support from Lily Zhang, M.S. This work was conducted before Dr. Broitman began official duties as a U.S. government employee. NR 33 TC 11 Z9 11 U1 2 U2 16 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2012 VL 63 IS 4 BP 357 EP 363 DI 10.1176/appi.ps.201100126 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 925KN UT WOS:000302760200012 PM 22388476 ER PT J AU Choyke, PL AF Choyke, Peter L. TI Science to Practice: Imaging of Cellular Microparticles-Magic Dust or Just Dirt? SO RADIOLOGY LA English DT Article ID PROTAGONISTS AB Al Faraj et al (1) are to be congratulated on having the insight to label endothelial microparticles (MPs) with iron oxides to image their fate in vivo. Their experiment is a good example of how imaging can be an important scientific tool. By bringing the concept of MPs to the attention of the radiology community, this article stimulates thinking about how to make MPs into imaging agents and/or therapeutic agents. MPs are already making an impact as serum biomarkers. Their size and biology make them challenging to develop as general imaging biomarkers; however, their potential as highly targeted natural drug-imaging carrier platforms for vascular disease should not be ignored because they fulfill so many of the desirable preconditions for such platforms. We are just beginning to understand how to harness this magic "dust" for medical purposes. C1 NCI, Mol Imaging Program, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, 9000 Rockville Pike,Bldg 10,Room B3B69F, Bethesda, MD 20892 USA. EM pchoyke@mail.nih.gov NR 5 TC 1 Z9 1 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2012 VL 263 IS 1 BP 1 EP 2 DI 10.1148/radiol.12120076 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 923TP UT WOS:000302642700001 PM 22438438 ER PT J AU Strully, KW Fowler, JH Murabito, JM Benjamin, EJ Levy, D Christakis, NA AF Strully, Kate W. Fowler, James H. Murabito, Joanne M. Benjamin, Emelia J. Levy, Daniel Christakis, Nicholas A. TI Aspirin use and cardiovascular events in social networks SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE USA; Aspirin; Prevention; Cardiovascular disease; Social networks ID PRIMARY PREVENTION; UNITED-STATES; DISEASE; RISK; BEHAVIOR; SPREAD; UPDATE; ADULTS AB We tested whether friends' and family members' cardiovascular health events and also their own aspirin use are associated with the likelihood that an individual takes aspirin regularly. Analyses were based on longitudinal data on 2724 members of the Framingham Heart Study (based in Massachusetts, U.S.A.) who were linked to friends and family members who were also participants in the same study. Men were more likely to take aspirin if a male friend had recently been taking aspirin, and women were more likely to take aspirin if a brother had recently been taking aspirin. Men were also more likely to take aspirin if a brother recently had a cardiovascular event, and women were more likely to take aspirin if a female friend recently experienced a cardiovascular event. Aspirin use is correlated with the health and behavior of friends and family. These findings add to a growing body of evidence which suggests that behavioral changes that promote cardiovascular health may spread through social networks. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Strully, Kate W.] SUNY Albany, Dept Sociol, Coll Arts & Sci, Albany, NY 12222 USA. [Strully, Kate W.] SUNY Albany, Sch Publ Hlth, Dept Epidemiol, Albany, NY 12222 USA. [Fowler, James H.] Univ Calif San Diego, Div Med Genet, La Jolla, CA 92093 USA. [Fowler, James H.] Univ Calif San Diego, Dept Polit Sci, La Jolla, CA 92093 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Murabito, Joanne M.; Benjamin, Emelia J.; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Levy, Daniel] NHLBI, Bethesda, MD 20892 USA. [Christakis, Nicholas A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Christakis, Nicholas A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Christakis, Nicholas A.] Harvard Univ, Dept Sociol, Fac Arts & Sci, Cambridge, MA 02138 USA. RP Strully, KW (reprint author), SUNY Albany, Dept Sociol, Coll Arts & Sci, 1400 Washington Ave, Albany, NY 12222 USA. EM kstrully@albany.edu RI Fowler, James/C-2750-2008; OI Fowler, James/0000-0001-7795-1638; Murabito, Joanne/0000-0002-0192-7516; Benjamin, Emelia/0000-0003-4076-2336 FU NIH [P-01 AG031093]; Robert Wood Johnson Foundation; [N01-HC-25195] FX This was work was supported by NIH (P-01 AG031093) and by the Pioneer Portfolio of the Robert Wood Johnson Foundation; NHLBI 's Framingham Heart Study is supported by contract number N01-HC-25195. NR 18 TC 10 Z9 12 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD APR PY 2012 VL 74 IS 7 BP 1125 EP 1129 DI 10.1016/j.socscimed.2011.12.033 PG 5 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 920ZW UT WOS:000302448800022 PM 22361089 ER PT J AU Cable, RG Glynn, SA Kiss, JE Mast, AE Steele, WR Murphy, EL Wright, DJ Sacher, RA Gottschall, JL Tobler, LH Simon, TL AF Cable, Ritchard G. Glynn, Simone A. Kiss, Joseph E. Mast, Alan E. Steele, Whitney R. Murphy, Edward L. Wright, David J. Sacher, Ronald A. Gottschall, Jerry L. Tobler, Leslie H. Simon, Toby L. CA NHLBI Retrovirus Epidemiology Dono TI Iron deficiency in blood donors: the REDS-II Donor Iron Status Evaluation (RISE) study SO TRANSFUSION LA English DT Article ID SERUM TRANSFERRIN RECEPTOR; FERRITIN; HEMOGLOBIN; DONATION; STORES; HEMOCHROMATOSIS; DISEASE; ANEMIA AB BACKGROUND: Blood donors are at risk of iron deficiency. We evaluated the effects of blood donation intensity on iron and hemoglobin (Hb) in a prospective study. STUDY DESIGN AND METHODS: Four cohorts of frequent and first-time or reactivated (FT/RA) blood donors (no donation in 2 years), female and male, totaling 2425, were characterized and followed as they donated blood frequently. At enrollment and the final visit, ferritin, soluble transferrin receptor (sTfR), and Hb were determined. Models to predict iron deficiency and Hb deferral were developed. Iron depletion was defined at two levels: iron deficiency erythropoiesis (IDE) [log(sTfR/ferritin) >= 2.07] and absent iron stores (AIS; ferritin < 12 ng/mL). RESULTS: Among returning female FT and RA donors, 20 and 51% had AIS and IDE at their final visit, respectively; corresponding proportions for males were 8 and 20%. Among female frequent donors who returned, 27 and 62% had AIS and IDE, respectively, while corresponding proportions for males were 18 and 47%. Predictors of IDE and/or AIS included a higher frequency of blood donation in the past 2 years, a shorter interdonation interval, and being female and young; conversely, taking iron supplements reduced the risk of iron depletion. Predictors of Hb deferral included female sex, black race, and a shorter interdonation interval. CONCLUSIONS: There is a high prevalence of iron depletion in frequent blood donors. Increasing the interdonation interval would reduce the prevalence of iron depletion and Hb deferral. Alternatively, replacement with iron supplements may allow frequent donation without the adverse outcome of iron depletion. C1 [Cable, Ritchard G.] Amer Red Cross Blood Serv, Farmington, CT 06032 USA. NHLBI, Bethesda, MD 20892 USA. Inst Transfus Med, Pittsburgh, PA USA. Med Coll Wisconsin, BloodCtr Wisconsin, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI 53226 USA. Westat Corp, Rockville, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Blood Syst Res Inst, San Francisco, CA USA. Univ Cincinnati, Hoxworth Blood Ctr, Acad Hlth Ctr, Cincinnati, OH USA. CSL Plasma, Boca Raton, FL USA. RP Cable, RG (reprint author), Amer Red Cross Blood Serv, 209 Farmington Ave, Farmington, CT 06032 USA. EM CableR@usa.redcross.org FU NHLBI [N01-HB-47168, N01-HB-47169, N01-HB-47171, N01-HB-47172, N01-HB-47174, N01-HB-47175] FX This work was supported by NHLBI Contracts N01-HB-47168, -47169, -47171, -47172, -47174, and -47175. NR 27 TC 65 Z9 69 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD APR PY 2012 VL 52 IS 4 BP 702 EP 711 DI 10.1111/j.1537-2995.2011.03401.x PG 10 WC Hematology SC Hematology GA 923LT UT WOS:000302621500003 PM 22023513 ER PT J AU Booth, GS Lozier, JN Nghiem, K Clibourn, D Klein, HG Flegel, WA AF Booth, Garrett S. Lozier, Jay N. Nghiem, Khanh Clibourn, Douglas Klein, Harvey G. Flegel, Willy A. TI Spray: single-donor plasma product for room temperature storage SO TRANSFUSION LA English DT Article ID TRAUMA-ASSOCIATED COAGULOPATHY; DRIED ANIMAL PLASMA; FRESH-FROZEN PLASMA; MASSIVE TRANSFUSION; LYOPHILIZED PLASMA; BLOOD-TRANSFUSION; ESCHERICHIA-COLI AB BACKGROUND: Spray-drying techniques are commonly utilized in the pharmaceutical, dairy, and animal feed industries for processing liquids into powders but have not been applied to human blood products. Spray-dried protein products are known to maintain stability during storage at room temperature. STUDY DESIGN AND METHODS: Plasma units collected at the donor facility were shipped overnight at room temperature to a processing facility where single-use spray drying occurred. After 48 hours' storage at room temperature, the spray-dried plasma product was split in two and rehydrated with 1.5% glycine or deionized water and assayed for chemistry analytes and coagulation factors. Matched fresh-frozen plasma was analyzed in parallel as controls. RESULTS: Reconstitution was achieved for both rehydration groups within 5 minutes (n = 6). There was no significant intergroup difference in recovery for total protein, albumin, immunoglobulin (Ig) G, IgA, and IgM (96% or higher). With the exception of Factor VIII (58%), the recovery of clotting factors in the glycine reconstituted products ranged from 72% to 93%. Glycine reconstitution was superior to deionized water. CONCLUSION: We documented proteins and coagulation activities were recovered in physiologic quantities in reconstituted spray-dried plasma products. Further optimization of the spray-drying method and reconstitution fluid may result in even better recoveries. Spray drying is a promising technique for preparing human plasma that can be easily stored at room temperature, shipped, and reconstituted. Rapid reconstitution of the microparticles results in a novel plasma product from single donors. C1 NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. Velico Med Inc, Beverly, MA USA. RP Booth, GS (reprint author), Vanderbilt Univ, Sch Med, Pathol Labs, Blood Bank, TVC 4605, Nashville, TN 37232 USA. EM garrett.s.booth@vanderbilt.edu FU Intramural NIH HHS [Z99 CL999999] NR 27 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD APR PY 2012 VL 52 IS 4 BP 828 EP 833 DI 10.1111/j.1537-2995.2011.03419.x PG 6 WC Hematology SC Hematology GA 923LT UT WOS:000302621500019 PM 22043873 ER PT J AU Summers, RM AF Summers, Ronald M. TI Evaluation of Computer-aided Detection Devices: Consensus Is Developing SO ACADEMIC RADIOLOGY LA English DT Editorial Material ID INTRACRANIAL ANEURYSMS; MR-ANGIOGRAPHY; DIAGNOSIS; CT; COLONOGRAPHY C1 NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10,Room 1C224D,MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov NR 26 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD APR PY 2012 VL 19 IS 4 BP 377 EP 379 DI 10.1016/j.acra.2012.01.010 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 916NH UT WOS:000302110000001 PM 22444672 ER PT J AU Gallas, BD Chan, HP D'Orsi, CJ Dodd, LE Giger, ML Gur, D Krupinski, EA Metz, CE Myers, KJ Obuchowski, NA Sahiner, B Toledano, AY Zuley, ML AF Gallas, Brandon D. Chan, Heang-Ping D'Orsi, Carl J. Dodd, Lori E. Giger, Maryellen L. Gur, David Krupinski, Elizabeth A. Metz, Charles E. Myers, Kyle J. Obuchowski, Nancy A. Sahiner, Berkman Toledano, Alicia Y. Zuley, Margarita L. TI Evaluating Imaging and Computer-aided Detection and Diagnosis Devices at the FDA SO ACADEMIC RADIOLOGY LA English DT Article DE Reader studies; designs; methods; ROC; premarket; postmarket; consensus ID DIGITAL BREAST TOMOSYNTHESIS; FINITE-SAMPLE SIZE; OBSERVER PERFORMANCE; FREE-RESPONSE; SCREENING MAMMOGRAPHY; ROC CURVES; RADIOLOGISTS PERFORMANCE; LABORATORY ENVIRONMENT; SERIAL MAMMOGRAMS; VERIFICATION BIAS AB This report summarizes the Joint FDA-MIPS Workshop on Methods for the Evaluation of Imaging and Computer-Assist Devices. The purpose of the workshop was to gather information on the current state of the science and facilitate consensus development on statistical methods and study designs for the evaluation of imaging devices to support US Food and Drug Administration submissions. Additionally, participants expected to identify gaps in knowledge and unmet needs that should be addressed in future research. This summary is intended to document the topics that were discussed at the meeting and disseminate the lessons that have been learned through past studies of imaging and computer-aided detection and diagnosis device performance. C1 [Gallas, Brandon D.; Myers, Kyle J.; Sahiner, Berkman] US FDA, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Chan, Heang-Ping] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [D'Orsi, Carl J.] Emory Univ, Atlanta, GA 30322 USA. [Dodd, Lori E.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. [Giger, Maryellen L.; Metz, Charles E.] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Gur, David] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA 15260 USA. [Krupinski, Elizabeth A.] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. [Obuchowski, Nancy A.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Toledano, Alicia Y.] Stat Collaborat Inc, Washington, DC USA. RP Gallas, BD (reprint author), US FDA, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Room 3124, Silver Spring, MD 20993 USA. EM brandon.gallas@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620; Giger, Maryellen/0000-0001-5482-9728 NR 110 TC 16 Z9 16 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD APR PY 2012 VL 19 IS 4 BP 463 EP 477 DI 10.1016/j.acra.2011.12.016 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 916NH UT WOS:000302110000014 PM 22306064 ER PT J AU Soerensen, M Thinggaard, M Nygaard, M Dato, S Tan, QH Hjelmborg, J Andersen-Ranberg, K Stevnsner, T Bohr, VA Kimura, M Aviv, A Christensen, K Christiansen, L AF Soerensen, Mette Thinggaard, Mikael Nygaard, Marianne Dato, Serena Tan, Qihua Hjelmborg, Jacob Andersen-Ranberg, Karen Stevnsner, Tinna Bohr, Vilhelm A. Kimura, Masayuki Aviv, Abraham Christensen, Kaare Christiansen, Lene TI Genetic variation in TERT and TERC and human leukocyte telomere length and longevity: a cross-sectional and longitudinal analysis SO AGING CELL LA English DT Article DE association study; cross-sectional data and longitudinal data; human longevity; leukocyte telomere length; telomerase reverse transcriptase; telomerase RNA component ID COMMON VARIANTS; LIFE-SPAN; ASSOCIATION; POPULATION; TWIN; AGE; CENTENARIANS; HERITABILITY; MORTALITY; BIOLOGY AB Telomerase is of key importance for telomere maintenance, and variants of the genes encoding its major subunits, telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC), are candidates for interindividual variation in telomere length. Recently, the two SNPs rs3772190 and rs12696304 in the TERC locus were reported to be associated with leukocyte telomere length (LTL) in two genome-wide association studies, while one haplotype of TERT (rs2853669, rs2736098, rs33954691, and rs2853691) has been reported to be associated with both LTL and longevity in a candidate gene study. In this study, we investigated the two TERC and four TERT SNPs in middle-aged, old, and oldest-old Danes (58100 years) and their association with LTL (n = 864) and longevity (n = 1069). Furthermore, data on 11 TERT tagging SNPs in 1089 oldest-old and 736 middle-aged Danes were investigated with respect to longevity. For all SNPs, the association with longevity was investigated using both a cross-sectional and a longitudinal approach. Applying an additive model, we found association of LTL with the minor TERC alleles of rs3772190 (A) and rs12696304 (G), such that a shorter LTL was seen in rs3772190 A carriers (regression coefficient = -0.08, P = 0.011) and in male rs12696304 G carriers (regression coefficient = -0.13, P = 0.014). No TERT variations showed association. Moreover, the A allele of rs3772190 (TERC) was found to be associated with longevity [hazard rate (AG + AA) = 1.31, P = 0.006]. No associations with longevity were observed for the TERT SNPs or haplotypes. Our study, thus, indicates that TERC is associated with both LTL and longevity in humans. C1 [Soerensen, Mette; Thinggaard, Mikael; Nygaard, Marianne; Dato, Serena; Tan, Qihua; Hjelmborg, Jacob; Andersen-Ranberg, Karen; Christensen, Kaare; Christiansen, Lene] Univ So Denmark, Inst Publ Hlth, Danish Aging Res Ctr, DK-5000 Odense C, Denmark. [Soerensen, Mette; Nygaard, Marianne; Dato, Serena; Tan, Qihua; Christensen, Kaare; Christiansen, Lene] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark. [Soerensen, Mette; Nygaard, Marianne; Dato, Serena; Tan, Qihua; Christensen, Kaare; Christiansen, Lene] Odense Univ Hosp, Dept Biochem & Clin Pharmacol, DK-5000 Odense C, Denmark. [Dato, Serena] Univ Calabria, Dept Cell Biol, I-87036 Arcavacata Di Rende, Cs, Italy. [Stevnsner, Tinna; Bohr, Vilhelm A.] Aarhus Univ, Dept Mol Biol, Danish Aging Res Ctr, DK-8000 Aarhus C, Denmark. [Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Kimura, Masayuki; Aviv, Abraham] Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Human Dev & Aging, Newark, NJ 07103 USA. RP Soerensen, M (reprint author), Univ So Denmark, Inst Publ Hlth, Danish Aging Res Ctr, JB Winsloews Vej 9B, DK-5000 Odense C, Denmark. EM msoerensen@health.sdu.dk RI Christensen, Kaare/C-2360-2009; Soerensen, Mette/O-1817-2015; Andersen-Ranberg, Karen/P-7053-2015; OI Christensen, Kaare/0000-0002-5429-5292; Andersen-Ranberg, Karen/0000-0003-1970-7076; Soerensen, Mette/0000-0001-5268-3366; dato, serena/0000-0003-2589-7929 FU Max-Planck Institute for Demographic Research, (Rostock, Germany); INTERREG 4 A programme Syddanmark-Schleswig-K.E.R.N.; EU; National Institute on Aging [P01 AG08761, R01AG030678]; Novo Nordisk Foundation; Aase and Ejnar Danielsen Foundation; Augustinus Foundation; Brodrene Hartmann Foundation; King Christian the 10th Foundation; Einar Willumsens Mindelegat Foundation; VELUX Foundation FX This study was supported by the Max-Planck Institute for Demographic Research, (Rostock, Germany), the INTERREG 4 A programme Syddanmark-Schleswig-K.E.R.N. (by EU funds from the European Regional Development Fund), the National Institute on Aging (P01 AG08761 and R01AG030678), the Novo Nordisk Foundation, the Aase and Ejnar Danielsen Foundation, the Augustinus Foundation, the Brodrene Hartmann Foundation, the King Christian the 10th Foundation, and the Einar Willumsens Mindelegat Foundation. The Danish Aging Research Center is supported by a grant from the VELUX Foundation. Marlene Graff Sorensen, Susanne Knudsen, Steen Gregersen, Ulla Munk, and Shuxia Li are thanked for excellent technical work. NR 29 TC 41 Z9 42 U1 3 U2 22 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD APR PY 2012 VL 11 IS 2 BP 223 EP 227 DI 10.1111/j.1474-9726.2011.00775.x PG 5 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 908WF UT WOS:000301523000006 PM 22136229 ER PT J AU Harries, LW Pilling, LC Hernandez, LDG Bradley-Smith, R Henley, W Singleton, AB Guralnik, JM Bandinelli, S Ferrucci, L Melzer, D AF Harries, Lorna W. Pilling, Luke C. Hernandez, L. Dena G. Bradley-Smith, Rachel Henley, William Singleton, Andrew B. Guralnik, Jack M. Bandinelli, Stefania Ferrucci, Luigi Melzer, David TI CCAAT-enhancer-binding protein-beta expression in vivo is associated with muscle strength SO AGING CELL LA English DT Article DE inflammation; macrophage; mechanism; population; regeneration; transcription ID C/EBP-BETA; SKELETAL-MUSCLE; MACROPHAGE POLARIZATION; GENE-EXPRESSION; OLD RATS; INJURY; ACTIVATION; CELLS; REGENERATION; AGE AB Declining muscle strength is a core feature of aging. Several mechanisms have been postulated, including CCAAT/enhancer-binding protein-beta (C/EBP-beta)-triggered macrophage-mediated muscle fiber regeneration after micro-injury, evidenced in a mouse model. We aimed to identify in vivo circulating leukocyte gene expression changes associated with muscle strength in the human adult population. We undertook a genome-wide expression microarray screen, using peripheral blood RNA samples from InCHIANTI study participants (aged 30 and 104). Logged expression intensities were regressed with muscle strength using models adjusted for multiple confounders. Key results were validated by real-time PCR. The Short Physical Performance Battery (SPPB) score tested walk speed, chair stand, and balance. CEBPB expression levels were associated with muscle strength (beta coefficient = 0.20560, P = 1.03*10-6, false discovery rate q = 0.014). The estimated handgrip strength in 70-year-old men in the lowest CEBPB expression tertile was 35.2 kg compared with 41.2 kg in the top tertile. CEBPB expression was also associated with hip, knee, ankle, and shoulder strength and the SPPB score (P = 0.018). Near-study-wide associations were also noted for TGF-beta 3 (P = 3.4*10-5, q = 0.12) and CEBPD expression (P = 9.7*10-5, q = 0.18) but not for CEBPA expression. We report here a novel finding that raised CEBPB expression in circulating leukocyte-derived RNA samples in vivo is associated with greater muscle strength and better physical performance in humans. This association may be consistent with mouse model evidence of CEBPB-triggered muscle repair: if this mechanism is confirmed, it may provide a target for intervention to protect and enhance aging muscle. C1 [Harries, Lorna W.; Bradley-Smith, Rachel; Melzer, David] Univ Exeter, Inst Biomed & Clin Sci, Peninsula Coll Med & Dent, Exeter EX1 2LU, Devon, England. [Hernandez, L. Dena G.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Henley, William] Univ Plymouth, Sch Math & Stat, Plymouth PL4 8AA, Devon, England. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA. RP Melzer, D (reprint author), Peninsula Med Sch, Barrack Rd, Exeter EX2 5DW, Devon, England. EM david.melzer@pms.ac.uk RI Singleton, Andrew/C-3010-2009; Pilling, Luke/E-4917-2013; Harries, Lorna/D-2241-2014; OI Pilling, Luke/0000-0002-3332-8454; Melzer, David/0000-0002-0170-3838 FU Peninsula College of Medicine and Dentistry (John Bull Building, Tamar Science Park, Research Way, Plymouth, UK) FX The authors declare no conflict of interest. This analysis was supported by funding from the Peninsula College of Medicine and Dentistry (John Bull Building, Tamar Science Park, Research Way, Plymouth PL6 8BU, UK). NR 44 TC 10 Z9 11 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD APR PY 2012 VL 11 IS 2 BP 262 EP 268 DI 10.1111/j.1474-9726.2011.00782.x PG 7 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 908WF UT WOS:000301523000011 PM 22152057 ER PT J AU Sheydina, A Volkova, M Jiang, LQ Juhasz, O Zhang, J Tae, HJ Perino, MG Wang, MY Zhu, Y Lakatta, EG Boheler, KR AF Sheydina, Anna Volkova, Maria Jiang, Liqun Juhasz, Ondrej Zhang, Jing Tae, Hyun-Jin Perino, Maria G. Wang, Mingyi Zhu, Yi Lakatta, Edward G. Boheler, Kenneth R. TI Linkage of cardiac gene expression profiles and ETS2 with lifespan variability in rats SO AGING CELL LA English DT Article DE aging; mortality; rat; microarrays; prediction analysis of microarrays; transcription factors ID APOPTOSIS-INDUCING FACTOR; PROGRAMMED NECROSIS; CALORIC RESTRICTION; DIETARY RESTRICTION; HEART-FAILURE; SENESCENCE; PATTERNS; DISSECTION; CARCINOMAS; EXTENSION AB Longevity variability is a common feature of aging in mammals, but the mechanisms responsible for this remain largely unknown. Using microarray datasets coupled with prediction analysis of microarrays (PAM), we identified a set of 252 cardiac transcripts predictive of relative lifespan in Wistar and Fisher 344 rats. Prediction analysis of microarrays tests of rat heart transcriptomes from a third longer lived Fisher x Norway Brown rat strain validated the predictive value of this gene subset. The expression patterns of these genes were highly conserved, and corresponding promoter regions were employed to identify common ciselements and trans-activating factors implicated in their control. Specifically, four transcription factors (Max, Ets2, Erg, and Msx2) present in heart displayed longevity-dependent, strain-independent changes in abundance, but only ETS2 had an expression profile that directly correlated with the relative lifespan gene set. In heart, ETS2 was prevalent in cardiomyocytes (CMs) and showed a high degree of myocyte-to-myocyte variability predominantly in adult rat hearts prior to the exponential increase in the rate of mortality. Exclusively in this group, elevated ETS2 significantly overlapped with TUNEL staining in heart myocytes. In response to sympathetic stimuli, ETS2 is also up-regulated, and functionally, adenovirus-mediated over-expression of ETS2 promotes apoptosis-inducing factor-mediated, caspase-independent programmed necrosis exclusively in CMs that can be fully inhibited by the PARP-1 inhibitor DPQ. We conclude that variations in ETS2 abundance in hearts of adult rodents and the associated loss of CMs contribute at least partially, to the longevity variability observed during normal aging of rats through activation of programmed necrosis. C1 [Boheler, Kenneth R.] NIA, Mol Cardiol & Stem Cell Unit, LCS, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP Boheler, KR (reprint author), NIA, Mol Cardiol & Stem Cell Unit, LCS, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bohelerk@grc.nia.nih.gov FU NIH, National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging. NR 43 TC 5 Z9 6 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD APR PY 2012 VL 11 IS 2 BP 350 EP 359 DI 10.1111/j.1474-9726.2012.00794.x PG 10 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 908WF UT WOS:000301523000021 PM 22247964 ER PT J AU Agwu, AL Bethel, J Hightow-Weidman, LB Sleasman, JW Wilson, CM Rudy, B Kapogiannis, BG AF Agwu, Allison L. Bethel, James Hightow-Weidman, Lisa B. Sleasman, John W. Wilson, Craig M. Rudy, Bret Kapogiannis, Bill G. CA ATN 061 Team Adolescent Med Trials Network HIV TI Substantial Multiclass Transmitted Drug Resistance and Drug-Relevant Polymorphisms Among Treatment-Naive Behaviorally HIV-Infected Youth SO AIDS PATIENT CARE AND STDS LA English DT Letter ID PREVALENCE; MEN; SEX; TRANSMISSION; TRIALS C1 [Agwu, Allison L.] Johns Hopkins Univ, Sch Med, Dept Pediat & Adult Infect Dis, Baltimore, MD USA. [Bethel, James] WESTAT Corp, Rockville, MD 20850 USA. [Hightow-Weidman, Lisa B.] Univ N Carolina, Dept Med, Div Infect Dis, Chapel Hill, NC USA. [Sleasman, John W.] Univ S Florida, Dept Pediat, Div Allergy Immunol & Rheumatol, St Petersburg, FL 33701 USA. [Wilson, Craig M.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Rudy, Bret] NYU, Dept Pediat, Sch Med, New York, NY 10016 USA. [Kapogiannis, Bill G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA. RP Agwu, AL (reprint author), Johns Hopkins Med Inst, Dept Pediat Infect Dis, 200 N Wolfe St,Room 3145, Baltimore, MD 21287 USA. EM ageorg10@jhmi.edu FU NCRR NIH HHS [M01RR020359, UL1RR024131, UL1 RR024134, UL1 RR025780, MO1-RR010284]; NIAID NIH HHS [K23 AI084549]; NICHD NIH HHS [U01 HD040533, U01 HD068070, U01 HD 040474, U01 HD040474, U01 HD 040533]; PHS HHS [U01 A1068632] NR 12 TC 8 Z9 8 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD APR PY 2012 VL 26 IS 4 BP 193 EP 196 DI 10.1089/apc.2011.0420 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 918BX UT WOS:000302225000001 PM 22563607 ER PT J AU Mills, KC Sangueza, OP Beaty, MW Raffeld, M Pang, CS AF Mills, Kyle C. Sangueeza, Omar P. Beaty, Michael W. Raffeld, Mark Pang, Changlee S. TI Composite B-cell and T-cell Lineage Post-transplant Lymphoproliferative Disorder of the Lung with Unusual Cutaneous Manifestations of Mycosis Fungoides SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE post-transplant lymphoproliferative disorder; B-cell; T-cell; composite; mycosis fungoides ID EPSTEIN-BARR-VIRUS; TRANSPLANT RECIPIENT; LYMPHOMA; PATHOGENESIS; PATHOLOGY; PATIENT AB We present the case of a 17-year-old male kidney transplant recipient who presented initially with dermatologic symptoms and was found to have histologic changes in the skin that were consistent with mycosis fungoides. Shortly after this diagnosis was made, imaging studies demonstrated multifocal interstitial and airspace consolidation in both lungs. Physical examination revealed no lymphadenopathy or hepatosplenomegaly, but an open lung biopsy revealed an Epstein-Barr virus (EBV)-negative monomorphic T-cell posttransplant lymphoproliferative disorder (PTLD) with a concomitant EBV-positive B-cell PTLD involving the same lesion of the lung. Polymerase chain reaction analysis demonstrated clonal T-cell receptor gene rearrangements in both the skin and the lung biopsies. Interestingly, 1 clone was shared between the skin and lung while a second clone was present only in the lung. To our knowledge, this is the first reported case of a PTLD presenting in the skin in which there was a subsequent discovery of composite, bilineal B-and T-cell PTLD of the lung. C1 [Mills, Kyle C.] Wake Forest Univ, Baptist Med Ctr, Sch Med, Dept Pathol, Winston Salem, NC 27157 USA. [Sangueeza, Omar P.] Wake Forest Univ, Dept Dermatol, Sch Med, Winston Salem, NC 27157 USA. [Raffeld, Mark] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Mills, KC (reprint author), Wake Forest Univ, Baptist Med Ctr, Sch Med, Dept Pathol, 2nd Floor,Watlington Hall,Med Ctr Blvd, Winston Salem, NC 27157 USA. EM kmills@wfubmc.edu NR 15 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD APR PY 2012 VL 34 IS 2 BP 220 EP 225 DI 10.1097/DAD.0b013e31823067f8 PG 6 WC Dermatology SC Dermatology GA 917AD UT WOS:000302143400021 PM 22214855 ER PT J AU Pazmino, PA AF Pazmino, Patricio A. TI DABIGATRAN ASSOCIATED ACUTE RENAL FAILURE (DAARF) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation CY MAY 09-13, 2012 CL Washington, DC SP Natl Kidney Fdn C1 [Pazmino, Patricio A.] Internal Med & Hypertens NIH Ctr, El Paso, TX USA. [Pazmino, Patricio A.] PFSM Texas Tech Univ, Hlth Sci Ctr, El Paso, TX USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2012 VL 59 IS 4 MA 196 BP A63 EP A63 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 916QE UT WOS:000302117500198 ER PT J AU Pattabiraman, PP Lih, FB Tomer, KB Rao, PV AF Pattabiraman, Padmanabhan P. Lih, Fred B. Tomer, Kenneth B. Rao, Ponugoti Vasantha TI The role of calcium-independent phospholipase A(2)gamma in modulation of aqueous humor drainage and Ca2+ sensitization of trabecular meshwork contraction SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE Rho GTPase; arachidonic acid; glaucoma ID OPEN-ANGLE GLAUCOMA; MECHANISM-BASED DISCRIMINATION; VASCULAR SMOOTH-MUSCLE; NONMUSCLE MYOSIN-II; PROTEIN-KINASE-C; RHO-KINASE; ARACHIDONIC-ACID; GENETIC ABLATION; A(2) ENZYMES; P388D(1) MACROPHAGES AB Pattabiraman PP, Lih FB, Tomer KB, Rao PV. The role of calcium-independent phospholipase A(2)gamma in modulation of aqueous humor drainage and Ca2+ sensitization of trabecular meshwork contraction. Am J Physiol Cell Physiol 302: C979-C991, 2012. First published January 11, 2012; doi:10.1152/ajpcell.00396.2011.-The contractile and relaxation characteristics of trabecular meshwork (TM) are presumed to influence aqueous humor (AH) drainage and intraocular pressure. The mechanisms underlying regulation of TM cell contractile properties, however, are not well understood. This study investigates the role of calcium-independent phospholipase A(2) (iPLA(2)), which controls eicosanoid synthesis, in regulation of TM cell contraction and AH outflow using mechanism-based isoform specific inhibitors (R)-bromoenol lactone (R-BEL, iPLA(2)gamma specific) and (S)bromoenol lactone (S-BEL, iPLA(2)beta specific). Immunohistochemical analysis revealed intense staining for both iPLA(2)gamma and gamma isoforms throughout the TM, juxtacanalicular tissue, and Schlemm's canal of human eye. Inhibition of iPLA(2)gamma by R-BEL or small interfering RNA-mediated silencing of iPLA(2)gamma expression induced dramatic changes in TM cell morphology, and decreased actin stress fibers, focal adhesions, and myosin light-chain (MLC) phosphorylation. AH outflow facility increased progressively and significantly in enucleated porcine eyes perfused with R-BEL. This response was associated with a significant decrease in TM tissue MLC phosphorylation and alterations in the morphology of aqueous plexi in R-BEL-perfused eyes. In contrast, S-BEL did not affect either of these parameters. Additionally, R-BEL-induced cellular relaxation of the TM was associated with a significant decrease in the levels of active Rho GTPase, phospho-MLC phosphatase, phospho-CPI-17, and arachidonic acid. Taken together, these observations demonstrate that iPLA(2)gamma plays a significant and isoform-specific role in regulation of AH outflow facility by altering the contractile characteristics of the TM. The effects of iPLA(2)gamma on TM contractile status appear to involve arachidonic acid and Rho GTPase signaling pathways. C1 [Pattabiraman, Padmanabhan P.; Rao, Ponugoti Vasantha] Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC 27710 USA. [Lih, Fred B.; Tomer, Kenneth B.] NIEHS, Mass Spectrometry Grp, Res Triangle Pk, NC 27709 USA. [Rao, Ponugoti Vasantha] Duke Univ, Sch Med, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. RP Rao, PV (reprint author), Duke Univ, Sch Med, Dept Ophthalmol, AERI Bldg,Rm 4010, Durham, NC 27710 USA. EM rao00011@mc.duke.edu RI Tomer, Kenneth/E-8018-2013 FU National Institutes of Health [EY018590, EY12201]; National Eye Institute [P30-EY5722]; National Institute of Environmental Health Sciences/National Institutes of Health [ES050167] FX This work was supported in part by National Institutes of Health Grants to P. V. Rao (EY018590 and EY12201), National Eye Institute Core Grant for Vision Research (P30-EY5722), and by the Intramural Research Program of the National Institute of Environmental Health Sciences/National Institutes of Health, ES050167. NR 57 TC 10 Z9 10 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 2012 VL 302 IS 7 BP C979 EP C991 DI 10.1152/ajpcell.00396.2011 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 919QG UT WOS:000302342700004 PM 22237407 ER PT J AU Miettinen, M Rikala, MS Rys, J Lasota, J Wang, ZF AF Miettinen, Markku Rikala, Maarit-Sarlomo Rys, Janusz Lasota, Jerzy Wang, Zeng-Feng TI Vascular Endothelial Growth Factor Receptor 2 as a Marker for Malignant Vascular Tumors and Mesothelioma: An Immunohistochemical Study of 262 Vascular Endothelial and 1640 Nonvascular Tumors SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE angiosarcoma; Kaposi sarcoma; malignant mesothelioma; VEGFR2; endothelial cell; mesothelial cell; fetal tissue; adult tissue ID COLORECTAL-CANCER; KAPOSIS-SARCOMA; BREAST-CANCER; EXPRESSION; VEGF; ANGIOSARCOMA; ANGIOGENESIS; HEMANGIOMA; INHIBITOR; CARCINOMA AB Vascular endothelial growth factor receptor 2 (VEGFR2) is a primary responder to vascular endothelial growth factor signal and thereby regulates endothelial migration and proliferation. This receptor is expressed in endothelial cells and in some vascular tumors, but many reports also detail its expression in carcinomas and lymphomas. VEGFR2 is a potential cell-type marker, and data on VEGFR2 expression may also have therapeutic significance in view of recent availability of VEGFR2 inhibitors. In this study, we immunohistochemically examined 262 vascular endothelial and 1640 nonvascular tumors and selected non-neoplastic tissues with a VEGFR2-specific rabbit monoclonal antibody 55B11. In early human embryo, VEFGR2 was expressed in endothelia of developing capillaries and in the thoracic duct, great vessels, hepatic sinusoids, epidermis, and mesothelia. In late first trimester fetus peripheral soft tissues, VEGFR2 was restricted to capillary endothelia, chondrocytes, and superficial portion of the epidermis. In normal adult tissues, it was restricted to endothelia and mesothelia. VEGFR2 was consistently expressed in angiosarcomas, Kaposi sarcomas, and retiform hemangioendotheliomas. It was detected in only half of epithelioid hemangioendotheliomas (15/27), usually focally. VEGFR2 was strongly expressed in most capillary hemangiomas and weakly or focally in cavernous, venous, and spindle cell hemangiomas and in lymphangiomas. Malignant epithelial mesothelioma was found to be a unique epithelial neoplasm with a strong and nearly consistent VEGFR2 expression, including membrane staining (35/38). Approximately 10% of squamous cell carcinomas and 23% of pulmonary adenocarcinomas contained focal positivity. The only nonendothelial mesenchymal tumors found to be VEGFR2 positive were biphasic synovial sarcoma (focal epithelial expression) and chordoma. All melanomas and lymphomas were negative. VEGFR2 is a promising marker for malignant vascular tumors and malignant epithelioid mesothelioma. Expression in biphasic synovial sarcoma epithelium, chordoma, and some carcinomas has to be considered in differential diagnosis. Information on VEGFR2 tissue expression may be useful in development of targeted oncologic therapy through VEGFR2-specific tyrosine kinase inhibitors. C1 [Miettinen, Markku; Lasota, Jerzy; Wang, Zeng-Feng] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Rikala, Maarit-Sarlomo] Univ Helsinki, Cent Hosp, Dept Pathol, HUSLAB, Helsinki, Finland. [Rys, Janusz] Maria Sklodowska Curie Mem Inst Oncol, Krakow Branch, Ctr Oncol, Dept Tumor Pathol, Krakow, Poland. RP Miettinen, M (reprint author), NCI, Pathol Lab, 9000 Rockville Pike,Bldg 10,Rm 2B50, Bethesda, MD 20892 USA. EM miettinenmm@mail.nih.gov FU NCI FX The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Supported as a part of NCI's intramural research program. NR 37 TC 18 Z9 19 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2012 VL 36 IS 4 BP 629 EP 639 DI 10.1097/PAS.0b013e318243555b PG 11 WC Pathology; Surgery SC Pathology; Surgery GA 916ZQ UT WOS:000302142100017 PM 22314185 ER PT J AU Ali, M Keen, L Bygrave, D Jones, V Gholson, G Mwendwa, D Sims, R Ricks, M Callender, C Sumner, A AF Ali, Mana Keen, Larry Bygrave, Desiree Jones, Victor Gholson, Georica Mwendwa, Denee Sims, Regina Ricks, Madia Callender, Clive Sumner, Anne TI CHRONIC KIDNEY DISEASE RISK IN AFRICAN IMMIGRANTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Ali, Mana; Keen, Larry; Bygrave, Desiree; Jones, Victor; Gholson, Georica; Mwendwa, Denee] Howard Univ, Washington, DC 20059 USA. [Sims, Regina] Univ Delaware, Newark, DE USA. [Ricks, Madia; Sumner, Anne] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD USA. [Callender, Clive] Howard Univ Hosp, Washington, DC USA. EM ms.manaali@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S244 EP S244 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092401036 ER PT J AU Allen, AJ McNeely, JM Waldstein, SR Evans, MK Zonderman, AB AF Allen, Allyssa J. McNeely, Jessica M. Waldstein, Shari R. Evans, Michele K. Zonderman, Alan B. TI RACIAL DIFFERENCES IN THE RELATION OF SUBJECTIVE SOCIOECONOMIC STATUS TO CARDIOVASCULAR DISEASE RISK IN THE HEALTHY AGING IN NEIGHBORHOODS OF DIVERSITY ACROSS THE LIFESPAN STUDY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Allen, Allyssa J.; McNeely, Jessica M.; Waldstein, Shari R.] UMBC, Baltimore, MD 21212 USA. [McNeely, Jessica M.; Evans, Michele K.; Zonderman, Alan B.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. EM allyssaallen@gmail.com NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S16 EP S16 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400057 ER PT J AU Bennett, GG Warner, E Glasgow, R Askew, S Emmons, KM Rosner, B Colditz, GA AF Bennett, Gary G. Warner, Erica Glasgow, Russell Askew, Sandy Emmons, Karen M. Rosner, Bernard Colditz, Graham A. TI WEIGHT LOSS AMONG SOCIOECONOMICALLY DISADVANTAGED PRIMARY CARE PATIENTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Bennett, Gary G.; Askew, Sandy] Duke Univ, Durham, NC 27608 USA. [Warner, Erica; Emmons, Karen M.; Rosner, Bernard] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Glasgow, Russell] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci,Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. EM gary.bennett@duke.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S272 EP S272 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092401145 ER PT J AU Cerully, JL Klein, WMP AF Cerully, Jennifer L. Klein, William M. P. TI USING A SELF-AFFIRMATION INTERVENTION TO DECREASE ALCOHOL CONSUMPTION SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Cerully, Jennifer L.] RAND Corp, Pittsburgh, PA 15213 USA. [Klein, William M. P.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. EM jcerully@rand.org NR 0 TC 0 Z9 0 U1 2 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S125 EP S125 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400486 ER PT J AU Chou, WYS Glasgow, R Hesse, B AF Chou, Wen-ying Sylvia Glasgow, Russell Hesse, Bradford TI FOSTERING COMMUNITY ENGAGEMENT THROUGH SOCIAL MEDIA: EXAMPLES FROM HEALTH PROMOTION PROGRAMS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Chou, Wen-ying Sylvia; Glasgow, Russell; Hesse, Bradford] NCI, Bethesda, MD 20892 USA. EM chouws@mail.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S73 EP S73 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400284 ER PT J AU Czajkowski, SM Davidson, KW Fitz-Simmons, SC Keefe, FJ Nilsen, WJ Stirratt, MJ Wiebe, DJ AF Czajkowski, Susan M. Davidson, Karina W. Fitz-Simmons, Stacey C. Keefe, Francis J. Nilsen, Wendy J. Stirratt, Michael J. Wiebe, Deborah J. TI NIH GRANT WRITING SEMINAR FOR EARLY CAREER RESEARCHERS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Czajkowski, Susan M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Davidson, Karina W.] Columbia Univ, Med Ctr, New York, NY USA. [Fitz-Simmons, Stacey C.] NIH, Ctr Sci Review, Bethesda, MD 20892 USA. [Keefe, Francis J.] Duke Univ, Durham, NC USA. [Nilsen, Wendy J.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Stirratt, Michael J.] NIMH, NIH, Bethesda, MD 20892 USA. [Wiebe, Deborah J.] UT SW Med Ctr, Dallas, TX USA. EM Czajkows@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S1 EP S1 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400002 ER PT J AU Diefenbach, MA Marcus, A Stanton, AL Raich, P Miller, SM Tran, Z Hesse, B AF Diefenbach, Michael A. Marcus, Al Stanton, Annette L. Raich, Peter Miller, Susan M. Tran, Zung Hesse, Bradford TI CANCER PATIENT AND SURVIVOR RESEARCH FROM THE CANCER INFORMATION SERVICE RESEARCH CONSORTIUM: INITIAL RESULTS FROM THREE RANDOMIZED TRIALS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Diefenbach, Michael A.] Mt Sinai Sch Med, New York, NY 10029 USA. [Stanton, Annette L.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Marcus, Al; Raich, Peter; Tran, Zung] U CO Ca Ctr, Aurora, CO USA. [Miller, Susan M.] Fox Chase Ca Ctr, Philadelphia, PA USA. [Hesse, Bradford] NCI, Bethesda, MD 20892 USA. EM michael.diefenbach@mountsinai.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S64 EP S64 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400248 ER PT J AU Driscoll, M Davis, M Aiken, L Nelson, L AF Driscoll, Mary Davis, Mary Aiken, Leona Nelson, Lawrence TI DISTINCT COPING PATTERNS: IMPLICATIONS FOR ADAPTATION IN INFERTILITY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Driscoll, Mary; Davis, Mary; Aiken, Leona] Arizona State Univ, Tempe, AZ USA. [Nelson, Lawrence] NIMH, Bethesda, MD 20892 USA. [Driscoll, Mary] VA CT Healthcare Syst, West Haven, CT USA. EM mary.a.driscoll@asu.edu NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S115 EP S115 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400445 ER PT J AU Duffecy, J Begale, M Mohr, DC Riley, W AF Duffecy, Jennifer Begale, Mark Mohr, David C. Riley, William TI GOING DIGITAL: BUILDING EVIDENCE BASED EHEALTH AND MHEALTH INTERVENTIONS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Duffecy, Jennifer; Begale, Mark; Mohr, David C.] Northwestern Univ, Ctr Behav Intervent Technol, Chicago, IL 60611 USA. [Riley, William] NHLBI, Bethesda, MD 20892 USA. EM jduffecy@hotmail.com NR 0 TC 0 Z9 0 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S4 EP S4 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400011 ER PT J AU Medina-Mora, ME Buenabad, NA Pentz, MA Sevilla, CA Baler, R Lloyd, J AF Elena Medina-Mora, Maria Amador Buenabad, Nancy Ann Pentz, Mary Sevilla, Celina A. Baler, Ruben Lloyd, Jacqueline TI THE MEXICO AMBAR MUSEUM INITIATIVE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Elena Medina-Mora, Maria; Amador Buenabad, Nancy] Inst Natl Psiquiatria Ramon Fuente, Delegac Tlalpan, Mexico. [Ann Pentz, Mary] Univ So Calif, Inst Hlth Promot & Dis Prevent Res, Los Angeles, CA 90032 USA. [Sevilla, Celina A.] Ctr Nacl Prevenc & Control Adicciones, Subsecretaria Prevenc Promoc Salud, Mexico City, DF, Mexico. [Lloyd, Jacqueline] NIDA, NIH, Bethesda, MD 20892 USA. EM pentz@usc.edu 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S67 EP S67 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400260 ER PT J AU Forsythe, L Alfano, CM George, SM McTiernan, A Baumgartner, KB Bernstein, L Ballard-Barbash, R AF Forsythe, Laura Alfano, Catherine M. George, Stephanie M. McTiernan, Anne Baumgartner, Kathy B. Bernstein, Leslie Ballard-Barbash, Rachel TI PAIN IN LONG-TERM BREAST CANCER SURVIVORS: THE EFFECT OF BODY MASS INDEX SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Forsythe, Laura; Alfano, Catherine M.; George, Stephanie M.; Ballard-Barbash, Rachel] NCI, Bethesda, MD 20892 USA. [McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Baumgartner, Kathy B.] Univ Louisville, Louisville, KY 40292 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Duarte, CA 91010 USA. EM laura.forsythe@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S75 EP S75 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400288 ER PT J AU Goergen, A Wilkinson, AV Koehly, LM AF Goergen, Andrea Wilkinson, Anna V. Koehly, Laura M. TI BARRIERS TO FHH KNOWLEDGE WITHIN IMMIGRANT FAMILIES OF MEXICAN ORIGIN IN PROJECT RAMA SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Goergen, Andrea; Koehly, Laura M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Wilkinson, Anna V.] Univ Texas Austin, Div Epidemiol Human Genet & Environm Sci, Sch Publ Hlth Austin, Austin, TX 78712 USA. EM girouxag@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S117 EP S117 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400455 ER PT J AU Hamilton, JG Han, PKJ Hutson, SP Rife, SC Kobrin, SC Moser, RP Alter, BP AF Hamilton, Jada G. Han, Paul K. J. Hutson, Sadie P. Rife, Sean C. Kobrin, Sarah C. Moser, Richard P. Alter, Blanche P. TI RESPONSES TO MEDICAL AMBIGUITY ARE NOT UNIVERSAL: THE MODERATING ROLE OF NEED FOR COGNITIVE CLOSURE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hamilton, Jada G.] NCI, Canc Prevent Fellowship Program, Rockville, MD 20892 USA. [Hamilton, Jada G.; Kobrin, Sarah C.] NCI, Proc Care Res Branch, DCCPS, Rockville, MD 20892 USA. [Han, Paul K. J.] Maine Med Ctr, Ctr Outcomes Res & Evaluat, Scarborough, ME USA. [Hutson, Sadie P.] Univ Tennessee, Coll Nursing, Knoxville, TN USA. [Hutson, Sadie P.; Alter, Blanche P.] NCI, Clin Genet Branch, DCEG, Rockville, MD 20892 USA. [Rife, Sean C.] Kent State Univ, Dept Psychol, Kent, OH 44242 USA. [Moser, Richard P.] NCI, Sci Res & Technol Branch, DCCPS, Rockville, MD 20892 USA. EM hamiltonjg@mail.nih.gov 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S167 EP S167 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400647 ER PT J AU Kaufman, A Kennedy, CE Moore, PJ AF Kaufman, Annette Kennedy, Caitlin E. Moore, Philip J. TI IMPLICIT THEORIES OF HEALTH: PEOPLE WHO SMOKE (PROBABLY WON'T) QUIT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kaufman, Annette] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Kennedy, Caitlin E.; Moore, Philip J.] George Washington Univ, Washington, DC USA. EM kaufmana@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S144 EP S144 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400558 ER PT J AU Kent, EE Alfano, CM Smith, AW McTiernan, A Bernstein, L Baumgartner, KB Ballard-Barbash, R AF Kent, Erin E. Alfano, Catherine M. Smith, Ashley Wilder McTiernan, Anne Bernstein, Leslie Baumgartner, Kathy B. Ballard-Barbash, Rachel TI THE RELATIONSHIPS BETWEEN SEEKING SUPPORT FROM HEALTHCARE PROVIDERS AND GROUPS, RACE/ETHNICITY, AND POSTTRAUMATIC GROWTH IN A DIVERSE POPULATION OF BREAST CANCER SURVIVORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kent, Erin E.; Alfano, Catherine M.] NCI, Div Canc Control & Populat Sci, Off Canc Survivorship, Rockville, MD 20892 USA. [Smith, Ashley Wilder] NCI, Div Canc Control & Populat Sci, Outcomes Res Branch, Appl Res Program, Rockville, MD 20892 USA. [McTiernan, Anne] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Hlth Sci, Seattle, WA 98195 USA. [McTiernan, Anne] Univ Washington, Sch Med, Seattle, WA 98195 USA. [McTiernan, Anne] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Dept Canc Etiol, Duarte, CA 91010 USA. [Baumgartner, Kathy B.] Univ Louisville, Dept Epidemiol & Clin Informat Sci, Louisville, KY USA. [Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. EM Erin.Kent@nih.gov NR 0 TC 0 Z9 0 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S9 EP S9 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400028 ER PT J AU King, DK Toobert, DJ Dickman, JM Strycker, LA Doty, A Martin, C Boggs, J Faber, A Geno, C Glasgow, RE AF King, Diane K. Toobert, Deborah J. Dickman, Jennifer M. Strycker, Lisa A. Doty, Alyssa Martin, Carmen Boggs, Jennifer Faber, Andrew Geno, Cristy Glasgow, Russell E. TI WHAT PATIENTS WANT: RELEVANT HEALTH INFORMATION TECHNOLOGY FOR DIABETES SELF-MANAGEMENT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [King, Diane K.] Univ Alaska, Ctr Behav Hlth Res & Serv, Anchorage, AK 99508 USA. [Toobert, Deborah J.; Strycker, Lisa A.] Oregon Res Inst, Eugene, OR 97403 USA. [Dickman, Jennifer M.; Doty, Alyssa; Martin, Carmen; Boggs, Jennifer; Faber, Andrew; Geno, Cristy] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Glasgow, Russell E.] NCI, Rockville, MD USA. EM dkking@uaa.alaska.edu NR 0 TC 0 Z9 0 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S99 EP S99 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400382 ER PT J AU Kisser, J Sprung, MR Waldstein, SR Evans, MK Zonderman, AB AF Kisser, Jason Sprung, Mollie R. Waldstein, Shari R. Evans, Michele K. Zonderman, Alan B. TI PERCEIVED SOCIAL SUPPORT IS ASSOCIATED WITH POORER COGNITIVE PERFORMANCE IN AFRICAN-AMERICAN MEN SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kisser, Jason; Sprung, Mollie R.; Waldstein, Shari R.] UMBC, Baltimore, MD 21250 USA. [Evans, Michele K.; Zonderman, Alan B.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. EM jason.kisser@gmail.com 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S23 EP S23 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400086 ER PT J AU Mustian, K Alfano, C Piper, B Smith, T Sprod, L Scarpato, J Leach, C Peppone, L Palesh, O Jing, L Mohr, D Spring, B Berendsen, M Heckler, C Miller, S AF Mustian, Karen Alfano, C. Piper, B. Smith, T. Sprod, L. Scarpato, J. Leach, C. Peppone, L. Palesh, O. Jing, L. Mohr, D. Spring, B. Berendsen, M. Heckler, C. Miller, S. TI A META-ANALYTIC COMPARISON OF EXERCISE, PSYCHOLOGICAL, EXERCISE COMBINED WITH PSYCHOLOGICAL AND PHARMACEUTICAL INTERVENTIONS FOR CANCER-RELATED FATIGUE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Mustian, Karen; Sprod, L.; Peppone, L.; Heckler, C.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Scarpato, J.; Miller, S.] FCCC, Philadelphia, PA USA. [Alfano, C.] NCI, Bethesda, MD 20892 USA. [Smith, T.; Leach, C.] ACS, Atlanta, GA USA. [Jing, L.; Mohr, D.; Spring, B.; Berendsen, M.] Northwestern, Chicago, IL USA. [Palesh, O.] Standford, Palo Alto, CA USA. [Piper, B.] Univ Arizona, Scottsdale, AZ USA. EM karen_mustian@urmc.rochester.edu NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S54 EP S54 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400207 ER PT J AU Nansel, TR Iannotti, RJ Liu, AY AF Nansel, Tonja R. Iannotti, Ronald J. Liu, Aiyi TI CLINIC-INTEGRATED BEHAVIORAL INTERVENTION FOR FAMILIES OF YOUTH WITH TYPE 1 DIABETES: EFFECTS ON GLYCEMIC AND FAMILY MANAGEMENT OUTCOMES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Nansel, Tonja R.; Iannotti, Ronald J.; Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. EM nanselt@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S81 EP S81 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400313 ER PT J AU Naveed, S Kerr, J Norman, GJ Adams, MA Morgan, CG Langer, RD Macera, CA Alcaraz, JE Sallis, JF Allison, MA AF Naveed, Sana Kerr, Jacqueline Norman, Gregory J. Adams, Marc A. Morgan, Cindy G. Langer, Robert D. Macera, Caroline A. Alcaraz, John E. Sallis, James F. Allison, Matthew A. TI NEIGHBORHOOD FOOD ENVIRONMENTS AND INCIDENT MYOCARDIAL INFARCTION IN POST MENOPAUSAL WOMEN SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Naveed, Sana] NCI, Div Canc Control & Populat Sci, NIH, Rockville, MD 20852 USA. [Kerr, Jacqueline; Norman, Gregory J.; Adams, Marc A.; Morgan, Cindy G.; Langer, Robert D.] Univ Calif San Diego, San Diego, CA 92103 USA. [Macera, Caroline A.; Alcaraz, John E.] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. [Sallis, James F.; Allison, Matthew A.] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA. EM naveeds@mail.nih.gov RI Adams, Marc/C-3513-2013 OI Adams, Marc/0000-0001-6310-1472 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S97 EP S97 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400372 ER PT J AU Nilsen, W AF Nilsen, Wendy TI NIH ADHERENCE RESEARCH NETWORK: FUNDING OPPORTUNITIES IN ADHERENCE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Nilsen, Wendy] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. EM nilsenwj@od.nih.gov 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S145 EP S145 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400562 ER PT J AU Nilsen, W AF Nilsen, Wendy TI HEALTH BRANDING: MARKETING AND BRANDING TECHNIQUES IN HEALTH BEHAVIOR CHANGE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Nilsen, Wendy] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. EM nilsenwj@od.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S142 EP S142 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400551 ER PT J AU Patrick, H Canevello, A Williams, GC AF Patrick, Heather Canevello, Amy Williams, Geoffrey C. TI TESTING THE TENETS OF SELF-DETERMINATION THEORY IN THE DIGITAL WORLD TO PROMOTE PHYSICAL ACTIVITY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Patrick, Heather] NCI, Hlth Promot Res Branch, Bethesda, MD 20892 USA. [Canevello, Amy] Univ N Carolina, Charlotte, NC 28223 USA. [Williams, Geoffrey C.] Univ Rochester, Rochester, NY USA. EM patrickha@mail.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S143 EP S143 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400557 ER PT J AU Patrick, H AF Patrick, Heather TI PERSONALITY AND SOCIAL CONTEXT: MOTIVATIONAL PERSPECTIVES ON HEALTH BEHAVIOR SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Patrick, Heather] NCI, Hlth Behav Res Branch, Bethesda, MD 20892 USA. EM patrickha@mail.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S143 EP S143 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400556 ER PT J AU Pinard, C Finney-Rutten, L Nebeling, L Yaroch, A AF Pinard, Courtney Finney-Rutten, Lila Nebeling, Linda Yaroch, Amy TI EXPLORATION OF GROCERY SHOPPING BEHAVIORS AND SOCIODEMOGRAPHIC FACTORS ASSOCIATED WITH VENUE OF MEAL CONSUMPTION: RESULTS FROM THE NATIONAL CANCER INSTITUTE'S FOOD ATTITUDES AND BEHAVIORS (FAB) SURVEY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Pinard, Courtney; Finney-Rutten, Lila; Yaroch, Amy] Gretchen Swanson Ctr Nutr, Omaha, NE 68105 USA. [Finney-Rutten, Lila] SAIC Inc Frederick, NCI, Frederick, MD 21701 USA. [Nebeling, Linda] NCI, Bethesda, MD 20892 USA. EM cpinard@centerfornutrition.org NR 0 TC 0 Z9 0 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S110 EP S110 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400427 ER PT J AU Portnoy, DB AF Portnoy, David B. TI HOW INFORMATIONAL GOALS AND UNCERTAINTY AFFECT HEALTH DECISION MAKING: OVERVIEW AND RECENT FINDINGS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Portnoy, David B.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Portnoy, David B.] NCI, Behav Res Program, Bethesda, MD 20892 USA. EM portnoydb@mail.nih.gov 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S166 EP S166 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400645 ER PT J AU Prados, S Skeath, P Berger, A Katheria, V AF Prados, Sheila Skeath, Perry Berger, Ann Katheria, Vani TI EXPLORING THE PSYCHO-SOCIO-SPIRITUAL RESPONSES OF CANCER PATIENTS AND SURVIVORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Skeath, Perry; Berger, Ann] NIH, Pain & Palliat Care Serv, Bethesda, MD 20892 USA. [Prados, Sheila] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. [Katheria, Vani] Georgetown Univ, Washington, DC USA. EM pradossm@cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S6 EP S6 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400019 ER PT J AU Prestin, A Chou, WYS AF Prestin, Abby Chou, Wen-Ying Sylvia TI THE DESIGN AND EVALUATION OF A MEDIA-BASED COPING INTERVENTION SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Prestin, Abby; Chou, Wen-Ying Sylvia] NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20852 USA. [Prestin, Abby] Univ Calif Santa Barbara, Goleta, CA USA. EM abigail.prestin@nih.gov 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S49 EP S49 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400191 ER PT J AU Robertson, LB Schoen, RE Zimmerman, RK Terry, M Silverman, M Cooper, KL Dzubinski, L Land, SR Bovbjerg, DH AF Robertson, Linda B. Schoen, Robert E. Zimmerman, Richard K. Terry, Martha Silverman, Myrna Cooper, Kristine L. Dzubinski, Lynda Land, Stephanie R. Bovbjerg, Dana H. TI EXPLORATION OF DECISION MAKING PROCESSES OF INDIVIDUALS REGARDING A PREVENTATIVE VACCINE FOR COLORECTAL CANCER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Zimmerman, Richard K.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15232 USA. [Land, Stephanie R.] NCI, Behav Res Program, Bethesda, MD 20892 USA. EM robertsonlk@upmc.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S8 EP S8 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400027 ER PT J AU Shah, M Waldstein, SR Zonderman, AB AF Shah, Mauli Waldstein, Shari R. Zonderman, Alan B. TI NONLINEAR LONGITUDINAL ASSOCIATIONS OF SLEEP DURATION WITH BLOOD PRESSURE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Shah, Mauli; Waldstein, Shari R.] Univ Maryland, Baltimore, MD 21250 USA. [Shah, Mauli; Zonderman, Alan B.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM maulishah@umbc.edu NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S209 EP S209 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400812 ER PT J AU Smith, TM Pinard, CA Oh, A Yaroch, AL AF Smith, Teresa M. Pinard, Courtney A. Oh, April Yaroch, Amy L. TI PSYCHOSOCIAL CORRELATES OF PHYSICAL ACTIVITY IN ADOLESCENTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Smith, Teresa M.; Pinard, Courtney A.; Yaroch, Amy L.] Gretchen Swanson Ctr Nutr, Omaha, NE USA. [Smith, Teresa M.; Pinard, Courtney A.; Yaroch, Amy L.] Univ Nebraska Med Ctr, Omaha, NE 68198 USA. [Oh, April] NCI, SAIC Inc Frederick, Frederick, MD 21701 USA. EM tgrosser@unmc.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S274 EP S274 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092401152 ER PT J AU Sprung, MR Kisser, J Waldstein, SR Evans, MK Zonderman, AB AF Sprung, Mollie R. Kisser, Jason Waldstein, Shari R. Evans, Michele K. Zonderman, Alan B. TI PERCEIVED SOCIAL SUPPORT IS ASSOCIATED DIFFERENTIALLY WITH CARDIOVASCULAR RISK FACTORS IN AFRICAN AMERICAN AND WHITE MEN AND WOMEN SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Sprung, Mollie R.; Kisser, Jason; Waldstein, Shari R.] Univ Maryland Baltimore Cty, Baltimore, MD 21250 USA. [Evans, Michele K.; Zonderman, Alan B.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. EM mollie.sprung@gmail.com NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S17 EP S17 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400060 ER PT J AU Stover, AM Reeve, B Piper, B Alfano, C Bernstein, L Baumgartner, KB McTiernan, A Ballard-Barbash, R AF Stover, Angela M. Reeve, Bryce Piper, Barbara Alfano, Catherine Bernstein, Leslie Baumgartner, Katherine B. McTiernan, Anne Ballard-Barbash, Rachel TI THE PIPER FATIGUE SCALE-SHORT FORM (PFS-SF): PSYCHOMETRIC FINDINGS AND ITEM REDUCTION IN A COHORT OF BREAST CANCER SURVIVORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Stover, Angela M.; Reeve, Bryce] Univ N Carolina, Chapel Hill, NC 27514 USA. [Piper, Barbara] Univ Arizona, Tucson, AZ USA. [Alfano, Catherine; Ballard-Barbash, Rachel] NCI, Bethesda, MD 20892 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Baumgartner, Katherine B.] Univ Louisville, Louisville, KY 40292 USA. [McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. EM stoveram@email.unc.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S92 EP S92 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400354 ER PT J AU von Wagner, C Klein, W AF von Wagner, Christian Klein, William TI INFORMATION PROCESSING AND DECISION MAKING ABOUT CANCER SCREENING: CHALLENGES AND OPPORTUNITIES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [von Wagner, Christian] UCL, London WC1E 6BT, England. [Klein, William] NCI, Bethesda, MD USA. [Klein, William] Univ Pittsburgh, Pittsburgh, PA USA. EM c.wagner@ucl.ac.uk 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S135 EP S135 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400523 ER PT J AU Wallen, GR Middleton, KR Velummylum, S Miller-Davis, C Koratich, C Krumlauf, K Handel, D AF Wallen, Gwenyth R. Middleton, K. R. Velummylum, S. Miller-Davis, C. Koratich, C. Krumlauf, K. Handel, D. TI CLINICAL HYPNOSIS: A STRATEGY TO MODIFY PAIN IMPACT AND DEPRESSION IN SICKLE CELL PATIENTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Wallen, Gwenyth R.; Middleton, K. R.; Velummylum, S.; Miller-Davis, C.; Koratich, C.; Krumlauf, K.; Handel, D.] NIH, Ctr Clin, Olney, MD 20832 USA. EM gwallen@cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S266 EP S266 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092401120 ER PT J AU Waters, EA Kincaid, CS Stock, ML Peterson, L Kaufman, AR Muscanell, NL Guadagno, RE AF Waters, Erika A. Kincaid, Caroline S. Stock, Michelle L. Peterson, Laurel Kaufman, Annette R. Muscanell, Nicole L. Guadagno, Rosanna E. TI LIMITATIONS OF USING MULTIFACTORIAL GENETIC RISK INFORMATION TO EDUCATE SMOKERS ABOUT THE RISK OF TOBACCO USE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Waters, Erika A.; Kincaid, Caroline S.] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO 63110 USA. [Stock, Michelle L.; Peterson, Laurel] George Washington Univ, Washington, DC USA. [Kaufman, Annette R.] Univ Alabama, Tuscaloosa, AL USA. [Muscanell, Nicole L.; Guadagno, Rosanna E.] NCI, Behav Res Program, Rockville, MD USA. EM waterse@wudosis.wustl.edu 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S126 EP S126 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400488 ER PT J AU Weaver, K Alfano, C Foraker, R Arora, N Bellizzi, K Rowland, J AF Weaver, Kathryn Alfano, Catherine Foraker, Randi Arora, Neeraj Bellizzi, Keith Rowland, Julia TI ARE BEHAVIORAL RISK FACTORS FOR CVD ADDRESSED AMONG LONG-TERM CANCER SURVIVORS? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Weaver, Kathryn] Wake Forest Univ, Sch Med, Winston Salem, NC 27157 USA. [Alfano, Catherine; Arora, Neeraj; Rowland, Julia] NCI, Bethesda, MD 20892 USA. [Foraker, Randi] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA. [Bellizzi, Keith] Univ Connecticut, Storrs, CT USA. EM keweaver@wfubmc.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 SU 1 BP S7 EP S7 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 916HQ UT WOS:000302092400024 ER PT J AU Miller, FW AF Miller, Frederick W. TI New approaches to the assessment and treatment of the idiopathic inflammatory myopathies SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID INCLUSION-BODY MYOSITIS; JUVENILE DERMATOMYOSITIS; INTERNATIONAL CONSENSUS; REFRACTORY POLYMYOSITIS; MYCOPHENOLATE-MOFETIL; ADULT; THERAPY; DISEASE; PATHOGENESIS; RITUXIMAB AB The rarity and heterogeneity of the idiopathic inflammatory myopathies (IIM), and the few validated assessment tools available, have limited information to guide the management of patients with polymyositis, dermatomyositis or inclusion body myositis. In light of the need for such tools, the International Myositis Assessment and Clinical Studies Group (IMACS) was formed as a multidisciplinary consortium of rheumatologists, neurologists, dermatologists, physiatrists and other myositis experts to develop consensus and standards for the conduct and reporting of myositis studies, and to facilitate myositis research. IMACS has developed consensus core set measures of disease activity, disease damage and patient-reported outcomes, and compiled a preliminary definition of improvement. The IMACS tools assist in the evaluation of the extent of disease activity and damage, although other approaches-including key clinical features, laboratory tests, muscle T1 and short tau inversion recovery MRI and immunological markers-are also helpful. Clinical remission is a realistic objective for most patients and should be pursued aggressively to optimise outcomes. Physical therapy and rehabilitation should be applied early and consistently to achieve optimal strength and function. Treatments that have been developed for other immune-mediated diseases are also being used and tested in the IIM, and some have shown anecdotal evidence of benefit. Recent advances in understanding the pathogenesis of myositis, development of assessments and treatments for other diseases that can be applied to myositis, and international collaborations and consensus standards for evaluating the IIM, all promise improvements in the assessment and treatment of myositis in the future. C1 NIEHS, Environm Autoimmun Grp, Program Clin Res, NIH,Clin Res Ctr, Bethesda, MD 20892 USA. RP Miller, FW (reprint author), NIEHS, Environm Autoimmun Grp, Program Clin Res, NIH,Clin Res Ctr, NIH 10,Room 4-2352,10 Ctr Dr,MSC 1301, Bethesda, MD 20892 USA. EM millerf@mail.nih.gov OI Miller, Frederick/0000-0003-2831-9593 FU Office of Rare Diseases, NIH; Myositis Association; UK Myositis Support Group; American College of Rheumatology; NIH, National Institute of Environmental Health Sciences FX The IMACS project has been supported in part by the Office of Rare Diseases, NIH; the Myositis Association; the UK Myositis Support Group and the American College of Rheumatology. This research was also supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 39 TC 24 Z9 24 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD APR PY 2012 VL 71 SU 2 BP 82 EP 85 DI 10.1136/annrheumdis-2011-200587 PG 4 WC Rheumatology SC Rheumatology GA 917ME UT WOS:000302180400010 ER PT J AU Sanchez, C Pesesse, L Gabay, O Delcour, JP Msika, P Baudouin, C Henrotin, YE AF Sanchez, Christelle Pesesse, Laurence Gabay, Odile Delcour, Jean-Pierre Msika, Philippe Baudouin, Caroline Henrotin, Yves E. TI Regulation of Subchondral Bone Osteoblast Metabolism by Cyclic Compression SO ARTHRITIS AND RHEUMATISM LA English DT Article ID DEGENERATIVE JOINT DISEASE; ENDOTHELIAL GROWTH-FACTOR; PROSTAGLANDIN E-2; CYNOMOLGUS MACAQUES; OSTEOARTHRITIC BONE; PARATHYROID-HORMONE; MECHANICAL-STRESS; IN-VITRO; CELLS; EXPRESSION AB Objective. Recent data have shown that abnormal subchondral bone remodeling plays an important role in osteoarthritis (OA) onset and progression, and it was suggested that abnormal mechanical pressure applied to the articulation was responsible for these metabolic changes. This study was undertaken to evaluate the effects of cyclic compression on osteoblasts from OA subchondral bone. Methods. Osteoblasts were isolated from sclerotic and nonsclerotic areas of human OA subchondral bone. After 28 days, the osteoblasts were surrounded by an abundant extracellular matrix and formed a resistant membrane, which was submitted to cyclic compression (1 MPa at 1 Hz) for 4 hours. Gene expression was evaluated by reverse transcription-polymerase chain reaction. Protein production in culture supernatants was quantified by enzyme-linked immunosorbent assay or visualized by immunohistochemistry. Results. Compression increased the expression of genes coding for interleukin-6 (IL-6), cyclooxygenase 2, RANKL, fibroblast growth factor 2, IL-8, matrix metalloproteinase 3 (MMP-3), MMP-9, and MMP-13 but reduced the expression of osteoprotegerin in osteoblasts in both sclerotic and nonsclerotic areas. Col alpha 1(I) and MMP-2 were not significantly affected by mechanical stimuli. Nonsclerotic osteoblasts were significantly more sensitive to compression than sclerotic ones, but after compression, differences in messenger RNA levels between nonsclerotic and sclerotic osteoblasts were largely reduced or even abolished. Under basal conditions, sclerotic osteoblasts expressed similar levels of alpha 5, alpha v, beta 1, and beta 3 integrins and CD44 as nonsclerotic osteoblasts but 30% less connexin 43, an important mechanoreceptor. Conclusion. Genes involved in subchondral bone sclerosis are mechanosensitive. After compression, nonsclerotic and sclerotic osteoblasts expressed a similar phenotype, suggesting that compression could be responsible for the phenotype changes in OA subchondral osteoblasts. C1 [Sanchez, Christelle; Pesesse, Laurence; Henrotin, Yves E.] Univ Liege, Liege, Belgium. [Gabay, Odile] NIAMSD, NIH, Bethesda, MD 20892 USA. [Delcour, Jean-Pierre] Ctr Hosp Bois de Abbaye, Seraing, Belgium. [Msika, Philippe; Baudouin, Caroline] Labs Expansci, Epernon, France. RP Henrotin, YE (reprint author), Inst Pathol, Bone & Cartilage Res Unit, CHU Bat B23, B-4000 Liege, Belgium. EM yhenrotin@ulg.ac.be FU National Institute of Arthritis and Musculoskeletal Diseases, NIH; FNRS FX Supported in part by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal Diseases, NIH. Dr. Sanchez is a postdoctoral researcher at the FNRS; her work was supported by a postdoctoral research grant from the FNRS. NR 49 TC 29 Z9 29 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD APR PY 2012 VL 64 IS 4 BP 1193 EP 1203 DI 10.1002/art.33445 PG 11 WC Rheumatology SC Rheumatology GA 921KC UT WOS:000302475500030 PM 22034083 ER PT J AU Pang, T Wang, J Benicky, J Saavedra, JM AF Pang, Tao Wang, Juan Benicky, Julius Saavedra, Juan M. TI Minocycline ameliorates LPS-induced inflammation in human monocytes by novel mechanisms including LOX-1, Nur77 and LITAF inhibition SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE Minocycline; Lipopolysaccharide; Nuclear receptor; LITAF; Inflammation; Human monocytes ID NUCLEAR RECEPTOR NUR77; INNATE IMMUNE-RESPONSE; TNF-ALPHA FACTOR; NF-KAPPA-B; SIGNALING PATHWAYS; PI3K-AKT PATHWAY; INDUCED CYTOKINE; GENE-EXPRESSION; CELL-CULTURES; OXIDIZED LDL AB Background: Minocycline exhibits anti-inflammatory properties independent of its antibiotic activity, ameliorating inflammatory responses in monocytes and macrophages. However, the mechanisms of minocycline anti-inflammatory effects are only partially understood. Methods: Human circulating monocytes were cultured in the presence of lipopolysaccharide (LPS), 50 ng/ml, and minocycline (10-40 mu M). Gene expression was determined by RT-PCR, cytokine and prostaglandin E-2 (PGE(2)) release by ELISA, protein expression, phosphorylation and nuclear translocation by Western blotting. Results: Minocycline significantly reduced the inflammatory response in LPS-challenged monocytes, decreasing U'S-induced transcription of pro-inflammatory tumor-necrosis factor alpha (TNF-alpha), interleukin-1 beta, interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2), and the LPS-stimulated TNF-alpha, IL-6 and PGE(2) release. Minocycline inhibited LPS-induced activation of the lectin-like oxidized low density lipoprotein receptor-1 (LOX-1), NF-kappa B, LPS-induced TNF-alpha factor (LITAF) and the Nur77 nuclear receptor. Mechanisms involved in the anti-inflammatory effects of minocycline include a reduction of LPS-stimulated p38 mitogen-activated protein kinase (p38 MAPK) activation and stimulation of the phosphoinositide 3-kinase (PI3K)/Ala pathway. Conclusions: We provide novel evidence demonstrating that the anti-inflammatory effects of minocycline in human monocytes include, in addition to decreased NF-kappa B activation, abrogation of the U'S-stimulated LOX-1, LITAF, Nur77 pathways, p38 MAPK inhibition and PI3K/Akt activation. Our results reveal that minocycline inhibits points of convergence of distinct and interacting signaling pathways mediating multiple inflammatory signals which may influence monocyte activation, traffic and recruitment into the brain. General significance: Our results in primary human monocytes contribute to explain the profound anti-inflammatory and protective effects of minocycline in cardiovascular and neurological diseases and may have direct translational relevance. Published by Elsevier B.V. C1 [Pang, Tao; Wang, Juan; Benicky, Julius; Saavedra, Juan M.] NIMH, Pharmacol Sect, DIRP, NIH,DHHS, Bethesda, MD 20892 USA. RP Pang, T (reprint author), NIMH, Pharmacol Sect, DIRP, NIH,DHHS, 10 Ctr Dr,Bldg 10,Room 20-57, Bethesda, MD 20892 USA. EM pangt@mail.nih.gov FU National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, USA FX This study was supported by the Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, USA. NR 43 TC 24 Z9 26 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD APR PY 2012 VL 1820 IS 4 BP 503 EP 510 DI 10.1016/j.bbagen.2012.01.011 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 921OK UT WOS:000302486700007 PM 22306153 ER PT J AU Huang, JD Amaral, J Lee, JW Larrayoz, IM Rodriguez, IR AF Huang, Jiahn-Dar Amaral, Juan Lee, Jung Wha Larrayoz, Ignacio M. Rodriguez, Ignacio R. TI Sterculic acid antagonizes 7-ketocholesterol-mediated inflammation and inhibits choroidal neovascularization SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Article DE ER stress; 7-ketocholesterol; Inflammation; Sterculic acid; CHOP; RPE ID LOW-DENSITY-LIPOPROTEIN; MACULAR DEGENERATION; CYTOTOXICITY; CHOLESTEROL; OXIDATION; PRODUCTS; CELLS AB Sterculic acid is a cyclopropene fatty acid with numerous biological activities. In this study we demonstrate that sterculic acid is a potent inhibitor of endoplasmic reticulum (ER) stress and related inflammation caused by 7-ketocholesterol (7KCh). 7KCh is a highly toxic oxysterol suspected in the pathogenesis of various age-related diseases such as atherosclerosis, Alzheimer's disease and age-related macular degeneration. Sterculic acid demonstrated to be 5-10 times more effective than other anti-inflammatory fatty acids at inhibiting 7KCh-mediated inflammatory responses in cultured cells. In vivo, sterculic acid was effective at inhibiting the formation of choroidal neovascularization (CNV) in the laser-injury rat model. Our data suggests that sterculic acid may be useful in treating CNV in certain forms of age-related macular degeneration. Published by Elsevier B.V. C1 [Huang, Jiahn-Dar; Amaral, Juan; Lee, Jung Wha; Larrayoz, Ignacio M.; Rodriguez, Ignacio R.] NEI, NIH, Sect Mech Retinal Dis, LRCMB, Bethesda, MD 20892 USA. [Larrayoz, Ignacio M.] Ctr Biomed Res La Rioja CIBIR, Angiogenesis Unit, La Rioja, Spain. RP Rodriguez, IR (reprint author), NEI, NIH, Sect Mech Retinal Dis, LRCMB, 6 Ctr Dr,MSC0608,Bldg 6 Rm 136, Bethesda, MD 20892 USA. EM rodriguezi@nei.nih.gov RI Larrayoz, Ignacio/I-5613-2012 OI Larrayoz, Ignacio/0000-0003-1629-152X FU National Eye Institute FX The authors would like to thank Dr. Maria Campos at the NEI's Biological Imaging Core facility for her assistance in imaging of the laser lesions. This work is supported by National Eye Institute Intramural Research Program. NR 44 TC 12 Z9 12 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD APR PY 2012 VL 1821 IS 4 BP 637 EP 646 DI 10.1016/j.bbalip.2012.01.013 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 921OI UT WOS:000302486500009 PM 22342272 ER PT J AU Aghaeepour, N Chattopadhyay, PK Ganesan, A O'Neill, K Zare, H Jalali, A Hoos, HH Roederer, M Brinkman, RR AF Aghaeepour, Nima Chattopadhyay, Pratip K. Ganesan, Anuradha O'Neill, Kieran Zare, Habil Jalali, Adrin Hoos, Holger H. Roederer, Mario Brinkman, Ryan R. TI Early immunologic correlates of HIV protection can be identified from computational analysis of complex multivariate T-cell flow cytometry assays(*) SO BIOINFORMATICS LA English DT Article ID ANTIRETROVIRAL THERAPY; VACCINE ENTERPRISE; MASS CYTOMETRY; SIV INFECTION; STEM-CELLS; FUTURE; TETRAMERS; RESPONSES; SURVIVAL; HAART AB Motivation: Polychromatic flow cytometry (PFC), has enormous power as a tool to dissect complex immune responses (such as those observed in HIV disease) at a single cell level. However, analysis tools are severely lacking. Although high-throughput systems allow rapid data collection from large cohorts, manual data analysis can take months. Moreover, identification of cell populations can be subjective and analysts rarely examine the entirety of the multidimensional dataset (focusing instead on a limited number of subsets, the biology of which has usually already been well-described). Thus, the value of PFC as a discovery tool is largely wasted. Results: To address this problem, we developed a computational approach that automatically reveals all possible cell subsets. From tens of thousands of subsets, those that correlate strongly with clinical outcome are selected and grouped. Within each group, markers that have minimal relevance to the biological outcome are removed, thereby distilling the complex dataset into the simplest, most clinically relevant subsets. This allows complex information from PFC studies to be translated into clinical or resource-poor settings, where multiparametric analysis is less feasible. We demonstrate the utility of this approach in a large (n=466), retrospective, 14-parameter PFC study of early HIV infection, where we identify three T-cell subsets that strongly predict progression to AIDS (only one of which was identified by an initial manual analysis). C1 [Aghaeepour, Nima; O'Neill, Kieran; Zare, Habil; Jalali, Adrin; Brinkman, Ryan R.] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. [Chattopadhyay, Pratip K.; Roederer, Mario] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Ganesan, Anuradha] Walter Reed Natl Mil Med Ctr, Rockville, MD 20889 USA. [Zare, Habil; Hoos, Holger H.] Univ British Columbia, Dept Comp Sci, Vancouver, BC V5Z 4S6, Canada. [Brinkman, Ryan R.] Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 4S6, Canada. [Aghaeepour, Nima] Univ British Columbia, CIHR MSFHR Strateg Training Bioinformat Hlth Res, Vancouver, BC V5Z 4S6, Canada. RP Brinkman, RR (reprint author), British Columbia Canc Agcy, Terry Fox Lab, 601 W 10th Ave, Vancouver, BC V5Z 1L3, Canada. EM rbrinkman@bccrc.ca RI Brinkman, Ryan/B-1108-2008; OI Brinkman, Ryan/0000-0002-9765-2990; O'Neill, Kieran/0000-0001-7609-5905; Zare, Habil/0000-0001-5902-6238; Chattopadhyay, Pratip/0000-0002-5457-9666 FU NIAID; NIH/NIBIB [EB008400]; NSERC; NIH [HSN261200800001E]; NCI; Infectious Disease Clinical Research Program; Uniformed Services University of the Health Sciences; Terry Foundation; Terry Fox Research Institute; UBC4YF; CIHR/MSFHR; Michael Smith Foundation for Health Research FX This work was supported by NIAID Intramural Research Program; NIH/NIBIB grant EB008400; an NSERC discovery grant held by HHH; NIH (contract HSN261200800001E); NCI; Infectious Disease Clinical Research Program; Uniformed Services University of the Health Sciences, The Terry Foundation and The Terry Fox Research Institute. NA was supported by a UBC4YF scholarship and a CIHR/MSFHR scholarship. RRB was supported in part by a Michael Smith Foundation for Health Research Scholar Award. This research was enabled by the use of computing resources provided by the Western Canada Research Grid (WestGrid) and Compute/Calcul Canada. NR 41 TC 36 Z9 36 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD APR 1 PY 2012 VL 28 IS 7 BP 1009 EP 1016 DI 10.1093/bioinformatics/bts082 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 919CR UT WOS:000302298900014 PM 22383736 ER PT J AU Samson, F Shrager, R Tai, CH Sam, V Lee, B Munson, PJ Gibrat, JF Garnier, J AF Samson, Franck Shrager, Richard Tai, Chin-Hsien Sam, Vichetra Lee, Byungkook Munson, Peter J. Gibrat, Jean-Francois Garnier, Jean TI DOMIRE: a web server for identifying structural domains and their neighbors in proteins SO BIOINFORMATICS LA English DT Article AB The DOMIRE web server implements a novel, automatic, protein structural domain assignment procedure based on 3D substructures of the query protein which are also found within structures of a non-redundant protein database. These common 3D substructures are transformed into a co-occurrence matrix that offers a global view of the protein domain organization. Three different algorithms are employed to define structural domain boundaries from this co-occurrence matrix. For each query, a list of structural neighbors and their alignments are provided. DOMIRE, by displaying the protein structural domain organization, can be a useful tool for defining protein common cores and for unravelling the evolutionary relationship between different proteins. C1 [Samson, Franck; Gibrat, Jean-Francois; Garnier, Jean] INRA, UR1077, Unite Math Informat & Genome, F-78350 Jouy En Josas, France. [Shrager, Richard; Sam, Vichetra; Munson, Peter J.; Garnier, Jean] NCI, Math & Stat Comp Lab, Ctr Informat Technol, NIH, Bethesda, MD 20892 USA. [Tai, Chin-Hsien; Lee, Byungkook] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Garnier, J (reprint author), INRA, UR1077, Unite Math Informat & Genome, F-78350 Jouy En Josas, France. EM jean.garnier@jouy.inra.fr FU Center for Cancer Research, National Cancer Institute; Division of Computational Bioscience, Center for Information Technology, NIH in USA; Institut National de la Recherche Agronomique in France FX Intramural Research Program of the Center for Cancer Research, National Cancer Institute and of the Division of Computational Bioscience, Center for Information Technology, NIH in USA and financially supported by the Institut National de la Recherche Agronomique in France (in part). NR 5 TC 2 Z9 2 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD APR 1 PY 2012 VL 28 IS 7 BP 1040 EP 1041 DI 10.1093/bioinformatics/bts076 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 919CR UT WOS:000302298900024 PM 22345617 ER PT J AU Xie, G Nie, T Mackenzie, GG Sun, Y Huang, L Ouyang, N Alston, N Zhu, C Murray, OT Constantinides, PP Kopelovich, L Rigas, B AF Xie, G. Nie, T. Mackenzie, G. G. Sun, Y. Huang, L. Ouyang, N. Alston, N. Zhu, C. Murray, O. T. Constantinides, P. P. Kopelovich, L. Rigas, B. TI The metabolism and pharmacokinetics of phospho-sulindac (OXT-328) and the effect of difluoromethylornithine SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE metabolism; pharmacokinetics; phospho-sulindac; difluoromethylornithine; liver microsomes; gastrointestinal toxicity ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLON-CANCER; SULFOXIDE REDUCTION; LIVER-MICROSOMES; RAT-LIVER; IN-VITRO; NSAIDS; ASPIRIN; PREVENTION; APOPTOSIS AB BACKGROUND AND PURPOSE Phospho-sulindac (PS; OXT-328) prevents colon cancer in mice, especially when combined with difluoromethylornithine (DFMO). Here, we explored its metabolism and pharmacokinetics. EXPERIMENTAL APPROACH PS metabolism was studied in cultured cells, liver microsomes and cytosol, intestinal microsomes and in mice. Pharmacokinetics and biodistribution of PS were studied in mice. KEY RESULTS PS undergoes reduction and oxidation yielding PS sulphide and PS sulphone; is hydrolysed releasing sulindac, which generates sulindac sulphide (SSide) and sulindac sulphone (SSone), all of which are glucuronidated. Liver and intestinal microsomes metabolized PS extensively but cultured cells converted only 10% of it to PS sulphide and PS sulphone. In mice, oral PS is rapidly absorbed, metabolized and distributed to the blood and other tissues. PS survives only partially intact in blood; of its three major metabolites (sulindac, SSide and SSone), sulindac has the highest Cmax and SSone the highest t1/ 2; their AUC0-24h are similar. Compared with conventional sulindac, PS generated more SSone but less SSide, which may contribute to the safety of PS. In the gastroduodenal wall of mice, 71% of PS was intact; sulindac, SSide and SSone together accounted for < 30% of the total. This finding may explain the lack of gastrointestinal toxicity by PS. DFMO had no effect on PS metabolism but significantly reduced drug level in mouse plasma and other tissues. CONCLUSIONS AND IMPLICATIONS Our findings establish the metabolism of PS define its pharmacokinetics and biodistribution, describe its interactions with DFMO and largely explain its gastrointestinal safety. C1 [Rigas, B.] SUNY Stony Brook, Canc Prevent Div, HSC, Dept Med, Stony Brook, NY 11794 USA. [Constantinides, P. P.] Medicon Pharmaceut Inc, Stony Brook, NY USA. [Kopelovich, L.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Rigas, B (reprint author), SUNY Stony Brook, Canc Prevent Div, HSC, Dept Med, T17-080, Stony Brook, NY 11794 USA. EM basil.rigas@stonybrook.edu FU National Institute of Health [R01-CA139453, N01-CN-43302, RCA153662A, HHSN261201000109C]; National Cancer Institute; NIH/NCRR [1 S10 RR023680-1] FX This work was supported by the National Institute of Health Grants R01-CA139453, N01-CN-43302 WA#7, RCA153662A and HHSN261201000109C. This research was also supported in part by the Intramural Research Program of the National Cancer Institute. We thank R. Rieger and T. Koller, Stony Brook University, for the expert LC-MS/MS analysis of our samples and the shared instrumentation grant, NIH/NCRR 1 S10 RR023680-1. NR 48 TC 12 Z9 12 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD APR PY 2012 VL 165 IS 7 BP 2152 EP 2166 DI 10.1111/j.1476-5381.2011.01705.x PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 905OJ UT WOS:000301281700015 PM 21955327 ER PT J AU DuBois, SG Shusterman, S Reid, JM Ingle, AM Ahern, CH Baruchel, S Glade-Bender, J Ivy, P Adamson, PC Blaney, SM AF DuBois, Steven G. Shusterman, Suzanne Reid, Joel M. Ingle, Ashish M. Ahern, Charlotte H. Baruchel, Sylvain Glade-Bender, Julia Ivy, Percy Adamson, Peter C. Blaney, Susan M. TI Tolerability and pharmacokinetic profile of a sunitinib powder formulation in pediatric patients with refractory solid tumors: a Children's Oncology Group study SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Sunitinib; Pediatric; Pharmacokinetics; Formulation ID TYROSINE KINASE INHIBITOR; RENAL-CELL CARCINOMA; ANTITUMOR-ACTIVITY; PHASE-I; MALATE SU11248; GROWTH-FACTOR; IMATINIB; CANCER; VIVO AB Purpose Sunitinib is an oral tyrosine kinase inhibitor of VEGF, PDGF, c-KIT, and flt-3 receptors. A pediatric phase I study of sunitinib capsules identified the maximum tolerated dose as 15 mg/m(2)/day. This study was conducted to evaluate sunitinib given as a powder formulation. Methods Sunitinib 15 mg/m(2) was administered orally daily for 4 weeks on/2 weeks off to patients <21 years old with refractory solid tumors. Sunitinib capsules were opened, and the powder sprinkled onto applesauce or yogurt. Plasma levels of sunitinib and an active metabolite, SU12662, were measured, and pharmacokinetic parameters were estimated. Results 12 patients, median age 13 (range 4-21) years, were treated. The most common first-cycle toxicities were leucopenia (n = 6), fatigue (n = 5), neutropenia (n = 4), and hypertension (n = 4). Three patients had dose-limiting toxicities (DLTs) in cycle 1 (dizziness/back pain, hand-foot syndrome, and intratumoral hemorrhage/hypoxia). A median peak plasma sunitinib concentration of 21 (range 636) ng/ml was reached at a median of 4 (range 4-8) h after the first dose. The median exposure (AUC(0-48)) was 585 (range 196-1,059) h ng/l. The median half-life was 23 (range 13-36) h. The median trough concentration measured before day 14 dosing was 32 (range 12-58) ng/ml. Conclusions The pharmacokinetic profile of sunitinib appears similar between a powder formulation and published data using capsules. The powder formulation allows patients unable to swallow capsules to receive sunitinib. C1 [DuBois, Steven G.] UCSF Sch Med, Dept Pediat, San Francisco, CA 94143 USA. [Shusterman, Suzanne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp Boston,Dept Pediat, Boston, MA 02115 USA. [Reid, Joel M.] Mayo Coll Med, Dept Pharmacol, Rochester, MN USA. [Ingle, Ashish M.] Childrens Oncol Grp Operat Ctr, Arcadia, CA USA. [Ahern, Charlotte H.] Baylor Coll Med, Div Biostat, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Baruchel, Sylvain] Hosp Sick Children, Dept Hematol Oncol, Toronto, ON M5G 1X8, Canada. [Glade-Bender, Julia] Columbia Univ, Dept Pediat, Morgan Stanley Childrens Hosp, Sch Med, New York, NY 10027 USA. [Ivy, Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Adamson, Peter C.] Univ Penn, Childrens Hosp Philadelphia, Dept Oncol, Philadelphia, PA 19104 USA. [Blaney, Susan M.] Baylor Coll Med, Dept Pediat, Texas Childrens Canc Ctr, Houston, TX 77030 USA. RP DuBois, SG (reprint author), UCSF Sch Med, Dept Pediat, 505 Parnassus Ave,M646, San Francisco, CA 94143 USA. EM duboiss@peds.ucsf.edu FU Campini Foundation; Pfizer; NIH/NCRR/OD UCSF-CTSI [KL2 RR024130]; NCI [U01 CA97452] FX This study was supported by the Campini Foundation, Pfizer, NIH/NCRR/OD UCSF-CTSI Grant Number KL2 RR024130, and NCI U01 CA97452. Pfizer provided partial support for the analyses of sunitinib pharmacokinetics. NR 18 TC 13 Z9 14 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 2012 VL 69 IS 4 BP 1021 EP 1027 DI 10.1007/s00280-011-1798-2 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 919LF UT WOS:000302327300020 PM 22179104 ER PT J AU Iyer, G Morris, MJ Rathkopf, D Slovin, SF Steers, M Larson, SM Schwartz, LH Curley, T DeLaCruz, A Ye, Q Heller, G Egorin, MJ Ivy, SP Rosen, N Scher, HI Solit, DB AF Iyer, Gopa Morris, Michael J. Rathkopf, Dana Slovin, Susan F. Steers, Macaulay Larson, Steven M. Schwartz, Lawrence H. Curley, Tracy DeLaCruz, Anthony Ye, Qing Heller, Glenn Egorin, Merrill J. Ivy, S. Percy Rosen, Neal Scher, Howard I. Solit, David B. TI A phase I trial of docetaxel and pulse-dose 17-allylamino-17-demethoxygeldanamycin in adult patients with solid tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE 17-AAG; Geldanamycin; Hsp90; Docetaxel; Phase I ID ADVANCED CANCER; HSP90 FUNCTION; BREAST-CANCER; LUNG-CANCER; 17-ALLYLAMINO; GELDANAMYCIN; PACLITAXEL; INHIBITOR; COMPLEX; 17-DEMETHOXYGELDANAMYCIN AB Purpose To define maximum tolerated dose (MTD), clinical toxicities, and pharmacokinetics of 17-allylamino-17-demethoxygeldanamycin (17-AAG) when administered in combination with docetaxel once every 21 days in patients with advanced solid tumor malignancies. Experimental design Docetaxel was administered over 1 h at doses of 55, 70, and 75 mg/m(2). 17-AAG was administered over 1-2 h, following the completion of the docetaxel infusion, at escalating doses ranging from 80 to 650 mg/m(2) in 12 patient cohorts. Serum was collected for pharmacokinetic and pharmacodynamic studies during cycle 1. Docetaxel, 17-AAG, and 17-AG levels were determined by high-performance liquid chromatography. Biologic effects of 17-AAG were monitored in peripheral blood mononuclear cells by immunoblot. Results Forty-nine patients received docetaxel and 17-AAG. The most common all-cause grade 3 and 4 toxicities were leukopenia, lymphopenia, and neutropenia. An MTD was not deWned; however, three dose-limiting toxicities were observed, including 2 incidences of neutropenic fever and 1 of junctional bradycardia. Dose escalation was halted at docetaxel 75 mg/m(2)-17-AAG 650 mg/m(2) due to delayed toxicities attributed to patient intolerance of the DMSO-based 17-AAG formulation. Of 46 evaluable patients, 1 patient with lung cancer experienced a partial response. Minor responses were observed in patients with lung, prostate, melanoma, and bladder cancers. A correlation between reduced docetaxel clearance and 17-AAG dose level was observed. Conclusions The combination of docetaxel and 17-AAG was well tolerated in adult patients with solid tumors, although patient intolerance to the DMSO formulation precluded further dose escalation. The recommended phase II dose is docetaxel 70 mg/m(2) and 17-AAG 500 mg/m(2). C1 [Iyer, Gopa; Morris, Michael J.; Rathkopf, Dana; Slovin, Susan F.; Steers, Macaulay; Curley, Tracy; DeLaCruz, Anthony; Rosen, Neal; Scher, Howard I.; Solit, David B.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Larson, Steven M.] Mem Sloan Kettering Canc Ctr, Dept Nucl Med, New York, NY 10021 USA. [Schwartz, Lawrence H.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. [Ye, Qing; Rosen, Neal] Mem Sloan Kettering Canc Ctr, Dept Mol Pharmacol & Chem, New York, NY 10021 USA. [Heller, Glenn] Mem Sloan Kettering Canc Ctr, Dept Biostat, New York, NY 10021 USA. [Egorin, Merrill J.] Univ Pittsburgh, Sch Med, Mol Therapeut Drug Discovery Program, Pittsburgh, PA USA. [Ivy, S. Percy] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Ctr, Bethesda, MD 20892 USA. RP Solit, DB (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA. EM solitd@mskcc.org OI Rathkopf, Dana/0000-0002-4503-7582; Morris, Michael J./0000-0002-9454-0096 FU National Cancer Institute [P50-CA92629, U01-CA69856] FX We would like to thank Kin Tse for his assistance with data collection and analysis. National Cancer Institute grants P50-CA92629 and U01-CA69856 and the generous support of the Prostate Cancer Foundation. NR 33 TC 18 Z9 18 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 2012 VL 69 IS 4 BP 1089 EP 1097 DI 10.1007/s00280-011-1789-3 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 919LF UT WOS:000302327300027 PM 22124669 ER PT J AU Huo, DZ Zheng, YL Ogundiran, TO Adebamowo, C Nathanson, KL Domchek, SM Rebbeck, TR Simon, MS John, EM Hennis, A Nemesure, B Wu, SY Leske, MC Ambs, S Niu, Q Zhang, J Cox, NJ Olopade, OI AF Huo, Dezheng Zheng, Yonglan Ogundiran, Temidayo O. Adebamowo, Clement Nathanson, Katherine L. Domchek, Susan M. Rebbeck, Timothy R. Simon, Michael S. John, Esther M. Hennis, Anselm Nemesure, Barbara Wu, Suh-Yuh Leske, M. Cristina Ambs, Stefan Niu, Qun Zhang, Jing Cox, Nancy J. Olopade, Olufunmilayo I. TI Evaluation of 19 susceptibility loci of breast cancer in women of African ancestry SO CARCINOGENESIS LA English DT Article ID GENOME-WIDE ASSOCIATION; AMERICAN WOMEN; CONFER SUSCEPTIBILITY; POPULATION-STRUCTURE; COMMON VARIANTS; GENOTYPE DATA; RISK; FGFR2; ESTROGEN; POLYMORPHISMS AB Multiple breast cancer susceptibility loci have been identified in genome-wide association studies (GWAS) in populations of European and Asian ancestry using array chips optimized for populations of European ancestry. It is important to examine whether these loci are associated with breast cancer risk in women of African ancestry. We evaluated 25 single nucleotide polymorphisms (SNPs) at 19 loci in a pooled case-control study of breast cancer, which included 1509 cases and 1383 controls. Cases and controls were enrolled in Nigeria, Barbados and the USA; all women were of African ancestry. We found significant associations for three SNPs, which were in the same direction and of similar magnitude as those reported in previous fine-mapping studies in women of African ancestry. The allelic odds ratios were 1.24 [95% confidence interval (CI): 1.04-1.47; P = 0.018] for the rs2981578-G allele (10q26/FGFR2), 1.34 (95% CI: 1.10-1.63; P = 0.0035) for the rs9397435-G allele (6q25) and 1.12 (95% CI: 1.00-1.25; P = 0.04) for the rs3104793-C allele (16q12). Although a significant association was observed for an additional index SNP (rs3817198), it was in the opposite direction to prior GWAS studies. In conclusion, this study highlights the complexity of applying current GWAS findings across racial/ethnic groups, as none of GWAS-identified index SNPs could be replicated in women of African ancestry. Further fine-mapping studies in women of African ancestry will be needed to reveal additional and causal variants for breast cancer. C1 [Huo, Dezheng] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Zheng, Yonglan; Niu, Qun; Zhang, Jing; Cox, Nancy J.; Olopade, Olufunmilayo I.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Ogundiran, Temidayo O.] Univ Ibadan, Dept Surg, Coll Med, Ibadan, Nigeria. [Adebamowo, Clement] Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. [Nathanson, Katherine L.; Domchek, Susan M.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Simon, Michael S.] Wayne State Univ, Karmanos Canc Inst, Dept Oncol, Detroit, MI USA. [John, Esther M.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [John, Esther M.] Stanford Canc Inst, Stanford, CA USA. [John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA. [Hennis, Anselm] Univ W Indies, Res Inst, Chron Dis Res Ctr & Trop Med, Bridgetown, Barbados. [Nemesure, Barbara; Wu, Suh-Yuh; Leske, M. Cristina] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA. [Ambs, Stefan] NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Huo, DZ (reprint author), Univ Chicago, Dept Hlth Studies, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM dhuo@health.bsd.uchicago.edu OI Nathanson, Katherine/0000-0002-6740-0901; Adebamowo, Clement/0000-0002-6571-2880 FU National Cancer Institute [R01CA141712, P01CA82707]; Breast Cancer Research Foundation; United States National Cancer Institute, National Institutes of Health [RFA-CA-06-503]; Georgetown University Medical Center Informatics Support Center [HHSN261200900010C] FX National Cancer Institute (R01CA141712 and P01CA82707). Support was also given by the Breast Cancer Research Foundation. The Northern California site of the Breast Cancer Family Registry (BCFR) was supported by the United States National Cancer Institute, National Institutes of Health under (RFA-CA-06-503) and through cooperative agreements with members of the BCFR and Principal Investigators, including the Northern California Cancer Center (U01 CA69417) and Georgetown University Medical Center Informatics Support Center (HHSN261200900010C). NR 44 TC 39 Z9 40 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2012 VL 33 IS 4 BP 835 EP 840 DI 10.1093/carcin/bgs093 PG 6 WC Oncology SC Oncology GA 921RC UT WOS:000302493800014 PM 22357627 ER PT J AU Ahmet, I Turner, T Lakatta, EG Talan, MI AF Ahmet, Ismayil Turner, Tia Lakatta, Edward G. Talan, Mark I. TI Fenoterol Enantiomers Do Not Possess Beneficial Therapeutic Properties of Their Racemic Mixture in the Rat Model of Post Myocardial Infarction Dilated Cardiomyopathy SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Article DE Chronic heart failure; Cardiac remodeling; beta(2) adrenergic receptor agonists; Fenoterol; Stereoisomers of fenoterol ID CARDIAC MYOCYTES; ISCHEMIC CARDIOMYOPATHY; CELL-DEATH; BETA(2)-ADRENOCEPTOR; STIMULATION; DERIVATIVES; PROTEINS; SURVIVAL; AGONIST AB A salutary effect of beta(2) adrenergic receptor (AR) agonist, fenoterol has been demonstrated in a rat model of post-myocardial infarction (MI) dilated cardiomyopathy (DCM). Recent reports on single cardiomyocyte experiments suggested that out of two enantiomers, RR and SS, that constitute a racemic mixture of fenoterol, only RR-enantiomer is an active component that might be a promising new drug for treatment of chronic heart failure. The objective of this study was to compare the efficacy of the RR enantiomer of fenoterol with efficacy of racemic fenoterol, and SS, an inactive enantiomer, in whole animal experimental models of DCM. Two weeks after induction of MI by permanent ligation of the anterior descending coronary artery early cardiac remodeling and MI size were assessed via echocardiography and rats were divided into treatment groups. Treatment (placebo, racemic fenoterol, RR- or SS-enantiomers of fenoterol) continued for 6 months while progression of DCM was followed by serial echocardiography. Compared with untreated rats, rats treated with racemic fenoterol demonstrated previously described attenuation of LV remodeling, functional decline and the arrest of the MI expansion during the first 2 months of treatment. On the contrary, the treatment with either RR-, or with SS-enantiomers of fenoterol was completely ineffective. The conclusion drawn on the basis of previous experiments with single cardiomyocytes that RR-enantiomer of fenoterol represents an active component of racemic fenoterol and can be further investigated as a new drug for treatment of chronic heart failure was not confirmed in the whole animal model of DCM. C1 [Ahmet, Ismayil; Turner, Tia; Lakatta, Edward G.; Talan, Mark I.] NIA, Cardiovasc Sci Lab, Intramural Res Program, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP Talan, MI (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM talanm@grc.nia.nih.gov FU NIH, National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging. NR 17 TC 2 Z9 2 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-3206 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD APR PY 2012 VL 26 IS 2 BP 101 EP 108 DI 10.1007/s10557-011-6366-9 PG 8 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 918XS UT WOS:000302285500003 PM 22328006 ER PT J AU Liu, XD Xu, LQ Chen, QQ Sun, LG Wang, YH Yan, H Liu, Y Luo, YH Huang, J AF Liu, Xiaodong Xu, Liqiang Chen, Qianqian Sun, Liguang Wang, Yuhong Yan, Hong Liu, Yi Luo, Yuhan Huang, Jing TI Historical change of mercury pollution in remote Yongle archipelago, South China Sea SO CHEMOSPHERE LA English DT Article DE South China Sea; Yongle archipelago; Hg pollution; Anthropogenic Hg flux; Ornithogenic sediments ID POLYCYCLIC AROMATIC-HYDROCARBONS; LAKE SEDIMENT CORES; PEARL RIVER ESTUARY; ATMOSPHERIC MERCURY; GEOCHEMICAL EVIDENCE; EMISSIONS; DEPOSITION; TRENDS; FLUXES; SILVER AB We collected three ornithogenic coral sand sedimentary profiles from Jinyin Island, Jinqing Island and Guangjin Island of Yongle archipelago, South China Sea and reconstructed the deposition flux of anthropogenic Hg over the past 700 years in the study area. On the whole, the anthropogenic Hg flux is relatively low; it remained at a low level before the Industrial Revolution with a small peak at about 1450-1550 AD, which may record the enhanced metallurgy activity in Ming Dynasty of China. During the 20th century, the deposition flux of anthropogenic Hg increased rapidly, but two troughs occurred during the periods around 1940s and 1970s, corresponding to the economic depression caused by World War II, Civil War in China (1945-1949), and the Culture Revolution (1966-1976) in China. Since the 1970s the deposition flux of anthropogenic Hg has been persistently increasing, apparently the result of fast economic development in East and Southeast Asia countries around South China Sea. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Liu, Xiaodong; Xu, Liqiang; Chen, Qianqian; Sun, Liguang; Yan, Hong; Liu, Yi; Luo, Yuhan; Huang, Jing] Univ Sci & Technol China, Inst Polar Environm, Sch Earth & Space Sci, Hefei 230026, Anhui, Peoples R China. [Wang, Yuhong] NIH, NIH Chem Genom Ctr, Rockville, MD 20850 USA. RP Liu, XD (reprint author), Univ Sci & Technol China, Inst Polar Environm, Sch Earth & Space Sci, Hefei 230026, Anhui, Peoples R China. EM ycx@ustc.edu.cn; slg@ustc.edu.cn RI Yan, Hong/I-8970-2014 FU National Natural Science Foundation of China [40730107, 40876096]; Ministry of Education of China's Ph.D. Programs Foundation for the new teachers [20093402120004]; CAS [KZCX2-EW-QN50] FX This work was funded by the National Natural Science Foundation of China (Nos. 40730107, 40876096), the Ministry of Education of China's Ph.D. Programs Foundation for the new teachers (20093402120004), Knowledge Innovation Program of CAS (KZCX2-EW-QN50). All members of field study team, including the Chinese People's Liberation Army, are acknowledged for their help in sample collection. We thank two anonymous reviewers and editor for their constructive comments on this manuscript. NR 60 TC 7 Z9 8 U1 7 U2 52 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD APR PY 2012 VL 87 IS 5 BP 549 EP 556 DI 10.1016/j.chemosphere.2011.12.065 PG 8 WC Environmental Sciences SC Environmental Sciences & Ecology GA 922CJ UT WOS:000302524100016 PM 22284978 ER PT J AU Lee, D Schwope, DM Milman, G Barnes, AJ Gorelick, DA Huestis, MA AF Lee, Dayong Schwope, David M. Milman, Garry Barnes, Allan J. Gorelick, David A. Huestis, Marilyn A. TI Cannabinoid Disposition in Oral Fluid after Controlled Smoked Cannabis SO CLINICAL CHEMISTRY LA English DT Article ID 11-NOR-DELTA(9)-TETRAHYDROCANNABINOL-9-CARBOXYLIC ACID; CYTOCHROME-P450 EXPRESSION; PHARMACOKINETIC PROPERTIES; DELTA(9)-TETRAHYDROCANNABINOL; METABOLISM; MARIJUANA; DRUGS; THC; TETRAHYDROCANNABINOL; IDENTIFICATION AB BACKGROUND: We measured Delta(9)-tetrahydrocannabinol (THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), and cannabinol (CBN) disposition in oral fluid (OF) following controlled cannabis smoking to evaluate whether monitoring multiple cannabinoids in OF improved OF test interpretation. METHODS: Cannabis smokers provided written informed consent for this institutional review board-approved study. OF was collected with the Quantisal (TM) device following ad libitum smoking of one 6.8% THC cigarette. Cannabinoids were quantified by 2-dimensional GC-MS. We evaluated 8 alternative cutoffs based on different drug testing program needs. RESULTS: 10 participants provided 86 OF samples -0.5 h before and 0.25, 0.5, 1, 2, 3, 4, 6, and 22 h after initiation of smoking. Before smoking, OF samples of 4 and 9 participants were positive for THC and THCCOOH, respectively, but none were positive for CBD and CBN. Maximum THC, CBD, and CBN concentrations occurred within 0.5 h, with medians of 644, 30.4, and 49.0 mu g/L, respectively. All samples were THC positive at 6 h (2.1-44.4 mu g/L), and 4 of 6 were positive at 22 h. CBD and CBN were positive only up to 6 h in 3 (0.6-2.1 mu g/L) and 4 (1.0-4.4 mu g/L) participants, respectively. The median maximum THCCOOH OF concentration was 115 ng/L, with all samples positive to 6 h (14.8-263 ng/L) and 5 of 6 positive at 22 h. CONCLUSIONS: By quantifying multiple cannabinoids and evaluating different analytical cutoffs after controlled cannabis smoking, we determined windows of drug detection, found suggested markers of recent smoking, and minimized the potential for passive contamination. (C) 2011 American Association for Clinical Chemistry C1 [Huestis, Marilyn A.] NIDA, IRP, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, IRP, NIH, Biomed Res Ctr, 251 Bayview Blvd Ste 200,Rm 05A-721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU National Institute on Drug Abuse, NIH FX The Intramural Research Program, National Institute on Drug Abuse, NIH. NR 40 TC 29 Z9 29 U1 2 U2 20 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 APR PY 2012 VL 58 IS 4 BP 748 EP 756 DI 10.1373/clinchem.2011.177881 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 917NW UT WOS:000302185700018 PM 22273566 ER PT J AU Frye, R Myers, M Axelrod, KC Ness, EA Piekarz, RL Bates, SE Booher, S AF Frye, Robin Myers, Mary Axelrod, Karen C. Ness, Elizabeth A. Piekarz, Richard L. Bates, Susan E. Booher, Susan TI Romidepsin: A New Drug for the Treatment of Cutaneous T-Cell Lymphoma SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; MYCOSIS-FUNGOIDES; SEZARY-SYNDROME; CANCER-THERAPY; DEPSIPEPTIDE FR901228; CLINICAL DEVELOPMENT; TRIAL AB Patients with cutaneous T-cell lymphoma (CTCL) have a rare, disfiguring, and life-threatening subtype of non-Hodgkin lymphoma primarily localized to the skin. Their immune systems are altered and their skin is compromised. In addition, they are highly prone to infections-the most common cause of death in patients with this disease. Patients presenting with early-stage disease involvement typically are treated with topical therapies; patients with advanced-stage and recurrent disease require systemic treatment. Specialized knowledge is required by oncology healthcare providers to manage the wide array of symptoms experienced by these patients as a part of the natural course of this disease. A new drug, romidepsin, approved by the U.S. Food and Drug Administration, is indicated in the treatment of relapsed CTCL. The authors discuss use of romidepsin in the context of CTCL and the information needed to safely administer romidepsin and manage its side effects. C1 [Frye, Robin] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Myers, Mary; Axelrod, Karen C.] NIH, Nursing Serv, Ctr Clin, Bethesda, MD 20892 USA. [Myers, Mary; Axelrod, Karen C.] NIH, Patient Care Serv, Ctr Clin, Bethesda, MD 20892 USA. [Piekarz, Richard L.] NCI, Canc Therapy Evaluat Program, NIH, Rockville, MD USA. [Booher, Susan] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Frye, R (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM nurserobinf@yahoo.com FU NIH, NCI, Center for Cancer Research; CRADA; Gloucester Pharmaceuticals FX Robin Frye, RN, BSN, is a research nurse specialist in the Medical Oncology Branch at the Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH); Mary Myers, BSN, PCCN, is a clinical research nurse and Karen C. Axelrod, RN, CWOCN, is a wound, ostomy, and continence nurse consultant, both in Nursing and Patient Care Services at the Clinical Center at NIH; Elizabeth A. Ness, RN, MS, is the director of staff development at the Center for Cancer Research, NCI, NIH, all in Bethesda, MD; Richard L. Piekarz, MD, PhD, is a medical officer of the Cancer Therapy Evaluation Program at NCI, NIH, in Rockville, MD; and Susan E. Bates, MD, is a senior investigator in the Medical Oncology Branch and Susan Booher, RN, MS, is a research nurse specialist in the Dermatology Branch, both at NCI, NIH, in Bethesda. The authors take full responsibility for the content of the article. Romidepsin, NSC 630176, was provided by the Cancer Therapy Evaluation Program. This research was supported, in part, by the Intramural Research Program of the NIH, NCI, Center for Cancer Research, and by a CRADA with Gloucester Pharmaceuticals. 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. The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers or editorial staff. Mention of specific products and opinions related to those products do not indicate or imply endorsement by the Clinical Journal of Oncology Nursing or the Oncology Nursing Society. Frye can be reached at nurserobinf@yahoo.com, with copy to editor at CJONEditor@ons.org. (First submission December 2010. Revision submitted July 2011. Accepted for publication July 25, 2011.) NR 38 TC 7 Z9 10 U1 0 U2 3 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD APR PY 2012 VL 16 IS 2 BP 195 EP 204 DI 10.1188/12.CJON.195-204 PG 10 WC Oncology; Nursing SC Oncology; Nursing GA 918VS UT WOS:000302280000014 PM 22459529 ER PT J AU Redford, KH Segre, JA Salafsky, N del Rio, CM McAloose, D AF Redford, Kent H. Segre, Julia A. Salafsky, Nick del Rio, Carlos Martinez McAloose, Denise TI Conservation and the Microbiome SO CONSERVATION BIOLOGY LA English DT Editorial Material ID INFECTIOUS-DISEASES; PROJECT C1 [Redford, Kent H.] Wildlife Conservat Soc, WCS Inst, Bronx, NY 10460 USA. [Segre, Julia A.] Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Salafsky, Nick] Fdn Success, Bethesda, MD 20816 USA. [del Rio, Carlos Martinez] Univ Wyoming, Dept Zool & Physiol, Laramie, WY 82070 USA. [McAloose, Denise] Wildlife Conservat Soc, Bronx, NY 10460 USA. RP Redford, KH (reprint author), Archipelago Consulting, Irvington, NY 10533 USA. EM kredford@wcs.org FU Intramural NIH HHS [ZIA HG000180-11] NR 17 TC 9 Z9 9 U1 4 U2 27 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0888-8892 J9 CONSERV BIOL JI Conserv. Biol. PD APR PY 2012 VL 26 IS 2 BP 195 EP 197 DI 10.1111/j.1523-1739.2012.01829.x PG 3 WC Biodiversity Conservation; Ecology; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 914VO UT WOS:000301981100001 PM 22443125 ER PT J AU Rosenberg, HF Domachowske, JB AF Rosenberg, H. F. Domachowske, J. B. TI Inflammatory Responses to Respiratory Syncytial Virus (RSV) Infection and the Development of Immunomodulatory Pharmacotherapeutics SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE Cytokines; Inflammation; Granulocytes; Pneumovirus; Leukocytes; Innate Immunity ID EOSINOPHIL CATIONIC PROTEIN; PNEUMOVIRUS INFECTION; IMMUNE-RESPONSES; COTTON RATS; BALB/C MICE; TNF-ALPHA; IN-VIVO; AIRWAY HYPERRESPONSIVENESS; CHEMOKINE EXPRESSION; LUNG INFLAMMATION AB Respiratory syncytial virus (RSV; Family Paramyxoviridae, Genus Pneumovirus) is a major respiratory pathogen of infants and children and an emerging pathogen of the elderly. Current management of RSV disease includes monoclonal antibody prophylaxis for infants identified as high risk and supportive care for those with active infection; there is no vaccine, although several are under study. In this manuscript, we review published findings from human autopsy studies, as well as experiments that focus on human clinical samples and mouse models of acute pneumovirus infection that elucidate basic principles of disease pathogenesis. Consideration of these data suggests that the inflammatory responses to RSV and related pneumoviral pathogens can be strong, persistent, and beyond the control of conventional antiviral and anti-inflammatory therapies, and can have profound negative consequences to the host. From this perspective, we consider the case for specific immunomodulatory strategies that may have the potential to alleviate some of the more serious sequelae of this disease. C1 [Rosenberg, H. F.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Domachowske, J. B.] SUNY Upstate Med Univ, Dept Pediat, Div Infect Dis, Syracuse, NY USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C215, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov FU NIAID Division of Intramural Research [AI000943]; Children's Miracle Network of New York FX Dr. Rosenberg's laboratory is supported by NIAID Division of Intramural Research (AI000943). Dr. Domachowske's laboratory is supported by the Children's Miracle Network of New York. NR 97 TC 19 Z9 22 U1 0 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD APR PY 2012 VL 19 IS 10 BP 1424 EP 1431 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 916QP UT WOS:000302118600002 PM 22360479 ER PT J AU Bray, GA Edelstein, SL Crandall, JP Aroda, VR Franks, PW Fujimoto, W Horton, E Jeffries, S Montez, M Mudaliar, S Pi-Sunyer, FX White, NH Knowler, WC AF Bray, George A. Edelstein, Sharon L. Crandall, Jill P. Aroda, Vanita R. Franks, Paul W. Fujimoto, Wilfred Horton, Edward Jeffries, Susan Montez, Maria Mudaliar, Sunder Pi-Sunyer, F. Xavier White, Neil H. Knowler, William C. CA Diabet Prevention Program Res Grp TI Long-Term Safety, Tolerability, and Weight Loss Associated With Metformin in the Diabetes Prevention Program Outcomes Study SO DIABETES CARE LA English DT Article ID ACTIVATED PROTEIN-KINASE; LIFE-STYLE INTERVENTION; TYPE-2; EXERCISE; MELLITUS; THERAPY; OBESITY; MUSCLE; DIET AB OBJECTIVE-Metformin produced weight loss and delayed or prevented diabetes in the Diabetes Prevention Program (DPP). We examined its long-term safety and tolerability along with weight loss, and change in waist circumference during the DPP and its long-term follow-up. RESEARCH DESIGN AND METHODS-The randomized double-blind clinical trial of metformin or placebo followed by a 7-8-year open-label extension and analysis of adverse events, tolerability, and the effect of adherence on change in weight and waist circumference. RESULTS-No significant safety issues were identified. Gastrointestinal symptoms were more common in metformin than placebo participants and declined over time. During the DPP, average hemoglobin and hematocrit levels were slightly lower in the metformin group than in the placebo group. Decreases in hemoglobin and hematocrit in the metformin group occurred during the first year following randomization, with no further changes observed over time. During the DPP, metformin participants had reduced body weight and waist circumference compared with placebo (weight by 2.06 +/- 5.65% vs. 0.02 +/- 5.52%, P < 0.001, and waist circumference by 2.13 +/- 7.06 cm vs. 0.79 +/- 6.54 cm, P < 0.001 in metformin vs. placebo, respectively). The magnitude of weight loss during the 2-year double-blind period was directly related to adherence (P < 0.001). Throughout the unblinded follow-up, weight loss remained significantly greater in the metformin group than in the placebo group (2.0 vs. 0.2%, P < 0.001), and this was related to the degree of continuing metformin adherence (P < 0.001). CONCLUSIONS-Metformin used for diabetes prevention is safe and well tolerated. Weight loss is related to adherence to metformin and is durable for at least 10 years of treatment. C1 [Bray, George A.] Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Edelstein, Sharon L.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Crandall, Jill P.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Aroda, Vanita R.] Medstar Hlth Res Inst, Hyattsville, MD USA. [Franks, Paul W.] Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden. [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Fujimoto, Wilfred] Univ Washington, Seattle, WA 98195 USA. [Horton, Edward] Joslin Diabet Ctr, Boston, MA 02215 USA. [Jeffries, Susan] Univ Pittsburgh, Pittsburgh, PA USA. [Montez, Maria] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Mudaliar, Sunder] Univ Calif San Diego, San Diego, CA 92103 USA. [Pi-Sunyer, F. Xavier] Columbia Univ, St Lukes Roosevelt Hosp Ctr, New York, NY USA. [White, Neil H.] Washington Univ, Sch Med, St Louis, MO USA. [Knowler, William C.] NIDDK, Phoenix, AZ USA. RP Bray, GA (reprint author), Pennington Biomed Res Ctr, Baton Rouge, LA USA. OI Franks, Paul/0000-0002-0520-7604 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health; NIDDK; Indian Health Service; National Institute of Child Health and Human Development; National Institute on Aging; National Eye Institute; National Heart, Lung, and Blood Institute; Office of Research on Women's Health; National Institute on Minority Health and Health Disparities; Centers for Disease Control and Prevention; American Diabetes Association; Bristol-Myers Squibb; Parke-Davis; Novo Nordisk; Swedish Heart-Lung Foundation; Swedish Diabetes Association; Swedish Research Council FX The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding to the clinical centers and the DPP Coordinating Center for the design and conduct of the study, and collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program, and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, supported data collection at many of the clinical centers. Funding was also provided by the National Institute of Child Health and Human Development; the National Institute on Aging; the National Eye Institute; the National Heart, Lung, and Blood Institute; the Office of Research on Women's Health; the National Institute on Minority Health and Health Disparities; the Centers for Disease Control and Prevention; and the American Diabetes Association.; Bristol-Myers Squibb and Parke-Davis provided additional funding and material support during the DPP. Lipha (Merck-Sante) provided medication, and Life Scan Inc. donated materials during the DPP and the DPPOS. P.W.F. was supported in part by grants from Novo Nordisk, the Swedish Heart-Lung Foundation, the Swedish Diabetes Association, and the Swedish Research Council. No other potential conflicts of interest relevant to this article were reported. NR 22 TC 53 Z9 54 U1 2 U2 11 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 APR PY 2012 VL 35 IS 4 BP 731 EP 737 DI 10.2337/dc11-1299 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 914OB UT WOS:000301959600013 ER PT J AU Punthakee, Z Miller, ME Launer, LJ Williamson, JD Lazar, RM Cukierman-Yaffee, T Seaquist, ER Ismail-Beigi, F Sullivan, MD Lovato, LC Bergenstal, RM Gerstein, HC AF Punthakee, Zubin Miller, Michael E. Launer, Lenore J. Williamson, Jeff D. Lazar, Ronald M. Cukierman-Yaffee, Tali Seaquist, Elizabeth R. Ismail-Beigi, Faramarz Sullivan, Mark D. Lovato, Laura C. Bergenstal, Richard M. Gerstein, Hertzel C. CA ACCORD Grp Investigators ACCORD-MIND Investigators TI Poor Cognitive Function and Risk of Severe Hypoglycemia in Type 2 Diabetes Post hoc epidemiologic analysis of the ACCORD trial SO DIABETES CARE LA English DT Article ID PSYCHOMOTOR PERFORMANCE; ATHEROSCLEROSIS RISK; MELLITUS; ADULTS; AGE; COMPLICATIONS; ASSOCIATION; COMMUNITIES; DYSFUNCTION; MORTALITY AB OBJECTIVE-Self-management of type 2 diabetes including avoidance of hypoglycemia is complex, but the impact of cognition on safe self-management is not well understood. This study aimed to assess the effect of baseline cognitive function and cognitive decline on subsequent risk of severe hypoglycemia and to assess the effect of different glycemic strategies on these relationships. RESEARCH DESIGN AND METHODS-Prospective cohort analysis of data from the ACCORD trial included 2,956 adults aged >= 55 years with type 2 diabetes and additional cardiovascular risk factors. Cognitive tests (Digit Symbol Substitution Test [DSST], Rey Auditory Verbal Learning Test, Stroop Test, and Mini Mental Status Examination) were conducted at baseline and 20 months. Study outcomes were incident confirmed severe hypoglycemia requiring medical assistance (HMA) and hypoglycemia requiring any assistance (HAA). RESULTS-After a median 3.25-year follow-up, a 5-point-poorer baseline score on the DSST was predictive of a first episode of HMA (hazard ratio 1.13 [95% CI 1.08-1.18]). Analyses of the other cognitive tests and of HAA were consistent with the DSST results. Cognitive decline over 20 months increased the risk of subsequent hypoglycemia to a greater extent in those with lower baseline cognitive function (P-interaction = 0.037). Randomization to an intensive versus standard glycemic strategy had no impact on the relationship between cognitive function and the risk of severe hypoglycemia. CONCLUSIONS-Poor cognitive function increases the risk of severe hypoglycemia in patients with type 2 diabetes. Clinicians should consider cognitive function in assessing and guiding their patients regarding safe diabetes self-management regardless of their glycemic targets. C1 [Punthakee, Zubin; Gerstein, Hertzel C.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Miller, Michael E.] Wake Forest Univ, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. [Launer, Lenore J.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Williamson, Jeff D.] Wake Forest Univ, Dept Med, Winston Salem, NC 27109 USA. [Williamson, Jeff D.] Wake Forest Univ, Kulynych Ctr Memory & Cognit Res, Winston Salem, NC 27109 USA. [Lazar, Ronald M.] Columbia Univ, Dept Neurol, New York, NY USA. [Cukierman-Yaffee, Tali] Tel Aviv Univ, Chaim Sheba Med Ctr, Gertner Inst Epidemiol & Hlth Policy Res, Inst Endocrinol,Epidemiol Dept, IL-69978 Tel Aviv, Israel. [Seaquist, Elizabeth R.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Ismail-Beigi, Faramarz] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. [Sullivan, Mark D.] Univ Washington, Seattle, WA 98195 USA. [Lovato, Laura C.] Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. [Bergenstal, Richard M.] Int Diabet Ctr Pk Nicollet, Minneapolis, MN USA. RP Punthakee, Z (reprint author), McMaster Univ, Dept Med, Hamilton, ON, Canada. EM zubin.punthakee@mcmaster.ca RI Gerstein, Hertzel/B-1235-2013 OI Gerstein, Hertzel/0000-0001-8072-2836 FU National Heart, Lung, and Blood Institute (NHLBI); National Institute of Diabetes and Digestive and Kidney Diseases; National Eye Institute; National Institute on Aging (NIA); Centers for Disease Control and Prevention FX ACCORD was sponsored by the National Heart, Lung, and Blood Institute (NHLBI), and ACCORD-MIND was sponsored by NHLBI, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Eye Institute, the National Institute on Aging (NIA) and the Intramural Research Program at NIA, and the Centers for Disease Control and Prevention. NR 33 TC 82 Z9 84 U1 1 U2 10 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 APR PY 2012 VL 35 IS 4 BP 787 EP 793 DI 10.2337/dc11-1855 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 914OB UT WOS:000301959600022 PM 22374637 ER PT J AU McDannald, MA Takahashi, YK Lopatina, N Pietras, BW Jones, JL Schoenbaum, G AF McDannald, Michael A. Takahashi, Yuji K. Lopatina, Nina Pietras, Brad W. Jones, Josh L. Schoenbaum, Geoffrey TI Model-based learning and the contribution of the orbitofrontal cortex to the model-free world SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE model-based; model-free; orbitofrontal cortex; Pavlovian; striatum ID NUCLEUS-ACCUMBENS CORE; DOPAMINE NEURONS ENCODE; BASOLATERAL AMYGDALA; VENTRAL STRIATUM; UNCONDITIONED STIMULUS; INSTRUMENTAL TRANSFER; DEVALUATION TASK; DORSAL STRIATUM; REWARD; LESIONS AB Learning is proposed to occur when there is a discrepancy between reward prediction and reward receipt. At least two separate systems are thought to exist: one in which predictions are proposed to be based on model-free or cached values; and another in which predictions are model-based. A basic neural circuit for model-free reinforcement learning has already been described. In the model-free circuit the ventral striatum (VS) is thought to supply a common-currency reward prediction to midbrain dopamine neurons that compute prediction errors and drive learning. In a model-based system, predictions can include more information about an expected reward, such as its sensory attributes or current, unique value. This detailed prediction allows for both behavioral flexibility and learning driven by changes in sensory features of rewards alone. Recent evidence from animal learning and human imaging suggests that, in addition to model-free information, the VS also signals model-based information. Further, there is evidence that the orbitofrontal cortex (OFC) signals model-based information. Here we review these data and suggest that the OFC provides model-based information to this traditional model-free circuitry and offer possibilities as to how this interaction might occur. C1 [McDannald, Michael A.; Jones, Josh L.; Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Takahashi, Yuji K.; Schoenbaum, Geoffrey] NIDA IRP, Baltimore, MD USA. [Lopatina, Nina; Pietras, Brad W.] Univ Maryland, Program Neurosci, College Pk, MD 20742 USA. RP Schoenbaum, G (reprint author), Univ Maryland, Sch Med, 20 Penn St HSF 2, Baltimore, MD 21201 USA. EM schoenbg@schoenbaumlab.org FU [R01DA015718] FX This study was supported by R01DA015718 to G.S. NR 57 TC 41 Z9 41 U1 3 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-816X EI 1460-9568 J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD APR PY 2012 VL 35 IS 7 SI SI BP 991 EP 996 DI 10.1111/j.1460-9568.2011.07982.x PG 6 WC Neurosciences SC Neurosciences & Neurology GA 919VX UT WOS:000302360500002 PM 22487030 ER PT J AU Hilario, M Holloway, T Jin, X Costa, RM AF Hilario, Monica Holloway, Terrell Jin, Xin Costa, Rui M. TI Different dorsal striatum circuits mediate action discrimination and action generalization SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE basal ganglia; goal-directed; habit; learning; motor; mouse ID MULTIPLE MEMORY-SYSTEMS; BASAL GANGLIA; DORSOMEDIAL STRIATUM; CAUDATE-NUCLEUS; CONTINGENCY; LESIONS; CORTEX; ROLES; INACTIVATION; DEVALUATION AB Generalization is an important process that allows animals to extract rules from regularities of past experience and apply them to analogous situations. In particular, the generalization of previously learned actions to novel instruments allows animals to use past experience to act faster and more efficiently in an ever-changing environment. However, generalization of actions to a dissimilar instrument or situation may also be detrimental. In this study, we investigated the neural bases of action generalization and discrimination in mice trained on a lever-pressing task. Using specific schedules of reinforcement known to bias animals towards habitual or goal-directed behaviors, we confirmed that action generalization is more prominent in animals using habitual rather than goal-directed strategies. We discovered that selective excitotoxic lesions of the dorsolateral and dorsomedial striatum have opposite effects on the generalization of a previously learned action to a novel lever. Whereas lesions of the dorsolateral striatum impair action generalization, dorsomedial striatum lesions affect action discrimination and bias subjects towards action generalization. Importantly, these lesions do not affect the ability of animals to explore or match their lever-pressing rate to the reinforcement rate, or the ability to distinguish between different levers. The data presented here reveal that dorsolateral and dorsomedial striatal circuits have opposing roles in the generalization of previously learned actions to novel instruments, and suggest that these circuits compete for the expression of generalization in novel situations. C1 [Costa, Rui M.] Champalimaud Ctr Unknown, Champalimaud Neurosci Programme, P-1400038 Lisbon, Portugal. [Hilario, Monica; Holloway, Terrell; Jin, Xin; Costa, Rui M.] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD USA. RP Costa, RM (reprint author), Champalimaud Ctr Unknown, Champalimaud Neurosci Programme, Av Brasilia, P-1400038 Lisbon, Portugal. EM ruicosta@fchampalimaud.org OI Costa, Rui/0000-0003-0495-8374 FU National Institute on Alcohol Abuse and Alcoholism [239527]; European Research Council [STG 243393] FX We thank M. Child for comments on the manuscript. This work was supported by the Intramural Research Program at the National Institute on Alcohol Abuse and Alcoholism, Marie Curie International Reintegration Grant 239527, and European Research Council STG 243393. NR 38 TC 15 Z9 15 U1 2 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD APR PY 2012 VL 35 IS 7 SI SI BP 1105 EP 1114 DI 10.1111/j.1460-9568.2012.08073.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 919VX UT WOS:000302360500012 PM 22487040 ER PT J AU Roesch, MR Esber, GR Li, J Daw, ND Schoenbaum, G AF Roesch, Matthew R. Esber, Guillem R. Li, Jian Daw, Nathaniel D. Schoenbaum, Geoffrey TI Surprise! Neural correlates of Pearce-Hall and Rescorla-Wagner coexist within the brain SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Review DE amygdala; attention; dopamine; learning; prediction error ID ANTERIOR CINGULATE CORTEX; VENTRAL TEGMENTAL AREA; MIDBRAIN DOPAMINE NEURONS; AMYGDALA CENTRAL NUCLEUS; REWARD-SEEKING BEHAVIOR; ORBITOFRONTAL CORTEX; LATERAL HABENULA; PREDICTION ERRORS; BASOLATERAL AMYGDALA; DECISION-MAKING AB Learning theory and computational accounts suggest that learning depends on errors in outcome prediction as well as changes in processing of or attention to events. These divergent ideas are captured by models, such as RescorlaWagner (RW) and temporal difference (TD) learning on the one hand, which emphasize errors as directly driving changes in associative strength, vs. models such as PearceHall (PH) and more recent variants on the other hand, which propose that errors promote changes in associative strength by modulating attention and processing of events. Numerous studies have shown that phasic firing of midbrain dopamine (DA) neurons carries a signed error signal consistent with RW or TD learning theories, and recently we have shown that this signal can be dissociated from attentional correlates in the basolateral amygdala and anterior cingulate. Here we will review these data along with new evidence: (i) implicating habenula and striatal regions in supporting error signaling in midbrain DA neurons; and (ii) suggesting that the central nucleus of the amygdala and prefrontal regions process the amygdalar attentional signal. However, while the neural instantiations of the RW and PH signals are dissociable and complementary, they may be linked. Any linkage would have implications for understanding why one signal dominates learning in some situations and not others, and also for appreciating the potential impact on learning of neuropathological conditions involving altered DA or amygdalar function, such as schizophrenia, addiction or anxiety disorders. C1 [Esber, Guillem R.; Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. [Roesch, Matthew R.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Roesch, Matthew R.] Univ Maryland, Program Neurosci & Cognit Sci, College Pk, MD 20742 USA. [Li, Jian; Daw, Nathaniel D.] NYU, Dept Psychol, New York, NY 10003 USA. [Li, Jian; Daw, Nathaniel D.] NYU, Ctr Neural Sci, New York, NY 10003 USA. [Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Schoenbaum, Geoffrey] NIDA Intramural Res Program, Baltimore, MD 21224 USA. RP Schoenbaum, G (reprint author), Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. EM schoenbg@schoenbaumlab.org FU NIDA; NIMH; NIA FX This work was supported by grants to G.S. from NIDA, NIMH and NIA, and to M. R. from NIDA. This article was prepared, in part, while G. S. was employed at UMB. The opinions expressed in this article are the author's own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. NR 121 TC 39 Z9 39 U1 3 U2 30 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD APR PY 2012 VL 35 IS 7 SI SI BP 1190 EP 1200 DI 10.1111/j.1460-9568.2011.07986.x PG 11 WC Neurosciences SC Neurosciences & Neurology GA 919VX UT WOS:000302360500019 PM 22487047 ER PT J AU Zanotti-Fregonara, P Maroy, R Peyronneau, MA Trebossen, R Bottlaender, M AF Zanotti-Fregonara, Paolo Maroy, Renaud Peyronneau, Marie-Anne Trebossen, Regine Bottlaender, Michel TI Minimally invasive input function for 2-F-18-fluoro-A-85380 brain PET studies SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE Input function; 2-F-18-Fluoro-A-85380; Brain studies with PET ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL METABOLIC-RATE; NICOTINIC ACETYLCHOLINE-RECEPTORS; BLOOD-SAMPLING SITE; FDG-PET; SIMPLIFIED QUANTIFICATION; GLUCOSE-METABOLISM; DRUG CONCENTRATION; MARKED DEPENDENCE; QUANTITATIVE PET AB Quantitative neuroreceptor positron emission tomography (PET) studies often require arterial cannulation to measure input function. While population-based input function (PBIF) would be a less invasive alternative, it has only rarely been used in conjunction with neuroreceptor PET tracers. The aims of this study were (1) to validate the use of PBIF for 2-F-18-fluoro-A-85380, a tracer for nicotinic receptors; (2) to compare the accuracy of measures obtained via PBIF to those obtained via blood-scaled image-derived input function (IDIF) from carotid arteries; and (3) to explore the possibility of using venous instead of arterial samples for both PBIF and IDIF. Ten healthy volunteers underwent a dynamic 2-F-18-fluoro-A-85380 brain PET scan with arterial and, in seven subjects, concurrent venous serial blood sampling. PBIF was obtained by averaging the normalized metabolite-corrected arterial input function and subsequently scaling each curve with individual blood samples. IDIF was obtained from the carotid arteries using a blood-scaling method. Estimated Logan distribution volume (V (T)) values were compared to the reference values obtained from arterial cannulation. For all subjects, PBIF curves scaled with arterial samples were similar in shape and magnitude to the reference arterial input function. The Logan V (T) ratio was 1.00 +/- 0.05; all subjects had an estimation error < 10%. IDIF gave slightly less accurate results (V (T) ratio 1.03 +/- 0.07; eight of ten subjects had an error < 10%). PBIF scaled with venous samples yielded inaccurate results (V (T) ratio 1.13 +/- 0.13; only three of seven subjects had an error < 10%). Due to arteriovenous differences at early time points, IDIF could not be calculated using venous samples. PBIF scaled with arterial samples accurately estimates Logan V (T) for 2-F-18-fluoro-A-85380. Results obtained with PBIF were slightly better than those obtained with IDIF. Due to arteriovenous concentration differences, venous samples cannot be substituted for arterial samples. C1 [Zanotti-Fregonara, Paolo] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Maroy, Renaud; Peyronneau, Marie-Anne; Trebossen, Regine] Serv Hosp Frederic Joliot, CEA, DSV, I2BM, F-91401 Orsay, France. [Bottlaender, Michel] CEA, DSV, I2BM, F-91191 Gif Sur Yvette, France. RP Zanotti-Fregonara, P (reprint author), NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr,MSC 1026, Bethesda, MD 20892 USA. EM zanottifregonp@mail.nih.gov FU National Institute of Mental Health, National Institutes of Health (NIMH-NIH) FX This study was supported in part by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH). NR 42 TC 10 Z9 10 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD APR PY 2012 VL 39 IS 4 BP 651 EP 659 DI 10.1007/s00259-011-2004-9 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 918YL UT WOS:000302287500012 PM 22231015 ER PT J AU Gao, HK Lang, LX Guo, N Cao, F Quan, QM Hu, S Kiesewetter, DO Niu, G Chen, XY AF Gao, Haokao Lang, Lixin Guo, Ning Cao, Feng Quan, Qimeng Hu, Shuo Kiesewetter, Dale O. Niu, Gang Chen, Xiaoyuan TI PET imaging of angiogenesis after myocardial infarction/reperfusion using a one-step labeled integrin-targeted tracer F-18-AlF-NOTA-PRGD2 SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE PET imaging; Angiogenesis; Myocardial infarction; Integrin; RGD peptide ID ALPHA(V)BETA(3) EXPRESSION; INFARCTION; PEPTIDES; THERAPY; F-18-FPPRGD2; ANTAGONISTS; AGENT; ACID; MICE AB The alpha(v)beta(3) integrin represents a potential target for noninvasive imaging of angiogenesis. The purpose of this study was to evaluate a novel one-step labeled integrin alpha(v)beta(3)-targeting positron emission tomography (PET) probe, F-18-AlF-NOTA-PRGD2, for angiogenesis imaging in a myocardial infarction/reperfusion (MI/R) animal model. Male Sprague-Dawley rats underwent 45-min transient left coronary artery occlusion followed by reperfusion. The myocardial infarction was confirmed by ECG, F-18-fluorodeoxyglucose (FDG) imaging, and cardiac ultrasound. In vivo PET imaging was used to determine myocardial uptake of F-18-AlF-NOTA-PRGD2 at different time points following reperfusion. The control peptide RAD was labeled with a similar procedure and used to confirm the specificity. Ex vivo autoradiographic analysis and CD31/CD61 double immunofluorescence staining were performed to validate the PET results. Myocardial origin of the F-18-AlF-NOTA-PRGD2 accumulation was confirmed by F-18-FDG and autoradiography. PET imaging demonstrated increased focal accumulation of F-18-AlF-NOTA-PRGD2 in the infarcted area which started at day 3 (0.28 +/- 0.03%ID/g, p < 0.05) and peaked between 1 and 3 weeks (0.59 +/- 0.16 and 0.55 +/- 0.13%ID/g, respectively). The focal accumulation decreased but still kept at a higher level than the sham group after 4 months of reperfusion (0.31 +/- 0.01%ID/g, p < 0.05). Pretreatment with unlabeled arginine-glycine-aspartic acid (RGD) peptide significantly decreased tracer uptake, indicating integrin specificity of this tracer. At 1 week after MI/R, uptake of the control tracer F-18-AlF-NOTA-RAD that does not bind to integrin, in the infarcted area, was only 0.21 +/- 0.01%ID/g. Autoradiographic imaging showed the same trend of uptake in the myocardial infarction area. The time course of focal tracer uptake was consistent with the pattern of vascular density and integrin beta(3) expression as measured by CD31 and CD61 immunostaining analysis. PET imaging using one-step labeled F-18-AlF-NOTA-PRGD2 allows noninvasive visualization of ischemia/reperfusion-induced myocardial angiogenesis longitudinally. The favorable in vivo kinetics and easy production method of this integrin-targeted PET tracer facilitates its future clinical translation for lesion evaluation and therapy response monitoring in patients with occlusive cardiovascular diseases. C1 [Gao, Haokao; Lang, Lixin; Guo, Ning; Quan, Qimeng; Hu, Shuo; Kiesewetter, Dale O.; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Gao, Haokao; Cao, Feng] Fourth Mil Med Univ, Dept Cardiol, Xijing Hosp, Xian 710032, Peoples R China. RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA. EM niug@mail.nih.gov; shawn.chen@nih.gov FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH); National Science Foundation of China (NSFC) [81028009, 81100234] FX This project was supported by the Intramural Research Program of the 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). H. G. is partly supported by the National Science Foundation of China (NSFC) (81100234). NR 35 TC 36 Z9 36 U1 1 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD APR PY 2012 VL 39 IS 4 BP 683 EP 692 DI 10.1007/s00259-011-2052-1 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 918YL UT WOS:000302287500016 PM 22274731 ER PT J AU Bentley, AR Kritchevsky, SB Harris, TB Holvoet, P Jensen, RL Newman, AB Lee, JS Yende, S Bauer, D Cassano, PA AF Bentley, A. R. Kritchevsky, S. B. Harris, T. B. Holvoet, P. Jensen, R. L. Newman, A. B. Lee, J. S. Yende, S. Bauer, D. Cassano, P. A. CA Hlth ABC Study TI Dietary antioxidants and forced expiratory volume in 1 s decline: the Health, Aging and Body Composition study SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE Ageing; dietary intake; lung function measurements; oxidants/antioxidants; smoking and health ID OBSTRUCTIVE PULMONARY-DISEASE; LUNG-FUNCTION DECLINE; MIDDLE-AGED MEN; GENERAL-POPULATION; AIRWAY-OBSTRUCTION; OXIDATIVE STRESS; WEIGHT CHANGE; OLDER-ADULTS; COPD; LIMITATION AB Increased antioxidant defences are hypothesised to decrease age-and smoking-related decline in lung function. The relationship between dietary antioxidants, smoking and forced expiratory volume in 1 s (FEV1) was investigated in community-dwelling older adults in the Health, Aging and Body Composition study. 1,443 participants completed a food frequency questionnaire, self-reported smoking history and had measurements taken of FEV1 at both baseline and after 4 yrs of follow-up. The association of dietary intake of nutrients and foods with antioxidant properties and rate of FEV1 decline was investigated using hierarchical linear regression models. In continuing smokers (current smokers at both time-points), higher vitamin C intake and higher intake of fruit and vegetables were associated with an 18 and 24 mL.yr(-1) slower rate of FEV1 decline compared with a lower intake (p<0.0001 and p=0.003, respectively). In quitters (a current smoker at study baseline who had quit during follow-up), higher intake was associated with an attenuated rate of decline for each nutrient studied (p <= 0.003 for all models). In nonsmoking participants, there was little or no association of diet and rate of decline in FEV1. The intake of nutrients with antioxidant properties may modulate lung function decline in older adults exposed to cigarette smoke. C1 [Bentley, A. R.; Cassano, P. A.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. [Kritchevsky, S. B.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [Harris, T. B.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Jensen, R. L.] Univ Utah, Sch Med, Div Pulm, LDS Hosp, Salt Lake City, UT USA. [Newman, A. B.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Yende, S.] Univ Pittsburgh, Dept Crit Care Med, CRISMA Lab, Pittsburgh, PA USA. [Lee, J. S.] Univ Georgia, Athens, GA 30602 USA. [Bauer, D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Holvoet, P.] Katholieke Univ Leuven, Dept Cardiovasc Dis, Louvain, Belgium. RP Cassano, PA (reprint author), Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. EM pac6@cornell.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Institutes of Health (NIH) [T32 DK007158-31, R01HL74104, R01HL071022]; National Institute on Aging [N01-AG-6-2101, N01-AG-2103, N01-AG-6-2106]; NIH, National Institute on Aging FX This work was supported by the National Institutes of Health (NIH) (grant number T32 DK007158-31 to A. R. Bentley; grant number R01HL74104 to S. B. Kritchevsky; grant number R01HL071022 to P. A. Cassano) and the National Institute on Aging (grant numbers N01-AG-6-2101, N01-AG-2103 and N01-AG-6-2106 to the Health ABC Study). This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. NR 29 TC 16 Z9 17 U1 1 U2 8 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD APR PY 2012 VL 39 IS 4 BP 979 EP 984 DI 10.1183/09031936.00190010 PG 6 WC Respiratory System SC Respiratory System GA 919UL UT WOS:000302354900027 PM 22005919 ER PT J AU Becker, RE Greig, NH AF Becker, Robert E. Greig, Nigel H. TI Increasing the success rate for Alzheimer's disease drug discovery and development SO EXPERT OPINION ON DRUG DISCOVERY LA English DT Editorial Material DE Alzheimer's disease; clinical trials; drug development; methodological errors ID CLINICAL-TRIALS; FUTURE AB This paper responds to the fact that over 200 Alzheimer's disease (AD) drug candidates have failed to date and draws on searches of the literature for studies of error effects in drug developments and the authors' published works. In the same period, basic knowledge of AD pathology has greatly expanded providing both potential therapeutic targets and rationales for modifications in strategies for testing AD drug candidates. Current opinion generally holds that AD drug candidates have failed because they address pathology that is already too advanced. Less attention is paid to numerous reported methodological weaknesses capable of biasing AD clinical trials and drug developments and thus invalidating conclusions to be reached about the drugs being tested. The costs of quality controls possibly needed to better insure validity in AD drug developments raises concerns that progress toward success in AD drug development may be hindered by the costs of intervening against current methodological barriers to the successful completions of AD drug developments. C1 [Becker, Robert E.] Aristea Translat Med Corp, S Freeport, ME 04078 USA. [Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Becker, RE (reprint author), Aristea Translat Med Corp, POB 442, S Freeport, ME 04078 USA. EM rebecker2008@comcast.net FU Intramural NIH HHS NR 18 TC 6 Z9 6 U1 1 U2 4 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 APR PY 2012 VL 7 IS 4 BP 367 EP 370 DI 10.1517/17460441.2012.672409 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 917HO UT WOS:000302163700007 PM 22439785 ER PT J AU Meliopoulos, VA Andersen, LE Birrer, KF Simpson, KJ Lowenthal, JW Bean, AGD Stambas, J Stewart, CR Tompkins, SM van Beusechem, VW Fraser, I Mhlanga, M Barichievy, S Smith, Q Leake, D Karpilow, J Buck, A Jona, G Tripp, RA AF Meliopoulos, Victoria A. Andersen, Lauren E. Birrer, Katherine F. Simpson, Kaylene J. Lowenthal, John W. Bean, Andrew G. D. Stambas, John Stewart, Cameron R. Tompkins, S. Mark van Beusechem, Victor W. Fraser, Iain Mhlanga, Musa Barichievy, Samantha Smith, Queta Leake, Devin Karpilow, Jon Buck, Amy Jona, Ghil Tripp, Ralph A. TI Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens SO FASEB JOURNAL LA English DT Review DE antivirals; HTS; genome; pathway; meta-analysis ID PROTEIN-PROTEIN INTERACTIONS; MICROARRAY EXPERIMENT MIAME; VIRUS-REPLICATION; A VIRUS; IMMUNE-RESPONSE; NS1 PROTEIN; CAENORHABDITIS-ELEGANS; TRANSCRIPTION FACTORS; MINIMUM INFORMATION; SIGNAL-TRANSDUCTION AB Influenza virus encodes only 11 viral proteins but replicates in a broad range of avian and mammalian species by exploiting host cell functions. Genome-wide RNA interference (RNAi) has proven to be a powerful tool for identifying the host molecules that participate in each step of virus replication. Meta-analysis of findings from genome-wide RNAi screens has shown influenza virus to be dependent on functional nodes in host cell pathways, requiring a wide variety of molecules and cellular proteins for replication. Because rapid evolution of the influenza A viruses persistently complicates the effectiveness of vaccines and therapeutics, a further understanding of the complex host cell pathways coopted by influenza virus for replication may provide new targets and strategies for antiviral therapy. RNAi genome screening technologies together with bioinformatics can provide the ability to rapidly identify specific host factors involved in resistance and susceptibility to influenza virus, allowing for novel disease intervention strategies.-Meliopoulos, V. A., Andersen, L. E., Birrer, K. F., Simpson, K. J., Lowenthal, J. W., Bean, A. G. D., Stambas, J., Stewart, C. R., Tompkins, S. M., van Beusechem, V. W., Fraser, I., Mhlanga, M., Barichievy, S., Smith, Q., Leake, D., Karpilow, J., Buck, A., Jona, G., Tripp, R. A. Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens. FASEB J. 26, 1372-1386 (2012). www.fasebj.org C1 [Tripp, Ralph A.] Univ Georgia, Dept Infect Dis, Anim Hlth Res Ctr, Athens, GA 30602 USA. [Birrer, Katherine F.; Lowenthal, John W.; Bean, Andrew G. D.; Stewart, Cameron R.] Commonwealth Sci & Ind Res Org, Australian Anim Hlth Lab, Geelong, Vic, Australia. [Simpson, Kaylene J.] Peter MacCallum Canc Ctr, Victorian Ctr Funct Genom, Melbourne, Vic, Australia. [Birrer, Katherine F.; Stambas, John] Deakin Univ, Sch Med, Geelong, Vic 3217, Australia. [van Beusechem, Victor W.] Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, Amsterdam, Netherlands. [Fraser, Iain] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Mhlanga, Musa; Barichievy, Samantha] CSIR, Synthet Biol Emerging Res Area, Gene Express & Biophys Grp, Pretoria, South Africa. [Smith, Queta; Leake, Devin; Karpilow, Jon] Thermo Fisher Sci, Lafayette, CO USA. [Simpson, Kaylene J.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. [Buck, Amy] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh, Midlothian, Scotland. [Jona, Ghil] Weizmann Inst Sci, Dept Biol Serv, IL-76100 Rehovot, Israel. RP Tripp, RA (reprint author), Univ Georgia, Dept Infect Dis, Anim Hlth Res Ctr, 111 Carlton St, Athens, GA 30602 USA. EM ratripp@uga.edu RI Tompkins, Stephen/A-3317-2008; lowenthal, john/G-4459-2010; Mhlanga, Musa/D-1283-2011; Stewart, Cameron/E-6823-2011; OI Tompkins, Stephen/0000-0002-1523-5588; lowenthal, john/0000-0002-0548-2497; Mhlanga, Musa/0000-0003-1381-3409; Simpson, Kaylene/0000-0001-9136-1781; Tripp, Ralph/0000-0002-2924-9956; Stambas, John/0000-0002-5690-2551 FU Biotechnology and Biological Sciences Research Council [BB/G01552X/1]; Intramural NIH HHS [ZIA AI001107-04, ZIA AI001106-04] NR 137 TC 24 Z9 26 U1 0 U2 19 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 IS 4 BP 1372 EP 1386 DI 10.1096/fj.11-193466 PG 15 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 919VS UT WOS:000302359700001 PM 22247330 ER PT J AU Hwang, SY Putney, JW AF Hwang, Sung-Yong Putney, James W. TI Orai1-mediated calcium entry plays a critical role in osteoclast differentiation and function by regulating activation of the transcription factor NFATc1 SO FASEB JOURNAL LA English DT Article DE store-operated channels; bone remodeling; osteoporosis; receptor activator of nuclear factor kappa B ligand; tartrate-resistant acid phosphatase ID KAPPA-B LIGAND; T-CELLS C1; BONE-RESORPTION; GENE-EXPRESSION; TERMINAL DIFFERENTIATION; OSTEOPROTEGERIN LIGAND; RECEPTOR ACTIVATOR; SIGNALING PATHWAY; PROTEIN-KINASE; NUCLEAR FACTOR AB Bone diseases such as postmenopausal osteoporosis are primarily caused by excessive formation and activity of osteoclasts (OCLs). Receptor activator of nuclear factor-kappa B ligand (RANKL) is a key initiating cytokine for OCL differentiation and function. RANKL induces calcium (Ca2+) oscillations, resulting in selective and robust induction of nuclear factor of activated T cells c1 (NFATc1), a Ca2+-responsive transcription factor that drives osteoclastogenesis. Store-operated Ca2+ entry (SOCE) is a major Ca2+ influx pathway in most nonexcitable cell types and is activated by any stimulus that depletes Ca2+ stores in the endoplasmic reticulum. Although the role of Orai1, a SOCE channel in the plasma membrane, in maintaining Ca2+ oscillations and transactivation of NFAT in other cell types is well known, its contribution to osteoclastogenesis remains unclear. We show here that silencing of the Orai1 gene with viral delivery of shRNA reduces SOCE and inhibits RANKL-induced osteoclastogenesis of RAW264.7 cells, a murine monocyte/macrophage cell line, by suppressing the induction of NFATc1. This was accompanied by defective induction of OCL-specific genes, such as tartrate-resistant acid phosphatase and immunoreceptor OCL-associated receptor, which are known to be direct transcriptional targets of NFATc1 during osteoclastogenesis. In addition, maturation of OCLs was abrogated by defective cell fusion of pre-OCLs depleted of Orai1, consistent with defective RANKL-mediated induction of d2 isoform of vacuolar ATPase V-o domain that is involved in cell fusion of pre-OCLs. We found that the functional bone resorbing capacity was severely impaired in OCLs depleted of Orai1, potentially related to the observed decrease in the induction of cathepsin K, a major bone matrix degrading protease. Our results indicate that Orai1 plays a critical role in the differentiation and function of OCLs, suggesting that Orai1 might be a potential therapeutic target for the treatment or prevention of bone loss caused by OCLs.-Hwang, S.-Y., Putney, J. W. Orai1-mediated calcium entry plays a critical role in osteoclast differentiation and function by regulating activation of the transcription factor NFATc1. FASEB J. 26, 1484 -1492 (2012). www.fasebj.org C1 [Hwang, Sung-Yong; Putney, James W.] NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Hwang, SY (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM hwangs3@niehs.nih.gov FU U.S. National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS) FX This research was supported by the Intramural Research Program of the U.S. National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS). The authors thank Dr. Xiaoling Li and Dr. Robert Oakley for helpful comments. The authors thank Dr. Gary Bird for technical advice and helpful discussion. The authors also thank Dr. Charles Romeo and Dr. Negin Martin (Viral Vector Core, NIEHS) for lentivirus preparations. NR 48 TC 20 Z9 20 U1 0 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 IS 4 BP 1484 EP 1492 DI 10.1096/fj.11-194399 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 919VS UT WOS:000302359700011 PM 22198385 ER PT J AU Beall, SA DeCherney, A AF Beall, Stephanie A. DeCherney, Alan TI History and challenges surrounding ovarian stimulation in the treatment of infertility SO FERTILITY AND STERILITY LA English DT Review DE Gonadotropin; ovarian stimulation; ovulation induction; history; multiple births ID IN-VITRO FERTILIZATION; RECOMBINANT HUMAN FSH; OVULATION INDUCTION; HUMAN EMBRYO; PREGNANCY; FOLLICLE; HORMONE; SEQUENCE; SUPEROVULATION; REIMPLANTATION AB Objective: To examine the history of superovulation for ovulation induction, its contributions to reproductive medicine, and its impact on multiple births. Design: A search of the relevant literature using PubMed and other online tools. Result(s): Infertility has been a condition known and studied for thousands of years. However, it was not until this past century that effective treatments were developed. With the advancement of our knowledge of the hypothalamic-pituitary axis, therapies utilizing gonadotropins were developed to stimulate ovulation. Not only could we now treat anovulatory infertility but also induce superovulation for IVF. With these successes came consequences, including increased multiple pregnancies. Several countries recognized the high costs associated with multiple births and implemented regulations on the infertility industry. The rate of triplet and higher-order multiples has declined over the past decade. This is largely attributed to a decreased number of embryos transferred. Nonetheless, the twin rate has remained consistently high. Conclusion(s): Superovulation has become a routine medical therapy used for ovulation induction and IVF. With the development of this technology have come effective therapies for infertility and new ethical and medical challenges. Since the advent of gonadotropin therapy we have already developed technologies to improve monitoring and decrease hyperstimulation and high-order multiple pregnancies. In the future we anticipate new tools devised to optimize one embryo for one singleton live birth. (Fertil Steril (R) 2012;97:795-801. (C)2012 by American Society for Reproductive Medicine.) C1 [DeCherney, Alan] NICHHD, Reprod Biol & Med Branch, NIH, CRC, Bethesda, MD 20892 USA. RP DeCherney, A (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, CRC, Bldg 10,Room 1E-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM decherna@mail.nih.gov FU Intramural NIH HHS [Z01 HD008737-08] NR 40 TC 7 Z9 9 U1 0 U2 11 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 APR PY 2012 VL 97 IS 4 BP 795 EP 801 DI 10.1016/j.fertnstert.2012.02.030 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 917AE UT WOS:000302143500006 PM 22463773 ER PT J AU Harlow, SD Gass, M Hall, JE Lobo, R Maki, P Rebar, RW Sherman, S Sluss, PM de Villiers, TJ AF Harlow, Sioban D. Gass, Margery Hall, Janet E. Lobo, Roger Maki, Pauline Rebar, Robert W. Sherman, Sherry Sluss, Patrick M. de Villiers, Tobie J. CA STRAW Collaborative Group TI Executive summary of the Stages of Reproductive Aging Workshop+10: addressing the unfinished agenda of staging reproductive aging SO FERTILITY AND STERILITY LA English DT Article DE Reproductive aging; ovarian aging; menopause; follicle-stimulating hormone; antimullerian hormone; antral follicle count; inhibin-B ID FOLLICLE-STIMULATING-HORMONE; ANTI-MULLERIAN HORMONE; EARLY MENOPAUSAL TRANSITION; POLYCYSTIC-OVARY-SYNDROME; MIDDLE-AGED WOMEN; REGULAR MENSTRUAL CYCLES; INHIBIN-B; ANTIMULLERIAN HORMONE; LONGITUDINAL CHANGES; DEPRESSIVE SYMPTOMS AB Objective: The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period. Method(s): Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimullerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus. Result(s): STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage -3) and the early postmenopause stage (Stage +1), provided information on the duration of the late transition (Stage -1) and early postmenopause (Stage +1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics. Conclusion(s): STRAW + 10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW + 10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified. (Fertil Steril (R) 2012;97:843-51. (C)2012 by American Society for Reproductive Medicine.) C1 [Harlow, Sioban D.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Gass, Margery] N Amer Menopause Soc, Mayfield Hts, OH USA. [Hall, Janet E.] Harvard Univ, Sch Med, Dept Med, Endocrine Soc, Boston, MA USA. [Lobo, Roger] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. [Maki, Pauline] Univ Illinois, Dept Psychiat & Psychol, Chicago, IL USA. [Rebar, Robert W.] Amer Soc Reprod Med, Birmingham, AL USA. [Sherman, Sherry] NIA, Bethesda, MD 20892 USA. [Sluss, Patrick M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [de Villiers, Tobie J.] Int Menopause Soc, Cape Town, South Africa. RP Harlow, SD (reprint author), Univ Michigan, Dept Epidemiol, 1415 Washington Hts, Ann Arbor, MI 48109 USA. EM harlow@umich.edu FU National Institute on Aging (NIA); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); North American Menopause Society (NAMS); Endocrine Society; National Institute on Mental Health (NIMH); National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Drug Abuse (NIDA); Royal Ottawa Foundation for Mental Health; Mayo Clinic; Baycrest; Northwestern University; Society for Women's Health Research; International Menopause Society; Pfizer; Australasian Pacific Menopause Society; Virginia Commonwealth University Institute for Women's Health; Adcock Ingram; Servier; Amgen; Bayer; National Institutes of Health (NIH); Department of Health and Human Services (DHHS), through the National Institute on Aging (NIA) [AG039961]; NIH Office of Research on Women's Health (ORWH); International Menopause Society (IMS) FX S. D. H. has grant support from the National Institute on Aging (NIA) and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and receives travel support from NAMS. M. G. receives salary support from The North American Menopause Society (NAMS). J.E.H. has grant support from NIA and receives travel support from the Endocrine Society. R. L. is past president of the American Society for Reproductive Medicine (ASRM). P. M. receives grant support from the National Institute on Mental Health (NIMH), the NIA, the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute on Drug Abuse (NIDA); is on the Board of Trustees for NAMS; and has previously consulted for Noven Pharmaceuticals, received lecture fees from the Royal Ottawa Foundation for Mental Health, the Mayo Clinic, Baycrest, and Northwestern University and received travel support from the Society for Women's Health Research, the International Menopause Society, Pfizer, the Australasian Pacific Menopause Society, Virginia Commonwealth University Institute for Women's Health. R. W. R. receives salary support from ASRM. S. S. has nothing to disclose. P. M. S. has nothing to disclose. T.J.d.V. declares no direct conflict of interest as regards the submitted article but has in the past received consultancy fees from Adcock Ingram and Pfizer; speaker's fees from Servier; and travel support from Amgen, Pfizer, and Bayer.; The Stages of Reproductive Aging Workshop (STRAW) + 10 had grant support from the National Institutes of Health (NIH), Department of Health and Human Services (DHHS), through the National Institute on Aging (NIA) (AG039961), and the NIH Office of Research on Women's Health (ORWH) as well as from The North American Menopause Society (NAMS), the American Society for Reproductive Medicine (ASRM), the International Menopause Society (IMS), and the Endocrine Society. NR 90 TC 35 Z9 36 U1 0 U2 9 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 APR PY 2012 VL 97 IS 4 BP 843 EP 851 DI 10.1016/j.fertnstert.2012.01.128 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 917AE UT WOS:000302143500013 PM 22341880 ER PT J AU Huang, H Hansen, KR Factor-Litvak, P Carson, SA Guzick, DS Santoro, N Diamond, MP Eisenberg, E Zhang, HP AF Huang, Hao Hansen, Karl R. Factor-Litvak, Pamela Carson, Sandra A. Guzick, David S. Santoro, Nanette Diamond, Michael P. Eisenberg, Esther Zhang, Heping CA Natl Inst Child Hlth Human Dev TI Predictors of pregnancy and live birth after insemination in couples with unexplained or male-factor infertility SO FERTILITY AND STERILITY LA English DT Article DE Infertility; lifestyle; pregnancy; live birth; insemination; superovulation ID ALCOHOL-CONSUMPTION; CAFFEINE INTAKE; CIGARETTE-SMOKING; LIFE-STYLE; INTRAUTERINE INSEMINATION; EUROPEAN MULTICENTER; OCCUPATIONAL FACTORS; SEMEN QUALITY; FECUNDABILITY; FERTILITY AB Objective: To identify risk factors for pregnancy outcomes in couples treated with intracervical or intrauterine insemination, with or without superovulation for unexplained or male-factor infertility. Design: Secondary analysis of data from a randomized superovulation and intrauterine insemination trial. Setting: Academic medical centers. Intervention(s): Treatment continued for four cycles unless pregnancy was achieved. Patient(s): Out of 932 couples randomized to four treatment groups, 664 couples who had completed the lifestyle questionnaires were assessed for occurrence of pregnancy and live birth. Main Outcome Measure(s): Pregnancy and live birth. Result(s): The pregnancy and live birth rates were significantly higher in couples in which the female partners reported that they had consumed coffee or tea in the past or drank alcoholic beverages in the past (past users) compared with those who had never consumed coffee, tea, or alcoholic beverages. Past users also had significantly higher pregnancy and live birth rates than those currently consuming coffee or tea or alcoholic beverages. Demographic, occupational exposure, and other lifestyle factors were not significant. Conclusion(s): Couples in which the female partners drank coffee, tea, or alcoholic beverages in the past had higher pregnancy and live birth rates compared with never or current users. When discontinuing these habits, they might have made other lifestyle changes to improve the pregnancy outcome. (Fertil Steril (R) 2012; 97: 959-67. (C) 2012 by American Society for Reproductive Medicine.) C1 [Huang, Hao; Zhang, Heping] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Hansen, Karl R.] Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Sect Reprod Endocrinol & Infertil, Oklahoma City, OK 73190 USA. [Factor-Litvak, Pamela] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Carson, Sandra A.] Women & Infants Hosp Rhode Isl, Div Reprod Endocrinol & Infertil, Providence, RI 02908 USA. [Guzick, David S.] Univ Florida, Hlth Sci Ctr, Gainesville, FL USA. [Santoro, Nanette] Univ Colorado, Sch Med, Dept Obstet & Gynecol, Aurora, CO USA. [Diamond, Michael P.] Wayne State Univ, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Detroit, MI USA. [Eisenberg, Esther] Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Nashville, TN 37232 USA. [Eisenberg, Esther] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Med Network, Reprod Sci Branch, Ctr Populat Res,NIH, Bethesda, MD USA. RP Zhang, HP (reprint author), 60 Coll St, New Haven, CT 06520 USA. EM heping.zhang@yale.edu OI Diamond, Michael/0000-0001-6353-4489 FU National Institutes of Health (NIH)/National Institute of Child Health and Human Development (NICHD) [HD55925, U10 HD39005] FX Supported by National Institutes of Health (NIH)/National Institute of Child Health and Human Development (NICHD) grants HD55925 and U10 HD39005. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD or NIH. NR 39 TC 3 Z9 3 U1 0 U2 5 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 APR PY 2012 VL 97 IS 4 BP 959 EP U374 DI 10.1016/j.fertnstert.2012.01.090 PG 14 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 917AE UT WOS:000302143500031 PM 22270557 ER PT J AU Rasmussen, DL Kobayashi, SD DeLeo, FR AF Rasmussen, Devon L. Kobayashi, Scott D. DeLeo, Frank R. TI Flexicate molecules as a potential new class of antibiotics SO FUTURE MICROBIOLOGY LA English DT Article DE antibiotic; antimicrobial; flexicate; helicate ID OPTICALLY PURE; DNA-BINDING; SUPRAMOLECULAR CYLINDERS; BIS(PYRIDYLIMINE) LIGAND; DINUCLEAR COMPLEXES AB Evaluation of: Howson SE, Bolhuis A, Brabec V et al. Optically pure, water-stable metallo-helical 'flexicate' assemblies with antibiotic activity. Nat. Chem. 4(1), 31-36 (2011). Helicates are a-helical, nonpeptide complexes that bind to DNA and exhibit antimicrobial activity. In the past, enthusiasm for the use of helicates in biological applications was limited, at least in part, by the presence of a racemic mixture of enantiomers or the formation of complexes that are insoluble in aqueous solutions. Recently, Howson et al, overcame the barriers associated with helicate synthesis by generating helicate-like complexes that are soluble and stable in water, optically pure and synthetically flexible. The mechanism synthesizes nonpeptide mimetic a-helical 'flexicates' that bind to DNA and show broad-spectrum antimicrobial activity against representative Gram-positive and Gram-negative bacterial pathogens. Although the application of flexicates as an antimicrobial therapy remains to be determined, this study provides important insight into flexicate activity and the prospective use of flexicates as microbicidal agents. C1 [Rasmussen, Devon L.; Kobayashi, Scott D.; DeLeo, Frank R.] NIAID, Lab Bacteriol Pathogenesis, Rocky Mt Lab, NIH, Hamilton, MT 59840 USA. RP DeLeo, FR (reprint author), NIAID, Lab Bacteriol Pathogenesis, Rocky Mt Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516 FU National Institute of Allergy and Infectious Diseases, NIH FX The authors are supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH. 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 18 TC 0 Z9 0 U1 1 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0913 J9 FUTURE MICROBIOL JI Future Microbiol. PD APR PY 2012 VL 7 IS 4 BP 445 EP 448 DI 10.2217/FMB.12.26 PG 4 WC Microbiology SC Microbiology GA 917SN UT WOS:000302199000008 PM 22439721 ER PT J AU Cook, MB Shaheen, NJ Anderson, LA Giffen, C Chow, WH Vaughan, TL Whiteman, DC Corley, DA AF Cook, Michael B. Shaheen, Nicholas J. Anderson, Lesley A. Giffen, Carol Chow, Wong-Ho Vaughan, Thomas L. Whiteman, David C. Corley, Douglas A. TI Cigarette Smoking Increases Risk of Barrett's Esophagus: An Analysis of the Barrett's and Esophageal Adenocarcinoma Consortium SO GASTROENTEROLOGY LA English DT Article DE BEACON; Esophageal Cancer; Population Study; Tobacco ID GASTROESOPHAGEAL-REFLUX DISEASE; GASTRIC CARDIA; GENERAL-POPULATION; LUNG-CANCER; ACID REFLUX; ESOPHAGOGASTRIC JUNCTION; PROSPECTIVE COHORT; TOTAL EXPOSURE; ALCOHOL; TOBACCO AB BACKGROUND & AIMS: Cigarette smoking has been implicated in the etiology of esophageal adenocarcinoma, but it is not clear if smoking is a risk factor for Barrett's esophagus. We investigated whether tobacco smoking and other factors increase risk for Barrett's esophagus. METHODS: We analyzed data from 5 case-control studies included in the international Barrett's and Esophageal Adenocarcinoma Consortium. We compared data from subjects with Barrett's esophagus (n = 1059) with those from subjects with gastroesophageal reflux disease (gastroesophageal reflux disease controls, n = 1332), and population-based controls (n = 1143), using multivariable logistic regression models to test associations with cigarette smoking. We also tested whether cigarette smoking has synergistic effects with other exposures, which might further increase risk for Barrett's esophagus. RESULTS: Subjects with Barrett's esophagus were significantly more likely to have ever smoked cigarettes than the population-based controls (odds ratio [OR] = 1.67; 95% confidence interval [CI]: 1.04-2.67) or gastroesophageal reflux disease controls (OR = 1.61; 95% CI: 1.33-1.96). Increasing pack-years of smoking increased the risk for Barrett's esophagus. There was evidence of a synergy between ever-smoking and heartburn or regurgitation; the attributable proportion of disease among individuals who ever smoked and had heartburn or regurgitation was estimated to be 0.39 (95% CI: 0.25-0.52). CONCLUSIONS: Cigarette smoking is a risk factor for Barrett's esophagus. The association was strengthened with increased exposure to smoking until similar to 20 pack-years, when it began to plateau. Smoking has synergistic effects with heartburn or regurgitation, indicating that there are various pathways by which tobacco smoking might contribute to development of Barrett's esophagus. C1 [Cook, Michael B.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20852 USA. [Shaheen, Nicholas J.] Univ N Carolina, Chapel Hill, NC USA. [Anderson, Lesley A.] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland. [Giffen, Carol] Informat Management Serv Inc, Bethesda, MD USA. [Vaughan, Thomas L.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. [Whiteman, David C.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Corley, Douglas A.] Kaiser Permanente, Div Res, Oakland, CA USA. [Corley, Douglas A.] Kaiser Permanente, Oakland Med Ctr, Oakland, CA USA. RP Cook, MB (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS,Suite 550,Room 5014, Bethesda, MD 20852 USA. EM michael.cook@nih.gov RI Shaheen, Nicholas/A-1898-2013; Cook, Michael/A-5641-2009; Whiteman, David/P-2728-2014; OI Cook, Michael/0000-0002-0533-7302; Whiteman, David/0000-0003-2563-9559; Anderson, Lesley/0000-0002-1000-3649 FU National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases [K23DK59311, R03DK75842]; Ireland-Northern Ireland Co-operation Research Project; Northern Ireland Research and Development Office; Health Research Board, Ireland; Ulster Cancer Foundation (Belfast, Northern Ireland); National Institutes of Health Epidemiology and Incidence of Barrett's Esophagus [RO1 DK63616-01]; Barrett's Esophagus and Women [1R21DK077742-01A1]; National Cancer Institute [5 RO1 CA 001833-02, R01 CA72866]; Established Investigator Award in Cancer Prevention and Control [K05 CA124911] FX M.B.C. and W.-H.C. were supported by the Intramural Program of the National Institutes of Health. The Epidemiologic Case-Control Study of Barrett's Esophagus was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (K23DK59311 and R03DK75842) awarded to N.J.S. The Factors Influencing the Barrett's Adenocarcinoma Relationship Study was funded by an Ireland-Northern Ireland Co-operation Research Project Grant sponsored by the Northern Ireland Research and Development Office, and the Health Research Board, Ireland (All-Ireland Case-Control Study of Oesophageal Adenocarcinoma and Barrett's Oesophagus, awarded to L.J.M. and Harry Comber). Additional funding was provided by the Ulster Cancer Foundation (Belfast, Northern Ireland) and the Northern Ireland Research and Development Office Clinical Fellowship. The Kaiser Permanente Barrett's Esophagus studies and the data integration for the current project were funded by National Institutes of Health Epidemiology and Incidence of Barrett's Esophagus RO1 DK63616-01 (D.A.C.) and Barrett's Esophagus and Women 1R21DK077742-01A1 (D.A.C., N.J.S.). The Study of Digestive Health was supported by grant number 5 RO1 CA 001833-02 from the National Cancer Institute awarded to D.C.W., Adele C. Green, Nicholas K. Hayward, Peter G. Parsons, Sandra J. Pavey, David M. Purdie, Penelope M. Webb, David Gotley, B. Mark Smithers, Glyn G. Jamieson, Paul Drew, David I. Watson, Andrew Clouston. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. The Study of Reflux Disease was funded by the National Cancer Institute (R01 CA72866) awarded to T.L.V. and Diana Farrow; Established Investigator Award in Cancer Prevention and Control (K05 CA124911) awarded to T.L.V. NR 65 TC 55 Z9 56 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2012 VL 142 IS 4 BP 744 EP 753 DI 10.1053/j.gastro.2011.12.049 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 919BU UT WOS:000302296400023 PM 22245667 ER PT J AU Roessler, S Long, EL Budhu, A Chen, YD Zhao, XL Ji, JF Walker, R Jia, HL Ye, QH Qin, LX Tang, ZY He, P Hunter, KW Thorgeirsson, SS Meltzer, PS Wang, XW AF Roessler, Stephanie Long, Ezhou Lori Budhu, Anuradha Chen, Yidong Zhao, Xuelian Ji, Junfang Walker, Robert Jia, Hu-Liang Ye, Qing-Hai Qin, Lun-Xiu Tang, Zhao-You He, Ping Hunter, Kent W. Thorgeirsson, Snorri S. Meltzer, Paul S. Wang, Xin Wei TI Integrative Genomic Identification of Genes on 8p Associated With Hepatocellular Carcinoma Progression and Patient Survival SO GASTROENTEROLOGY LA English DT Article DE Liver Cancer; Tumor Profiling; Cancer Driver Genes ID GTPASE-ACTIVATING PROTEIN; NEGATIVE BREAST-CANCER; ARRAY CGH DATA; TUMOR-SUPPRESSOR; LIVER-CANCER; EXPRESSION; DLC-1; METASTASIS; CELLS; PREDICTION AB BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is an aggressive malignancy; its mechanisms of development and progression are poorly understood. We used an integrative approach to identify HCC driver genes, defined as genes whose copy numbers associate with gene expression and cancer progression. METHODS: We combined data from high-resolution, array-based comparative genomic hybridization and transcriptome analysis of HCC samples from 76 patients with hepatitis B virus infection with data on patient survival times. Candidate genes were functionally validated using in vitro and in vivo models. RESULTS: Unsupervised analyses of array comparative genomic hybridization data associated loss of chromosome 8p with poor outcome (reduced survival time); somatic copy number alterations correlated with expression of 27.3% of genes analyzed. We associated expression levels of 10 of these genes with patient survival times in 2 independent cohorts (comprising 319 cases of HCC with mixed etiology) and 3 breast cancer cohorts (637 cases). Among the 10-gene signature, a cluster of 6 genes on 8p, (DLC1, CCDC25, ELP3, PROSC, SH2D4A, and SORBS3) were deleted in HCCs from patients with poor outcomes. In vitro and in vivo analyses indicated that the products of PROSC, SH2D4A, and SORBS3 have tumor-suppressive activities, along with the known tumor suppressor gene DLC1. CONCLUSIONS: We used an unbiased approach to identify 10 genes associated with HCC progression. These might be used in assisting diagnosis and to stage tumors based on gene expression patterns. C1 [Roessler, Stephanie; Budhu, Anuradha; Zhao, Xuelian; Ji, Junfang; Wang, Xin Wei] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Long, Ezhou Lori; Chen, Yidong; Walker, Robert] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. [Jia, Hu-Liang; Ye, Qing-Hai; Qin, Lun-Xiu; Tang, Zhao-You] Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China. [He, Ping] FDA CBER OBRR, Div Hematol, Bethesda, MD USA. [Hunter, Kent W.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Wang, XW (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. EM xw3u@nih.gov RI Wang, Xin/B-6162-2009 FU Center for Cancer Research, the US National Cancer Institute [Z01 BC 010313, Z01 BC 010876] FX Supported in part by the Intramural Research Program of the Center for Cancer Research, the US National Cancer Institute (Z01 BC 010313 and Z01 BC 010876). NR 48 TC 71 Z9 73 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2012 VL 142 IS 4 BP 957 EP U451 DI 10.1053/j.gastro.2011.12.039 PG 22 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 919BU UT WOS:000302296400045 PM 22202459 ER PT J AU Thomas, E Gonzalez, VD Li, QS Modi, AA Chen, WP Noureddin, M Rotman, Y Liang, TJ AF Thomas, Emmanuel Gonzalez, Veronica D. Li, Qisheng Modi, Ankit A. Chen, Weiping Noureddin, Mazen Rotman, Yaron Liang, T. Jake TI HCV Infection Induces a Unique Hepatic Innate Immune Response Associated With Robust Production of Type III Interferons SO GASTROENTEROLOGY LA English DT Article DE IRF; Cytokine; IL29; Nonresponder ID C VIRUS-INFECTION; ADAPTIVE IMMUNITY; CHIMPANZEES; REPLICATION; RECOGNITION; MECHANISM; KINETICS; CULTURE; SYSTEM; GENOME AB BACKGROUND & AIMS: Polymorphisms in the IL28B gene have been associated with clearance of hepatitis C virus (HCV), indicating a role for type III interferons (IFNs) in HCV infection. Little is known about the function of type III IFNs in intrinsic antiviral innate immunity. METHODS: We used in vivo and in vitro models to characterize the role of the type III IFNs in HCV infection and analyzed gene expression in liver biopsy samples from HCV-infected chimpanzees and patients. Messenger RNA and protein expression were studied in HCV-infected hepatoma cell lines and primary human hepatocytes. RESULTS: HCV infection of primary human hepatocytes induced production of chemokines and type III IFNs, including interleukin (IL)-28, and led to expression of IFN-stimulated genes (ISGs). Chimpanzees infected with HCV showed rapid induction of hepatic type III IFN, associated with up-regulation of ISGs and minimal induction of type I IFNs. In liver biopsy specimens from HCV-infected patients, hepatic expression of IL-28 correlated with levels of ISGs but not of type I IFNs. HCV infection produced extensive changes with gene expression in addition to ISGs in primary human hepatocytes. The induction of type III IFNs is regulated by IFN regulatory factor 3 and nuclear factor kappa B. Type III IFNs up-regulate ISGs with a different kinetic profile than type 1 IFNs and induce a distinct set of genes, which might account for their functional differences. CONCLUSIONS: HCV infection results predominantly in induction of type III IFNs in livers of humans and chimpanzees; the level of induction correlates with hepatic levels of ISGs. These findings might account for the association among IL-28, level of ISGs, and recovery from HCV infection and provide a therapeutic strategy for patients who do not respond to IFN therapy. C1 [Thomas, Emmanuel; Gonzalez, Veronica D.; Li, Qisheng; Modi, Ankit A.; Noureddin, Mazen; Rotman, Yaron; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Chen, Weiping] NIDDK, Microarray Core Facil, NIH, Bethesda, MD 20892 USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9B16, Bethesda, MD 20892 USA. EM jakel@bdg10.niddk.nih.gov RI Li, Qisheng/K-1909-2013; OI Rotman, Yaron/0000-0002-7549-8216 FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health [N01-DK-7-0004/HHSN26700700004C]; Swedish Research Council; Wenner-Gren Foundation FX Supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. E. T. was supported by funding from the National Institutes of Health Loan Repayment Program. V. D. G. was supported by the Swedish Research Council and the Wenner-Gren Foundation. PHH cultures were provided by the National Institutes of Health-funded Liver Tissue Procurement and Cell Distribution System (N01-DK-7-0004/HHSN26700700004C) (principal investigator: Stephen Strom, University of Pittsburgh). NR 27 TC 139 Z9 142 U1 0 U2 9 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 APR PY 2012 VL 142 IS 4 BP 978 EP 988 DI 10.1053/j.gastro.2011.12.055 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 919BU UT WOS:000302296400047 PM 22248663 ER PT J AU Andersen, JB Spee, B Blechacz, BR Avital, I Komuta, M Barbour, A Conner, EA Gillen, MC Roskams, T Roberts, LR Factor, VM Thorgeirsson, SS AF Andersen, Jesper B. Spee, Bart Blechacz, Boris R. Avital, Itzhak Komuta, Mina Barbour, Andrew Conner, Elizabeth A. Gillen, Matthew C. Roskams, Tania Roberts, Lewis R. Factor, Valentina M. Thorgeirsson, Snorri S. TI Genomic and Genetic Characterization of Cholangiocarcinoma Identifies Therapeutic Targets for Tyrosine Kinase Inhibitors SO GASTROENTEROLOGY LA English DT Article DE Genetic Analysis; Gene Expression; CCA; Hepatic ID HEPATOCELLULAR-CARCINOMA; INTRAHEPATIC CHOLANGIOCARCINOMA; BILIARY CANCER; EXPRESSION PROFILES; BREAST-CANCER; LUNG-CANCER; PHASE-II; RECEPTOR; MUTATIONS; SURVIVAL AB BACKGROUND & AIMS: Cholangiocarcinoma is a heterogeneous disease with a poor outcome that accounts for 5% - 10% of primary liver cancers. We characterized its genomic and genetic features and associated these with patient responses to therapy. METHODS: We profiled the transcriptomes from 104 surgically resected cholangiocarcinoma samples collected from patients in Australia, Europe, and the United States; epithelial and stromal compartments from 23 tumors were laser capture micro-dissected. We analyzed mutations in KRAS, epidermal growth factor receptor (EGFR), and BRAF in samples from 69 tumors. Changes in gene expression were validated by immunoblotting and immunohistochemistry; integrative genomics combined data from the patients with data from 7 human cholangiocarcinoma cell lines, which were then exposed to trastuzumab and lapatinib. RESULTS: Patients were classified into 2 subclasses, based on 5-year survival rate (72% vs 30%; chi(2) = 11.61; P < .0007), time to recurrence (13.7 vs 22.7 months; P < .001), and the absence or presence of KRAS mutations (24.6%), respectively. Class comparison identified 4 survival subgroups (SGI-IV; chi(2) = 8.34; P < .03); SGIII was characterized by genes associated with proteasomal activity and the worst prognosis. The tumor epithelium was defined by deregulation of the HER2 network and frequent overexpression of EGFR, the hepatocyte growth factor receptor (MET), pRPS6, and Ki67, whereas stroma was enriched in inflammatory cytokines. Lapatinib, an inhibitor of HER2 and EGFR, was more effective in inhibiting growth of cholangiocarcinoma cell lines than trastuzumab. CONCLUSIONS: We provide insight into the pathogenesis of cholangiocarcinoma and identify previously unrecognized subclasses of patients, based on KRAS mutations and increased levels of EGFR and HER2 signaling, who might benefit from dual-target tyrosine kinase inhibitors. The group of patients with the worst prognosis was characterized by transcriptional enrichment of genes that regulate proteasome activity, indicating new therapeutic targets. C1 [Andersen, Jesper B.; Conner, Elizabeth A.; Gillen, Matthew C.; Factor, Valentina M.; Thorgeirsson, Snorri S.] NIH, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. [Avital, Itzhak] NIH, Surg Branch, Bethesda, MD 20892 USA. [Spee, Bart; Komuta, Mina; Roskams, Tania] Univ Leuven, Louvain, Belgium. [Blechacz, Boris R.; Roberts, Lewis R.] Mayo Clin, Rochester, MN USA. [Barbour, Andrew] Univ Queensland, Brisbane, Qld, Australia. RP Thorgeirsson, SS (reprint author), NCI, Bldg 37,Room 4146A,37 Convent Dr, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov RI Barbour, Andrew/F-4717-2010; OI Roberts, Lewis/0000-0001-7885-8574; Andersen , Jesper B/0000-0003-1760-5244 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health; National Institutes of Health [CA100882, CA128633, P30DK084567]; Danish Medical Research Council [271-070712] FX Supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health; National Institutes of Health grants CA100882 and CA128633 (to L.R.R.) and P30DK084567 (Mayo Clinic Center for Cell Signaling in Gastroenterology); and grant 271-070712 from the Danish Medical Research Council (to J.B.A.). NR 31 TC 115 Z9 120 U1 0 U2 11 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 APR PY 2012 VL 142 IS 4 BP 1021 EP U552 DI 10.1053/j.gastro.2011.12.005 PG 26 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 919BU UT WOS:000302296400051 PM 22178589 ER PT J AU Logue, JS Morrison, DK AF Logue, Jeremy S. Morrison, Deborah K. TI Complexity in the signaling network: insights from the use of targeted inhibitors in cancer therapy SO GENES & DEVELOPMENT LA English DT Review DE cancer therapy; signal transduction; targeted inhibitors ID SRC FAMILY KINASES; CELL LUNG-CANCER; TYROSINE KINASE; ACQUIRED-RESISTANCE; BREAST-CANCER; TUMOR-SUPPRESSOR; PHOSPHATIDYLINOSITOL 3-KINASE/AKT; TRASTUZUMAB RESISTANCE; PATHWAY ACTIVATION; MET AMPLIFICATION AB Cancer often arises when normal cellular growth goes awry due to defects in critical signal transduction pathways. A growing number of inhibitors that target specific components of these pathways are in clinical use, but the success of these agents has been limited by the resistance to inhibitor therapy that ultimately develops. Studies have now shown that cancer cells respond to chronic drug treatment by adapting their signaling circuitry, taking advantage of pathway redundancy and routes of feedback and cross-talk to maintain their function. This review focuses on the compensatory signaling mechanisms highlighted by the use of targeted inhibitors in cancer therapy. C1 [Logue, Jeremy S.; Morrison, Deborah K.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. RP Morrison, DK (reprint author), NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. EM morrisod@mail.nih.gov FU National Cancer Institute FX Our work is supported by federal funds from the National Cancer Institute. NR 80 TC 87 Z9 88 U1 0 U2 12 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 APR 1 PY 2012 VL 26 IS 7 BP 641 EP 650 DI 10.1101/gad.186965.112 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 921UJ UT WOS:000302502900003 PM 22474259 ER PT J AU Biesecker, LG AF Biesecker, Leslie G. TI Opportunities and challenges for the integration of massively parallel genomic sequencing into clinical practice: lessons from the ClinSeq project SO GENETICS IN MEDICINE LA English DT Article DE genetic mutation; incidental findings; inherited disease; massively parallel sequencing ID MEDICINE; MUTATION; DNA AB Purpose: The debate surrounding the return of results from high-throughput genomic interrogation encompasses many important issues including ethics, law, economics, and social policy. As well, the debate is also informed by the molecular, genetic, and clinical foundations of the emerging field of clinical genomics, which is based on this new technology. This article outlines the main biomedical considerations of sequencing technologies and demonstrates some of the early clinical experiences with the technology to enable the debate to stay focused on real-world practicalities. Methods: These experiences are based on early data from the ClinSeq project, which is a project to pilot the use of massively parallel sequencing in a clinical research context with a major aim to develop modes of returning results individual subjects. Results: The study has enrolled >900 subjects and generated exome sequence data on 572 subjects. These data are beginning to be interpreted and returned to the subjects, which provides examples of the potential usefulness and pitfalls of clinical genomics. Conclusion: There are numerous genetic results that can be readily derived from a genome including rare, high-penetrance traits, and carrier states. However, much work needs to be done to develop the tools and resources for genomic interpretation. The main lesson learned is that a genome sequence may be better considered as a health-care resource, rather than a test, one that can be interpreted and used over the lifetime of the patient. C1 [Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Biesecker, Leslie G.] NHGRI, Natl Inst Hlth Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. RP Biesecker, LG (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. EM leslieb@helix.nih.gov FU National Institutes of Health, National Human Genome Research Institute [2-R01-HG003178] FX The author acknowledges and thanks all members of both the ClinSeq and the rare disease research teams for their outstanding efforts in these programs, which have generated and pursued many of the ideas described here. The author is supported entirely by the Intramural Research Program of the National Human Genome Research Institute of the National Institutes of Health. The symposium at which the oral version of this article was presented was supported by National Institutes of Health, National Human Genome Research Institute grant no. 2-R01-HG003178 on "Managing Incidental Findings and Research Results in Genomic Biobanks & Archives" (S. Wolf, principal investigator). NR 14 TC 83 Z9 85 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD APR PY 2012 VL 14 IS 4 SI SI BP 393 EP 398 DI 10.1038/gim.2011.78 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 922RL UT WOS:000302565600005 PM 22344227 ER PT J AU Green, RC Berg, JS Berry, GT Biesecker, LG Dimmock, DP Evans, JP Grody, WW Hegde, MR Kalia, S Korf, BR Krantz, I McGuire, AL Miller, DT Murray, MF Nussbaum, RL Plon, SE Rehm, HL Jacob, HJ AF Green, Robert C. Berg, Jonathan S. Berry, Gerard T. Biesecker, Leslie G. Dimmock, David P. Evans, James P. Grody, Wayne W. Hegde, Madhuri R. Kalia, Sarah Korf, Bruce R. Krantz, Ian McGuire, Amy L. Miller, David T. Murray, Michael F. Nussbaum, Robert L. Plon, Sharon E. Rehm, Heidi L. Jacob, Howard J. TI Exploring concordance and discordance for return of incidental findings from clinical sequencing SO GENETICS IN MEDICINE LA English DT Article DE incidental findings; whole-exome sequencing; whole-genome sequencing ID GENOMIC MEDICINE; PATIENT AB Purpose: The aim of this study was to explore specific conditions and types of genetic variants that specialists in genetics recommend should be returned as incidental findings in clinical sequencing. Methods: Sixteen specialists in clinical genetics and/or molecular medicine selected variants in 99 common conditions to return to the ordering physician if discovered incidentally through whole-genome sequencing. For most conditions, the specialists independently considered three molecular scenarios for both adults and minor children: a known pathogenic mutation, a truncating variant presumed pathogenic (where other truncating variants are known to be pathogenic), and a missense variant predicted in silico to be pathogenic. Results: On average, for adults and children, respectively, each specialist selected 83.5 and 79.0 conditions or genes of 99 in the known pathogenic mutation categories, 57.0 and 53.5 of 72 in the truncating variant categories, and 33.4 and 29.7 of 72 in the missense variant categories. Concordance in favor of disclosure within the adult/known pathogenic mutation category was 100% for 21 conditions or genes and 80% or higher for 64 conditions or genes. Conclusion: Specialists were highly concordant for the return of findings for 64 conditions or genes if discovered incidentally during whole-exome sequencing or whole-genome sequencing. C1 [Green, Robert C.; Kalia, Sarah; Murray, Michael F.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Green, Robert C.; Berry, Gerard T.; Kalia, Sarah; Miller, David T.; Murray, Michael F.; Rehm, Heidi L.] Harvard Univ, Sch Med, Boston, MA USA. [Green, Robert C.; Murray, Michael F.; Rehm, Heidi L.] Partners Ctr Personalized Genet Med, Boston, MA USA. [Berg, Jonathan S.; Evans, James P.] Univ N Carolina Chapel Hill Sch Med, Dept Genet, Chapel Hill, NC USA. [Berry, Gerard T.; Miller, David T.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Berry, Gerard T.] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20892 USA. [Dimmock, David P.] Med Coll Wisconsin, Dept Pediat, Div Genet, Milwaukee, WI 53226 USA. [Grody, Wayne W.] Univ Calif Los Angeles, Sch Med, Dept Human Genet, Div Med Genet, Los Angeles, CA USA. [Grody, Wayne W.] Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Div Mol Pathol, Los Angeles, CA 90024 USA. [Grody, Wayne W.] Univ Calif Los Angeles, Sch Med, Dept Pediat, Div Pediat Genet, Los Angeles, CA 90024 USA. [Hegde, Madhuri R.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA. [Korf, Bruce R.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA. [Krantz, Ian] Childrens Hosp Philadelphia, Div Human Genet & Mol Biol, Philadelphia, PA 19104 USA. [McGuire, Amy L.] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA. [Miller, David T.] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med, Div Med Genet, San Francisco, CA USA. [Plon, Sharon E.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Nussbaum, Robert L.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Plon, Sharon E.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Rehm, Heidi L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Jacob, Howard J.] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. RP Green, RC (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA. EM rcgreen@genetics.med.harvard.edu RI Dimmock, David/I-7913-2015; OI Dimmock, David/0000-0001-6690-2523; Berry, Gerard/0000-0001-5299-3313 FU National Institutes of Health [HG02213, AG027841, HG005491, HG005092, HG006615, HG003178, HG006500, CA138836, HG006485]; Manton Center for Orphan Disease Research; National Human Genome Research Institute; Baylor College of Medicine; Baylor Annual Fund FX Funding for this work was provided by National Institutes of Health grants HG02213, AG027841, HG005491, HG005092, HG006615, HG003178, HG006500, CA138836, and HG006485. G.T.B. is supported by the Manton Center for Orphan Disease Research. L.G.B. is supported by intramural funding from the National Human Genome Research Institute. A.L.M. is supported by the Baylor College of Medicine Clinical and Translational Research Program and the Baylor Annual Fund. NR 18 TC 93 Z9 93 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD APR PY 2012 VL 14 IS 4 SI SI BP 405 EP 410 DI 10.1038/gim.2012.21 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 922RL UT WOS:000302565600007 PM 22422049 ER PT J AU Lockhart, NC Yassin, R Weil, CJ Compton, CC AF Lockhart, Nicole C. Yassin, Rihab Weil, Carol J. Compton, Carolyn C. TI Intersection of biobanking and clinical care: should discrepant diagnoses and pathological findings be returned to research participants? SO GENETICS IN MEDICINE LA English DT Article DE biobank; biospecimen; diagnostic discrepancy; incidental finding; return of research results ID MANAGING INCIDENTAL FINDINGS AB Diagnostic discrepancies occur when the diagnosis made on a biospecimen during the course of review at a biobank differs from the original clinical diagnosis. These diagnostic discrepancies detected during biobanking present: unique challenges that are distinct from other types of research results or incidental findings. The proposed process for reporting diagnostic discrepancies or pathological incidental findings identified through a quality assurance evaluation at the biobank includes verification of the biospecimen identity, verification of the diagnosis within the biobank, and re-review of the case by the pathologist at the biospecimen collection site. If the pathologist at the biobank and the original pathologist do not reach agreement, an impartial and knowledgeable third party is consulted. The decision as to whether and how to notify research participants of any confirmed changes in diagnosis would be determined by institutional procedures. Implementation of this proposed process will require clear delineation of the roles and responsibilities of all involved parties in order to promote excellence in patient care and ensure that researchers have access to biospecimens of requisite quality. C1 [Lockhart, Nicole C.; Weil, Carol J.; Compton, Carolyn C.] NCI, Off Biorepositories & Biospecimen Res, NIH, Bethesda, MD 20892 USA. [Yassin, Rihab] NCI, Div Canc Biol, NIH, Bethesda, MD 20892 USA. RP Lockhart, NC (reprint author), NCI, Off Biorepositories & Biospecimen Res, NIH, Bethesda, MD 20892 USA. EM lockhani@mail.nih.gov FU National Cancer Institute (NCI); National Institutes of Health (NIH)/National Human Genome Research Institute [2-R01-HG003178] FX We thank all who participated in discussions at the National Cancer Institute (NCI)-sponsored workshop on Release of Research Results to Participants in Biospecimen Studies, particularly participants in the diagnostic discrepancy session. The diagnostic discrepancy session was chaired by Jared Schwartz and cochaired by N.C.L. Participants in the diagnostic discrepancy session included Joy Boyer, Lynn Dressler, Symma Finn, Marianne Henderson, Jennifer Hunt, Jennifer Loud, Mary Majumder, Mary Lou Smith, and Sheila Cohen Zimmet. Andrea Kelly of Rose Li and associates prepared the meeting summary. The meeting was held 8-9 July 2010, and the complete meeting summary and attendee list may be found at http://biospecimens.cancer.gov/resources/publications/workshop/rrra.asp. This article was prepared for this symposium as part of work on National Institutes of Health (NIH)/National Human Genome Research Institute grant no. 2-R01-HG003178 on "Managing Incidental Findings and Research Results in Genomic Biobanks & Archives" (S. Wolf, principal investigator), although the authors did not receive direct NIH funding for the preparation of this article. The opinions expressed in this article are the authors' own. The contents of this publication should not be construed to reflect the views or policies of the Department of Health and Human Services, the NIH, or the NCI. The work was supported by general appropriations to the NCI. NR 22 TC 3 Z9 3 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD APR PY 2012 VL 14 IS 4 SI SI BP 417 EP 423 DI 10.1038/gim.2012.11 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 922RL UT WOS:000302565600009 PM 22344228 ER PT J AU Fullerton, SM Wolf, WA Brothers, KB Clayton, EW Crawford, DC Denny, JC Greenland, P Koenig, BA Leppig, KA Lindor, NM McCarty, CA McGuire, AL Hinz, ERM Mirel, DB Ramos, EM Ritchie, MD Smith, ME Waudby, CJ Burke, W Jarvik, GP AF Fullerton, Stephanie M. Wolf, Wendy A. Brothers, Kyle B. Clayton, Ellen Wright Crawford, Dana C. Denny, Joshua C. Greenland, Philip Koenig, Barbara A. Leppig, Kathleen A. Lindor, Noralane M. McCarty, Catherine A. McGuire, Amy L. Hinz, Eugenia R. McPeek Mirel, Daniel B. Ramos, Erin M. Ritchie, Marylyn D. Smith, Maureen E. Waudby, Carol J. Burke, Wylie Jarvik, Gail P. TI Return of individual research results from genome-wide association studies: experience of the Electronic Medical Records and Genomics (eMERGE) Network SO GENETICS IN MEDICINE LA English DT Article DE biorepository; context; deliberation; electronic medical records; result return ID V-LEIDEN R506Q; TURNER-SYNDROME; HEREDITARY HEMOCHROMATOSIS; KLINEFELTER-SYNDROME; WORKING GROUP; PERSONALIZED MEDICINE; VENOUS THROMBOSIS; PARTICIPANTS; RECOMMENDATIONS; CONSORTIUM AB Purpose: Return of individual genetic results to research participants, including participants in archives and biorepositories, is receiving increased attention. However, few groups have deliberated on specific results or weighed deliberations against relevant local contextual factors. Methods: The Electronic Medical Records and Genomics (eMERGE) Network, which includes five biorepositories conducting genome-wide association studies, convened a return of results oversight committee to identify potentially returnable results. Network-wide deliberations were then brought to local constituencies for final decision making. Results: Defining results that should be considered for return required input from clinicians with relevant expertise and much deliberation. The return of results oversight committee identified two sex chromosomal anomalies, Klinefelter syndrome and Turner syndrome, as well as homozygosity for factor V Leiden, as findings that could warrant reporting. Views about returning findings of HFE gene mutations associated with hemochromatosis were mixed due to low penetrance. Review of electronic medical records suggested that most participants with detected abnormalities were unaware of these findings. Local considerations relevant to return varied and, to date, four sites have elected not to return findings (return was not possible at one site). Conclusion: The eMERGE experience reveals the complexity of return of results decision making and provides a potential deliberative model for adoption in other collaborative contexts. C1 [Fullerton, Stephanie M.; Burke, Wylie; Jarvik, Gail P.] Univ Washington, Seattle, WA 98195 USA. [Wolf, Wendy A.] Childrens Hosp, Boston, MA 02115 USA. [Brothers, Kyle B.; Clayton, Ellen Wright; Crawford, Dana C.; Denny, Joshua C.; Hinz, Eugenia R. McPeek] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Greenland, Philip; Smith, Maureen E.] Northwestern Univ, Chicago, IL 60611 USA. [Koenig, Barbara A.; Lindor, Noralane M.] Mayo Clin, Rochester, MN USA. [Koenig, Barbara A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Leppig, Kathleen A.] Grp Hlth Cooperat Puget Sound, Seattle, WA USA. [McCarty, Catherine A.; Waudby, Carol J.] Marshfield Clin Res Fdn, Marshfield, WI USA. [McCarty, Catherine A.] Essentia Inst Rural Hlth, Duluth, MN USA. [McGuire, Amy L.] Baylor Coll Med, Houston, TX 77030 USA. [Mirel, Daniel B.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Ramos, Erin M.] NHGRI, NIH, Bethesda, MD 20892 USA. [Ritchie, Marylyn D.] Penn State Univ, University Pk, PA 16802 USA. RP Fullerton, SM (reprint author), Univ Washington, Seattle, WA 98195 USA. EM smfllrtn@uw.edu RI Ritchie, Marylyn/C-1114-2012; Crawford, Dana/C-1054-2012; Jarvik, Gail/N-6476-2014; OI Jarvik, Gail/0000-0002-6710-8708; Clayton, Ellen/0000-0002-0308-4110; Fullerton, Stephanie/0000-0002-0938-6048 FU NHGRI; National Institutes of Health, Bethesda, Maryland [HG004610, AG06781, HG004608, HG04599, HG004609, HG004438, HG004424, HG004603, R01 HG003178]; State of Washington Life Sciences Discovery Fund award FX This work was supported by the following U01 grants from the NHGRI, a component of the National Institutes of Health, Bethesda, Maryland: HG004610, AG06781 (Group Health Cooperative); HG004608 (Marshfield Clinic); HG04599 (Mayo Clinic); HG004609 (Northwestern University); HG004438 (Center for Inherited Disease Research, Johns Hopkins University); HG004424 (Broad Institute); HG004603 (Vanderbilt University, also serving as the eMERGE Administrative Coordinating Center), and R01 HG003178 (University of Minnesota). Additional support was provided by a State of Washington Life Sciences Discovery Fund award to the Northwest Institute of Genetic Medicine. NR 41 TC 47 Z9 47 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD APR PY 2012 VL 14 IS 4 SI SI BP 424 EP 431 DI 10.1038/gim.2012.15 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 922RL UT WOS:000302565600010 PM 22361898 ER PT J AU Tavora, F Zhang, MC Franco, M Oliveira, JB Li, L Fowler, D Zhao, ZQ Cresswell, N Burke, A AF Tavora, Fabio Zhang, Mingchang Franco, Marcello Oliveira, Joao Bosco Li, Ling Fowler, David Zhao, Ziqin Cresswell, Nathaniel Burke, Allen TI Distribution of biventricular disease in arrhythmogenic cardiomyopathy: an autopsy study SO HUMAN PATHOLOGY LA English DT Article DE Arrhythmia; Right ventricular cardiomyopathy; Sudden death; Myocarditis ID RIGHT-VENTRICULAR CARDIOMYOPATHY; SUDDEN-DEATH; DYSPLASIA; INVOLVEMENT; DYSPLASIA/CARDIOMYOPATHY; ABNORMALITIES; DIAGNOSIS AB Arrhythmogenic cardiomyopathy is a rare cardiomyopathy characterized by fibrofatty replacement primarily of the right ventricular myocardium. It is a major cause of sudden death in the young and in athletes. There are few autopsy studies of the ventricular distribution of the disease. Fifty cases of sudden cardiac death with fibrofatty replacement in either ventricle from a single medical examiner's office were studied. Distribution of disease as determined grossly and microscopically was correlated with activity at time of death, race, and presence of inflammation. Extent of disease was right ventricular in 6 cases (12%; age, 25 +/- 5 years), biventricular in 25 (50%; age, 36 +/- 3 years), and left ventricular in 19 (38%; age, 37 +/- 3 years) (P = .13). Inflammation was present in 44% of biventricular arrhythmogenic cardiomyopathy versus 74% of left ventricular arrhythmogenic cardiomyopathy and 83% of right ventricular arrhythmogenic cardiomyopathy (P = .06). Arrhythmogenic cardiomyopathy, when presenting with sudden death, is usually biventricular. There is a trend that univentricular involvement occurs at an earlier age and that right ventricular involvement shows more inflammation, suggesting different stages of disease. (C) 2012 Elsevier Inc. All rights reserved. C1 [Burke, Allen] Univ Maryland, Dept Pathol, Med Ctr, Baltimore, MD 21201 USA. [Zhang, Mingchang; Oliveira, Joao Bosco] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Zhang, Mingchang; Zhao, Ziqin] Fudan Univ, Shanghai Med Coll, Dept Forens Med, Shanghai 200032, Peoples R China. [Tavora, Fabio; Franco, Marcello] Univ Fed Sao Paulo, Escola Paulista Med, Dept Pathol, BR-04023900 Sao Paulo, Brazil. RP Burke, A (reprint author), Univ Maryland, Dept Pathol, Med Ctr, Baltimore, MD 21201 USA. EM allen.burke@gmail.com RI Tavora, Fabio/A-7561-2009; OI Oliveira, Joao/0000-0001-9388-8173 NR 24 TC 9 Z9 10 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD APR PY 2012 VL 43 IS 4 BP 592 EP 596 DI 10.1016/j.humpath.2011.06.014 PG 5 WC Pathology SC Pathology GA 913RE UT WOS:000301894300014 PM 21937076 ER PT J AU Anto, JM Pinart, M Akdis, M Auffray, C Bachert, C Basagana, X Carlsen, KH Guerra, S von Hertzen, L Illi, S Kauffmann, F Keil, T Kiley, JP Koppelman, GH Lupinek, C Martinez, FD Nawijn, MC Postma, DS Siroux, V Smit, HA Sterk, PJ Sunyer, J Valenta, R Valverde, S Akdis, CA Annesi-Maesano, I Ballester, F Benet, M Cambon-Thomsen, A Chatzi, L Coquet, J Demoly, P Gan, WN Garcia-Aymerich, J Gimeno-Santos, E Guihenneuc-Jouyaux, C Haahtela, T Heinrich, J Herr, M Hohmann, C Jacquemin, B Just, J Kerkhof, M Kogevinas, M Kowalski, ML Lambrecht, BN Lau, S Carlsen, KCL Maier, D Momas, I Noel, P Oddie, S Palkonen, S Pin, I Porta, D Punturieri, A Ranciere, F Smith, RA Stanic, B Stein, RT van de Veen, W van Oosterhout, AJM Varraso, R Wickman, M Wijmenga, C Wright, J Yaman, G Zuberbier, T Bousquet, J AF Anto, Josep M. Pinart, Mariona Akdis, Muebeccel Auffray, Charles Bachert, Claus Basagana, Xavier Carlsen, Kai-Hakon Guerra, Stefano von Hertzen, Leena Illi, Sabina Kauffmann, Francine Keil, Thomas Kiley, James P. Koppelman, Gerard H. Lupinek, Christian Martinez, Fernando D. Nawijn, Martijn C. Postma, Dirkje S. Siroux, Valerie Smit, Henriette A. Sterk, Peter J. Sunyer, Jordi Valenta, Rudolf Valverde, Sergio Akdis, Cezmi A. Annesi-Maesano, Isabella Ballester, Ferran Benet, Marta Cambon-Thomsen, Anne Chatzi, Leda Coquet, Jonathan Demoly, Pascal Gan, Weiniu Garcia-Aymerich, Judith Gimeno-Santos, Elena Guihenneuc-Jouyaux, Chantal Haahtela, Tari Heinrich, Joachim Herr, Marie Hohmann, Cynthia Jacquemin, Benedicte Just, Jocelyne Kerkhof, Marjan Kogevinas, Manolis Kowalski, Marek L. Lambrecht, Bart N. Lau, Susanne Carlsen, Karin C. Lodrup Maier, Dieter Momas, Isabelle Noel, Patricia Oddie, Sam Palkonen, Susanna Pin, Isabelle Porta, Daniela Punturieri, Antonello Ranciere, Fanny Smith, Robert A. Stanic, Barbara Stein, Renato T. van de Veen, Willem van Oosterhout, Antoon J. M. Varraso, Raphaelle Wickman, Magnus Wijmenga, Cisca Wright, John Yaman, Gorkem Zuberbier, Torsten Bousquet, Jean CA WHO Collaborating Ctr Asthma TI Understanding the complexity of IgE-related phenotypes from childhood to young adulthood: A Mechanisms of the Development of Allergy (MeDALL) Seminar SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Allergy; Mechanisms of the Development of Allergy; Seventh Framework Program; phenotypes; IgE; asthma ID ASTHMA RESEARCH-PROGRAM; OBSTRUCTIVE PULMONARY-DISEASE; WORLD-HEALTH-ORGANIZATION; T-REGULATORY-CELLS; BIRTH-COHORT; CLUSTER-ANALYSIS; RUSSIAN KARELIA; LUNG-FUNCTION; BRONCHIAL HYPERRESPONSIVENESS; DIAGNOSTIC GATEKEEPERS AB Mechanisms of the Development of Allergy (MeDALL), a Seventh Framework Program European Union project, aims to generate novel knowledge on the mechanisms of initiation of allergy. Precise phenotypes of IgE-mediated allergic diseases will be defined in MeDALL. As part of MeDALL, a scientific seminar was held on January 24, 2011, to review current knowledge on the IgE-related phenotypes and to explore how a multidisciplinary effort could result in a new integrative translational approach. This article provides a summary of the meeting. It develops challenges in IgE-related phenotypes and new clinical and epidemiologic approaches to the investigation of allergic phenotypes, including cluster analysis, scale-free models, candidate biomarkers, and IgE microarrays; the particular case of severe asthma was reviewed. Then novel approaches to the IgE-associated phenotypes are reviewed from the individual mechanisms to the systems, including epigenetics, human in vitro immunology, systems biology, and animal models. The last chapter deals with the understanding of the population-based IgE-associated phenotypes in children and adolescents, including age effect in terms of maturation, observed effects of early-life exposures and shift of focus from early life to pregnancy, gene-environment interactions, cohort effects, and time trends in patients with allergic diseases. This review helps to define phenotypes of allergic diseases in MeDALL. (J Allergy Clin Immunol 2012;129:943-54.) C1 [Anto, Josep M.; Pinart, Mariona; Basagana, Xavier; Guerra, Stefano; Sunyer, Jordi; Benet, Marta; Garcia-Aymerich, Judith; Gimeno-Santos, Elena; Kogevinas, Manolis; Stein, Renato T.] CREAL Ctr Res Environm Epidemiol, Barcelona 08003, Spain. [Anto, Josep M.; Pinart, Mariona; Basagana, Xavier; Guerra, Stefano; Sunyer, Jordi; Benet, Marta; Garcia-Aymerich, Judith; Gimeno-Santos, Elena; Kogevinas, Manolis] Hosp Mar Res Inst IMIM, Barcelona, Spain. [Anto, Josep M.; Pinart, Mariona; Basagana, Xavier; Guerra, Stefano; Sunyer, Jordi; Ballester, Ferran; Benet, Marta; Garcia-Aymerich, Judith; Gimeno-Santos, Elena; Kogevinas, Manolis] CIBERESP, Barcelona, Spain. [Anto, Josep M.; Sunyer, Jordi; Garcia-Aymerich, Judith] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona, Spain. [Akdis, Muebeccel; Akdis, Cezmi A.; Stanic, Barbara; van de Veen, Willem; Yaman, Gorkem] Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, Davos, Switzerland. [Auffray, Charles] CNRS Inst Biol Sci, Villejuif, France. [Bachert, Claus] Univ Hosp Ghent, URL Upper Airways Res Lab, Ghent, Belgium. [Carlsen, Kai-Hakon; Carlsen, Karin C. Lodrup] Oslo Univ Hosp, Dept Paediat, Oslo, Norway. [Carlsen, Kai-Hakon; Carlsen, Karin C. Lodrup] Univ Oslo, N-0316 Oslo, Norway. [Guerra, Stefano; Martinez, Fernando D.] Univ Arizona, Arizona Resp Ctr, Tucson, AZ USA. [von Hertzen, Leena; Haahtela, Tari] Helsinki Univ Hosp, Dept Allergy, Skin & Allergy Hosp, Helsinki, Finland. [Illi, Sabina] Univ Munich, Dept Pulm & Allergy, Univ Childrens Hosp Munich, Munich, Germany. [Kauffmann, Francine; Jacquemin, Benedicte; Varraso, Raphaelle; Bousquet, Jean] INSERM, CESP Ctr Res Epidemiol & Populat Hlth, U1018, Resp & Environm Epidemiol Team, Villejuif, France. [Kauffmann, Francine; Jacquemin, Benedicte; Varraso, Raphaelle] Univ Paris 11, UMRS 1018, F-94807 Villejuif, France. [Keil, Thomas; Hohmann, Cynthia] Charite, Inst Social Med Epidemiol & Hlth Econ, D-13353 Berlin, Germany. [Kiley, James P.; Gan, Weiniu; Noel, Patricia; Punturieri, Antonello; Smith, Robert A.] NHLBI, Div Lung Dis, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Koppelman, Gerard H.] Univ Groningen, Dept Pediat Pulmonol & Pediat Allergol, Beatrix Childrens Hosp, GRIAC Res Inst,Univ Med Ctr Groningen, Groningen, Netherlands. [Lupinek, Christian; Valenta, Rudolf] Med Univ Vienna, Div Immunopathol, Dept Pathophysiol & Allergy Res, Ctr Pathophysiol Infectiol & Immunol, Vienna, Austria. [Nawijn, Martijn C.; van Oosterhout, Antoon J. M.] Univ Groningen, Univ Med Ctr Groningen, Lab Allergol & Pulm Dis, Dept Pathol & Med Biol,GRIAC Res Inst, Groningen, Netherlands. [Postma, Dirkje S.] Univ Groningen, Univ Med Ctr Groningen, Dept Resp Med, Beatrix Childrens Hosp,GRIAC Res Inst, Groningen, Netherlands. [Siroux, Valerie] Univ Grenoble 1, INSERM, Team Environm Epidemiol Appl Reprod & Resp Hlth, U823, Grenoble, France. [Smit, Henriette A.] Univ Utrecht, Julius Ctr Hlth Sci & Primary Care, Univ Med Ctr Utrecht, NL-3508 TC Utrecht, Netherlands. [Sterk, Peter J.] Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands. [Sterk, Peter J.] Univ Amsterdam, Acad Med Ctr, Dept Pulmonol, NL-1105 AZ Amsterdam, Netherlands. [Valverde, Sergio] Univ Pompeu Fabra, ICREA Complex Syst Lab, Barcelona, Spain. [Annesi-Maesano, Isabella] EPAR U707 INSERM, Paris, France. [Annesi-Maesano, Isabella] EPAR UMR S UPMC, Paris, France. [Ballester, Ferran] Ctr Publ Hlth Res CSISP, Div Environm & Hlth, Valencia, Spain. [Ballester, Ferran] Univ Valencia, Sch Nursing, E-46003 Valencia, Spain. [Cambon-Thomsen, Anne] UMR Inserm U1027, Toulouse, France. [Cambon-Thomsen, Anne] Univ Toulouse 3, F-31062 Toulouse, France. [Chatzi, Leda] Univ Crete, Dept Social Med, Iraklion, Greece. [Coquet, Jonathan] Univ Ghent, Dept Resp Dis, Lab Immunoregulat & Mucosal Immunol, Ghent, Belgium. [Demoly, Pascal; Lambrecht, Bart N.] World Hlth Org Collaborating Ctr Asthma & Rhiniti, Montpellier, France. [Demoly, Pascal; Bousquet, Jean] Hop Arnaud de Villeneuve, Univ Hosp Montpellier, Montpellier, France. [Guihenneuc-Jouyaux, Chantal; Herr, Marie; Just, Jocelyne; Momas, Isabelle; Ranciere, Fanny] Paris Descartes Univ, Dept Publ Hlth & Biostat, Paris, France. [Heinrich, Joachim] Helmholtz Zentrum, Inst Epidemiol 1, Munich, Germany. [Just, Jocelyne] Univ Paris 06, Grp Hosp Trousseau La Roche Guyon, APHP, Ctr Asthme & Allergies, Paris, France. [Kerkhof, Marjan] Univ Groningen, Dept Epidemiol, GRIAC Res Inst, Univ Med Ctr Groningen, Groningen, Netherlands. [Kogevinas, Manolis] Natl Sch Publ Hlth, Athens, Greece. [Kowalski, Marek L.] Med Univ Lodz, Dept Immunol Rheumatol & Allergy, Lodz, Poland. [Lau, Susanne] Charite Campus Virchow, Dept Pneumol & Immunol, Berlin, Germany. [Maier, Dieter] Biomax Informat AG, Munich, Germany. [Momas, Isabelle; Ranciere, Fanny] Paris Municipal Dept Social Act Childhood & Hlth, Paris, France. [Oddie, Sam; Wright, John] Bradford Teaching Hosp Fdn Trust, Bradford Inst Hlth Res, Bradford, W Yorkshire, England. [Oddie, Sam; Wright, John] Bradford Royal Infirm, Bradford, W Yorkshire, England. [Palkonen, Susanna] EFA European Federat Allergy & Airways Dis Patien, Brussels, Belgium. [Pin, Isabelle] CHU Grenoble, F-38043 Grenoble, France. [Pin, Isabelle] Univ Grenoble 1, INSERM, U823, Inst Albert Bonniot, Grenoble, France. [Porta, Daniela] Reg Hlth Serv Lazio Reg, Dept Epidemiol, Rome, Italy. [Stein, Renato T.] Pontificia Univ Catolica RGS, Sch Med, Porto Alegre, RS, Brazil. [Wickman, Magnus] Karolinska Inst, Sachs Childrens Hosp, Stockholm, Sweden. [Wickman, Magnus] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Zuberbier, Torsten] Charite, Allergy Ctr Charite, Dept Dermatol, D-13353 Berlin, Germany. RP Anto, JM (reprint author), CREAL Ctr Res Environm Epidemiol, Barcelona Biomedical Res Pk,Dr Aiguader 88, Barcelona 08003, Spain. EM jmanto@creal.cat RI Varraso, Raphaelle/R-8740-2016; Coquet, Jonathan/A-5551-2015; Basagana, Xavier/C-3901-2017; Kogevinas, Manolis/C-3918-2017; Sunyer, J/G-6909-2014; Anto, J/H-2676-2014; Wright, John/H-1624-2012; Stein, Renato/G-2975-2012; siroux, valerie/N-1865-2013; PIN, Isabelle/N-3020-2013; Wijmenga, Cisca/D-2173-2009; Garcia-Aymerich, J/G-6867-2014; Valverde, Sergi/J-3275-2012; Stein, Renato/K-2568-2014; Annesi-Maesano, Isabella/D-9173-2016; Pinart, Mariona/L-1931-2015; Porta, Daniela/J-9042-2016; Lambrecht, Bart/K-2484-2014 OI Varraso, Raphaelle/0000-0002-3338-7825; Coquet, Jonathan/0000-0002-5967-4857; Basagana, Xavier/0000-0002-8457-1489; Sunyer, J/0000-0002-2602-4110; Anto, J/0000-0002-4736-8529; Ranciere, Fanny/0000-0003-3485-2247; Wijmenga, Cisca/0000-0002-5635-1614; Wright, John/0000-0001-9572-7293; Garcia-Aymerich, J/0000-0002-7097-4586; Valverde, Sergi/0000-0002-2150-9610; Pinart, Mariona/0000-0002-8223-1325; Porta, Daniela/0000-0002-3431-2729; Lambrecht, Bart/0000-0003-4376-6834 FU Swiss National Foundation; European Union; Helse Sor-Ost; Juselius Foundation; Helsinki University; French Agency of Research; Netherlands Asthma Foundation; GlaxoSmithKline; Abbott; National Institutes of Health; Nycomed, Topinstitute Pharma; AstraZeneca; Innovative Medicines Initiative by IMI-EU (U-BIOPRED); Novartis; Stallergenes; Swiss National Science Foundation; Global Allergy and Asthma European Network; Christine Kuhne Center for Allergy Research; European Commission; Norwegian Research Council; University of Oslo; Eastern Norway Regional Health Authority; Norwegian Institute of Public Health; Norwegian Foundation for Health and Rehabilitation; Norwegian Association for Asthma and Allergy; Kloster Foundation; Voksentoppen BKL; Ulleval University Hospital; Phadia; Novartis, GlaxoSmithKline; Boehringer Ingelheim; Pfizer; Chiesi; ALK-Abello; Nycomed; Air Liquid Healthcare; Christne Kuhne Center for Allergy Research FX M. Akdis has received research support from the Swiss National Foundation and the European Union. C. Auffray has received research support from the European Union. K.-H. Carlsen has received research support from Helse Sor-Ost. L. von Hertzen has received research support from the Juselius Foundation and Helsinki University. F. Kauffmann has received research support from the French Agency of Research and the European Union. T. Keil has received research support from the European Union. G. H. Koppelman has received research support from the European Union, the Netherlands Asthma Foundation, and GlaxoSmithKline. F. D. Martinez is a consultant for MedImmune, has received lecture fees from Abbott, and has received research support from the National Institutes of Health. D. S. Postma has received research support from Nycomed, Topinstitute Pharma, and AstraZeneca. P. J. Sterk has received research support from Innovative Medicines Initiative by IMI-EU (U-BIOPRED). C. A. Akdis has received research support from Novartis, Stallergenes, the Swiss National Science Foundation, the Global Allergy and Asthma European Network, and the Christine Kuhne Center for Allergy Research; has provided legal consultation/expert witness testimony on the topics of Actellion TH2-specific receptors, Aventis T-cell, B-cell regulation, and Allergopharma allergen-specific immunotherapy; is an American Academy of Allergy, Asthma & Immunology (AAAAI) fellow and interest group member; is Vice President of the European Academy of Allergy and Clinical Immunology (EAACI); and is a GA2LEN ex-committee member WP leader. A. Cambon-Thomsen has received research support from the European Commission FP7. K. C. Lodrup Carlsen has received research support from the Norwegian Research Council, the University of Oslo, the Eastern Norway Regional Health Authority, the Norwegian Institute of Public Health, the Norwegian Foundation for Health and Rehabilitation, the Norwegian Association for Asthma and Allergy, the Kloster Foundation, Voksentoppen BKL, AstraZeneca, Ulleval University Hospital, and Phadia; was an EACCI member at large; is chair of the Asthma and Allergy group in the pediatric section of the European Respiratory Society; and is on the GA2LEN executive board. D. Maier has received research support from the European Commission. S. Palkonen is employed by the European Federation of Allergy and Airways Diseases Patients' Associations, which has received grants from Novartis, GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Chiesi, ALK-Abello, Stallergenes, Nycomed, AstraZeneca, and Air Liquid Healthcare. B. Stanic has received research support from the Christne Kuhne Center for Allergy Research and Education and the European Commission's Seventh Framework Programme. W. van de Veen has received research support from the Swiss National Science Foundation and the European Commission's Seventh Framework Programme. T.; Zuberbier has provided consultation for Ansell, Bayer Schering, DST, Fujisawa, HAL, Henkel, Kryolan, Leti, MSD, Novartis, Procter & Gamble, Sanofi-Aventis, Schering-Plough, Stallergenes, and UCB; is on the Scientific Advisory Board, German Society for Allergy and Clinical Immunology; is on the Expert Commission "Novel Food'' of the German Federal Ministry of Consumer Protection; is Head of the European Centre for Allergy Research Foundation (ECARF); is a committee member of the World Health Organization Initiative Allergic Rhinitis and its Impact on Asthma (ARIA); is a member of the World Allergy Organization Communications Council; and is Secretary General of the Global Allergy and Asthma European Network (GA2LEN). J. Bousquet has received honoraria from Stallergenes, Actelion, Almirall, AstraZeneca, Chiesi, GlaxoSmithKline, Merck, MSD, Novartis, OM Pharma, Sanofi-Aventis, Schering-Plough, Teva, and Uriach. The rest of the authors declare that they have no relevant conflicts of interest. NR 137 TC 39 Z9 42 U1 1 U2 25 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2012 VL 129 IS 4 BP 943 EP U421 DI 10.1016/j.jaci.2012.01.047 PG 16 WC Allergy; Immunology SC Allergy; Immunology GA 917AP UT WOS:000302144600008 PM 22386796 ER PT J AU Haleem-Smith, H Calderon, R Song, YJ Tuan, RS Chen, FH AF Haleem-Smith, Hana Calderon, Raul Song, Yingjie Tuan, Rocky S. Chen, Faye H. TI Cartilage oligomeric matrix protein enhances matrix assembly during chondrogenesis of human mesenchymal stem cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE CARTILAGE OLIGOMERIC MATRIX PROTEIN; MESENCHYMAL STEM CELLS; EXTRACELLULAR MATRIX; CARTILAGE DEVELOPMENT ID MULTIPLE EPIPHYSEAL DYSPLASIA; BONE-MARROW; ARTICULAR-CARTILAGE; INTERSTITIAL FLUID; IN-VITRO; COMP; PSEUDOACHONDROPLASIA; MUTATIONS; COLLAGEN; GENE AB Cartilage oligomeric matrix protein/thrombospondin-5 (COMP/TSP5) is an abundant cartilage extracellular matrix (ECM) protein that interacts with major cartilage ECM components, including aggrecan and collagens. To test our hypothesis that COMP/TSP5 functions in the assembly of the ECM during cartilage morphogenesis, we have employed mesenchymal stem cell (MSC) chondrogenesis in vitro as a model to examine the effects of COMP over-expression on neo-cartilage formation. Human bone marrow-derived MSCs were transfected with either full-length COMP cDNA or control plasmid, followed by chondrogenic induction in three-dimensional pellet or alginate hydrogel culture. MSC chondrogenesis and ECM production was estimated based on quantitation of sulfated glycosaminoglycan (sGAG) accumulation, immunohistochemistry of the presence and distribution of cartilage ECM proteins, and real-time RT-PCR analyis of mRNA expression of cartilage markers. Our results showed that COMP over-expression resulted in increased total sGAG content during the early phase of MSC chondrogenesis, and increased immuno-detectable levels of aggrecan and collagen type II in the ECM of COMP-transfected pellet and alginate cultures, indicating more abundant cartilaginous matrix. COMP transfection did not significantly increase the transcript levels of the early chondrogenic marker, Sox9, or aggrecan, suggesting that enhancement of MSC cartilage ECM was effected at post-transcriptional levels. These findings strongly suggest that COMP functions in mesenchymal chondrogenesis by enhancing cartilage ECM organization and assembly. The action of COMP is most likely mediated not via direct changes in cartilage matrix gene expression but via interactions of COMP with other cartilage ECM proteins, such as aggrecan and collagens, that result in enhanced assembly and retention. J. Cell. Biochem. 113: 12451252, 2012. Published 2011. This article is a U.S. Government work and is in the public domain in the USA. C1 [Tuan, Rocky S.] Univ Pittsburgh, Dept Orthopaed Surg, Ctr Cellular & Mol Engn, Pittsburgh, PA 15219 USA. [Haleem-Smith, Hana; Calderon, Raul; Song, Yingjie; Tuan, Rocky S.; Chen, Faye H.] NIAMSD, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Calderon, Raul] NIAMSD, Dept Hlth & Human Serv, Howard Hughes Med Inst, Natl Inst Hlth Res Scholars Program,NIH, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), Univ Pittsburgh, Dept Orthopaed Surg, Ctr Cellular & Mol Engn, Room 221,Bridgeside Point 2,450 Technol Dr, Pittsburgh, PA 15219 USA. EM rst13@pitt.edu FU National Institutes of Health [Z01AR41131]; Howard Hughes Medical Institute-National Institutes of Health; Commonwealth of Pennsylvania Department of Health FX Grant sponsor: Intramural Research Program of the National Institutes of Health; Grant number: Z01AR41131; Grant sponsor: Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program; Grant sponsor: Commonwealth of Pennsylvania Department of Health. NR 46 TC 24 Z9 24 U1 1 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR PY 2012 VL 113 IS 4 BP 1245 EP 1252 DI 10.1002/jcb.23455 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 898EN UT WOS:000300719000018 PM 22095699 ER PT J AU Thambisetty, M Gallardo, KA Liow, JS Beason-Held, LL Umhau, JC Bhattacharjee, AK Der, M Herscovitch, P Rapoport, JL Rapoport, SI AF Thambisetty, Madhav Gallardo, Kathy A. Liow, Jeih-San Beason-Held, Lori L. Umhau, John C. Bhattacharjee, Abesh K. Der, Margaret Herscovitch, Peter Rapoport, Judith L. Rapoport, Stanley I. TI The utility of C-11-arachidonate PET to study in vivo dopaminergic neurotransmission in humans SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE apomorphine; cPLA(2); D-1/D-2 receptors; [1-C-11]arachidonate PET; regional cerebral blood flow ID POSITRON-EMISSION-TOMOGRAPHY; ARACHIDONIC-ACID RELEASE; UNANESTHETIZED RATS; PARKINSONS-DISEASE; BRAIN INCORPORATION; SIGNAL-TRANSDUCTION; BLOOD-FLOW; HIPPOCAMPAL-NEURONS; ALZHEIMERS-DISEASE; PHOSPHOLIPASE A(2) AB We developed a novel method to study dopaminergic neurotransmission using positron emission tomography (PET) with [1-C-11] arachidonic acid ([1-C-11]AA). Previous preclinical studies have shown the utility of [1-C-11] AA as a marker of signal transduction coupled to cytosolic phospholipase A(2) (cPLA(2)). Using [1-C-11] AA and [O-15] water PET, we measured regional incorporation coefficients K* for AA and regional cerebral blood flow (rCBF), respectively, in healthy male volunteers given the D-1/D-2 agonist (10 or 20 mu g/kg subcutaneous) apomorphine. We confirmed a robust central dopaminergic response to apomorphine by observing significant increases in the serum concentration of growth hormone. We observed significant increases, as well as decreases in K* and increases in rCBF in response to apomorphine. These changes remained significant after covarying for handedness and apomorphine dosage. The magnitude of increases in K* was lower than those in our previous animal experiments, likely reflecting the smaller dose of apomorphine used in the current human study. Changes in K* may reflect neuronal signaling downstream of activated D-2-like receptors coupled to cPLA(2). Changes in rCBF are consistent with previous studies showing net functional effects of D-1/D-2 activation. [1-C-11]AA PET may be useful for studying disturbances of dopaminergic neurotransmission in conditions such as Parkinson's disease and schizophrenia. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 676-684; doi:10.1038/jcbfm.2011.171; published online 14 December 2011 C1 [Thambisetty, Madhav; Bhattacharjee, Abesh K.; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. [Gallardo, Kathy A.; Rapoport, Judith L.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Liow, Jeih-San] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Beason-Held, Lori L.] NIA, Lab Behav Neurosci, NIH, Bethesda, MD 20892 USA. [Umhau, John C.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Der, Margaret; Herscovitch, Peter] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Thambisetty, M (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Room 1S-126,Bluiding 9,9000 Rockville Pike, Bethesda, MD 20892 USA. EM thambisettym@mail.nih.gov FU National Institute of Mental Health; National Institute on Aging; National Institute of Neurological Disorders and Stroke; National Institute of Alcohol Abuse and Alcoholism FX This study was supported by the Intramural Program of the National Institute of Mental Health, National Institute on Aging, National Institute of Neurological Disorders and Stroke, and National Institute of Alcohol Abuse and Alcoholism. NR 58 TC 9 Z9 9 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD APR PY 2012 VL 32 IS 4 BP 676 EP 684 DI 10.1038/jcbfm.2011.171 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 921IU UT WOS:000302472100009 PM 22167235 ER PT J AU Sant'Anna, G Laptook, AR Shankaran, S Bara, R McDonald, SA Higgins, RD Tyson, JE Ehrenkranz, RA Das, A Goldberg, RN Walsh, MC AF Sant'Anna, Guilherme Laptook, Abbot R. Shankaran, Seetha Bara, Rebecca McDonald, Scott A. Higgins, Rosemary D. Tyson, Jon E. Ehrenkranz, Richard A. Das, Abhik Goldberg, Ronald N. Walsh, Michele C. CA Eunice Kennedy Shriver Natl Inst C Human Dev Neonatal Res Network TI Phenobarbital and Temperature Profile During Hypothermia for Hypoxic-Ischemic Encephalopathy SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE phenobarbital; hypoxic-ischemic encephalopathy; hypothermia; temperature control; anticonvulsant; seizures; barbiturates ID WHOLE-BODY HYPOTHERMIA; NEONATAL ENCEPHALOPATHY; REGULATED HYPOTHERMIA; BRAIN-INJURY; SYSTEMIC HYPOTHERMIA; OXYGEN-CONSUMPTION; NEWBORN RATS; THERMOGENESIS; MANAGEMENT; ASPHYXIA AB Data from the whole-body hypothermia trial was analyzed to examine the effects of phenobarbital administration prior to cooling (+PB) on the esophageal temperature (T-e) profile, during the induction phase of hypothermia. A total of 98 infants were analyzed. At enrollment, +PB infants had a higher rate of severe hypoxic-ischemic encephalopathy and clinical seizures and lower T-e and cord pH than infants that have not received phenobarbital (-PB). There was a significant effect of phenobarbital itself and an interaction between phenobarbital and time in the T-e profile. Mean T-e in the +PB group was lower than in the -PB group, and the differences decreased over time. In +PB infants, the time to surpass target T-e of 33.5 degrees C and to reach the minimum T-e during overshoot were shorter. In conclusion, the administration of phenobarbital before cooling was associated with changes that may reflect a reduced thermogenic response associated with barbiturates. C1 [Sant'Anna, Guilherme] McGill Univ, Div Neonatol, Dept Pediat, Ctr Hlth, Montreal, PQ H3H 1P3, Canada. [Laptook, Abbot R.] Brown Univ, Providence, RI 02912 USA. [Shankaran, Seetha; Bara, Rebecca] Wayne State Univ, Sch Med, Detroit, MI USA. [McDonald, Scott A.; Das, Abhik] RTI Int, Dept Stat & Epidemiol, Res Triangle Pk, NC USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Tyson, Jon E.] Univ Texas Houston, Houston, TX USA. [Ehrenkranz, Richard A.] Yale Univ, New Haven, CT USA. [Goldberg, Ronald N.] Duke Univ, Durham, NC USA. [Walsh, Michele C.] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Sant'Anna, G (reprint author), McGill Univ, Div Neonatol, Dept Pediat, Ctr Hlth, 2300 Tupper St,Room C912, Montreal, PQ H3H 1P3, Canada. EM guilherme.santanna@mcgill.ca FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) FX The National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) provided grant support for the NICHD Neonatal Research Network's Whole-Body Cooling for Hypoxic Ischemic Encephalopathy Study. Participating NRN sites collected data and transmitted it to RTI International, the data coordinating center (DCC) for the network, which stored, managed, and analyzed the data for this study. On behalf of the NRN, Dr Abhik Das (DCC Principal Investigator) and Mr Scott A. McDonald (DCC Statisticians) had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of data analysis. NR 36 TC 10 Z9 10 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD APR PY 2012 VL 27 IS 4 BP 451 EP 457 DI 10.1177/0883073811419317 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 918EK UT WOS:000302231900004 PM 21960671 ER PT J AU Shibusawa, Y Yanagida, A Ogihara, A Ma, Y Chen, XY Ito, Y AF Shibusawa, Yoichi Yanagida, Akio Ogihara, Atsushi Ma, Ying Chen, Xiaoyuan Ito, Yoichiro TI Separation of nucleobases and their derivatives with organic-high ionic strength aqueous phase systems by spiral high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article ID SOLVENT SYSTEM AB A set of nucleic acid constituents were separated with ultra polar two-phase solvent systems by a spiral multilayer coil mounted on the rotary frame of a type-J coil planet centrifuge. These two-phase systems were composed of 1-butanol/ethanol/50% saturated aqueous ammonium sulfate at various volume ratios. Nucleobases including adenine, cytosine, uracil, and thymine; nucleosides including adenosine, guanosine, cytidine, and uridine; and nucleotides including, AMP, GMP, CMP, UMP, and TMP are partitioned in each group with suitable solvent ratios. Adenine derivatives such as adenosine, AMP, ADP, and ATP were well resolved in the most polar solvent system composed of ethanol/50% saturated aqueous ammonium sulfate at a volume ratio of 1:2. It was found that cytosine and cytidine peaks showed some irregular two peaks probably due to their keto and enol isomers, while the separation of AMP forms two peaks especially when TMP was added in the sample solution, the mechanism of which is now under investigation in our laboratory. (C) 2012 Elsevier B.V. All rights reserved. C1 [Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Ma, Ying; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Shibusawa, Yoichi; Yanagida, Akio; Ogihara, Atsushi] Tokyo Univ Pharm & Life Sci, Sch Pharm, Div Pharmaceut & Biomed Anal, Hachioji, Tokyo 1920392, Japan. RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bldg 10,Room 8N230,10 Ctr Dr, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov FU Intramural NIH HHS [ZIA HL005107-04] NR 15 TC 9 Z9 9 U1 4 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD APR 1 PY 2012 VL 891 BP 94 EP 97 DI 10.1016/j.jchromb.2012.02.012 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 922YO UT WOS:000302585100015 PM 22391329 ER PT J AU Mattson, MP AF Mattson, Mark P. TI Parkinson's disease: don't mess with calcium SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID NEUROTROPHIC FACTOR; STRESS; MITOCHONDRIA; SYNUCLEIN; NEURONS AB The hallmark of the movement disorder Parkinson's disease (PD) is progressive degeneration of dopaminergic neurons. Mitochondrial dysfunction, impaired ubiquitin-mediated proteolysis of a-synuclein, and ER stress are each implicated in the complex and poorly understood sequence of events leading to dopaminergic neuron demise. In this issue of the JCI, Selvaraj et al. report that in a mouse neurotoxin-based model of PD, reduced Ca2+ influx through transient receptor potential Cl (TRPC1) channels in the plasma membrane of dopaminergic neurons triggers a cell death-inducing ER stress response. These new findings suggest that TRPC1 channels normally function in Ca2+-mediated signaling pathways that couple adaptive/neurotrophic responses to metabolic and oxidative stress and suggest that disruption of these pathways may contribute to PD. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 17 TC 13 Z9 14 U1 2 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2012 VL 122 IS 4 BP 1195 EP 1198 DI 10.1172/JCI62835 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 918WJ UT WOS:000302281800014 PM 22446181 ER PT J AU Rachel, RA May-Simera, HL Veleri, S Gotoh, N Choi, BY Murga-Zamalloa, C McIntyre, JC Marek, J Lopez, I Hackett, AN Brooks, M den Hollander, AI Beales, PL Li, TS Jacobson, SG Sood, R Martens, JR Liu, P Friedman, TB Khanna, H Koenekoop, RK Kelley, MW Swaroop, A AF Rachel, Rivka A. May-Simera, Helen L. Veleri, Shobi Gotoh, Norimoto Choi, Byung Yoon Murga-Zamalloa, Carlos McIntyre, Jeremy C. Marek, Jonah Lopez, Irma Hackett, Alice N. Brooks, Matthew den Hollander, Anneke I. Beales, Philip L. Li, Tiansen Jacobson, Samuel G. Sood, Raman Martens, Jeffrey R. Liu, Paul Friedman, Thomas B. Khanna, Hemant Koenekoop, Robert K. Kelley, Matthew W. Swaroop, Anand TI Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BARDET-BIEDL-SYNDROME; LEBER CONGENITAL AMAUROSIS; INTRAFLAGELLAR TRANSPORT MOTORS; PLANAR CELL POLARITY; JOUBERT-SYNDROME; PRIMARY CILIUM; RETINAL DEGENERATION; KUPFFERS VESICLE; ZEBRAFISH MODEL; NPHP6 GENE AB Cilia are highly specialized microtubule-based organelles that have pivotal roles in numerous biological processes, including transducing sensory signals. Defects in cilia biogenesis and transport cause pleiotropic human ciliopathies. Mutations in over 30 different genes can lead to cilia defects, and complex interactions exist among ciliopathy-associated proteins. Mutations of the centrosomal protein 290 kDa (CEP290) lead to distinct clinical manifestations, including Leber congenital amaurosis (LCA), a hereditary cause of blindness due to photoreceptor degeneration. Mice homozygous for a mutant Cep290 allele (Cep290(rd16) mice) exhibit LCA-like early-onset retinal degeneration that is caused by an in-frame deletion in the CEP290 protein. Here, we show that the domain deleted in the protein encoded by the Cep290(rd16) allele directly interacts with another ciliopathy protein, MKKS. MKKS mutations identified in patients with the ciliopathy Bardet-Biedl syndrome disrupted this interaction. In zebrafish embryos, combined subminimal knockdown of mkks and cep290 produced sensory defects in the eye and inner ear. Intriguingly, combinations of Cep290(rd16) and Mkks(ko) alleles in mice led to improved ciliogenesis and sensory functions compared with those of either mutant alone. We propose that altered association of CEP290 and MKKS affects the integrity of multiprotein complexes at the cilia transition zone and basal body. Amelioration of the sensory phenotypes caused by specific mutations in one protein by removal of an interacting domain/protein suggests a possible novel approach for treating human ciliopathies. C1 [Rachel, Rivka A.; Veleri, Shobi; Gotoh, Norimoto; Hackett, Alice N.; Brooks, Matthew; Li, Tiansen; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. [May-Simera, Helen L.; Kelley, Matthew W.] Natl Inst Deafness & Other Commun Disorders, Lab Cochlear Dev, NIH, Bethesda, MD USA. [Choi, Byung Yoon; Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Bethesda, MD USA. [Murga-Zamalloa, Carlos; Khanna, Hemant] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [McIntyre, Jeremy C.; Martens, Jeffrey R.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Marek, Jonah; Lopez, Irma; Koenekoop, Robert K.] McGill Univ, Ctr Hlth, McGill Ocular Genet Lab, Montreal, PQ, Canada. [den Hollander, Anneke I.] Radboud Univ Nijmegen, Med Ctr, Dept Ophthalmol, NL-6525 ED Nijmegen, Netherlands. [den Hollander, Anneke I.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Beales, Philip L.] UCL Inst Child Hlth, Mol Med Unit, London, England. [Jacobson, Samuel G.] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Sood, Raman; Liu, Paul] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. EM swaroopa@nei.nih.gov RI Liu, Paul/A-7976-2012; Hollander, Anneke/N-4911-2014; OI Liu, Paul/0000-0002-6779-025X; Swaroop, Anand/0000-0002-1975-1141 FU National Eye Institute; National Institute on Deafness and Other Communication Disorders; National Human Genome Research Institute FX We are grateful to Chi-Chao Chan, Robert Fariss, Jun Zhang, Jacob Nellissery, Awais Zia, Milton English, Kevin Bishop, Anastasia Krasnoperova, Rima Kikani, Tiziana Cogliati, Christopher Brinson, and Corey Williams for discussions or assistance. This work was supported by intramural and extramural funds from the National Eye Institute, National Institute on Deafness and Other Communication Disorders, and National Human Genome Research Institute. Additional support was provided by CIHR, FFB-C, FRSQ, Midwest Eye Banks and Transplantation Center, Reseau Vision, and TFFR. P.L. Beales is a Wellcome Trust Senior Research Fellow. NR 68 TC 32 Z9 32 U1 2 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2012 VL 122 IS 4 BP 1233 EP 1245 DI 10.1172/JCI60981 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 918WJ UT WOS:000302281800020 PM 22446187 ER PT J AU Selvaraj, S Sun, YY Watt, JA Wang, SP Lei, SB Birnbaumer, L Singh, BB AF Selvaraj, Senthil Sun, Yuyang Watt, John A. Wang, Shouping Lei, Saobo Birnbaumer, Lutz Singh, Brij B. TI Neurotoxin-Induced ER stress in mouse dopaminergic neurons involves downregulation of TRPC1 and inhibition of AKT/mTOR signaling SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; OPERATED CA2+ ENTRY; PARKINSONS-DISEASE; STORE DEPLETION; CALCIUM-CHANNEL; MONOAMINE-OXIDASE; DEATH; ORAI; ACTIVATION AB Individuals with Parkinson's disease (PD) experience a progressive decline in motor function as a result of selective loss of dopaminergic (DA) neurons in the substantia nigra. The mechanism(s) underlying the loss of DA neurons is not known. Here, we show that a neurotoxin that causes a disease that mimics PD upon administration to mice, because it induces the selective loss of DA neurons in the substantia nigra, alters Ca2+ homeostasis and induces ER stress. In a human neuroblastoma cell line, we found that endogenous store-operated Ca2+ entry (SOCE), which is critical for maintaining ER Ca2+ levels, is dependent on transient receptor potential channel 1 (TRPC1) activity. Neurotoxin treatment decreased TRPC1 expression, TRPC1 interaction with the SOCE modulator stromal interaction molecule 1 (STIM1), and Ca2+ entry into the cells. Overexpression of functional TRPC1 protected against neurotoxin-induced loss of SOCE, the associated decrease in ER Ca2+ levels, and the resultant unfolded protein response (UPR). In contrast, silencing of TRPC1 or STIM1 increased the UPR. Furthermore, Ca2+ entry via TRPC1 activated the AKT pathway, which has a known role in neuroprotection. Consistent with these in vitro data, Trpc1(-/-) mice had an increased UPR and a reduced number of DA neurons. Brain lysates of patients with PD also showed an increased UPR and decreased TRPC1 levels. Importantly, overexpression of TRPC1 in mice restored AKT/mTOR signaling and increased DA neuron survival following neurotoxin administration. Overall, these results suggest that TRPC1 is involved in regulating Ca2+ homeostasis and inhibiting the UPR and thus contributes to neuronal survival. C1 [Selvaraj, Senthil; Sun, Yuyang; Singh, Brij B.] Univ N Dakota, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Grand Forks, ND 58201 USA. [Watt, John A.] Univ N Dakota, Sch Med & Hlth Sci, Dept Anat & Cell Biol, Grand Forks, ND 58201 USA. [Watt, John A.; Wang, Shouping; Lei, Saobo] Univ N Dakota, Sch Med & Hlth Sci, Dept Physiol Pharmacol & Therapeut, Grand Forks, ND 58201 USA. [Birnbaumer, Lutz] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Singh, BB (reprint author), Univ N Dakota, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, 501 N Columbia Rd, Grand Forks, ND 58201 USA. EM senthilbio@gmail.com; brij.singh@med.und.edu OI selvaraj, senthil/0000-0002-0185-6033; Singh, Brij/0000-0003-0535-5997 FU National Science Foundation [0548733]; NIH [DE017102, 5P20RR017699, Z01-ES-101684]; National Institute of Neurological Disorders and Stroke (NINDS) [P50 NS-053488] FX We greatly acknowledge the use of the Edward C. Carlson Imaging and Image Analysis Core Facility. We especially thank Laura Leiphon and Virginia Achen for their help. We greatly acknowledge the UK Parkinson's Disease Society Tissue Bank at Imperial College and John Trojanowski (University of Pennsylvania) for providing the PD and control samples. Also, grant support from the National Science Foundation (no. 0548733) and the NIH (DE017102 and 5P20RR017699) awarded to B.B Singh; from the NIH Intramural Program (project Z01-ES-101684) to L. Birnbaumer; and from the National Institute of Neurological Disorders and Stroke (NINDS; P50 NS-053488) awarded to John Trojanowski is acknowledged. NR 59 TC 63 Z9 66 U1 0 U2 12 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2012 VL 122 IS 4 BP 1354 EP 1367 DI 10.1172/JCI61332 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 918WJ UT WOS:000302281800029 PM 22446186 ER PT J AU Higashimoto, Y Ohta, A Nishiyama, Y Ihira, M Sugata, K Asano, Y Peterson, DL Ablashi, DV Lusso, P Yoshikawa, T AF Higashimoto, Yuki Ohta, Akane Nishiyama, Yukihiro Ihira, Masaru Sugata, Ken Asano, Yoshizo Peterson, Daniel L. Ablashi, Dharam V. Lusso, Paolo Yoshikawa, Tetsushi TI Development of a Human Herpesvirus 6 Species-Specific Immunoblotting Assay SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INDUCED HYPERSENSITIVITY SYNDROME; MARROW TRANSPLANT RECIPIENTS; POLYMERASE CHAIN-REACTION; VARIANT-B; HUMAN-HERPESVIRUS-6 INFECTION; HEALTHY-INDIVIDUALS; EXANTHEM-SUBITUM; IDENTIFICATION; BLOOD; DNA AB In order to assess the full spectrum of human herpesvirus 6A (HHV-6A)- and HHV-6B-associated diseases, we sought to develop an HHV-6 species-specific serological assay based on immunoblot analysis. The immunodominant proteins encoded by open reading frame U11, p100 for HHV-6A (strain U1102) and 101K for HHV-6B (strain Z29), were selected to generate virus species-specific antigens. Recombinant p100 and 101K were produced in a prokaryotic expression system. The expression of these proteins was confirmed by using anti-His tag and 101K-specific monoclonal antibodies. HHV-6 species-specific antibodies were detected by immunoblotting in patient sera. Eighty-seven serum samples obtained from various subjects were utilized to determine the reliability of the method for clinical use. Ten of twelve exanthem subitum convalescent-phase sera reacted exclusively with 101K, whereas none of twelve acute-phase sera reacted with either protein. Two of three sera collected from HHV-6A-infected patients reacted with p100 and 101K. Although all five acute and convalescent-phase sera obtained from transplant recipients reacted exclusively with 101K, two of six convalescent-phase sera obtained from patients with drug-induced hypersensitivity syndrome reacted with both p100 and 101K. Of 38 sera obtained from healthy adults, 31 were positive for 101K antibody, while 4 reacted with both proteins. However, PCR analysis of peripheral blood mononuclear cells and saliva from these subjects did not detect HHV-6A DNA. In conclusion, this novel serological assay based on immunoblot analysis using recombinant HHV-6A p100 and HHV-6B 101K allowed us to discriminate between HHV-6A- and HHV-6B-specific antibodies. C1 [Higashimoto, Yuki; Sugata, Ken; Asano, Yoshizo; Yoshikawa, Tetsushi] Fujita Hlth Univ, Sch Med, Dept Pediat, Toyoake, Aichi 47011, Japan. [Ihira, Masaru] Fujita Hlth Univ, Sch Hlth Sci, Fac Clin Engn, Toyoake, Aichi, Japan. [Ohta, Akane; Nishiyama, Yukihiro] Nagoya Univ, Grad Sch Med, Dept Virol, Nagoya, Aichi 4648601, Japan. [Peterson, Daniel L.] Sierra Internal Med, Incline Village, NV USA. [Ablashi, Dharam V.] HHV 6 Fdn, Santa Barbara, CA USA. [Lusso, Paolo] NIAID, Sect Viral Pathogenesis, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Yoshikawa, T (reprint author), Fujita Hlth Univ, Sch Med, Dept Pediat, Toyoake, Aichi 47011, Japan. EM tetsushi@fujita-hu.ac.jp RI Asano, Yoshizo/F-6870-2012 FU Ministry of Education, Culture, Sports, Science, and Technology; Ministry of Health, Labor, and Welfare of Japan [H21-Shinko-009, H21-Shinko-011] FX This study was supported by research grants from the Ministry of Education, Culture, Sports, Science, and Technology and the Ministry of Health, Labor, and Welfare of Japan (H21-Shinko-009 and H21-Shinko-011). NR 35 TC 7 Z9 7 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2012 VL 50 IS 4 BP 1245 EP 1251 DI 10.1128/JCM.05834-11 PG 7 WC Microbiology SC Microbiology GA 917CC UT WOS:000302148700019 PM 22278837 ER PT J AU Conville, PS Brown-Elliott, BA Wallace, RJ Witebsky, FG Koziol, D Hall, GS Killian, SB Knapp, CC Warshauer, D Van, T Wengenack, NL Deml, S Woods, GL AF Conville, Patricia S. Brown-Elliott, Barbara A. Wallace, Richard J., Jr. Witebsky, Frank G. Koziol, Deloris Hall, Geraldine S. Killian, Scott B. Knapp, Cindy C. Warshauer, David Van, Tam Wengenack, Nancy L. Deml, Sharon Woods, Gail L. TI Multisite Reproducibility of the Broth Microdilution Method for Susceptibility Testing of Nocardia Species SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LABORATORY FEATURES; BETA-LACTAMASE; FARCINICA; BRASILIENSIS; RESISTANCE AB Antimicrobial susceptibility testing (AST) of clinical isolates of Nocardia is recommended to detect resistance to commonly used antimicrobial agents; such testing is complicated by difficulties in inoculum preparation and test interpretation. In this study, six laboratories performed repetitive broth microdilution testing on single strains of Nocardia brasiliensis, Nocardia cyriacigeorgica, Nocardia farcinica, Nocardia nova, and Nocardia wallacei. For each isolate, a total of 30 microdilution panels from three different lots were tested at most sites. The goal of the study was to determine the inter-and intralaboratory reproducibility of susceptibility testing of this group of isolates. Acceptable agreement (>90% agreement at +/- 1 dilution of the MIC mode) was found for amikacin, ciprofloxacin, clarithromycin, and moxifloxacin. After eliminating MIC values from single laboratories whose results showed the greatest deviation from those of the remaining laboratories, acceptable agreement was also found for amoxicillin-clavulanic acid, linezolid, minocycline, and tobramycin. Results showed unsatisfactory reproducibility of broth microdilution testing of ceftriaxone with N. cyriacigeorgica and N. wallacei, tigecycline with N. brasiliensis and N. cyriacigeorgica, and sulfonamides with N. farcinica and N. wallacei. N. nova ATCC BAA-2227 is proposed as a quality control organism for AST of Nocardia sp., and the use of a disk diffusion test for sulfisoxazole is proposed as a check of the adequacy of the inoculum and to confirm sulfonamide MIC results. C1 [Conville, Patricia S.; Witebsky, Frank G.] NIH, Microbiol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Koziol, Deloris] NIH, Biostat & Clin Epidemiol Serv, Warren G Magnuson Clin Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Brown-Elliott, Barbara A.; Wallace, Richard J., Jr.] Univ Texas Hlth Sci Ctr, Dept Microbiol, Tyler, TX USA. [Hall, Geraldine S.] Cleveland Clin, Cleveland, OH 44106 USA. [Warshauer, David; Van, Tam] Univ Wisconsin, Wisconsin State Lab Hyg, Madison, WI 53706 USA. [Killian, Scott B.; Knapp, Cindy C.] ThermoFisher Sci, Cleveland, OH USA. [Wengenack, Nancy L.; Deml, Sharon] Mayo Clin, Div Clin Microbiol, Rochester, MN USA. [Woods, Gail L.] Cent Arkansas Vet Healthcare Syst, Pathol & Lab Med Serv, Little Rock, AR USA. RP Conville, PS (reprint author), NIH, Microbiol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr,Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. EM patricia.conville@fda.hhs.gov FU Pfizer (New York, NY); Wyeth (Madison, NJ); ThermoFisher Scientific (Cleveland, OH); BD (Franklin Lakes, NJ) FX This work was supported in part by grants from Pfizer (New York, NY), Wyeth (Madison, NJ), ThermoFisher Scientific (Cleveland, OH), and BD (Franklin Lakes, NJ). NR 19 TC 19 Z9 21 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2012 VL 50 IS 4 BP 1270 EP 1280 DI 10.1128/JCM.00994-11 PG 11 WC Microbiology SC Microbiology GA 917CC UT WOS:000302148700023 PM 22219309 ER PT J AU Orru, CD Hughson, AG Race, B Raymond, GJ Caughey, B AF Orru, Christina D. Hughson, Andrew G. Race, Brent Raymond, Gregory J. Caughey, Byron TI Time Course of Prion Seeding Activity in Cerebrospinal Fluid of Scrapie-Infected Hamsters after Intratongue and Intracerebral Inoculations SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CONVERSION; PROTEIN; DISEASE AB To assess prospects for early diagnosis of prion disease based on prion seeding activity in cerebrospinal fluid (CSF), we measured the activity over time in scrapie-infected hamsters by real-time quaking-induced conversion (RT-QuIC). After intracerebral inoculation, activity appeared in CSF within 1 day and plateaued weeks before the onset of clinical signs. However, after intratongue inoculation, activity first appeared in CSF with the onset of clinical signs, well after higher-level accumulation of seeding activity in brain. C1 [Orru, Christina D.; Hughson, Andrew G.; Race, Brent; Raymond, Gregory J.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Caughey, B (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. EM bcaughey@nih.gov FU NIAID; NIH FX This work was supported by the Intramural Research Program of the NIAID, NIH. NR 12 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2012 VL 50 IS 4 BP 1464 EP 1466 DI 10.1128/JCM.06099-11 PG 3 WC Microbiology SC Microbiology GA 917CC UT WOS:000302148700060 ER PT J AU Grady, KL Naftel, DC Stevenson, L Dew, MA Weidner, G Pagani, FD Kirklin, JK Myers, S Baldwin, JT Shah, MR Young, JB AF Grady, K. L. Naftel, D. C. Stevenson, L. Dew, M. A. Weidner, G. Pagani, F. D. Kirklin, J. K. Myers, S. Baldwin, J. T. Shah, M. R. Young, J. B. TI Improvement in Quality of Life after Left Ventricular Assist Device Implant Is Similar, Regardless of Baseline Severity of Heart Failure SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation/Meeting of the ISHLT Academy - Core Competencies in Mechanical Circulatory Support CY APR 17-21, 2012 CL Prague, CZECH REPUBLIC SP Int Soc Heart & Lung Transplantat (ISHLT), Int Soc Heart & Lung Transplantat Acad (ISHLT) C1 [Grady, K. L.] Northwestern Univ, Chicago, IL 60611 USA. [Naftel, D. C.; Kirklin, J. K.; Myers, S.] Univ Alabama, Birmingham, AL USA. [Stevenson, L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Dew, M. A.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Weidner, G.] San Francisco State Univ, Tiburon, CA USA. [Pagani, F. D.] Univ Michigan, Ann Arbor, MI 48109 USA. [Baldwin, J. T.; Shah, M. R.] NHLBI, NIH, Bethesda, MD 20892 USA. [Young, J. B.] Cleveland Clin, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2012 VL 31 IS 4 SU S MA 28 BP S18 EP S19 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 917VY UT WOS:000302207900028 ER PT J AU Naftel, DC Kirklin, JK Myers, SL Clark, ML Hollifield, KA Collum, SC Miller, MA AF Naftel, D. C. Kirklin, J. K. Myers, S. L. Clark, M. L. Hollifield, K. A. Collum, S. C. Miller, M. A. TI Can a Registry Match the Data Quality of a Clinical Trial? Lessons Learned from INTERMACS SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation/Meeting of the ISHLT Academy - Core Competencies in Mechanical Circulatory Support CY APR 17-21, 2012 CL Prague, CZECH REPUBLIC SP Int Soc Heart & Lung Transplantat (ISHLT), Int Soc Heart & Lung Transplantat Acad (ISHLT) C1 [Naftel, D. C.; Kirklin, J. K.; Myers, S. L.; Clark, M. L.; Hollifield, K. A.; Collum, S. C.] Univ Alabama, Birmingham, AL USA. [Miller, M. A.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2012 VL 31 IS 4 SU S MA 765 BP S261 EP S261 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 917VY UT WOS:000302207900765 ER PT J AU Dutta, M Schwartzberg, PL AF Dutta, Mala Schwartzberg, Pamela L. TI Characterization of Ly108 in the Thymus: Evidence for Distinct Properties of a Novel Form of Ly108 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LINKED LYMPHOPROLIFERATIVE-DISEASE; ACTIVATION MOLECULE SLAM; SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENE-PRODUCT SAP/SH2D1A; NATURAL-KILLER-CELLS; SH2 DOMAIN; TYROSINE PHOSPHORYLATION; INFECTIOUS-MONONUCLEOSIS; DIFFERENTIAL EXPRESSION; HOMOPHILIC INTERACTION AB Ly108 (CD352) is a member of the signaling lymphocyte activation molecule (SLAM) family of receptors that signals through SLAM-associated protein (SAP), an SH2 domain protein that can function by the recruitment of Src family kinases or by competition with phosphatases. Ly108 is expressed on a variety of hematopoietic cells, with especially high levels on developing thymocytes. We find that Ly108 is constitutively tyrosine phosphorylated in murine thymi in a SAP- and Fyn kinase-dependent manner. Phosphorylation of Ly108 is rapidly lost after thymocyte disaggregation, suggesting dynamic contact-mediated regulation of Ly108. Similar to recent reports, we find at least three isoforms of Ly108 mRNA and protein in the thymus, which are differentially expressed in the thymi of C57BL/6 and 129S6 mice that express the lupus-resistant and lupus-prone haplotypes of Ly108, respectively. Notably, the recently described novel isoform Ly108-H1 is not expressed in mice having the lupus-prone haplotype of Ly108, but is expressed in C57BL/6 mice. We further provide evidence for differential phosphorylation of these isoforms; the novel Ly108-H1does not undergo tyrosine phosphorylation, suggesting that it functions as a decoy isoform that contributes to the reduced overall phosphorylation of Ly108 seen in C57BL/6 mice. Our study suggests that Ly108 is dynamically regulated in the thymus, shedding light on Ly108 isoform expression and phosphorylation. The Journal of Immunology, 2012, 188: 3031-3041. C1 [Dutta, Mala; Schwartzberg, Pamela L.] NHGRI, NIH, Bethesda, MD 20892 USA. [Dutta, Mala] George Washington Univ, Inst Biomed Sci, Washington, DC 20052 USA. RP Schwartzberg, PL (reprint author), NHGRI, NIH, 49 Convent Dr,Room 4A38, Bethesda, MD 20892 USA. EM pams@mail.nih.gov FU National Human Genome Research Institute FX This work was supported by intramural funding of the National Human Genome Research Institute. NR 53 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2012 VL 188 IS 7 BP 3031 EP 3041 DI 10.4049/jimmunol.1103226 PG 11 WC Immunology SC Immunology GA 917CP UT WOS:000302150300017 PM 22393150 ER PT J AU Davey, AM Pierce, SK AF Davey, Angel M. Pierce, Susan K. TI Intrinsic Differences in the Initiation of B Cell Receptor Signaling Favor Responses of Human IgG(+) Memory B Cells over IgM(+) Naive B Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FC-GAMMA-RIIB; ANTIGEN-RECEPTOR; LYMPH-NODE; T-CELLS; SUBCAPSULAR SINUS; SYNAPSE FORMATION; IMMUNE-RESPONSES; ACTIVATION; BCR; EXPRESSION AB The acquisition of long-lived memory B cells (MBCs) is critical for the defense against many infectious diseases. Despite their importance, little is known about how Ags trigger human MBCs, even though our understanding of the molecular basis of Ag activation of B cells in model systems has advanced considerably. In this study, we use quantitative, high-resolution, live-cell imaging at the single-cell and single-molecule levels to describe the earliest Ag-driven events in human isotype-switched, IgG-expressing MBCs and compare them with those in IgM-expressing naive B cells. We show that human MBCs are more robust than naive B cells at each step in the initiation of BCR signaling, including interrogation of Ag-containing membranes, formation of submicroscopic BCR oligomers, and recruitment and activation of signaling-associated kinases. Despite their robust response to Ag, MBCs remain highly sensitive to Fc gamma RIIB-mediated inhibition. We also demonstrate that in the absence of Ag, a portion of MBC receptors spontaneously oligomerized, and phosphorylated kinases accumulated at the membrane and speculate that heightened constitutive signaling may play a role in maintaining MBC longevity. Using high-resolution imaging, we have provided a description of the earliest events in the Ag activation of MBCs and evidence for acquired cell-intrinsic differences in the initiation of BCR signaling in human naive and MBCs. The Journal of Immunology, 2012, 188: 3332-3341. C1 [Davey, Angel M.; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2,12441 Parklawn Dr,Room 200B,MSC 8180, Rockville, MD 20852 USA. EM spierce@nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 50 TC 14 Z9 14 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2012 VL 188 IS 7 BP 3332 EP 3341 DI 10.4049/jimmunol.1102322 PG 10 WC Immunology SC Immunology GA 917CP UT WOS:000302150300047 PM 22379037 ER PT J AU Beurskens, FJ Lindorfer, MA Farooqui, M Beum, PV Engelberts, P Mackus, WJM Parren, PWHI Wiestner, A Taylor, RP AF Beurskens, Frank J. Lindorfer, Margaret A. Farooqui, Mohammed Beum, Paul V. Engelberts, Patrick Mackus, Wendy J. M. Parren, Paul W. H. I. Wiestner, Adrian Taylor, Ronald P. TI Exhaustion of Cytotoxic Effector Systems May Limit Monoclonal Antibody-Based Immunotherapy in Cancer Patients SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; DEPENDENT CELLULAR CYTOTOXICITY; FRESH-FROZEN PLASMA; B-CELLS; COMPLEMENT ACTIVATION; ALTERNATIVE PATHWAY; NK ACTIVATION; KILLER-CELLS; TUMOR-CELLS; HUMAN CD20 AB The CD20 mAb of atumumab (OFA) induces complement-mediated lysis of B cells. In an investigator-initiated phase II trial of OFA plus chemotherapy for chronic lymphocytic leukemia (CLL), OFA treatment promoted partial CLL B cell depletion that coincided with reduced complement titers. Remaining CLL B cells circulated with bound OFA and covalently bound complement breakdown product C3d, indicative of ongoing complement activation. Presumably, neither complement-nor effector cell-based mechanisms were sufficiently robust to clear these remaining B cells. Instead, almost all of the bound OFA and CD20 was removed from the cells, in accordance with previous clinical studies that demonstrated comparable loss of CD20 from B cells after treatment of CLL patients with rituximab. In vitro experiments with OFA and rituximab addressing these observations suggest that host effector mechanisms that support mAb-mediated lysis and tumor cell clearance are finite, and they can be saturated or exhausted at high B cell burdens, particularly at high mAb concentrations. Interestingly, only a fraction of available complement was required to kill cells with CD20 mAbs, and killing could be tuned by titrating the mAb concentration. Consequently, maximal B cell killing of an initial and secondary B cell challenge was achieved with intermediate mAb concentrations, whereas high concentrations promoted lower overall killing. Therefore, mAb therapies that rely substantially on effector mechanisms subject to exhaustion, including complement, may benefit from lower, more frequent dosing schemes optimized to sustain and maximize killing by cytotoxic immune effector systems. The Journal of Immunology, 2012, 188: 3532-3541. C1 [Lindorfer, Margaret A.; Beum, Paul V.; Taylor, Ronald P.] Univ Virginia, Dept Biochem & Mol Genet, Sch Med, Charlottesville, VA 22908 USA. [Beurskens, Frank J.; Engelberts, Patrick; Mackus, Wendy J. M.; Parren, Paul W. H. I.] Genmab, NL-3584 CM Utrecht, Netherlands. [Farooqui, Mohammed; Wiestner, Adrian] NHLBI, Hematol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Taylor, RP (reprint author), Univ Virginia, Dept Biochem & Mol Genet, Sch Med, POB 800733, Charlottesville, VA 22908 USA. EM rpt@virginia.edu OI Parren, Paul/0000-0002-4365-3859 FU GlaxoSmithKline; Genmab; National Heart, Lung and Blood Institute, National Institutes of Health FX This work was supported by GlaxoSmithKline, which supported the correlative studies and provided ofatumumab for the trial, and by Genmab, which supported the in vitro studies. The clinical trial was funded by the National Heart, Lung and Blood Institute, National Institutes of Health. NR 51 TC 54 Z9 54 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2012 VL 188 IS 7 BP 3532 EP 3541 DI 10.4049/jimmunol.1103693 PG 10 WC Immunology SC Immunology GA 917CP UT WOS:000302150300067 PM 22368276 ER PT J AU Millum, J AF Millum, Joseph TI Sharing the benefits of research fairly: two approaches SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID DEVELOPING-COUNTRIES; INTERNATIONAL RESEARCH; CLINICAL-TRIALS AB Research projects sponsored by rich countries or companies and carried out in developing countries are often described as exploitative. One important debate about the prevention of exploitation in research centres on whether and how clinical research in developing countries should be responsive to local health problems. This paper analyses the responsiveness debate and draws out more general lessons for how policy makers can prevent exploitation in various research contexts. There are two independent ways to do this in the face of entrenched power differences: to impose restrictions on the content of benefit-sharing arrangements, and to institute independent effective oversight. Which method should be chosen is highly dependent on context. C1 NIH, Ctr Clin, Dept Bioeth, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Millum, J (reprint author), NIH, Ctr Clin, Dept Bioeth, Fogarty Int Ctr, Bldg 10,1C118,10 Ctr Dr, Bethesda, MD 20892 USA. EM millumj@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 25 TC 10 Z9 10 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD APR PY 2012 VL 38 IS 4 BP 219 EP 223 DI 10.1136/medethics-2011-100118 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 916SQ UT WOS:000302123900008 PM 21947808 ER PT J AU Gainer, H AF Gainer, H. TI Cell-Type Specific Expression of Oxytocin and Vasopressin Genes: An Experimental Odyssey SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Review DE cell-type specific gene expression; transcription factors; transcription factor binding sites; magnocellular neurones; phenotype ID GREEN FLUORESCENT PROTEIN; HYPOTHALAMIC SUPRAOPTIC NEURONS; ADENOASSOCIATED VIRAL VECTOR; MESSENGER RIBONUCLEIC-ACIDS; TRANSGENIC MICE; MAGNOCELLULAR NEURONS; DIABETES-INSIPIDUS; ARGININE-VASOPRESSIN; RAT VASOPRESSIN; HYPOTHALAMONEUROHYPOPHYSEAL SYSTEM AB The supraoptic nucleus (SON) is a particularly good model for the study of cell-type specific gene expression because it contains two distinct neuronal phenotypes, the oxytocin (OT) and vasopressin (AVP) synthesising magnocellular neurones (MCNs). The MCNs are found in approximately equal numbers and selectively express either the OT or the AVP gene in approximately 97% of the MCN population in the SON. An unresolved issue has been to determine what mechanisms are responsible for the highly selective regulation of the cell-type specific expression of OT and AVP genes in the MCNs. Previous attempts to address this question have used various bioinformatic and molecular approaches, which included using heterologous cell lines to study the putative cis-elements in the OT and AVP genes, and the use of OT and/or AVP transgenes in transgenic rodents. The data from all of the above studies identified a region < 0.6 kbp upstream of OT exon I and approximately 3 kb upstream of AVP exon I as being sufficient to produce cell-specific expression of the OT and AVP genes, respectively, although they failed to identify the specific cis-domains responsible for the MCN-specific gene expression. An alternative experimental approach to perform promoter deletion analysis in vivo (i.e. to use stereotaxic viral vector gene transfer into the SON to further dissect the cis-elements in the OT and AVP genes) will be described here. This in vivo method uses adeno-associated viral (AAV) vectors expressing OT-promoter deletion constructs and utilises the enhanced green fluorescent protein (EGFP) as the reporter. The AAV constructs are stereotaxically injected into the rat brain above the SON and, 2 weeks post injection, the rats are sacrificed and assayed for EGFP expression. Using this method, it has been possible to identify specific regions upstream of the transcription start site in the OT and AVP gene promoters that are responsible for conferring the cell-type specificity of the OT and AVP gene expression in the SON. C1 NINDS, Mol Neurosci Sect, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Gainer, H (reprint author), NINDS, Mol Neurosci Sect, Neurochem Lab, NIH, Bldg 49,Room 5A78, Bethesda, MD 20892 USA. EM gainerh@ninds.nih.gov FU NINDS, NIH FX This research was supported by the Intramural Research Program of the NINDS, NIH. I thank my many colleagues who contributed to this work, including Ray Fields, Todd Ponzio, Shirley House, Daniel Lubelski, Makoto Kawasaki, Madison Stevens, Omar Rashid, Yasmmyn Salinas, Yijun Shi, Babru Samal and Korey Johnson. NR 84 TC 16 Z9 17 U1 3 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD APR PY 2012 VL 24 IS 4 BP 528 EP 538 DI 10.1111/j.1365-2826.2011.02236.x PG 11 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 914CA UT WOS:000301925100002 PM 21985498 ER PT J AU Williams, SK Barber, JS Jamieson-Drake, AW Enns, JA Townsend, LB Walker, CH Johns, JM AF Williams, S. K. Barber, J. S. Jamieson-Drake, A. W. Enns, J. A. Townsend, L. B. Walker, C. H. Johns, J. M. TI Chronic Cocaine Exposure During Pregnancy Increases Postpartum Neuroendocrine Stress Responses SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE cocaine; postpartum; stress; oxytocin; corticosterone ID SPRAGUE-DAWLEY RATS; MESSENGER-RNA EXPRESSION; MATERNAL-BEHAVIOR; OXYTOCIN RELEASE; PLASMA-LEVELS; BRAIN OXYTOCIN; BLOOD-PRESSURE; FEMALE RATS; ANXIETY; DEPRESSION AB The cycle of chronic cocaine (CC) use and withdrawal results in increased anxiety, depression and disrupted stress-responsiveness. Oxytocin and corticosterone (CORT) interact to mediate hormonal stress responses and can be altered by cocaine use. These neuroendocrine signals play important regulatory roles in a variety of social behaviours, specifically during the postpartum period, and are sensitive to disruption by CC exposure in both clinical settings and preclinical models. To determine whether CC exposure during pregnancy affected behavioural and hormonal stress response in the early postpartum period in a rodent model, SpragueDawley rats were administered cocaine daily (30 mg/kg) throughout gestation (days 120). Open field test (OFT) and forced swim test (FST) behaviours were measured on postpartum day 5. Plasma CORT concentrations were measured before and after testing throughout the test day, whereas plasma and brain oxytocin concentrations were measured post-testing only. The results obtained indicated increased CORT response after the OFT in CC-treated dams (P = 0.05). CC-treated dams also exhibited altered FST behaviour (P = 0.05), suggesting abnormal stress responsiveness. Peripheral, but not central, oxytocin levels were increased by cocaine treatment (P = 0.05). Peripheral oxytocin and CORT increased after the FST, regardless of treatment condition (P = 0.05). Changes in stress-responsiveness, both behaviourally and hormonally, may underlie some deficits in maternal behaviour; thus, a clearer understanding of the effect of CC on the stress response system may potentially lead to treatment interventions that could be relevant to clinical populations. Additionally, these results indicate that CC treatment can have long-lasting effects on peripheral oxytocin regulation in rats, similar to changes observed in persistent social behaviour and stress-response deficits in clinical populations. C1 [Williams, S. K.; Jamieson-Drake, A. W.; Enns, J. A.; Walker, C. H.; Johns, J. M.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Barber, J. S.; Enns, J. A.] Univ N Carolina, Dept Biol, Chapel Hill, NC USA. [Townsend, L. B.; Johns, J. M.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. RP Williams, SK (reprint author), NIMH, Sect Neural Gene Express, 49 Convent Rd,RM 5A51, Bethesda, MD 20892 USA. EM williamssk@mail.nih.gov RI Williams, Sarah/K-4118-2012 FU National Institute on Drug Abuse [P01DA022446] FX We thank the invaluable assistance of Dr Hsiao Tien, Dr Matthew McMurray, Dr Sheryl Moy, Elizabeth Cox, Dave Gardner, Thomas Jarrett, Cara Heaton, Nisel Desai, Marlana Radcliffe and Ben Thompson for their help in the preparation of this manuscript and data collection, as well as their thoughtful discussions with the authors. The authors were supported by Award Number P01DA022446 (J.M.J.) from the National Institute on Drug Abuse. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Drug Abuse or the National Institutes of Health. NR 69 TC 3 Z9 3 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD APR PY 2012 VL 24 IS 4 BP 701 EP 711 DI 10.1111/j.1365-2826.2012.02291.x PG 11 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 914CA UT WOS:000301925100017 PM 22309318 ER PT J AU Jain, P Manuel, S Makedonas, G Betts, M Gardner, J Goedert, J Khan, ZK AF Jain, P. Manuel, S. Makedonas, G. Betts, M. Gardner, J. Goedert, J. Khan, Z. K. TI Dynamics of Dendritic Cells and T Cells in HTLV-1 Associated Oncogenesis and Neuroinflammation: Implications in Immunomodulatory Therapies and Diagnostic Tools SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Meeting Abstract C1 [Jain, P.; Manuel, S.; Khan, Z. K.] Drexel Univ, Dept Microbiol & Immunol, Coll Med, Doylestown, PA 18902 USA. [Makedonas, G.; Betts, M.; Gardner, J.] Univ Penn, Dept Microbiol & Immunol, Sch Med, Philadelphia, PA 19104 USA. [Goedert, J.] NCI, Div Canc Epidemiol & Genet, 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 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD APR PY 2012 VL 7 SU 1 BP S70 EP S70 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 918YY UT WOS:000302288800169 ER PT J AU Karn, J Alvarez, D Dobrowolski, C Das, B Harvey, BK AF Karn, J. Alvarez, D. Dobrowolski, C. Das, B. Harvey, B. K. TI Distinct Epigenetic Control Mechanisms Regulating HIV Silencing in T-cells and Microglial Cells. SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Meeting Abstract C1 [Karn, J.; Alvarez, D.; Dobrowolski, C.; Das, B.] Case Western Reserve Univ, Sch Med, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA. [Harvey, B. K.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 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 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD APR PY 2012 VL 7 SU 1 BP S18 EP S18 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 918YY UT WOS:000302288800017 ER PT J AU Hafed, ZM Krauzlis, RJ AF Hafed, Ziad M. Krauzlis, Richard J. TI Similarity of superior colliculus involvement in microsaccade and saccade generation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE voluntary eye movement; fixational eye movement; fixation ID DORSOLATERAL PREFRONTAL CORTEX; FIXATIONAL EYE-MOVEMENTS; NEURONAL-ACTIVITY; VOLUNTARY CONTROL; COVERT ATTENTION; MOTOR PREPARATION; NEURAL ACTIVITY; VISUAL-CORTEX; GAZE SHIFTS; MONKEY AB Hafed ZM, Krauzlis RJ. Similarity of superior colliculus involvement in microsaccade and saccade generation. J Neurophysiol 107: 1904-1916, 2012. First published January 11, 2012; doi: 10.1152/jn.01125.2011.-The characteristics of microsaccades, or small fixational saccades, and their influence on visual function have been studied extensively. However, the detailed mechanisms for generating these movements are less understood. We recently found that the superior colliculus (SC), a midbrain structure involved in saccade generation, also plays a role in microsaccade generation. Here we compared the dynamics of neuronal activity in the SC associated with microsaccades to those observed in this structure in association with larger voluntary saccades. We found that microsaccade-related activity in the SC is characterized by a gradual increase in firing rate starting similar to 100 ms prior to microsaccade onset, a peak of neuronal discharge just after movement onset, and a subsequent gradual decrease in firing rate until similar to 100 ms after movement onset. These properties were shared with saccade-related SC neurons, recorded from the same monkeys but preferring larger eye movements, suggesting that at the level of the SC the neuronal control of microsaccades is similar to that for larger voluntary saccades. We also found that neurons exhibiting microsaccade-related activity often also exhibited saccade-related activity for slightly larger movements of similar direction, suggesting a continuity of the spatial representation in the SC, in both amplitude and direction, down to the smallest movements. Our results indicate that the mechanisms controlling microsaccades may be fundamentally the same as those for larger saccades, and thus shed new light on the functional role of these eye movements and their possible influence on sensory and sensory-motor processes. C1 [Hafed, Ziad M.] Werner Reichardt Ctr Integrat Neurosci, D-72076 Tubingen, Germany. [Krauzlis, Richard J.] Salk Inst Biol Studies, Syst Neurobiol Lab, La Jolla, CA 92037 USA. [Krauzlis, Richard J.] NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. RP Hafed, ZM (reprint author), Werner Reichardt Ctr Integrat Neurosci, Paul Ehrlich Str 17, D-72076 Tubingen, Germany. EM ziad.m.hafed@cin.uni-tuebingen.de FU Werner Reichardt Centre for Integrative Neuroscience; National Eye Institute (NEI) [EY-12212]; National Institutes of Health FX Z. M. Hafed was funded by the Werner Reichardt Centre for Integrative Neuroscience and the National Eye Institute (NEI) (Grant EY-12212). R. J. Krauzlis was funded by NEI (Grant EY-12212) and the NEI Intramural Research Program at the National Institutes of Health. NR 74 TC 40 Z9 42 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 2012 VL 107 IS 7 BP 1904 EP 1916 DI 10.1152/jn.01125.2011 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 922GG UT WOS:000302534600011 PM 22236714 ER PT J AU Mena, E Turkbey, B Mani, H Adler, S Valera, VA Bernardol, M Shah, V Pohida, T McKinney, Y Kwarteng, G Daar, D Lindenberg, ML Eclarinal, P Wade, R Linehan, WM Merino, MJ Pinto, PA Choyke, PL Kurdziel, KA AF Mena, Esther Turkbey, Baris Mani, Haresh Adler, Stephen Valera, Vladimir A. Bernardol, Marcelino Shah, Vijay Pohida, Thomas McKinney, Yolanda Kwarteng, Gideon Daar, Dagane Lindenberg, Maria L. Eclarinal, Philip Wade, Revia Linehan, W. Marston Merino, Maria J. Pinto, Peter A. Choyke, Peter L. Kurdziel, Karen A. TI C-11-Acetate PET/CT in Localized Prostate Cancer: A Study with MRI and Histopathologic Correlation SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE prostate cancer; C-11-acetate PET; multiparametric prostate MRI ID POSITRON-EMISSION-TOMOGRAPHY; RADICAL PROSTATECTOMY; 1-C-11-ACETATE; DIAGNOSIS; RELAPSE; DISEASE AB This work characterizes the uptake of C-11-acetate in prostate cancer (PCa), benign prostate hyperplasia, and normal prostate tissue in comparison with multiparametric MRI, whole-mount histopathology, and clinical markers to evaluate the potential utility of C-11-acetate for delineating intraprostatic tumors in a population of patients with localized PCa. Methods: Thirtynine men with presumed localized PCa underwent dynamicstatic abdominal-pelvic C-11-acetate PET/CT for 30 min and 3-T multiparametric MRI before prostatectomy. PET/CT images were registered to MR images using pelvic bones for initial rotation-translation, followed by manual adjustments to account for prostate motion and deformation from the MRI endorectal coil. Whole-mount pathology specimens were sectioned using an MRI-based patient-specific mold resulting in improved registration between the MRI, PET, and pathology. C-11-acetate PET standardized uptake values were compared with multiparametric MRI and pathology. Results: C-11-acetate uptake was rapid but reversible, peaking at 3-5 min after injection and reaching a relative plateau at approximately 10 min. The average maximum standardized uptake value (10-12 min) of tumors was significantly higher than that of normal prostate tissue (4.4 +/- 2.05 [range, 1.8-9.2] vs. 2.1 +/- 0.94 [range, 0.7-3.4], respectively; P < 0.001); however, it was not significantly different from that of benign prostatic hyperplasia (4.8 +/- 2.01 [range, 1.8-8.8]). A sector-based comparison with histopathology, including all tumors greater than 0.5 cm, revealed a sensitivity and specificity of 61.6% and 80.0%, respectively, for C-11-acetate PET/CT and 82.3% and 95.1%, respectively, for MRI. The C-11-acetate accuracy was comparable to that of MRI when only tumors greater than 0:9 cm were considered. In a small cohort (n = 9), C-11-acetate uptake was independent of fatty acid synthase expression using immunohistochemistry. Conclusion: C-11-acetate PET/CT demonstrates higher uptake in tumor foci than in normal prostate tissue; however, C-11-acetate uptake in tumors is similar to that in benign prostate hyperplasia nodules. Although C-11-acetate PET/CT is not likely to have utility as an independent modality for evaluation of localized PCa, the high uptake in tumors may make it useful for monitoring focal therapy when tissue damage after therapy may limit anatomic imaging methods. C1 [Mena, Esther; Turkbey, Baris; Adler, Stephen; Bernardol, Marcelino; Shah, Vijay; McKinney, Yolanda; Kwarteng, Gideon; Daar, Dagane; Lindenberg, Maria L.; Eclarinal, Philip; Wade, Revia; Choyke, Peter L.; Kurdziel, Karen A.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Mani, Haresh; Valera, Vladimir A.; Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Bernardol, Marcelino; Shah, Vijay] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. [Pohida, Thomas] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Linehan, W. Marston; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Kurdziel, KA (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182,Bldg 10,Room B3B69, Bethesda, MD 20892 USA. EM karen.kurdziel@nih.gov RI Shah, Vijay/D-4083-2014 OI Shah, Vijay/0000-0003-3856-156X FU NIH, National Cancer Institute, Center for Cancer Research FX We thank Michael Channing and the NIH Clinical Center PET Department for providing the 11C-acetate. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. No other potential conflict of interest relevant to this article was reported. NR 25 TC 53 Z9 53 U1 0 U2 5 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR PY 2012 VL 53 IS 4 BP 538 EP 545 DI 10.2967/jnumed.111.096032 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920BV UT WOS:000302377300034 PM 22343504 ER PT J AU Zhou, Y Sojkoval, J Resnick, SM Wong, DF AF Zhou, Yun Sojkoval, Jitka Resnick, Susan M. Wong, Dean F. TI Relative Equilibrium Plot Improves Graphical Analysis and Allows Bias Correction of Standardized Uptake Value Ratio in Quantitative C-11-PiB PET Studies SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE RE plot; C-11-PiB; PET; SUVR; bias ID POSITRON-EMISSION-TOMOGRAPHY; REFERENCE TISSUE MODEL; MILD COGNITIVE IMPAIRMENT; PITTSBURGH COMPOUND-B; RECEPTOR DYNAMIC PET; ALZHEIMERS-DISEASE; SEROTONIN TRANSPORTER; AMYLOID DEPOSITION; SPATIAL CONSTRAINT; HUMAN BRAIN AB Both the standardized uptake value ratio (SUVR) and the Logan plot result in biased distribution volume ratios (DVRs) in ligand-receptor dynamic PET studies. The objective of this study was to use a recently developed relative equilibrium-based graphical (RE) plot method to improve and simplify the 2 commonly used methods for quantification of C-11-Pittsburgh compound B (C-11-PiB) PET. Methods: The overestimation of DVR in SUVR was analyzed theoretically using the Logan and the RE plots. A bias-corrected SUVR (bcSUVR) was derived from the RE plot. Seventy-eight C-11-PiB dynamic PET scans (66 from controls and 12 from participants with mild cognitive impaired [MCI] from the Baltimore Longitudinal Study of Aging) were acquired over 90 min. Regions of interest (ROIs) were defined on coregistered MR images. Both the ROI and the pixelwise time-activity curves were used to evaluate the estimates of DVR. DVRs obtained using the Logan plot applied to ROI time-activity curves were used as a reference for comparison of DVR estimates. Results: Results from the theoretic analysis were confirmed by human studies. ROI estimates from the RE plot and the bcSUVR were nearly identical to those from the Logan plot with ROI time-activity curves. In contrast, ROI estimates from DVR images in frontal, temporal, parietal, and cingulate regions and the striatum were underestimated by the Logan plot (controls, 4%-12%; MCI, 9%-16%) and overestimated by the SUVR (controls, 8%-16%; MCI, 16%-24%). This bias was higher in the MCI group than in controls (P < 0.01) but was not present when data were analyzed using either the RE plot or the bcSUVR. Conclusion: The RE plot improves pixelwise quantification of C-11-PiB dynamic PET, compared with the conventional Logan plot. The bcSUVR results in lower bias and higher consistency of DVR estimates than of SUVR. The RE plot and the bcSUVR are practical quantitative approaches that improve the analysis of C-11-PiB studies. C1 [Zhou, Yun; Sojkoval, Jitka; Wong, Dean F.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. [Sojkoval, Jitka; Resnick, Susan M.] NIA, Lab Behav Neurosci, Intramural Res Program, NIH, Baltimore, MD USA. RP Zhou, Y (reprint author), Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, 601 N Caroline St,JHOC Room 3245, Baltimore, MD 21287 USA. EM yunzhou@jhmi.edu FU NIH; National Institute on Aging (NIA) [N01-AG-0012, N01-AG-3-2124] FX We thank the cyclotron staff, PET staff, and MRI staff of the Johns Hopkins Medical Institutions and Andrew H. Crabb for data transfer and computer administration. This study was supported in part by the Intramural Research Program of the NIH and by the National Institute on Aging (NIA) (R&D contracts N01-AG-0012 and N01-AG-3-2124). No other potential conflict of interest relevant to this article was reported. This work was presented in part at the 56th Society of Nuclear Medicine conference, June 13-17, 2009, Toronto, Canada, and at the 57th Society of Nuclear Medicine conference, June 5-9, 2010, Salt Lake City, Utah. NR 39 TC 6 Z9 6 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR PY 2012 VL 53 IS 4 BP 622 EP 628 DI 10.2967/jnumed.111.095927 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920BV UT WOS:000302377300045 PM 22414634 ER PT J AU Kramer-Marek, G Gijsen, M Kiesewetter, DO Bennett, R Roxanis, I Zielinski, R Kong, A Capala, J AF Kramer-Marek, Gabriela Gijsen, Mere Kiesewetter, Dale O. Bennett, Ruth Roxanis, Ioannis Zielinski, Rafal Kong, Anthony Capala, Jacek TI Potential of PET to Predict the Response to Trastuzumab Treatment in an ErbB2-Positive Human Xenograft Tumor Model SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE breast cancer HER2/ErbB2; trastuzumab; PET imaging; Affibody molecules ID METASTATIC BREAST-CANCER; ADJUVANT CHEMOTHERAPY; THERAPY; TARGETS; HER2; EFFICACY; ANTIBODY; SAFETY AB Currently, an alteration in the gross volume of a tumor is used to assess its response to trastuzumab; however, this approach provides only a late indication of response. Tissue-sample ex vivo assays are potentially valuable, but their procurement through biopsies is invasive and might be biased by tumor heterogeneity. We studied the feasibility of using PET to quantify changes in ErbB2 (HER2/neu) expression and to predict the response to trastuzumab in BT474 breast cancer xenografts with N-[2-(4-F-18-fluorobenzamido)ethyl]maleimide (F-18-FBEM)-HER2:342 Affibody. Methods: Mice bearing BT474 tumors were given trastuzumab (50 mg/kg loading dose, 25 mg/kg maintenance dose, administered intraperitoneally twice a week) or saline (control) for a total of 5 doses. Tumor size was monitored twice a week. Animals were scanned before the treatment, at 48 h, and 2 wk after the beginning of therapy. After the final scan, PET results were correlated with tumor response and immunohistochemical assessment of ErbB2 level, as well as with vasculature in the treated tumors. Results: Analysis of PET images indicated that tracer uptake was significantly reduced after 1 dose of trastuzumab, compared with baseline, suggesting applicability as an early indicator of changes in ErbB2 expression. After 5 doses of trastuzumab, the overall decrease in F-18-FBEM-HER2:342 Affibody uptake also correlated with tumor response and downregulation of ErbB2 expression by immunohistochemical assessment. However, individual animals had different responses. There was a correlation between bigger PET changes and a higher vessel count in the tumors, suggesting that an increased number of vessels could lead to better trastuzumab delivery. We confirmed that the difference in average vessel count in the tumors was not related to the size of the tumors and therefore was not due to the selection of more vascular tumors. This finding is consistent with previous findings demonstrating that the number of vessels in a tumor could be a useful prognostic marker for treatment response. Conclusion: Our data suggest that Affibody-based PET can noninvasively provide specific information on changes in receptor expression and could be a valuable strategy for predicting tumor response to trastuzumab. C1 [Kramer-Marek, Gabriela; Zielinski, Rafal; Capala, Jacek] Natl Canc Inst, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20852 USA. [Gijsen, Mere; Bennett, Ruth; Kong, Anthony] Univ Oxford, Weatherall Inst Mol Med, Oxford, England. [Kiesewetter, Dale O.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Roxanis, Ioannis] Oxford Univ Hosp, Dept Cellular Pathol, Oxford, England. [Roxanis, Ioannis] Oxford Biomed Res Ctr, Oxford, England. RP Capala, J (reprint author), Natl Canc Inst, NIH, 6130 Executive Blvd,Room 6010, Rockville, MD 20852 USA. EM anthony.kong@imm.ox.ac.uk; capalaj@mail.nih.gov FU Center for Cancer Research; National Cancer Institute [N01-CO-12400, N01-CO-12401]; Imaging Probe Development Center; National Heart, Lung, and Blood Institute; Breast Cancer Research Stamp Fund; NIHR Biomedical Research Centre, Oxford; Breakthrough Breast Cancer through the Holbeck Charitable Trust FX We appreciate the support of Affibody AB and the technical assistance of Monika Kuban and Alesia Holly. 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 Center for Cancer Research, an Intramural Research Program of the National Cancer Institute; the Imaging Probe Development Center, National Heart, Lung, and Blood Institute; the Breast Cancer Research Stamp Fund, awarded through competitive peer review; the National Cancer Institute under contracts N01-CO-12400 and N01-CO-12401; the NIHR Biomedical Research Centre, Oxford; and Breakthrough Breast Cancer through the Holbeck Charitable Trust. No other potential conflict of interest relevant to this article was reported. NR 23 TC 21 Z9 21 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR PY 2012 VL 53 IS 4 BP 629 EP 637 DI 10.2967/jnumed.111.096685 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920BV UT WOS:000302377300046 PM 22410461 ER PT J AU Abd-Elmoniem, KZ Zahiri, H Pettigrew, RI Gharib, AM AF Abd-Elmoniem, K. Z. Zahiri, H. Pettigrew, R. I. Gharib, A. M. TI Assessment of coronary artery wall remodeling using phase-sensitive dual inversion recovery MRI SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 3rd Symposium on Multimodality Cardiovascular Molecular Imaging CY APR 19-21, 2012 CL Natl Inst Hlth (NIH), Bethesda, MD HO Natl Inst Hlth (NIH) C1 [Abd-Elmoniem, K. Z.; Pettigrew, R. I.; Gharib, A. M.] NIDDK, NIH, Bethesda, MD USA. [Zahiri, H.] NIH, CC, Bethesda, MD 20892 USA. RI Gharib, Ahmed/O-2629-2016; Abd-Elmoniem, Khaled/B-9289-2008 OI Gharib, Ahmed/0000-0002-2476-481X; Abd-Elmoniem, Khaled/0000-0002-1001-1702 NR 0 TC 0 Z9 0 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR PY 2012 VL 53 IS 4 MA 1 BP 665 EP 665 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920BV UT WOS:000302377300055 ER PT J AU Xu, B Wu, H Bhattacharyya, F Lane, K Li, C Sulima, A Griffiths, GL Jagoda, E Green, M Seidel, J Choyke, P AF Xu, B. Wu, H. Bhattacharyya, F. Lane, K. Li, C. Sulima, A. Griffiths, G. L. Jagoda, E. Green, M. Seidel, J. Choyke, P. TI F-18 radiolabeling of preformed liposomes for PET imaging of the vascular system SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 3rd Symposium on Multimodality Cardiovascular Molecular Imaging CY APR 19-21, 2012 CL Natl Inst Hlth (NIH), Bethesda, MD HO Natl Inst Hlth (NIH) C1 [Xu, B.; Wu, H.; Bhattacharyya, F.; Lane, K.; Li, C.; Sulima, A.; Griffiths, G. L.] NHLBI, Rockville, MD USA. [Jagoda, E.; Green, M.; Seidel, J.; Choyke, P.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR PY 2012 VL 53 IS 4 MA 21 BP 670 EP 671 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920BV UT WOS:000302377300075 ER PT J AU Shankaran, S Laptook, AR Tyson, JE Ehrenkranz, RA Bann, CM Das, A Higgins, RD Bara, R Pappas, A McDonald, SA Goldberg, RN Walsh, MC AF Shankaran, Seetha Laptook, Abbot R. Tyson, Jon E. Ehrenkranz, Richard A. Bann, Carla M. Das, Abhik Higgins, Rosemary D. Bara, Rebecca Pappas, Athina McDonald, Scott A. Goldberg, Ronald N. Walsh, Michele C. CA Eunice Kennedy Shriver Natl Inst TI Evolution of Encephalopathy during Whole Body Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy SO JOURNAL OF PEDIATRICS LA English DT Article ID CEREBRAL-PALSY; SYSTEMIC HYPOTHERMIA; ANTECEDENTS; OUTCOMES; INFANTS AB Objective To examine the predictive ability of stage of hypoxic-ischemic encephalopathy (HIE) for death or moderate/severe disability at 18 months among neonates undergoing hypothermia. Study design Stage of encephalopathy was evaluated at <6 hours of age, during study intervention, and at discharge among 204 participants in the National Institute of Child Health and Human Development Neonatal Research Network Trial of whole body hypothermia for HIE. HIE was examined as a predictor of outcome by regression models. Results Moderate and severe HIE occurred at <6 hours of age among 68% and 32% of 101 hypothermia group infants and 60% and 40% of 103 control group infants, respectively. At 24 and 48 hours of study intervention, infants in the hypothermia group had less severe HIE than infants in the control group. Persistence of severe HIE at 72 hours increased the risk of death or disability after controlling for treatment group. The discharge exam improved the predictive value of stage of HIE at <6 hours for death/disability. Conclusions On serial neurologic examinations, improvement in stage of HIE was associated with cooling. Persistence of severe HIE at 72 hours and an abnormal neurologic exam at discharge were associated with a greater risk of death or disability. (J Pediatr 2012;160:567-72). C1 [Shankaran, Seetha; Bara, Rebecca; Pappas, Athina] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [Laptook, Abbot R.] Women & Infants Hosp Rhode Isl, Dept Pediat, Providence, RI 02908 USA. [Tyson, Jon E.] Univ Texas Houston, Dept Pediat, Houston, TX USA. [Ehrenkranz, Richard A.] Yale Univ, Dept Pediat, New Haven, CT 06520 USA. [Bann, Carla M.; Das, Abhik; McDonald, Scott A.] RTI Int, Stat Design & Epidemiol, Res Triangle Pk, NC USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. [Goldberg, Ronald N.] Duke Univ, Dept Pediat, Durham, NC 27706 USA. [Walsh, Michele C.] Case Western Univ, Dept Pediat, Cleveland, OH USA. RP Shankaran, S (reprint author), Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD27904, U10 HD34216, U10 HD36790, U10 HD40461, U10 HD40492, U10 HD40498] FX Supported in part by the following grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development: U10 HD21364 (Case), U10 HD21373 (Houston), U10 HD21385 (Wayne), U10 HD21397 (Miami), U10 HD27851 (Emory), U10 HD27853 (Cincinnati), U10 HD27856 (Indiana), U10 HD27871 (Yale), U10 HD27880 (Stanford), U10 HD27904 (Brown), U10 HD34216 (Alabama), U10 HD36790 (RTI), U10 HD40461 (UCSD), U10 HD40492 (Duke), U10 HD40498 (Wake). NR 20 TC 31 Z9 31 U1 0 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 2012 VL 160 IS 4 BP 567 EP + DI 10.1016/j.jpeds.2011.09.018 PG 9 WC Pediatrics SC Pediatrics GA 921PP UT WOS:000302489800010 PM 22050871 ER PT J AU Johnson, LH Mapp, DC Rouse, DJ Spong, CY Mercer, BM Leveno, KJ Varner, MW Iams, JD Sorokin, Y Ramin, SM Miodovnik, M O'Sullivan, MJ Peaceman, AM Caritis, SN AF Johnson, Lynn H. Mapp, Delicia C. Rouse, Dwight J. Spong, Catherine Y. Mercer, Brian M. Leveno, Kenneth J. Varner, Michael W. Iams, Jay D. Sorokin, Yoram Ramin, Susan M. Miodovnik, Menachem O'Sullivan, Mary J. Peaceman, Alan M. Caritis, Steve N. CA Eunice Kennedy Shriver Natl Inst TI Association of Cord Blood Magnesium Concentration and Neonatal Resuscitation SO JOURNAL OF PEDIATRICS LA English DT Article ID PRETERM BIRTH; CONTROLLED-TRIAL; SULFATE; HYPERMAGNESEMIA; NEWBORN; INFANT AB Objective To assess the relationship between umbilical cord blood magnesium concentration and level of delivery room resuscitation received by neonates. Study design This was a secondary analysis of a controlled fetal neuroprotection trial that enrolled women at imminent risk for delivery between 24 and 31 weeks' gestation and randomly allocated them to receive either intravenous magnesium sulfate or placebo. The cohort included 1507 infants with data available on total cord blood Mg concentration and delivery room resuscitation. Multivariate logistic regression was used to estimate the association between cord blood Mg concentration and highest level of delivery room resuscitation, using the following hierarchy: none, oxygen only, bag-mask ventilation with oxygen, intubation, and chest compressions. Results There was no relationship between cord blood Mg and delivery room resuscitation (OR, 0.92 for each 1.0-mEq/L increase in Mg; 95% CI, 0.83-1.03). Maternal general anesthesia was associated with increased neonatal resuscitation (OR, 2.51; 95% CI, 1.72-3.68). Each 1-week increase in gestational age at birth was associated with decreased neonatal resuscitation (OR, 0.63; 95% CI, 0.60-0.66). Conclusion Cord blood Mg concentration does not correlate with the level of delivery room resuscitation of infants exposed to magnesium sulfate for fetal neuroprotection. (J Pediatr 2012;160:573-7). C1 [Johnson, Lynn H.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. [Mapp, Delicia C.] George Washington Univ, Ctr Biostat, Washington, DC USA. [Rouse, Dwight J.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Mercer, Brian M.] Case Western Reserve Univ, Metro Hlth Med Ctr, Cleveland, OH 44106 USA. [Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Varner, Michael W.] Univ Utah, Salt Lake City, UT USA. [Iams, Jay D.] Ohio State Univ, Columbus, OH 43210 USA. [Sorokin, Yoram] Wayne State Univ, Detroit, MI USA. [Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Miodovnik, Menachem] Univ Cincinnati, Cincinnati, OH USA. [O'Sullivan, Mary J.] Univ Miami, Miami, FL USA. [Peaceman, Alan M.] Northwestern Univ, Chicago, IL 60611 USA. [Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA. RP Johnson, LH (reprint author), UNC Hosp, Div Neonatal Perinatal Med, CB7596, Chapel Hill, NC 27599 USA. EM lynn.johnson@me.com RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850; Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD27869, HD34208, HD34116, HD40544, HD27915, HD34136, HD21414, HD27917, HD27860, HD40560, HD40545, HD40485, HD40500, HD27905, HD27861, HD34122, HD40512, HD53907, HD34210, HD21410, HD36801, HD19897, MO1-RR-000080]; National Institute of Neurological Disorders and Stroke; US government [National Institutes of Health] [1K23HL092225-01] FX Supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Grants HD27869, HD34208, HD34116, HD40544, HD27915, HD34136, HD21414, HD27917, HD27860, HD40560, HD40545, HD40485, HD40500, HD27905, HD27861, HD34122, HD40512, HD53907, HD34210, HD21410, HD36801, HD19897, MO1-RR-000080) and the National Institute of Neurological Disorders and Stroke. This report does not necessarily represent the official views of the National Institute of Child Health and Human Development, National Institute of Neurological Disorders and Stroke, or the National Institutes of Health. The authors declare no conflicts of interest.; We thank the subcommittee members who participated in protocol development and coordination between clinical research centers (Allison T. Northen, MSN, RN), protocol/data management and statistical analysis (Elizabeth Thom, PhD and Steven J. Weiner, MS), and protocol development and oversight (Deborah G. Hirtz, MD and John M. Thorp, Jr, MD). We also thank Matthew M. Laughon, MD, MPH (supported by the US government for his work in pediatric and neonatal clinical pharmacology [National Institutes of Health Grant 1K23HL092225-01]), University of North Carolina at Chapel Hill, for providing additional support with analysis and manuscript review. NR 20 TC 15 Z9 15 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 2012 VL 160 IS 4 BP 573 EP + DI 10.1016/j.jpeds.2011.09.016 PG 6 WC Pediatrics SC Pediatrics GA 921PP UT WOS:000302489800011 PM 22056282 ER PT J AU Boztug, K Rosenberg, PS Dorda, M Banka, S Moulton, T Curtin, J Rezaei, N Corns, J Innis, JW Avci, Z Tran, HC Pellier, I Pierani, P Fruge, R Parvaneh, N Mamishi, S Mody, R Darbyshire, P Motwani, J Murray, J Buchanan, GR Newman, WG Alter, BP Boxer, LA Donadieu, J Welte, K Klein, C AF Boztug, Kaan Rosenberg, Philip S. Dorda, Marie Banka, Siddharth Moulton, Thomas Curtin, Julie Rezaei, Nima Corns, John Innis, Jeffrey W. Avci, Zekai Hung Chi Tran Pellier, Isabelle Pierani, Paolo Fruge, Rachel Parvaneh, Nima Mamishi, Setareh Mody, Rajen Darbyshire, Phil Motwani, Jayashree Murray, Jennie Buchanan, George R. Newman, William G. Alter, Blanche P. Boxer, Laurence A. Donadieu, Jean Welte, Karl Klein, Christoph TI Extended Spectrum of Human Glucose-6-Phosphatase Catalytic Subunit 3 Deficiency: Novel Genotypes and Phenotypic Variability in Severe Congenital Neutropenia SO JOURNAL OF PEDIATRICS LA English DT Article ID STEM-CELL TRANSPLANTATION; LEUKEMIC TRANSFORMATION; MUTATIONS; G6PC3; EXPERIENCE; MORTALITY; ELASTASE; DISEASE; RISK; HAX1 AB Objective To delineate the phenotypic and molecular spectrum of patients with a syndromic variant of severe congenital neutropenia (SCN) due to mutations in the gene encoding glucose-6-phosphatase catalytic subunit 3 (G6PC3). Study design Patients with syndromic SCN were characterized for associated malformations and referred to us for G6PC3 mutational analysis. Results In a cohort of 31 patients with syndromic SCN, we identified 16 patients with G6PC3 deficiency including 11 patients with novel biallelic mutations. We show that nonhematologic features of G6PC3 deficiency are good predictive indicators for mutations in G6PC3. Additionally, we demonstrate genetic variability in this disease and define novel features such as growth hormone deficiency, genital malformations, disrupted bone remodeling, and abnormalities of the integument. G6PC3 mutations may be associated with hydronephrosis or facial dysmorphism. The risk of transition to myelodysplastic syndrome/acute myeloid leukemia may be lower than in other genetically defined SCN subgroups. Conclusions The phenotypic and molecular spectrum in G6PC3 deficiency is wider than previously appreciated. The risk of transition to myelodysplastic syndrome or acute myeloid leukemia may be lower in G6PC3 deficiency compared with other subgroups of SCN. (J Pediatr 2012;160:679-83). C1 [Boztug, Kaan] Austrian Acad Sci CeMM, Res Ctr Mol Med, A-1090 Vienna, Austria. [Boztug, Kaan] Med Univ Vienna, Dept Pediat & Adolescent Med, Vienna, Austria. [Boztug, Kaan; Dorda, Marie; Klein, Christoph] Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany. [Welte, Karl] Hannover Med Sch, Dept Mol Hematopoiesis, D-3000 Hannover, Germany. [Rosenberg, Philip S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Banka, Siddharth; Newman, William G.] St Marys Hosp, Manchester Acad Hlth Sci Ctr, Manchester M13 0JH, Lancs, England. [Moulton, Thomas] Bronx Lebanon Hosp Ctr, Dept Pediat Hematol Oncol, Bronx, NY USA. [Curtin, Julie] Childrens Hosp Westmead, Dept Hematol, Sydney, NSW, Australia. [Rezaei, Nima] Univ Tehran Med Sci, Mol Immunol Res Ctr, Tehran, Iran. [Rezaei, Nima] Univ Tehran Med Sci, Dept Immunol, Sch Med, Tehran, Iran. [Rezaei, Nima; Parvaneh, Nima] Univ Tehran Med Sci, Childrens Med Ctr, Res Ctr Immunodeficiencies, Tehran, Iran. [Mamishi, Setareh] Univ Tehran Med Sci, Infect Dis Res Ctr, Tehran, Iran. [Corns, John] Nationwide Childrens Hosp, Dept Pediat Hematol Oncol, Columbus, OH USA. [Innis, Jeffrey W.] Univ Michigan, Div Pediat Genet, Ann Arbor, MI 48109 USA. [Mody, Rajen; Boxer, Laurence A.] Univ Michigan Hosp, Dept Pediat, Ann Arbor, MI 48109 USA. [Avci, Zekai] Kecioren Res & Training Hosp, Dept Pediat Hematol, Ankara, Turkey. [Hung Chi Tran] Childrens Hosp Los Angeles, Dept Pediat, Div Hematol Oncol, Los Angeles, CA 90027 USA. [Pellier, Isabelle] CHU Angers, Angers, France. [Pierani, Paolo] Polytech Univ Marche, G Salesi Womens & Childrens Hosp, Inst Mother & Child Hlth, Div Pediat Hematol Oncol, Ancona, Italy. [Fruge, Rachel] Childrens Med Ctr, Ctr Canc & Blood Disorders, Dallas, TX 75235 USA. [Buchanan, George R.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Div Hematol Oncol, Dallas, TX 75390 USA. [Darbyshire, Phil; Motwani, Jayashree] Birmingham Childrens Hosp, Dept Haematol, Birmingham, W Midlands, England. [Murray, Jennie] Western Gen Hosp, SE Scotland Clin Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland. [Donadieu, Jean] Hop Trousseau, Serv Hemato Oncol Pediat, F-75571 Paris, France. [Klein, Christoph] Univ Munich, Univ Childrens Hosp, Munich, Germany. RP Boztug, K (reprint author), Austrian Acad Sci CeMM, Res Ctr Mol Med, Lazarettgasse 14,AKH BT 25-3, A-1090 Vienna, Austria. EM kboztug@cemm.oeaw.ac.at RI Rezaei, Nima/B-4245-2008; isabelle, pellier/L-5683-2015; OI Rezaei, Nima/0000-0002-3836-1827; Banka, Siddharth/0000-0002-8527-2210; Newman, William/0000-0002-6382-4678 FU Fritz-Thyssen-Foundation; BMBF E-RARE; NIHR Manchester Biomedical Research Centre; National Institutes of Health; National Cancer Institute of the United States FX Supported by grants from the Fritz-Thyssen-Foundation (to C. K. and K. B.), the BMBF E-RARE program (to C. K.), the NIHR Manchester Biomedical Research Centre (S. B.), and the Intramural Research Program of the National Institutes of Health and the National Cancer Institute of the United States (to P. R. and B. A.). The authors declare no conflicts of interest. NR 34 TC 26 Z9 27 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 2012 VL 160 IS 4 BP 679 EP + DI 10.1016/j.jpeds.2011.09.019 PG 7 WC Pediatrics SC Pediatrics GA 921PP UT WOS:000302489800031 PM 22050868 ER PT J AU Higgins, RD Raju, TNK Edwards, AD AF Higgins, Rosemary D. Raju, Tonse N. K. Edwards, A. David TI Hypothermia for neonatal encephalopathy in resource-poor environments Reply SO JOURNAL OF PEDIATRICS LA English DT Letter C1 [Higgins, Rosemary D.; Raju, Tonse N. K.; Edwards, A. David] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, Bethesda, MD USA. RP Higgins, RD (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, Bethesda, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 2012 VL 160 IS 4 BP 709 EP 710 DI 10.1016/j.jpeds.2012.01.013 PG 3 WC Pediatrics SC Pediatrics GA 921PP UT WOS:000302489800043 ER PT J AU Fowler, CB Waybright, TJ Veenstra, TD O'Leary, TJ Mason, JT AF Fowler, Carol B. Waybright, Timothy J. Veenstra, Timothy D. O'Leary, Timothy J. Mason, Jeffrey T. TI Pressure-Assisted Protein Extraction: A Novel Method for Recovering Proteins from Archival Tissue for Proteomic Analysis SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE FFPE; formalin-fixed paraffin-embedded; high-pressure protein extraction; mouse liver; mass spectrometry; heat and pressure; proteomics ID PARAFFIN-EMBEDDED TISSUES; MODELING FORMALIN FIXATION; ANTIGEN RETRIEVAL; MASS-SPECTROMETRY; PROSTATE-CANCER; SPECIMENS; IMMUNOHISTOCHEMISTRY; SURROGATES; BIOMARKER; SECTIONS AB Formaldehyde-fixed, paraffin-embedded (FFPE) tissue repositories represent a valuable resource for the retrospective study of disease progression and response to therapy. However, the proteomic analysis of FFPE tissues has been hampered by formaldehyde-induced protein modifications, which reduce protein extraction efficiency and may lead to protein misidentification. Here, we demonstrate the use of heat augmented with high hydrostatic pressure (40,000 psi) as a novel method for the recovery of intact proteins from FFPE mouse liver. When FFPE mouse liver was extracted using heat and elevated pressure, there was a 4-fold increase in protein extraction efficiency, a 3-fold increase in the extraction of intact proteins, and up to a 30-fold increase in the number of nonredundant proteins identified by mass spectrometry, compared to matched tissue extracted with heat alone. More importantly, the number of nonredundant proteins identified in the FFPE tissue was nearly identical to that of matched fresh-frozen tissue. C1 [Fowler, Carol B.; Mason, Jeffrey T.] Armed Forces Inst Pathol, Dept Biophys, Rockville, MD USA. [Fowler, Carol B.; O'Leary, Timothy J.] Vet Hlth Adm, Biomed Lab, Res & Dev Serv, Washington, DC USA. [Waybright, Timothy J.; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD USA. RP Mason, JT (reprint author), Armed Forces Inst Pathol, Dept Biophys, Rockville, MD USA. EM jeffrey.mason.afip@gmail.com FU National Cancer Institute, National Institutes of Health [1R21 CA134359, NO1-CO-12400]; Veterans Health Administration FX The authors declare the following competing financial interest(s): This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under grant 1R21 CA134359 (C.B.F.), and contract NO1-CO-12400 (T.D.V.), and the Veterans Health Administration under a Merit Review award (J.T.M. and T,J.O.). Carol B Fowler, Jeffrey T Mason, and Timothy J O'Leary are named as lead contributors in a patent application filed with the USPTO by the Veterans Health Administration and the Armed Forces Institute of Pathology. NR 33 TC 17 Z9 17 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD APR PY 2012 VL 11 IS 4 BP 2602 EP 2608 DI 10.1021/pr201005t PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 920FL UT WOS:000302388100048 PM 22352854 ER PT J AU Pope, K Luna, B Thomas, CR AF Pope, Kayla Luna, Beatriz Thomas, Christopher R. TI Developmental Neuroscience and the Courts: How Science Is Influencing the Disposition of Juvenile Offenders SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material C1 [Pope, Kayla] NIMH, Unit Affect Cognit Neurosci, Bethesda, MD 20892 USA. [Luna, Beatriz] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. [Thomas, Christopher R.] Univ Texas Med Branch Galveston, Galveston, TX USA. RP Pope, K (reprint author), NIMH, Unit Affect Cognit Neurosci, Bldg 15K,Room 115, Bethesda, MD 20892 USA. EM pkayla@mail.nih.gov NR 6 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 2012 VL 51 IS 4 BP 341 EP 342 DI 10.1016/j.jaac.2012.01.003 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 918SQ UT WOS:000302271800001 PM 22449636 ER PT J AU Swedo, SE Baird, G Cook, EH Happe, FG Harris, JC Kaufmann, WE King, BH Lord, CE Piven, J Rogers, SJ Spence, SJ Wetherby, A Wright, HH AF Swedo, Susan E. Baird, Gillian Cook, Edwin H., Jr. Happe, Francesca G. Harris, James C. Kaufmann, Walter E. King, Bryan H. Lord, Catherine E. Piven, Joseph Rogers, Sally J. Spence, Sarah J. Wetherby, Amy Wright, Harry H. TI Commentary from the DSM-5 Workgroup on Neurodevelopmental Disorders SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID AUTISM SPECTRUM DISORDER; CRITERIA RP Swedo, SE (reprint author), NIMH, Pediat & Dev Neurosci Branch, 10 Ctr Dr,MSC 1255,Bldg 10,Room 4N208, Bethesda, MD 20892 USA. EM swedos@mail.nih.gov OI Happe, Francesca/0000-0001-9226-4000 NR 5 TC 29 Z9 29 U1 2 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 2012 VL 51 IS 4 BP 347 EP 349 DI 10.1016/j.jaac.2012.02.013 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 918SQ UT WOS:000302271800004 PM 22449639 ER PT J AU DeKlotz, CC DeWitt, CA Cardin, E Ried, T AF DeKlotz, Cynthia Carver DeWitt, Christine A. Cardin, Eric Ried, Thomas TI All-trans-retinoic acid and cetuximab: Effects on colon adenocarcinoma cell viability SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Academy-of-Dermatology (AAD) CY MAR 16-20, 2012 CL San Diego, CA SP Amer Acad Dermatol (AAD) C1 [DeKlotz, Cynthia Carver] Georgetown Univ Hosp, Washington Hosp Ctr, Washington, DC 20007 USA. [Cardin, Eric; Ried, Thomas] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2012 VL 66 IS 4 SU S BP AB34 EP AB34 PG 1 WC Dermatology SC Dermatology GA 919JF UT WOS:000302319800136 ER PT J AU Smith, G Franks, A Cronstein, B Chan, E Liu, HL Fernandez, P AF Smith, Gideon Franks, Andrew Cronstein, Bruce Chan, Edwin Liu, Hailing Fernandez, Patricia TI Adenosine-mediated dermal fibrosis and Fli-1 expression in CD39 and CD73 knockout mice SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Academy-of-Dermatology (AAD) CY MAR 16-20, 2012 CL San Diego, CA SP Amer Acad Dermatol (AAD) C1 [Smith, Gideon; Cronstein, Bruce; Chan, Edwin; Liu, Hailing] NYU, Dept Translat Med, New York, NY USA. [Smith, Gideon; Franks, Andrew] NYU, Dept Dermatol, New York, NY 10016 USA. [Fernandez, Patricia] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2012 VL 66 IS 4 SU S BP AB2 EP AB2 PG 1 WC Dermatology SC Dermatology GA 919JF UT WOS:000302319800006 ER PT J AU Brown, M Simonsick, E Thorpe, R Ferrucci, L AF Brown, M. Simonsick, E. Thorpe, R. Ferrucci, L. TI Do Race-Related Functional Disparities Exist in Well-Educated Financially Secure Older Adults? Findings from the BLSA. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Brown, M.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Simonsick, E.; Ferrucci, L.] NIA IRP Intramural Res Program, Baltimore, MD USA. [Thorpe, R.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S107 EP S107 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800310 ER PT J AU Cleinman, A Griswold, ME Simonsick, E Meeks, WM Gregg, K Ferrucci, L Windham, BG AF Cleinman, A. Griswold, M. E. Simonsick, E. Meeks, W. M. Gregg, K. Ferrucci, L. Windham, B. G. TI Falls and Orthostatic Hypotension: Re-examining Limits SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Cleinman, A.; Meeks, W. M.; Gregg, K.; Windham, B. G.] Univ Mississippi, Med Ctr, Dept Med, Div Geriatr, Jackson, MS 39216 USA. [Griswold, M. E.] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA. [Simonsick, E.; Ferrucci, L.] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S11 EP S11 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800029 ER PT J AU Hanlon, JT Zheng, Y Boudreau, RM Strotmeyer, ES Newman, AB Simonsick, EM Shorr, RI Bauer, DC Donohue, JM AF Hanlon, J. T. Zheng, Y. Boudreau, R. M. Strotmeyer, E. S. Newman, A. B. Simonsick, E. M. Shorr, R. I. Bauer, D. C. Donohue, J. M. TI Antilipemic Use and Lipid Control in Older Black and White Adults with Coronary Heart Disease and/or Diabetes Mellitus Pre- and Post- Medicare Part D. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Hanlon, J. T.; Zheng, Y.; Boudreau, R. M.; Strotmeyer, E. S.; Newman, A. B.; Donohue, J. M.] UPITT, Pittsburgh, PA USA. [Simonsick, E. M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Shorr, R. I.] VA GRECC, Gainesville, FL USA. [Bauer, D. C.] UCSF, San Francisco, CA USA. RI Strotmeyer, Elsa/F-3015-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S110 EP S110 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800320 ER PT J AU Higuchi, M Chen, R Bell, C Wongvarcharoen, L Ross, W Petrovitch, H Launer, L Abbott, R Masaki, K AF Higuchi, M. Chen, R. Bell, C. Wongvarcharoen, L. Ross, W. Petrovitch, H. Launer, L. Abbott, R. Masaki, K. TI Proteinuria in Mid-Life and Cognitive Function in Late-Life: The Honolulu-Asia Aging Study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Higuchi, M.; Bell, C.; Wongvarcharoen, L.; Ross, W.; Petrovitch, H.; Abbott, R.; Masaki, K.] Univ Hawaii, Honolulu, HI 96822 USA. [Chen, R.; Petrovitch, H.; Masaki, K.] Kuakini Med Ctr, Honolulu, HI USA. [Ross, W.] VA Pacific Isl Healthcare Syst, Honolulu, HI USA. [Launer, L.] NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S115 EP S115 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800333 ER PT J AU Hile, ES Brach, JS Yang, M Studenski, SA Boudreau, RM Caserotti, P Satterfield, S Schwartz, AV Simonsick, E Ferrucci, L Harris, TB Newman, AB Strotmeyer, ES AF Hile, E. S. Brach, J. S. Yang, M. Studenski, S. A. Boudreau, R. M. Caserotti, P. Satterfield, S. Schwartz, A. V. Simonsick, E. Ferrucci, L. Harris, T. B. Newman, A. B. Strotmeyer, E. S. TI Sensory and motor nerve function differentially relate to gait parameters: the Health ABC Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Hile, E. S.; Brach, J. S.; Yang, M.; Studenski, S. A.; Boudreau, R. M.; Newman, A. B.; Strotmeyer, E. S.] Univ Pittsburgh, Pittsburgh, PA USA. [Caserotti, P.; Simonsick, E.; Ferrucci, L.; Harris, T. B.] NIA, Bethesda, MD 20892 USA. [Caserotti, P.] Univ So Denmark, Odense, Denmark. [Schwartz, A. V.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Satterfield, S.] Univ Tennessee, Memphis, TN USA. RI Strotmeyer, Elsa/F-3015-2014 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S11 EP S11 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800030 ER PT J AU Kojima, G Lui, F Chen, R Bell, C Abbott, RD Launer, L Ross, GW Curb, JD Masaki, KH AF Kojima, G. Lui, F. Chen, R. Bell, C. Abbott, R. D. Launer, L. Ross, G. W. Curb, J. D. Masaki, K. H. TI D as in Death - Dietary Vitamin D in Mid-Life and Total Mortality: The Honolulu Heart Program. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Kojima, G.; Lui, F.; Bell, C.; Abbott, R. D.; Ross, G. W.; Curb, J. D.; Masaki, K. H.] Univ Hawaii, John A Hartford Fdn Ctr Excellence Geriatr, Dept Geriatr Med, Honolulu, HI 96822 USA. [Chen, R.; Curb, J. D.; Masaki, K. H.] Kuakini Med Ctr, Honolulu, HI USA. [Ross, G. W.] Vet Affairs Pacific Isl Healthcare Syst, Honolulu, HI USA. [Launer, L.] NIA, Bethesda, MD 20892 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S150 EP S150 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800435 ER PT J AU Liu, C Lyass, A Massaro, J D'Agostino, R Fox, CS Murabito, JM AF Liu, C. Lyass, A. Massaro, J. D'Agostino, R. Fox, C. S. Murabito, J. M. TI Chronic kidney disease as defined by cystatin C predicts mobility disability: The Framingham Offspring Study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Liu, C.; Murabito, J. M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Liu, C.] Tufts Univ, JM USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Lyass, A.; Massaro, J.; D'Agostino, R.; Fox, C. S.; Murabito, J. M.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Massaro, J.; D'Agostino, R.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Fox, C. S.] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S117 EP S117 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800339 ER PT J AU Marcum, ZA Zheng, Y Perera, S Strotmeyer, E Newman, A Simonsick, E Shorr, R Bauer, DC Donohue, JM Hanlon, JT AF Marcum, Z. A. Zheng, Y. Perera, S. Strotmeyer, E. Newman, A. Simonsick, E. Shorr, R. Bauer, D. C. Donohue, J. M. Hanlon, J. T. TI Prevalence and Correlates of Self-Reported Medication Non-Adherence among Older Adults with Diabetes Mellitus, Coronary Heart Disease, and/or Hypertension. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Marcum, Z. A.; Zheng, Y.; Perera, S.; Strotmeyer, E.; Newman, A.; Donohue, J. M.; Hanlon, J. T.] Univ Pittsburgh, Pittsburgh, PA USA. [Simonsick, E.] NIA Intramural Res Program, Baltimore, MD USA. [Shorr, R.] VA GRECC, Gainesville, FL USA. [Bauer, D. C.] UCSF, San Francisco, CA USA. RI Perera, Subashan/D-7603-2014; Strotmeyer, Elsa/F-3015-2014 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S90 EP S90 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800260 ER PT J AU Peron, EP Zheng, Y Perera, S Newman, AB Resnick, NM Shorr, RI Bauer, DC Simonsick, EM Gray, SL Hanlon, JT Ruby, CM AF Peron, E. P. Zheng, Y. Perera, S. Newman, A. B. Resnick, N. M. Shorr, R. I. Bauer, D. C. Simonsick, E. M. Gray, S. L. Hanlon, J. T. Ruby, C. M. TI Antihypertensive Drug Class Use Associated with Urinary Incontinence in Community-Dwelling Elderly Women? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Peron, E. P.; Zheng, Y.; Perera, S.; Newman, A. B.; Resnick, N. M.; Hanlon, J. T.; Ruby, C. M.] Univ Pittsburgh, Pittsburgh, PA USA. [Shorr, R. I.] Gainesville VA Geriatr Res Educ & Clin Ctr, Gainesville, FL USA. [Simonsick, E. M.] Johns Hopkins Univ, Baltimore, MD USA. [Bauer, D. C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Simonsick, E. M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Gray, S. L.] Univ Washington, Seattle, WA 98195 USA. RI Perera, Subashan/D-7603-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S101 EP S101 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800292 ER PT J AU Wilson, V Neiberg, R Tooze, JA Sink, KM Shea, K Williamson, J Kitzman, DW Hausman, DB Cauley, J Bauer, D Harris, T Kritchevsky, SB Houston, DK AF Wilson, V. Neiberg, R. Tooze, J. A. Sink, K. M. Shea, K. Williamson, J. Kitzman, D. W. Hausman, D. B. Cauley, J. Bauer, D. Harris, T. Kritchevsky, S. B. Houston, D. K. TI 25-hydroxyvitamin D and Cardiovascular Disease in the Health ABC Study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Wilson, V.; Neiberg, R.; Tooze, J. A.; Sink, K. M.; Shea, K.; Williamson, J.; Kitzman, D. W.; Kritchevsky, S. B.; Houston, D. K.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Hausman, D. B.] Univ Georgia, Athens, GA 30602 USA. [Cauley, J.] Univ Pittsburgh, Pittsburgh, PA USA. [Bauer, D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Harris, T.] NIA, Bethesda, MD 20892 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S89 EP S89 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800259 ER PT J AU Daugirdas, JT Chertow, GM Larive, B Pierratos, A Greene, T Ayus, JC Kendrick, CA James, SH Miller, BW Schulman, G Salusky, IB Kliger, AS AF Daugirdas, John T. Chertow, Glenn M. Larive, Brett Pierratos, Andreas Greene, Tom Ayus, Juan Carlos Kendrick, Cynthia A. James, Sam H. Miller, Brent W. Schulman, Gerald Salusky, Isidro B. Kliger, Alan S. CA FHN Trial Grp TI Effects of Frequent Hemodialysis on Measures of CKD Mineral and Bone Disorder SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; PHOSPHATE BINDERS; CONVENTIONAL HEMODIALYSIS; METABOLISM; MORTALITY; TRIALS AB More frequent hemodialysis sessions and longer session lengths may offer improved phosphorus control. We analyzed data from the Frequent Hemodialysis Network Daily and Nocturnal Trials to examine the effects of treatment assignment on predialysis serum phosphorus and on prescribed dose of phosphorus binder, expressed relative to calcium carbonate on a weight basis. In the Daily Trial, with prescribed session lengths of 1.5-2.75 hours six times per week, assignment to frequent hemodialysis associated with both a 0.46 mg/dl decrease (95% confidence interval [95% CI], 0.13-0.78 mg/dl) in mean serum phosphorus and a 1.35 g/d reduction (95% CI, 0.20-2.50 g/d) in equivalent phosphorus binder dose at month 12 compared with assignment to conventional hemodialysis. In the Nocturnal Trial, with prescribed session lengths of 6-8 hours six times per week, assignment to frequent hemodialysis associated with a 1.24 mg/dl decrease (95% CI, 0.68-1.79 mg/dl) in mean serum phosphorus compared with assignment to conventional hemodialysis. Among patients assigned to the group receiving six sessions per week, 73% did not require phosphorus binders at month 12 compared with only 8% of patients assigned to sessions three times per week (P<0.001). At month 12, 42% of patients on nocturnal hemodialysis required the addition of phosphorus into the dialysate to prevent hypophosphatemia. Frequent hemodialysis did not have major effects on calcium or parathyroid hormone concentrations in either trial. In conclusion, frequent hemodialysis facilitates control of hyperphosphatemia and extended session lengths could allow more liberal diets and freedom from phosphorus binders. C1 [Daugirdas, John T.] Univ Illinois, Chicago, IL 60612 USA. [Chertow, Glenn M.] Stanford Univ, Stanford, CA 94305 USA. [Kendrick, Cynthia A.] Cleveland Clin, Cleveland, OH 44106 USA. [Pierratos, Andreas] Univ Toronto, Toronto, ON, Canada. [Greene, Tom] Univ Utah, Salt Lake City, UT USA. [Ayus, Juan Carlos] Renal Consultants Houston, Houston, TX USA. [James, Sam H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Miller, Brent W.] Washington Univ, St Louis, MO USA. [Schulman, Gerald] Vanderbilt Univ, Nashville, TN USA. [Salusky, Isidro B.] Univ Calif Los Angeles, Los Angeles, CA USA. [Kliger, Alan S.] Yale Univ, New Haven, CT USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Daugirdas, JT (reprint author), Univ Illinois, 820 S Wood St, Chicago, IL 60612 USA. EM jtdaugir@uic.edu FU National Institutes of Health (NIH), National Institutes of Diabetes and Digestive and Kidney Diseases; Center for Medicare and Medical Services; NIH Research Foundation; FHN trials included Amgen; Baxter; Dialysis Clinics Inc.; DaVita; Dialysis Clinics Inc; Fresenius Medical Care; Renal Advantage; Renal Research Institute; Satellite Healthcare FX This study was supported by the National Institutes of Health (NIH), National Institutes of Diabetes and Digestive and Kidney Diseases, the Center for Medicare and Medical Services, and the NIH Research Foundation. Contributors to the NIH Foundation in support of the FHN trials included Amgen, Baxter, and Dialysis Clinics Inc. Additional support was provided by DaVita, Dialysis Clinics Inc, Fresenius Medical Care, Renal Advantage, Renal Research Institute, and Satellite Healthcare. NR 22 TC 55 Z9 57 U1 0 U2 16 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 2012 VL 23 IS 4 BP 727 EP 738 DI 10.1681/ASN.2011070688 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 919MZ UT WOS:000302333300020 PM 22362907 ER PT J AU Brown, P AF Brown, Patricia TI A word from OLAW SO LAB ANIMAL LA English DT Editorial Material C1 NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD APR PY 2012 VL 41 IS 4 BP 98 EP 98 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 918TU UT WOS:000302274800015 PM 22430472 ER PT J AU Chen, ZD Mantha, RR Chen, JS Slivano, OJ Takahashi, H AF Chen, Zhidong Mantha, Rebecca R. Chen, Janice S. Slivano, Orazio J. Takahashi, Hideko TI Non-invasive genotyping of transgenic animals using fecal DNA SO LAB ANIMAL LA English DT Article ID PCR AMPLIFICATION; EXTRACTION; MICE; FECES; SAMPLES; IDENTIFICATION; BACTERIAL AB For genotyping of transgenic animals, many IACUC guidelines recommend the use of fecal DNA when possible because this approach is non-invasive. Existing methods for extracting fecal DNA may be costly or involve the use of toxic organic solvents. Furthermore, feces contain an abundance of PCR inhibitors that may hinder DNA amplification when they are co-purified with fecal DNA. Here the authors describe a cost-effective, non-toxic method for genotyping transgenic animals by using the reagent Aqua Stool to extract fecal DNA and remove PCR inhibitors. Genotyping results obtained from fecal DNA samples extracted using Aqua Stool were reliably accurate when compared with results obtained from tail DNA samples. Because it is non-invasive, the authors believe that use of this method for genotyping transgenic animals using fecal DNA samples may improve animal welfare. C1 [Chen, Zhidong] MultiTarget Pharmaceut LLC, Salt Lake City, UT 84103 USA. [Mantha, Rebecca R.] Atom Energy Canada Ltd, Chalk River Labs, Chalk River, ON K0J 1J0, Canada. [Chen, Janice S.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Slivano, Orazio J.] Univ Rochester, Sch Med & Dent, Aab Cardiovasc Res Inst, Rochester, NY USA. [Takahashi, Hideko] NEI, NIH, Bethesda, MD 20892 USA. RP Chen, ZD (reprint author), MultiTarget Pharmaceut LLC, Salt Lake City, UT 84103 USA. EM zchen@multitargetpharm.com FU Johns Hopkins Center for Alternatives to Animal Testing (CAAT) FX This work was funded in part by a grant from the Johns Hopkins Center for Alternatives to Animal Testing (CAAT). NR 20 TC 0 Z9 1 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD APR PY 2012 VL 41 IS 4 BP 102 EP 107 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 918TU UT WOS:000302274800017 PM 22430476 ER PT J AU Roberts, DD Miller, TW Rogers, NM Yao, MY Isenberg, JS AF Roberts, David D. Miller, Thomas W. Rogers, Natasha M. Yao, Mingyi Isenberg, Jeffrey S. TI The matricellular protein thrombospondin-1 globally regulates cardiovascular function and responses to stress via CD47 SO MATRIX BIOLOGY LA English DT Review DE Thrombospondin-1; Nitric oxide; Blood pressure; Ischemia; CD47; cGMP ID ENDOTHELIAL GROWTH-FACTOR; SOLUBLE GUANYLATE-CYCLASE; ISCHEMIA-REPERFUSION INJURY; INTEGRIN-ASSOCIATED PROTEIN; MUSCLE-CELL RESPONSES; NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE; HUMAN PLATELETS; BLOOD-PRESSURE; ENDOGENOUS THROMBOSPONDIN-1 AB Matricellular proteins play diverse roles in modulating cell behavior by engaging specific cell surface receptors and interacting with extracellular matrix proteins, secreted enzymes, and growth factors. Studies of such interactions involving thrombospondin-1 have revealed several physiological functions and roles in the pathogenesis of injury responses and cancer, but the relatively mild phenotypes of mice lacking thrombospondin-1 suggested that thrombospondin-1 would not be a central player that could be exploited therapeutically. Recent research focusing on signaling through its receptor CD47, however, has uncovered more critical roles for thrombospondin-1 in acute regulation of cardiovascular dynamics, hemostasis, immunity, and mitochondrial homeostasis. Several of these functions are mediated by potent and redundant inhibition of the canonical nitric oxide pathway. Conversely, elevated tissue thrombospondin-1 levels in major chronic diseases of aging may account for the deficient nitric oxide signaling that characterizes these diseases, and experimental therapeutics targeting CD47 show promise for treating such chronic diseases as well as acute stress conditions that are associated with elevated thrombospondin-1 expression. Published by Elsevier B.V. C1 [Roberts, David D.; Miller, Thomas W.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Isenberg, Jeffrey S.] Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA. [Rogers, Natasha M.; Yao, Mingyi; Isenberg, Jeffrey S.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15213 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10 Room 2A33,10 Ctr Dr MSC1500, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov; jsi5@pitt.edu RI Roberts, David/A-9699-2008; Miller, Thomas/G-1215-2011 OI Roberts, David/0000-0002-2481-2981; Miller, Thomas/0000-0001-8645-2785 FU National Cancer Institute, NIH; NIH [K22CA128616, R01 HL-108954]; American Heart Association [11BGIA7210001, 1P01HL103455-01]; Vascular Medicine Institute; Institute for Transfusion Medicine; Hemophilia Center of Western PA FX This work was supported by the Intramural Research Program of the National Cancer Institute, NIH to DDR and K22CA128616, R01 HL-108954 (NIH), American Heart Association grant 11BGIA7210001, 1P01HL103455-01 (NIH), the Vascular Medicine Institute, the Institute for Transfusion Medicine, and the Hemophilia Center of Western PA to JSI. NR 94 TC 46 Z9 47 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD APR PY 2012 VL 31 IS 3 BP 162 EP 169 DI 10.1016/j.matbio.2012.01.005 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 921AE UT WOS:000302449600003 PM 22266027 ER PT J AU Glaser, R Dimitrakakis, C Trimble, N Martin, V AF Glaser, Rebecca Dimitrakakis, Constantine Trimble, Nancy Martin, Vincent TI Testosterone pellet implants and migraine headaches: A pilot study SO MATURITAS LA English DT Article DE Androgens; Testosterone; Implant; Migraine headache; Pre-menopausal; Post-menopausal ID POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; ANDROGENS; AGE AB The purpose of this prospective pilot study was to determine the therapeutic effect of continuous testosterone, delivered as a subcutaneous implant, on the severity of migraine headaches in pre- and post-menopausal patients. Twenty-seven women with a history of documented migraine headache were asked to rate their headache severity using a five-point scale at baseline (prior to therapy); and again, 3 months following treatment with testosterone implants. Improvement in headache severity was noted by 92% of patients and the mean level of improvement was statistically significant (3.3 on a 5 point scale). In addition, there was no difference in the level of improvement between pre- and post-menopausal cohorts. Seventy-four percent of patients reported a headache severity score of '0' (none) on testosterone implant therapy for the 3-month treatment period. Continuous testosterone was effective therapy in reducing the severity of migraine headaches in both pre- and post-menopausal women. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Glaser, Rebecca] Millennium Wellness Ctr, Dayton, OH 45458 USA. [Glaser, Rebecca] Wright State Univ, Boonshoft Sch Med, Dept Surg, Dayton, OH 45435 USA. [Dimitrakakis, Constantine] Univ Athens, Sch Med, Dept Ob Gyn 1, Athens 11528, Greece. [Dimitrakakis, Constantine] NICHD, NIH, Bethesda, MD 20892 USA. [Trimble, Nancy] Hosp Dayton, Dayton, OH 45420 USA. [Martin, Vincent] Univ Cincinnati, Coll Med, Dept Internal Med, Cincinnati, OH 45267 USA. RP Glaser, R (reprint author), Millennium Wellness Ctr, 228 E Spring Valley Rd, Dayton, OH 45458 USA. EM rglaser@woh.rr.com; dimitrac@mail.nih.gov; ntrimble@woh.rr.com; martinvt@ucmail.uc.edu NR 21 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-5122 EI 1873-4111 J9 MATURITAS JI Maturitas PD APR PY 2012 VL 71 IS 4 BP 385 EP 388 DI 10.1016/j.maturitas.2012.01.006 PG 4 WC Geriatrics & Gerontology; Obstetrics & Gynecology SC Geriatrics & Gerontology; Obstetrics & Gynecology GA 920US UT WOS:000302434200012 PM 22310106 ER PT J AU Harlow, SD Gass, M Hall, JE Lobo, R Maki, P Rebar, RW Sherman, S Sluss, PM de Villiers, TJ AF Harlow, Sioban D. Gass, Margery Hall, Janet E. Lobo, Roger Maki, Pauline Rebar, Robert W. Sherman, Sherry Sluss, Patrick M. de Villiers, Tobie J. CA STRAW 10 Collaborative Grp TI Executive summary of the Stages of Reproductive Aging Workshop+10: addressing the unfinished agenda of staging reproductive aging SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Reproductive aging; Ovarian aging; Menopause; Follicle-stimulating hormone; Antimullerian hormone; Antral follicle count; Inhibin-B ID FOLLICLE-STIMULATING-HORMONE; ANTI-MULLERIAN HORMONE; EARLY MENOPAUSAL TRANSITION; POLYCYSTIC-OVARY-SYNDROME; MIDDLE-AGED WOMEN; REGULAR MENSTRUAL CYCLES; INHIBIN-B; ANTIMULLERIAN HORMONE; LONGITUDINAL CHANGES; DEPRESSIVE SYMPTOMS AB Objective: The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period. Methods: Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimullerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus. Results: STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage -3) and the early postmenopause stage (Stage + 1), provided information on the duration of the late transition (Stage -1) and early postmenopause (Stage + 1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics. Conclusions: STRAW + 10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW + 10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified. C1 [Harlow, Sioban D.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Gass, Margery] N Amer Menopause Soc, Mayfield Hts, OH USA. [Hall, Janet E.] Harvard Univ, Sch Med, Dept Med, Endocrine Soc, Boston, MA USA. [Lobo, Roger] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. [Maki, Pauline] Univ Illinois, Dept Psychiat & Psychol, Chicago, IL USA. [Rebar, Robert W.] Amer Soc Reprod Med, Birmingham, AL USA. [Sherman, Sherry] NIA, Bethesda, MD 20892 USA. [Sluss, Patrick M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [de Villiers, Tobie J.] Internat Menopause Soc, Cape Town, South Africa. RP Harlow, SD (reprint author), Univ Michigan, Dept Epidemiol, 1415 Washington Hts, Ann Arbor, MI 48109 USA. EM harlow@umich.edu FU National Institutes of Health (NIH), Department of Health and Human Services (DHHS), through the National Institute on Aging (NIA) [AG039961]; NIH Office of Research on Women's Health (ORWH); North American Menopause Society (NAMS); American Society for Reproductive Medicine (ASRM); International Menopause Society (IMS); Endocrine Society; National Institute on Aging (NIA); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute on Mental Health (NIMH); National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Drug Abuse (NIDA); Royal Ottawa Foundation for Mental Health; Mayo Clinic; Northwestern University; ASRM; Adcock Ingram; Pfizer; Servier; Amgen; Bayer; Board of Trustees for NAMS; Baycrest FX Funding/support: The Stages of Reproductive Aging Workshop (STRAW) + 10 had grant support from the National Institutes of Health (NIH), Department of Health and Human Services (DHHS), through the National Institute on Aging (NIA) (AG039961), and the NIH Office of Research on Women's Health (ORWH) as well as from The North American Menopause Society (NAMS), the American Society for Reproductive Medicine (ASRM), the International Menopause Society (IMS), and the Endocrine Society.; Financial disclosure/conflicts of interest: P. M. S. and S. S. declare no conflict of interest. M. G. receives salary support from The North American Menopause Society (NAMS). S. D. H. has grant support from the National Institute on Aging (NIA) and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and receives travel support from NAMS. J.E.H. has grant support from NIA and receives travel support from the Endocrine Society. R. L. is past president of the American Society for Reproductive Medicine (ASRM). P. M. receives grant support from the National Institute on Mental Health (NIMH), the NIA, the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute on Drug Abuse (NIDA); is on the Board of Trustees for NAMS; and has previously consulted for Noven Pharmaceuticals, received lecture fees from the Royal Ottawa Foundation for Mental Health, the Mayo Clinic, Baycrest, and Northwestern University and received travel support from the Society for Women's Health Research, the International Menopause Society, Pfizer, the Australasian Pacific Menopause Society, Virginia Commonwealth University Institute for Women's Health. R. W. R. receives salary support from ASRM. T.J.d.V. declares no direct conflict of interest as regards the submitted article but has in the past received consultancy fees from Adcock Ingram and Pfizer; speaker's fees from Servier; and travel support from Amgen, Pfizer, and Bayer. NR 90 TC 72 Z9 78 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD APR PY 2012 VL 19 IS 4 BP 387 EP 395 DI 10.1097/gme.0b013e31824d8f40 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 916ZM UT WOS:000302141700005 PM 22343510 ER PT J AU Cheung, GYC Duong, AC Otto, M AF Cheung, Gordon Y. C. Duong, Anthony C. Otto, Michael TI Direct and synergistic hemolysis caused by Staphylococcus phenol-soluble modulins: implications for diagnosis and pathogenesis SO MICROBES AND INFECTION LA English DT Article DE Staphylococcus aureus; Staphylococcus epidermidis; Hemolysis; Beta-toxin; Delta-toxin; Phenol-soluble modulin ID VIRULENCE DETERMINANTS; AUREUS; AGR; EXPRESSION; EPIDERMIDIS; MUTATION; IDENTIFICATION; PEPTIDES; STREPTOCOCCI; EVOLUTION AB Phenol-soluble modulins are secreted staphylococcal peptides with an amphipathic alpha-helical structure. Some PSMs are strongly cytolytic toward human neutrophils and represent major virulence determinants during Staphylococcus aureus skin and blood infection. However, capacities of PSMs to lyse human erythrocytes have not been investigated. Here, we demonstrate that many S. aureus and Staphylococcus epidermidis PSMs lyse human erythrocytes. Furthermore, synergism with S. aureus beta-toxin considerably increased the hemolytic capacities of several PSMs. This synergism may be of key importance in PSM and beta-toxin-producing S. aureus or in mixed-strain or -species infections with PSM and beta-toxin producers. Of specific interest, several PSMs, in particular PSM alpha peptides, contributed to a considerable extent to synergistic hemolysis with beta-toxin or when using the beta-toxin-producing strain RN4220 in CAMP assays. Thus, CAMP-type assays should not be used to detect or quantify S. aureus delta-toxin production, but may be used for an overall assessment of Agr functionality. Our study suggests an additional role of PSMs in staphylococcal pathogenesis and demonstrates that the repertoire of staphylococcal hemolysins is not limited to S. aureus and is much larger and diverse than previously thought. Published by Elsevier Masson SAS on behalf of Institut Pasteur. C1 [Cheung, Gordon Y. C.; Duong, Anthony C.; Otto, Michael] NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. RP Otto, M (reprint author), NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bldg 33,Room 1W10A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM motto@niaid.nih.gov RI Cheung, Yiu Chong /K-3565-2012; OI Otto, Michael/0000-0002-2222-4115 FU National Institute of Allergy and Infectious Diseases (NIAID), The National Institutes of Health (NIH) FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), The National Institutes of Health (NIH). NR 33 TC 38 Z9 38 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD APR PY 2012 VL 14 IS 4 BP 380 EP 386 DI 10.1016/j.micinf.2011.11.013 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 920SR UT WOS:000302428300011 PM 22178792 ER PT J AU Kagan, BL Jang, H Capone, R Arce, FT Ramachandran, S Lal, R Nussinov, R AF Kagan, Bruce L. Jang, Hyunbum Capone, Ricardo Arce, Fernando Teran Ramachandran, Srinivasan Lal, Ratnesh Nussinov, Ruth TI Antimicrobial Properties of Amyloid Peptides SO MOLECULAR PHARMACEUTICS LA English DT Review DE amyloid ion channels; beta-strand-turn-beta-strand motif; cytotoxicity; antimicrobial activity ID LIPID-BILAYER-MEMBRANES; CATION-SELECTIVE CHANNELS; PRION PROTEIN-FRAGMENT; LONG-TERM POTENTIATION; FORMS ION CHANNELS; ALZHEIMERS-DISEASE; BETA-PROTEIN; PRECURSOR PROTEIN; CALCIUM-CHANNELS; CORTICAL-NEURONS AB More than two dozen clinical syndromes known as amyloid diseases are characterized by the buildup of extended insoluble fibrillar deposits in tissues. These amorphous Congo red staining deposits known as amyloids exhibit a characteristic green birefringence and cross-beta structure. Substantial evidence implicates oligomeric intermediates of amyloids as toxic species in the pathogenesis of these chronic disease states. A growing body of data has suggested that these toxic species form ion channels in cellular. membranes causing disruption of calcium homeostasis, membrane depolarization, energy drainage, and in some cases apoptosis. Amyloid peptide channels exhibit a number of common biological properties including the universal U-shape beta-strand-turn-beta-strand structure, irreversible and spontaneous insertion into membranes, production of large heterogeneous single-channel conductances, relatively poor ion selectivity, inhibition by Congo red, and channel blockade by zinc. Recent evidence has suggested that increased amounts of amyloids not only are toxic to its host target cells but also possess antimicrobial activity. Furthermore, at least one human antimicrobial peptide, protegrin-1, which kills microbes by a channel-forming mechanism, has been shown to possess the ability to form extended amyloid fibrils very similar to those of classic disease-forming amyloids. In this paper, we will review the reported antimicrobial properties of amyloids and the implications of these discoveries for our understanding of amyloid structure and function. C1 [Kagan, Bruce L.] Univ Calif Los Angeles, Dept Psychiat, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Jang, Hyunbum; Nussinov, Ruth] NCI, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Capone, Ricardo; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Capone, Ricardo; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Dept Mech & Aerosp Engn, La Jolla, CA 92093 USA. [Capone, Ricardo; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Mat Sci Program, La Jolla, CA 92093 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. RP Kagan, BL (reprint author), Univ Calif Los Angeles, Dept Psychiat, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. EM bkagan@mednet.ucla.edu; rlal@ucsd.edu RI Capone, Ricardo/D-1943-2010; Ramachandran, Srinivasan/G-5300-2010 OI Capone, Ricardo/0000-0002-7327-9837; Ramachandran, Srinivasan/0000-0002-4912-0279 FU National Institutes of Health (National Institute on Aging) [AG028709]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the National Institutes of Health (National Institute on Aging AG028709 to RL.). 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. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. All simulations had been performed using the high-performance computational facilities of the Biowulf PC/Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). NR 91 TC 41 Z9 41 U1 3 U2 37 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD APR PY 2012 VL 9 IS 4 BP 708 EP 717 DI 10.1021/mp200419b PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 917OE UT WOS:000302186700003 PM 22081976 ER PT J AU Bahta, M Liu, F Kim, SE Stephen, AG Fisher, RJ Burke, TR AF Bahta, Medhanit Liu, Fa Kim, Sung-Eun Stephen, Andrew G. Fisher, Robert J. Burke, Terrence R., Jr. TI Oxime-based linker libraries as a general approach for the rapid generation and screening of multidentate inhibitors SO NATURE PROTOCOLS LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; SITU CLICK CHEMISTRY; TSG101 UEV DOMAIN; YERSINIA-PESTIS; SUBSTRATE-SPECIFICITY; ENZYME-INHIBITORS; TERMINAL ALKYNES; STRUCTURAL BASIS; SALICYLIC-ACID; SOLID-PHASE AB The described oxime-based library protocol provides detailed procedures for the linkage of aminooxy functionality with aldehyde building blocks that result in the generation of libraries of multidentate inhibitors. Synthesis of inhibitors for protein tyrosine phosphatases (PTPs) and antagonists directed against the human tumor susceptibility gene 101 (TSG101) are shown as examples. Three steps are involved: (i) the design and synthesis of aminooxy platforms; (ii) tethering with aldehydes to form oxime-based linkages with sufficient purity; and (iii) direct in vitro biological evaluation of oxime products without purification. Each coupling reaction is (i) performed in capped microtubes at room temperature (20-23 degrees C); (ii) diluted for inhibitory evaluation; and (iii) screened with targets in microplates to provide IC50 or K-d values. The synthesis of the aminooxy platforms takes 3-5 d; tethering with the aldehydes takes 24 h; and inhibition assay of enzymes and protein-protein interactions takes 30 min and 2 h, respectively. C1 [Bahta, Medhanit; Liu, Fa; Kim, Sung-Eun; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,US Natl Inst Hlth, Frederick, MD 21701 USA. [Stephen, Andrew G.; Fisher, Robert J.] SAIC Frederick Inc, Adv Technol Program, Prot Chem Lab, Frederick, MD USA. RP Burke, TR (reprint author), NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,US Natl Inst Hlth, Frederick, MD 21701 USA. EM tburke@helix.nih.gov RI Burke, Terrence/N-2601-2014 FU US National Institutes of Health, Center for Cancer Research, National Cancer Institute-Frederick [HHSN261200800001E]; National Cancer Institute, National Institutes of Health FX This work was supported in part by the Intramural Research Program and under the Contract No. HHSN261200800001E of the US National Institutes of Health, Center for Cancer Research, National Cancer Institute-Frederick and the National Cancer Institute, National Institutes of Health. 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. NR 53 TC 12 Z9 12 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PD APR PY 2012 VL 7 IS 4 BP 686 EP 702 DI 10.1038/nprot.2012.007 PG 17 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 917AU UT WOS:000302145100006 PM 22422315 ER PT J AU Joffe, S Miller, FG AF Joffe, Steven Miller, Franklin G. TI Equipoise: asking the right questions for clinical trial design SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Article ID BREAST-CANCER; THERAPY; ETHICS; TAMOXIFEN; CHEMOTHERAPY; ONDANSETRON; LETROZOLE; WOMEN; RISK AB Randomized controlled trials (RCTs) are central to evidence-based clinical and health-policy decisions. However, RCTs highlight the tension between the therapeutic obligations of the physician and the scientific obligations of the investigator. Clinical equipoise, defined as honest professional disagreement among expert clinicians about the preferred treatment, is often cited as the solution to this RCT dilemma. Nevertheless, there are numerous practical and conceptual problems with the notion of equipoise. These problems include its mistaken imposition of therapeutic norms on the scientific enterprise of research, the difficulty of knowing when a state of equipoise exists, the susceptibility of expert judgment to bias and weak evidence, and its inability to support evidence necessary for health-policy decisions. An alternate approach to risk-benefit assessment that is congruent with the scientific purpose of RCTs can better guide ethical evaluation of these trials, as discussed in this Perspective. C1 [Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Miller, Franklin G.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Joffe, S (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM steven_joffe@dfci.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 NR 36 TC 8 Z9 8 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD APR PY 2012 VL 9 IS 4 BP 230 EP 235 DI 10.1038/nrclinonc.2011.211 PG 6 WC Oncology SC Oncology GA 916VD UT WOS:000302130400010 PM 22231753 ER PT J AU Bromberg, JE Augustson, EM Backinger, CL AF Bromberg, Julie E. Augustson, Erik M. Backinger, Cathy L. TI Portrayal of Smokeless Tobacco in YouTube Videos SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SMOKING INITIATION; MOVIE SMOKING; YOUNG-ADULTS; INFORMATION; WEB; EXPOSURE; INTERNET AB Videos of smokeless tobacco (ST) on YouTube are abundant and easily accessible, yet no studies have examined the content of ST videos. This study assesses the overall portrayal, genre, and messages of ST YouTube videos. In August 2010, researchers identified the top 20 search results on YouTube by "relevance" and "view count" for the following search terms: "ST," "chewing tobacco," "snus," and "Skoal." After eliminating videos that were not about ST (n = 26), non-English (n = 14), or duplicate (n = 42), a final sample of 78 unique videos was coded for overall portrayal, genre, and various content measures. Among the 78 unique videos, 15.4% were anti-ST, while 74.4% were pro-ST. Researchers were unable to determine the portrayal of ST in the remaining 10.3% of videos because they involved excessive or "sensationalized" use of the ST, which could be interpreted either positively or negatively, depending on the viewer. The most common ST genre was positive video diaries (or "vlogs"), which made up almost one third of the videos (29.5%), followed by promotional advertisements (20.5%) and anti-ST public service announcements (12.8%). While YouTube is intended for user-generated content, 23.1% of the videos were created by professional organizations. These results demonstrate that ST videos on YouTube are overwhelmingly pro-ST. More research is needed to determine who is viewing these ST YouTube videos and how they may affect people's knowledge, attitudes, and behaviors regarding ST use. C1 [Bromberg, Julie E.] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Backinger, Cathy L.] US FDA, Ctr Tobacco Prod, Rockville, MD 20857 USA. RP Bromberg, JE (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4047, Bethesda, MD 20892 USA. EM brombergje@mail.nih.gov FU National Cancer Institute FX This research was funded by the National Cancer Institute [Cancer Research Training Award (CRTA) Program]. NR 35 TC 21 Z9 21 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD APR PY 2012 VL 14 IS 4 BP 455 EP 462 DI 10.1093/ntr/ntr235 PG 8 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 919CM UT WOS:000302298400010 PM 22080585 ER PT J AU Michos, ED Reis, JP Post, WS Lutsey, PL Gottesman, RF Mosley, TH Sharrett, AR Melamed, ML AF Michos, Erin D. Reis, Jared P. Post, Wendy S. Lutsey, Pamela L. Gottesman, Rebecca F. Mosley, Thomas H. Sharrett, A. Richey Melamed, Michal L. TI 2.5-Hydroxyvitamin D deficiency is associated with fatal stroke among whites but not blacks: The NHANES-III linked mortality files SO NUTRITION LA English DT Article DE Vitamin D; Stroke; Racial differences ID NUTRITION EXAMINATION SURVEY; VITAMIN-D DEFICIENCY; 3RD NATIONAL-HEALTH; UNITED-STATES; 25-HYDROXYVITAMIN-D LEVELS; CARDIOVASCULAR-DISEASE; RISK; POPULATION; ADULTS AB Objective: Deficient 25-hydroxyvitamin D (25[OH ID) levels are associated with cardiovascular disease (CVD) events and mortality. 25(OH)D deficiency and stroke are more prevalent in blacks. We examined whether low 25(OH)D contributes to the excess risk of fatal stroke in blacks compared with whites. Methods: The Third National Health and Nutrition Examination Survey, a probability sample of U.S. civilians, measured 25(OH)D levels and CVD risk factors from 1988 through 1994. Vital status through December 2006 was obtained by a linkage with the National Death Index. In white and black adults without CVD reported at baseline (n = 7981), Cox regression models were fit to estimate hazard ratios (HR) for fatal stroke by 25(OH)D status and race. Results: During a median of 14.1 y, there were 116 and 60 fatal strokes in whites and blacks, respectively. The risk of fatal stroke was greater in blacks compared with whites in models adjusted for socioeconomic status and CVD risk factors (HR 1.60, 95% confidence interval 1.01-2.53). Mean baseline 25(OH)D levels were significantly lower in blacks compared with whites (19.4 versus 30.8 ng/mL, respectively). In multivariable-adjusted models, deficient 25(OH)D levels lower than 15 ng/mL were associated with fatal stroke in whites (HR 2.13.1.01-4.50) but not blacks (HR 0.93, 0.49-1.80). Conclusions: Vitamin D deficiency was associated with an increased risk of stroke death in whites but not in blacks. Although blacks had a higher rate of fatal stroke compared with whites, the low 25(OH)D levels in blacks were unrelated to stroke incidence. Therefore 25(OH)D levels did not explain this excess risk. (C) 2012 Elsevier Inc. All rights reserved. C1 [Michos, Erin D.; Post, Wendy S.] Johns Hopkins Sch Med, Div Cardiol, Baltimore, MD 21205 USA. [Reis, Jared P.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Lutsey, Pamela L.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Gottesman, Rebecca F.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA. [Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Geriatr Med, Jackson, MS 39216 USA. [Michos, Erin D.; Post, Wendy S.; Sharrett, A. Richey] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Melamed, Michal L.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Melamed, Michal L.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Michos, ED (reprint author), Johns Hopkins Sch Med, Div Cardiol, Baltimore, MD 21205 USA. EM edonnell@jhmi.edu FU NIH/NINDS [R01N5072243-01]; NIH/NIDDK [K23-078774] FX Dr. Michos is supported by grant R01N5072243-01 from the NIH/NINDS and the P. J. Schafer Cardiovascular Research Fund. Dr. Melamed is supported by grant K23-078774 from the NIH/NIDDK. NR 31 TC 46 Z9 46 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD APR PY 2012 VL 28 IS 4 BP 367 EP 371 DI 10.1016/j.nut.2011.10.015 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 920HV UT WOS:000302395800005 PM 22261577 ER PT J AU Reddy, UM Page, GP Saade, GR AF Reddy, Uma M. Page, Grier P. Saade, George R. TI The role of DNA microarrays in the evaluation of fetal death SO PRENATAL DIAGNOSIS LA English DT Article DE Array CGH; General cytogenetics; Spontaneous abortion; Stillbirth; Fetal death; Fetal demise ID COMPARATIVE GENOMIC HYBRIDIZATION; SPONTANEOUS-ABORTIONS; PRENATAL-DIAGNOSIS; GENETIC EVALUATION; STILLBIRTH; PREGNANCY AB Fetal death occurs in 15% of clinically recognized pregnancies. Cytogenetic abnormalities are present in 50% of spontaneous abortions (fetal deaths?1,500/mL to aggressive disease complicated by life-threatening end organ involvement, including endomyocardial fibrosis and thromboembolism. To complicate matters further, similar clinical manifestations can occur in the setting of marked eosinophilia due to helminth infection, drug hypersensitivity, and other causes. In the past, therapy was guided only by the exclusion of these secondary causes of eosinophilia and the severity of the clinical manifestations. More recently, the availability of novel targeted therapies and a better understanding of the etiologies of some subtypes of HES have necessitated a more structured approach. Semin Hematol 49:160-170. Published by Elsevier Inc. C1 [Simon, Hans-Uwe] Univ Bern, Inst Pharmacol, Bern, Switzerland. [Klion, Amy] NIAID, Eosinophil Pathol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Klion, A (reprint author), Bldg 4,Room B1-28,9000 Rockville Pike, Bethesda, MD 20892 USA. EM AKLION@niaid.nih.gov OI Simon, Hans-Uwe/0000-0002-9404-7736; Klion, Amy/0000-0002-4986-5326 FU NIAID/NIH; Swiss National Science Foundation FX This work was supported by the Intramural Program of the NIAID/NIH (A.K.) and the Swiss National Science Foundation (H-.U.S.). NR 58 TC 12 Z9 12 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 2012 VL 49 IS 2 BP 160 EP 170 DI 10.1053/j.seminhematol.2012.01.002 PG 11 WC Hematology SC Hematology GA 920SI UT WOS:000302427300007 PM 22449626 ER PT J AU Boulanger, CA Bruno, RD Rosu-Myles, M Smith, GH AF Boulanger, Corinne A. Bruno, Robert D. Rosu-Myles, Michael Smith, Gilbert H. TI The Mouse Mammary Microenvironment Redirects Mesoderm-Derived Bone Marrow Cells to a Mammary Epithelial Progenitor Cell Fate SO STEM CELLS AND DEVELOPMENT LA English DT Article ID HEMATOPOIETIC STEM-CELLS; IN-VIVO; GLAND; MORPHOGENESIS; EXPRESSION; MICE; DIFFERENTIATION; PROLIFERATION; MULTIPOTENT; PHENOTYPE AB Mammary stem cells reside in protected tissue locales (niches), where their reproductive potency remains essentially unchanged through life. Disruption of the tissue leads to a reduced capacity of dispersed epithelial cells to recapitulate complete functional mammary structures. Previous studies demonstrate that during the reformation of mammary stem cell niches by dispersed epithelial cells in the mammary stroma, nonmammary cells of ectodermal germ origin may be sequestered and reprogrammed to perform mammary epithelial cell (MEC) functions, including those ascribed to mammary stem/progenitor cells. To test whether tissue cells from organs derived from different germ layers could respond to mammary epithelial-specific signals, we utilized fluorescence-activated cell sorting-purified Lin(-) and Lin(-)/cKit+ adult male bone marrow cells to mix with MECs. Our evidence shows that the signals provided by the mammary microenvironment are capable of redirecting mesoderm-derived adult progenitor cells to produce functional MEC progeny. C1 [Boulanger, Corinne A.; Bruno, Robert D.; Smith, Gilbert H.] NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. [Rosu-Myles, Michael] Biol & Genet Therapies Directorate, Ottawa, ON, Canada. RP Smith, GH (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. EM gs4d@nih.gov OI Bruno, Robert/0000-0003-3329-9478 NR 25 TC 10 Z9 10 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD APR PY 2012 VL 21 IS 6 BP 948 EP 954 DI 10.1089/scd.2011.0148 PG 7 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 918BB UT WOS:000302222700012 PM 21649558 ER PT J AU Korthuis, PT Feaster, DJ Gomez, ZL Das, M Tross, S Wiest, K Douaihy, A Mandler, RN Sorensen, JL Colfax, G McCarty, D Cohen, SE Penn, PE Lape, D Metsch, LR AF Korthuis, P. Todd Feaster, Daniel J. Gomez, Zoilyn L. Das, Moupali Tross, Susan Wiest, Katharina Douaihy, Antoine Mandler, Raul N. Sorensen, James L. Colfax, Grant McCarty, Dennis Cohen, Stephanie E. Penn, Patricia E. Lape, Diane Metsch, Lisa R. TI Injection behaviors among injection drug users in treatment: The role of hepatitis C awareness SO ADDICTIVE BEHAVIORS LA English DT Article DE Injection drug use; Hepatitis C; Syringe/needle sharing; Alcoholism; Opioid-related disorders ID 5 US CITIES; RISK BEHAVIORS; UNITED-STATES; VIRUS-INFECTION; PEER INFLUENCES; HIV RISK; INTERVENTIONS; KNOWLEDGE; BLEACH; LEVEL AB Background: Injection drug use (IDU) is a primary vector for blood-borne infections. Awareness of Hepatitis C virus (HCV) infection status may affect risky injection behaviors. This study determines the prevalence of risky injection practices and examines associations between awareness of positive HCV status and risky injection behaviors. Methods: We surveyed individuals seeking treatment for substance use at 12 community treatment programs as part of a national HIV screening trial conducted within the National Drug Abuse Treatment Clinical Trials Network. Participants reported socio-demographic characteristics, substance use, risk behaviors, and HCV status. We used multivariable logistic regression to test associations between participant characteristics and syringe/needle sharing. Results: The 1281 participants included 244 (19.0%) individuals who reported injecting drugs in the past 6 months and 37.7% of IDUs reported being HCV positive. During the six months preceding baseline assessment, the majority of IDUs reported obtaining sterile syringes from pharmacies (51.6%) or syringe exchange programs (25.0%), but fewer than half of IDUs always used a sterile syringe (46.9%). More than one-third (38.5%) shared syringe/needles with another injector in the past 6 months. Awareness of positive HCV vs. negative/unknown status was associated with increased recent syringe/needle sharing (aOR 2.37, 95% Cl 1.15, 4.88) in multivariable analysis. Conclusions: Risky injection behaviors remain prevalent and awareness of HCV infection was associated with increased risky injection behaviors. New approaches are needed to broadly implement HCV prevention interventions for IDUs seeking addiction treatment. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Korthuis, P. Todd; McCarty, Dennis; Lape, Diane] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Korthuis, P. Todd; McCarty, Dennis; Lape, Diane] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Feaster, Daniel J.; Gomez, Zoilyn L.; Metsch, Lisa R.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Das, Moupali; Sorensen, James L.] Univ Calif San Francisco, San Francisco, CA 94110 USA. [Das, Moupali; Colfax, Grant; Cohen, Stephanie E.] San Francisco Dept Publ Hlth, San Francisco, CA 94103 USA. [Tross, Susan] NYS Psychiat Inst, HIV Ctr Clin & Behav Studies, New York, NY 10032 USA. [Wiest, Katharina] CODA, Portland, OR 97214 USA. [Douaihy, Antoine] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Mandler, Raul N.] NIDA, NIH, Bethesda, MD 20892 USA. [Penn, Patricia E.] La Frontera Arizona, Tucson, AZ 85713 USA. RP Korthuis, PT (reprint author), Oregon Hlth & Sci Univ, Dept Med, 3181 SW Sam Jackson Pk Rd,Mail Code L-475, Portland, OR 97239 USA. EM korthuis@ohsu.edu RI Ghartouchent, malek/B-9088-2012; Feaster, Daniel/I-6079-2013; OI Feaster, Daniel/0000-0002-6172-7460 FU National Institute on Drug Abuse : California-Arizona Node [U10 DA15815]; National Institute on Drug Abuse : Florida Node Alliance [U10 DA13720]; National Institute on Drug Abuse : Mid-Atlantic Node [U10 DA13034]; National Institute on Drug Abuse : New England Node [U10 DA13038]; National Institute on Drug Abuse : New York Node [U10 DA13046]; National Institute on Drug Abuse : Ohio Valley Node [U10 DA13732]; National Institute on Drug Abuse : Oregon/Hawaii Node [U10 DA13036]; National Institute on Drug Abuse : Appalachian Tri-State Node [U10 DA020036]; National Institute on Drug Abuse : Southern Consortium Node [U10 DA13727]; National Institute on Drug Abuse : Southwest Node [U10 DA15833]; National Institute on Drug Abuse [K23 DA019809] FX Cooperative agreements from the National Institute on Drug Abuse supported the design, distribution, collection and analysis of the clinical trial: California-Arizona Node (U10 DA15815), Florida Node Alliance (U10 DA13720), Mid-Atlantic Node (U10 DA13034), New England Node (U10 DA13038), New York Node (U10 DA13046), Ohio Valley Node (U10 DA13732), Oregon/Hawaii Node (U10 DA13036), Appalachian Tri-State Node (U10 DA020036). Southern Consortium Node (U10 DA13727), and Southwest Node (U10 DA15833). Dr. Korthuis' time was supported through a grant from the National Institute on Drug Abuse (K23 DA019809). The contents of the publication are solely the responsibility of the authors and do not necessarily represent the views of the funding agencies or the U.S. government. NR 25 TC 10 Z9 10 U1 3 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD APR PY 2012 VL 37 IS 4 BP 552 EP 555 DI 10.1016/j.addbeh.2011.12.001 PG 4 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 911BD UT WOS:000301691400033 PM 22209655 ER PT J AU Chen, CH Walker, J Momenan, R Rawlings, R Heilig, M Hommer, DW AF Chen, Chun-Hsin Walker, Jonathan Momenan, Reza Rawlings, Robert Heilig, Markus Hommer, Daniel W. TI Relationship Between Liver Function and Brain Shrinkage in Patients with Alcohol Dependence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Dependence; MRI; Liver Function; Brain Shrinkage ID GAMMA-GLUTAMYL-TRANSPEPTIDASE; OXIDATIVE STRESS STATUS; LIPID-PEROXIDATION; CELL-DEATH; DISEASE; CONSUMPTION; WOMEN; GRAY; VOLUMES; ENZYME AB Background: Oxidative stress has been proposed as one of the mechanisms of alcohol-induced brain shrinkage and alcohol-induced hepatotoxicity. The aim of this study was to assess the correlations between liver function and brain volume (BV) measurements in patients with alcohol dependence. Methods: We recruited 124 patients with alcohol dependence and 111 healthy control subjects from National Institute of Health, National Institute on Alcohol Abuse and Alcoholism inpatient alcohol treatment program. Gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), as well as hematocrit (Hct) and albumin were assayed shortly after admission. Magnetic resonance imaging examination was conducted in both groups (after 3-week abstinence in the patient group). We used stepwise linear regression analyses to determine the variables most strongly correlated with brain shrinkage. Results: Patients with alcohol dependence had lower BV, and greater brain shrinkage as measured by gray matter ratio (GMR), white matter ratio (WMR), brain ratio (BR), and higher cerebrospinal fluid ratio ratio (CSFR) compared with their healthy counterparts. Age and sex were significantly correlated with some BV measurements in both patient and control groups. Body mass index (BMI) was significantly correlated with CSFR, BR, GMR, and WMR; Hct with CSFR and BR; serum GGT level with BV, CSFR, BR, GMR, and WMF in the patient group. No biological variables were correlated with BV indices in the control group. In gender-stratified analysis, age was significantly correlated with brain shrinkage in male patients but not in female patients. Serum GGT level in male and female patients, Hct in male patients, and AST levels in female patients were significantly correlated with brain shrinkage. Conclusions: Our results showed that the higher levels of liver function indices, especially GGT, correlated with BV shrinkage as measured using CSFR, BR, GMR, and WMR in patients with alcohol dependence but not in controls. Serum GGT level outweighed aging effect on brain shrinkage in female patients. C1 [Chen, Chun-Hsin; Walker, Jonathan; Momenan, Reza; Rawlings, Robert; Heilig, Markus; Hommer, Daniel W.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. [Chen, Chun-Hsin] Taipei Med Univ, Wan Fang Hosp, Dept Psychiat, Taipei, Taiwan. [Chen, Chun-Hsin] Taipei Med Univ, Sch Med, Dept Psychiat, Taipei, Taiwan. RP Hommer, DW (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr,Bldg 10 CRC Hatfield Clin Res Ctr,Room, Bethesda, MD 20892 USA. EM danh@mail.nih.gov OI Heilig, Markus/0000-0003-2706-2482 FU Laboratory of Clinical and Translational Studies; National Institute on Alcohol Abuse and Alcoholism FX The study was funded by the Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism. The authors thank Michael Kerich for computer system management and programming, and the nursing and social work staff of the Alcohol Treatment Unit of NIH Clinical Center. Finally, we thank all participants in this study. NR 51 TC 6 Z9 6 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2012 VL 36 IS 4 BP 625 EP 632 DI 10.1111/j.1530-0277.2011.01662.x PG 8 WC Substance Abuse SC Substance Abuse GA 916AN UT WOS:000302068900010 PM 21995416 ER PT J AU Chou, SP Lee, HK Cho, MJ Park, JI Dawson, DA Grant, BF AF Chou, S. Patricia Lee, Hae K. Cho, Maeng J. Park, Jong-Ik Dawson, Deborah A. Grant, Bridget F. TI Alcohol Use Disorders, Nicotine Dependence, and Co-Occurring Mood and Anxiety Disorders in the United States and South KoreauA Cross-National Comparison SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Use Disorders; Nicotine Dependence; Comorbidity; Mood and Anxiety Disorders; Multivariate Logistic Regression ID SUBSTANCE USE DISORDERS; MENTAL-DISORDERS; AUDADIS-ADR; DRUG MODULES; DEPRESSION; COMORBIDITY; RELIABILITY; HEALTH; CONCORDANCE; DIAGNOSES AB Background: The strong comorbidity between substance use disorders (SUDs) and mood and anxiety disorders has been well documented. In view of lack of research findings addressing the co-occurrence of SUDs and mood and anxiety disorders, this study examined the pattern of comorbidity of alcohol use disorders (AUDs) and nicotine dependence (ND) between 2 culturally diverse countries, the United States and South Korea. Methods: Using the nationally representative samples of the U. S. and Korean general populations, we directly compared rates and comorbidity patterns of AUDs, ND, and mood and anxiety disorders between the 2 countries. We further examined the rates and the comorbidity pattern among individuals with AUDs who sought treatment in the last 12 months. Twelve-month prevalence rates were derived to estimate country differentials, and odds ratios (ORs) and 95% confidence intervals were estimated to measure the strength of comorbid associations while adjusting for all sociodemographic characteristics in multivariate logistic models specific to each country. Results: The 12-month prevalence rates of AUDs, ND, and any mood disorder and any anxiety disorder were 9.7, 14.4, 9.5, and 11.9% among Americans, whereas the corresponding rates were 7.1, 6.6, 2.0, and 5.2% among Koreans. These rates were significantly greater (except for any AUD) among Americans than among their Korean counterparts. With respect to comorbidity, both countries showed comparable patterns that the prevalence rates of mood and anxiety disorders were consistently the highest among persons with alcohol dependence (AD). Also, a disparate pattern was observed in Korea that the prevalence rates of mood and anxiety disorders were generally lower among individuals with ND than among those with alcohol abuse and AD. Furthermore, despite significantly greater prevalence of AD in Korea (5.1%) than in the United States (4.4%), alcohol-dependent Americans were 4 times (OR = 3.93) more likely to seek treatment compared to their Korean counterparts. Conclusions: Our results indicated that the prevalence of AD in Korea was substantially greater than that in both Western and other Asian countries, suggesting a maladaptive pattern of alcohol use in Korea, which is different from the general use pattern of other East Asian countries. The low rate of treatment utilization among Koreans might be attributable to perceived social stigma toward SUDs or mental health problems despite the fact that the Korean government offers national health insurance. C1 [Lee, Hae K.] Catholic Univ Korea, Dept Psychiat, Uijongbu St Marys Hosp, Seoul, South Korea. [Chou, S. Patricia; Dawson, Deborah A.; Grant, Bridget F.] NIAAA, US Natl Inst Hlth, Bethesda, MD USA. [Cho, Maeng J.] Seoul Natl Univ, Coll Med, Dept Psychiat & Behav Sci, Inst Behav Med, Seoul, South Korea. [Park, Jong-Ik] Kangwon Natl Univ, Coll Med, Dept Psychiat, Chunchon, South Korea. RP Lee, HK (reprint author), Catholic Univ Korea, Dept Psychiat, Uijongbu St Marys Hosp, Seoul, South Korea. EM nplhk@catholic.ac.kr RI Cho, Maeng Je/F-8837-2012 NR 41 TC 14 Z9 15 U1 3 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2012 VL 36 IS 4 BP 654 EP 662 DI 10.1111/j.1530-0277.2011.01639.x PG 9 WC Substance Abuse SC Substance Abuse GA 916AN UT WOS:000302068900013 PM 21919925 ER PT J AU McKinnon, RA Reedy, J Berrigan, D Krebs-Smith, SM AF McKinnon, Robin A. Reedy, Jill Berrigan, David Krebs-Smith, Susan M. CA NCCOR Catalogue & Registry Working TI The National Collaborative on Childhood Obesity Research Catalogue of Surveillance Systems and Measures Registry New Tools to Spur Innovation and Increase Productivity in Childhood Obesity Research SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material C1 [McKinnon, Robin A.; Reedy, Jill; Berrigan, David; Krebs-Smith, Susan M.; NCCOR Catalogue & Registry Working] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP McKinnon, RA (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4028,MSC 7344, Bethesda, MD 20892 USA. EM mckinnonr@mail.nih.gov NR 0 TC 4 Z9 4 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 APR PY 2012 VL 42 IS 4 BP 433 EP 435 DI 10.1016/j.amepre.2012.01.004 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 912LQ UT WOS:000301799900016 PM 22424259 ER PT J AU Doubeni, CA Schootman, M Major, JM Stone, RAT Laiyemo, AO Park, Y Lian, M Messer, L Graubard, BI Sinha, R Hollenbeck, AR Schatzkin, A AF Doubeni, Chyke A. Schootman, Mario Major, Jacqueline M. Stone, Rosalie A. Torres Laiyemo, Adeyinka O. Park, Yikyung Lian, Min Messer, Lynne Graubard, Barry I. Sinha, Rashmi Hollenbeck, Albert R. Schatzkin, Arthur TI Health Status, Neighborhood Socioeconomic Context, and Premature Mortality in the United States: The National Institutes of Health-AARP Diet and Health Study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SELF-RATED HEALTH; ACUTE MYOCARDIAL-INFARCTION; RETIRED-PERSONS DIET; SOCIAL INEQUALITIES; LIFE EXPECTANCY; AMERICAN-ASSOCIATION; FOLLOW-UP; US; POPULATION; COHORT AB Objectives. We examined whether the risk of premature mortality associated with living in socioeconomically deprived neighborhoods varies according to the health status of individuals. Methods. Community-dwelling adults (n=566402; age=50-71 years) in 6 US states and 2 metropolitan areas participated in the ongoing prospective National Institutes of Health-AARP Diet and Health Study, which began in 1995. We used baseline data for 565679 participants on health behaviors, self-rated health status, and medical history, collected by mailed questionnaires. Participants were linked to 2000 census data for an index of census tract socioeconomic deprivation. The main outcome was all-cause mortality ascertained through 2006. Results. In adjusted survival analyses of persons in good-to-excellent health at baseline, risk of mortality increased with increasing levels of census tract socioeconomic deprivation. Neighborhood socioeconomic mortality disparities among persons in fair-to-poor health were not statistically significant after adjustment for demographic characteristics, educational achievement, lifestyle, and medical conditions. Conclusions. Neighborhood socioeconomic inequalities lead to large disparities in risk of premature mortality among healthy US adults but not among those in poor health. (Am J Public Health. 2012;102:680-688. doi:10.2105/AJPH.2011.300158) C1 [Doubeni, Chyke A.] Univ Massachusetts, Dept Family Med & Community Hlth, Sch Med, Worcester, MA 01655 USA. [Stone, Rosalie A. Torres] Univ Massachusetts, Dept Psychiat, Sch Med, Worcester, MA 01655 USA. [Schootman, Mario; Lian, Min] Washington Univ, Sch Med, Dept Med, Div Hlth Behav Res, St Louis, MO 63110 USA. [Major, Jacqueline M.; Park, Yikyung; Graubard, Barry I.; Sinha, Rashmi; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Laiyemo, Adeyinka O.] Howard Univ, Dept Med, Washington, DC 20059 USA. [Messer, Lynne] Duke Univ, Ctr Hlth Policy, Durham, NC USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. RP Doubeni, CA (reprint author), Univ Massachusetts, Dept Family Med & Community Hlth, Sch Med, 55 Lake Ave N, Worcester, MA 01655 USA. EM chyke.doubeni@umassmed.edu RI Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Schootman, Mario/0000-0003-1162-8824; Doubeni, Chyke/0000-0001-7495-0285; Park, Yikyung/0000-0002-6281-489X FU NIH; National Cancer Institute [5K01CA127118-04, 1R01CA151736-01, 5R01CA137750-02] FX This research was supported in part by the Intramural Research Program of the NIH and the National Cancer Institute. C. A. Doubeni was supported by grants from the National Cancer Institute (5K01CA127118-04 and 1R01CA151736-01). M. Schootman and H. Lian were supported in part by a grant from the National Cancer Institute (5R01CA137750-02). NR 45 TC 23 Z9 23 U1 2 U2 11 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2012 VL 102 IS 4 BP 680 EP 688 DI 10.2105/AJPH.2011.300158 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 913IF UT WOS:000301870000020 PM 21852636 ER PT J AU Zafrani, L Gerotziafas, G Byrnes, C Hu, XZ Perez, J Levi, C Placier, S Letavernier, E Leelahavanichkul, A Haymann, JP Elalamy, I Miller, JL Star, RA Yuen, PST Baud, L AF Zafrani, Lara Gerotziafas, Grigoris Byrnes, Colleen Hu, Xuzhen Perez, Joelle Levi, Charlene Placier, Sandrine Letavernier, Emmanuel Leelahavanichkul, Asada Haymann, Jean-Philippe Elalamy, Ismail Miller, Jeffrey L. Star, Robert A. Yuen, Peter S. T. Baud, Laurent TI Calpastatin Controls Polymicrobial Sepsis by Limiting Procoagulant Microparticle Release SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE sepsis/multiple organ failure; calpain; calpastatin; microparticles; disseminated intravascular coagulation ID ACUTE KIDNEY INJURY; SEPTIC SHOCK; CIRCULATING MICROPARTICLES; KAPPA-B; MYOCARDIAL DYSFUNCTION; CALPAIN ACTIVATION; INFLAMMATION; MICE; INHIBITION; EXPRESSION AB Rationale: Sepsis, a leading cause of death worldwide, involves widespread activation of inflammation, massive activation of coagulation, and lymphocyte apoptosis. Calpains, calcium-activated cysteine proteases, have been shown to increase inflammatory reactions and lymphocyte apoptosis. Moreover, calpain plays an essential role in microparticle release. Objectives: We investigated the contribution of calpain in eliciting tissue damage during sepsis. Methods: To test our hypothesis, we induced polymicrobial sepsis by cecal ligation and puncture in wild-type (WT) mice and transgenic mice expressing high levels of calpastatin, a calpain-specific inhibitor. Measurements and Main Results: In WT mice, calpain activity increased transiently peaking at 6 hours after cecal ligation and puncture surgery. Calpastatin overexpression improved survival, organ dysfunction (including lung, kidney, and liver damage), and lymphocyte apoptosis. It decreased the sepsis-induced systemic proinflammatory response and disseminated intravascular coagulation, by reducing the number of procoagulant circulating microparticles and therefore delaying thrombin generation. The deleterious effect of microparticles in this model was confirmed by transferring microparticles from septic WT to septic transgenic mice, worsening their survival and coagulopathy. Conclusions: These results demonstrate an important role of the calpain/calpastatin system in coagulation/inflammation pathways during sepsis, because calpain inhibition is associated with less severe disseminated intravascular coagulation and better overall outcomes in sepsis. C1 [Zafrani, Lara; Perez, Joelle; Levi, Charlene; Placier, Sandrine; Letavernier, Emmanuel; Haymann, Jean-Philippe; Baud, Laurent] Univ Paris 06, UMR S 702, Paris, France. [Zafrani, Lara; Hu, Xuzhen; Leelahavanichkul, Asada; Star, Robert A.; Yuen, Peter S. T.] NIDDKD, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. [Byrnes, Colleen; Miller, Jeffrey L.] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Gerotziafas, Grigoris; Elalamy, Ismail] Tenon Hosp, AP HP, Serv Hematol Biol, Paris, France. RP Zafrani, L (reprint author), Unite INSERM U702, 4 Rue Chine, F-75020 Paris, France. EM larazafrani@hotmail.com RI Yuen, Peter/B-1954-2008 OI Yuen, Peter/0000-0001-9557-3909 FU Institut National de la Sante et de la Recherche Medicale; National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases FX Supported by the Institut National de la Sante et de la Recherche Medicale and by the Intramural Research Program at National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. NR 48 TC 18 Z9 19 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR 1 PY 2012 VL 185 IS 7 BP 744 EP 755 DI 10.1164/rccm.201109-1686OC PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 915QY UT WOS:000302043700013 PM 22268136 ER PT J AU Liu, J Cai, WD Liu, WS Han, BQ Chang, J Yang, Y AF Liu, Ji Cai, Wendi Liu, Wanshun Han, Baoqin Chang, Jing Yang, Yan TI Modulation of Liver L-gamma-Glutamyl-L-cysteinylglycine Homeostasis By N-Acetyl-Glucosamine-thiazolidine-4(R)-carboxylic Acid in Mice SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE GlcNAcCys; GCLc; GSH; BSO ID OXIDATIVE STRESS; GLUTATHIONE SYNTHESIS; N-ACETYLCYSTEINE; CELL INJURY; L-CYSTEINE; SYNTHETASE; PROTECTION; INDUCTION; PROTEIN; TRANSCRIPTION AB The properties of modulating liver L-gamma-glutamyl-L-cysteinylglycine (GSH) homeostasis by thiazolidine derivative N-acetyl-glucosamine-thiazolidine-4(R)-carboxylic acid (GlcNAcCys) and the underlying mechanisms were investigated in L-buthionine-[S,R]-sulfoximine (BSO)-induced mice liver GSH depletion model. The data show that BSO (6 mmol/kg body weight; intraperitoneally) significantly decreased liver total sulfhydryl and GSH concentrations when compared with control. When mice were treated with different doses of GlcNAcCys (200, 400, 900 mg/kg body weight; intraperitoneally, respectively), total sulfhydryl and GSH concentrations were significantly increased when measured 6 hours after treatment. The activities of GSH-associated enzymes were also measured. Liver glutathione S-transferase (GST) activities were significantly decreased by BSO compared with the control, and GlcNAcCys significantly increased GST activity. Moreover, reverse-transcriptase polymerase chain reaction data indicated that GlcNAcCys could significantly induce glutamylcysteine ligase catalytic subunit c mRNA transcription. The mRNA levels of transcription factors c-jun and c-fos were increased by BSO administration but were decreased back to normal after the administration of GlcNAcCys. In a conclusion, GlcNAcCys can modulate liver GSH homeostasis, which may be related to its ability to induce glutamylcysteine ligase catalytic subunit transcription. GlcNAcCys has potential hepatoprotective properties by increasing GSH content, increasing GST activity. C1 [Liu, Ji; Liu, Wanshun; Han, Baoqin; Chang, Jing; Yang, Yan] Ocean Univ China, Coll Marine Life Sci, Qingdao 266003, Peoples R China. [Yang, Yan] NCI, Lab Mol Inflammat, Ctr Canc Res, Frederick, MD 21701 USA. [Cai, Wendi] Weifang Med Coll, Dept Biochem, Weifang, Peoples R China. RP Yang, Y (reprint author), Ocean Univ China, Coll Marine Life Sci, Yushan Rd 5, Qingdao 266003, Peoples R China. EM yany@ouc.edu.cn FU Natural Science Foundation of Shandong Province [2007BS07001, Y2008D17] FX This study was supported by Natural Science Foundation of Shandong Province graft 2007BS07001 and Y2008D17. NR 34 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD APR PY 2012 VL 343 IS 4 BP 310 EP 315 DI 10.1097/MAJ.0b013e31822b02f4 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 917FR UT WOS:000302158400009 PM 21825963 ER PT J AU Lohse, B Bailey, RL Krall, JS Wall, DE Mitchell, DC AF Lohse, Barbara Bailey, Regan L. Krall, Jodi Stotts Wall, Denise E. Mitchell, Diane C. TI Diet quality is related to eating competence in cross-sectional sample of low-income females surveyed in Pennsylvania SO APPETITE LA English DT Article DE Eating competence; Dietary quality; Low-income; Eating behavior; Dietary guidance ID CARDIOVASCULAR-DISEASE RISK; PATTERNS; CANCER; WOMEN; ASSOCIATION; ADULTS; BIOMARKERS; OBESITY; PROFILE; ENERGY AB Women participants of two federally administered nutrition education programs (n = 149, 56% white, 64% food secure, 86% 18-50 years of age,) completed telephone interviews that included three 24-hour dietary recalls and the Satter Eating Competence Inventory. Eating competence is delineated by an Inventory score >= 32. Competent eaters had significantly greater intakes of fiber, vitamin A, vitamin E, vitamin C, most B-vitamins, magnesium, iron, zinc, potassium and a higher Healthy Eating Index. Two dietary patterns defined as Prudent and Western were observed. The Prudent pattern was correlated with eating competence and characterized by more healthful foods such as fruits, vegetables and low-fat dairy products. The Western pattern, characterized by foods higher in fat, salt, and sugar, was not related to eating competence. Findings suggest that dietary guidance using an eating competence approach for low-income women is compatible with goals to improve dietary quality and eating patterns. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Lohse, Barbara; Mitchell, Diane C.] Penn State Univ, Dept Nutr Sci, Diet Assessment Ctr, University Pk, PA 16802 USA. [Bailey, Regan L.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Krall, Jodi Stotts] Univ Pittsburgh, Med Ctr, Weight Management Div, Pittsburgh, PA 15213 USA. [Wall, Denise E.] Penn State Univ, Penn Nutr Educ TRACKS, State Coll, PA 16801 USA. RP Lohse, B (reprint author), Penn State Univ, Dept Nutr Sci, Diet Assessment Ctr, University Pk, PA 16802 USA. EM lohseb@psu.edu FU Pennsylvania Department of Public Welfare through the Pennsylvania Nutrition Education TRACKS, USDA FX Research was supported by the Pennsylvania Department of Public Welfare through the Pennsylvania Nutrition Education TRACKS as part of USDA's Supplemental Nutrition Assistance Program. We sincerely thank Cooperative Extension Nutrition Links and The Diet Assessment Center, both of The Pennsylvania State University. Competing interest: The authors declare that they have no competing interest. NR 51 TC 17 Z9 17 U1 1 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-6663 J9 APPETITE JI Appetite PD APR PY 2012 VL 58 IS 2 BP 645 EP 650 DI 10.1016/j.appet.2011.11.022 PG 6 WC Behavioral Sciences; Nutrition & Dietetics SC Behavioral Sciences; Nutrition & Dietetics GA 913SX UT WOS:000301898800034 PM 22142509 ER PT J AU Kessler, RC Avenevoli, S Costello, EJ Georgiades, K Green, JG Gruber, MJ He, JP Koretz, D McLaughlin, KA Petukhova, M Sampson, NA Zaslavsky, AM Merikangas, KR AF Kessler, Ronald C. Avenevoli, Shelli Costello, E. Jane Georgiades, Katholiki Green, Jennifer Greif Gruber, Michael J. He, Jian-ping Koretz, Doreen McLaughlin, Katie A. Petukhova, Maria Sampson, Nancy A. Zaslavsky, Alan M. Merikangas, Kathleen Ries TI Prevalence, Persistence, and Sociodemographic Correlates of DSM-IV Disorders in the National Comorbidity Survey Replication Adolescent Supplement SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID GREAT SMOKY MOUNTAINS; NCS-A; LIFETIME PREVALENCE; MENTAL-DISORDERS; PSYCHIATRIC-DISORDERS; DEPRESSION; CHILDREN; PSYCHOPATHOLOGY; EPIDEMIOLOGY; 10-YEAR AB Context: Community epidemiological data on the prevalence and correlates of adolescent mental disorders are needed for policy planning purposes. Only limited data of this sort are available. Objective: To present estimates of 12-month and 30-day prevalence, persistence (12-month prevalence among lifetime cases and 30-day prevalence among 12-month cases), and sociodemographic correlates of commonly occurring DSM-IV disorders among adolescents in the National Comorbidity Survey Replication Adolescent Supplement. Design: The National Comorbidity Survey Replication Adolescent Supplement is a US national survey of DSM-IV anxiety, mood, behavior, and substance disorders among US adolescents based on face-to-face interviews in the homes of respondents with supplemental parent questionnaires. Setting: Dual-frame household and school samples of US adolescents. Participants: A total of 10 148 adolescents aged 13 to 17 years (interviews) and 1 parent of each adolescent (questionnaires). Main Outcome Measures: The DSM-IV disorders assessed with the World Health Organization Composite International Diagnostic Interview and validated with blinded clinical interviews based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Good concordance (area under the receiver operating characteristic curve >= 0.80) was found between Composite International Diagnostic Interview and Schedule for Affective Disorders and Schizophrenia for School-Age Children diagnoses. Results: The prevalence estimates of any DSM-IV disorder are 40.3% at 12 months (79.5% of lifetime cases) and 23.4% at 30 days (57.9% of 12-month cases). Anxiety disorders are the most common class of disorders, followed by behavior, mood, and substance disorders. Although relative disorder prevalence is quite stable over time, 30-day to 12-month prevalence ratios are higher for anxiety and behavior disorders than mood or substance disorders, suggesting that the former are more chronic than the latter. The 30-day to 12-month prevalence ratios are generally lower than the 12-month to lifetime ratios, suggesting that disorder persistence is due more to episode recurrence than to chronicity. Sociodemographic correlates are largely consistent with previous studies. Conclusions: Among US adolescents, DSM-IV disorders are highly prevalent and persistent. Persistence is higher for adolescents than among adults and appears to be due more to recurrence than chronicity of child-adolescent onset disorders. C1 [Kessler, Ronald C.; Gruber, Michael J.; Petukhova, Maria; Sampson, Nancy A.; Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [McLaughlin, Katie A.] Harvard Univ, Sch Med, Div Gen Pediat, Childrens Hosp Boston, Boston, MA 02115 USA. [Green, Jennifer Greif] Boston Univ, Sch Med, Boston, MA 02118 USA. [Koretz, Doreen] Harvard Univ, Off Provost, Boston, MA 02115 USA. [Avenevoli, Shelli] NIMH, Div Dev Translat Res, Bethesda, MD 20892 USA. [He, Jian-ping; Merikangas, Kathleen Ries] NIMH, Div Intramural Res Programs, Bethesda, MD 20892 USA. [Costello, E. Jane] Duke Univ, Sch Med, Ctr Dev Epidemiol, Dept Psychiat & Behav Sci, Durham, NC USA. [Georgiades, Katholiki] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM ncs@hcp.med.harvard.edu OI McLaughlin, Katie/0000-0002-1362-2410 FU Analysis Group; Bristol-Myers Squibb; Eli Lilly and Co; EPI-Q; GlaxoSmithKline; Johnson & Johnson Pharmaceuticals; Ortho-McNeil Janssen Scientific Affairs; Pfizer Inc; sanofi-aventis; Shire US Inc.; National Institute of Mental Health [U01-MH60220, R01-MH66627, U01MH060220-09S1, R01-MH070884, R13-MH066849, R01-MH069864, R01-MH077883]; Robert Wood Johnson Foundation [044780]; John W. Alden Trust; National Institute on Drug Abuse; Fogarty International Center of the National Institutes of Health [FIRCA R03-TW006481]; John D. and Catherine T. MacArthur Foundation; Pfizer Foundation; Pan American Health Organization; AstraZeneca; Ortho-McNeil; Pfizer; Wyeth FX Financial Disclosure: Dr Kessler has been a consultant for AstraZeneca, Analysis Group, Bristol-Myers Squibb, Cerner-Galt Associates, Eli Lilly and Co, GlaxoSmithKline, HealthCore Inc, Health Dialog, Integrated Benefits Institute, John Snow Inc, Kaiser Permanente, Matria Inc, Mensante, Merck and Co Inc, Ortho-McNeil Janssen Scientific Affairs, Pfizer Inc, Primary Care Network, Research Triangle Institute, sanofi-aventis, Shire US Inc, SRA International Inc, Takeda Global Research and Development, Transcept Pharmaceuticals Inc, and Wyeth-Ayerst; has served on advisory boards for Appliance Computing II, Eli Lilly and Co, Mindsite, Ortho-McNeil Janssen Scientific Affairs, and Wyeth-Ayerst; and has had research support for his epidemiological studies from Analysis Group, Bristol-Myers Squibb, Eli Lilly and Co, EPI-Q, GlaxoSmithKline, Johnson & Johnson Pharmaceuticals, Ortho-McNeil Janssen Scientific Affairs, Pfizer Inc, sanofi-aventis, and Shire US Inc.; The NCS-A is supported by grants U01-MH60220, R01-MH66627, and U01MH060220-09S1 from the National Institute of Mental Health, with supplemental support from the National Institute on Drug Abuse, the Substance Abuse and Mental Health Services Administration, grant 044780 from the Robert Wood Johnson Foundation, and the John W. Alden Trust. The work of Ms He and Dr Merikangas is supported by the Intramural Research Program of the National Institute of Mental Health. The World Mental Health Data Coordination Centres have been supported by grants R01-MH070884, R13-MH066849, R01-MH069864, and R01-MH077883 from the National Institute of Mental Health, grant R01-DA016558 from the National Institute on Drug Abuse, grant FIRCA R03-TW006481 from the Fogarty International Center of the National Institutes of Health, the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the Pan American Health Organization, and unrestricted educational grants from AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Co, GlaxoSmithKline, Ortho-McNeil, Pfizer, sanofi-aventis, and Wyeth. NR 37 TC 210 Z9 214 U1 5 U2 72 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 2012 VL 69 IS 4 BP 372 EP 380 DI 10.1001/archgenpsychiatry.2011.160 PG 9 WC Psychiatry SC Psychiatry GA 919JL UT WOS:000302320600005 PM 22147808 ER PT J AU Kessler, RC Avenevoli, S Costello, J Green, JG Gruber, MJ McLaughlin, KA Petukhova, M Sampson, NA Zaslavsky, AM Merikangas, KR AF Kessler, Ronald C. Avenevoli, Shelli Costello, Jane Green, Jennifer Greif Gruber, Michael J. McLaughlin, Katie A. Petukhova, Maria Sampson, Nancy A. Zaslavsky, Alan M. Merikangas, Kathleen Ries TI Severity of 12-Month DSM-IV Disorders in the National Comorbidity Survey Replication Adolescent Supplement SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SERIOUS EMOTIONAL DISTURBANCE; NCS-A; PSYCHIATRIC-DISORDERS; MENTAL-DISORDERS; BIRTH COHORT; PREVALENCE; DEPRESSION; YOUTH; CONSEQUENCES; EPIDEMIOLOGY AB Context: Estimates of DSM-IV disorder prevalence are high; stringent criteria to define need for services are desired. Objective: To present US national data on the prevalence and sociodemographic correlates of 12-month serious emotional disturbance (SED), defined by the US Substance Abuse and Mental Health Services Administration, from the National Comorbidity Survey Replication Adolescent Supplement. Design: The National Comorbidity Survey Replication Adolescent Supplement is a national survey of DSM-IV anxiety, mood, behavior, and substance disorders among US adolescents. Setting: Dual-frame household and school samples of US adolescents. Participants: Total of 6483 pairs of adolescents aged 13 to 17 (interviews) and parents (questionnaires). Main Outcome Measures: The DSM-IV disorders were assessed with the World Health Organization Composite International Diagnostic Interview and validated with blinded clinical interviews based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Serious emotional disturbance was operationalized as a DSM-IV/Composite International Diagnostic Interview disorder with a score of 50 or less on the Children's Global Assessment Scale (ie, moderate impairment in most areas of functioning or severe impairment in at least 1 area). Concordance of Composite International Diagnostic Interview SED diagnoses with blinded Schedule for Affective Disorders and Schizophrenia for School-Age Children diagnoses was good. Results: The estimated prevalence of SED was 8.0%. Most SEDs were due to behavior (54.5%) or mood (31.4%) disorders. Although respondents with 3 or more disorders made up only 29.0% of those with 12-month DSM-IV/Composite International Diagnostic Interview disorders, they constituted 63.5% of SEDs. Predictive effects of high comorbidity were significantly greater than the product of their disorder-specific odds ratios and consistent across disorder types. Associations of sociodemographic variables with SED were generally nonsignificant after controlling for disorder type and number. Conclusions: The high estimated 12-month prevalence of DSM-IV disorders among US adolescents is largely due to mild cases. The significant between-disorder differences in risk of SED and the significant effect of high comorbidity have important public health implications for targeting interventions. C1 [Kessler, Ronald C.; Gruber, Michael J.; Petukhova, Maria; Sampson, Nancy A.; Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [McLaughlin, Katie A.] Harvard Univ, Sch Med, Div Gen Pediat, Childrens Hosp Boston, Boston, MA 02115 USA. [Green, Jennifer Greif] Boston Univ, Sch Educ, Boston, MA 02215 USA. [Avenevoli, Shelli] NIMH, Div Dev Translat Res, Bethesda, MD 20892 USA. [Merikangas, Kathleen Ries] NIMH, Div Intramural Res Programs, Bethesda, MD 20892 USA. [Costello, Jane] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Ctr Dev Epidemiol, Durham, NC USA. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM ncs@hcp.med.harvard.edu OI McLaughlin, Katie/0000-0002-1362-2410 FU Analysis Group, Inc; Bristol-Myers Squibb; Eli Lilly and Company; EPI-Q; GlaxoSmithKline, Inc; Johnson & Johnson Pharmaceuticals; Ortho-McNeil Janssen Scientific Affairs; Pfizer, Inc; sanofi-aventis; Shire US, Inc.; National Institute of Mental Health [U01-MH60220, R01-MH66627, U01MH060220-09S1, R01-MH070884, R13-MH066849, R01-MH069864, R01-MH077883, R01-DA016558]; Substance Abuse and Mental Health Services Administration; Robert Wood Johnson Foundation [044780]; John W. Alden Trust; National Institute on Drug Abuse; Fogarty International Center of the National Institutes of Health [FIRCA R03-TW006481]; John D. and Catherine T. MacArthur Foundation; Pfizer Foundation; Pan American Health Organization; AstraZeneca; BristolMyers Squibb; Ortho-McNeil; Wyeth FX Dr Kessler has been a consultant for AstraZeneca; Analysis Group; Bristol-Myers Squibb; Cerner-Galt Associates; Eli Lilly and Company; GlaxoSmithKline, Inc; HealthCore, Inc; Health Dialog; Integrated Benefits Institute; John Snow, Inc; Kaiser Permanente; Matria, Inc; Mensante; Merck & Co, Inc; Ortho-McNeil Janssen Scientific Affairs; Pfizer, Inc; Primary Care Network; Research Triangle Institute; sanofi-aventis; Shire US, Inc; SRA International, Inc; Takeda Global Research & Development; Transcept Pharmaceuticals, Inc; and Wyeth-Ayerst; has served on advisory boards for Appliance Computing II; Eli Lilly & Company; Mindsite; Ortho-McNeil Janssen Scientific Affairs; and Wyeth-Ayerst; and has had research support for his epidemiologic studies from Analysis Group, Inc; Bristol-Myers Squibb; Eli Lilly and Company; EPI-Q; GlaxoSmithKline, Inc; Johnson & Johnson Pharmaceuticals; Ortho-McNeil Janssen Scientific Affairs; Pfizer, Inc; sanofi-aventis; and Shire US, Inc.; The NCS-A is supported by grants U01-MH60220, R01-MH66627, and U01MH060220-09S1 from the National Institute of Mental Health with supplemental support from the National Institute on Drug Abuse, the Substance Abuse and Mental Health Services Administration, the Robert Wood Johnson Foundation (grant 044780), and the John W. Alden Trust. The work of Dr Merikangas is supported by the National Institute of Mental Health Intramural Research Program. The work of Dr Zaslavsky is supported by grant R01-MH66627 from the National Institute of Mental Health. The World Mental Health Data Coordination Centers have received grants R01-MH070884, R13-MH066849, R01-MH069864, and R01-MH077883 from the National Institute of Mental Health; R01-DA016558 from the National Institute on Drug Abuse; and FIRCA R03-TW006481 from the Fogarty International Center of the National Institutes of Health; and support from the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, and the Pan American Health Organization. The World Mental Health Data Coordination Centers have also received unrestricted educational grants from AstraZeneca; BristolMyers Squibb; Eli Lilly and Company; GlaxoSmithKline, Inc; Ortho-McNeil; Pfizer, Inc; sanofi-aventis; and Wyeth. NR 40 TC 54 Z9 54 U1 5 U2 29 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X EI 1538-3636 J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 2012 VL 69 IS 4 BP 381 EP 389 PG 9 WC Psychiatry SC Psychiatry GA 919JL UT WOS:000302320600006 PM 22474106 ER PT J AU Swendsen, J Burstein, M Case, B Conway, KP Dierker, L He, JP Merikangas, KR AF Swendsen, Joel Burstein, Marcy Case, Brady Conway, Kevin P. Dierker, Lisa He, Jianping Merikangas, Kathleen R. TI Use and Abuse of Alcohol and Illicit Drugs in US Adolescents Results of the National Comorbidity Survey-Adolescent Supplement SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SUBSTANCE USE DISORDERS; 10-YEAR FOLLOW-UP; SURVEY REPLICATION; UNITED-STATES; EPIDEMIOLOGIC SURVEY; NCS-A; MENTAL-DISORDERS; LIFETIME PREVALENCE; EARLY ADULTHOOD; RISK-FACTORS AB Context: Comprehensive descriptions of substance use and abuse trajectories have been lacking in nationally representative samples of adolescents. Objective: To examine the prevalence, age at onset, and sociodemographic correlates of alcohol and illicit drug use and abuse among US adolescents. Design: Cross-sectional survey of adolescents using a modified version of the Composite International Diagnostic Interview. Setting: Combined household and school adolescent samples. Participants: Nationally representative sample of 10 123 adolescents aged 13 to 18 years. Main Outcome Measures: Lifetime estimates of alcohol and illicit substance use and DSM-IV diagnoses of abuse, with or without dependence. Results: By late adolescence, 78.2% of US adolescents had consumed alcohol, 47.1% had reached regular drinking levels defined by at least 12 drinks within a given year, and 15.1% met criteria for lifetime abuse. The opportunity to use illicit drugs was reported by 81.4% of the oldest adolescents, drug use by 42.5%, and drug abuse by 16.4%. The median age at onset was 14 years for alcohol abuse with or without dependence, 14 years for drug abuse with dependence, and 15 years for drug abuse without dependence. The associations observed by age, sex, and race/ethnicity often varied significantly by previous stage of use. Conclusions: Alcohol and drug use is common in US adolescents, and the findings of this study indicate that most cases of abuse have their initial onset in this important period of development. Prevention and treatment efforts would benefit from careful attention to the correlates and risk factors that are specific to the stage of substance use in adolescents. C1 [Burstein, Marcy; He, Jianping; Merikangas, Kathleen R.] NIMH, Intramural Res Program, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA. [Case, Brady] Emma Pendleton Bradley Hosp, Hlth Serv Res Program, E Providence, RI USA. [Conway, Kevin P.] Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, NIH, Rockville, MD USA. [Dierker, Lisa] Wesleyan Univ, Dept Psychol, Middletown, CT USA. [Swendsen, Joel] Univ Bordeaux, Natl Ctr Sci Res, CNRS 5287, Bordeaux, France. RP Merikangas, KR (reprint author), NIMH, Intramural Res Program, Genet Epidemiol Res Branch, 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA. EM merikank@mail.nih.gov RI Case, Brady/M-1879-2015; OI Case, Brady/0000-0001-9512-0416; Conway, Kevin/0000-0002-7638-339X FU National Institute of Mental Health [Z01 MH002808-08, U01-MH60220] FX This work was supported by grant Z01 MH002808-08 from the Intramural Research Program of the National Institute of Mental Health. The NCS-A and the larger program of related National Comorbidity Surveys are supported by grant U01-MH60220 from the National Institute of Mental Health. NR 44 TC 97 Z9 99 U1 8 U2 42 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 2012 VL 69 IS 4 BP 390 EP 398 PG 9 WC Psychiatry SC Psychiatry GA 919JL UT WOS:000302320600007 PM 22474107 ER PT J AU Tektonidou, MG Ward, MM AF Tektonidou, Maria G. Ward, Michael M. TI Screening for depression and risk of suicide in patients with arthritis: Comment on the article by Tektonidou et al Reply SO ARTHRITIS CARE & RESEARCH LA English DT Letter C1 [Tektonidou, Maria G.] Natl Tech Univ Athens, Athens, Greece. [Ward, Michael M.] NIAMSD, Bethesda, MD 20892 USA. RP Tektonidou, MG (reprint author), Natl Tech Univ Athens, Athens, Greece. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD APR PY 2012 VL 64 IS 4 BP 623 EP 624 DI 10.1002/acr.21561 PG 2 WC Rheumatology SC Rheumatology GA 915YR UT WOS:000302064000022 ER PT J AU Haring, R Volzke, H Vasan, RS Felix, SB Nauck, M Dorr, M Wallaschofski, H AF Haring, Robin Voelzke, Henry Vasan, Ramachandran S. Felix, Stephan B. Nauck, Matthias Doerr, Marcus Wallaschofski, Henri TI Sex-specific associations of serum prolactin concentrations with cardiac remodeling: Longitudinal results from the Study of Health Pomerania (SHIP) SO ATHEROSCLEROSIS LA English DT Article DE Prolactin; Cardiac remodeling; Left ventricular mass; Hypertrophy; Population-based cohort ID LEFT-VENTRICULAR MASS; CONGESTIVE-HEART-FAILURE; CARDIOVASCULAR HEALTH; CHAMBER QUANTIFICATION; POSTMENOPAUSAL WOMEN; EJECTION FRACTION; RISK; HYPERPROLACTINEMIA; MORTALITY; DISEASE AB Background: Previous experimental and patient-based studies suggest that prolactin (PRL) and its 16 kDa fragment influence cardiovascular phenotypes by modulating angiogenesis. The association between serum PRL and cardiac remodeling in the general population is unknown. Methods: We evaluated 804 individuals (441 women) from the population-based Study of Health in Pomerania, aged >= 45 years, with available baseline serum PRL who underwent serial echocardiography at baseline and five-year follow-up. Left ventricular mass (LVM) was calculated and left ventricular hypertrophy (LVH) defined by sex-specific distributions of LVM. LV geometry was defined on the basis of relative wall thickness (RWT) and LVH. Sex-specific multivariable regression analyses were performed relating PRL (independent variable modelled as a continuous variable and as sex-specific quartiles) to change in LVM, RWT, and to incident LVH and abnormal geometry. Results: Baseline PRL concentrations were inversely associated with LVM change in men, but not in women (beta per 10% decrease in PRL: 0.37; 95% CI, 0.13-0.60 in men and -0.02; 95% CI, -0.21 to 0.17 in women, respectively). In men, baseline PRL concentrations were also inversely associated with incident LVH [first vs. fourth PRL quartile: relative risk (RR) 2.26 (95% CI, 1.20-4.24)] and altered LV geometry on follow-up [RR for incident concentric hypertrophy per 10% decrease in PRL: 1.20 (95% CI, 1.06-1.37)]. None of the longitudinal associations were observed in women. Conclusion: We observed inverse associations of PRL with LVM change, incident LVH, and altered LV geometry in men, but not in women. Additional studies are warranted to confirm our findings and to elucidate the mechanisms underlying these sex-specific associations. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Haring, Robin; Nauck, Matthias; Wallaschofski, Henri] Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17475 Greifswald, Germany. [Voelzke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Vasan, Ramachandran S.] Boston Univ, Prevent Med & Epidemiol Sect, Sch Med, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Felix, Stephan B.; Doerr, Marcus] Univ Med Greifswald, Dept Cardiol, D-17475 Greifswald, Germany. RP Haring, R (reprint author), Univ Med Greifswald, Inst Clin Chem & Lab Med, Ferdinand Sauerbruch Str, D-17475 Greifswald, Germany. EM robin.haring@uni-greifswald.de OI Ramachandran, Vasan/0000-0001-7357-5970 FU Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403]; Ministry of Cultural Affairs; Social Ministry of the Federal State of Mecklenburg-West Pomerania; Federal Ministry of Education and Research; Ministry of Cultural Affairs of the Federal State of Mecklenburg, West Pomerania, Germany; Pfizer; DPC Biermann GmbH, Bad Nauheim, Germany FX SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants nos. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania. This study was carried out in collaboration with the German Centre for Cardiovascular Research (GCCR), which is funded by the Federal Ministry of Education and Research and the Ministry of Cultural Affairs of the Federal State of Mecklenburg, West Pomerania, Germany. Robin Haring 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. Pfizer provided partial grant support for the determination of plasma samples and data analysis. The PRL reagent used was sponsored DPC Biermann GmbH, Bad Nauheim, Germany. NR 46 TC 7 Z9 7 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD APR PY 2012 VL 221 IS 2 BP 570 EP 576 DI 10.1016/j.atherosclerosis.2012.01.017 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 914TI UT WOS:000301974900043 PM 22293228 ER PT J AU Gao, S Liu, ZP Li, H Little, PJ Liu, PQ Xu, SW AF Gao, Si Liu, Zhiping Li, Hong Little, Peter J. Liu, Peiqing Xu, Suowen TI Cardiovascular actions and therapeutic potential of tanshinone IIA (vol 220, pg 3, 2012) SO ATHEROSCLEROSIS LA English DT Correction C1 [Gao, Si; Liu, Zhiping; Li, Hong; Liu, Peiqing; Xu, Suowen] Sun Yat Sen Univ, Dept Pharmacol & Toxicol, Sch Pharmaceut Sci, Higher Educ Mega Ctr, Guangzhou 510006, Guangdong, Peoples R China. [Little, Peter J.] RMIT Univ, Discipline Pharm, Sch Med Sci, Melbourne, Vic 3086, Australia. [Little, Peter J.] RMIT Univ, Diabet Complicat Grp, Hlth Innovat Res Inst, Melbourne, Vic 3086, Australia. [Xu, Suowen] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. RP Liu, PQ (reprint author), Sun Yat Sen Univ, Dept Pharmacol & Toxicol, Sch Pharmaceut Sci, Higher Educ Mega Ctr, 132 E Wai Huan Rd, Guangzhou 510006, Guangdong, Peoples R China. EM liupq@mail.sysu.edu.cn; suo-wen.xu@nih.gov NR 1 TC 0 Z9 0 U1 4 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD APR PY 2012 VL 221 IS 2 BP 604 EP 604 DI 10.1016/j.atherosclerosis.2012.01.014 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 914TI UT WOS:000301974900049 ER PT J AU Rhodes, SEV Charles, DP Howland, EJ Murray, EA AF Rhodes, Sarah E. V. Charles, David P. Howland, Emily J. Murray, Elisabeth A. TI Amygdala Lesions in Rhesus Monkeys Fail to Disrupt Object Choices Based on Internal Context SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE satiety; reward; internal state; motivation; hunger; thirst ID BASOLATERAL AMYGDALA; DEVALUATION; HIPPOCAMPUS; CORTEX; STIMULI AB We assessed the involvement of the amygdala in a task in which object choices were guided by internal context. Rhesus monkeys were trained on a biconditional discrimination whereby objects associated with food (but not water) were baited when the monkey was hungry, and objects associated with water (but not food) were baited when the monkey was thirsty. To solve this task, monkeys were required to choose objects yielding the reward congruent with their internal motivational state. Lesions of the amygdala did not disrupt learning or performance of this task. We conclude that the involvement of the amygdala in selective-satiation tasks, which depends in part on a change in internal context, is not due to the amygdala playing a general role in representing, or using, internal context. C1 [Rhodes, Sarah E. V.; Charles, David P.; Howland, Emily J.; Murray, Elisabeth A.] NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Rhodes, SEV (reprint author), NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bldg 49,Room 1B80,49 Convent Dr, Bethesda, MD 20892 USA. EM sarah.rhodes@mail.nih.gov OI 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 Alicia Izquierdo for assisting with surgical procedures and Luke J. Humphrey for help testing monkeys. NR 19 TC 2 Z9 2 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD APR PY 2012 VL 126 IS 2 BP 270 EP 278 DI 10.1037/a0027229 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 913WY UT WOS:000301909300006 PM 22352788 ER PT J AU Cao, YFA Featherstone, RE Gandal, MJ Liang, YL Jutzeler, C Saunders, J Tatard-Leitman, V Chen, JS Weinberger, DR Lerman, C Siegel, SJ AF Cao, Yufei A. Featherstone, Robert E. Gandal, Michael J. Liang, Yuling Jutzeler, Catherine Saunders, John Tatard-Leitman, Valerie Chen, Jingshan Weinberger, Daniel R. Lerman, Caryn Siegel, Steven J. TI Nicotine Normalizes Event Related Potentials in COMT-Val-tg Mice and Increases Gamma and Theta Spectral Density SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE catechol-O-methyltransferase; COMT; mouse; nicotine; event-related potential; EEG; gamma; theta ID CATECHOL-O-METHYLTRANSFERASE; AUDITORY-EVOKED POTENTIALS; DORSOLATERAL PREFRONTAL CORTEX; PARKINSONS-DISEASE; WORKING-MEMORY; ANTIPSYCHOTIC MEDICATIONS; VAL(158)MET POLYMORPHISM; FREQUENCY OSCILLATIONS; COGNITIVE PERFORMANCE; PREPULSE INHIBITION AB Regulation of dopamine neurotransmission is essential for cognitive processes. In humans and rodents, the relationship between dopamine signaling and cognitive performance is described as a dose-dependent, inverted-U curve whereby excess or insufficiency of dopamine in prefrontal cortex has detrimental effects. Previous studies have indicated that prefrontal dopamine levels are associated with genetic variation in catechol-O-methyltransferase (COMT), a regulatory enzyme that controls dopamine availability. Furthermore, smokers who carry the high-activity COMT-Val allele are more prone to cognitive deficits and have an increased risk of smoking relapse. The present study employed transgenic mice expressing the human COMT-Val variant to determine the effects of the high-activity COMT allele on electrophysiological markers, including the P20, N40, and P80 components of the auditory event-related potential, as well as baseline and auditory event-related power and phase-synchrony in theta and gamma ranges. We also examined the effects of nicotine on these measures to investigate the potential effects of smoking on COMT-mediated electrophysiological activity. COMT-Val-tg mice displayed increased N40 latency and decreased P80 amplitude as well as reduced baseline theta and gamma power. Nicotine increased P20 and P80 amplitudes, decreased N40 amplitude, increased P20 and N40 latencies, and reduced P80 latency. Nicotine also increased the event-related power and phase synchrony, yielding an increase in signal-to-noise ratio across theta and gamma ranges. COMT activity specifically alters long-latency components of the event-related response. Nicotine restored normal event-related activity among COMT-Val-tg mice, suggesting one mechanism through which nicotine may normalize cognitive function among people with the high-activity allele. C1 [Siegel, Steven J.] Univ Penn, Dept Psychiat, Translat Res Labs, Translat Neurosci Program, Philadelphia, PA 19104 USA. [Chen, Jingshan; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. [Lerman, Caryn] Univ Penn, Dept Psychiat, Ctr Res Nicotine Addict, Philadelphia, PA 19104 USA. RP Siegel, SJ (reprint author), Univ Penn, Dept Psychiat, Translat Res Labs, Translat Neurosci Program, Room 2202,125 S 31st St, Philadelphia, PA 19104 USA. EM siegels@upenn.edu OI Gandal, Michael/0000-0001-5800-5128; Siegel, Steven/0000-0001-8058-9713 FU Academic Development Funds; National Institute of Mental Health; Astra Zeneca; Glaxo SmithKline; Novartis; Pfizer; NuPathe; Merck; [1-P50-DA143187] FX Supported by Grant 1-P50-DA143187; Academic Development Funds, to University of Pennsylvania; and the Genes, Cognition and Psychosis Program, National Institute of Mental Health. Yufei Cao, Robert Featherstone, Michael Gandal, Yuling Liang, Catherine Jutzeler, John Saunders, Jingshan Chen, and Daniel Weinberger have no financial conflicts of interest; Caryn Lerman has been a consultant and/or has received grant support from the following companies that develop and/or market smoking cessation medications: Astra Zeneca, Glaxo SmithKline, Novartis, and Pfizer; Steven Siegel has been a consultant and/or has received grant support from the following companies that develop and/or market medications: NuPathe, AstraZeneca, and Merck. NR 103 TC 7 Z9 7 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD APR PY 2012 VL 126 IS 2 BP 332 EP 343 DI 10.1037/a0027047 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 913WY UT WOS:000301909300012 PM 22309446 ER PT J AU Adamczyk, A Mejias, R Takamiya, K Yocum, J Krasnova, IN Calderon, J Cadet, JL Huganir, RL Pletnikov, MV Wang, T AF Adamczyk, Abby Mejias, Rebeca Takamiya, Kogo Yocum, Jennifer Krasnova, Irina N. Calderon, Juan Cadet, Jean Lud Huganir, Richard L. Pletnikov, Mikhail V. Wang, Tao TI GluA3-deficiency in mice is associated with increased social and aggressive behavior and elevated dopamine in striatum SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Glutamate receptor; GluA3; Striatum; Dopamine; Serotonin; Olfactory bulb; Aggression; Sociability; Social interaction; Mice ID GLUTAMATE-RECEPTOR SUBUNITS; AMPA RECEPTORS; CHANNELS; EXPRESSION; PLASTICITY; SEROTONIN; NEURONS; IDENTIFICATION; VULNERABILITY; TESTOSTERONE AB Glutamate signaling has been implicated in the regulation of social behavior. AMPA-glutamate receptors are assembled from four subunits (GluA1-4) of mainly GluA1/2 and GluA2/3 tetramers that form ion channels of distinct functional properties. Mice lacking GluA1 showed a reduced anxiety and male aggression. To understand the role of GluA3 in modulating social behavior, we investigated GluA3-deficient mice (Gria3 -/Y) on C57BL/6J background. Compared to wild type (WT) littermates (n = 14), Gria3 -/Y mice (n = 13) showed an increase in isolation-induced male aggression (p = 0.011) in home cage resident-intruder test; an increase in sociability (p = 0.01), and increase in male-male social interactions in neutral arena (p = 0.005); an increase in peripheral activities in open field test (p = 0.037) with normal anxiety levels in elevated plus maze and light-dark box; and minor deficits in motor and balance function in accelerating rotarod test (p = 0.016) with normal grip strength. Gria3 -/Y mice showed no significant deficit in spatial memory function in Morris-water maze and Y-maze tests, and normal levels of testosterone. Increased dopamine concentrations in stratum (p = 0.034) and reduced serotonin turnover in olfactory bulb (p = 0.002) were documented in Gria3 -/Y mice. These results support a role of GluA3 in the modulation of social behavior through brain dopamine and/or serotonin signaling and different AMPA receptor subunits affect social behavior through distinct mechanisms. (C) 2012 Elsevier B.V. All rights reserved. C1 [Adamczyk, Abby; Mejias, Rebeca; Calderon, Juan; Wang, Tao] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Dept Pediat, Baltimore, MD 21205 USA. [Takamiya, Kogo; Huganir, Richard L.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Takamiya, Kogo; Huganir, Richard L.] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. [Yocum, Jennifer; Pletnikov, Mikhail V.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Krasnova, Irina N.; Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, NIH, DHHS, Baltimore, MD 21224 USA. RP Wang, T (reprint author), Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Dept Pediat, 733 N Broadway BRB 513, Baltimore, MD 21205 USA. EM twang9@jhmi.edu RI Adamczyk, Abby/E-4457-2014; Mejias-Estevez, Rebeca/B-4696-2008; OI Adamczyk, Abby/0000-0001-7653-295X; Mejias-Estevez, Rebeca/0000-0003-1936-7219; Calderon, Juan/0000-0003-2072-704X FU March of Dimes Foundation; NICHD [HD044789, HD052680]; Ministry of Education and Science of Spain FX This study was supported in part by research grants from a Basil O'Connor Award of the March of Dimes Foundation (to T.W.) and NICHD (HD044789 and HD052680, to T.W.): a postdoctoral fellowship from Ministry of Education and Science of Spain (to R.M.); RH is an Investigator with the Howard Hughes Medical Institute. NR 42 TC 19 Z9 20 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 APR 1 PY 2012 VL 229 IS 1 BP 265 EP 272 DI 10.1016/j.bbr.2012.01.007 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 915SL UT WOS:000302047600033 PM 22285418 ER PT J AU Batkai, S Mukhopadhyay, P Horvath, B Rajesh, M Gao, RY Mahadevan, A Amere, M Battista, N Lichtman, AH Gauson, LA Maccarrone, M Pertwee, RG Pacher, P AF Batkai, Sandor Mukhopadhyay, Partha Horvath, Bela Rajesh, Mohanraj Gao, Rachel Y. Mahadevan, Anu Amere, Mukkanti Battista, Natalia Lichtman, Aron H. Gauson, Lisa A. Maccarrone, Mauro Pertwee, Roger G. Pacher, Pal TI Delta(8)-Tetrahydrocannabivarin prevents hepatic ischaemia/reperfusion injury by decreasing oxidative stress and inflammatory responses through cannabinoid CB2 receptors SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE cannabinoids; oxidative stress; inflammation; ischaemia-reperfusion ID ISCHEMIA-REPERFUSION INJURY; NITRIC-OXIDE; CELL-DEATH; IN-VIVO; ISCHEMIA/REPERFUSION INJURY; DIABETIC CARDIOMYOPATHY; DELTA(9)-TETRAHYDROCANNABIVARIN; PEROXYNITRITE; DYSFUNCTION; PROTECTS AB BACKGROUND AND PURPOSE Activation of cannabinoid CB2 receptors protects against various forms of ischaemia-reperfusion (I/R) injury. Delta(8)-Tetrahydrocannabivarin (Delta(8)-THCV) is a synthetic analogue of the plant cannabinoid Delta(9)-tetrahydrocannabivarin, which exhibits anti-inflammatory effects in rodents involving activation of CB2 receptors. Here, we assessed effects of Delta(8)-THCV and its metabolite 11-OH-Delta(8)-THCV on CB2 receptors and against hepatic I/R injury. EXPERIMENTAL APPROACH Effects in vitro were measured with human CB2 receptors expressed in CHO cells. Hepatic I/R injury was assessed in mice with 1h ischaemia and 2, 6 or 24h reperfusion in vivo. KEY RESULTS Displacement of [H-3]CP55940 by Delta(8)-THCV or 11-OH-Delta(8)-THCV from specific binding sites in CHO cell membranes transfected with human CB2 receptors (hCB(2)) yielded K-i values of 68.4 and 59.95 nM respectively. Delta(8)-THCV or 11-OH-Delta(8)-THCV inhibited forskolin-stimulated cAMP production by hCB(2) CHO cells (EC50 = 12.95 and 14.3 nM respectively). Delta(8)-THCV, given before induction of I/R, attenuated hepatic injury (measured by serum alanine aminotransferase and aspartate aminotransferase levels), decreased tissue protein carbonyl adducts, 4-hydroxy-2-nonenal, the chemokines CCL3 and CXCL2, TNF-alpha, intercellular adhesion molecule 1 (CD54) mRNA levels, tissue neutrophil infiltration, caspase 3/7 activity and DNA fragmentation. Protective effects of Delta(8)-THCV against liver damage were still present when the compound was given at the beginning of reperfusion. Pretreatment with a CB2 receptor antagonist attenuated the protective effects of Delta(8)-THCV, while a CB1 antagonist tended to enhance it. CONCLUSIONS AND IMPLICATIONS Delta(8)-THCV activated CB2 receptors in vitro, and decreased tissue injury and inflammation in vivo, associated with I/R partly via CB2 receptor activation. C1 [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Mahadevan, Anu; Amere, Mukkanti] Organix Inc, Woburn, MA USA. [Battista, Natalia; Maccarrone, Mauro] Univ Teramo, Dept Biomed Sci, Teramo, Italy. [Battista, Natalia; Maccarrone, Mauro] Santa Lucia Fdn, European Ctr Brain Res CERC, Rome, Italy. [Lichtman, Aron H.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA USA. [Gauson, Lisa A.; Pertwee, Roger G.] Univ Aberdeen, Inst Med Sci, Sch Med Sci, Aberdeen, Scotland. [Horvath, Bela] Semmelweis Univ, Inst Human Physiol & Clin Expt Res, Budapest, Hungary. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC 9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI perumal, murugiah/D-1565-2012; Pacher, Pal/B-6378-2008; Ji, Haofeng/G-6206-2012; MUKHOPADHYAY, PARTHA/G-3890-2010; Horvath, Bela/A-7368-2009; Batkai, Sandor/H-7983-2014 OI Pacher, Pal/0000-0001-7036-8108; MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; FU National Institutes of Health [DA-03672, DA-005488, DA-009789]; NIH/NIAAA; Hungarian Research Council [MB08-80238]; GW Pharmaceuticals FX This study was supported by the National Institutes of Health (DA-03672, DA-005488 and DA-009789) and Intramural Research Program of NIH/NIAAA. Dr Horvath is a recipient of a Hungarian Research Council Scientific Research Fund Fellowship (NKTH-OTKA-EU, MB08-80238). The authors are indebted to Dr George Kunos for providing key resources and support.; R.G.P. receives funding from GW Pharmaceuticals; other authors have no conflicts. NR 39 TC 14 Z9 15 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD APR PY 2012 VL 165 IS 8 SI SI BP 2450 EP 2461 DI 10.1111/j.1476-5381.2011.01410.x PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 914CB UT WOS:000301925200006 PM 21470208 ER PT J AU Horvath, B Magid, L Mukhopadhyay, P Batkai, S Rajesh, M Park, O Tanchian, G Gao, RY Goodfellow, CE Glass, M Mechoulam, R Pacher, P AF Horvath, Bela Magid, Lital Mukhopadhyay, Partha Batkai, Sandor Rajesh, Mohanraj Park, Ogyi Tanchian, Galin Gao, Rachel Y. Goodfellow, Catherine E. Glass, Michelle Mechoulam, Raphael Pacher, Pal TI A new cannabinoid CB2 receptor agonist HU-910 attenuates oxidative stress, inflammation and cell death associated with hepatic ischaemia/reperfusion injury SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE cannabinoids; oxidative stress; inflammation; ischaemia-reperfusion ID ISCHEMIA-REPERFUSION INJURY; NITRIC-OXIDE; LIVER-INJURY; ISCHEMIA/REPERFUSION INJURY; DIABETIC CARDIOMYOPATHY; ENDOCANNABINOID SYSTEM; REACTIVE OXYGEN; IN-VIVO; PEROXYNITRITE; DYSFUNCTION AB BACKGROUND AND PURPOSE Cannabinoid CB2 receptor activation has been reported to attenuate myocardial, cerebral and hepatic ischaemia-reperfusion (I/R) injury. EXPERIMENTAL APPROACH We have investigated the effects of a novel CB2 receptor agonist ((1S,4R)-2-(2,6-dimethoxy-4-(2-methyloctan-2-yl)phenyl)-7,7-dimethylbicyclo[2.2.1]hept-2-en-1-yl) methanol (HU-910) on liver injury induced by 1 h of ischaemia followed by 2, 6 or 24 h of reperfusion, using a well-established mouse model of segmental hepatic I/R. KEY RESULTS Displacement of [H-3]CP55940 by HU-910 from specific binding sites in CHO cell membranes transfected with human CB2 or CB1 receptors (hCB(1/2)) yielded K-i values of 6 nM and 1.4 mM respectively. HU-910 inhibited forskolin-stimulated cyclic AMP production by hCB(2) CHO cells (EC50 = 162 nM) and yielded EC50 of 26.4 nM in [S-35]GTP gamma S binding assays using hCB(2) expressing CHO membranes. HU-910 given before ischaemia significantly attenuated levels of I/R-induced hepatic proinflammatory chemokines (CCL3 and CXCL2), TNF-alpha, inter-cellular adhesion molecule-1, neutrophil infiltration, oxidative stress and cell death. Some of the beneficial effect of HU-910 also persisted when given at the beginning of the reperfusion or 1 h after the ischaemic episode. Furthermore, HU-910 attenuated the bacterial endotoxin-triggered TNF-alpha production in isolated Kupffer cells and expression of adhesion molecules in primary human liver sinusoidal endothelial cells stimulated with TNF-alpha. Pretreatment with a CB2 receptor antagonist attenuated the protective effects of HU-910, while pretreatment with a CB1 antagonist tended to enhance them. CONCLUSION AND IMPLICATIONS HU-910 is a potent CB2 receptor agonist which may exert protective effects in various diseases associated with inflammation and tissue injury. C1 [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Magid, Lital] Hebrew Univ Jerusalem, Inst Drug Res, Fac Med, Jerusalem, Israel. [Goodfellow, Catherine E.; Glass, Michelle] Univ Auckland, Fac Med & Hlth Sci, Dept Pharmacol & Clin Pharmacol, Auckland 1, New Zealand. [Horvath, Bela] Semmelweis Univ, Inst Human Physiol & Clin Expt Res, Budapest, Hungary. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC 9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Pacher, Pal/B-6378-2008; Ji, Haofeng/G-6206-2012; MUKHOPADHYAY, PARTHA/G-3890-2010; Horvath, Bela/A-7368-2009; Batkai, Sandor/H-7983-2014; OI Pacher, Pal/0000-0001-7036-8108; MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Gao, Yue/0000-0002-7890-1605; Glass, Michelle/0000-0002-5997-6898 FU NIH/NIAAA; NIDA [9789]; Hungarian Research Council [OTKA-NKTH-EU MB08-80238] FX This study was supported by the Intramural Research Program of NIH/NIAAA (to P. P.) and by NIDA grant #9789 (to R. M.). Dr Bela Horvath is a recipient of a Hungarian Research Council Scientific Research Fund Fellowship (OTKA-NKTH-EU MB08-80238). The authors are indebted to Drs George Kunos and Bin Gao for providing key resources and support. NR 39 TC 37 Z9 40 U1 1 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD APR PY 2012 VL 165 IS 8 SI SI BP 2462 EP 2478 DI 10.1111/j.1476-5381.2011.01381.x PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 914CB UT WOS:000301925200007 PM 21449982 ER PT J AU Panlilio, LV Ferre, S Yasar, S Thorndike, EB Schindler, CW Goldberg, SR AF Panlilio, Leigh V. Ferre, Sergi Yasar, Sevil Thorndike, Eric B. Schindler, Charles W. Goldberg, Steven R. TI Combined effects of THC and caffeine on working memory in rats SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE delayed spatial matching; mediating response; rehearsal; marijuana; adenosine receptor antagonist; caffeine; THC ID ADENOSINE A(1) RECEPTORS; SHORT-TERM-MEMORY; A(2A) RECEPTORS; BEHAVIORAL-ANALYSIS; RHESUS-MONKEYS; INVOLVEMENT; IMPAIRMENT; DRUGS; DELTA(9)-TETRAHYDROCANNABINOL; DELTA-9-TETRAHYDROCANNABINOL AB BACKGROUND AND PURPOSE Cannabis and caffeine are two of the most widely used psychoactive substances. Delta(9)-Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, induces deficits in short-term memory. Caffeine, a non-selective adenosine receptor antagonist, attenuates some memory deficits, but there have been few studies addressing the effects of caffeine and THC in combination. Here, we evaluate the effects of these drugs using a rodent model of working memory. EXPERIMENTAL APPROACH Rats were given THC (0, 1 and 3 mg.kg(-1), i.p.) along with caffeine (0, 1, 3 and 10 mg.kg(-1), i.p.), the selective adenosine A(1)-receptor antagonist CPT (0, 3 and 10 mg.kg(-1)) or the selective adenosine A(2A)-receptor antagonist SCH58261 (0 and 5 mg.kg(-1)) and were tested with a delayed non-matching-to-position procedure in which behaviour during the delay was automatically recorded as a model of memory rehearsal. KEY RESULTS THC alone produced memory deficits at 3 mg.kg(-1). The initial exposure to caffeine (10 mg.kg(-1)) disrupted the established pattern of rehearsal-like behaviour, but tolerance developed rapidly to this effect. CPT and SCH58261 alone had no significant effects on rehearsal or memory. When a subthreshold dose of THC (1 mg.kg(-1)) was combined with caffeine (10 mg.kg(-1)) or CPT (10 mg.kg(-1)), memory performance was significantly impaired, even though performance of the rehearsal-like pattern was not significantly altered. CONCLUSION AND IMPLICATIONS Caffeine did not counteract memory deficits induced by THC but actually exacerbated them. These results are consistent with recent findings that adenosine A(1) receptors modulate cannabinoid signalling in the hippocampus. C1 [Panlilio, Leigh V.; Ferre, Sergi; Thorndike, Eric B.; Schindler, Charles W.; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Yasar, Sevil] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD 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. EM lpanlili@intra.nida.nih.gov RI Ferre, Sergi/K-6115-2014 OI Ferre, Sergi/0000-0002-1747-1779 FU NIH, National Institute on Drug Abuse FX This research was supported by the Intramural Research Program of the NIH, National Institute on Drug Abuse. NR 41 TC 10 Z9 10 U1 0 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD APR PY 2012 VL 165 IS 8 SI SI BP 2529 EP 2538 DI 10.1111/j.1476-5381.2011.01554.x PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 914CB UT WOS:000301925200012 PM 21699509 ER PT J AU Scherma, M Justinova, Z Zanettini, C Panlilio, LV Mascia, P Fadda, P Fratta, W Makriyannis, A Vadivel, SK Gamaleddin, I Le Foll, B Goldberg, SR AF Scherma, Maria Justinova, Zuzana Zanettini, Claudio Panlilio, Leigh V. Mascia, Paola Fadda, Paola Fratta, Walter Makriyannis, Alexandros Vadivel, Subramanian K. Gamaleddin, Islam Le Foll, Bernard Goldberg, Steven R. TI The anandamide transport inhibitor AM404 reduces the rewarding effects of nicotine and nicotine-induced dopamine elevations in the nucleus accumbens shell in rats SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE reward; tobacco dependence; nicotine; anandamide; AM404; conditioned place preference; reinstatement; microdialysis; dopamine ID ACID AMIDE HYDROLASE; CONDITIONED PLACE PREFERENCES; CANNABINOID RECEPTORS; ENDOCANNABINOID SYSTEM; HIPPOCAMPAL-NEURONS; MEMBRANE-TRANSPORT; CB1 RECEPTORS; ESTER URB597; ADDICTION; ACTIVATION AB BACKGROUND AND PURPOSE The fatty acid amide hydrolase inhibitor URB597 can reverse the abuse-related behavioural and neurochemical effects of nicotine in rats. Fatty acid amide hydrolase inhibitors block the degradation (and thereby magnify and prolong the actions) of the endocannabinoid anandamide (AEA), and also the non-cannabinoid fatty acid ethanolamides oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). OEA and PEA are endogenous ligands for peroxisome proliferator-activated receptors alpha (PPAR-alpha). Since recent evidence indicates that PPAR-alpha can modulate nicotine reward, it is unclear whether AEA plays a role in the effects of URB597 on nicotine reward. EXPERIMENTAL APPROACH A way to selectively increase endogenous levels of AEA without altering OEA or PEA levels is to inhibit AEA uptake into cells by administering the AEA transport inhibitor N-(4-hydroxyphenyl)-arachidonamide (AM404). To clarify AEA's role in nicotine reward, we investigated the effect of AM404 on conditioned place preference (CPP), reinstatement of abolished CPP, locomotor suppression and anxiolysis in an open field, and dopamine elevations in the nucleus accumbens shell induced by nicotine in Sprague-Dawley rats. KEY RESULTS AM404 prevented the development of nicotine-induced CPP and impeded nicotine-induced reinstatement of the abolished CPP. Furthermore, AM404 reduced nicotine-induced increases in dopamine levels in the nucleus accumbens shell, the terminal area of the brain's mesolimbic reward system. AM404 did not alter the locomotor suppressive or anxiolytic effect of nicotine. CONCLUSIONS AND IMPLICATIONS These findings suggest that AEA transport inhibition can counteract the addictive effects of nicotine and that AEA transport may serve as a new target for development of medications for treatment of tobacco dependence. C1 [Scherma, Maria; Justinova, Zuzana; Zanettini, Claudio; Panlilio, Leigh V.; Mascia, Paola; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neuroscience Res Branch, IRP,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Scherma, Maria; Fadda, Paola; Fratta, Walter] Univ Cagliari, Bb Brodie Dept Neurosci, I-09124 Cagliari, Italy. [Justinova, Zuzana] Univ Maryland, Sch Med, Dept Psychiat, MPRC, Baltimore, MD 21201 USA. [Makriyannis, Alexandros; Vadivel, Subramanian K.] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA. [Gamaleddin, Islam; Le Foll, Bernard] Ctr Addict & Mental Hlth, Translat Addict Res Lab, Toronto, ON, Canada. [Gamaleddin, Islam; Le Foll, Bernard] Ctr Addict & Mental Hlth, Addict Program, Toronto, ON, Canada. [Le Foll, Bernard] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Le Foll, Bernard] Univ Toronto, Dept Family & Community Med, Toronto, ON M5S 1A1, Canada. [Le Foll, Bernard] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neuroscience Res Branch, IRP,NIH,Dept Hlth & Human Serv, Bayview Blvd, Baltimore, MD 21224 USA. EM sgoldber@mail.nih.gov RI Justinova, Zuzana/A-9109-2011; Le Foll, Bernard/K-2952-2014; OI Justinova, Zuzana/0000-0001-5793-7484; Le Foll, Bernard/0000-0002-6406-4973; FADDA, PAOLA/0000-0002-0642-6710 FU National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD, USA; Italian Ministry of University and Scientific Research; Centre of Excellence on 'Neurobiology of Dependence', Cagliari, Italy; Division of Geriatric Medicine and Gerontology of Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Drug Discovery, Northeastern University, Boston, MA, USA; Centre for Addiction and Mental Health of the University of Toronto, Toronto, Canada FX This study was supported in part by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD, USA, by the Italian Ministry of University and Scientific Research and the Centre of Excellence on 'Neurobiology of Dependence', Cagliari, Italy, by the Division of Geriatric Medicine and Gerontology of Johns Hopkins University School of Medicine, Baltimore, MD, USA, by the Center for Drug Discovery, Northeastern University, Boston, MA, USA, and by the Centre for Addiction and Mental Health of the University of Toronto, Toronto, Canada. NR 55 TC 17 Z9 18 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD APR PY 2012 VL 165 IS 8 SI SI BP 2539 EP 2548 DI 10.1111/j.1476-5381.2011.01467.x PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 914CB UT WOS:000301925200013 PM 21557729 ER PT J AU Thun, MJ Hoover, RN Hunter, DJ AF Thun, Michael J. Hoover, Robert N. Hunter, David J. TI Bigger, Better, Sooner-Scaling Up for Success SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ESTROGEN-PROGESTIN REPLACEMENT; GENOME-WIDE ASSOCIATION; BREAST-CANCER; POSTMENOPAUSAL WOMEN; PLUS PROGESTIN; RISK; THERAPY; MORTALITY; OBESITY; SCIENCE AB Over the last twenty years, the field of epidemiology has seen a rapidly increasing interest in, and need for, addressing low-level risks, interactions as well as main effects, and simultaneous assessment of vast numbers of biomarkers. Multiple examples over this time have shown the necessity for very large, high-quality individual studies (e. g., biobanks) or consortia of studies for these efforts to be successful. The need for this will continue to increase in the foreseeable future. It will also be important to analyze and publish aggregated data much earlier in the discovery process than typical for past efforts. Cancer Epidemiol Biomarkers Prev; 21(4); 571-5. (C) 2012 AACR. C1 [Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Cambridge, MA 02138 USA. [Hunter, David J.] Harvard Univ, Sch Med, Boston, MA USA. [Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Hoover, RN (reprint author), 6120 Execut Blvd,EPS 8094, Bethesda, MD 20892 USA. EM hooverr@mail.nih.gov FU NIEHS NIH HHS [P30 ES002109] NR 36 TC 7 Z9 7 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2012 VL 21 IS 4 BP 571 EP 575 DI 10.1158/1055-9965.EPI-12-0191 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 918AG UT WOS:000302220600001 PM 22374992 ER PT J AU Couch, FJ Gaudet, MM Antoniou, AC Ramus, SJ Kuchenbaecker, KB Soucy, P Beesley, J Chen, XQ Wang, XS Kirchhoff, T McGuffog, L Barrowdale, D Lee, A Healey, S Sinilnikova, OM Andrulis, IL Ozcelik, H Mulligan, AM Thomassen, M Gerdes, AM Jensen, UB Skytte, AB Kruse, TA Caligo, MA von Wachenfeldt, A Barbany-Bustinza, G Loman, N Soller, M Ehrencrona, H Karlsson, P Nathanson, KL Rebbeck, TR Domchek, SM Jakubowska, A Lubinski, J Jaworska, K Durda, K Zlowocka, E Huzarski, T Byrski, T Gronwald, J Cybulski, C Gorski, B Osorio, A Duran, M Tejada, MI Benitez, J Hamann, U Hogervorst, FBL van Os, TA van Leeuwen, FE Meijers-Heijboer, HEJ Wijnen, J Blok, MJ Kets, M Hooning, MJ Oldenburg, RA Ausems, MGEM Peock, S Frost, D Ellis, SD Platte, R Fineberg, E Evans, DG Jacobs, C Eeles, RA Adlard, J Davidson, R Eccles, DM Cole, T Cook, J Paterson, J Brewer, C Douglas, F Hodgson, SV Morrison, PJ Walker, L Porteous, ME Kennedy, MJ Side, LE Bove, B Godwin, AK Stoppa-Lyonnet, D Fassy-Colcombet, M Castera, L Cornelis, F Mazoyer, S Leone, M Boutry-Kryza, N Bressac-de Paillerets, B Caron, O Pujol, P Coupier, I Delnatte, C Akloul, L Lynch, HT Snyder, CL Buys, SS Daly, MB Terry, M Chung, WK John, EM Miron, A Southey, MC Hopper, JL Goldgar, DE Singer, CF Rappaport, C Tea, MKM Fink-Retter, A Hansen, TVO Nielsen, FC Arason, A Vijai, J Shah, S Sarrel, K Robson, ME Piedmonte, M Phillips, K Basil, J Rubinstein, WS Boggess, J Wakeley, K Ewart-Toland, A Montagna, M Agata, S Imyanitov, EN Isaacs, C Janavicius, R Lazaro, C Blanco, I Feliubadalo, L Brunet, J Gayther, SA Pharoah, PPD Odunsi, KO Karlan, BY Walsh, CS Olah, E Teo, SH Ganz, PA Beattie, MS van Rensburg, EJ Dorfling, CM Diez, O Kwong, A Schmutzler, RK Wappenschmidt, B Engel, C Meindl, A Ditsch, N Arnold, N Heidemann, S Niederacher, D Preisler-Adams, S Gadzicki, D Varon-Mateeva, R Deissler, H Gehrig, A Sutter, C Kast, K Fiebig, B Heinritz, W Caldes, T de la Hoya, M Muranen, TA Nevanlinna, H Tischkowitz, M Spurdle, AB Neuhausen, SL Ding, YC Lindor, NM Fredericksen, Z Pankratz, VS Peterlongo, P Manoukian, S Peissel, B Zaffaroni, D Barile, M Bernard, L Viel, A Giannini, G Varesco, L Radice, P Greene, MH Mai, PL Easton, DF Chenevix-Trench, G Offit, K Simard, J AF Couch, Fergus J. Gaudet, Mia M. Antoniou, Antonis C. Ramus, Susan J. Kuchenbaecker, Karoline B. Soucy, Penny Beesley, Jonathan Chen, Xiaoqing Wang, Xianshu Kirchhoff, Tomas McGuffog, Lesley Barrowdale, Daniel Lee, Andrew Healey, Sue Sinilnikova, Olga M. Andrulis, Irene L. Ozcelik, Hilmi Mulligan, Anna Marie Thomassen, Mads Gerdes, Anne-Marie Jensen, Uffe Birk Skytte, Anne-Bine Kruse, Torben A. Caligo, Maria A. von Wachenfeldt, Anna Barbany-Bustinza, Gisela Loman, Niklas Soller, Maria Ehrencrona, Hans Karlsson, Per Nathanson, Katherine L. Rebbeck, Timothy R. Domchek, Susan M. Jakubowska, Ania Lubinski, Jan Jaworska, Katarzyna Durda, Katarzyna Zlowocka, Elzbieta Huzarski, Tomasz Byrski, Tomasz Gronwald, Jacek Cybulski, Cezary Gorski, Bohdan Osorio, Ana Duran, Mercedes Isabel Tejada, Maria Benitez, Javier Hamann, Ute Hogervorst, Frans B. L. van Os, Theo A. van Leeuwen, Flora E. Meijers-Heijboer, Hanne E. J. Wijnen, Juul Blok, Marinus J. Kets, Marleen Hooning, Maartje J. Oldenburg, Rogier A. Ausems, Margreet G. E. M. Peock, Susan Frost, Debra Ellis, Steve D. Platte, Radka Fineberg, Elena Evans, D. Gareth Jacobs, Chris Eeles, Rosalind A. Adlard, Julian Davidson, Rosemarie Eccles, Diana M. Cole, Trevor Cook, Jackie Paterson, Joan Brewer, Carole Douglas, Fiona Hodgson, Shirley V. Morrison, Patrick J. Walker, Lisa Porteous, Mary E. Kennedy, M. John Side, Lucy E. Bove, Betsy Godwin, Andrew K. Stoppa-Lyonnet, Dominique Fassy-Colcombet, Marion Castera, Laurent Cornelis, Francois Mazoyer, Sylvie Leone, Melanie Boutry-Kryza, Nadia Bressac-de Paillerets, Brigitte Caron, Olivier Pujol, Pascal Coupier, Isabelle Delnatte, Capucine Akloul, Linda Lynch, Henry T. Snyder, Carrie L. Buys, Saundra S. Daly, Mary B. Terry, MaryBeth Chung, Wendy K. John, Esther M. Miron, Alexander Southey, Melissa C. Hopper, John L. Goldgar, David E. Singer, Christian F. Rappaport, Christine Tea, Muy-Kheng M. Fink-Retter, Anneliese Hansen, Thomas V. O. Nielsen, Finn C. Arason, Adalgeir Vijai, Joseph Shah, Sohela Sarrel, Kara Robson, Mark E. Piedmonte, Marion Phillips, Kelly Basil, Jack Rubinstein, Wendy S. Boggess, John Wakeley, Katie Ewart-Toland, Amanda Montagna, Marco Agata, Simona Imyanitov, Evgeny N. Isaacs, Claudine Janavicius, Ramunas Lazaro, Conxi Blanco, Ignacio Feliubadalo, Lidia Brunet, Joan Gayther, Simon A. Pharoah, Paul P. D. Odunsi, Kunle O. Karlan, Beth Y. Walsh, Christine S. Olah, Edith Teo, Soo Hwang Ganz, Patricia A. Beattie, Mary S. van Rensburg, Elizabeth J. Dorfling, Cecelia M. Diez, Orland Kwong, Ava Schmutzler, Rita K. Wappenschmidt, Barbara Engel, Christoph Meindl, Alfons Ditsch, Nina Arnold, Norbert Heidemann, Simone Niederacher, Dieter Preisler-Adams, Sabine Gadzicki, Dorothea Varon-Mateeva, Raymonda Deissler, Helmut Gehrig, Andrea Sutter, Christian Kast, Karin Fiebig, Britta Heinritz, Wolfram Caldes, Trinidad de la Hoya, Miguel Muranen, Taru A. Nevanlinna, Heli Tischkowitz, Marcd. Spurdle, Amanda B. Neuhausen, Susan L. Ding, Yuan Chun Lindor, Noralane M. Fredericksen, Zachary Pankratz, V. Shane Peterlongo, Paolo Manoukian, Siranoush Peissel, Bernard Zaffaroni, Daniela Barile, Monica Bernard, Loris Viel, Alessandra Giannini, Giuseppe Varesco, Liliana Radice, Paolo Greene, Mark H. Mai, Phuong L. Easton, Douglas F. Chenevix-Trench, Georgia Offit, Kenneth Simard, Jacques CA OCGN SWE-BRCA HEBON EMBRACE GEMO Study Collaborators kConFab Investigators Consortium Investigators Modifiers TI Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; URIC-ACID NEPHROLITHIASIS; SUSCEPTIBILITY LOCI; TUMOR SUBTYPES; ALLELES; CONSORTIUM; RECEPTOR; DISEASE; GENE; 8Q24 AB Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 x 10(-4)] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05-1.29; P = 3.8 x 10(-4)) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10-1.52; P = 1.8 x 10(-3)). Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(4); 645-57. (C) 2012 AACR. C1 [Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Lindor, Noralane M.] Mayo Clin, Dept Med Genet, Rochester, MN 55905 USA. [Fredericksen, Zachary; Pankratz, V. Shane] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Antoniou, Antonis C.; Kuchenbaecker, Karoline B.; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB2 1TN, England. [Pharoah, Paul P. D.] Univ Cambridge, Dept Oncol, Cambridge CB2 1TN, England. [Paterson, Joan] Addenbrookes Hosp, E Anglian Reg Genet Serv, Dept Clin Genet, Cambridge, England. [Ramus, Susan J.; Gayther, Simon A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. [Karlan, Beth Y.; Walsh, Christine S.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Soucy, Penny; Simard, Jacques] Ctr Hosp Univ Quebec, Canc Genom Lab, Quebec City, PQ, Canada. [Soucy, Penny; Simard, Jacques] Univ Laval, Quebec City, PQ, Canada. [Tischkowitz, Marcd.] McGill Univ, Dept Human Genet, Program Canc Genet, Montreal, PQ H3A 2T5, Canada. [Tischkowitz, Marcd.] McGill Univ, Dept Oncol, Program Canc Genet, Montreal, PQ H3A 2T5, Canada. [Tischkowitz, Marcd.] McGill Univ, Jewish Gen Hosp, Segal Canc Ctr, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada. [Beesley, Jonathan; Chen, Xiaoqing; Healey, Sue; Spurdle, Amanda B.; Chenevix-Trench, Georgia] Queensland Inst Med Res, Dept Genet, Herston, Qld 4006, Australia. [Kirchhoff, Tomas; Vijai, Joseph; Shah, Sohela; Sarrel, Kara; Robson, Mark E.; Offit, Kenneth] Mem Sloane Kettering Canc Ctr, Clin Canc Genet Lab, New York, NY USA. [Terry, MaryBeth; Chung, Wendy K.] Columbia Univ, Dept Epidemiol, New York, NY USA. [Sinilnikova, Olga M.; Leone, Melanie; Boutry-Kryza, Nadia] Ctr Hosp Univ Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France. [Sinilnikova, Olga M.; Mazoyer, Sylvie] Univ Lyon 1, Ctr Rech Cancerol Lyon, CNRS, INSERM,UMR5286,U1052, F-69622 Villeurbanne, France. [Stoppa-Lyonnet, Dominique] Federat Natl Ctr Lutte Canc, GEMO Study Collaborators Canc Genet Network, Grp Genet & Canc, Lyon, France. [Andrulis, Irene L.] Univ Toronto, Canc Care Ontario, Mt Sinai Hosp, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. [Andrulis, Irene L.; Ozcelik, Hilmi; Mulligan, Anna Marie] Univ Toronto, Canc Care Ontario, Mt Sinai Hosp, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada. [Andrulis, Irene L.; Ozcelik, Hilmi; Mulligan, Anna Marie] Univ Toronto, Canc Care Ontario, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5S 1A1, Canada. [Andrulis, Irene L.] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Li Ka Shing Knowledge Inst, Dept Lab Med, Toronto, ON M5B 1W8, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada. [Thomassen, Mads; Kruse, Torben A.] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark. [Gerdes, Anne-Marie] Rigshosp, Dept Clin Genet, Copenhagen, Denmark. [Jensen, Uffe Birk] Skejby Hosp, Dept Clin Genet, Aarhus, Denmark. [Skytte, Anne-Bine] Vejle Hosp, Dept Clin Genet, Vejle, Denmark. [Caligo, Maria A.] Univ Hosp Pisa, Sect Genet Oncol, Pisa, Italy. [von Wachenfeldt, Anna] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden. [Barbany-Bustinza, Gisela] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Loman, Niklas] Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden. [Soller, Maria] Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden. [Ehrencrona, Hans] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden. [Karlsson, Per] Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden. [Nathanson, Katherine L.; Domchek, Susan M.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Bove, Betsy] Clin Mol Genet Lab, Philadelphia, PA USA. [Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Jakubowska, Ania; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Zlowocka, Elzbieta; Huzarski, Tomasz; Byrski, Tomasz; Gronwald, Jacek; Cybulski, Cezary; Gorski, Bohdan] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Jaworska, Katarzyna] Warsaw Med Univ, Postgrad Sch Mol Med, Warsaw, Poland. [Osorio, Ana; Benitez, Javier] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain. [Benitez, Javier] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Genotyping Unit, Madrid, Spain. Spanish Network Rare Dis CIBERER, Valencia, Spain. [Caldes, Trinidad; de la Hoya, Miguel] Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain. [Duran, Mercedes] Univ Valladolid IBGM UVA, Inst Biol & Mol Genet, Valladolid, Spain. [Isabel Tejada, Maria] Cruces Hosp Barakaldo, Dept Biochem, Mol Genet Lab, Bizkaia, Spain. [Hamann, Ute] Deutsch Krebsforschungszentrum DKFZ, Heidelberg, Germany. [Sutter, Christian] Univ Heidelberg, Div Mol Genet, Inst Human Genet, D-6900 Heidelberg, Germany. [Hogervorst, Frans B. L.] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands. [van Leeuwen, Flora E.] Netherlands Canc Inst, Dept Epidemiol, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands. [van Os, Theo A.] Acad Med Ctr, Dept Clin Genet, Forfar, Angus, Scotland. [Meijers-Heijboer, Hanne E. J.] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [Wijnen, Juul] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. [Wijnen, Juul] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands. [Blok, Marinus J.] Univ Med Ctr, Dept Genet & Cell Biol, Maastricht, Netherlands. [Kets, Marleen] Radboud Univ Nijmegen, Med Ctr, Hereditary Canc Clin, NL-6525 ED Nijmegen, Netherlands. [Hooning, Maartje J.] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands. [Oldenburg, Rogier A.] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Clin Genet, Rotterdam, Netherlands. [Ausems, Margreet G. E. M.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Evans, D. Gareth] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Jacobs, Chris] Guys & St Thomas NHS Fdn Trust, London, England. [Hodgson, Shirley V.] Univ London, Med Genet Unit, London WC1E 7HU, England. [Side, Lucy E.] Great Ormond St Hosp Sick Children, NE Thames Reg Genet Serv, London, England. [Eeles, Rosalind A.] Inst Canc Res, Oncogenet Team, London, England. [Eeles, Rosalind A.] Royal Marsden NHS Fdn Trust, London, England. [Adlard, Julian] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Davidson, Rosemarie] Yorkhill Hosp, Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland. [Eccles, Diana M.] Univ Southampton, Fac Med, Southampton Univ Hosp NHS Trust, Southampton SO9 5NH, Hants, England. [Cole, Trevor] Birmingham Womens Hosp Healthcare NHS Trust, W Midlands Reg Genet Serv, Birmingham, W Midlands, England. [Cook, Jackie] Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield, S Yorkshire, England. [Brewer, Carole] Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England. [Douglas, Fiona] Newcastle Upon Tyne Hosp NHS Trust, Inst Med Genet, Ctr Life, Newcastle Upon Tyne, Tyne & Wear, England. [Morrison, Patrick J.] Belfast Hlth & Social Care Trust, No Ireland Reg Genet Ctr, Belfast, Antrim, North Ireland. [Morrison, Patrick J.] Queens Univ Belfast, Dept Med Genet, Belfast, Antrim, North Ireland. [Walker, Lisa] Churchill Hosp, Oxford Reg Genet Serv, Oxford, England. [Porteous, Mary E.] Western Gen Hosp, SE Scotland Reg Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland. [Kennedy, M. John] Trinity Coll Dublin, Acad Unit Clin & Mol Oncol, Dublin, Ireland. [Kennedy, M. John] St James Hosp, Dublin, Ireland. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Lawrence, KS 66045 USA. [Stoppa-Lyonnet, Dominique] Inst Curie, Serv Genet Oncol, F-75231 Paris, France. [Stoppa-Lyonnet, Dominique] Inst Curie, INSERM, Unite U830, F-75231 Paris, France. [Stoppa-Lyonnet, Dominique; Fassy-Colcombet, Marion; Castera, Laurent] Univ Paris 05, Fac Med, Paris, France. [Cornelis, Francois] Avicenne Hosp, AP HP, Genet Unit, Paris, France. [Cornelis, Francois] Sud Francilien Hosp, Evry, France. [Cornelis, Francois] Univ Hosp, Clermont Ferrand, France. [Bressac-de Paillerets, Brigitte] Inst Cancerol Gustave Roussy, Dept Genet, Villejuif, France. [Caron, Olivier] Inst Cancerol Gustave Roussy, Dept Med, Villejuif, France. [Pujol, Pascal; Coupier, Isabelle] CHU Arnaud Villeneuve, Unite Oncogenet, Montpellier, France. [Delnatte, Capucine; Akloul, Linda] Ctr Rene Gauducheau, Med Oncol Serv, F-44035 Nantes, France. [Lynch, Henry T.; Snyder, Carrie L.] Creighton Univ, Dept Prevent Med, Omaha, NE 68178 USA. [Buys, Saundra S.] Univ Utah, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT 84112 USA. [Goldgar, David E.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. [John, Esther M.] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA USA. [Miron, Alexander] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic 3010, Australia. [Hopper, John L.] Univ Melbourne, Peter MacCallum Canc Ctr, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Phillips, Kelly] Univ Melbourne, Peter MacCallum Canc Ctr, Div Canc Med, Melbourne, Vic, Australia. Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic, Australia. [Singer, Christian F.; Rappaport, Christine; Tea, Muy-Kheng M.; Fink-Retter, Anneliese] Med Univ Vienna, Dept OB GYN, Vienna, Austria. [Singer, Christian F.; Rappaport, Christine; Tea, Muy-Kheng M.; Fink-Retter, Anneliese] Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria. [Hansen, Thomas V. O.; Nielsen, Finn C.] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, Copenhagen, Denmark. [Arason, Adalgeir] Landspitali Univ Hosp, Dept Pathol, Liborius, Iceland. [Arason, Adalgeir] Univ Iceland, Fac Med, Reykjavik, Iceland. [Piedmonte, Marion] Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA. [Odunsi, Kunle O.] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. [Basil, Jack] GOGaffilitate, Dept Obstet & Gynecol, Good Samaritan Hosp, Cincinnati, OH USA. [Rubinstein, Wendy S.] NorthShore Univ Hlth Syst, Ctr Med Genet, Evanston, IL USA. [Rubinstein, Wendy S.] Univ Chicago, Pritzker Sch Med, Dept Med, Chicago, IL 60637 USA. [Boggess, John] Univ N Carolina, Chapel Hill, NC USA. [Wakeley, Katie] S Shore Hosp, Dana Farber Brigham & Womens Canc Ctr, S Weymouth, MA USA. [Ewart-Toland, Amanda] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol, Columbus, OH 43210 USA. [Ewart-Toland, Amanda] Ohio State Univ, Ctr Comprehens Canc, Dept Immunol & Med Genet, Columbus, OH 43210 USA. [Ewart-Toland, Amanda] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Columbus, OH 43210 USA. [Montagna, Marco; Agata, Simona] Ist Oncol Veneto IOV IRCCS, Immunol & Mol Oncol Unit, Padua, Italy. [Imyanitov, Evgeny N.] NN Petrov Inst Oncol, Oncol Mol Lab, St Petersburg, Russia. [Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Fisher Ctr Familial Canc Res, Washington, DC USA. [Janavicius, Ramunas] Vilnius Univ Hosp Santariskiu Clin, Hematol Oncol & Transfus Med Ctr, Dept Mol & Regenerat Med, Vilnius, Lithuania. [Lazaro, Conxi; Feliubadalo, Lidia] IDIBELL Catalan Inst Oncol, Hereditari Canc Program, Mol Diagnost Unit, Barcelona, Spain. [Blanco, Ignacio; Brunet, Joan] IDIBELL Catalan Inst Oncol, Hereditari Canc Program, Genet Counseling Unit, Barcelona, Spain. [Diez, Orland] Vall dHebron Univ Hosp, VHIO, Oncogenet Lab, Mol Med & Genet Program, Barcelona, Spain. [Olah, Edith] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary. [Teo, Soo Hwang] Univ Malaya, Univ Malaya Canc Res Inst, Breast Canc Res Unit, Subang Jaya, Malaysia. [Teo, Soo Hwang] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia. [Beattie, Mary S.] Univ Calif San Francisco, Dept Med Epidemiol & Biostat, San Francisco, CA 94143 USA. [van Rensburg, Elizabeth J.; Dorfling, Cecelia M.] Univ Pretoria, Dept Genet, Canc Genet Lab, ZA-0002 Pretoria, South Africa. [Kwong, Ava] Hong Kong Sanat & Hosp, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China. [Kwong, Ava] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong, Hong Kong, Peoples R China. [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, Dept Obstet & Gynaecol, Ctr Familial Breast & Ovarian Canc, Cologne, Germany. [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, CIO, Cologne, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Heinritz, Wolfram] Univ Leipzig, Inst Human Genet, Leipzig, Germany. [Meindl, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Div Tumor Genet, Dept Gynecol & Obstet, D-8000 Munich, Germany. [Ditsch, Nina] Univ Munich, Dept Obstet & Gynaecol, Munich, Germany. [Arnold, Norbert] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Obstet & Gynaecol, Kiel, Germany. [Heidemann, Simone] Univ Kiel, Univ Hosp Schleswig Holstein, Inst Human Genet, Kiel, Germany. [Niederacher, Dieter] Univ Dusseldorf, Univ Hosp Dusseldorf, Dept Obstet & Gynaecol, D-40225 Dusseldorf, Germany. [Preisler-Adams, Sabine] Univ Munster, Inst Human Genet, D-4400 Munster, Germany. [Gadzicki, Dorothea] Hannover Med Sch, Inst Cell & Mol Pathol, D-3000 Hannover, Germany. [Varon-Mateeva, Raymonda] Campus Virchov Klinikum, Inst Human Genet, Berlin, Germany. [Deissler, Helmut] Univ Hosp Ulm, Dept Obstet & Gynaecol, Ulm, Germany. [Gehrig, Andrea] Univ Wurzburg, Inst Human Genet, Dept Med Genet, Ctr Familial Breast & Ovarian Canc, D-8700 Wurzburg, Germany. [Kast, Karin] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Obstet & Gynaecol, D-01062 Dresden, Germany. [Fiebig, Britta] Univ Regensburg, Inst Human Genet, Regensburg, Germany. [Muranen, Taru A.; Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. [Muranen, Taru A.; Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Biomedicum, Helsinki, Finland. [Neuhausen, Susan L.; Ding, Yuan Chun] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA USA. [Peterlongo, Paolo; Radice, Paolo] Fdn Ist FIRC Oncol Mol, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predicted Med, Barcelona, Spain. [Peterlongo, Paolo; Radice, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy. [Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela] Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Predicted Med, Milan, Italy. [Barile, Monica] Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy. [Bernard, Loris] Ist Europeo Oncol, Dept Expt Oncol, Milan, Italy. [Bernard, Loris] Consortium Genom Technol Cogentech, Milan, Italy. [Viel, Alessandra] IRCCS, Ctr Riferimento Oncol, Unit Expt Oncol 1, Aviano, PN, Italy. [Giannini, Giuseppe] Univ Roma La Sapienza, Dept Expt Med, Rome, Italy. [Varesco, Liliana] Ist Nazl Ric Cancro IST, Dept Epidemiol Prevent & Special Funct, Unit Hereditary Canc, Genoa, Italy. [Greene, Mark H.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Couch, FJ (reprint author), Mayo Clin, Dept Lab Med & Pathol, Stabile 2-42,200 1st St SW, Rochester, MN 55905 USA. EM couch.fergus@mayo.edu RI Spurdle, Amanda/A-4978-2011; Feliubadalo, Lidia/G-4577-2016; , Ivan/D-6804-2012; Osorio, Ana/I-4324-2014; Bernard, Loris/K-5953-2014; BYRSKI, Tomasz/I-2844-2014; Ehrencrona, Hans/M-5619-2014; Jakubowska, Anna/O-8050-2014; Kets, M./L-4429-2015; Gronwald, Jacek/A-4576-2017; manoukian, siranoush/E-7132-2017; Peissel, Bernard/E-8187-2017; Shah, Sohela/B-3137-2013; Giannini, Giuseppe/B-5672-2013; Kwong, Ava/D-8005-2013; Andrulis, Irene/E-7267-2013; Joseph, Vijai/J-9158-2013; Radice, Paolo/O-3119-2013; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Blanco, Ignacio/D-2565-2013; Ditsch, Nina/F-6267-2014; Teo, Soo-hwang/H-2353-2014; Arnold, Norbert/E-3012-2010; montagna, marco/E-2225-2012; M Isabel, Tejada/E-2394-2012 OI Evans, Gareth/0000-0002-8482-5784; Spurdle, Amanda/0000-0003-1337-7897; Phillips, Kelly-Anne/0000-0002-0475-1771; Feliubadalo, Lidia/0000-0002-1736-0112; Kirchhoff, Tomas/0000-0002-9055-2364; Brunet, Joan/0000-0003-1945-3512; Nevanlinna, Heli/0000-0002-0916-2976; Jacobs, Chris/0000-0002-9557-9080; Muranen, Taru/0000-0002-5895-1808; Barrowdale, Daniel/0000-0003-1661-3939; TEJADA, Maria-Isabel/0000-0002-7334-1864; , Ivan/0000-0002-3108-058X; Eeles, Rosalind/0000-0002-3698-6241; Janavicius, Ramunas/0000-0002-3773-8485; Nathanson, Katherine/0000-0002-6740-0901; Ramus, Susan/0000-0003-0005-7798; Osorio, Ana/0000-0001-8124-3984; Ehrencrona, Hans/0000-0002-5589-3622; Gronwald, Jacek/0000-0002-3643-2871; manoukian, siranoush/0000-0002-6034-7562; Peissel, Bernard/0000-0001-9233-3571; Rappaport-Fuerhauser, Christine/0000-0002-6820-0020; Giannini, Giuseppe/0000-0003-0299-4056; Kwong, Ava/0000-0002-6968-9489; Joseph, Vijai/0000-0002-7933-151X; Blanco, Ignacio/0000-0002-7414-7481; Arnold, Norbert/0000-0003-4523-8808; montagna, marco/0000-0002-4929-2150; FU NIH [CA128978]; NCI [CA116201]; U.S. Department of Defence [W81XWH-10-1-0341]; Breast Cancer Research Foundation; Komen Foundation for the Cure; Cancer Research UK (CR-UK) [C12292/A11174, C1287/A10118]; European Community [223175 (HEALTH-F2-2009-223175)]; Canadian Institutes of Health Research; Canadian Breast Cancer Research Alliance [019511]; Research Council of Lithuania [LIG-19/2010]; Cancer Association of South Africa (CANSA); National Cancer Institute, NIH [RFA-CA-06-503]; Breast Cancer Family Registry (BCFR); Neye Foundation; Fundacion Mutua Madrilena; Asociacion Espanola Contra el Cancer; Spanish Ministry of Science and Innovation [FIS PI08 1120]; Basque Foundation for Health Innovation and Research (BIOEF) [BIO07/CA/006]; Ministero della Salute; Ministero dell'Universita' e Ricerca [RBLAO3-BETH]; Fondazione Italiana per la Ricerca sul Cancro; Associazione Italiana per la Ricerca sulCancro [4017]; Fondazione IRCCS Istituto Nazionale Tumori; DKFZ; CR-UK [C1287/A10118, C1287/A11990]; NIHR; Royal Marsden NHS Foundation Trust; German Cancer Aid [109076]; Centre of Molecular Medicine Cologne (CMMC); Ligue National Contre le Cancer; Association for International Cancer Research Grant [AICR-07-0454]; Association "Le cancer du sein, parlons-en!"; Familial Cancer Registry at Georgetown University (NIH/NCI) [P30-CA051008]; Cancer Genetics Network [HHSN261200744000C]; Swing Fore the Cure; Clinical Genetics Branch, DCEG; Community Oncology and Prevention Trials Program-COPTRG; Helsinki University Central Hospital; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]; ZonMW [91109024]; Hungarian Research Grant [KTIA-OTKACK-80745]; Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute; Autonomous Government of Catalonia; Polish Foundation of Science; Postgraduate School of Molecular Medicine, Warsaw Medical University; Icelandic Association "Walking for Breast Cancer Research"; Landspitali University Hospital; Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR); "Ministero della Salute" [RFPS 2006-5-341353, ACC2/R6.9]; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania; Cancer Foundation of Western Australia; NHMRC [145684, 288704, 454508]; FCCC; University of Kansas Cancer Center; Kansas Bioscience Authority Eminent Scholar Program; Jewish General Hospital; Starr Cancer Consortium; Norman and Carol Stone Cancer Research Initiative; Kate and Robert Niehaus Clinical Cancer Research Initiative; Lymphoma Foundation; Sabin Family Research Initiative; U.S. National Cancer Institute; Westat, Inc.; Russian Federation for Basic Research [10-04-92601, 10-04-92110, 11-04-00227]; Federal Agency for Science and Innovations [16.512.11.2237]; Cancer Care Ontario; U.S. National Cancer Institute, NIH under RFA [CA-06-503]; Ohio State University Comprehensive Cancer Center; Instituto Toscano Tumori grant; CARIF; University Malaya; Helen Diller Family Comprehensive Cancer Center at UCSF; Avon Foundation; Center for Translational and Policy Research in Personalized Medicine (TRANSPERS); NIH/NCI [P01 CA130818-02A1]; CRUK; American Cancer Society [SIOP-06-258-06-COUN]; [ISCIIIRETIC RD06/0020/1051]; [PI10/01422]; [PI10/31488]; [2009SGR290]; [U01CA69631]; [5U01CA113916]; [NO2-CP-11019-50]; [N02-CP-65504] FX This research was supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341), and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. This work was also supported by Cancer Research UK (CR-UK) grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement no. 223175 (HEALTH-F2-2009-223175). Support was also provided by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and by the Canadian Breast Cancer Research Alliance-grant #019511. A. C. Antoniou is a CR-UK Senior Cancer Research Fellow. D. F. Easton is CR-UK Principal Research Fellow. G. Chenevix-Trench6 is a NHMRC Senior Principal Research Fellow. BFBOCC was supported by the Research Council of Lithuania grant LIG-19/2010 to R. Janavicius. BMBSA was supported by grants from the Cancer Association of South Africa (CANSA) to E.J. van Rensburg. BCFR was supported by the National Cancer Institute, NIH under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Cancer Prevention Institute of California (formerly the Northern California Cancer Center; U01 CA69417), University of Melbourne (U01 CA69638), and Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46). CBCS was supported by The Neye Foundation. CNIO was partially supported by Fundacion Mutua Madrilena, Asociacion Espanola Contra el Cancer, the Spanish Ministry of Science and Innovation (FIS PI08 1120), and the Basque Foundation for Health Innovation and Research (BIOEF): BIO07/CA/006. CONSIT TEAM was supported by grants from Ministero della Salute (Extraordinary National Cancer Program 2006 "Alleanza contro il Cancro" to L. Varesco and P. Radice, and "Progetto Tumori Femminili" to P. Radice), Ministero dell'Universita' e Ricerca (RBLAO3-BETH to P. Radice), Fondazione Italiana per la Ricerca sul Cancro (Special Project "Hereditary tumors" to P. Radice), Associazione Italiana per la Ricerca sulCancro (4017 to P. Pujol), and by funds from Italian citizens who allocated the 5 x 1,000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects "5 x 1000"). The DKFZ study was supported by funds from the DKFZ. EMBRACE was supported by CR-UK Grants C1287/A10118 and C1287/A11990. D. G. Evans and Fiona Lalloo were supported by an NIHR grant to the Biomedical Research Centre, Manchester, UK. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust were supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. R. A. Eeles, Elizabeth Bancroft, and Lucia D'Mello were supported by CR-UK Grant C5047/A8385. GC-HBOC was supported by a grant of the German Cancer Aid (grant 109076) and by the Centre of Molecular Medicine Cologne (CMMC). The GEMO study was supported by the Ligue National Contre le Cancer; Association for International Cancer Research Grant (AICR-07-0454); and the Association "Le cancer du sein, parlons-en!" Award.; The Georgetown study was supported by the Familial Cancer Registry at Georgetown University (NIH/NCI grant P30-CA051008), the Cancer Genetics Network (HHSN261200744000C), and Swing Fore the Cure. GOG was supported through funding provided by both intramural (Clinical Genetics Branch, DCEG) and extramural (Community Oncology and Prevention Trials Program-COPTRG) NCI programs. K. Phillips is the Cancer Council Victoria, Colebatch Clinical Research Fellow. HEBCS was supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HEBON study was supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, and the ZonMW grant 91109024. HUNBOCS was supported by the Hungarian Research Grant KTIA-OTKACK-80745. ICO was supported by Asociacion Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia; contract grant numbers ISCIIIRETIC RD06/0020/1051, PI10/01422, PI10/31488, and 2009SGR290. IHCC was supported by a Polish Foundation of Science award to K. Jaworska, a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University. ILUH was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund. INHERIT was supported with J. Simard, Chairholder of the Canada Research Chair in Oncogenetics. IOVHBOCS was supported by Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR), and "Ministero della Salute" ("Progetto Tumori Femminili and grant numbers RFPS 2006-5-341353, ACC2/R6.9"). kConFab was supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC), and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. The kConFab Clinical Follow-Up Study was funded by the NHMRC [145684, 288704, 454508]. A.-B. Skytte is supported by a NHMRC Senior Research Fellowship. A. K. Godwin was funded by U01CA69631, 5U01CA113916, and the Eileen Stein Jacoby Fund while at FCCC. The author acknowledges support from The University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program. A. K. Godwin is the Chancellors Distinguished Chair in Biomedical Sciences endowed Professor. The McGill study was supported by the Jewish General Hospital Weekend to End Breast Cancer. M. Thomassen holds a Fonds de la Recherche en Sante du Quebec clinician-scientist award. The MSKCC study was supported by the Starr Cancer Consortium, the Breast Cancer Research Foundation, the Norman and Carol Stone Cancer Research Initiative, the Kate and Robert Niehaus Clinical Cancer Research Initiative, the Lymphoma Foundation, and the Sabin Family Research Initiative. The NCI study was supported by the Intramural Research Program of the U.S. National Cancer Institute and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc. NNPIO was supported by the Russian Federation for Basic Research (grants 10-04-92601, 10-04-92110, 11-04-00227) and the Federal Agency for Science and Innovations (contract 16.512.11.2237). OCGN was supported by Cancer Care Ontario and the U.S. National Cancer Institute, NIH under RFA # CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators.; OSU-CCG was supported by the Ohio State University Comprehensive Cancer Center. PBCS was supported by an Instituto Toscano Tumori grant to M. A. Caligo. SEABASS was supported by CARIF and University Malaya. The UCSF study was supported by the Helen Diller Family Comprehensive Cancer Center at UCSF, the Avon Foundation, and the Center for Translational and Policy Research in Personalized Medicine (TRANSPERS), NIH/NCI P01 CA130818-02A1. UKFOCR was supported by a project grant from CRUK to P. P. D. Pharoah. The UPENN study was supported Komen Foundation for the Cure to S. M. Domchek, the Breast Cancer Research Foundation to K. L. Nathanson, and NIH grants R01-CA083855 and R01-CA102776 to T. R. Rebbeck. WCRI was supported by the American Cancer Society Clinical Research Professorship # SIOP-06-258-06-COUN. NR 24 TC 24 Z9 24 U1 2 U2 24 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2012 VL 21 IS 4 BP 645 EP 657 DI 10.1158/1055-9965.EPI-11-0888 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 918AG UT WOS:000302220600010 PM 22351618 ER PT J AU Orom, UA Lim, MK Savage, JE Jin, LJ Saleh, AD Lisanti, MP Simone, NL AF Orom, Ulf Andersson Lim, Meng K. Savage, Jason E. Jin, Lianjin Saleh, Anthony D. Lisanti, Michael P. Simone, Nicole L. TI MicroRNA-203 regulates caveolin-1 in breast tissue during caloric restriction SO CELL CYCLE LA English DT Article DE microRNA; caloric restriction; breast cancer; caveolin-1; p63; longevity ID PROSTATE-CANCER; MESSENGER-RNAS; EXPRESSION; MIR-203; CELLS; TRANSLATION; MECHANISMS; CARCINOMA; STEMNESS; TARGETS AB Caloric restriction has been shown to increase lifespan in several organisms and to delay onset of age-related diseases. The transcriptional response to caloric restriction has been studied for mRNAs, while the microRNA signature following caloric restriction remains unexplored. Here, we characterize the microRNA expression in mouse breast tissue before and after caloric restriction, reporting several changes in the microRNA expression profile. In particular, miR-203 is found to be highly induced by caloric restriction, and we demonstrate that caveolin-1 as well as p63 are direct targets of miR-203 in vivo during caloric restriction. Using tissue culture models, we suggest that this regulation is important in both mouse and human. In conclusion, we show that the microRNA response induced by caloric restriction can regulate important factors in processes such as longevity and aging and is an integral and important component of the cellular response to caloric restriction. C1 [Orom, Ulf Andersson; Lim, Meng K.; Jin, Lianjin; Simone, Nicole L.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Radiat Oncol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. [Savage, Jason E.; Saleh, Anthony D.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Lisanti, Michael P.] Thomas Jefferson Univ, Jefferson Med Coll, Stem Cell Biol & Regenerat Med Ctr, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. RP Simone, NL (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Radiat Oncol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. EM nicole.simone@jeffersonhospital.org RI Lisanti, Michael/C-6866-2013; OI Orom, Ulf/0000-0002-0643-0592 FU NIH; Kimmel Cancer Center Radiation Oncology Facility; NCI Cancer Center [P30 CA56036] FX This research was supported in part by the Intramural Research Program of the NIH and also the Kimmel Cancer Center Radiation Oncology Facility, which is supported partly by NCI Cancer Center Grant P30 CA56036. NR 35 TC 19 Z9 20 U1 2 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR 1 PY 2012 VL 11 IS 7 BP 1291 EP 1295 DI 10.4161/cc.11.7.19704 PG 5 WC Cell Biology SC Cell Biology GA 918XQ UT WOS:000302285300011 PM 22421148 ER PT J AU Quijano, C Cao, L Fergusson, MM Romero, H Liu, J Gutkind, S Rovira, II Mohney, RP Karoly, ED Finkel, T AF Quijano, Celia Cao, Liu Fergusson, Maria M. Romero, Hector Liu, Jie Gutkind, Sarah Rovira, Ilsa I. Mohney, Robert P. Karoly, Edward D. Finkel, Toren TI Oncogene-induced senescence results in marked metabolic and bioenergetic alterations SO CELL CYCLE LA English DT Article DE oncogene-induced senescence; metabolomics; Ras; fatty acid oxidation ID CELLULAR SENESCENCE; LIFE-SPAN; CELLS; STRESS; PURIFICATION; CONTRIBUTES; CARBOXYLASE; MORTALITY; OXIDATION; ELEGANS AB Oncogene-induced senescence (OIS) is characterized by permanent growth arrest and the acquisition of a secretory, pro-inflammatory state. Increasingly, OIS is viewed as an important barrier to tumorgenesis. Surprisingly, relatively little is known about the metabolic changes that accompany and therefore may contribute to OIS. Here, we have performed a metabolomic and bioenergetic analysis of Ras-induced senescence. Profiling approximately 300 different intracellular metabolites reveals that cells that have undergone OIS develop a unique metabolic signature that differs markedly from cells undergoing replicative senescence. A number of lipid metabolites appear uniquely increased in OIS cells, including a marked increase in the level of certain intracellular long chain fatty acids. Functional studies reveal that this alteration in the metabolome reflects substantial changes in overall lipid metabolism. In particular, Ras-induced senescent cells manifest a decline in lipid synthesis and a significant increase in fatty acid oxidation. Increased fatty acid oxidation results in an unexpectedly high rate of basal oxygen consumption in cells that have undergone OIS. Pharmacological or genetic inhibition of carnitine palmitoyltransferase 1, the rate-limiting step in mitochondrial fatty acid oxidation, restores a pre-senescent metabolic rate and, surprisingly, selectively inhibits the secretory, pro-inflammatory state that accompanies OIS. Thus, Ras-induced senescent cells demonstrate profound alterations in their metabolic and bioenergetic profiles, particularly with regards to the levels, synthesis and oxidation of free fatty acids. Furthermore, the inflammatory phenotype that accompanies OIS appears to be related to these underlying changes in cellular metabolism. C1 [Quijano, Celia; Cao, Liu; Fergusson, Maria M.; Liu, Jie; Gutkind, Sarah; Rovira, Ilsa I.; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. [Quijano, Celia] Univ Republica, Dept Bioquim, Fac Med, Montevideo, Uruguay. [Romero, Hector] Univ Republica, Lab Org & Evoluc Genoma, Fac Ciencias CURE, Montevideo, Uruguay. [Mohney, Robert P.; Karoly, Edward D.] Metabolon Incorporated, Res Triangle Pk, NC USA. RP Finkel, T (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA. EM finkelt@nih.gov FU NIH FX This work was supported by NIH Intramural funds. NR 50 TC 23 Z9 24 U1 0 U2 15 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD APR 1 PY 2012 VL 11 IS 7 BP 1383 EP 1392 DI 10.4161/cc.11.7.19800 PG 10 WC Cell Biology SC Cell Biology GA 918XQ UT WOS:000302285300021 PM 22421146 ER PT J AU Samoshkin, A Dulev, S Loukinov, D Rosenfeld, JA Strunnikov, AV AF Samoshkin, Alexander Dulev, Stanimir Loukinov, Dmitry Rosenfeld, Jeffrey A. Strunnikov, Alexander V. TI Condensin dysfunction in human cells induces nonrandom chromosomal breaks in anaphase, with distinct patterns for both unique and repeated genomic regions SO CHROMOSOMA LA English DT Article ID DNA-DAMAGE RESPONSE; CENTROMERIC CHROMATIN; SOMATIC MUTATIONS; CANCER GENOME; TRANSCRIPTION; SEGREGATION; RDNA; CATALOG; COHESIN AB Condensin complexes are essential for chromosome condensation and segregation in mitosis, while condensin dysfunction, among other pathways leading to chromosomal bridging in mitosis, may play a role in tumor genomic instability, including recently discovered chromotripsis. To characterize potential double-strand breaks specifically occurring in late anaphase, human chromosomes depleted of condensin were analyzed by gamma-H2AX ChIP followed by high-throughput sequencing (ChIP-seq). In condensin-depleted cells, the nonrepeated parts of the genome were shown to contain distinct gamma-H2AX enrichment zones 75% of which overlapped with known hemizygous deletions in cancers. Furthermore, some tandemly repeated DNA sequences, analyzed separately from the rest of the genome, showed significant gamma-H2AX enrichment in condensin-depleted anaphases. The most commonly occurring targets of such enrichment included simple repeats, centromeric satellites, and rDNA. The two latter categories indicate that acrocentric human chromosomes are especially susceptible to breaks upon condensin deficiency. The genomic regions that are specifically destabilized upon condensin dysfunction may constitute a condensin-specific chromosome destabilization pattern. C1 [Loukinov, Dmitry; Strunnikov, Alexander V.] NIAID, NIH, Immunopathol Lab, Rockville, MD 20852 USA. [Samoshkin, Alexander] NCI, NIH, Genome Struct & Funct Sect, Bethesda, MD 20892 USA. [Dulev, Stanimir] Univ Munich, Adolf Butenandt Inst, D-80539 Munich, Germany. [Rosenfeld, Jeffrey A.] Univ Med & Dent New Jersey, Div High Performance & Res Comp, Newark, NJ 07103 USA. RP Strunnikov, AV (reprint author), NIAID, NIH, Immunopathol Lab, Rockville, MD 20852 USA. EM strunnik@mail.nih.gov RI perumal, murugiah/D-1565-2012; OI Strunnikov, Alexander/0000-0002-9058-2256 NR 31 TC 11 Z9 11 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-5915 EI 1432-0886 J9 CHROMOSOMA JI Chromosoma PD APR PY 2012 VL 121 IS 2 BP 191 EP 199 DI 10.1007/s00412-011-0353-6 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 915UZ UT WOS:000302054300007 PM 22179743 ER PT J AU Tarique, AA Kalsy, A Arifuzzaman, M Rollins, SM Charles, RC Leung, DT Harris, JB LaRocque, RC Sheikh, A Bhuiyan, MS Saksena, R Clements, JD Calderwood, SB Qadri, F Kovac, P Ryan, ET AF Tarique, A. A. Kalsy, A. Arifuzzaman, M. Rollins, S. M. Charles, R. C. Leung, D. T. Harris, J. B. LaRocque, R. C. Sheikh, A. Bhuiyan, M. S. Saksena, R. Clements, J. D. Calderwood, S. B. Qadri, F. Kovac, P. Ryan, E. T. TI Transcutaneous Immunization with a Vibrio cholerae O1 Ogawa Synthetic Hexasaccharide Conjugate following Oral Whole-Cell Cholera Vaccination Boosts Vibriocidal Responses and Induces Protective Immunity in Mice SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID HEAT-LABILE ENTEROTOXIN; INFECTION-DERIVED IMMUNITY; ADP-RIBOSYLATING EXOTOXINS; ESCHERICHIA-COLI; MUCOSAL ADJUVANTS; VECTOR STRAINS; SEROTYPE OGAWA; CVD 103-HGR; EL-TOR; TOXIN AB A shortcoming of currently available oral cholera vaccines is their induction of relatively short-term protection against cholera compared to that afforded by wild-type disease. We were interested in whether transcutaneous or subcutaneous boosting using a neoglycoconjugate vaccine made from a synthetic terminal hexasaccharide of the O-specific polysaccharide of Vibrio cholerae O1 (Ogawa) coupled to bovine serum albumin as a carrier (CHO-BSA) could boost lipopolysaccharide (LPS)-specific and vibriocidal antibody responses and result in protective immunity following oral priming immunization with whole-cell cholera vaccine. We found that boosting with CHO-BSA with immunoadjuvantative cholera toxin (CT) or Escherichia coli heat-labile toxin (LT) following oral priming with attenuated V. cholerae O1 vaccine strain O395-NT resulted in significant increases in serum anti-V. cholerae LPS IgG, IgM, and IgA (P < 0.01) responses as well as in anti-Ogawa (P < 0.01) and anti-Inaba (P < 0.05) vibriocidal titers in mice. The LPS-specific IgA responses in stool were induced by transcutaneous (P < 0.01) but not subcutaneous immunization. Immune responses following use of CT or LT as an adjuvant were comparable. In a neonatal mouse challenge assay, immune serum from boosted mice was associated with 79% protective efficacy against death. Our results suggest that transcutaneous and subcutaneous boosting with a neoglycoconjugate following oral cholera vaccination may be an effective strategy to prolong protective immune responses against V. cholerae. C1 [Tarique, A. A.; Kalsy, A.; Arifuzzaman, M.; Rollins, S. M.; Charles, R. C.; Leung, D. T.; Harris, J. B.; LaRocque, R. C.; Calderwood, S. B.; Ryan, E. T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Tarique, A. A.; Arifuzzaman, M.; Sheikh, A.; Bhuiyan, M. S.; Qadri, F.] Icddr B, Ctr Vaccine Sci, Dhaka, Bangladesh. [Charles, R. C.; Leung, D. T.; LaRocque, R. C.; Calderwood, S. B.; Ryan, E. T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Harris, J. B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Saksena, R.; Kovac, P.] NIDDK, LBC, NIH, Bethesda, MD USA. [Clements, J. D.] Tulane Univ, Sch Med, Dept Microbiol & Immunol, New Orleans, LA 70112 USA. [Calderwood, S. B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Ryan, E. T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM etryan@partners.org RI Tarique, Abdullah/M-2860-2013; Kovac, Pavol/B-8813-2008; OI Tarique, Abdullah/0000-0003-3782-345X; Kovac, Pavol/0000-0001-5044-3449; Rollins, Sean/0000-0002-3724-1989; leung, daniel/0000-0001-8401-0801 FU National Institutes of Health-NIDDK; International Centre for Diarrheal Diseases Research, Bangladesh (icddr,b); National Institutes of Health; National Institute of Allergy & Infectious Diseases [U01 AI077883, U01 AI058935, R03 AI063079]; Fogarty International Center [D43 TW005572]; American Recovery and Reinvestment Act (ARRA) Postdoctoral Fellowship in Global Infectious Diseases [TW005572, K01 TW07409, TW07144, K08 AI089721]; Howard Hughes Medical Institute; Harvard Initiative for Global Health Postdoctoral Fellowship in Global Infectious Diseases FX This work was supported by the Intramural Research Program of the National Institutes of Health-NIDDK, the International Centre for Diarrheal Diseases Research, Bangladesh (icddr,b) (F. Q., A. A. T.), grants from the National Institutes of Health, including the National Institute of Allergy & Infectious Diseases (U01 AI077883 [E. T. R.], U01 AI058935 [S. B. C., E. T. R.], and R03 AI063079 [F. Q.]), the Fogarty International Center Training Grant in Vaccine Development and Public Health (D43 TW005572 [A. A. T., M. A., A. S., M. S. B., F. Q., E. T. R.]), an American Recovery and Reinvestment Act (ARRA) Postdoctoral Fellowship in Global Infectious Diseases (TW005572 [D. T. L., R. C. L.]), and Career Development Awards (K01 TW07409 [J.B.H.], TW07144 [R. C. L.], and K08 AI089721 [R. C. C.]), a Physician-Scientist Early Career Award from the Howard Hughes Medical Institute (R. C. L.), and a Harvard Initiative for Global Health Postdoctoral Fellowship in Global Infectious Diseases (D.T.L.). NR 49 TC 11 Z9 12 U1 1 U2 6 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 APR PY 2012 VL 19 IS 4 BP 594 EP 602 DI 10.1128/CVI.05689-11 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 917FA UT WOS:000302156700018 PM 22357651 ER PT J AU Bowen, RAR Dowdell, KC Dale, JK Drake, SK Fleisher, TA Hortin, GL Remaley, AT Nexo, E Rao, VK AF Bowen, Raffick A. R. Dowdell, Kennichi C. Dale, Janet K. Drake, Steven K. Fleisher, Thomas A. Hortin, Glen L. Remaley, Alan T. Nexo, Ebba Rao, V. Koneti TI Elevated vitamin B-12 levels in autoimmune lymphoproliferative syndrome attributable to elevated haptocorrin in lymphocytes SO CLINICAL BIOCHEMISTRY LA English DT Article DE ALPS; Vitamin B12; Cobalamin; Germline; Haptocorrin; Transcobolamin ID TRANSCOBALAMIN; COBALAMIN; APOPTOSIS AB Objective: Identify the etiology of elevated B-12 in autoimmune lymphoproliferative syndrome (ALPS). Design: Peripheral blood of ALPS patients with elevated B-12 and controls were evaluated. Results: Total and holo-haptocorrin (HC) levels were 26- and 23-fold higher in ALPS patients, respectively. No abnormal B-12-binding proteins were found. Western blot revealed HC in lymphocyte lysates only from ALPS patients. Conclusion: Elevated concentrations of B-12 found in ALPS patients were due to increased lymphocyte expression of HC. (C) 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. C1 [Bowen, Raffick A. R.] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. [Dowdell, Kennichi C.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Dale, Janet K.] NIAID, DAIT, Clin Res Program, NIH, Bethesda, MD 20892 USA. [Drake, Steven K.] NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. [Fleisher, Thomas A.; Remaley, Alan T.] NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. [Hortin, Glen L.; Nexo, Ebba] Aarhus Univ Hosp, Dept Clin Biochem, DK-8000 Aarhus, Denmark. [Rao, V. Koneti] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Bowen, RAR (reprint author), Stanford Univ, Sch Med, Dept Pathol, 300 Pasteur Dr,Room H1507B, Stanford, CA 94305 USA. EM rbowen@stanfordmed.org FU National Institute of Allergy and Infectious Diseases; Warren Grant Magnuson Clinical Center FX This research was supported by the intramural programs of the National Institute of Allergy and Infectious Diseases and the Warren Grant Magnuson Clinical Center. NR 10 TC 7 Z9 8 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0009-9120 J9 CLIN BIOCHEM JI Clin. Biochem. PD APR PY 2012 VL 45 IS 6 BP 490 EP 492 DI 10.1016/j.clinbiochem.2012.01.016 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 916OA UT WOS:000302111900023 PM 22306884 ER PT J AU Marchbanks, PA Curtis, KM Mandel, MG Wilson, HG Jeng, G Folger, SG McDonald, JA Daling, JR Bernstein, L Malone, KE Wingo, PA Simon, MS Norman, SA Strom, BL Ursin, G Weiss, LK Burkman, RT Spirtas, R AF Marchbanks, Polly A. Curtis, Kathryn M. Mandel, Michele G. Wilson, Hoyt G. Jeng, Gary Folger, Suzanne G. McDonald, Jill A. Daling, Janet R. Bernstein, Leslie Malone, Kathleen E. Wingo, Phyllis A. Simon, Michael S. Norman, Sandra A. Strom, Brian L. Ursin, Giske Weiss, Linda K. Burkman, Ronald T. Spirtas, Robert TI Oral contraceptive formulation and risk of breast cancer SO CONTRACEPTION LA English DT Article DE Oral contraceptives; Breast cancer; Hormones; Epidemiology; Case-control studies ID YOUNG-WOMEN; POTENCY AB Background: While evidence on the association between oral contraceptive (OC) use and breast cancer generally suggests little or no increased risk, the question of whether breast cancer risk varies by OC formulation remains controversial. Few studies have examined this issue because large samples and extensive OC histories are required. Study Design: We used data from a multicenter, population-based, case control investigation. Women aged 35-64 years were interviewed. To explore the association between OC formulation and breast cancer risk, we used conditional logistic regression to derive adjusted odds ratios, and we used likelihood ratio tests for heterogeneity to assess whether breast cancer risk varied by OC formulation. Key OC exposure variables were ever use, current or former use, duration of use and time since last use. To strengthen inferences about specific formulations, we restricted most analyses to the 2282 women with breast cancer and the 2424 women without breast cancer who reported no OC use or exclusive use of one OC. Results: Thirty-eight formulations were reported by the 2674 women who used one OC; most OC formulations were used by only a few women. We conducted multivariable analyses on the 10 formulations that were each used by at least 50 women and conducted supplemental analyses on selected formulations of interest based on recent research. Breast cancer risk did not vary significantly by OC formulation, and no formulation was associated with a significantly increased breast cancer risk. Conclusions: These results add to the small body of literature on the relationship between OC formulation and breast cancer. Our data are reassuring in that, among women 35-64 years of age, we found no evidence that specific OC formulations increase breast cancer risk. Published by Elsevier Inc. C1 [Marchbanks, Polly A.; Curtis, Kathryn M.; Mandel, Michele G.; Wilson, Hoyt G.; Jeng, Gary; Folger, Suzanne G.; McDonald, Jill A.; Wingo, Phyllis A.] Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA 30333 USA. [Daling, Janet R.; Malone, Kathleen E.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA USA. [Simon, Michael S.] Wayne State Univ, Karmanos Canc Inst, Div Hematol & Oncol, Detroit, MI USA. [Simon, Michael S.] Wayne State Univ, Karmanos Canc Inst, Populat Studies & Prevent Program, Detroit, MI USA. [Norman, Sandra A.; Strom, Brian L.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Norman, Sandra A.; Strom, Brian L.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Ursin, Giske] Canc Registry Norway, Oslo, Norway. [Ursin, Giske] Univ Oslo, Dept Nutr, Oslo, Norway. [Ursin, Giske] Univ So Calif, Los Angeles, CA USA. [Weiss, Linda K.] NCI, Off Canc Ctr, Bethesda, MD 20892 USA. [Burkman, Ronald T.] Tufts Univ, Sch Med, Dept Obstet & Gynecol, Springfield, MA 01199 USA. [Burkman, Ronald T.] Baystate Med Ctr, Springfield, MA USA. [Spirtas, Robert] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. RP Marchbanks, PA (reprint author), Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA 30333 USA. EM pam2@cdc.gov FU National Institute of Child Health and Human Development; National Cancer institute; Emory University [N01-HD-3-3168]; Fred Hutchinson Cancer Research Center [N01-HD-2-3166]; Karmanos Cancer Institute at Wayne State University [N01-HD-3-3174]; University of Pennsylvania [N01-HD-3-3176]; University of Southern California [N01-HD-3-3175]; Centers for Disease Control and Prevention [Y01-HD-7022] FX This 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-3-3168), Fred Hutchinson Cancer Research Center (N01-HD-2-3166), Karmanos Cancer Institute at Wayne State University (N01-HD-3-3174), University of Pennsylvania (N01-HD-3-3176) and University of Southern California (N01-HD-3-3175) and through an intra-agency agreement with the Centers for Disease Control and Prevention (Y01-HD-7022). The Centers for Disease Control and Prevention contributed additional staff and computer support. Surveillance, Epidemiology and End Results (SEER) Programs of the National Cancer Institute provided assistance for study sites in Atlanta (N01-PC-67006), Detroit (N01-CN-65064), Los Angeles (N01-PC-67010) and Seattle (N01-CN-0532). NR 30 TC 13 Z9 13 U1 3 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD APR PY 2012 VL 85 IS 4 BP 342 EP 350 DI 10.1016/j.contraception.2011.08.007 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 915BY UT WOS:000301999100004 PM 22067757 ER PT J AU Cassidy, OL Matheson, B Osborn, R Vannucci, A Kozlosky, M Shomaker, LB Yanovski, SZ Tanofsky-Kraff, M AF Cassidy, Omni L. Matheson, Brittany Osborn, Robyn Vannucci, Anna Kozlosky, Merel Shomaker, Lauren B. Yanovski, Susan Z. Tanofsky-Kraff, Marian TI Loss of control eating in African-American and Caucasian youth SO EATING BEHAVIORS LA English DT Article DE African-American; Loss of control eating; Child; Adolescent; Energy intake; Obesity ID BODY-MASS INDEX; WEIGHT-GAIN; INTERPERSONAL PSYCHOTHERAPY; OVERWEIGHT CHILDREN; ADOLESCENT GIRLS; PUBERTAL CHANGES; FOOD INSECURITY; COLLEGE-WOMEN; US CHILDREN; WHITE AB Loss of control (LOC) eating, a disinhibited eating behavior shown to predict excessive weight gain in youth, has been reported by African-American children and adolescents. Yet, little is known about how LOC-eating manifests in this population. To investigate potential racial differences in LOC-eating, the Eating Disorder Examination was administered to 185 non-Hispanic African-American and Caucasian youth ages 8-17 y. Objective eating was assessed at two test meals during which youth ate ad libitum from a multi-item lunchtime food array. African-American and Caucasian youth reported a similar prevalence of LOC episodes (24.2% vs. 28.9%, p=.75). Yet, accounting for sex, age, fat-free mass, percent fat mass, height, and socioeconomic status, African-Americans consumed more total energy at both laboratory meals (1608 +/- 57 kcal vs. 1362 +/- 44 kcal; p<.001). Furthermore, African-American youth reporting LOC consumed the most total energy across both meals (1855 +/- 104 kcal) compared to African-Americans without LOC (1524 +/- 60 kcal), Caucasians with LOC (1278 +/- 68 kcal), and Caucasians without LOC (1399 +/- 46 kcal; p<.001). Future research is required to examine whether LOC-eating contributes to the high rates of obesity in African-American youth. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Cassidy, Omni L.; Matheson, Brittany; Osborn, Robyn; Vannucci, Anna; Shomaker, Lauren B.; Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. [Cassidy, Omni L.; Matheson, Brittany; Shomaker, Lauren B.; Yanovski, Susan Z.; Tanofsky-Kraff, Marian] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, Bethesda, MD 20814 USA. [Kozlosky, Merel] Ctr Clin, Dept Nutr, Bethesda, MD 20814 USA. [Yanovski, Susan Z.] Natl Inst Diabet & Digest & Kidney Dis NIDDK, Div Digest Dis & Nutr, NIH, DHHS, Bethesda, MD 20814 USA. RP Tanofsky-Kraff, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM mtanofsky@usuhs.edu FU Intramural NIH HHS [Z01 HD000641-12]; NICHD NIH HHS [ZIA HD000641]; PHS HHS [1ZIAHD000641] NR 49 TC 7 Z9 7 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1471-0153 J9 EAT BEHAV JI Eat. Behav. PD APR PY 2012 VL 13 IS 2 BP 174 EP 178 DI 10.1016/j.eatbeh.2012.01.003 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 915BI UT WOS:000301997500021 PM 22365807 ER PT J AU Appel, S Duke, ES Martinez, AR Khan, OI Dustin, IM Reeves-Tyer, P Berl, MB Sato, S Gaillard, WD Theodore, WH AF Appel, Shmuel Duke, Elizabeth S. Martinez, Ashley R. Khan, Omar I. Dustin, Irene M. Reeves-Tyer, Patricia Berl, Madison B. Sato, Susumu Gaillard, William D. Theodore, William H. TI Cerebral blood flow and fMRI BOLD auditory language activation in temporal lobe epilepsy SO EPILEPSIA LA English DT Article DE Positron emission tomography; Cerebral blood flow; Functional magnetic resonance imaging; Temporal lobe epilepsy; Language; Blood oxygen level-dependent ID LOCALIZATION-RELATED EPILEPSY; VASCULAR MALFORMATIONS; CORTICAL STIMULATION; FUNCTIONAL-ANATOMY; ATYPICAL LANGUAGE; FOCAL EPILEPSY; HUMAN-BRAIN; LATERALIZATION; CHILDREN; REORGANIZATION AB Purpose: Blood oxygen leveldependent (BOLD) functional magnetic resonance imaging (fMRI), an important research and clinical tool, depends on relatively greater transient increases in (regional cerebral blood flow) rCBF than cerebral metabolic rate for oxygen during neural activity. We investigated whether reduced resting rCBF in patients with temporal lobe epilepsy affects BOLD signal during fMRI language mapping. Methods: We used [O-15] water positron emission tomography (PET) to measure rCBF, and 3 Tesla echo planar imaging (EPI) BOLD fMRI with an auditory description decision task in 33 patients with temporal lobe epilepsy (16 men; mean age 33.6 +/- standard deviation [SD] 10.6 years; epilepsy onset 14.8 +/- 10.6 years; mean duration 18.8 +/- 13.2 years; 23 left focus, 10 right focus). Anatomic regions drawn on structural MRI, based on the Wake Forest Pick Atlas, included Wernicke's area (WA), inferior frontal gyrus (IFG), middle frontal gyrus (MFG), and hippocampus (HC). Laterality indices (LIs), and asymmetry indices (AIs), were calculated on coregistered fMRI and PET. Key Findings: Twelve patients had mesial temporal sclerosis (seven on the left), two patients had a tumor or malformation of cortical development (both left), one patient a right temporal cyst, and 18 patients had normal MRI (14 left). Decreasing relative left WA CBF correlated with decreased left IFG voxel activation and decreasing left IFG LI. However, CBF WA AI was not related to left WA voxel activation itself or WA LI. There was a weak positive correlation between absolute CBF and fMRI activation in left IFG, right IFG, and left WA. Patients with normal and abnormal MRI did not differ in fMRI activation or rCBF AIs. Significance: Reduced WA rCBF is associated with reduced fMRI activation in IFG but notWAitself, suggesting distributed network effects, but not impairment of underlying BOLD response. Hypoperfusion in TLE does not affect fMRI clinical value. C1 [Appel, Shmuel; Duke, Elizabeth S.; Martinez, Ashley R.; Khan, Omar I.; Dustin, Irene M.; Reeves-Tyer, Patricia; Gaillard, William D.; Theodore, William H.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. [Appel, Shmuel; Khan, Omar I.; Sato, Susumu] NINDS, EEG Lab, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Duke, Elizabeth S.; Berl, Madison B.; Gaillard, William D.] Childrens Natl Med Ctr, Ctr Neurosci, Washington, DC 20010 USA. RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, NIH, Bldg 10,Room 7C-103, Bethesda, MD 20892 USA. EM theodorw@ninds.nih.gov FU NINDS NIH Division of Intramural Research FX Supported by NINDS NIH Division of Intramural Research. NR 42 TC 5 Z9 5 U1 2 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD APR PY 2012 VL 53 IS 4 BP 631 EP 638 DI 10.1111/j.1528-1167.2012.03403.x PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 915ZG UT WOS:000302065600011 PM 22332720 ER PT J AU Cabib, E Blanco, N Arroyo, J AF Cabib, Enrico Blanco, Noelia Arroyo, Javier TI Presence of a Large beta(1-3)Glucan Linked to Chitin at the Saccharomyces cerevisiae Mother-Bud Neck Suggests Involvement in Localized Growth Control SO EUKARYOTIC CELL LA English DT Article ID YEAST-CELL WALL; ONE-STEP PURIFICATION; BUDDING YEAST; CROSS-LINKING; ARCHITECTURE; PROTEIN; CYCLE; RING; CYTOKINESIS; SEPTINS AB Previous results suggested that the chitin ring present at the yeast mother-bud neck, which is linked specifically to the nonreducing ends of beta(1-3) glucan, may help to suppress cell wall growth at the neck by competing with beta(1-6) glucan and thereby with mannoproteins for their attachment to the same sites. Here we explored whether the linkage of chitin to beta(1-3) glucan may also prevent the remodeling of this polysaccharide that would be necessary for cell wall growth. By a novel mild procedure, beta(1-3) glucan was isolated from cell walls, solubilized by carboxymethylation, and fractionated by size exclusion chromatography, giving rise to a very high-molecular-weight peak and to highly polydisperse material. The latter material, soluble in alkali, may correspond to glucan being remodeled, whereas the large-size fraction would be the final cross-linked structural product. In fact, the beta(1-3) glucan of buds, where growth occurs, is solubilized by alkali. A gas1 mutant with an expected defect in glucan elongation showed a large increase in the polydisperse fraction. By a procedure involving sodium hydroxide treatment, carboxymethylation, fractionation by affinity chromatography on wheat germ agglutinin-agarose, and fractionation by size chromatography on Sephacryl columns, it was shown that the beta(1-3) glucan attached to chitin consists mostly of high-molecular-weight material. Therefore, it appears that linkage to chitin results in a polysaccharide that cannot be further remodeled and does not contribute to growth at the neck. In the course of these experiments, the new finding was made that part of the chitin forms a noncovalent complex with beta(1-3) glucan. C1 [Cabib, Enrico] NIDDK, Natl Inst Hlth, Dept Hlth & Human Serv, Lab Biochem & Genet, Bethesda, MD USA. [Blanco, Noelia; Arroyo, Javier] Univ Complutense Madrid, Fac Farm, Dept Microbiol 2, Madrid, Spain. RP Cabib, E (reprint author), NIDDK, Natl Inst Hlth, Dept Hlth & Human Serv, Lab Biochem & Genet, Bethesda, MD USA. EM enricoc@bdg10.niddk.nih.gov RI Arroyo, Javier/E-9308-2016 OI Arroyo, Javier/0000-0002-1971-1721 FU National Institutes of Health (NIDDK); Ministerio de Ciencia e Innovacion [MICINN], Spain [BIO2010-22146, GR58/08, 920640]; Universidad Complutense de Madrid; European Science Foundation [06-RNP-132]; MICINN [BES-2008-003171] FX This study was supported by a National Institutes of Health grant (Intramural Research Program, NIDDK). J.A. and N.B. were supported by projects BIO2010-22146 (Ministerio de Ciencia e Innovacion [MICINN], Spain) and GR58/08 (reference no. 920640; Universidad Complutense de Madrid) and the European Science Foundation Research Networking Programme (06-RNP-132). N.B. is the recipient of an FPI Ph.D. fellowship (BES-2008-003171) from MICINN. NR 30 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 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD APR PY 2012 VL 11 IS 4 BP 388 EP 400 DI 10.1128/EC.05328-11 PG 13 WC Microbiology; Mycology SC Microbiology; Mycology GA 917ZT UT WOS:000302219300002 PM 22366124 ER PT J AU Kemmerich, K Drechsler, M Weber, C Murphy, PM Soehnlein, O AF Kemmerich, K. Drechsler, M. Weber, C. Murphy, P. M. Soehnlein, O. TI Lack of Formyl-peptide receptor 1 reduces atherosclerotic lesion formation SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Meeting Abstract C1 [Kemmerich, K.; Drechsler, M.; Weber, C.; Soehnlein, O.] Univ Munich, Inst Cardiovasc Prevent, Munich, Germany. [Murphy, P. M.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD APR PY 2012 VL 42 SU 1 BP 22 EP 22 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 914WY UT WOS:000301985000058 ER PT J AU Peng, F Tao, QF Wu, XM Dou, H Spencer, S Mang, CY Xu, L Sun, LL Zhao, Y Li, HB Zeng, S Liu, GM Hao, XJ AF Peng, Fang Tao, Qiaofeng Wu, Xiumei Dou, Hui Spencer, Shawn Mang, Chaoyong Xu, Lu Sun, Lianli Zhao, Yu Li, Haibo Zeng, Su Liu, Guangming Hao, Xiaojiang TI Cytotoxic, cytoprotective and antioxidant effects of isolated phenolic compounds from fresh ginger SO FITOTERAPIA LA English DT Article DE Ginger phenolics; Antioxidant; Cytotoxicity; Neuroprotection; Hepatoprotectant; alpha-Glucosidase; QSAR ID ZINGIBER-OFFICINALE ROSCOE; NEONATAL-RAT HEPATOCYTES; XANTHINE-OXIDASE; ALPINIA-OFFICINARUM; LIPID-PEROXIDATION; DIABETIC-RATS; IN-VITRO; HYDROGEN-PEROXIDE; CURCUMIN ANALOGS; OXIDATIVE STRESS AB Twenty-nine phenolic compounds were isolated from the root bark of fresh (Yunnan) ginger and their structures fully characterized. Selected compounds were divided into structural categories and twelve compounds subjected to in-vitro assays including DPPH radical scavenging, xanthine-oxidase inhibition, monoamine oxidase inhibition, rat-brain homogenate lipid peroxidation, and rat pheochromocytoma PC12 cell and primary liver cell viability to determine their antioxidant and cytoprotective properties. Isolated compounds were also tested against nine human tumor cell lines to characterize anticancer potency. Several diarylheptanoids and epoxidic diarylheptanoids were effective DPPH radical scavengers and moderately effective at inhibiting xanthine oxidase. An enone-dione analog of 6-shogaol (compound 2) was isolated and identified to be most effective at protecting PC12 cells from H2O2-induced damage. Almost all tested compounds inhibited lipid peroxidation. Three compounds, 6-shogaol, 10-gingerol and an enone-diatylheptanoid analog of curcumin (compound 6) were identified to be cytotoxic in cell lines tested, with KB and HL60 cells most susceptible to 6-shogaol and the curcumin analog with IC50<10 mu M. QSAR analysis revealed cytotoxicity was related to compound lipophilicity and chemical reactivity. In conclusion, we observed distinct compounds in fresh ginger to have biological activities relevant in diseases associated with reactive oxygen species. (C) 2012 Elsevier B.V. All rights reserved. C1 [Peng, Fang; Wu, Xiumei; Mang, Chaoyong; Xu, Lu; Zhao, Yu; Li, Haibo; Liu, Guangming] Dali Univ, Coll Pharmaceut Sci, Key Lab Yunnan Insect Drug R&D, Dali 671000, Peoples R China. [Tao, Qiaofeng; Dou, Hui; Sun, Lianli; Li, Haibo; Zeng, Su] Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China. [Spencer, Shawn] NCI, Clin Pharmacol Program, Ctr Canc Res, SAIC Frederick Inc, Frederick, MD 21702 USA. [Hao, Xiaojiang] Key Lab Chem & Nat Prod Guizhou Prov, Guiyang 550002, Peoples R China. [Hao, Xiaojiang] Chinese Acad Sci, Guiyang 550002, Peoples R China. RP Zhao, Y (reprint author), Dali Univ, Coll Pharmaceut Sci, Key Lab Yunnan Insect Drug R&D, Wanhua Rd, Dali 671000, Peoples R China. EM dryuzhao@126.com; zengsu@zju.edu.cn FU High Rank Talents Invited Project [2009CI121]; Yunnan Science and Technology Department (Modernization of Chinese Technology Industry Base Construction in Yunnan Province) [2008IF012]; Foundation for the Science and Technology Innovation Team of Yunnan Universities [11]; Zhejiang University FX The authors thank the High Rank Talents Invited Project (No. 2009CI121), Key Industrialization Innovation Project of Yunnan Science and Technology Department (Modernization of Chinese Technology Industry Base Construction in Yunnan Province, No. 2008IF012), Foundation for the Science and Technology Innovation Team of Yunnan Universities (2010-No.11) and 985 fund of Zhejiang University for the financial supports. NR 92 TC 28 Z9 29 U1 5 U2 45 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0367-326X J9 FITOTERAPIA JI Fitoterapia PD APR PY 2012 VL 83 IS 3 BP 568 EP 585 DI 10.1016/j.fitote.2011.12.028 PG 18 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 916NB UT WOS:000302109400020 PM 22248534 ER PT J AU Lee, TL Raygada, MJ Rennert, OM AF Lee, Tin-Lap Raygada, Margarita J. Rennert, Owen M. TI Integrative gene network analysis provides novel regulatory relationships, genetic contributions and susceptible targets in autism spectrum disorders SO GENE LA English DT Article DE Autism; Genetics; Genomics; CNV; Systems biology ID COPY NUMBER VARIATION; CHILDREN; ASSOCIATION; VARIANTS; EXPRESSION; REVEALS; 5P14.1; COMMON; BRAIN AB Autism spectrum disorders (ASDs) are a group of diseases exhibiting impairment in social drive, communication/language skills and stereotyped behaviors. Though an increased number of candidate genes and molecular interactions have been identified by various approaches, the pathogenesis remains elusive. Based on clinical observations, data from accessible GWAS and expression datasets we identified ASDs gene candidates. Integrative gene network and a novel CNV-centric Node Network (CNN) analysis method highlighted ASDs-associated key elements and biological processes. Functional analysis identified neurological functions including synaptic cholinergic receptor (CHRNA) families, dopamine receptor (DRD2), and correlations between social behavior and oxytocin related pathways. CNN analysis of genome-wide genetic and expression data identified inheritance-related clusters related to PTEN/TSC1/FMR1 and mTor/PI3K regulation. Integrative analysis identified potential regulators of networks, specifically TNF and beta-estradiol, suggesting a potential central role in ASDs. Our data provide information on potential disease mechanisms. and key regulators that may generate novel postulations, and diagnostic molecular biomarkers. Published by Elsevier B.V. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin & Dev Gen, Natl Inst Hlth, Bethesda, MD 20892 USA. [Lee, Tin-Lap] Chinese Univ Hong Kong, Sch Biomed Sci, Sha Tin, Hong Kong, Peoples R China. [Lee, Tin-Lap] Chinese Univ Hong Kong, Sch Biomed Sci, Dev & Endocrinol Program, Hong Kong, Hong Kong, Peoples R China. RP Rennert, OM (reprint author), 49 Convent Dr Room 2A06,MSC 4429, Bethesda, MD 20892 USA. EM leetl@mail.nih.gov; RaygadaM@mail.nih.gov; rennerto@mail.nih.gov RI Lee, Tin-Lap/A-7853-2009 OI Lee, Tin-Lap/0000-0002-6654-0988 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This work was supported by the Intramural Research Program of Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 36 TC 18 Z9 19 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 1 PY 2012 VL 496 IS 2 BP 88 EP 96 DI 10.1016/j.gene.2012.01.020 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 915CE UT WOS:000301999700003 PM 22306264 ER PT J AU Nogales, FF Goyenaga, P Preda, O Nicolae, A Vieites, B Ruiz-Marcellan, MC Pedrosa, A Merino, MJ AF Nogales, Francisco F. Goyenaga, Pablo Preda, Ovidiu Nicolae, Alina Vieites, Begona Carmen Ruiz-Marcellan, Maria Pedrosa, Alberto Merino, Maria J. TI An analysis of five clear cell papillary cystadenomas of mesosalpinx and broad ligament: four associated with von Hippel-Lindau disease and one aggressive sporadic type SO HISTOPATHOLOGY LA English DT Article DE clear cell papillary cystadenoma; clear cell papillary renal cell carcinoma; mesonephric rests; mesosalpinx; sporadic; von Hippel-Lindau disease ID TUMOR; CARCINOMA; EPIDIDYMIS; ADENOCARCINOMA; EXPRESSION; DIAGNOSIS; MUTATION; TISSUES; CERVIX; TRACT AB Aims: Clear cell papillary cystadenoma (CCPC) is associated with von Hippel- Lindau disease (VHLD), but rarely involves mesosalpinx and broad ligament (M/BL). This study provides new data about its behaviour and immunophenotype. Methods and results: We performed an analysis of four benign cases of CCPC of M/BL with either characteristic clinical features or genetic markers [loss of heterozygosity (LOH)] of VHLD in patients ranging from 24 to 36 years and a sporadic case in a 52- yearold presenting with peritoneal metastases. All CCPCs were papillary but had solid and tubular areas. Haemorrhage, thrombosis and scarring were constant features and related to an unusual pattern of subepithelial vascularity. All clear or oxyphilic cells coexpressed cytokeratin 7 (CK7), CAM5.2 and vimentin, with strong apical CD10 and nuclear paired box gene 2 (PAX2) immunoreactivity. Three cases also showed positivity for VHL40, epithelial membrane antigen (EMA), Wilms' tumour suppressor gene (WT-1) and cancer antigen 125 (CA125) but only one expressed renal cell carcinoma (RCC) antigen. Vascular plexus overexpressed nuclear and cytoplasmic WT-1. Conclusion: The VHLD-associated cases appeared to be benign, but the sporadic case exhibited a low malignant potential. CCPCs show histological and immunophenotypical similarities with the recently reported clear cell papillary RCC, although the previously unreported apical CD10 and nuclear PAX2 expression may be related to their mesonephric origin. CCPC has a distinctive sub-epithelial vascular pattern that is consistent with its pathogenesis. C1 [Nogales, Francisco F.; Goyenaga, Pablo; Preda, Ovidiu; Nicolae, Alina] Hosp Univ San Cecilio, Dept Pathol, Granada 18012, Spain. [Vieites, Begona] Hosp Univ Virgen Rocio, Seville, Spain. [Carmen Ruiz-Marcellan, Maria] Hosp Gen Valle Hebron, Barcelona, Spain. [Pedrosa, Alberto] Complejo Hosp Univ, Vigo, Spain. NCI, Translat Surg Pathol Sect, Bethesda, MD 20892 USA. RP Nogales, FF (reprint author), Hosp Univ San Cecilio, Dept Pathol, Av Madrid 11, Granada 18012, Spain. EM fnogales@ugr.es NR 26 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD APR PY 2012 VL 60 IS 5 BP 748 EP 757 DI 10.1111/j.1365-2559.2011.04151.x PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 915GO UT WOS:000302012300007 PM 22296276 ER PT J AU Zhang, MF Liang, LM Morar, N Dixon, AL Lathrop, GM Ding, J Moffatt, MF Cookson, WOC Kraft, P Qureshi, AA Han, JL AF Zhang, Mingfeng Liang, Liming Morar, Nilesh Dixon, Anna L. Lathrop, G. Mark Ding, Jun Moffatt, Miriam F. Cookson, William O. C. Kraft, Peter Qureshi, Abrar A. Han, Jiali TI Integrating pathway analysis and genetics of gene expression for genome-wide association study of basal cell carcinoma SO HUMAN GENETICS LA English DT Article ID RENAL-TRANSPLANT RECIPIENTS; SKIN-CANCER; MOLECULAR TARGETS; COMPLEX DISEASES; COMMON VARIANTS; HLA ANTIGENS; RISK; SUSCEPTIBILITY; LOCI; INTERLEUKIN-6 AB Genome-wide association studies (GWASs) have primarily focused on marginal effects for individual markers and have incorporated external functional information only after identifying robust statistical associations. We applied a new approach combining the genetics of gene expression and functional classification of genes to the GWAS of basal cell carcinoma (BCC) to identify potential biological pathways associated with BCC. We first identified 322,324 expression-associated single-nucleotide polymorphisms (eSNPs) from two existing GWASs of global gene expression in lymphoblastoid cell lines (n = 955), and evaluated the association of these functionally annotated SNPs with BCC among 2,045 BCC cases and 6,013 controls in Caucasians. We then grouped them into 99 KEGG pathways for pathway analysis and identified two pathways associated with BCC with p value < 0.05 and false discovery rate (FDR) < 0.5: the autoimmune thyroid disease pathway (mainly HLA class I and II antigens, p < 0.001, FDR = 0.24) and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway (p = 0.02, FDR = 0.49). Seventy-nine (25.7%) out of 307 significant eSNPs in the JAK-STAT pathway were associated with BCC risk (p < 0.05) in an independent replication set of 278 BCC cases and 1,262 controls. In addition, the association of JAK-STAT signaling pathway was marginally validated using 16,691 eSNPs identified from 110 normal skin samples (p = 0.08). Based on the evidence of biological functions of the JAK-STAT pathway on oncogenesis, it is plausible that this pathway is involved in BCC pathogenesis. C1 [Zhang, Mingfeng; Qureshi, Abrar A.; Han, Jiali] Harvard Univ, Sch Med, Brigham & Womens Hosp, Clin Res Program,Dept Dermatol, Boston, MA 02115 USA. [Zhang, Mingfeng] Nanjing Med Univ, Dept Epidemiol & Biostat, Ctr Canc, Nanjing, Jiangsu, Peoples R China. [Liang, Liming; Kraft, Peter; Han, Jiali] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Liang, Liming; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Morar, Nilesh; Dixon, Anna L.; Moffatt, Miriam F.; Cookson, William O. C.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Lathrop, G. Mark] Ctr Natl Genotypage, Evry, France. [Ding, Jun] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. [Qureshi, Abrar A.; Han, Jiali] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. RP Han, JL (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Clin Res Program,Dept Dermatol, 181 Longwood Ave,5th Floor, Boston, MA 02115 USA. EM jiali.han@channing.harvard.edu RI Ding, Jun/G-3918-2011 FU NIH [CA87969, CA055075, CA49449] FX The authors thank Dr. David Hunter, Dr. Frank B. Hu, and Dr. Eric B. Rimm for their work on the five GWAS sets (BC_NHS, T2D_NHS, T2D_HPFS CHD_NHS and CHD_HPFS). They thank Dr. Hongmei Nan for her work in BCC GWAS dataset construction and Dr. Mousheng Xu for his technical support in programing. They thank the participants in the Nurses' Health Study and the Health Professionals Follow-Up Study for their dedication and commitment. They also thank the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The NHS and HPFS cohorts are supported by NIH grants CA87969, CA055075, and CA49449. NR 55 TC 14 Z9 15 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD APR PY 2012 VL 131 IS 4 BP 615 EP 623 DI 10.1007/s00439-011-1107-5 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 911NX UT WOS:000301725900007 PM 22006220 ER PT J AU Crosslin, DR McDavid, A Weston, N Nelson, SC Zheng, XW Hart, E de Andrade, M Kullo, IJ McCarty, CA Doheny, KF Pugh, E Kho, A Hayes, MG Pretel, S Saip, A Ritchie, MD Crawford, DC Crane, PK Newton, K Li, RL Mirel, DB Crenshaw, A Larson, EB Carlson, CS Jarvik, GP AF Crosslin, David R. McDavid, Andrew Weston, Noah Nelson, Sarah C. Zheng, Xiuwen Hart, Eugene de Andrade, Mariza Kullo, Iftikhar J. McCarty, Catherine A. Doheny, Kimberly F. Pugh, Elizabeth Kho, Abel Hayes, M. Geoffrey Pretel, Stephanie Saip, Alexander Ritchie, Marylyn D. Crawford, Dana C. Crane, Paul K. Newton, Katherine Li, Rongling Mirel, Daniel B. Crenshaw, Andrew Larson, Eric B. Carlson, Chris S. Jarvik, Gail P. CA Med Records Genomics eMERGE TI Genetic variants associated with the white blood cell count in 13,923 subjects in the eMERGE Network SO HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; LARGE-SCALE; ASTHMA; RISK; LOCI; SUSCEPTIBILITY; POPULATION; CONSORTIUM; COMMON AB White blood cell count (WBC) is unique among identified inflammatory predictors of chronic disease in that it is routinely measured in asymptomatic patients in the course of routine patient care. We led a genome-wide association analysis to identify variants associated with WBC levels in 13,923 subjects in the electronic Medical Records and Genomics (eMERGE) Network. We identified two regions of interest that were each unique to subjects of genetically determined ancestry to the African continent (AA) or to the European continent (EA). WBC varies among different ancestry groups. Despite being ancestry specific, these regions were identifiable in the combined analysis. In AA subjects, the region surrounding the Duffy antigen/chemokine receptor gene (DARC) on 1q21 exhibited significant association (p value = 6.71e-55). These results validate the previously reported association between WBC and of the regulatory variant rs2814778 in the promoter region, which causes the Duffy negative phenotype (Fy-/-). A second missense variant (rs12075) is responsible for the two principal antigens, Fya and Fyb of the Duffy blood group system. The two variants, consisting of four alleles, act in concert to produce five antigens and subsequent phenotypes. We were able to identify the marginal and novel interaction effects of these two variants on WBC. In the EA subjects, we identified significantly associated SNPs tagging three separate genes in the 17q21 region: (1) GSDMA, (2) MED24, and (3) PSMD3. Variants in this region have been reported to be associated with WBC, neutrophil count, and inflammatory diseases including asthma and Crohn's disease. C1 [Crosslin, David R.; Nelson, Sarah C.; Zheng, Xiuwen] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Crosslin, David R.; Jarvik, Gail P.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [McDavid, Andrew; Carlson, Chris S.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Weston, Noah; Hart, Eugene; Newton, Katherine; Larson, Eric B.] Grp Hlth Res Inst, Seattle, WA 98124 USA. [de Andrade, Mariza] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA. [Kullo, Iftikhar J.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN 55905 USA. [McCarty, Catherine A.] Essentia Inst Rural Hlth, Duluth, MN 55805 USA. [Doheny, Kimberly F.; Pugh, Elizabeth] Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD 21224 USA. [Kho, Abel] Northwestern Univ, Div Gen Internal Med, Chicago, IL 60611 USA. [Kho, Abel] Northwestern Univ, Div Hlth & Biomed Informat, Chicago, IL 60611 USA. [Hayes, M. Geoffrey] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA. [Pretel, Stephanie] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Saip, Alexander] Vanderbilt Univ, Vanderbilt Inst Clin & Translat Res, Nashville, TN 37232 USA. [Ritchie, Marylyn D.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. [Crawford, Dana C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Crawford, Dana C.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37232 USA. [Crane, Paul K.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. [Li, Rongling] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA. [Mirel, Daniel B.; Crenshaw, Andrew] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. RP Crosslin, DR (reprint author), Univ Washington, Dept Biostat, Floor 15,UW Tower,Campus Mail Box 359461, Seattle, WA 98195 USA. EM davidcr@u.washington.edu RI Ritchie, Marylyn/C-1114-2012; Crawford, Dana/C-1054-2012; Crane, Paul/C-8623-2014; Jarvik, Gail/N-6476-2014; OI McDavid, Andrew/0000-0002-6581-1213; Zheng, Xiuwen/0000-0002-1390-0708; Jarvik, Gail/0000-0002-6710-8708; Crane, Paul/0000-0003-4278-7465; Nelson, Sarah/0000-0002-2109-6465 FU National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, MD, USA [HG004610, AG06781, HG04599, HG004608, HG004609, HG004438, HG004424, HG004603]; University of Washington's Northwest Institute of Genetic Medicine [265508] FX The authors are grateful to all the participants in the eMERGE study. They also acknowledge Xiuwen Zheng and the fast PCA program to make principal component analysis on this many subjects achievable. This study was supported by the following U01 grants from the National Human Genome Research Institute (NHGRI), a component of the National Institutes of Health (NIH), Bethesda, MD, USA: (1) HG004610, AG06781 (Group Health Cooperative), (2) HG04599 (Mayo Clinic), (3) HG004608 (Marsh-field Clinic), (4) HG004609 (Northwestern University), (5) HG004438 (CIDR), (6) HG004424 (BROAD), and (7) HG004603 (Vanderbilt University). Additional support was provided by the University of Washington's Northwest Institute of Genetic Medicine from Washington State Life Sciences Discovery funds (Grant 265508). NR 35 TC 52 Z9 52 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD APR PY 2012 VL 131 IS 4 BP 639 EP 652 DI 10.1007/s00439-011-1103-9 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 911NX UT WOS:000301725900009 PM 22037903 ER PT J AU Mendonca, VRR Luz, NF Santos, NJG Borges, VM Goncalves, MS Andrade, BB Barral-Netto, M AF Mendonca, Vitor R. R. Luz, Nivea F. Santos, Nadja J. G. Borges, Valeria M. Goncalves, Marilda S. Andrade, Bruno B. Barral-Netto, Manoel TI Association between the Haptoglobin and Heme Oxygenase 1 Genetic Profiles and Soluble CD163 in Susceptibility to and Severity of Human Malaria SO INFECTION AND IMMUNITY LA English DT Article ID HEMOGLOBIN SCAVENGER RECEPTOR; PLASMODIUM-FALCIPARUM MALARIA; MICROSATELLITE POLYMORPHISM; HUMAN MONOCYTES; RISK-FACTOR; HEMOPHAGOCYTIC SYNDROME; RHEUMATOID-ARTHRITIS; BRAZILIAN AMAZON; CEREBRAL MALARIA; ELEVATED LEVELS AB Intravascular hemolysis is a hallmark event in the immunopathology of malaria that results in increased systemic concentrations of free hemoglobin (Hb). The oxidation of Hb by free radicals causes the release of heme, which amplifies inflammation. To circumvent the detrimental effects of free heme, hosts have developed several homeostatic mechanisms, including the enzyme haptoglobin (Hp), which scavenges cell-free Hb, the monocyte receptor CD163, which binds to Hb-Hp complexes, and heme oxygenase-1 (HO-1), which degrades intracellular free heme. We tested the association between these three main components of the host response to hemolysis and susceptibility to malaria in a Brazilian population. The genetic profiles of the HMOX1 and Hp genes and the plasma levels of a serum inflammatory marker, the soluble form of the CD163 receptor (sCD163), were studied in 264 subjects, including 78 individuals with symptomatic malaria, 106 individuals with asymptomatic malaria, and 80 uninfected individuals. We found that long (GT)n repeats in the microsatellite polymorphism region of the HMOX1 gene, the Hp2 allele, and the Hp2.2 genotype were associated with symptomatic malaria. Moreover, increased plasma concentrations of heme, Hp, HO-1, and sCD163 were associated with susceptibility to malaria. The validation of these results could support the development of targeted therapies and aid in reducing the severity of malaria. C1 [Mendonca, Vitor R. R.; Luz, Nivea F.; Santos, Nadja J. G.; Borges, Valeria M.; Goncalves, Marilda S.; Barral-Netto, Manoel] Fundacao Oswaldo Cruz FIOCRUZ, Ctr Pesquisas Goncalo Moniz, Salvador, BA, Brazil. [Mendonca, Vitor R. R.; Luz, Nivea F.; Borges, Valeria M.; Barral-Netto, Manoel] Univ Fed Bahia, Fac Med, Salvador, BA, Brazil. [Borges, Valeria M.; Barral-Netto, Manoel] Inst Nacl Ciencia & Tecnol Invest Imunol Iii INCT, Sao Paulo, Brazil. [Goncalves, Marilda S.] Univ Fed Bahia, Fac Farm, Salvador, BA, Brazil. [Andrade, Bruno B.] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Barral-Netto, M (reprint author), Fundacao Oswaldo Cruz FIOCRUZ, Ctr Pesquisas Goncalo Moniz, Salvador, BA, Brazil. EM mbarral@bahia.fiocruz.br RI Andrade, Bruno/J-9111-2012; Barral Netto, Manoel/B-3904-2009; Imunologia, Inct/I-2124-2013; Goncalves, Marilda/B-5904-2014; Borges, Valeria/G-2009-2014; OI Andrade, Bruno/0000-0001-6833-3811; Barral Netto, Manoel/0000-0002-5823-7903; Borges, Valeria/0000-0002-2775-5409 NR 70 TC 26 Z9 26 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2012 VL 80 IS 4 BP 1445 EP 1454 DI 10.1128/IAI.05933-11 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 914EL UT WOS:000301931900016 PM 22290142 ER PT J AU Tutterrow, YL Avril, M Singh, K Long, CA Leke, RJ Sama, G Salanti, A Smith, JD Leke, RGF Taylor, DW AF Tutterrow, Yeung L. Avril, Marion Singh, Kavita Long, Carole A. Leke, Robert J. Sama, Grace Salanti, Ali Smith, Joseph D. Leke, Rose G. F. Taylor, Diane W. TI High Levels of Antibodies to Multiple Domains and Strains of VAR2CSA Correlate with the Absence of Placental Malaria in Cameroonian Women Living in an Area of High Plasmodium falciparum Transmission SO INFECTION AND IMMUNITY LA English DT Article ID PREGNANCY-ASSOCIATED MALARIA; CHONDROITIN-SULFATE-A; LOW-BIRTH-WEIGHT; ADHESION-INHIBITORY ANTIBODIES; VACCINE CANDIDATE VAR2CSA; VARIANT SURFACE-ANTIGENS; INFECTED ERYTHROCYTES; INFANT-MORTALITY; PROTEIN VAR2CSA; VAR GENES AB Placental malaria, caused by sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, is associated with increased risk of maternal morbidity and poor birth outcomes. The parasite antigen VAR2CSA (variant surface antigen 2-chondroitin sulfate A) is expressed on infected erythrocytes and mediates binding to chondroitin sulfate A, initiating inflammation and disrupting homeostasis at the maternal-fetal interface. Although antibodies can prevent sequestration, it is unclear whether parasite clearance is due to antibodies to a single Duffy binding-like (DBL) domain or to an extensive repertoire of antibodies to multiple DBL domains and allelic variants. Accordingly, plasma samples collected longitudinally from pregnant women were screened for naturally acquired antibodies against an extensive panel of VAR2CSA proteins, including 2 to 3 allelic variants for each of 5 different DBL domains. Analyses were performed on plasma samples collected from 3 to 9 months of pregnancy from women living in areas in Cameroon with high and low malaria transmission. The results demonstrate that high antibody levels to multiple VAR2CSA domains, rather than a single domain, were associated with the absence of placental malaria when antibodies were present from early in the second trimester until term. Absence of placental malaria was associated with increasing antibody breadth to different DBL domains and allelic variants in multigravid women. Furthermore, the antibody responses of women in the lower-transmission site had both lower magnitude and lesser breadth than those in the high-transmission site. These data suggest that immunity to placental malaria results from high antibody levels to multiple VAR2CSA domains and allelic variants and that antibody breadth is influenced by malaria transmission intensity. C1 [Tutterrow, Yeung L.; Taylor, Diane W.] Univ Hawaii, John A Burns Sch Med, Dept Trop Med Med Microbiol & Pharmacol, Honolulu, HI 96822 USA. [Avril, Marion; Smith, Joseph D.] Seattle Biomed Res Inst, Seattle, WA 98109 USA. [Singh, Kavita] NIAID, Struct Biol Sect, Res Technol Branch, NIH, Rockville, MD USA. [Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [Leke, Robert J.; Sama, Grace; Leke, Rose G. F.] Univ Yaounde I, Fac Med & Biomed Res, Ctr Biotechnol, Yaounde, Cameroon. [Salanti, Ali] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Ctr Med Parasitol, Copenhagen, Denmark. [Salanti, Ali] Copenhagen Univ Hosp, Rigshosp, Dept Infect Dis, Copenhagen, Denmark. RP Taylor, DW (reprint author), Univ Hawaii, John A Burns Sch Med, Dept Trop Med Med Microbiol & Pharmacol, Honolulu, HI 96822 USA. EM dwtaylor@hawaii.edu FU Malaria Research Team at the Biotechnology Center, University of Yaounde I, Cameroon; NIAID, NIH [UO1AI43888, RO1AI071160, U19AI089688]; Division of Intramural Research, NIAID, NIH; STOPPAM [200889] FX We acknowledge the support of the Malaria Research Team at the Biotechnology Center, University of Yaounde I, Cameroon, for their outstanding work. A special thank you goes to the women and their families who participated in the studies. We also thank Ian Pagano, Cancer Research Center, University of Hawaii, for statistical support and Kazutoyo Miura for helpful suggestions in manuscript preparation.; The work was supported by grants UO1AI43888 and RO1AI071160 (D.W.T. and R.G.F.L.) and U19AI089688 (J.D.S.) from NIAID, NIH, by the intramural research program of the Division of Intramural Research, NIAID, NIH (K.S. and C.A.L.), and by FP7/2007-2013 under grant agreement no. 200889 (STOPPAM) (A.S.). NR 56 TC 32 Z9 32 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2012 VL 80 IS 4 BP 1479 EP 1490 DI 10.1128/IAI.00071-12 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 914EL UT WOS:000301931900019 PM 22331427 ER PT J AU Clark, EH Silva, CJ Weiss, GE Li, SP Padilla, C Crompton, PD Hernandez, JN Branch, OH AF Clark, Eva H. Silva, Claudia J. Weiss, Greta E. Li, Shanping Padilla, Carlos Crompton, Peter D. Hernandez, Jean N. Branch, OraLee H. TI Plasmodium falciparum Malaria in the Peruvian Amazon, a Region of Low Transmission, Is Associated with Immunologic Memory SO INFECTION AND IMMUNITY LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; C-TERMINAL FRAGMENT; BAY COHORT PROJECT; ANTIBODY-RESPONSES; CLINICAL IMMUNITY; CHILDREN; ANTIGEN; INFECTIONS; PARASITE; INVASION AB The development of clinical immunity to Plasmodium falciparum malaria is thought to require years of parasite exposure, a delay often attributed to difficulties in developing protective antibody levels. In this study, we evaluated several P. falciparum vaccine candidate antigens, including apical membrane antigen 1 (AMA-1), circumsporozoite protein (CSP), erythrocyte binding antigen 175 (EBA-175), and the 19-kDa region of merozoite surface protein 1 (MSP1(19)). After observing a more robust antibody response to MSP1(19), we evaluated the magnitude and longevity of IgG responses specific to this antigen in Peruvian adults and children before, during, and after P. falciparum infection. In this low-transmission region, even one reported prior infection was sufficient to produce a positive anti-MSP1(19) IgG response for > 5 months in the absence of reinfection. We also observed an expansion of the total plasmablast (CD19(+) CD27(+) CD38(high)) population in the majority of individuals shortly after infection and detected MSP1-specific memory B cells in a subset of individuals at various postinfection time points. This evidence supports our hypothesis that effective antimalaria humoral immunity can develop in low-transmission regions. C1 [Clark, Eva H.; Branch, OraLee H.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Silva, Claudia J.; Hernandez, Jean N.] Univ Nacl Amazonia Peruana, Lab Invest Prod Nat Antiparasitarios Amazonia, Iquitos, Peru. [Weiss, Greta E.; Li, Shanping; Crompton, Peter D.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Padilla, Carlos] Inst Nacl Salud, Lab Biotecnol & Biol Mol, Lima, Peru. [Branch, OraLee H.] NYU, Sch Med, Dept Med Parasitol, New York, NY USA. RP Branch, OH (reprint author), Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. EM Oralee.Branch@nyumc.org RI Crompton, Peter/N-1130-2016 FU National Institutes of Health/National Institute of Allergy and Infectious Disease [AI064831] FX This study was supported by R01 grant AI064831 from the National Institutes of Health/National Institute of Allergy and Infectious Disease (from 2005 to the present). NR 43 TC 24 Z9 24 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2012 VL 80 IS 4 BP 1583 EP 1592 DI 10.1128/IAI.05961-11 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 914EL UT WOS:000301931900030 PM 22252876 ER PT J AU Zanella, A Cressoni, M Epp, M Hoffmann, V Stylianou, M Kolobow, T AF Zanella, Alberto Cressoni, Massimo Epp, Myra Hoffmann, Viktoria Stylianou, Mario Kolobow, Theodor TI Effects of tracheal orientation on development of ventilator-associated pneumonia: an experimental study SO INTENSIVE CARE MEDICINE LA English DT Article DE Mechanical ventilation; Pneumonia; Ventilator-associated pneumonia; Semirecumbent position; Intubation; Postural drainage; Pulmonary; Pigs; Nosocomial infections; Respiration; Artificial/adverse effects; Intratracheal/adverse effects; Respiratory tract infections/prevention and control; Aspiration/prevention and control ID CARE-UNIT PATIENTS; NOSOCOMIAL PNEUMONIA; RESPIRATORY-TRACT; MECHANICAL VENTILATION; SEMIRECUMBENT POSITION; BACTERIAL-COLONIZATION; PULMONARY ASPIRATION; ENDOTRACHEAL-TUBE; BODY POSITION; PATHOGENESIS AB Orientation of the trachea and tracheal tube below horizontal may prevent aspiration of oropharyngeal secretions into the lungs, which is a pivotal pathway in the pathogenesis of ventilator-associated pneumonia (VAP). The incidence of VAP was evaluated in swine with orientation of trachea and tracheal tube above horizontal (model of semirecumbent position, currently recommended in patients) and below horizontal. Twenty-six mini-pigs were randomized into four groups: (A) eight mechanically ventilated with orientation of trachea 45A degrees above horizontal for 72 h. In the remaining groups (B, C, D) the trachea was oriented 10A degrees below horizontal, with (B) six mechanically ventilated for 72 h, (C) six mechanically ventilated for 72 h with enteral feeding, and (D) six mechanically ventilated for 168 h with enteral feeding. At the end of the study period, all pigs were sacrificed and the clinical diagnosis of VAP was microbiologically evaluated. No antibiotics were administered. All eight pigs kept orientated with the trachea 45A degrees above horizontal developed VAP and respiratory failure (PaO2/FiO2 = 132 +/- A 139 mmHg) with a median of 5.5 pulmonary lobes out of 6 colonized with average colonization of 9.3 x 10(7) CFU/g. None of the 18 pigs kept oriented with the trachea below horizontal developed VAP; 16 had sterile lungs, while 2, ventilated for 7 days, developed a low level of colonization. Orientation of the trachea above horizontal was uniformly associated with VAP and respiratory failure; positioning the trachea below horizontal consistently prevented development of VAP. C1 [Cressoni, Massimo] Univ Milan, Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Dipartimento Anestesiol Terapia Intens & Sci Derm, Milan, Italy. [Zanella, Alberto; Cressoni, Massimo; Epp, Myra; Kolobow, Theodor] NHLBI, NIH, Sect Pulm & Cardiac Assist Devices, Pulm & Crit Care Med Branch, Bethesda, MD 20892 USA. [Zanella, Alberto] Milano Bicocca Univ, San Gerardo Hosp, Dept Expt Med, Monza, Italy. [Hoffmann, Viktoria] NIH, Div Vet Res, Bethesda, MD 20892 USA. [Stylianou, Mario] NHLBI, NIH, Off Biostat Res, Bethesda, MD 20892 USA. [Cressoni, Massimo] Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Dipartimento Anestesia Rianimaz Intens & Subinten, Milan, Italy. RP Cressoni, M (reprint author), Univ Milan, Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Dipartimento Anestesiol Terapia Intens & Sci Derm, Milan, Italy. EM mcressoni@hotmail.com RI Cressoni, Massimo/B-7315-2017; OI Cressoni, Massimo/0000-0002-0089-2905; zanella, Alberto/0000-0002-2967-2527 FU Intramural NIH HHS NR 25 TC 15 Z9 16 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD APR PY 2012 VL 38 IS 4 BP 677 EP 685 DI 10.1007/s00134-012-2495-2 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 912EQ UT WOS:000301777900018 PM 22349422 ER PT J AU Guiard, BP El Mansari, M Murphy, DL Blier, P AF Guiard, Bruno P. El Mansari, Mostafa Murphy, Dennis L. Blier, Pierre TI Altered response to the selective serotonin reuptake inhibitor escitalopram in mice heterozygous for the serotonin transporter: an electrophysiological and neurochemical study SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Depression; electrophysiology; escitalopram; microdialysis; SERT ID MAJOR DEPRESSIVE DISORDER; GENE REGULATORY REGION; ANTIDEPRESSANT RESPONSE; KNOCKOUT MICE; FUNCTIONAL POLYMORPHISM; CLINICAL-RESPONSE; 5-HT1A RECEPTORS; PROMOTER REGION; DORSAL RAPHE; HUMAN BRAIN AB A serotonin (5-HT) transporter (5-HTT; SERT) polymorphism has been associated with depressive states and poor responses to selective serotonin reuptake inhibitors (SSRIs). Given the similar attenuation of SERT activity in SERT+/- mice and in humans with short allele(s) of SERT in its promoter region, it is conceivable that SERT+/- mice offer an adequate model to mimic the human subpopulation with respect to their altered response to SSRIs. This study investigated the effects of the most selective SSRI escitalopram, in heterozygous SERT+/- mice using a combined electrophysiological and neurochemical approach. Results indicated that administration of escitalopram for 2 d resulted in a 72% and 63% decrease in dorsal raphe 5-HT neuronal firing rate in SERT+/+ and SERT+/- mice, respectively. In contrast, administration of escitalopram for 21 d produced a gradual recovery of 5-HT neuronal firing rate to basal level in SERT+/+, but not in SERT+/- mice. In the hippocampus, microdialysis revealed that sustained administration of escitalopram produced a greater increase in extracellular 5-HT ([ 5-HT](ext)) outflow in SERT+/- than in the wild-types with or without a washout of the SSRI. Nevertheless, the ability of microiontophoretically applied 5-HT to inhibit the firing rate of CA3 pyramidal neurons was not different between SERT+/+ and SERT+/- mice given escitalopram for 21 d. The data indicate that the poor response to SSRIs of depressive patients with short allele(s) of SERT is not attributable to a lesser increase in 5-HT transmission in the hippocampus. C1 [Guiard, Bruno P.; El Mansari, Mostafa; Blier, Pierre] Univ Ottawa, Mental Hlth Res Inst, Ottawa, ON K1Z 7K4, Canada. [Guiard, Bruno P.] Univ Paris 11, Fac Pharm, EA3544, Neuropharmacol Lab, F-92290 Chatenay Malabry, France. [Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Blier, P (reprint author), Univ Ottawa, Mental Hlth Res Inst, 1145 Carling Ave, Ottawa, ON K1Z 7K4, Canada. EM pierre.blier@rohcg.on.ca RI Guiard, Bruno/A-3955-2016 FU Lundbeck FX This work was funded in part by Lundbeck. We acknowledge Dr A. M. Gardier for assistance with microdialysis experiments. NR 60 TC 6 Z9 6 U1 1 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD APR PY 2012 VL 15 IS 3 BP 349 EP 361 DI 10.1017/S1461145711000484 PG 13 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 915JQ UT WOS:000302020900006 PM 21439106 ER PT J AU Mirabello, L Sun, C Ghosh, A Rodriguez, AC Schiffman, M Wentzensen, N Hildesheim, A Herrero, R Wacholder, S Lorincz, A Burk, RD AF Mirabello, Lisa Sun, Chang Ghosh, Arpita Rodriguez, Ana C. Schiffman, Mark Wentzensen, Nicolas Hildesheim, Allan Herrero, Rolando Wacholder, Sholom Lorincz, Attila Burk, Robert D. TI Methylation of Human Papillomavirus Type 16 Genome and Risk of Cervical Precancer in a Costa Rican Population SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID L1 GENE METHYLATION; EPSTEIN-BARR-VIRUS; 16 E6 GENE; DNA METHYLATION; INTRAEPITHELIAL NEOPLASIA; CARCINOGENIC PROGRESSION; EPIGENETIC MECHANISMS; NATURAL-HISTORY; CPG METHYLATION; LIFE-CYCLE AB Background Previous studies have suggested an association between human papillomavirus type 16 (HPV16) genome methylation and cervical intraepithelial neoplasia grade 3 (CIN3) (ie, cervical precancer) and cancer, but the results have been inconsistent. Methods We designed a case-control study within a large prospective cohort of women who underwent multiple screenings for cervical cancer in Guanacaste, Costa Rica. Diagnostic specimens were collected at the time of CIN3 diagnosis (n = 30 case subjects) and persistent HPV16 infection (persistence; n = 35 case subjects), prediagnostic specimens at the first HPV16-positive screening visit (n = 20 CIN3 case subjects; n = 35 persistence case subjects), and control specimens from women with infection clearance within 2 years (n = 34 control subjects). DNA extracted from specimens (cervical cells) was analyzed for methylation levels at 67 CpG sites throughout the HPV16 genome using pyrosequencing. Benjamini-Hochberg method was used to account for multiple testing. Associations between methylation levels and risk of CIN3 or persistence were assessed using logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results Increased methylation in diagnostic vs control specimens at nine CpG sites, three in each L1, L2, and E2/E4 genomic regions, was associated with an increased risk of CIN3 (third tertile [high] vs first and second tertiles combined [low], OR = 3.29 [95% CI = 1.16 to 9.34] to 11.12 [95% CI = 2.29 to 76.80]) and persistence. High methylation at three of these CpG sites was associated with a much higher risk when combined compared with low methylation at these sites (OR = 52, 95% CI = 4.0 to 670). In prediagnostic vs control specimens, increased methylation at a CpG site (nucleotide position 4261) in L2 was associated with an increased risk of CIN3. Conclusion In this HPV16-infected cohort, increased methylation of CpG sites within the HPV16 genome before diagnosis and at the time of diagnosis was associated with cervical precancer. J Natl Cancer Inst 2012; 104: 556-565 C1 [Mirabello, Lisa] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Rockville, MD 20892 USA. [Sun, Chang; Burk, Robert D.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA. [Rodriguez, Ana C.; Herrero, Rolando] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. [Burk, Robert D.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. [Burk, Robert D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Burk, Robert D.] Albert Einstein Coll Med, Dept Obstet Gynecol & Womens Hlth, Bronx, NY 10461 USA. [Lorincz, Attila] Univ London, Ctr Canc Prevent, Wolfson Inst Prevent Med, London, England. RP Mirabello, L (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, 6120 Execut Blvd,EPS 7101, Rockville, MD 20892 USA. EM mirabellol@mail.nih.gov; robert.burk@einstein.yu.edu RI perumal, murugiah/D-1565-2012; Sun, Chang/I-6326-2012; Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU National Institutes of Health (NIH), National Cancer Institute [5U01CA078527]; Division of Cancer Epidemiology and Genetics; NIH [AI-51519]; Einstein Cancer Research Center [P30CA013330] FX This work was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (5U01CA078527 to RDB); Division of Cancer Epidemiology and Genetics Intramural Research Award (to LM) and through use of core facilities (CS, RDB) of the Einstein-Montefiore Center for AIDS funded by the NIH (AI-51519) and the Einstein Cancer Research Center (P30CA013330). NR 50 TC 40 Z9 43 U1 2 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR PY 2012 VL 104 IS 7 BP 556 EP 565 DI 10.1093/jnci/djs135 PG 10 WC Oncology SC Oncology GA 919AO UT WOS:000302293200011 PM 22448030 ER PT J AU Sun, YC Guo, XP Hinnebusch, BJ Darby, C AF Sun, Yi-Cheng Guo, Xiao-Peng Hinnebusch, B. Joseph Darby, Creg TI The Yersinia pestis Rcs Phosphorelay Inhibits Biofilm Formation by Repressing Transcription of the Diguanylate Cyclase Gene hmsT SO JOURNAL OF BACTERIOLOGY LA English DT Article ID STORAGE HMS(+) PHENOTYPE; ESCHERICHIA-COLI; CAENORHABDITIS-ELEGANS; ACETOBACTER-XYLINUM; CELLULOSE SYNTHESIS; FLEA VECTOR; PLAGUE; PSEUDOTUBERCULOSIS; SYSTEM; PATHOGENESIS AB Yersinia pestis, which causes bubonic plague, forms biofilms in fleas, its insect vectors, as a means to enhance transmission. Biofilm development is positively regulated by hmsT, encoding a diguanylate cyclase that synthesizes the bacterial second messenger cyclic-di-GMP. Biofilm development is negatively regulated by the Rcs phosphorelay signal transduction system. In this study, we show that Rcs-negative regulation is accomplished by repressing transcription of hmsT. C1 [Sun, Yi-Cheng; Guo, Xiao-Peng] Chinese Acad Med Sci, MOH Key Lab Syst Biol Pathogens, Inst Pathogen Biol, Beijing 100730, Peoples R China. [Sun, Yi-Cheng; Guo, Xiao-Peng] Peking Union Med Coll, Beijing 100021, Peoples R China. [Sun, Yi-Cheng; Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA. [Sun, Yi-Cheng; Darby, Creg] Univ Calif San Francisco, Dept Cell & Tissue Biol, Program Microbial Pathogenesis & Host Response, San Francisco, CA 94143 USA. RP Sun, YC (reprint author), Chinese Acad Med Sci, MOH Key Lab Syst Biol Pathogens, Inst Pathogen Biol, Beijing 100730, Peoples R China. EM sunyc@ipbcams.ac.cn OI Yang, Ruifu/0000-0003-3219-7269 FU NIH [AI057512]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); Institute of Pathogen Biology, Chinese Academy of Medical Sciences FX This work was supported by NIH grant AI057512 (to C.D.); the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and by the Institute of Pathogen Biology, Chinese Academy of Medical Sciences. NR 35 TC 19 Z9 20 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2012 VL 194 IS 8 BP 2020 EP 2026 DI 10.1128/JB.06243-11 PG 7 WC Microbiology SC Microbiology GA 917MC UT WOS:000302180200019 PM 22328676 ER PT J AU Bolton, KL Ganda, C Berchuck, A Pharaoh, PDP Gayther, SA AF Bolton, K. L. Ganda, C. Berchuck, A. Pharaoh, P. D. P. Gayther, S. A. TI Role of common genetic variants in ovarian cancer susceptibility and outcome: progress to date from the ovarian cancer association consortium (OCAC) SO JOURNAL OF INTERNAL MEDICINE LA English DT Review DE clinical outcome; ovarian cancer; susceptibility SNPs ID GENOME-WIDE ASSOCIATION; PROGESTERONE-RECEPTOR GENE; SINGLE-NUCLEOTIDE POLYMORPHISMS; PLATINUM-BASED CHEMOTHERAPY; S-TRANSFERASE POLYMORPHISMS; NEGATIVE BREAST-CANCER; DNA-REPAIR GENES; MUTATION CARRIERS; PROGNOSTIC-FACTORS; COLORECTAL-CANCER AB In this article, we review the current knowledge of the inherited genetics of epithelial ovarian cancer (EOC) susceptibility and clinical outcome. We focus on recent developments in identifying low-penetrance susceptibility genes and the role of the ovarian cancer association consortium (OCAC) in these discoveries. The OCAC was established to facilitate large-scale replication analyses for reported genetic associations for EOC. Since its inception, the OCAC has conducted both candidate gene and genome-wide association studies (GWAS); the latter has identified six established loci for EOC susceptibility, most of which showed stronger association with the serous histological subtype. Future GWAS and sequencing studies are likely to result in the discovery of additional susceptibility loci and may result in established associations with clinical outcome. Additional rare and uncommon ovarian cancer loci will likely be uncovered from high-throughput next-generation sequencing studies. Applying these novel findings to establish improved preventative and clinical intervention strategies will be one of the major challenges of future work. C1 [Gayther, S. A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Bolton, K. L.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. [Ganda, C.] UCL, EGA Inst Womens Hlth, Gynaecol Canc Res Labs, London, England. [Berchuck, A.] Duke Univ, Med Ctr, Div Gynecol Oncol, Dept Obstet & Gynaecol, Durham, NC USA. [Pharaoh, P. D. P.] Univ Cambridge, Dept Oncol, Cambridge, England. RP Gayther, SA (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, 1450 Biggy St,Rm 2517G,LG591,MC9601, Los Angeles, CA 90033 USA. EM gayther@usc.edu NR 102 TC 30 Z9 30 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD APR PY 2012 VL 271 IS 4 BP 366 EP 378 DI 10.1111/j.1365-2796.2011.02509.x PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 914CT UT WOS:000301927100007 PM 22443200 ER PT J AU Bell, JA Saikus, CE Ratnayaka, K Wu, V Sonmez, M Faranesh, AZ Colyer, JH Lederman, RJ Kocaturk, O AF Bell, Jamie A. Saikus, Christina E. Ratnayaka, Kanishka Wu, Vincent Sonmez, Merdim Faranesh, Anthony Z. Colyer, Jessica H. Lederman, Robert J. Kocaturk, Ozgur TI A deflectable guiding catheter for real-time MRI-guided interventions SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE interventional MRI; structural heart disease; catheter engineering; active MRI catheters ID REMOTE-CONTROL; TIP; OPPORTUNITY; DESIGN; MODEL AB Purpose: To design a deflectable guiding catheter that omits long metallic components yet preserves mechanical properties to facilitate therapeutic interventional MRI procedures. Materials and Methods: The catheter shaft incorporated Kevlar braiding. A 180 degrees deflection was attained with a 5-cm nitinol slotted tube, a nitinol spring, and a Kevlar pull string. We tested three designs: passive, passive incorporating an inductively coupled coil, and active receiver. We characterized mechanical properties, MRI properties, RF induced heating, and in vivo performance in swine. Results: Torque and tip deflection force were satisfactory. Representative procedures included hepatic and azygos vein access, laser cardiac septostomy, and atrial septal defect crossing. Visualization was best in the active configuration, delineating profile and tip orientation. The passive configuration could be used in tandem with an active guidewire to overcome its limited conspicuity. There was no RF-induced heating in all configurations under expected use conditions in vitro and in vivo. Conclusion: Kevlar and short nitinol component substitutions preserved mechanical properties. The active design offered the best visibility and usability but reintroduced metal conductors. We describe versatile deflectable guiding catheters with a 0.057'' lumen for interventional MRI catheterization. Implementations are feasible using active, inductive, and passive visualization strategies to suit application requirements. C1 [Bell, Jamie A.; Saikus, Christina E.; Ratnayaka, Kanishka; Wu, Vincent; Sonmez, Merdim; Faranesh, Anthony Z.; Colyer, Jessica H.; Lederman, Robert J.; Kocaturk, Ozgur] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Ratnayaka, Kanishka; Colyer, Jessica H.] Childrens Natl Med Ctr, Div Cardiol, Washington, DC 20010 USA. RP Lederman, RJ (reprint author), NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10,Room 2C713, Bethesda, MD 20892 USA. EM lederman@nih.gov RI Kocaturk, Ozgur/A-1419-2016; OI lederman, robert/0000-0003-1202-6673 FU Division of Intramural Research, National Heart Lung and Blood Institute, National Institutes of Health [Z01-HL005062-08, Z01-HL006041-01] FX Contract grant sponsor: Division of Intramural Research, National Heart Lung and Blood Institute, National Institutes of Health; Contract grant numbers: Z01-HL005062-08, Z01-HL006041-01. NR 15 TC 8 Z9 8 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD APR PY 2012 VL 35 IS 4 BP 908 EP 915 DI 10.1002/jmri.23520 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 911JF UT WOS:000301712400019 PM 22128071 ER PT J AU Pacher, P Mackie, K AF Pacher, Pal Mackie, Ken TI Interplay of cannabinoid 2 (CB2) receptors with nitric oxide synthases, oxidative and nitrative stress, and cell death during remote neurodegeneration SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article ID SYSTEM AB Remote neuronal degeneration and death/injury, which often occur in regions remote but functionally connected to the primary lesion site, may play a pivotal role in extending neuronal damage/dysfunction following traumatic brain injury, stroke, or peripheral nerve injury, as well as in chronic neurodegenerative diseases such as multiple sclerosis and amyotrophic lateral sclerosis. Even though the precise mechanisms of remote neuronal injury are poorly understood and no efficacious treatment options are available, it involves glial activation, inflammation, oxidative/nitrative stress, and apoptotic cell death. The newly discovered endocannabinoid signaling system consisting of endocannabinoids (endogenous bioactive lipid mediators), their synthetic and metabolizing enzymes, and their primary G protein-coupled cannabinoid 1 and 2 (CB1 and CB2) receptors has been implicated in the regulation of numerous physiological and pathological processes/functions, including those associated with neurodegeneration. Using a well-characterized rodent model of remote neuronal degeneration, Oddi et al. (J Mol Med 2012, in press, DOI 10.1007/s00109-012-0884-1) have demonstrated that targeting CB2 cannabinoid receptors may represent a promising novel approach to attenuate this pathological process. This editorial discusses the clinical significance of these interesting observations and the mechanisms of the possible interplay of CB2 receptors with nitric oxide synthases, oxidative and nitrative stress, and cell death during remote neurodegeneration. C1 [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Mackie, Ken] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Pacher, Pal/B-6378-2008; Mackie, Ken/E-3715-2013 OI Pacher, Pal/0000-0001-7036-8108; Mackie, Ken/0000-0001-8501-6199 FU Intramural NIH HHS [Z01 AA000375-03, Z99 AA999999, Z01 AA000375-02, ZIA AA000375-04, ZIA AA000375-05, ZIA AA000375-06] NR 16 TC 12 Z9 13 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 EI 1432-1440 J9 J MOL MED JI J. Mol. Med. PD APR PY 2012 VL 90 IS 4 BP 347 EP 351 DI 10.1007/s00109-012-0884-1 PG 5 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 916XM UT WOS:000302136500001 PM 22371074 ER PT J AU Lee, YH Kim, JH Zhou, H Kim, BW Wong, DT AF Lee, Yu-Hsiang Kim, Jae Hoon Zhou, Hui Kim, Bo Wook Wong, David T. TI Salivary transcriptomic biomarkers for detection of ovarian cancer: for serous papillary adenocarcinoma SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE Saliva; RNA; Salivary diagnostics; Ovarian cancer ID IDENTIFICATION; SERUM; UTILITY; CA-125 AB Ovarian cancer is the most lethal gynecological cancer due to lack of clear symptom and reliable screening biomarker in the early stage. The capability to detect the initiation of malignancy with a sensitive and effective approach is one of the most desirable goals for ovarian cancer therapy. In this study, we spearheaded noninvasive detection of ovarian cancer by salivary transcriptomic biomarkers, and evaluated the clinical utilities of discovered biomarkers using a clinical case-control study. To find salivary mRNA biomarkers, salivary transcriptomes in 11 ovarian cancer patients and 11 matched controls were profiled by Affymetrix HG-U133-Plus-2.0 array. The biomarker candidates selected from the microarray results were then subjected to clinical validation by RT-qPCR using an independent sample cohort including 21 ovarian cancer patients and 35 healthy controls. Seven downregulated mRNA biomarkers were validated. The logistic regression model revealed the combination of five validated biomarkers (AGPAT1, B2M, BASP2, IER3, and IL1B) can significantly discriminate ovarian cancer patients (n=21) from the healthy controls (n=35), yielding a receiver operating characteristic plot, area under the curve value of 0.909 with 85.7% sensitivity and 91.4% specificity. In summary, we have demonstrated that the RNA signatures in saliva could serve as biomarkers for detection of ovarian cancer with high sensitivity and specificity. This emerging approach with high-throughput, noninvasive, and effective advantages provides a feasible means for detection of systemic cancer, and opens a new avenue for early disease detection. C1 [Lee, Yu-Hsiang; Zhou, Hui; Wong, David T.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90095 USA. [Lee, Yu-Hsiang; Zhou, Hui; Wong, David T.] Dent Res Inst, Los Angeles, CA 90095 USA. [Lee, Yu-Hsiang] Natl Cent Univ, Grad Inst Biomed Engn, Jhongli 32001, Taiwan. [Wong, David T.] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. [Wong, David T.] Inst Mol Biol, Los Angeles, CA USA. [Wong, David T.] Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg Otolaryngol, Los Angeles, CA 90095 USA. [Wong, David T.] Univ Calif Los Angeles, Henry Samuel Sch Engn & Appl Sci, Los Angeles, CA 90095 USA. [Kim, Jae Hoon] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol,Gangnam Biomed Res Ctr, Seoul, South Korea. [Kim, Bo Wook] NCI, Tissue Array Res Program, Pathol Lab, Bethesda, MD 20892 USA. RP Wong, DT (reprint author), Univ Calif Los Angeles, Sch Dent, 73-017 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM dtww@ucla.edu FU National Research Foundation of Korean government [KRF-2008-314-E00121, 2011-0010286] FX This work was supported by National Research Foundation of Korean government (KRF-2008-314-E00121 and 2011-0010286). NR 35 TC 32 Z9 32 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED JI J. Mol. Med. PD APR PY 2012 VL 90 IS 4 BP 427 EP 434 DI 10.1007/s00109-011-0829-0 PG 8 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 916XM UT WOS:000302136500008 PM 22095100 ER PT J AU Moolgavkar, SH Holford, TR Levy, DT Kong, CY Foy, M Clarke, L Jeon, J Hazelton, WD Meza, R Schultz, F McCarthy, W Boer, R Gorlova, O Gazelle, GS Kimmel, M McMahon, PM de Koning, HJ Feuer, EJ AF Moolgavkar, Suresh H. Holford, Theodore R. Levy, David T. Kong, Chung Yin Foy, Millenia Clarke, Lauren Jeon, Jihyoun Hazelton, William D. Meza, Rafael Schultz, Frank McCarthy, William Boer, Robert Gorlova, Olga Gazelle, G. Scott Kimmel, Marek McMahon, Pamela M. de Koning, Harry J. Feuer, Eric J. TI Impact of Reduced Tobacco Smoking on Lung Cancer Mortality in the United States During 1975-2000 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MULTISTAGE CARCINOGENESIS; COLORECTAL-CANCER; CIGARETTE-SMOKING; MODEL; AGE; DURATION; SMOKERS; COHORTS; HEALTH; TRENDS AB Background Considerable effort has been expended on tobacco control strategies in the United States since the mid-1950s. However, we have little quantitative information on how changes in smoking behaviors have impacted lung cancer mortality. We quantified the cumulative impact of changes in smoking behaviors that started in the mid-1950s on lung cancer mortality in the United States over the period 1975-2000. Methods A consortium of six groups of investigators used common inputs consisting of simulated cohort-wise smoking histories for the birth cohorts of 1890 through 1970 and independent models to estimate the number of US lung cancer deaths averted during 1975-2000 as a result of changes in smoking behavior that began in the mid-1950s. We also estimated the number of deaths that could have been averted had tobacco control been completely effective in eliminating smoking after the Surgeon General's first report on Smoking and Health in 1964. Results Approximately 795 851 US lung cancer deaths were averted during the period 1975-2000: 552 574 among men and 243 277 among women. In the year 2000 alone, approximately 70 218 lung cancer deaths were averted: 44 135 among men and 26 083 among women. However, these numbers are estimated to represent approximately 32% of lung cancer deaths that could have potentially been averted during the period 1975-2000, 38% of the lung cancer deaths that could have been averted in 1991-2000, and 44% of lung cancer deaths that could have been averted in 2000. Conclusions Our results reflect the cumulative impact of changes in smoking behavior since the 1950s. Despite a large impact of changing smoking behaviors on lung cancer deaths, lung cancer remains a major public health problem. Continued efforts at tobacco control are critical to further reduce the burden of this disease. J Natl Cancer Inst 2012; 104: 541-548 C1 [Moolgavkar, Suresh H.; Jeon, Jihyoun; Hazelton, William D.; Meza, Rafael] Fred Hutchinson Canc Res Ctr, Program Biostat & Biomath, Seattle, WA 98109 USA. [Holford, Theodore R.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Levy, David T.] Univ Baltimore, Dept Econ, Baltimore, MD 21201 USA. [Levy, David T.] Pacific Inst Res & Evaluat, Calverton, MD USA. [Kong, Chung Yin; Gazelle, G. Scott; McMahon, Pamela M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kong, Chung Yin; Gazelle, G. Scott; McMahon, Pamela M.] Harvard Univ, Sch Med, Boston, MA USA. [Foy, Millenia] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX USA. [Gorlova, Olga] UT MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX USA. [Foy, Millenia; Kimmel, Marek] Rice Univ, Dept Stat, Houston, TX 77251 USA. [Clarke, Lauren] Cornerstone Syst NW Inc, Lynden, WA USA. [Meza, Rafael] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Schultz, Frank; Boer, Robert; de Koning, Harry J.] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands. [McCarthy, William] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [McCarthy, William] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Kimmel, Marek] Silesian Tech Univ, Syst Engn Grp, Gliwice, Poland. [Feuer, Eric J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Levy, David T.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Moolgavkar, SH (reprint author), Fred Hutchinson Canc Res Ctr, Program Biostat & Biomath, 1100 Fairview Ave N, Seattle, WA 98109 USA. EM smoolgav@fhcrc.org RI Boer, Rob/E-6473-2015 OI Boer, Rob/0000-0003-0680-001X FU National Cancer Institute's Cancer Intervention and Surveillance Modeling Network (CISNET); National Cancer Institute at the National Institutes of Health [5U01CA097415-04, 2U01CA097432-04, 5U01CA097450-04, 5U01CA097416-04, 2U01CA097431-04, 1U01CA152956-01, 5R01CA097337-02, K25CA133141, R00CA126147]; American Cancer Society (ACS) [RSG 2008A060554] FX The research reported in this article was funded by the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network (CISNET; http://cisnet.cancer.gov/). Specifically, this work was supported by grants from the National Cancer Institute at the National Institutes of Health (5U01CA097415-04 to SHM, 2U01CA097432-04 to TRH, 5U01CA097450-04 to DTL, 5U01CA097416-04 to RB and HJK, 2U01CA097431-04 to MK, 1U01CA152956-01 to PMM HJK, DTL, SHM, TRH). GSG acknowledges support from the National Cancer Institute at the National Institutes of Health (5R01CA097337-02) and the American Cancer Society (ACS RSG 2008A060554), PMM from the National Cancer Institute at the National Institutes of Health (R00CA126147), and CYK from the National Cancer Institute at the National Institutes of Health (K25CA133141). NR 29 TC 57 Z9 58 U1 0 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR PY 2012 VL 104 IS 7 BP 541 EP 548 DI 10.1093/jnci/djs136 PG 8 WC Oncology SC Oncology GA 919AO UT WOS:000302293200009 PM 22423009 ER PT J AU Raval, Z Liu, K Tian, L Ferrucci, L Guralnik, JM Liao, YH Criqui, MH McDermott, MM AF Raval, Zankhana Liu, Kiang Tian, Lu Ferrucci, Luigi Guralnik, Jack M. Liao, Yihua Criqui, Michael H. McDermott, Mary M. TI Higher body mass index is associated with more adverse changes in calf muscle characteristics in peripheral arterial disease SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 59th Annual Scientific Session of the American-College-of-Cardiology CY MAR 14-16, 2010 CL Atlanta, GA SP Amer Coll Cardiol ID LOWER-EXTREMITY ISCHEMIA; FUNCTIONAL IMPAIRMENT; CLASSIFICATION; OSTEOARTHRITIS; VALIDITY; CRITERIA; DECLINE AB Objective: This study investigated whether higher body mass index (BMI) is associated with more adverse lower extremity muscle characteristics at baseline and more adverse changes in muscle over time among participants with lower extremity peripheral arterial disease (PAD). Methods: This was a longitudinal, observational study of 425 men and women with PAD and 261 without PAD. Computed tomography was used to measure calf muscle characteristics at baseline and every 2 years. Knee extension isometric strength, power, and 6-minute walk distance were measured at baseline and annually. Baseline BMI (kg/m(2)) categories were ideal (20-25), overweight (>25-30), and obese (>30). Analyses adjust for age, race, sex, ankle brachial index, comorbidities, and other covariates. Results: At baseline, higher BMI among participants with PAD was associated with greater calf muscle area (ideal BMI: 5181 mm(2); overweight: 5513 mm(2); obese: 5695 mm(2); P = .0009 for trend), higher calf muscle percentage of fat (6.38%, 10.28%, 17.44%, respectively, P < .0001 for trend), lower calf muscle density (P < .0001 for trend), and higher isometric knee extension strength (P = .015 for trend). Among participants with PAD, higher BMI was associated with greater declines in calf muscle area (P = .030 for trend) and greater increases in calf muscle percentage of fat (P = .023 for trend). Among participants without PAD, there were no significant associations of baseline BMI with changes in lower extremity muscle outcomes over time. Conclusions: Among PAD participants, higher BMI is associated with greater calf muscle area at baseline. However, higher BMI is associated with more adverse calf muscle density and calf muscle percentage of fat at baseline and greater declines in calf muscle area over time. (J Vasc Surg 2012;55:1015-24.) C1 [Raval, Zankhana; McDermott, Mary M.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Liu, Kiang; Liao, Yihua; McDermott, Mary M.] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Tian, Lu] Stanford Univ, Dept Hlth & Res Policy, Palo Alto, CA 94304 USA. [Ferrucci, Luigi] Univ Maryland, Sch Med, Longitudinal Studies Sect, NIA, Baltimore, MD 21201 USA. [Tian, Lu] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Criqui, Michael H.] Univ Calif San Diego, Div Prevent Med, Dept Family Med, San Diego, CA 92103 USA. RP McDermott, MM (reprint author), 750 Lake Shore Dr,10th Flr, Chicago, IL 60611 USA. EM mdm608@northwestern.edu FU NHLBI NIH HHS [R01 HL064739-03, R01 HL058099, R01 HL058099-03, R01 HL064739, R01 HL064739-01A1, R01 HL071223, R01 HL071223-01, R01 HL071223-03, R01 HL076298-02, R01 HL076298-04, R01 HL083064, R01 HL083064-03, R01 HL058099-02, R01 HL058099-04, R01 HL064739-02, R01 HL064739-04, R01 HL071223-02, R01 HL071223-04, R01 HL076298, R01 HL076298-01A1, R01 HL076298-03, R01 HL083064-04] NR 16 TC 4 Z9 4 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD APR PY 2012 VL 55 IS 4 BP 1015 EP 1024 DI 10.1016/j.jvs.2011.10.105 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 917BA UT WOS:000302145700016 PM 22365177 ER PT J AU Shin, YK Cong, WN Cai, H Kim, W Maudsley, S Egan, JM Martin, B AF Shin, Yu-Kyong Cong, Wei-na Cai, Huan Kim, Wook Maudsley, Stuart Egan, Josephine M. Martin, Bronwen TI Age-Related Changes in Mouse Taste Bud Morphology, Hormone Expression, and Taste Responsivity SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Taste buds; Aging; Sweet taste; Glucagon-like peptide-1; T1R3 ID RECEPTOR-CELLS; MAMMALIAN TASTE; UMAMI TASTE; PGP 9.5; SWEET; MICE; LEPTIN; COMMUNICATION; PAPILLAE; BITTER AB Normal aging is a complex process that affects every organ system in the body, including the taste system. Thus, we investigated the effects of the normal aging process on taste bud morphology, function, and taste responsivity in male mice at 2, 10, and 18 months of age. The 18-month-old animals demonstrated a significant reduction in taste bud size and number of taste cells per bud compared with the 2- and 10-month-old animals. The 18-month-old animals exhibited a significant reduction of protein gene product 9.5 and sonic hedgehog immunoreactivity (taste cell markers). The number of taste cells expressing the sweet taste receptor subunit, T1R3, and the sweet taste modulating hormone, glucagon-like peptide-1, were reduced in the 18-month-old mice. Concordant with taste cell alterations, the 18-month-old animals demonstrated reduced sweet taste responsivity compared with the younger animals and the other major taste modalities (salty, sour, and bitter) remained intact. C1 [Shin, Yu-Kyong; Kim, Wook; Egan, Josephine M.] Natl Inst Aging, Diabet Sect, Clin Invest Lab, Baltimore, MD 21224 USA. [Cong, Wei-na; Cai, Huan; Martin, Bronwen] Natl Inst Aging, Metab Unit, Clin Invest Lab, Baltimore, MD 21224 USA. [Maudsley, Stuart] Natl Inst Aging, Receptor Pharmacol Unit, Neurosci Lab, Baltimore, MD 21224 USA. RP Egan, JM (reprint author), Natl Inst Aging, Diabet Sect, Clin Invest Lab, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM eganj@mail.nih.gov RI Cai, Huan/B-6578-2016 OI Cai, Huan/0000-0001-7731-8891 FU National Institutes of Health, National Institute on Aging FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 58 TC 13 Z9 14 U1 2 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD APR PY 2012 VL 67 IS 4 BP 336 EP 344 DI 10.1093/gerona/glr192 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 914TE UT WOS:000301974500003 PM 22056740 ER PT J AU Sanders, JL Fitzpatrick, AL Boudreau, RM Arnold, AM Aviv, A Kimura, M Fried, LF Harris, TB Newman, AB AF Sanders, Jason L. Fitzpatrick, Annette L. Boudreau, Robert M. Arnold, Alice M. Aviv, Abraham Kimura, Masayuki Fried, Linda F. Harris, Tamara B. Newman, Anne B. TI Leukocyte Telomere Length Is Associated With Noninvasively Measured Age-Related Disease: The Cardiovascular Health Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Leukocyte telomere length; Disease burden; Noninvasive measurements; Aging ID CAROTID ATHEROSCLEROSIS; OXIDATIVE STRESS; RISK-FACTORS; MORTALITY; ADULTS; DEMENTIA; DYNAMICS; PERFORMANCE; SENESCENCE; DEPRESSION AB Background. Most studies of leukocyte telomere length (LTL) focus on diagnosed disease in one system. A more encompassing depiction of health is disease burden, defined here as the sum of noninvasively measured markers of structure or function in different organ systems. We determined if (a) shorter LTL is associated with greater age-related disease burden and (b) shorter LTL is less strongly associated with disease in individual systems or diagnosed chronic conditions (cardiovascular disease, stroke, pulmonary disease, diabetes, kidney disease, arthritis, or depression). Methods. LTL was measured by Southern blots of terminal restriction fragment length. Age-related disease was measured noninvasively and included carotid intima-media thickness, lung vital capacity, white matter grade, cystatin-C, and fasting glucose; each graded 0 (best tertile), 1 (middle tertile), or 2 (worst tertile) and summed (0 to 10) to estimate disease burden. Of 419 participants randomly selected for LTL measurement, 236 had disease burden assessed (mean [SD] age 74.2 [4.9] years, 42.4% male, 86.8% white, and 13.2% black). Results. Mean (SD) LTL was 6,312 (615) bp, and disease score was 4.7 (2.1) points. An SD higher disease score (beta[SE] = -132 [47] bp, p < .01), age (beta[SE] = -107 [46], p = .02) or carotid thickness (beta[SE] = -95 [40] bp, p = .02) was associated with shorter LTL, but diagnosed conditions or number of conditions were not associated with LTL. Disease score attenuated the effect of age on LTL by 35%. Conclusion. LTL was associated with a characterization of age-related disease burden across multiple physiologic systems, which was comparable to, but independent of, its association with age. C1 [Sanders, Jason L.; Boudreau, Robert M.; Fried, Linda F.; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Sanders, Jason L.] Univ Pittsburgh, Sch Med, Med Scientist Training Program, Pittsburgh, PA 15213 USA. [Fitzpatrick, Annette L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Aviv, Abraham; Kimura, Masayuki] Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Human Dev & Aging, Newark, NJ 07103 USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Fried, Linda F.; Newman, Anne B.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. RP Sanders, JL (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Bellefield Profess Bldg,4th Floor,130 N Bellefiel, Pittsburgh, PA 15213 USA. EM sanders.jason@medstudent.pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187 FU Royalty Research Fund; University of Washington; Healthcare Foundation of New Jersey; National Institute on Aging [R01-AG-023629, 5-P30-AG-024827, AG-021593, AG-020132]; National Heart, Lung, and Blood Institute [R01-HL-80698-01, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-45133, N01-HC-75150, N01-HC-55222, U01 HL080295]; National Institute of Neurological Disorders and Stroke FX This research was supported by the Royalty Research Fund, the University of Washington, the Healthcare Foundation of New Jersey, the National Institute on Aging (grants R01-AG-023629 and 5-P30-AG-024827), and the National Heart, Lung, and Blood Institute (R01-HL-80698-01). The CHS is supported by the National Heart, Lung, and Blood Institute (contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-45133, N01-HC-75150, N01-HC-55222, and U01 HL080295), the National Institute on Aging (grants AG-021593 and AG-020132), and the National Institute of Neurological Disorders and Stroke. A full list of participating Cardiovascular Health Study investigators and institutions can be found at the study's website (http://www.chs-nhlbi.org). Role of sponsor(s): The investigators retained full independence in the conduct of this research. NR 45 TC 31 Z9 33 U1 4 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD APR PY 2012 VL 67 IS 4 BP 409 EP 416 DI 10.1093/gerona/glr173 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 914TE UT WOS:000301974500011 PM 21934123 ER PT J AU Majounie, E Renton, AE Mok, K Dopper, EGP Waite, A Rollinson, S Chio, A Restagno, G Nicolaou, N Simon-Sanchez, J van Swieten, JC Abramzon, Y Johnson, JO Sendtner, M Pamphlett, R Orrell, RW Mead, S Sidle, KC Houlden, H Rohrer, JD Morrison, KE Pall, H Talbot, K Ansorge, O Hernandez, DG Arepalli, S Sabatelli, M Mora, G Corbo, M Giannini, F Calvo, A Englund, E Borghero, G Foris, GL Remes, AM Laaksovirta, H McCluskey, L Trojanowski, JQ Van Deerlin, VM Schellenberg, GD Nalls, MA Drory, VE Lu, CS Yeh, TH Ishiura, H Takahashi, Y Tsuji, S Le Ber, I Brice, A Drepper, C Williams, N Kirby, J Shaw, P Hardy, J Tienari, PJ Heutink, P Morris, HR Pickering-Brown, S Traynor, BJ AF Majounie, Elisa Renton, Alan E. Mok, Kin Dopper, Elise G. P. Waite, Adrian Rollinson, Sara Chio, Adrian Restagno, Gabriella Nicolaou, Nayia Simon-Sanchez, Javier van Swieten, John C. Abramzon, Yevgeniya Johnson, Janel O. Sendtner, Michael Pamphlett, Roger Orrell, Richard W. Mead, Simon Sidle, Katie C. Houlden, Henry Rohrer, Jonathan D. Morrison, Karen E. Pall, Hardev Talbot, Kevin Ansorge, Olaf Hernandez, Dena G. Arepalli, Sampath Sabatelli, Mario Mora, Gabriele Corbo, Massimo Giannini, Fabio Calvo, Andrea Englund, Elisabet Borghero, Giuseppe Foris, Gian Luca Remes, Anne M. Laaksovirta, Hannu McCluskey, Leo Trojanowski, John Q. Van Deerlin, Vivianna M. Schellenberg, Gerard D. Nalls, Michael A. Drory, Vivian E. Lu, Chin-Song Yeh, Tu-Hsueh Ishiura, Hiroyuki Takahashi, Yuji Tsuji, Shoji Le Ber, Isabelle Brice, Alexis Drepper, Carsten Williams, Nigel Kirby, Janine Shaw, Pamela Hardy, John Tienari, Pentti J. Heutink, Peter Morris, Huw R. Pickering-Brown, Stuart Traynor, Bryan J. CA Chromosome 9-ALS FTD Consortium French Res Network FTLD FTLD ALS ITALSGEN Consortium TI Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study SO LANCET NEUROLOGY LA English DT Article ID POPULATION-BASED COHORT; LOBAR DEGENERATION; ALS; PREVALENCE; MUTATIONS; GENETICS; CRITERIA; TDP-43; FTD AB Background We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Methods We screened 4448 patients diagnosed with ALS (El Escorial criteria) and 1425 patients with FTD (Lund-Manchester criteria) from 17 regions worldwide for the GGGGCC hexanucleotide expansion using a repeat-primed PCR assay. We assessed familial disease status on the basis of self-reported family history of similar neurodegenerative diseases at the time of sample collection. We compared haplotype data for 262 patients carrying the expansion with the known Finnish founder risk haplotype across the chromosomal locus. We calculated age-related penetrance using the Kaplan-Meier method with data for 603 individuals with the expansion. Findings In patients with sporadic ALS, we identified the repeat expansion in 236 (7.0%) of 3377 white individuals from the USA, Europe, and Australia, two (4.1%) of 49 black individuals from the USA, and six (8.3%) of 72 Hispanic individuals from the USA. The mutation was present in 217 (39.3%) of 552 white individuals with familial MS from Europe and the USA. 59 (6.0%) of 981 white Europeans with sporadic FTD had the mutation, as did 99 (24.8%) of 400 white Europeans with familial FTD. Data for other ethnic groups were sparse, but we identified one Asian patient with familial ALS (from 20 assessed) and two with familial FTD (from three assessed) who carried the mutation. The mutation was not carried by the three Native Americans or 360 patients from Asia or the Pacific Islands with sporadic MS who were tested, or by 41 Asian patients with sporadic FTD. All patients with the repeat expansion had (partly or fully) the founder haplotype, suggesting a one-off expansion occurring about 1500 years ago. The pathogenic expansion was non-penetrant in individuals younger than 35 years, 50% penetrant by 58 years, and almost fully penetrant by 80 years. Interpretation A common Mendelian genetic lesion in C9472 is implicated in many cases of sporadic and familial ALS and FTD. Testing for this pathogenic expansion should be considered in the management and genetic counselling of patients with these fatal neurodegenerative diseases. C1 [Renton, Alan E.; Abramzon, Yevgeniya; Johnson, Janel O.; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Majounie, Elisa; Hernandez, Dena G.; Arepalli, Sampath; Nalls, Michael A.] NIA, Mol Genet Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Mok, Kin; Sidle, Katie C.; Houlden, Henry; Hardy, John] UCL, Inst Neurol, Dept Mol Neurosci, London, England. [Mok, Kin; Sidle, Katie C.; Hardy, John] UCL, Inst Neurol, Reta Lila Weston Labs, London, England. [Orrell, Richard W.] UCL, Dept Clin Neurosci, Inst Neurol, London, England. [Mead, Simon] UCL, Inst Neurol, MRC Prion Unit, Dept Neurodegenerat Dis, London, England. [Houlden, Henry] UCL, Inst Neurol, MRC Ctr Neuromuscular Dis, London, England. [Rohrer, Jonathan D.] UCL, Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, London, England. [Dopper, Elise G. P.; Nicolaou, Nayia; Simon-Sanchez, Javier; van Swieten, John C.; Heutink, Peter] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands. [Dopper, Elise G. P.; Nicolaou, Nayia; Simon-Sanchez, Javier; van Swieten, John C.; Heutink, Peter] Vrije Univ Amsterdam, Med Ctr, Sect Med Genom, Dept Clin Genet, Amsterdam, Netherlands. [Dopper, Elise G. P.; Nicolaou, Nayia; Simon-Sanchez, Javier; van Swieten, John C.] Erasmus MC Univ Med Ctr Rotterdam, Dept Neurol, Rotterdam, Netherlands. [Waite, Adrian; Williams, Nigel; Morris, Huw R.] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Cardiff, S Glam, Wales. [Rollinson, Sara; Pickering-Brown, Stuart] Univ Manchester, Fac Human & Med Sci, Manchester, Lancs, England. [Chio, Adrian; Calvo, Andrea] Univ Turin, Dept Neurosci, Turin, Italy. [Restagno, Gabriella] Azienda Osped Osped Infantile Regina Margherita S, Dept Clin Pathol, Mol Genet Unit, Turin, Italy. [Sendtner, Michael; Drepper, Carsten] Univ Wurzburg, Inst Clin Neurobiol, Wurzburg, Germany. [Pamphlett, Roger] Univ Sydney, Sydney Med Sch, Dept Pathol, Sydney, NSW 2006, Australia. [Morrison, Karen E.] Univ Birmingham, Coll Med & Dent Sci, Inst Biomed Res, Dept Neurol, Birmingham, W Midlands, England. [Pall, Hardev] Univ Hosp Birmingham NHS Fdn Trust, Queen Elizabeth Hosp, Queen Elizabeth Med Ctr, Birmingham, W Midlands, England. [Talbot, Kevin; Ansorge, Olaf] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England. [Sabatelli, Mario] Catholic Univ, Neurol Inst, Rome, Italy. [Sabatelli, Mario] ICOMM Assoc ALS Res, Rome, Italy. [Mora, Gabriele] Salvatore Maugeri Fdn, ALS Ctr, Milan, Italy. [Corbo, Massimo] Osped Niguarda Ca Granda, NeuroMuscular Omnictr, Milan, Italy. [Giannini, Fabio] Univ Siena, Dept Neurol Neurosurg & Behav Sci, Neurol Sect, I-53100 Siena, Italy. [Englund, Elisabet] Lund Univ, Dept Pathol, Reg Labs Reg Skane, Lund, Sweden. [Borghero, Giuseppe; Foris, Gian Luca] Azienda Univ Osped Cagliari, Dept Neurol, Cagliari, Italy. [Borghero, Giuseppe; Foris, Gian Luca] Univ Cagliari, Cagliari, Italy. [Remes, Anne M.] Oulu Univ Hosp, Clin Res Ctr, Oulu, Finland. [Remes, Anne M.] Univ Oulu, Inst Clin Med, Oulu, Finland. [Laaksovirta, Hannu; Tienari, Pentti J.] Univ Helsinki, Mol Neurol Programme, Biomedicum, Helsinki, Finland. [Laaksovirta, Hannu; Tienari, Pentti J.] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland. [McCluskey, Leo] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Trojanowski, John Q.; Van Deerlin, Vivianna M.; Schellenberg, Gerard D.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Drory, Vivian E.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Neurol, IL-69978 Tel Aviv, Israel. [Lu, Chin-Song; Yeh, Tu-Hsueh] Chang Gang Univ, Tao Yuan, Taiwan. [Lu, Chin-Song; Yeh, Tu-Hsueh] Chang Gung Mem Hosp, Linkou Med Ctr, Dept Neurol, Tao Yuan, Taiwan. [Lu, Chin-Song; Yeh, Tu-Hsueh] Chang Gung Mem Hosp, Linkou Med Ctr, Neurosci Res Ctr, Tao Yuan, Taiwan. [Ishiura, Hiroyuki; Takahashi, Yuji] Tokyo Univ Hosp, Dept Neurol, Bunkyo Ku, Tokyo 113, Japan. [Le Ber, Isabelle; Brice, Alexis] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, Paris, France. [Le Ber, Isabelle; Brice, Alexis] INSERM, U975, Paris, France. [Le Ber, Isabelle; Brice, Alexis] CNRS, UMR 7225, Paris, France. [Kirby, Janine; Shaw, Pamela] Univ Sheffield, Dept Neurosci, Sheffield, S Yorkshire, England. [Morris, Huw R.] Univ Wales Hosp, Cardiff CF4 4XW, S Glam, Wales. [Traynor, Bryan J.] Johns Hopkins Univ Hosp, Brain Sci Inst, Dept Neurol, Baltimore, MD 21287 USA. RP Traynor, BJ (reprint author), NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, 35 Convent Dr,Room 1A-1000, Bethesda, MD 20892 USA. EM traynorb@mail.nih.gov RI Pickering-Brown, Stuart/D-4008-2009; Hardy, John/C-2451-2009; Morris, Huw/B-8527-2008; Tienari, Pentti/A-4893-2012; Mok, Kin/F-5860-2012; Guerreiro, Rita/A-1327-2011; Traynor, Bryan/G-5690-2010; Mead, Simon/E-9414-2011; Houlden, Henry/C-1532-2008; Orrell, Richard/L-2123-2013; LICEND, CEMND/F-1296-2015; Battistini, Stefania/N-2596-2015; QUATTRONE, Aldo/A-6734-2016; Calvo, Andrea/K-4141-2016; LOGROSCINO, GIANCARLO/K-5148-2016; Spataro, Rossella/B-3656-2016; Lunetta, Christian/K-9214-2016; Sendtner, Michael/J-1542-2012; MANDRIOLI, JESSICA/K-7235-2016; Conforti, Francesca Luisa/K-8877-2016; OI Pickering-Brown, Stuart/0000-0003-1561-6054; Morris, Huw/0000-0002-5473-3774; Mead, Simon/0000-0002-4326-1468; Houlden, Henry/0000-0002-2866-7777; Battistini, Stefania/0000-0003-2887-7624; QUATTRONE, Aldo/0000-0003-2001-957X; Calvo, Andrea/0000-0002-5122-7243; Rohrer, Jonathan/0000-0002-6155-8417; Blanc, Frederic/0000-0002-6714-3247; Bayer, Antony/0000-0002-7514-248X; Gambardella , Antonio/0000-0001-7384-3074; Turner, Martin/0000-0003-0267-3180; Gwinn, Katrina/0000-0002-8277-651X; Scholz, Sonja/0000-0002-6623-0429; LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Spataro, Rossella/0000-0002-8910-3131; Lunetta, Christian/0000-0002-4788-1875; Sendtner, Michael/0000-0002-4737-2974; Mandich, Paola/0000-0003-3123-3512; Simone, Isabella Laura/0000-0002-7429-3091; Kirby, Janine/0000-0002-7468-5917; MANDRIOLI, JESSICA/0000-0002-9244-9782; Sabatelli, Mario/0000-0001-6635-4985; Conforti, Francesca Luisa/0000-0001-8364-1783; Chio, Adriano/0000-0001-9579-5341 FU US National Institutes of Health (NIH); National Institute on Aging [Z01-AG000949-02]; National Institute of Neurological Disorders and Stroke (NINDS); Packard Center for ALS Research at Hopkins; ALS Association; Microsoft Research; AriSLA; Hersenstichting Nederland Fellowship [B08.03]; Neuroscience Campus Amsterdam; Nuts Ohra Fonds; Stichting Dioraphte [09020300]; UK Motor Neurone Disease Association [6057, 6700/3]; Medical Research Council UK; Wellcome Trust [069388/z/02/z]; Oxford National Institute for Health Research Biomedical Research Centre; Helsinki University Central Hospital; Finnish Academy; Finnish Medical Society Duodecim; Kuopio University; Italian Health Ministry; Fondazione Vialli e Mauro ONLUS; Federazione Italiana Giuoco Calcio; Compagnia di San Paolo; French Agency for Research [ANR-08-MNPS-009-01]; France Alzheimer Union Nationale des Associations Alzheimer; Institut de France Subvention de la Fondation Thierry et Annick DESMAREST; European Community [259867]; Deutsche Forschungsgemeinschaft [SFT.581, TP4]; National Health and Medical Research Council [402703] FX This work was supported in part by the Intramural Research Programs of the US National Institutes of Health (NIH), National Institute on Aging (Z01-AG000949-02), and National Institute of Neurological Disorders and Stroke (NINDS). The work was also supported by the Packard Center for ALS Research at Hopkins (BJT), the ALS Association (BJT, ACh), Microsoft Research (BIT, PIT), AriSLA (BJT, ACh, MSa), Hersenstichting Nederland Fellowship project B08.03 and the Neuroscience Campus Amsterdam (JS-S), Nuts Ohra Fonds (JvS), Stichting Dioraphte (JvS; grant 09020300), the UK Motor Neurone Disease Association (HM [Motor Neurone Disease Association grant 6057], JH, RWO, KEM, PJS MNDA Grant 6700/3), The Medical Research Council UK (JH, HH, SP-B), the Wellcome Trust (JH, HH, 069388/z/02/z), The Oxford National Institute for Health Research Biomedical Research Centre (OA), the Helsinki University Central Hospital, the Finnish Academy (PJT), the Finnish Medical Society Duodecim, Kuopio University, the Italian Health Ministry (Ricerca Sanitaria Finalizzata 2007 to ACh), Fondazione Vialli e Mauro ONLUS (ACh), Federazione Italiana Giuoco Calcio (ACh, MSa, BJT) and Compagnia di San Paolo (ACh, GR), the French Agency for Research (ANR-08-MNPS-009-01; AB and ILB), France Alzheimer Union Nationale des Associations Alzheimer (ILB) and Institut de France Subvention de la Fondation Thierry et Annick DESMAREST (ILB), and the European Community's Health Seventh Framework Programme under grant agreements 259867 (ACh, JK, PJS, MS, CD), Deutsche Forschungsgemeinschaft (MSe; grant SFT.581, TP4). DNA samples for this study were obtained in part from the NINDS repository at the Coriell Cell Repositories (NJ, USA), and from the Australian Motor Neuron Disease DNA Bank, which is funded by National Health and Medical Research Council grant 402703. We thank the DNA extraction and storage facility of the NIH and Welfare/FIMM, Helsinki, Finland and the Institute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK, for their help in extraction of DNA from patients with amyotrophic lateral sclerosis; and also the patients and research participants who contributed samples for this study. NR 28 TC 356 Z9 365 U1 12 U2 74 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD APR PY 2012 VL 11 IS 4 BP 323 EP 330 DI 10.1016/S1474-4422(12)70043-1 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 915CD UT WOS:000301999600008 PM 22406228 ER PT J AU Demirer, E Miller, AC Kunter, E Kartaloglu, Z Barnett, SD Elamin, M AF Demirer, Ersin Miller, Andrew C. Kunter, Erdogan Kartaloglu, Zafer Barnett, Scott D. Elamin, M. TI Predictive Models for Tuberculous Pleural Effusions in a High Tuberculosis Prevalence Region SO LUNG LA English DT Article DE Adenosine deaminase enzyme; Lactate dehydrogenase enzyme; Pulmonary tuberculosis; Tuberculous pleural effusion ID DIAGNOSIS; BIOPSY; SPECIFICITY AB Patients with pleural effusions who reside in geographic areas with a high prevalence of tuberculosis frequently have similar clinical manifestations of other diseases. The aim of our study was to develop a simple but accurate clinical score for differential diagnosis of tuberculosis pleural effusion (TPE) from non-TB pleural effusion (NTPE). This was an unblinded, prospective study of Turkish patients 18 years of age or older with pleural effusion of indeterminate etiology conducted from June 2003 to June 2005. Unconditional logistic regression models were used to discriminate TPE cases from NTPE cases. Standard errors for the area under the curve (AUC) were calculated using the Mann-Whitney method. Data were statistically significance if two-tailed P < 0.05. A total of 63.3% (157/248) of the patients had TPE while 36.7% (91/248) of the patients had other etiologies for pleural effusions. We were able to provide a predictive model of TPE that included age < 47 years and either pleural fluid adenosine deaminase enzyme (PADA) > 35 U/l or pleural serum protein ratio > 0.710. However, only the combination of age < 47 and PADA > 35 U/l was significant (odds ratio [OR]: 7.46; 95% confidence interval [CI]: 3.99-13.96). The generated summary score (range = 0-6) was significantly predictive of TPE (OR: 2.91; 95% CI: 2.18-3.89) and with high AUC (0.79). We propose an affordable model that includes age < 47 years and PADA > 35 U/l for timely diagnosis of TPE in geographical regions with a high prevalence of TB. C1 [Demirer, Ersin; Kartaloglu, Zafer] GATA Haydarpasa Training Hosp, Dept Thorac Med, Istanbul, Turkey. [Miller, Andrew C.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Miller, Andrew C.] Univ Pittsburgh, Med Ctr, Dept Med Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Kunter, Erdogan] Istanbul Medipol Univ, Dept Thorac Med, Istanbul, Turkey. [Barnett, Scott D.] James A Haley Vet Hosp, Res Ctr Excellence, Tampa, FL 33612 USA. [Elamin, M.] Univ S Florida, Div Pulm Crit Care & Sleep Med, Sect 111C, James A Haley Vet Hosp, Tampa, FL 33612 USA. [Elamin, M.] Univ S Florida, Div Pulm Crit Care Med & Sleep, Tampa, FL 33612 USA. RP Elamin, M (reprint author), Univ S Florida, Div Pulm Crit Care & Sleep Med, Sect 111C, James A Haley Vet Hosp, 13000 Bruce B Downs Blvd, Tampa, FL 33612 USA. EM eelamin@health.usf.edu OI Miller, Andrew/0000-0001-8474-5090 NR 27 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2040 J9 LUNG JI Lung PD APR PY 2012 VL 190 IS 2 BP 239 EP 248 DI 10.1007/s00408-011-9342-z PG 10 WC Respiratory System SC Respiratory System GA 917BL UT WOS:000302146900015 PM 22057296 ER PT J AU Yu, SSK Castillo, DC Courville, AB Sumner, AE AF Yu, Sophia S. K. Castillo, Darleen C. Courville, Amber B. Sumner, Anne E. TI The Triglyceride Paradox in People of African Descent SO METABOLIC SYNDROME AND RELATED DISORDERS LA English DT Article ID CORONARY-HEART-DISEASE; HYPERTRIGLYCERIDEMIC-WAIST PHENOTYPE; LIPOPROTEIN CHOLESTEROL RATIO; INCIDENT DIABETES-MELLITUS; LOW-DENSITY LIPOPROTEINS; INSULIN-RESISTANCE; METABOLIC SYNDROME; ETHNIC-DIFFERENCES; GLUCOSE-INTOLERANCE; HEPATIC STEATOSIS AB Even though insulin resistance, cardiovascular disease (CVD), and type 2 diabetes (T2D) are associated with hypertriglyceridemia, blacks with these conditions usually have normal triglyceride (TG) levels. This is often called a lipid paradox. More precisely, it is a "TG paradox." The pathways that lead to hypertriglyceridemia have been intensively explored. Yet, the pathways that allow TG levels to be normal in the presence of insulin resistance have received little attention and this is problematic. Tests designed for the early detection of insulin-resistant conditions often use elevated TG levels as a diagnostic criterion. However, insulin resistance, CVD, and T2D are not usually associated with hypertriglyceridemia in people of African descent; therefore, the widespread use of TG levels to predict these conditions needs re-evaluation. This review focuses on black-white differences in: (1) the lipid profile across North America, Europe, and Africa; (2) the efficacy of TG-based screening tests, specifically the metabolic syndrome and its two abbreviated versions, the hypertriglycerdemic waist and TG/high-density lipoprotein cholesterol (HDL-C) ratio; and (3) the mechanisms that allow TG to be normal even in the presence of insulin resistance. Overall, a broader understanding of how TG physiology varies by race could lead to better diagnostic tests and improved health outcomes. C1 [Yu, Sophia S. K.; Castillo, Darleen C.; Sumner, Anne E.] NIDDK, DEOB, NIH, Bethesda, MD 20892 USA. [Courville, Amber B.] NIH, Dept Nutr, Ctr Clin, Bethesda, MD 20892 USA. RP Sumner, AE (reprint author), NIDDK, DEOB, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM annes@intra.niddk.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH); NIH; Pfizer Inc; Clinical Center, NIH FX S.S.K.Y., D.C.C., and A.E.S. are supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH). S.S.K.Y. is also supported through the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and Pfizer Inc (via a grant to the Foundation for NIH from Pfizer Inc). A.B.C. is supported by the Clinical Center, NIH. NR 52 TC 17 Z9 17 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-4196 J9 METAB SYNDR RELAT D JI Metab. Syndr. Relat. Disord. PD APR PY 2012 VL 10 IS 2 BP 77 EP 82 DI 10.1089/met.2011.0108 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 914NM UT WOS:000301957500001 PM 22224930 ER PT J AU Ebong, IA Bertoni, AG Soliman, EZ Guo, MY Sibley, CT Chen, YDI Rotter, JI Chen, YC Goff, DC AF Ebong, Imo A. Bertoni, Alain G. Soliman, Elsayed Z. Guo, Mengye Sibley, Christopher T. Chen, Yii-Der I. Rotter, Jerome I. Chen, Yi-Chun Goff, David C., Jr. TI Electrocardiographic Abnormalities Associated with the Metabolic Syndrome and Its Components: The Multi-Ethnic Study of Atherosclerosis SO METABOLIC SYNDROME AND RELATED DISORDERS LA English DT Article ID INTERNATIONAL-DIABETES-FEDERATION; CARDIOVASCULAR-DISEASE MORTALITY; CORONARY-ARTERY-DISEASE; HEART-DISEASE; ABDOMINAL OBESITY; BLOOD-PRESSURE; RISK; MEN; WOMEN; DEFINITION AB Background: The association between metabolic syndrome and electrocardiographic (ECG) abnormalities is not well established. Methods: ECG tracings of 6,765 men and women aged 45-84 years, free of clinical cardiovascular disease, from the Multi-Ethnic Study of Atherosclerosis were obtained (2000-2002) and classified as normal or having major or minor abnormalities. We evaluated the associations of metabolic syndrome and its components with ECG abnormalities, adjusting for age, ethnicity, and gender and testing for effect modification by ethnicity and gender. Results: The associations of metabolic syndrome, hypertension, and high triglycerides with ECG abnormalities varied significantly by gender. In males, metabolic syndrome and hypertension were significantly associated with major ECG abnormality [1.69 (1.33-2.13), and 2.22 (1.72-2.86), respectively] after adjusting for ethnicity and gender. Hypertension was also associated significantly with minor ECG abnormality in males after adjusting for age and ethnicity. In females, metabolic syndrome and hypertension were significantly associated with major [1.84 (1.44-2.37), and 1.68 (1.27-2.22), respectively] and minor [1.38 (1.19-1.59), and 1.53 (1.32-1.79), respectively] ECG abnormalities after adjusting for age and ethnicity. High triglycerides were only significantly associated with major ECG abnormality in females after adjusting for age and ethnicity. After adjusting for age, ethnicity, and gender, central obesity and high fasting blood glucose were significantly associated with major and minor ECG abnormalities, whereas low high-density lipoprotein cholesterol was significantly associated with major ECG abnormality only. Conclusions: Metabolic syndrome and its components are associated with major and/or minor ECG abnormalities. The relationship of metabolic syndrome, hypertension, and high triglycerides with ECG abnormalities varied according to gender. C1 [Ebong, Imo A.; Bertoni, Alain G.; Soliman, Elsayed Z.; Goff, David C., Jr.] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Ebong, Imo A.; Bertoni, Alain G.; Soliman, Elsayed Z.; Goff, David C., Jr.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Guo, Mengye] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Sibley, Christopher T.] NIH, Bethesda, MD 20892 USA. [Chen, Yii-Der I.; Rotter, Jerome I.; Chen, Yi-Chun] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Chen, Yi-Chun] Chang Gung Univ, Chang Gung Mem Hosp, Dept Neurol, Taipei, Taiwan. [Chen, Yi-Chun] Chang Gung Univ, Coll Med, Taipei, Taiwan. RP Ebong, IA (reprint author), Wake Forest Univ, Sch Med, Dept Epidemiol & Prevent, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM iebong@wfubmc.edu RI Sibley, Christopher/C-9900-2013 FU National Heart, Lung and Blood Institute [N01-HC-95159, N01-HC-95169] FX The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at www.mesa-nhlbi.org. We thank Charles N. Campbell, Jr., at Wake Forest University School of Medicine for assistance with ECG coding. The MESA study was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung and Blood Institute. NR 29 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-4196 J9 METAB SYNDR RELAT D JI Metab. Syndr. Relat. Disord. PD APR PY 2012 VL 10 IS 2 BP 92 EP 97 DI 10.1089/met.2011.0090 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 914NM UT WOS:000301957500003 PM 22053762 ER PT J AU Fera, A Farrington, JE Zimmerberg, J Reese, TS AF Fera, Andrea Farrington, Jane E. Zimmerberg, Joshua Reese, Thomas S. TI A Negative Stain for Electron Microscopic Tomography SO MICROSCOPY AND MICROANALYSIS LA English DT Article DE tomography; influenza virus; negative staining; back projection method; individual molecule imaging; native state imaging ID INFLUENZA-VIRUS; HEMAGGLUTININ; NEURAMINIDASE; RESOLUTION; RECONSTRUCTIONS; MACROMOLECULES; GLYCOPROTEIN; ORGANIZATION; IRRADIATION; MEMBRANE AB While negative staining can provide detailed, two-dimensional images of biological structures, the potential of combining tomography with negative staining to provide three-dimensional views has yet to be fully realized. Basic requirements of a negative stain for tomography are that the density and atomic number of the stain are optimal, and that the stain does not degrade or rearrange with the intensive electron dose (similar to 10(6) e/nm(2)) needed to collect a full set of tomographic images. A commercially available, tungsten-based stain appears to satisfy these prerequisites. Comparison of the surface structure of negatively stained influenza A virus with previous structural results served to evaluate this negative stain. The combination of many projections of the same structure yielded detailed images of single proteins on the viral surface. Corresponding surface renderings are a good fit to images of the viral surface derived from cryomicroscopy as well as to the shapes of crystallized surface proteins. Negative stain tomography with the appropriate stain yields detailed images of individual molecules in their normal setting on the surface of the influenza A virus. C1 [Fera, Andrea; Reese, Thomas S.] Natl Inst Neurol Disorders & Stroke, Neurobiol Lab, Bethesda, MD 20892 USA. [Farrington, Jane E.; Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Cellular Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Fera, A (reprint author), Natl Inst Neurol Disorders & Stroke, Neurobiol Lab, Bethesda, MD 20892 USA. EM feraandr@ninds.nih.gov FU Intramural NIH HHS [ZIA HD001409-26] NR 28 TC 2 Z9 2 U1 1 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1431-9276 J9 MICROSC MICROANAL JI Microsc. microanal. PD APR PY 2012 VL 18 IS 2 BP 331 EP 335 DI 10.1017/S1431927611012797 PG 5 WC Materials Science, Multidisciplinary; Microscopy SC Materials Science; Microscopy GA 916FM UT WOS:000302084700010 PM 22364718 ER PT J AU Virden, RA Thiele, CJ Liu, ZH AF Virden, Ryan A. Thiele, Carol J. Liu, Zhihui TI Characterization of Critical Domains within the Tumor Suppressor CASZ1 Required for Transcriptional Regulation and Growth Suppression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NERVOUS-SYSTEM; NEUROBLASTOMA-CELLS; GENE-EXPRESSION; IN-VIVO; DROSOPHILA; CASTOR; DIFFERENTIATION; TRKA; IDENTITY; RECEPTOR AB CASZ1 is a zinc finger (ZF) transcription factor that is critical for controlling the normal differentiation of subtypes of neural and cardiac muscle cells. In neuroblastoma tumors, loss of CASZ1 is associated with poor prognosis and restoration of CASZ1 function suppresses neuroblastoma tumorigenicity. However, the key domains by which CASZ1 transcription controls developmental processes and neuroblastoma tumorigenicity have yet to be elucidated. In this study, we show that loss of any one of ZF1 to ZF4 resulted in a 58 to 79% loss in transcriptional activity, as measured by induction of tyrosine hydroxylase promoter-luciferase activity, compared to that of wild-type (WT) CASZ1b. Mutation of ZF5 or deletion of the C-terminal sequence of amino acids (aa) 728 to 1166 (a truncation of 38% of the protein) does not significantly alter transcriptional function. A series of N-terminal truncations reveals a critical transcriptional activation domain at aa 31 to 185 and a nuclear localization signal at aa 23 to 29. Soft agar colony formation assays and xenograft studies show that WT CASZ1b is more active in suppressing neuroblastoma growth than CASZ1b with a ZF4 mutation or a deletion of aa 31 to 185. This study identifies key domains needed for CASZ1b to regulate gene transcription. Furthermore, we establish a link between loss of CASZ1b transcriptional activity and attenuation of CASZ1b-mediated inhibition of neuroblastoma growth and tumorigenicity. C1 [Virden, Ryan A.; Thiele, Carol J.; Liu, Zhihui] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Liu, ZH (reprint author), NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. EM thielec@mail.nih.gov; liuzhihu@mail.nih.gov FU NIH, National Cancer Institute, and Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, and Center for Cancer Research. NR 32 TC 7 Z9 7 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2012 VL 32 IS 8 BP 1518 EP 1528 DI 10.1128/MCB.06039-11 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 917DK UT WOS:000302152500017 PM 22331471 ER PT J AU Villar, J Tsai-Morris, CH Dai, LS Dufau, ML AF Villar, Joaquin Tsai-Morris, Chon-Hwa Dai, Lisheng Dufau, Maria L. TI Androgen-Induced Activation of Gonadotropin-Regulated Testicular RNA Helicase (GRTH/Ddx25) Transcription: Essential Role of a Nonclassical Androgen Response Element Half-Site SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HORMONE RECEPTOR GENE; HUMAN PROSTATE; IN-VITRO; SPERMATOGENESIS; PROTEIN; COACTIVATOR; EXPRESSION; BINDING; FAMILY; GROWTH AB GRTH, a testis-specific member of the DEAD-box family of RNA helicases essential for spermatogenesis, is present in Leydig cells (LC) and germ cells. In LC, it exerts an autocrine negative regulation on androgen production induced by gonadotropin. GRTH is transcriptionally upregulated by gonadotropin via cyclic AMP/androgen through androgen receptors (AR). For studies of GRTH regulation by androgen in LC, we utilized in vitro/in vivo models. Androgen-induced GRTH expression was prevented by an AR antagonist. Two putative atypical ARE half-sites are present at bp -200 and -827 (ARE1 and ARE2). Point mutation of ARE2 prevented androgen-induced AR binding/function and upregulation of GRTH transcription. Chromatin immunoprecipitation (ChIP) assays showed recruitment of AR, SRC-1, Med-1, transcription factor IIB (TFIIB), and polymerase II (PolII) to GRTH ARE2 (bp -980/-702) and to the promoter region (bp -80/+63). ChIP3C assays revealed short-range chromosomal looping between AR/ARE2 and the core transcriptional machinery at the promoter. Knockdown of Med-1 and/or SRC-1 demonstrated the presence of a nonproductive complex which included AR, TFIIB, and PolII and the essential role of these coactivators in the transcriptional activation of GRTH. Our findings provide new insights into the molecular mechanism of androgen-regulated transcription in LC. C1 [Villar, Joaquin; Tsai-Morris, Chon-Hwa; Dai, Lisheng; Dufau, Maria L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. RP Dufau, ML (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. EM dufaum@mail.nih.gov NR 37 TC 4 Z9 5 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2012 VL 32 IS 8 BP 1566 EP 1580 DI 10.1128/MCB.06002-11 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 917DK UT WOS:000302152500021 PM 22331472 ER PT J AU Roessler, E Velez, JI Zhou, N Muenke, M AF Roessler, Erich Velez, Jorge I. Zhou, Nan Muenke, Maximilian TI Utilizing prospective sequence analysis of SHH, ZIC2, SIX3 and TGIF in holoprosencephaly probands to describe the parameters limiting the observed frequency of mutant gene x gene interactions SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Holoprosencephaly; Digenic inheritance; Mutation spectrum; SHH; ZIC2; SIX3 and TGIF ID MAXILLARY CENTRAL INCISOR; GENOTYPE-PHENOTYPE CORRELATIONS; SONIC HEDGEHOG MUTATION; CLINICAL SPECTRUM; TERMINAL DOMAIN; VARIABILITY; REARRANGEMENTS; FAMILIES; MODELS; RATES AB Clinical molecular diagnostic centers routinely screen SHH, ZIC2, SIX3 and TGIF for mutations that can help to explain holoprosencephaly and related brain malformations. Here we report a prospective Sanger sequence analysis of 189 unrelated probands referred to our diagnostic lab for genetic testing. We identified 28 novel unique mutations in this group (15%) and no instances of deleterious mutations in two genes in the same subject. Our result extends that of other diagnostic centers and suggests that among the aggregate 475 prospectively sequenced holoprosencephaly probands there is negligible evidence for direct gene-gene interactions among these tested genes. We model the predictions of the observed mutation frequency in the context of the hypothesis that gene x gene interactions are a prerequisite for forebrain malformations, i.e. the "multiple-hit" hypothesis. We conclude that such a direct interaction would be expected to be rare and that more subtle genetic and environmental interactions are a better explanation for the clinically observed inter- and intra-familial variability. Published by Elsevier Inc. C1 [Roessler, Erich; Velez, Jorge I.; Zhou, Nan; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mmuenke@nhgri.nih.gov FU Division of Intramural Research of the National Human Genome Research Institute, National Institutes of Health FX The authors wish to thank the patients who participated in this research and the many clinicians who referred them. We thank BD Solomon and D Pineda-Alvarez for constructive comments. JIV would like to thank Prof. Juan Carlos Correa for helpful comments and suggestions on the statistical model. This research was supported by the Division of Intramural Research of the National Human Genome Research Institute, National Institutes of Health. NR 59 TC 15 Z9 15 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD APR PY 2012 VL 105 IS 4 BP 658 EP 664 DI 10.1016/j.ymgme.2012.01.005 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 917OW UT WOS:000302188700021 PM 22310223 ER PT J AU Markello, TC Carlson-Donohoe, H Sincan, M Adams, D Bodine, DM Farrar, JE Vlachos, A Lipton, JM Auerbach, AD Ostrander, EA Chandrasekharappa, SC Boerkoel, CF Gahl, WA AF Markello, Thomas C. Carlson-Donohoe, Hannah Sincan, Murat Adams, David Bodine, David M. Farrar, Jason E. Vlachos, Adrianna Lipton, Jeffrey M. Auerbach, Arleen D. Ostrander, Elaine A. Chandrasekharappa, Settara C. Boerkoel, Cornelius F. Gahl, William A. TI Sensitive quantification of mosaicism using high density SNP arrays and the cumulative distribution function SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Mosaicism; Continuous Distribution Function; Distribution Analysis by Fitting Integrated; Probabilities; DANFIP; CGH; Array comparative genomic hybridization ID TURNER-SYNDROME; MICROARRAY; CGH AB Medicine is rapidly applying exome and genome sequencing to the diagnosis and management of human disease. Somatic mosaicism, however, is not readily detectable by these means, and yet it accounts for a significant portion of undiagnosed disease. We present a rapid and sensitive method, the Continuous Distribution Function as applied to single nucleotide polymorphism (SNP) array data, to quantify somatic mosaic-ism throughout the genome. We also demonstrate application of the method to novel diseases and mechanisms. Published by Elsevier Inc. C1 [Markello, Thomas C.; Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Carlson-Donohoe, Hannah; Sincan, Murat; Adams, David; Gahl, William A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Adams, David; Boerkoel, Cornelius F.] NIH, NIH Undiagnosed Dis Program, Bethesda, MD 20892 USA. [Bodine, David M.] NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Farrar, Jason E.] Johns Hopkins Univ, Sch Med, Dept Oncol, Div Pediat Oncol,Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. [Vlachos, Adrianna; Lipton, Jeffrey M.] Steven & Alexandra Cohen Childrens Med Ctr New Yo, Bone Marrow Failure Program, New Hyde Pk, NY USA. [Vlachos, Adrianna; Lipton, Jeffrey M.] Long Isl Sch Med, Dept Pediat & Mol Med, Hempstead, NY USA. [Auerbach, Arleen D.] Rockefeller Univ, New York, NY USA. [Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Chandrasekharappa, Settara C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Markello, TC (reprint author), NHGRI, Off Clin Director, NIH, Bldg 10-10C107,10 Ctr Dr, Bethesda, MD 20892 USA. EM markellot@mail.nih.gov OI Farrar, Jason/0000-0003-2148-5839; Auerbach, Arleen/0000-0002-6911-8379; Ostrander, Elaine/0000-0001-6075-9738 FU National Human Genome Research Institute; NIH [K08 HL092224]; [RO1 HL 079571] FX This study was supported in part by the Intramural Program of the National Human Genome Research Institute.; We thank Roxanne Fischer, Richard Hess, MaryPat Jones and Ursula Harper in the NHGRI Genomics Core for their excellent technical contributions. This work was supported in part by the Intramural Research Program of the National Human Genome Research Institute. Dr. Farrar was supported by NIH grant K08 HL092224. Dr. Lipton and Dr. Vlachos are supported by RO1 HL 079571. NR 15 TC 4 Z9 4 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 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD APR PY 2012 VL 105 IS 4 BP 665 EP 671 DI 10.1016/j.ymgme.2011.12.015 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 917OW UT WOS:000302188700022 PM 22277120 ER PT J AU Thomason, MK Fontaine, F De Lay, N Storz, G AF Thomason, Maureen K. Fontaine, Fanette De Lay, Nicholas Storz, Gisela TI A small RNA that regulates motility and biofilm formation in response to changes in nutrient availability in Escherichia coli SO MOLECULAR MICROBIOLOGY LA English DT Article ID MESSENGER-RNA; POLYSACCHARIDE ADHESIN; OUTER-MEMBRANE; EXTRACELLULAR-MATRIX; POSITIVE REGULATION; ANTISENSE RNAS; NONCODING RNAS; CURLI; EXPRESSION; GENES AB In bacteria, many small regulatory RNAs (sRNAs) are induced in response to specific environmental signals or stresses and act by base-pairing with mRNA targets to affect protein translation or mRNA stability. In Escherichia coli, the gene for the sRNA IS061/IsrA, here renamed McaS, was predicted to reside in an intergenic region between abgR, encoding a transcription regulator and ydaL, encoding a small MutS-related protein. We show that McaS is a similar to 95 nt transcript whose expression increases over growth, peaking in early-to-mid stationary phase, or when glucose is limiting. McaS uses three discrete single-stranded regions to regulate mRNA targets involved in various aspects of biofilm formation. McaS represses csgD, the transcription regulator of curli biogenesis and activates flhD, the master transcription regulator of flagella synthesis leading to increased motility, a process not previously reported to be regulated by sRNAs. McaS also regulates pgaA, a porin required for the export of the polysaccharide poly beta-1,6-N-acetyl-d-glucosamine. Consequently, high levels of McaS result in increased biofilm formation while a strain lacking mcaS shows reduced biofilm formation. Based on our observations, we propose that, in response to limited nutrient availability, increasing levels of McaS modulate steps in the progression to a sessile lifestyle. C1 [Thomason, Maureen K.; Fontaine, Fanette; Storz, Gisela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA. [Thomason, Maureen K.] Georgetown Univ, Med Ctr, Dept Biochem & Mol & Cellular Biol, Washington, DC 20007 USA. [De Lay, Nicholas] NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Storz, G (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA. EM storz@helix.nih.gov OI Storz, Gisela/0000-0001-6698-1241 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX We thank M. Jarnik for help with the electron microscopy, S. Adhya for providing the purified CRP and N. Majdalani for providing the anti-RpoS antibody. We would like to thank S. Gottesman and current and former members of the Storz lab for comments on the manuscript. This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 75 TC 84 Z9 87 U1 2 U2 32 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD APR PY 2012 VL 84 IS 1 BP 17 EP 35 DI 10.1111/j.1365-2958.2012.07965.x PG 19 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 915HA UT WOS:000302013500003 PM 22289118 ER PT J AU Lee, H Lamichhane, AK Garraffo, HM Kwon-Chung, KJ Chang, YC AF Lee, Hyeseung Lamichhane, Ami Khanal Garraffo, H. Martin Kwon-Chung, Kyung J. Chang, Yun C. TI Involvement of PDK1, PKC and TOR signalling pathways in basal fluconazole tolerance in Cryptococcus neoformans SO MOLECULAR MICROBIOLOGY LA English DT Article ID CELL-WALL INTEGRITY; FUNGAL DRUG-RESISTANCE; CANDIDA-ALBICANS; SACCHAROMYCES-CEREVISIAE; AZOLE RESISTANCE; SCHIZOSACCHAROMYCES-POMBE; PROTEIN-KINASES; FISSION YEAST; MULTIDRUG-RESISTANCE; ANTIFUNGAL AGENTS AB This study shows the importance of PDK1, TOR and PKC signalling pathways to the basal tolerance of Cryptococcus neoformans towards fluconazole, the widely used drug for treatment of cryptococcosis. Mutations in genes integral to these pathway resulted in hypersensitivity to the drug. Upon fluconazole treatment, Mpk1, the downstream target of PKC was phosphorylated and its phosphorylation required Pdk1. We show genetically that the PDK1 and TOR phosphorylation sites in Ypk1 as well as the kinase activity of Ypk1 are required for the fluconazole basal tolerance. The involvement of these pathways in fluconazole basal tolerance was associated with sphingolipid homeostasis. Deletion of PDK1, SIN1 or YPK1 but not MPK1 affected cell viability in the presence of sphingolipid biosynthesis inhibitors. Concurrently, pdk1?, sin1?, ypk1? and mpk1? exhibited altered sphingolipid content and elevated fluconazole accumulation compared with the wild type. The fluconazole hypersensitivity phenotype of these mutants, therefore, appears to be the result of malfunction of the influx/efflux systems due to modifications of membrane sphingolipid content. Interestingly, the reduced virulence of these strains in mice suggests that the cryptococcal PDK1, PKC, and likely the TOR pathways play an important role in managing stress exerted either by fluconazole or by the host environment. C1 [Lee, Hyeseung; Lamichhane, Ami Khanal; Kwon-Chung, Kyung J.; Chang, Yun C.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Garraffo, H. Martin] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Chang, YC (reprint author), NIAID, Lab Clin Infect Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ychang@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, NIH FX We thank Y.J. Kim, T. Balla, M.A. Singh and M. Del Poeta for suggestion and technical help in analysis of complex sphingolipids, Andy Han for technical help in initial screening of the mutants and A. Varma for critical discussions and reading of the manuscript. This study was supported by funds from the intramural programme of the National Institute of Allergy and Infectious Diseases, NIH. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 91 TC 16 Z9 17 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD APR PY 2012 VL 84 IS 1 BP 130 EP 146 DI 10.1111/j.1365-2958.2012.08016.x PG 17 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 915HA UT WOS:000302013500011 PM 22339665 ER PT J AU Willour, VL Seifuddin, F Mahon, PB Jancic, D Pirooznia, M Steele, J Schweizer, B Goes, FS Mondimore, FM MacKinnon, DF Perlis, RH Lee, PH Huang, J Kelsoe, JR Shilling, PD Rietschel, M Nothen, M Cichon, S Gurling, H Purcell, S Smoller, JW Craddock, N DePaulo, JR Schulze, TG McMahon, FJ Zandi, PP Potash, JB AF Willour, V. L. Seifuddin, F. Mahon, P. B. Jancic, D. Pirooznia, M. Steele, J. Schweizer, B. Goes, F. S. Mondimore, F. M. MacKinnon, D. F. Perlis, R. H. Lee, P. H. Huang, J. Kelsoe, J. R. Shilling, P. D. Rietschel, M. Noethen, M. Cichon, S. Gurling, H. Purcell, S. Smoller, J. W. Craddock, N. DePaulo, J. R., Jr. Schulze, T. G. McMahon, F. J. Zandi, P. P. Potash, J. B. CA BiGS Consortium TI A genome-wide association study of attempted suicide SO MOLECULAR PSYCHIATRY LA English DT Article DE ACP1; LRRTM4; 2p25; Wnt; lithium ID PROTEIN-TYROSINE-PHOSPHATASE; BIPOLAR DISORDER; MAJOR DEPRESSION; GENE-EXPRESSION; EARLY-ONSET; GENOTYPE IMPUTATION; PREFRONTAL CORTEX; FAMILIAL PATHWAYS; BEHAVIOR; LINKAGE AB The heritable component to attempted and completed suicide is partly related to psychiatric disorders and also partly independent of them. Although attempted suicide linkage regions have been identified on 2p11-12 and 6q25-26, there are likely many more such loci, the discovery of which will require a much higher resolution approach, such as the genome-wide association study (GWAS). With this in mind, we conducted an attempted suicide GWAS that compared the single-nucleotide polymorphism (SNP) genotypes of 1201 bipolar (BP) subjects with a history of suicide attempts to the genotypes of 1497 BP subjects without a history of suicide attempts. In all, 2507 SNPs with evidence for association at P < 0.001 were identified. These associated SNPs were subsequently tested for association in a large and independent BP sample set. None of these SNPs were significantly associated in the replication sample after correcting for multiple testing, but the combined analysis of the two sample sets produced an association signal on 2p25 (rs300774) at the threshold of genome-wide significance (P = 5.07 x 10(-8)). The associated SNPs on 2p25 fall in a large linkage disequilibrium block containing the ACP1 (acid phosphatase 1) gene, a gene whose expression is significantly elevated in BP subjects who have completed suicide. Furthermore, the ACP1 protein is a tyrosine phosphatase that influences Wnt signaling, a pathway regulated by lithium, making ACP1 a functional candidate for involvement in the phenotype. Larger GWAS sample sets will be required to confirm the signal on 2p25 and to identify additional genetic risk factors increasing susceptibility for attempted suicide. Molecular Psychiatry (2012) 17, 433-444; doi: 10.1038/mp.2011.4; published online 22 March 2011 C1 [Willour, V. L.; Seifuddin, F.; Mahon, P. B.; Jancic, D.; Pirooznia, M.; Schweizer, B.; Goes, F. S.; Mondimore, F. M.; MacKinnon, D. F.; DePaulo, J. R., Jr.; Zandi, P. P.; Potash, J. B.] Johns Hopkins Univ Hosp, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Steele, J.; Schulze, T. G.; McMahon, F. J.] Natl Inst Mental Hlth Intramural Res Program, Genet Basis Mood & Anxiety Disorders Unit, NIH, US Dept HHS, Bethesda, MD USA. [Perlis, R. H.; Lee, P. H.; Huang, J.; Purcell, S.; Smoller, J. W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Perlis, R. H.; Lee, P. H.; Huang, J.; Purcell, S.; Smoller, J. W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kelsoe, J. R.; Shilling, P. D.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Rietschel, M.] Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. [Rietschel, M.] Univ Bonn, Dept Psychiat, Bonn, Germany. [Noethen, M.; Cichon, S.] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany. [Noethen, M.] Univ Bonn, Inst Human Genet, Bonn, Germany. [Cichon, S.] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany. [Gurling, H.] UCL, Dept Mental Hlth Sci, London, England. [Craddock, N.] Cardiff Univ, Sch Med, Dept Psychol, Cardiff, Wales. [Schulze, T. G.] Univ Gottingen, Dept Psychiat & Psychotherapy, Sect Psychiat Genet, Gottingen, Germany. RP Willour, VL (reprint author), Johns Hopkins Univ Hosp, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 4-132, Baltimore, MD 21287 USA. EM willour@jhmi.edu RI Smith, Erin/E-5933-2011; McInnis, Melvin/F-6963-2012; Schulze, Thomas/H-2157-2013; Gurling, Hugh/A-5029-2010; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Zhang, Peng/N-2920-2014; OI McInnis, Melvin/0000-0002-0375-6247; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Zhang, Peng/0000-0003-1182-1392; Nothen, Markus/0000-0002-8770-2464; McMahon, Francis/0000-0002-9469-305X FU Concordant Rater Systems; Proteus Biomedical; RIDVentures; National Institute of Mental Health [MH079240]; American Foundation for Suicide Prevention; Margaret Price Investigatorships; [R01 MH079799] FX The authors declare no conflict of interest. Dr Perlis has received consulting fees from Concordant Rater Systems, Proteus Biomedical, and RIDVentures, and royalties/patent fees from Concordant Rater Systems.; This work was supported by grants from the National Institute of Mental Health (MH079240 to VLW) and the American Foundation for Suicide Prevention (VLW). It was also supported in part by R01 MH079799 (JWS). Drs Willour and Potash were also supported by Margaret Price Investigatorships. DNA samples were prepared and distributed by Rutgers University under a contract from the NIMH. We are grateful to the many interviewers and diagnosticians who contributed to this project, and to the families who devoted their time and effort to the study. Genome-wide SNP genotyping of the NIMH samples was performed through the Genetic Association Information Network under the direction of The Bipolar Genome Study (BiGS) Consortium. The Principal Investigators and Co-Investigators were: University of California San Diego, La Jolla, CA: John R Kelsoe (PI), Tiffany A Greenwood, Thomas B Barrett, Caroline M Nievergelt, Rebecca McKinney, Paul D Shilling; Scripps Research Institute, La Jolla, CA: Nicholas Schork (PI), Erin N Smith, Cinnamon S Bloss; Indiana University, Bloomington, IN: John I Nurnberger, Jr (PI), Howard J Edenberg, Tatiana Foroud, Daniel M Koller; University of Chicago, Chicago, IL: Elliot Gershon (PI), Chunyu Liu, Judith A Badner; Rush University Medical Center, Chicago, IL: William A Scheftner; Howard University, Washington, DC: William B Lawson (PI), Evaristus A Nwulia, Maria Hipolito; University of Iowa, Iowa City, IA: William Coryell (PI); Washington University, St Louis, MO: John Rice (PI); University of California San Francisco, San Francisco, CA: William Byerley (PI); National Institute of Mental Health, Bethesda, MD: Francis McMahon (PI), Thomas G Schulze; University of Pennsylvania, Philadelphia, PA: Wade Berrettini (PI); Johns Hopkins University, Baltimore, MD: James B Potash (PI), Peter P Zandi, Pamela B Mahon; University of Michigan, Ann Arbor, MI: Melvin G McInnis (PI), Sebastian Zollner, Peng Zhang; The Translational Genomics Research Institute, Phoenix, AZ: David Craig (PI), Szabolics Szelinger. Data and biomaterials were collected in four projects that participated in the National Institute of Mental Health (NIMH) Bipolar Disorder Genetics Initiative. From 1991 to 1998, the Principal Investigators and Co-Investigators were: Indiana University, Indianapolis, IN, U01 MH46282: John Nurnberger, Marvin Miller and Elizabeth Bowman; Washington University, St Louis, MO, U01 MH46280: Theodore Reich, Allison Goate and John Rice; Johns Hopkins University, Baltimore, MD U01 MH46274: J Raymond DePaulo, Jr, Sylvia Simpson and Colin Stine; NIMH Intramural Research Program, Clinical Neurogenetics Branch, Bethesda, MD: Elliot Gershon, Diane Kazuba and Elizabeth Maxwell. Data and biomaterials were collected as part of 10 projects that participated in the National Institute of Mental Health (NIMH) Bipolar Disorder Genetics Initiative.; From 1999 to 2003, the Principal Investigators and Co-Investigators were: Indiana University, Indianapolis, IN, R01 MH59545: John Nurnberger, Marvin J Miller, Elizabeth S Bowman, N Leela Rau, P Ryan Moe, Nalini Samavedy, Rif El-Mallakh (at the University of Louisville), Husseini Manji (at the Wayne State University), Debra A Glitz (at the Wayne State University), Eric T Meyer, Carrie Smiley, Tatiana Foroud, Leah Flury, Danielle M Dick, Howard Edenberg; Washington University, St Louis, MO, R01 MH059534: John Rice, Theodore Reich, Allison Goate, Laura Bierut; Johns Hopkins University, Baltimore, MD, R01 MH59533: Melvin McInnis, J Raymond DePaulo, Jr, Dean F MacKinnon, Francis M Mondimore, James B Potash, Peter P Zandi, Dimitrios Avramopoulos and Jennifer Payne; University of Pennsylvania, PA, R01 MH59553: Wade Berrettini; University of California at Irvine, CA, R01 MH60068: William Byerley and Mark Vawter; University of Iowa, IA, R01 MH059548: William Coryell and Raymond Crowe; University of Chicago, IL, R01 MH59535: Elliot Gershon, Judith Badner, Francis McMahon, Chunyu Liu, Alan Sanders, Maria Caserta, Steven Dinwiddie, Tu Nguyen, Donna Harakal; University of California at San Diego, CA, R01 MH59567: John Kelsoe, Rebecca McKinney; Rush University, IL, R01 MH059556: William Scheftner, Howard M Kravitz, Diana Marta, Annette Vaughn-Brown and Laurie Bederow; NIMH Intramural Research Program, Bethesda, MD, 1Z01MH002810-01: Francis J Mc Mahon, Layla Kassem, Sevilla Detera-Wadleigh, Lisa Austin and Dennis L Murphy. Data and biomaterials were collected as part of 11 projects (Study 40) that participated in the National Institute of Mental Health (NIMH) Bipolar Disorder Genetics Initiative. From 2003 to 2007, the Principal Investigators and Co-Investigators were: Indiana University, Indianapolis, IN, R01 MH59545: John Nurnberger, Marvin J Miller, Elizabeth S Bowman, N Leela Rau, P Ryan Moe, Nalini Samavedy, Rif El-Mallakh (at the University of Louisville), Husseini Manji (at Johnson and Johnson), Debra A Glitz (at the Wayne State University), Eric T Meyer (at the Oxford University, UK), Carrie Smiley, Tatiana Foroud, Leah Flury, Danielle M Dick (at the Virginia Commonwealth University), Howard Edenberg; Washington University, St Louis, MO, R01 MH059534: John Rice, Theodore Reich, Allison Goate, Laura Bierut K02 DA21237; Johns Hopkins University, Baltimore, MD, R01 MH59533: Melvin McInnis, J Raymond DePaulo, Jr, Dean F MacKinnon, Francis M Mondimore, James B Potash, Peter P Zandi, Dimitrios Avramopoulos and Jennifer Payne; University of Pennsylvania, PA, R01 MH59553: Wade Berrettini; University of California at San Francisco, CA, R01 MH60068: William Byerley and Sophia Vinogradov; University of Iowa, IA, R01 MH059548: William Coryell, and Raymond Crowe; University of Chicago, IL, R01 MH59535: Elliot Gershon, Judith Badner, Francis McMahon, Chunyu Liu, Alan Sanders, Maria Caserta, Steven Dinwiddie, Tu Nguyen, Donna Harakal; University of California at San Diego, CA, R01 MH59567: John Kelsoe, Rebecca McKinney; Rush University, IL, R01 MH059556: William Scheftner, Howard M Kravitz, Diana Marta, Annette Vaughn-Brown, and Laurie Bederow; NIMH Intramural Research Program, Bethesda, MD, 1Z01MH002810-01: Francis J McMahon, Layla Kassem, Sevilla Detera-Wadleigh, Lisa Austin, Dennis L Murphy; Howard University: William B Lawson, Evarista Nwulia, and Maria Hipolito. NR 47 TC 43 Z9 43 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD APR PY 2012 VL 17 IS 4 BP 433 EP 444 DI 10.1038/mp.2011.4 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 917KL UT WOS:000302173900010 PM 21423239 ER PT J AU Zatorre, RJ Fields, RD Johansen-Berg, H AF Zatorre, Robert J. Fields, R. Douglas Johansen-Berg, Heidi TI Plasticity in gray and white: neuroimaging changes in brain structure during learning SO NATURE NEUROSCIENCE LA English DT Review ID VOXEL-BASED MORPHOMETRY; IN-VIVO MRI; ACTION-POTENTIALS; MULTIPLE-SCLEROSIS; VAL66MET POLYMORPHISM; CORTICAL THICKNESS; MATTER DEVELOPMENT; STRUCTURE PREDICTS; CORPUS-CALLOSUM; NERVOUS-SYSTEM AB Human brain imaging has identified structural changes in gray and white matter that occur with learning. However, ascribing imaging measures to underlying cellular and molecular events is challenging. Here we review human neuroimaging findings of structural plasticity and then discuss cellular and molecular level changes that could underlie observed imaging effects. Greater dialog between researchers in these different fields would help to facilitate cross-talk between cellular and systems level explanations of how learning sculpts brain structure. C1 [Johansen-Berg, Heidi] John Radcliffe Hosp, Oxford Ctr Funct MRI Brain FMRIB, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England. [Zatorre, Robert J.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Fields, R. Douglas] NICHHD, Nervous Syst Dev, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Fields, R. Douglas] NICHHD, Plast Sect, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Johansen-Berg, H (reprint author), John Radcliffe Hosp, Oxford Ctr Funct MRI Brain FMRIB, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England. EM heidi@fmrib.ox.ac.uk OI Johansen-Berg, Heidi/0000-0002-4134-9730 FU Canadian Institutes of Health Research; Natural Sciences and Engineering Research Council of Canada; US National Institutes of Health; Wellcome Trust FX R.J.Z. is supported by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada; R.D.F. is supported by funds for intramural research at the US National Institutes of Health; H.J.-B. is supported by the Wellcome Trust. NR 101 TC 395 Z9 402 U1 14 U2 121 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD APR PY 2012 VL 15 IS 4 BP 528 EP 536 DI 10.1038/nn.3045 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 916PA UT WOS:000302114500010 PM 22426254 ER PT J AU Restifo, NP Dudley, ME Rosenberg, SA AF Restifo, Nicholas P. Dudley, Mark E. Rosenberg, Steven A. TI Adoptive immunotherapy for cancer: harnessing the T cell response SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID CHIMERIC ANTIGEN RECEPTOR; VERSUS-HOST-DISEASE; ESTABLISHED PULMONARY METASTASES; TUMOR-INFILTRATING LYMPHOCYTES; SUPERIOR ANTITUMOR IMMUNITY; HEMATOPOIETIC STEM-CELLS; IN-VIVO; GENE-THERAPY; MELANOMA PATIENTS; ENGINEERED LYMPHOCYTES AB Immunotherapy based on the adoptive transfer of naturally occurring or gene-engineered T cells can mediate tumour regression in patients with metastatic cancer. Here, we discuss progress in the use of adoptively transferred T cells, focusing on how they can mediate tumour cell eradication. Recent advances include more accurate targeting of antigens expressed by tumours and the associated vasculature, and the successful use of gene engineering to re-target T cells before their transfer into the patient. We also describe how new research has helped to identify the particular T cell subsets that can most effectively promote tumour eradication. C1 [Restifo, Nicholas P.; Dudley, Mark E.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. EM restifon@mail.nih.gov; sar@mail.nih.gov RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Center for Cancer Research, US National Cancer Institute (NCI), National Institutes of Health FX This work was supported by the Intramural Research Program of the Center for Cancer Research, US National Cancer Institute (NCI), National Institutes of Health. The authors would like to thank C. Klebanoff, L. Gattinoni, C. Hinrichs and P. Muranski for discussions about T cell differentiation, M. Bachinski for editorial help, E. Tran for critically reading the manuscript, and all the members of the translational immunology team at the NCI, especially J. C. Yang, P. F. Robbins, R. A. Morgan, R. M. Sherry, S. Feldman, M. Parkhurst, M. Hughes, G. Phan and U. Kammula. NR 166 TC 546 Z9 556 U1 30 U2 302 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 EI 1474-1741 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD APR PY 2012 VL 12 IS 4 BP 269 EP 281 DI 10.1038/nri3191 PG 13 WC Immunology SC Immunology GA 916WA UT WOS:000302132700012 PM 22437939 ER PT J AU Weng, NP Araki, Y Subedi, K AF Weng, Nan-ping Araki, Yasuto Subedi, Kalpana TI The molecular basis of the memory T cell response: differential gene expression and its epigenetic regulation SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID HEMATOPOIETIC STEM-CELLS; IFN-GAMMA LOCI; HISTONE ACETYLATION; CUTTING EDGE; HUMAN GENOME; CPG ISLANDS; CHROMATIN-STRUCTURE; DNA METHYLATION; DYNAMIC CHANGES; B-CELLS AB How the immune system remembers a previous encounter with a pathogen and responds more efficiently to a subsequent encounter has been one of the central enigmas for immunologists for over a century. The identification of pathogen-specific memory lymphocytes that arise after an infection provided a cellular basis for immunological memory. But the molecular mechanisms of immunological memory remain only partially understood. The emerging evidence suggests that epigenetic changes have a key role in controlling the distinct transcriptional profiles of memory lymphocytes and thus in shaping their function. In this Review, we summarize the recent progress that has been made in assessing the differential gene expression and chromatin modifications in memory CD4(+) and CD8(+) T cells, and we present our current understanding of the molecular basis of memory T cell function. C1 [Weng, Nan-ping; Araki, Yasuto; Subedi, Kalpana] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. RP Weng, NP (reprint author), NIA, Lab Mol Biol & Immunol, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM Wengn@mail.nih.gov RI perumal, murugiah/D-1565-2012 FU US National Institute on Aging, National Institutes of Health FX We thank R. Hodes, K. Zhao and the anonymous reviewers for critical reading of the manuscript and helpful suggestions. This research was supported by the Intramural Research Programs of the US National Institute on Aging, National Institutes of Health. NR 67 TC 89 Z9 91 U1 2 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD APR PY 2012 VL 12 IS 4 BP 306 EP 315 DI 10.1038/nri3173 PG 10 WC Immunology SC Immunology GA 916WA UT WOS:000302132700015 PM 22421787 ER PT J AU Crowley, RW Asthagiri, AR Starke, RM Zusman, EE Chiocca, EA Lonser, RR AF Crowley, R. Webster Asthagiri, Ashok R. Starke, Robert M. Zusman, Edie E. Chiocca, E. Antonio Lonser, Russell R. CA Res Comm Congress Neurological TI In-training Factors Predictive of Choosing and Sustaining a Productive Academic Career Path in Neurological Surgery SO NEUROSURGERY LA English DT Article DE Academic career; Neurosurgery; Publications; Residency training ID MEDICAL-SCHOOL PERFORMANCE; RESIDENT-SELECTION; CRITERIA; CHOICE AB BACKGROUND: Factors during neurosurgical residency that are predictive of an academic career path and promotion have not been defined. OBJECTIVE: To determine factors associated with selecting and sustaining an academic career in neurosurgery by analyzing in-training factors for all graduates of American College of Graduate Medical Education (ACGME)-accredited programs between 1985 and 1990. METHODS: Neurological surgery residency graduates (between 1985 and 1990) from ACGME-approved training programs were analyzed to determine factors associated with choosing an academic career path and having academic success. RESULTS: Information was available for 717 of the 720 (99%) neurological surgery resident training graduates (678 male, 39 female). One hundred thirty-eight graduates (19.3%) held full-time academic positions. One hundred seven (14.9%) were professors and 35 (4.9%) were department chairs/chiefs. An academic career path/success was associated with more total (5.1 vs 1.9; P < .001) and first-author publications (3.0 vs 1.0; P < .001) during residency. Promotion to professor or chair/chief was associated with more publications during residency (P < .001). Total publications and first-author publications were independent predictors of holding a current academic position and becoming professor or chair/chief. Although male trainees published more than female trainees (2.6 vs 0.9 publications; P < .004) during training, no significant sex difference was observed regarding current academic position. Program size (>= 2 graduates a year; P = .02) was predictive of an academic career but not predictive of becoming professor or chair/chief (P > .05). CONCLUSION: Defined in-training factors including number of total publications, number of first-author publications, and program size are predictive of residents choosing and succeeding in an academic career path. C1 [Crowley, R. Webster; Starke, Robert M.] Univ Virginia Hlth Syst, Dept Neurol Surg, Charlottesville, VA USA. [Asthagiri, Ashok R.; Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Zusman, Edie E.] Sutter Neurosci Inst, Sacramento, CA USA. [Chiocca, E. Antonio] Ohio State Univ, Dept Neurol Surg, Columbus, OH 43210 USA. RP Crowley, RW (reprint author), Barrow Neurol Inst, 2910 N 3rd Ave, Phoenix, AZ 85013 USA. EM Webster.crowley@bnaneuro.net FU National Institutes of Health, National Institute of Neurological Disorders and Stroke FX We would like to thank the American Board of Neurological Surgeons, in particular Mary Louise Sanderson and Maggie Hall. Their assistance was invaluable in accumulating and providing the list of neurosurgical residency graduates included in this study. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke. The Research Committee of the Congress of Neurological Surgeons comprises the following individuals: Russell R. Lonser, MD (chair), National Institutes of Health, Bethesda, Maryland; P. David Adelson, MD, Phoenix Children's Hospital, Phoenix, Arizona; Ashok R. Asthagiri, MD, National Institutes of Health, Bethesda, Maryland; Mitchel S. Berger, MD, University of California, San Francisco, San Francisco, California; Nicholas M. Boulis, MD, Emory University, Atlanta, Georgia; Thomas C. Chen, MD, PhD, University of Southern California, Los Angeles, California; E. Antonio Chiocca, MD, PhD, Ohio State University, Columbus, Ohio; E. Sander Connolly, MD, Columbia University, New York, New York; R. Webster Crowley, MD, University of Virginia, Charlottesville, Virginia; Ralph G. Dacey, MD, Washington University, St. Louis, Missouri; Zoher Ghogawala, MD, Greenwich Hospital, Greenwich, Connecticut; Rachel Groman, American Association of Neurological Surgeons/Congress of Neurological Surgeons Washington Office, Washington, DC; Robert E. Gross, MD, PhD, Emory University, Atlanta, Georgia; Murat Gunel, MD, Yale University, New Haven, Connecticut; David D. Limbrick, MD, PhD, Washington University, St. Louis, Missouri; Guy McKhann, MD, Columbia University, New York, New York; John K. Park, MD, PhD, National Institutes of Health, Bethesda, Maryland; Ganesh Rao, MD, MD Anderson Cancer Center, Houston, Texas; Jonas Sheehan, MD, Pennsylvania State University, Hershey, Pennsylvania; Michael P. Steinmetz, MD, Cleveland Clinic, Cleveland, Ohio; Michael A. Vogelbaum, MD, PhD, Cleveland Clinic, Cleveland, Ohio; Gregory J. Zipfel, MD, Washington University, St. Louis, Missouri; and Edie E. Zusman, MD, Sutter Neuroscience Institute, Sacramento, California. NR 13 TC 8 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD APR PY 2012 VL 70 IS 4 BP 1024 EP 1032 DI 10.1227/NEU.0b013e3182367143 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 914FF UT WOS:000301934000079 PM 21946503 ER PT J AU Jackson, AB Nanda, PK Rold, TL Sieckman, GL Szczodroski, AF Hoffman, TJ Chen, XY Smith, CJ AF Jackson, Andrew B. Nanda, Prasant K. Rold, Tammy L. Sieckman, Gary L. Szczodroski, Ashley F. Hoffman, Timothy J. Chen, Xiaoyuan Smith, Charles J. TI Cu-64-NO2A-RGD-Glu-6-Ahx-BBN(7-14)NH2: a heterodimeric targeting vector for positron emission tomography imaging of prostate cancer SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE Cu-64; RGD-BBN; Heterodimeric peptide; Gastrin-releasing peptide receptor (GRPr); Integrin alpha(v)beta(3) receptor; Positron emission tomography (PET) ID PEPTIDE RADIOPHARMACEUTICALS; BREAST-CANCER; RGD PEPTIDES; IN-VIVO; BOMBESIN; EXPRESSION; TUMORS; PET; RADIOTRACERS; RECEPTORS AB Introduction: The present study describes the design and development of a new heterodimeric RGD-bombesin (BBN) agonist peptide ligand for dual receptor targeting of the form Cu-64-NO2A-RGD-Glu-6-Ahx-BBN(7-14)NH2 in which Cu-64=a positron emitting radiometal; NO2A=1,4,7-triazacyclononane-1,4-diacetic acid; Glu=glutamic acid; 6-Ahx=6-aminohexanoic acid; RGD=the amino acid sequence [Arg-Gly-Asp], a nonregulatory peptide that has been used extensively to target alpha(v)beta(3) receptors up-regulated on tumor cells and neovasculature; and BBN(7-14)NH2=Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2, an agonist analogue of bombesin peptide for specific targeting of the gastrin-releasing peptide receptor (GRPr). Methods: RGD-Glu-6-Ahx-BBN(7-14)NH2 was manually coupled with NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid), and the resulting conjugate was labeled with Cu-64 to yield Cu-64-NO2A-RGD-Glu-6-Ahx-BBN(7-14)NH2. Purification was achieved via reversed-phase high-performance liquid chromatography and characterization confirmed by electrospray ionization mass spectrometry. Results: Competitive displacement binding assays displayed single-digit nanomolar IC50 values showing very high binding affinities toward the GRPr for the new heterodimeric peptide analogues. In vivo biodistribution studies showed high uptake and retention of tumor-associated radioactivity in PC-3 tumor-bearing rodent models with little accumulation and retention in nontarget tissues. The radiolabeled conjugate also exhibited rapid urinary excretion and high tumor-to-background ratios. Micro-positron emission tomography (microPET) molecular imaging investigations produced high-quality, high-contrast images in PC-3 tumor-bearing mice 15 h postinjection. Conclusions: Based on microPET imaging experiments that show high-quality, high-contrast images with virtually no residual gastrointestinal radioactivity, this new heterodimeric RGD-BBN conjugate can be considered as a promising PET tracer candidate for the diagnosis of GRPr-positive tumors in human patients. Published by Elsevier Inc. C1 [Smith, Charles J.] Univ Missouri, Dept Radiol, MU Sch Med, Res Reactor Ctr, Columbia, MO 65211 USA. [Jackson, Andrew B.; Nanda, Prasant K.; Hoffman, Timothy J.; Smith, Charles J.] Univ Missouri, Sch Med, Dept Radiol, Columbia, MO 65211 USA. [Rold, Tammy L.; Sieckman, Gary L.; Szczodroski, Ashley F.; Hoffman, Timothy J.; Smith, Charles J.] Harry S Truman Mem Vet Hosp, Div Res, Columbia, MO 65201 USA. [Hoffman, Timothy J.; Smith, Charles J.] Univ Missouri, Sch Med, Dept Internal Med, Columbia, MO 65211 USA. [Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Smith, CJ (reprint author), Univ Missouri, Dept Radiol, MU Sch Med, Res Reactor Ctr, 1 Hosp Dr, Columbia, MO 65211 USA. EM smithcj@health.missouri.edu FU United States Department of Veterans' Affairs VA FX This material was the result of work supported with resources and the use of facilities at the Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, and the University of Missouri School of Medicine, Columbia, MO 65211, USA. This work was funded in part by The United States Department of Veterans' Affairs VA Merit Award. NR 29 TC 22 Z9 23 U1 3 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD APR PY 2012 VL 39 IS 3 BP 377 EP 387 DI 10.1016/j.nucmedbio.2011.10.004 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 914OV UT WOS:000301961700007 PM 22226021 ER PT J AU Leventhal, A Chen, G Negro, A Boehm, M AF Leventhal, A. Chen, G. Negro, A. Boehm, M. TI The benefits and risks of stem cell technology SO ORAL DISEASES LA English DT Review DE medicine; stem cell; induced pluripotent stem cell; embryonic stem cell; regenerative therapy ID UMBILICAL-CORD BLOOD; LONG-QT SYNDROME; BONE-MARROW; MYOCARDIAL-INFARCTION; PROGENITOR CELLS; MYELODYSPLASTIC SYNDROMES; DEFINED FACTORS; DENTAL-TISSUES; CARDIAC REPAIR; STROMAL CELLS AB The potential impact of stem cell technology on medical and dental practice is vast. Stem cell research will not only provide the foundation for future therapies, but also reveal unique insights into basic disease mechanisms. Therefore, an understanding of stem cell technology will be necessary for clinicians in the future. Herein, we give a basic overview of stem cell biology and therapeutics for the practicing clinician. Oral Diseases ( 2012) 18, 217-222 C1 [Boehm, M.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20817 USA. RP Boehm, M (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10 CRC,Room 5-3132, Bethesda, MD 20817 USA. EM boehmm@nhlbi.nih.gov FU Intramural NIH HHS [ZIA HL006079-03] NR 62 TC 1 Z9 1 U1 1 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1354-523X J9 ORAL DIS JI Oral Dis. PD APR PY 2012 VL 18 IS 3 BP 217 EP 222 DI 10.1111/j.1601-0825.2011.01870.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 901RZ UT WOS:000300985800001 PM 22093062 ER PT J AU Jarcho, JM Mayer, EA Jiang, ZK Feier, NA London, ED AF Jarcho, Johanna M. Mayer, Emeran A. Jiang, Ziyue Karen Feier, Natasha A. London, Edythe D. TI Pain, affective symptoms, and cognitive deficits in patients with cerebral dopamine dysfunction SO PAIN LA English DT Review DE Dopamine; Chronic pain; Depression; Anxiety; Parkinson disease; Drug abuse; Schizophrenia ID CATECHOL-O-METHYLTRANSFERASE; RECEPTOR-BINDING CHARACTERISTICS; COMT VAL(158)MET POLYMORPHISM; BURNING MOUTH SYNDROME; LONG-TERM NOCICEPTION; RAT NUCLEUS-ACCUMBENS; DECISION-MAKING TASK; PARKINSONS-DISEASE; HUMAN BRAIN; TRANSPORTER AVAILABILITY AB Converging preclinical, and human epidemiological, neuroimaging, and genetic evidence suggests a central role for dopamine neurotransmission in modulating pain perception and analgesia. Dysregulation in dopamine signaling may modulate the experience of pain both directly, by enhancing or diminishing the propagation of nociceptive signals, and indirectly, by influencing affective and cognitive processes, which affect the expectation, experience, and interpretation of nociceptive signals. Hypersensitivity to pain and high rates of comorbid chronic pain are common in disorders linked with deficits in dopamine system function, including disorders of mood and affect, substance abuse, and Parkinson disease. Hyposensitivity to pain, however, is common in patients with schizophrenia, which has been linked with excessive dopamine neurotransmission. Although patients are typically affected most by the primary symptoms of their disorders, alterations in pain perception may further increase the burden of their illness, compromising their quality of life. The present review focuses on this relationship, and discusses clinical and potential therapeutic implications for both patients with dopamine-related disorders and those with chronic pain syndromes. (C) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Mayer, Emeran A.] Univ Calif Los Angeles, Ctr Neurobiol Stress, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Jarcho, Johanna M.] NIMH, Bethesda, MD 20892 USA. [Jarcho, Johanna M.; Mayer, Emeran A.; Feier, Natasha A.; London, Edythe D.] Univ Calif Los Angeles, Oppenheimer Family Ctr Neurobiol Stress, Dept Med, Los Angeles, CA 90095 USA. [Jiang, Ziyue Karen; London, Edythe D.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. RP Mayer, EA (reprint author), Univ Calif Los Angeles, Ctr Neurobiol Stress, Dept Mol & Med Pharmacol, CHS 42-210,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM emayer@ucla.edu OI Jarcho, Johanna/0000-0001-9075-6968 FU National Institutes of Health [T32 MH017140, DK 64531, DK 48351, DK 082370]; Thomas P. and Katherine K. Pike Chair in Addiction Studies; Margaret Greene Family Trust FX This work was supported in part by National Institutes of Health Grants T32 MH017140 (JMJ), DK 64531, DK 48351, and DK 082370 (EM), and from the Thomas P. and Katherine K. Pike Chair in Addiction Studies, and the Margaret Greene Family Trust (EDL). NR 175 TC 45 Z9 46 U1 2 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD APR PY 2012 VL 153 IS 4 BP 744 EP 754 DI 10.1016/j.pain.2012.01.002 PG 11 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 913KS UT WOS:000301877300006 PM 22386471 ER PT J AU Morton, CL Maris, JM Keir, ST Gorlick, R Kolb, EA Billups, CA Wu, JR Smith, MA Houghton, PJ AF Morton, Christopher L. Maris, John M. Keir, Stephen T. Gorlick, Richard Kolb, E. Anders Billups, Catherine A. Wu, Jianrong Smith, Malcolm A. Houghton, Peter J. TI Combination testing of cediranib (AZD2171) against childhood cancer models by the pediatric preclinical testing program SO PEDIATRIC BLOOD & CANCER LA English DT Article DE AZD2171; cediranib; developmental therapeutics; preclinical testing ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; PHASE-I; COLORECTAL-CANCER; MAMMALIAN TARGET; MTOR INHIBITOR; RAPAMYCIN; ANGIOGENESIS; PATHWAY; POTENT AB Background Cediranib (AZD2171) is a potent small molecule inhibitor of vascular endothelial growth factor (VEGF) receptors. Cediranib has demonstrated single agent activity in several adult cancers and is being studied in combination with standard cytotoxic agents in multiple disease settings. Procedures. Cediranib was tested in vivo against six childhood tumor xenograft models (four sarcomas, one glioblastoma, one neuroblastoma) alone or combined with cyclophosphamide (two models), vincristine (three models) or cisplatin (one model), each administered at its maximum tolerated dose, or rapamycin (six models). Results. The combination of cediranib with standard cytotoxic agents was superior to the cytotoxic agent used alone for a single xenograft (one of the three xenografts evaluated for the vincristine-cediranib combination). The cediranib-cyclophosphamide combination was inferior to single agent cyclophosphamide in time to event for both models studied and was significantly inferior for one of the models. Cediranib combined with rapamycin was superior to each of the agents used alone in two of the six models and was determined to be additive or supra-additive with rapamycin in four models, although the effects were not large. Conclusions. Cediranib combined with cytotoxic chemotherapy agents demonstrated little or no benefit (and in one case was significantly inferior) compared to chemotherapy alone for the six pediatric cancer xenografts studied. By contrast, the combination of cediranib with rapamycin was additive or supra-additive in four of the six models in terms of prolongation of time to event, though tumor regressions were not observed for this combination. Pediatr Blood Cancer 2012; 58: 566-571. (C) 2011 Wiley Periodicals, Inc. C1 [Morton, Christopher L.; Billups, Catherine A.; Wu, Jianrong] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Houghton, Peter J.] Nationwide Childrens Hosp, Res Inst, Ctr Childhood Canc, Columbus, OH 43205 USA. [Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA. [Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA. [Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Houghton, PJ (reprint author), Nationwide Childrens Hosp, Res Inst, Ctr Childhood Canc, 700 Childrens Dr, Columbus, OH 43205 USA. EM peter.houghton@nationwidechildrens.org FU National Cancer Institute [NO1-CM-42216, NO1-CM91001-03, CA21765, CA108786] FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216, NO1-CM91001-03, CA21765, CA108786. NR 39 TC 10 Z9 11 U1 0 U2 0 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD APR PY 2012 VL 58 IS 4 BP 566 EP 571 DI 10.1002/pbc.23159 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 895NK UT WOS:000300502800017 PM 21538824 ER PT J AU Houghton, PJ Kang, MH Reynolds, CP Morton, CL Kolb, EA Gorlick, R Keir, ST Carol, H Lock, R Maris, JM Billups, CA Smith, MA AF Houghton, Peter J. Kang, Min H. Reynolds, C. Patrick Morton, Christopher L. Kolb, E. Anders Gorlick, Richard Keir, Stephen T. Carol, Hernan Lock, Richard Maris, John M. Billups, Catherine A. Smith, Malcolm A. TI Initial testing (stage 1) of LCL161, a SMAC mimetic, by the pediatric preclinical testing program SO PEDIATRIC BLOOD & CANCER LA English DT Article DE developmental therapeutics; preclinical testing; SMAC mimetic ID NF-KAPPA-B; APOPTOSIS PROTEINS; ACTIVATION; CANCER; XIAP; SMAC/DIABLO; INHIBITOR; THERAPIES; LEUKEMIA; CIAP1 AB LCL161, a SMAC mimetic, was tested against the PPTP in vitro panel (1.0?nM to 10.0?mu M) and the PPTP in vivo panels (30 or 75?mg/kg [solid tumors] or 100?mg/kg [ALL]) administered orally twice in a week. LCL161 showed a median relative IC50 value of >10?mu M, being more potent against several leukemia and lymphoma lines. In vivo LCL161 induced significant differences in EFS distribution in approximately one-third of solid tumor xenografts (osteosarcoma and glioblastoma), but not in ALL xenografts. No objective tumor responses were observed. In vivo LCL161 demonstrated limited single agent activity against the pediatric preclinical models studied. Pediatr Blood Cancer 2012; 58: 636639. (c) 2011 Wiley Periodicals, Inc. C1 [Houghton, Peter J.] Nationwide Childrens Hosp, Ctr Childhood Canc, Res Inst, Columbus, OH 43205 USA. [Kang, Min H.; Reynolds, C. Patrick] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Morton, Christopher L.; Billups, Catherine A.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA. [Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA. [Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA. [Carol, Hernan; Lock, Richard] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia. [Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. [Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Houghton, PJ (reprint author), Nationwide Childrens Hosp, Ctr Childhood Canc, Res Inst, 700 Childrens Dr, Columbus, OH 43205 USA. EM peter.houghton@nationwidechildrens.org RI Carol, Hernan/F-5750-2013; Lock, Richard/G-4253-2013; OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C. Patrick/0000-0002-2827-8536 FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786]; Novartis Pharmaceuticals [LCL161] FX This work was supported by NO1-CM-42216, CA21765, and CA108786 from the National Cancer Institute, and LCL161 was provided by Novartis Pharmaceuticals. In addition to the authors represents work contributed by the following: Sherry Ansher, Joshua Courtright, Edward Favours, Henry S. Friedman, Debbie Payne-Turner, Charles Stopford, Chandra Tucker, Amy Wozniak, Joe Zeidner, Ellen Zhang, and Jian Zhang. Children's Cancer Institute Australia for Medical Research is affiliated with the University of New South Wales and Sydney Children's Hospital. NR 23 TC 31 Z9 34 U1 0 U2 4 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD APR PY 2012 VL 58 IS 4 BP 636 EP 639 DI 10.1002/pbc.23167 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 895NK UT WOS:000300502800030 PM 21681929 ER PT J AU Wylie, L Philpott, A AF Wylie, Luke Philpott, Anna TI Neuroblastoma progress on many fronts: The neuroblastoma research symposium SO PEDIATRIC BLOOD & CANCER LA English DT Article DE molecular biology of neuroblastoma; neuroblastoma; neuroblastoma biology ID GENE; CELL AB Neuroblastoma (NBL) is a pediatric tumor of infancy derived from precursor cells of the sympathetic nervous system. Clinicians and researchers in developmental biology and genetics recently met to facilitate meaningful crosstalk and to discuss considerable progress made in the clinical treatment and basic biology of NBL. For instance, discoveries in familial NBL have identified genetic aberrations in Phox2b and Alk that predispose to NBL, while advances in epigenetics and MYCN regulation have also offered insight into NBL pathogenesis and future treatment. Moreover, novel therapeutic avenues are also being explored, including targeted immunotherapies, and innovative radiotherapeutic and chemotherapeutic approaches. This multi-disciplinary meeting was convened to aid the transfer of new biological findings into the clinic and to use clinical advances to inform the basic biological understanding of this devastating disease. Pediatr Blood Cancer 2012; 58: 649651. (C) 2011 Wiley Periodicals, Inc. C1 [Wylie, Luke; Philpott, Anna] Univ Cambridge, Dept Oncol, Hutchison Med Res Council MRC Res Ctr, Cambridge CB2 0XZ, England. [Wylie, Luke] NCI, NIH, Bethesda, MD 20892 USA. RP Philpott, A (reprint author), Univ Cambridge, Dept Oncol, Hutchison Med Res Council MRC Res Ctr, Cambridge CB2 0XZ, England. EM ap113@cam.ac.uk FU National Institutes of Health; Medical Research Council [G0700758] FX Grant sponsor: National Institutes of Health Oxford-Cambridge Scholars Program; Grant sponsor: Medical Research Council; Grant number: G0700758. NR 18 TC 1 Z9 1 U1 0 U2 4 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD APR PY 2012 VL 58 IS 4 BP 649 EP 651 DI 10.1002/pbc.23329 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 895NK UT WOS:000300502800036 PM 21922652 ER PT J AU Kim, HK Choi, IJ Kim, CG Kim, HS Oshima, A Yamada, Y Arao, T Nishio, K Michalowski, A Green, JE AF Kim, H. K. Choi, I. J. Kim, C. G. Kim, H. S. Oshima, A. Yamada, Y. Arao, T. Nishio, K. Michalowski, A. Green, J. E. TI Three-gene predictor of clinical outcome for gastric cancer patients treated with chemotherapy SO PHARMACOGENOMICS JOURNAL LA English DT Article DE gastric; cancer; chemotherapy; gene; expression ID C-MYC; GENE-EXPRESSION; THYMIDYLATE SYNTHASE; DNA MICROARRAYS; TUMOR RESPONSE; PHASE-II; CISPLATIN; CARCINOMA; SURVIVAL; ADENOCARCINOMA AB To identify transcriptional profiles predictive of the clinical benefit of cisplatin and fluorouracil (CF) chemotherapy to gastric cancer patients, endoscopic biopsy samples from 96 CF-treated metastatic gastric cancer patients were prospectively collected before therapy and analyzed using high-throughput transcriptional profiling and array comparative genomic hybridization. Transcriptional profiling identified 917 genes that are correlated with poor patient survival after CF at P<0.05 (poor prognosis signature), in which protein synthesis and DNA replication/recombination/repair functional categories are enriched. A survival risk predictor was then constructed using genes, which are included in the poor prognosis signature and are contained within identified genomic amplicons. The combined expression of three genes-MYC, EGFR and FGFR2-was an independent predictor for overall survival of 27 CF-treated patients in the validation set (adjusted P = 0.017), and also for survival of 40 chemotherapy-treated gastric cancer patients in a published data set (adjusted P = 0.026). Thus, combined expression of MYC, EGFR and FGFR2 is predictive of poor survival in CF-treated metastatic gastric cancer patients. The Pharmacogenomics Journal (2012) 12, 119-127; doi:10.1038/tpj.2010.87; published online 21 December 2010 C1 [Kim, H. K.; Oshima, A.; Michalowski, A.; Green, J. E.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Kim, H. K.; Choi, I. J.; Kim, C. G.; Kim, H. S.] Natl Canc Ctr, Goyang, Gyeonggi, South Korea. [Yamada, Y.] Natl Canc Ctr, Tokyo 104, Japan. [Arao, T.; Nishio, K.] Kinki Univ, Sch Med, Osaka 589, Japan. RP Green, JE (reprint author), NCI, Lab Canc Biol & Genet, 37 Convent Dr, Bethesda, MD 20892 USA. EM JEGreen@mail.nih.gov FU National Institute of Health; Center for Cancer Research; National Cancer Institute; Korean National Cancer Center [0910570]; Ministry of Education, Science and Technology of Korea [2010K001121] FX The work was supported in part by National Institute of Health Intramural Program, Center for Cancer Research, National Cancer Institute, Korean National Cancer Center Grant 0910570 and Converging Research Center Program through the Ministry of Education, Science and Technology of Korea (2010K001121). We thank Dr Richard Simon for valuable discussions and critical reading of the manuscript, Dr Lyuba Varticovski for critical review of the manuscript and Dr Chang-Hee Kim, Ms Susie Korolevich, Ms Eunbyul Lee, Ms Eugene Kim and Ms Ilji Jeon for technical help. NR 37 TC 22 Z9 22 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD APR PY 2012 VL 12 IS 2 BP 119 EP 127 DI 10.1038/tpj.2010.87 PG 9 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 916WK UT WOS:000302133700005 PM 21173787 ER PT J AU Xu, K Hong, KA Zhou, ZF Hauger, RL Goldman, D Sinha, R AF Xu, Ke Hong, Kwangik Adam Zhou, Zhifeng Hauger, Richard L. Goldman, David Sinha, Rajita TI Genetic modulation of plasma NPY stress response is suppressed in substance abuse: Association with clinical outcomes SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Neuropeptide Y; Functional haplotype; Stress; Substance use disorders ID COCAINE-DEPENDENT INDIVIDUALS; PITUITARY-ADRENAL AXIS; HEART-RATE-VARIABILITY; NEUROPEPTIDE-Y; ALCOHOL DEPENDENCE; POPULATION-SAMPLE; DRUG-USE; ADDICTION; RATS; POLYMORPHISM AB Background: Neuropeptide Y (NPY) is involved in stress regulation. Genetic variations predict plasma NPY and neural correlates of emotion and stress. We examined whether the functional NPY haplotype modulates stress-induced NPY and anxiety responses, and if plasma NPY stress responses are associated with substance dependence outcomes. Methods: Thirty-seven treatment-engaged, abstinent substance dependent (SD) patients and 28 healthy controls (HCs) characterized on NPY diplotypes (HH: high expression; HLLL: intermediate/low expression) were exposed to stress, alcohol/drug cues and neutral relaxing cues, using individualized guided imagery, in a 3-session laboratory experiment. Plasma NPY, heart rate and anxiety were assessed. Patients were prospectively followed for 90-days post-treatment to assess relapse outcomes. Results: HH individuals showed significantly lower stress-induced NPY with greater heart rate and anxiety ratings, while the HLLL group showed the reverse pattern of NPY, anxiety and heart rate responses. This differential genetic modulation of NPY stress response was suppressed in the SD group, who showed no stress-related increases in NPY and higher heart rate and greater anxiety, regardless of diplotype. Lower NPY predicted subsequent higher number of days and greater amounts of post-treatment drug use. Conclusion: These preliminary findings are the first to document chronic drug abuse influences on NPY diplotype expression where NPY diplotype modulation of stress-related plasma NPY, heart rate and anxiety responses was absent in the substance abuse sample. The finding that lower stress-related NPY is predictive of greater relapse severity provides support for therapeutic development of neuropeptide Y targets in the treatment of substance use disorders. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Xu, Ke; Hong, Kwangik Adam; Sinha, Rajita] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06519 USA. [Sinha, Rajita] Yale Child Study Ctr, New Haven, CT 06519 USA. [Zhou, Zhifeng; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Hauger, Richard L.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Sinha, R (reprint author), Yale Univ, Sch Med, Dept Psychiat, 2 Church St S,Suite 209, New Haven, CT 06519 USA. EM Rajita.sinha@yale.edu RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU National Institutes of Health [R01-AA013892, R01-AG022982, R01-MH074697, T32-MH019961, R25-MH071584, UL1-DE019586, UL1-RR024139]; Department of Mental Health; Addiction Services of the State of Connecticut; Department of Veterans Affairs; VA Center of Excellence for Stress and Mental Health (CESAMH) FX This research was supported by the National Institutes of Health grants R01-AA013892 (RS), R01-AG022982 (RLH), R01-MH074697 (RLH), T32-MH019961, R25-MH071584 and the NIH Roadmap Fund for Medical Research grants UL1-DE019586 (RS) and UL1-RR024139 (Yale CTSA) as well as the Department of Mental Health and Addiction Services of the State of Connecticut. Dr. Hauger was supported by a Merit Review grant from the Department of Veterans Affairs and the VISN22 VA Center of Excellence for Stress and Mental Health (CESAMH). NR 65 TC 3 Z9 3 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD APR PY 2012 VL 37 IS 4 BP 554 EP 564 DI 10.1016/j.psyneuen.2011.08.005 PG 11 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 915RJ UT WOS:000302044800011 PM 21917383 ER PT J AU Burke, JE Sashital, DG Zuo, XB Wang, YX Butcher, SE AF Burke, Jordan E. Sashital, Dipali G. Zuo, Xiaobing Wang, Yun-Xing Butcher, Samuel E. TI Structure of the yeast U2/U6 snRNA complex SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE NMR; RNA; SAXS; U6 snRNA; spliceosome ID GROUP-II INTRON; INTRAMOLECULAR STEM-LOOP; LIQUID-CRYSTALLINE PHASE; METAL-ION COORDINATION; PROTEIN-FREE SNRNAS; SMALL NUCLEAR RNAS; MESSENGER-RNA; U6 SNRNA; WEB SERVER; CATALYTIC ACTIVATION AB The U2/U6 snRNA complex is a conserved and essential component of the active spliceosome that interacts with the pre-mRNA substrate and essential protein splicing factors to promote splicing catalysis. Here we have elucidated the solution structure of a 111-nucleotide U2/U6 complex using an approach that integrates SAXS, NMR, and molecular modeling. The U2/U6 structure contains a three-helix junction that forms an extended "Y'' shape. The U6 internal stem-loop (ISL) forms a continuous stack with U2/U6 Helices Ib, Ia, and III. The coaxial stacking of Helix Ib on the U6 ISL is a configuration that is similar to the Domain V structure in group II introns. Interestingly, essential features of the complex-including the U80 metal binding site, AGC triad, and pre-mRNA recognition sites-localize to one face of the molecule. This observation suggests that the U2/U6 structure is well-suited for orienting substrate and cofactors during splicing catalysis. C1 [Burke, Jordan E.; Sashital, Dipali G.; Butcher, Samuel E.] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. [Zuo, Xiaobing] Argonne Natl Lab, Adv Photon Source, Chicago, IL 60437 USA. [Wang, Yun-Xing] NCI, NIH, Frederick, MD 21702 USA. RP Butcher, SE (reprint author), Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. EM butcher@biochem.wisc.edu RI Zuo, Xiaobing/F-1469-2010; ID, BioCAT/D-2459-2012; OI Sashital, Dipali/0000-0001-7681-6987 FU NIH [P41RR02301 (BRTP/NCRR), P41GM66326 (NIGMS), RR02781, RR08438, T32 GM07215-34, GM065166]; University of Wisconsin; NSF [DMB-8415048, OIA-9977486, BIR-9214394]; USDA; U.S. DOE [DE-AC02-06CH11357] FX We thank Lawrence Clos II, Marco Tonelli, and the National Magnetic Resonance Facility at Madison (NMRFAM) staff as well as Soenke Seifert and the Advanced Photon Source (APS) staff for technical support. We also thank David Brow, Alex Grishaev, and all the members of the Butcher laboratory for helpful discussions. This study made use of the National Magnetic Resonance Facility at Madison, which is supported by NIH grants P41RR02301 (BRTP/NCRR) and P41GM66326 (NIGMS). Additional equipment was purchased with funds from the University of Wisconsin, the NIH (RR02781, RR08438), the NSF (DMB-8415048, OIA-9977486, BIR-9214394), and the USDA. Use of the Advanced Photon Source, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357. J.E.B. was supported by NIH Predoctoral training grant T32 GM07215-34. This work was supported by NIH grant GM065166 to S.E.B. NR 72 TC 42 Z9 43 U1 2 U2 19 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD APR PY 2012 VL 18 IS 4 BP 673 EP 683 DI 10.1261/rna.031138.111 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 914MQ UT WOS:000301954600007 PM 22328579 ER PT J AU Baird, NJ Zhang, JW Hamma, T Ferre-D'Amare, AR AF Baird, Nathan J. Zhang, Jinwei Hamma, Tomoko Ferre-D'Amare, Adrian R. TI YbxF and YlxQ are bacterial homologs of L7Ae and bind K-turns but not K-loops SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE K-turn; K-loop; RNA-binding proteins; X-ray crystallography ID RNA TERTIARY INTERACTIONS; LARGE RIBOSOMAL-SUBUNIT; CRYSTAL-STRUCTURE; BACILLUS-SUBTILIS; MESSENGER-RNA; X-RAY; ANGSTROM RESOLUTION; LYSINE RIBOSWITCH; PROTEIN NHP2P; I RIBOSWITCH AB The archaeal protein L7Ae and eukaryotic homologs such as L30e and 15.5kD comprise the best characterized family of K-turn-binding proteins. K-turns are an RNA motif comprised of a bulge flanked by canonical and noncanonical helices. They are widespread in cellular RNAs, including bacterial gene-regulatory RNAs such as the c-di-GMP-II, lysine, and SAM-I riboswitches, and the T-box. The existence in bacteria of K-turn-binding proteins of the L7Ae family has not been proven, although two hypothetical proteins, YbxF and YlxQ, have been proposed to be L7Ae homologs based on sequence conservation. Using purified, recombinant proteins, we show that Bacillus subtilis YbxF and YlxQ bind K-turns (K-d similar to 270 nM and similar to 2300 nM, respectively). Crystallographic structure determination demonstrates that both YbxF and YlxQ adopt the same overall fold as L7Ae. Unlike the latter, neither bacterial protein recognizes K-loops, a structural motif that lacks the canonical helix of the K-turn. This property is shared between the bacterial and eukaryal family members. Comparison of our structure of YbxF in complex with the K-turn of the SAM-I riboswitch and previously determined structures of archaeal and eukaryal homologs bound to RNA indicates that L7Ae approaches the K-turn at a unique angle, which results in a considerably larger RNA-protein interface dominated by interactions with the noncanonical helix of the K-turn. Thus, the inability of the bacterial and eukaryal L7Ae homologs to bind K-loops probably results from their reliance on interactions with the canonical helix. The biological functions of YbxF and YlxQ remain to be determined. C1 [Baird, Nathan J.; Zhang, Jinwei; Ferre-D'Amare, Adrian R.] NHLBI, Lab RNA Biophys & Cellular Physiol, Bethesda, MD 20892 USA. [Hamma, Tomoko] Pacific NW Univ Hlth Sci, Yakima, WA 98901 USA. RP Ferre-D'Amare, AR (reprint author), NHLBI, Lab RNA Biophys & Cellular Physiol, Bethesda, MD 20892 USA. EM adrian.ferre@nih.gov RI Zhang, Jinwei/D-8953-2012 FU National Heart, Lung and Blood Institute, NIH FX We thank the staff of Beamlines 5.0.1 and 5.0.2 of the ALS for data collection support, G. Piszczek for ITC support, D.-Y. Lee and R. Levine for generous help with mass spectrometry, and W. Winkler for discussions. This work was supported by the intramural program of the National Heart, Lung and Blood Institute, NIH. NR 58 TC 19 Z9 21 U1 1 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD APR PY 2012 VL 18 IS 4 BP 759 EP 770 DI 10.1261/rna.031518.111 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 914MQ UT WOS:000301954600015 PM 22355167 ER PT J AU Xin, HW Hari, DM Mullinax, JE Ambe, CM Koizumi, T Ray, S Anderson, AJ Wiegand, GW Garfield, SH Thorgeirsson, SS Avital, I AF Xin, Hong-Wu Hari, Danielle M. Mullinax, John E. Ambe, Chenwi M. Koizumi, Tomotake Ray, Satyajit Anderson, Andrew J. Wiegand, Gordon W. Garfield, Susan H. Thorgeirsson, Snorri S. Avital, Itzhak TI Tumor-Initiating Label-Retaining Cancer Cells in Human Gastrointestinal Cancers Undergo Asymmetric Cell Division SO STEM CELLS LA English DT Article DE Adult stem cells; Cancer stem cells; Self-renewal; Asymmetric cell division; Cairns immortal strand hypothesis; Liver ID TEMPLATE DNA STRANDS; HEMATOPOIETIC STEM-CELLS; HUMAN SOMATIC-CELLS; NEUTRAL ENDOPEPTIDASE; SISTER CHROMATIDS; TRANSGENIC MICE; MAMMARY-GLAND; IDENTIFICATION; SEGREGATION; GENE AB Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. STEM CELLS 2012; 30:591598 C1 [Xin, Hong-Wu; Hari, Danielle M.; Mullinax, John E.; Ambe, Chenwi M.; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J.; Wiegand, Gordon W.; Avital, Itzhak] NCI, Gastrointestinal & Hepatobiliary Malignancies Sec, Surg Branch, NIH, Bethesda, MD 20892 USA. [Garfield, Susan H.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Avital, I (reprint author), NCI, Gastrointestinal & Hepatobiliary Malignancies Sec, Surg Branch, NIH, 10 Ctr Dr,CRC Room 4-3961, Bethesda, MD 20892 USA. EM itzhak.avital@gmail.com RI perumal, murugiah/D-1565-2012; Mullinax, John/L-2509-2014 FU NIH/National Cancer Institute FX This study was supported by the intramural grant provided by the NIH/National Cancer Institute. NR 54 TC 28 Z9 29 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD APR PY 2012 VL 30 IS 4 BP 591 EP 598 DI 10.1002/stem.1061 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 915DV UT WOS:000302005000003 PM 22331764 ER PT J AU Rossouw, JE Johnson, KC Pettinger, M Cushman, M Sandset, PM Kuller, L Rosendaal, F Rosing, J Wasserthal-Smoller, S Martin, LW Manson, JE Lakshminarayan, K Merino, JG Lynch, J AF Rossouw, Jacques E. Johnson, Karen C. Pettinger, Mary Cushman, Mary Sandset, Per Morten Kuller, Lewis Rosendaal, Frits Rosing, Jan Wasserthal-Smoller, Sylvia Martin, Lisa W. Manson, JoAnn E. Lakshminarayan, Kamakshi Merino, Jose G. Lynch, John TI Tissue Factor Pathway Inhibitor, Activated Protein C Resistance, and Risk of Ischemic Stroke due to Postmenopausal Hormone Therapy SO STROKE LA English DT Article DE cerebrovascular accident; estrogen; hemostasis; menopause; randomized controlled trials ID ESTROGEN PLUS PROGESTIN; RANDOMIZED CONTROLLED-TRIAL; CONJUGATED EQUINE ESTROGEN; VENOUS THROMBOSIS; ORAL-CONTRACEPTIVES; WOMEN AB Background and Purpose-To test whether changes in plasma tissue factor pathway inhibitor (TFPI) levels or activated protein C resistance (normalized activated protein C resistance ratio [nAPCsr]) modify the increased risk of ischemic stroke due to postmenopausal hormone therapy. Methods-Nested case-control study of 455 cases of ischemic stroke and 565 matched control subjects in the Women's Health Initiative trials of postmenopausal hormone therapy. Results-Baseline free TFPI was associated with ischemic stroke risk (OR per SD increase, 1.17; 95% CI, 1.01-1.37; P=0.039), but baseline nAPCsr was not (OR per SD increase, 0.89; 95% CI, 0.75-1.05; P=0.15). Baseline TFPI levels and nAPCsr did not modify the effect of postmenopausal hormone therapy on ischemic stroke. Treatment-induced mean changes of -28% in free TFPI and +65% in nAPCsr did not change the risk of ischemic stroke (interaction P=0.452 and 0.971, respectively). In subgroup analyses, baseline nAPCsr was inversely associated with lacunar strokes (OR per SD increase, 0.74; 95% CI, 0.57-0.96; P=0.025) and baseline free TFPI interacted with treatment to increase large vessel atherosclerotic strokes (P=0.008). Conclusions-Procoagulant changes in TFPI or nAPCsr do not modify the increased ischemic stroke risk due to postmenopausal hormone therapy. C1 [Rossouw, Jacques E.] NHLBI, Bethesda, MD 20892 USA. [Johnson, Karen C.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. [Pettinger, Mary] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Cushman, Mary] Univ Vermont, Burlington, VT USA. [Sandset, Per Morten] Oslo Univ Hosp, Oslo, Norway. [Kuller, Lewis] Univ Pittsburgh, Pittsburgh, PA USA. [Rosendaal, Frits] Leiden Univ, Med Ctr, Leiden, Netherlands. [Rosing, Jan] Maastricht Univ, Maastricht, Netherlands. [Wasserthal-Smoller, Sylvia] Albert Einstein Coll Med, New York, NY USA. [Martin, Lisa W.] George Washington Univ, Washington, DC USA. [Manson, JoAnn E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lakshminarayan, Kamakshi] Univ Minnesota, Minneapolis, MN USA. [Merino, Jose G.; Lynch, John] NINDS, Bethesda, MD 20892 USA. RP Rossouw, JE (reprint author), NHLBI, 6701 Rockledge Dr,Room 9192, Bethesda, MD 20892 USA. EM rossouwj@nih.gov OI Merino, Jose/0000-0002-6676-0008; Martin, Lisa Warsinger/0000-0003-4352-0914 FU National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221] FX The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. The study drugs were provided by Wyeth Research (St Davids, PA). The National Institutes of Health had input into the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation of the article. Wyeth did not participate in any aspect of the aforementioned. NR 27 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2012 VL 43 IS 4 BP 952 EP 957 DI 10.1161/STROKEAHA.111.643072 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 916ST UT WOS:000302124200012 PM 22363056 ER PT J AU Berger, JS McGinn, AP Howard, BV Kuller, L Manson, JE Otvos, J Curb, JD Eaton, CB Kaplan, RC Lynch, JK Rosenbaum, DM Wassertheil-Smoller, S AF Berger, Jeffrey S. McGinn, Aileen P. Howard, Barbara V. Kuller, Lewis Manson, JoAnn E. Otvos, Jim Curb, J. David Eaton, Charles B. Kaplan, Robert C. Lynch, John K. Rosenbaum, Daniel M. Wassertheil-Smoller, Sylvia TI Lipid and Lipoprotein Biomarkers and the Risk of Ischemic Stroke in Postmenopausal Women SO STROKE LA English DT Article DE lipids; lipoproteins; ischemic stroke; women; triglycerides ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; NONFASTING TRIGLYCERIDES; ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; CHOLESTEROL LEVELS; SERUM-CHOLESTEROL; ASSOCIATION; MEN; MORTALITY AB Background-Few studies simultaneously investigated lipids and lipoprotein biomarkers as predictors of ischemic stroke. The value of these biomarkers as independent predictors of ischemic stroke remains controversial. Methods-We conducted a prospective nested case-control study among postmenopausal women from the Women's Health Initiative Observational Study to assess the relationship between fasting lipids (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides), lipoproteins (LDL, HDL, and very low-density lipoprotein [VLDL] particle number and size, intermediate-density lipoprotein [IDL] particle number, and lipoprotein (a)), and risk of ischemic stroke. Among women free of stroke at baseline, 774 ischemic stroke patients were matched according to age and race to control subjects, using a 1: 1 ratio. Results-In bivariate analysis, baseline triglycerides (P<0.001), IDL particles (P<0.01), LDL particles (P<0.01), VLDL triglyceride (P<0.001), VLDL particles (P<0.01), VLDL size (P<0.001), LDL size (P=0.03), and total/HDL cholesterol ratio (P<0.01) were significantly higher among women with incident ischemic stroke, whereas levels of HDL-C (P<0.01) and HDL size (P<0.01) were lower. No significant baseline difference for total cholesterol (P=0.15), LDL-C (P=0.47), and lipoprotein (a) (P=0.11) was observed. In multivariable analysis, triglycerides (odds ratio for the highest versus lowest quartile, 1.56; 95% confidence interval, 1.13-2.17; P for trend=0.02), VLDL size (odds ratio, 1.59; 95% confidence interval, 1.10-2.28; P for trend=0.03), and IDL particle number (odds ratio, 1.46; 95% confidence interval, 1.04-2.04; P for trend=0.02) were significantly associated with ischemic stroke. Conclusions-Among a panel of lipid and lipoprotein biomarkers, baseline triglycerides, VLDL size, and IDL particle number were significantly associated with incident ischemic stroke in postmenopausal women. (Stroke. 2012;43:958-966.) C1 [Berger, Jeffrey S.] NYU, Sch Med, Med Ctr, New York, NY 10016 USA. [McGinn, Aileen P.; Kaplan, Robert C.; Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Howard, Barbara V.] MedStar Res Inst, Washington, DC USA. [Howard, Barbara V.] Georgetown Univ, Sch Med, Washington, DC USA. [Kuller, Lewis] Univ Pittsburgh, Pittsburgh, PA USA. [Manson, JoAnn E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Otvos, Jim] Liposci Inc, Raleigh, NC USA. [Curb, J. David] Univ Hawaii Manoa, John A Burns Sch Med, Honolulu, HI 96822 USA. [Eaton, Charles B.] Brown Univ, Mem Hosp Rhode Isl, Pawtucket, RI 02860 USA. [Lynch, John K.] NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA. [Rosenbaum, Daniel M.] SUNY Downstate, Dept Neurol, Brooklyn, NY USA. RP Berger, JS (reprint author), NYU, Sch Med, Med Ctr, 530 1st Ave,Skirball 9R, New York, NY 10016 USA. EM jeffrey.berger@nyumc.org FU National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; National Institutes of Neurological Disorders and Stroke [R01NS042618]; American Heart Association [0775074N]; Pfizer; Merck; Schering-Plough; Parexel; AstraZeneca; Auxilium; Forest Pharmaceuticals FX The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services, through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. This study was supported by a grant from the National Institutes of Neurological Disorders and Stroke (R01NS042618). J.S.B. was partially funded by an American Heart Association Fellow to Faculty Award (No. 0775074N).; The content is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS or the NIH. B. V. H. is a consultant for Merck and Egg Nutrition Council and has received research support (donation of drugs) from Pfizer, Merck, and Schering-Plough and lectures for Schering-Plough. J.O. is an employee and stockholder of Liposcience, Inc. C. B. E. has received research support from Pfizer, Parexel, AstraZeneca, Auxilium, and Forest Pharmaceuticals; is on the Speakers Bureau for Pfizer and Merck-Shering Plough; and is a consultant for Pfizer, Merck-Shering Plough, Merck, and Johnson & Johnson. NR 47 TC 22 Z9 26 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2012 VL 43 IS 4 BP 958 EP U96 DI 10.1161/STROKEAHA.111.641324 PG 13 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 916ST UT WOS:000302124200013 PM 22308251 ER PT J AU Saver, JL Warach, S Janis, S Odenkirchen, J Becker, K Benavente, O Broderick, J Dromerick, AW Duncan, P Elkind, MSV Johnston, K Kidwell, CS Meschia, JF Schwamm, L AF Saver, Jeffrey L. Warach, Steven Janis, Scott Odenkirchen, Joanne Becker, Kyra Benavente, Oscar Broderick, Joseph Dromerick, Alexander W. Duncan, Pamela Elkind, Mitchell S. V. Johnston, Karen Kidwell, Chelsea S. Meschia, James F. Schwamm, Lee CA Natl Inst Neurological Disorders TI Standardizing the Structure of Stroke Clinical and Epidemiologic Research Data The National Institute of Neurological Disorders and Stroke (NINDS) Stroke Common Data Element (CDE) Project SO STROKE LA English DT Article DE database; education; educational campaigns ID HEALTH; COLLECTION; NETWORK; BRAIN AB Background and Purpose-The National Institute of Neurological Disorders and Stroke initiated development of stroke-specific Common Data Elements (CDEs) as part of a project to develop data standards for funded clinical research in all fields of neuroscience. Standardizing data elements in translational, clinical, and population research in cerebrovascular disease could decrease study start-up time, facilitate data sharing, and promote well-informed clinical practice guidelines. Methods-A working group of diverse experts in cerebrovascular clinical trials, epidemiology, and biostatistics met regularly to develop a set of stroke CDEs, selecting among, refining, and adding to existing, field-tested data elements from national registries and funded trials and studies. Candidate elements were revised on the basis of comments from leading national and international neurovascular research organizations and the public. Results-The first iteration of the National Institute of Neurological Disorders and Stroke (NINDS) stroke-specific CDEs comprises 980 data elements spanning 9 content areas: (1) biospecimens and biomarkers; (2) hospital course and acute therapies; (3) imaging; (4) laboratory tests and vital signs; (5) long-term therapies; (6) medical history and prior health status; (7) outcomes and end points; (8) stroke presentation; and (9) stroke types and subtypes. A CDE website provides uniform names and structures for each element, a data dictionary, and template case report forms, using the CDEs. Conclusions-Stroke-specific CDEs are now available as standardized, scientifically vetted, variable structures to facilitate data collection and data sharing in cerebrovascular patient-oriented research. The CDEs are an evolving resource that will be iteratively improved based on investigator use, new technologies, and emerging concepts and research findings. (Stroke. 2012;43:967-973.) C1 [Warach, Steven; Janis, Scott; Odenkirchen, Joanne] NINDS, NIH, Bethesda, MD 20892 USA. [Becker, Kyra] Univ Washington, Sch Med, Seattle, WA USA. [Benavente, Oscar] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Broderick, Joseph] Univ Cincinnati, Cincinnati, OH USA. [Dromerick, Alexander W.] Georgetown Univ, Sch Med, Washington, DC USA. [Duncan, Pamela] Duke Univ, Durham, NC USA. [Elkind, Mitchell S. V.] Columbia Univ, New York, NY USA. [Johnston, Karen] Univ Virginia, Charlottesville, VA USA. [Meschia, James F.] Mayo Clin, Coll Med, Jacksonville, FL 32224 USA. [Schwamm, Lee] Harvard Univ, Sch Med, Boston, MA USA. RP Saver, JL (reprint author), Univ Calif Los Angeles, Stroke Ctr, 710 Westwood Plaza, Los Angeles, CA 90095 USA. EM jsaver@ucla.edu RI Lo, Warren/E-3531-2011; OI Saver, Jeffrey/0000-0001-9141-2251; Schwamm, Lee/0000-0003-0592-9145 FU National Institute of Neurological Disorders and Stroke, National Institutes of Health [N01-NS-7-2372]; NIH; AGA; EV3; IMS III Trial; UC SPOTRIAS Center; FIA; C-32 Cerebrovascular Fellowship; Genetic and Environmental Risk Factors for Hemorrhagic Stroke; Comparison of Hemorrhagic and Ischemic Stroke Among Blacks; Whites; IRIS Trial; CREST; COSS; SWISS; Wake Forest Baptist Medical Center; BMS; diaDexus; NIH/NINDS [U01NS064498]; NINDS [U01NS069208]; [NS057401]; [NS069763]; [NS044378] FX The Common Data Element Project is funded by the National Institute of Neurological Disorders and Stroke, National Institutes of Health (contract No. N01-NS-7-2372).; J.L.S. reports the following: Research grants: NIH, AGA, EV3, and Concentric; consultant/advisory boards: ALA, EV3, Lunseck, Concentric, Talecris, and BrainsGate; institution/employer: UCLA. J.O. reports the following: Institution/employer: NIH employee. O.B. reports the following: Research grant. J.B. reports the following: Research grants: IMS III Trial, UC SPOTRIAS Center, FIA study, C-32 Cerebrovascular Fellowship Training, Genetic and Environmental Risk Factors for Hemorrhagic Stroke, Comparison of Hemorrhagic and Ischemic Stroke Among Blacks and Whites, IRIS Trial, CREST, COSS, and SWISS; honoraria: Genentech, PhotoThera, and Oakstone Medical Publishing. A. W. D. reports the following: Research grant. P. D. reports the following: Institution/employer: Wake Forest Baptist Medical Center. M. S. V. E. reports the following: Research grants: BMS Sanofi Partnership and diaDexus; other research support: NIH/NINDS; speakers bureau: BMS Sanofi Partnership and Genentech; expert witness: GlaxoSmithKline and Organon. K.J. reports the following: Research grant: NIH-NINDS U01NS064498. C. S. K. reports the following: Research grants: NS057401, NS069763, and NS044378. J.F.M. reports the following: Research grant: NINDS Sign U01NS069208. NR 18 TC 50 Z9 53 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2012 VL 43 IS 4 BP 967 EP U108 DI 10.1161/STROKEAHA.111.634352 PG 11 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 916ST UT WOS:000302124200014 PM 22308239 ER PT J AU Cheng, YC Anderson, CD Bione, S Keene, K Maguire, JM Nalls, M Rasheed, A Zeginigg, M Attia, J Baker, R Barlera, S Biffi, A Bookman, E Brott, TG Brown, RD Chen, F Chen, WM Ciusani, E Cole, JW Cortellini, L Danesh, J Doheny, K Ferrucci, L Franzosi, MG Frossard, P Furie, KL Golledge, J Hankey, GJ Hernandez, D Holliday, EG Hsu, FC Jannes, J Kamal, A Khan, MS Kittner, SJ Koblar, SA Lewis, M Lincz, L Lisa, A Matarin, M Moscato, P Mychaleckyj, JC Parati, EA Parolo, S Pugh, E Rost, NS Schallert, M Schmidt, H Scott, RJ Sturm, JW Yadav, S Zaidi, M Boncoraglio, GB Levi, CR Meschia, JF Rosand, J Sale, M Saleheen, D Schmidt, R Sharma, P Worrall, B Mitchell, BD AF Cheng, Yu-Ching Anderson, Christopher D. Bione, Silvia Keene, Keith Maguire, Jane M. Nalls, Michael Rasheed, Asif Zeginigg, Marion Attia, John Baker, Ross Barlera, Simona Biffi, Alessandro Bookman, Ebony Brott, Thomas G. Brown, Robert D., Jr. Chen, Fang Chen, Wei-Min Ciusani, Emilio Cole, John W. Cortellini, Lynelle Danesh, John Doheny, Kimberly Ferrucci, Luigi Franzosi, Maria Grazia Frossard, Philippe Furie, Karen L. Golledge, Jonathan Hankey, Graeme J. Hernandez, Dena Holliday, Elizabeth G. Hsu, Fang-Chi Jannes, Jim Kamal, Ayeesha Khan, Muhammad Saleem Kittner, Steven J. Koblar, Simon A. Lewis, Martin Lincz, Lisa Lisa, Antonella Matarin, Mar Moscato, Pablo Mychaleckyj, Josyf C. Parati, Eugenio A. Parolo, Silvia Pugh, Elizabeth Rost, Natalia S. Schallert, Michael Schmidt, Helena Scott, Rodney J. Sturm, Jonathan W. Yadav, Sunaina Zaidi, Moazzam Boncoraglio, Giorgio B. Levi, Christopher Royce Meschia, James F. Rosand, Jonathan Sale, Michele Saleheen, Danish Schmidt, Reinhold Sharma, Pankaj Worrall, Bradford Mitchell, Braxton D. CA GARNET Collaborative Res Grp GENEVA Consortium Int Stroke Genetics Consortium TI Are Myocardial Infarction-Associated Single-Nucleotide Polymorphisms Associated With Ischemic Stroke? SO STROKE LA English DT Article DE cerebral infarct; genetics; ischemia ID CORONARY-ARTERY-DISEASE; GENOME-WIDE ASSOCIATION; AMERICAN-HEART-ASSOCIATION; VITAMIN INTERVENTION; CEREBRAL INFARCTION; SEQUENCE VARIANTS; FAMILY-HISTORY; PREVENTION; CLASSIFICATION; SUBTYPES AB Methods-Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific beta s and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model. Results-Despite having power to detect odds ratio of 1.09-1.14 for overall IS and 1.20-1.32 for major stroke subtypes, none of the SNPs were significantly associated with overall IS and/or stroke subtypes after adjusting for multiple comparisons. Conclusions-Our results suggest that the major common loci associated with MI risk do not have effects of similar magnitude on overall IS but do not preclude moderate associations restricted to specific IS subtypes. Disparate mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events. (Stroke. 2012; 43:980-986.) C1 [Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Anderson, Christopher D.; Biffi, Alessandro; Cortellini, Lynelle; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Anderson, Christopher D.; Biffi, Alessandro; Cortellini, Lynelle; Furie, Karen L.; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Anderson, Christopher D.; Biffi, Alessandro; Cortellini, Lynelle; Rost, Natalia S.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Bione, Silvia; Lisa, Antonella; Parolo, Silvia] CNR, Inst Mol Genet, Pavia, Italy. [Keene, Keith; Schallert, Michael] Univ Virginia, Dept Med, Charlottesville, VA USA. [Keene, Keith; Chen, Fang; Chen, Wei-Min; Mychaleckyj, Josyf C.; Schallert, Michael] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Maguire, Jane M.; Attia, John; Holliday, Elizabeth G.; Lincz, Lisa; Scott, Rodney J.; Levi, Christopher Royce] Univ Newcastle, HMRI, Newcastle, NSW 2300, Australia. [Maguire, Jane M.] Univ Newcastle, Sch Nursing & Midwifery, Newcastle, NSW 2300, Australia. [Nalls, Michael; Hernandez, Dena] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Rasheed, Asif; Frossard, Philippe; Zaidi, Moazzam; Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan. [Zeginigg, Marion; Schallert, Michael; Schmidt, Helena; Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Graz, Austria. [Zeginigg, Marion; Schallert, Michael; Schmidt, Helena; Schmidt, Reinhold] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria. [Baker, Ross] Murdoch Univ, Ctr Thrombosis & Haemophilia, Perth, WA, Australia. [Baker, Ross] Royal Perth Hosp, Dept Haematol, Perth, WA, Australia. [Barlera, Simona; Franzosi, Maria Grazia] Ist Ric Farmacol Mario Negri, Milan, Italy. [Bookman, Ebony] NHGRI, NIH, Rockville, MD USA. [Brott, Thomas G.; Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Brown, Robert D., Jr.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Chen, Wei-Min; Mychaleckyj, Josyf C.; Worrall, Bradford] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Ciusani, Emilio; Parati, Eugenio A.; Boncoraglio, Giorgio B.] Fdn IRCCS Ist Neurol Carlo Besta, Milan, Italy. [Cole, John W.; Kittner, Steven J.] Vet Affairs Med Ctr, Dept Neurol, Baltimore, MD USA. [Cole, John W.; Kittner, Steven J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Danesh, John; Saleheen, Danish] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Doheny, Kimberly; Pugh, Elizabeth] Johns Hopkins Univ, Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Bethesda, MD 20892 USA. [Golledge, Jonathan] James Cook Univ, Sch Med, Vasc Biol Unit, Townsville, Qld 4811, Australia. [Hankey, Graeme J.] Royal Perth Hosp, Dept Neurol, Perth, WA, Australia. [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Crawley, Australia. [Hsu, Fang-Chi] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Hsu, Fang-Chi] Wake Forest Sch Med, Ctr Canc Genom, Winston Salem, NC USA. [Jannes, Jim; Koblar, Simon A.; Lewis, Martin] Univ Adelaide, Stroke Res Programme, Sch Med, Adelaide, SA, Australia. [Jannes, Jim; Koblar, Simon A.; Lewis, Martin] Univ Adelaide, Stroke Res Programme, Sch Mol Biomed Sci, Adelaide, SA, Australia. [Kamal, Ayeesha] Aga Khan Univ, Neurol Sect, Karachi, Pakistan. [Khan, Muhammad Saleem; Yadav, Sunaina; Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, ICCRU, London, England. [Matarin, Mar] UCL Inst Neurol, Dept Clin & Expt Epilepsy, London, England. [Moscato, Pablo] Univ Newcastle, Ctr Bioinformat, Newcastle, NSW 2300, Australia. [Sturm, Jonathan W.] Univ Newcastle, Gosford Hosp, Dept Neurosci, Newcastle, NSW 2300, Australia. [Schallert, Michael] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA. [Worrall, Bradford] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Saleheen, Danish] Univ Penn, Philadelphia, PA 19104 USA. RP Mitchell, BD (reprint author), Univ Maryland, Sch Med, Dept Med, 660 W Redwood St,Howard Hall,Room 492, Baltimore, MD 21201 USA. EM bmitchel@medicine.umaryland.edu RI MOSCATO, PABLO/G-7668-2013; golledge, jonathan/I-2371-2013; Attia, John/F-5376-2013; Hankey, Graeme /H-4968-2014; Lisa, Antonella/B-3117-2015; Boncoraglio, Giorgio/B-8647-2011; Matarin, Mar/F-1771-2016; OI Lewis, Martin/0000-0002-3332-3776; Attia, John/0000-0001-9800-1308; Hankey, Graeme /0000-0002-6044-7328; Lisa, Antonella/0000-0003-2458-5499; Matarin, Mar/0000-0002-4717-5735; Bione, Silvia/0000-0002-3924-4606; Parolo, Silvia/0000-0002-3671-5353; Anderson, Christopher/0000-0002-0053-2002; Koblar, Simon/0000-0002-8667-203X; Mitchell, Braxton/0000-0003-4920-4744 FU Australian National and Medical Health Research Council (NHMRC) [569257]; Australian National Heart Foundation (NHF) [G 04S 1623]; University of Newcastle; Department of Health (United Kingdom); Henry Smith Charity; British Council (UKIERI); Italian Ministry of Health [RC 2007/LR6, RC 2008/LR6, RC 2009/LR8, RC 2010/LR8]; Cariplo Foundation [2010-0253]; University of Pavia; European Community [LSHM-CT-2007-037273]; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research [0775010N]; NIH-NINDS [K23NS064052, R01NS063925, P50NS051343]; Deane Institute for Integrative Study of Atrial Fibrillation and Stroke; Keane Stroke Genetics Research Fund; US National Institutes of Health; National Heart, Lung, and Blood Institute STAMPEED [R01 HL087676]; National Center for Research Resources; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research; National Institutes of Health Genes, Environment and Health Initiative (GEI), GENEVA consortium under GEI [U01 HG004436]; National Institutes of Health [HHSN268200782096C]; Office of Research and Development, Medical Research Service; Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs; National Institute of Neurological Disorders and Stroke (NINDS); NIH Office of Research on Women's Health [R01 NS45012, U01 NS069208-01]; Austrian Science Fund [P20545]; National Institute on Aging, National Institutes of Health, Department of Health and Human Services [Z01 AG000954-06, Z01 AG000015-50]; National Institute for Neurological Disorders and Stroke (United States) [R01 NS42733, R01 NS39987]; National Institute of Neurological Disorders And Stroke [21NS064908]; National Human Genome Research Institute (NHGRI) [U01 HG005160]; National Institutes of Health to the Johns Hopkins University; United States Public Health Service, National Institute of Neurological Disorders and Stroke of the National Institutes of Health, Bethesda, MD [R01 NS34447] FX The ASGC was funded by grants from the Australian National and Medical Health Research Council (NHMRC Project Grant ID: 569257) and the Australian National Heart Foundation (NHF Project Grant ID: G 04S 1623). Support was also received from the University of Newcastle. E. G. H. was supported by an NHMRC Training (Postdoctoral) Fellowship. BRAINS was supported by a Department of Health (United Kingdom) senior fellowship to P. S. and also by a grant from the Henry Smith Charity and the British Council (UKIERI). The Besta Cerebrovascular Diseases Registry (CEDIR) was supported by the Italian Ministry of Health, years 2007-2010 (Annual Research Funding; Grant Numbers: RC 2007/LR6, RC 2008/LR6; RC 2009/LR8; RC 2010/LR8). This study was supported also by Cariplo Foundation (grant No. 2010-0253). S. P. was supported by a PhD fellowship of the University of Pavia (PhD program in Genetic and Biomolecular Sciences). The PROCARDIS study was supported by the European Community Sixth Framework Program (LSHM-CT-2007-037273). GASROS was supported by the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (0775010N); NIH-NINDS grant Nos. K23NS064052 (N.S.R.), R01NS063925 (J.R.), and P50NS051343 (J.R and K. L. F.); the Deane Institute for Integrative Study of Atrial Fibrillation and Stroke; and the Keane Stroke Genetics Research Fund. The MIGen study was funded by the US National Institutes of Health and National Heart, Lung, and Blood Institute STAMPEED genomics research program (R01 HL087676) and a grant from the National Center for Research Resources. A. B., N.S.R., and C. D. A. were supported in part by the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research. The GEOS study was supported by the National Institutes of Health Genes, Environment and Health Initiative (GEI) Grant U01 HG004436, as part of the GENEVA consortium under GEI. Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the National Institutes of Health to the Johns Hopkins University (contract No. HHSN268200782096C). Assistance with data cleaning was provided by the GENEVA Coordinating Center (U01 HG 004446; PI, Bruce S. Weir). Study recruitment and collection of datasets were supported by the Office of Research and Development, Medical Research Service, and the Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs and by grants from the National Institute of Neurological Disorders and Stroke (NINDS) and the NIH Office of Research on Women's Health (R01 NS45012, U01 NS069208-01). Genetic studies of the Austrian Stroke Prevention Study (GRAZ) are supported by the Austrian Science Fund (P20545). ISGS/SWISS: This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services; project No. Z01 AG000954-06. This work used samples and clinical data from the NINDS Human Genetics Resource Center DNA and Cell Line Repository (http://ccr.coriell.org/ninds), human subjects protocol Nos. 2003-081 and 2004-147. The inclusion of Baltimore Longitudinal Study of Aging samples was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services; project No. Z01 AG000015-50, human subjects protocol number 2003-078.; The ISGS study was funded by a grant from the National Institute for Neurological Disorders and Stroke (United States), grant No. R01 NS42733 (PI, J. Meschia). The SWISS study was funded by a grant from the National Institute for Neurological Disorders and Stroke (United States), grant No. R01 NS39987 (PI, J. Meschia). This study used the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). The RACE study is supported by grants from the National Institute of Neurological Disorders And Stroke (Award No. 21NS064908) and educational awards to investigators at the Center for Noncommunicable Diseases, Pakistan. The GWAS component of the VISP study was supported by the National Human Genome Research Institute (NHGRI), Grant U01 HG005160 (PIs, Michele Sale and Bradford Worrall), as part of the Genomics and Randomized Trials Network (GARNET). Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the National Institutes of Health to the Johns Hopkins University. Assistance with data cleaning was provided by the GARNET Coordinating Center (U01 HG005157; PI, Bruce S. Weir). Study recruitment and collection of datasets for the VISP clinical trial were supported by an investigator-initiated research grant (R01 NS34447; PI, James Toole) from the United States Public Health Service, National Institute of Neurological Disorders and Stroke of the National Institutes of Health, Bethesda, MD. NR 36 TC 17 Z9 17 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD APR PY 2012 VL 43 IS 4 BP 980 EP U143 DI 10.1161/STROKEAHA.111.632075 PG 26 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 916ST UT WOS:000302124200016 PM 22363065 ER PT J AU Resnik, DB AF Resnik, David B. TI Limits on risks for healthy volunteers in biomedical research SO THEORETICAL MEDICINE AND BIOETHICS LA English DT Article DE Human participant research; Risk; Ethics; Regulations; Paternalism; Healthy volunteers ID TRIALS AB Healthy volunteers in biomedical research often face significant risks in studies that offer them no medical benefits. The U.S. federal research regulations and laws adopted by other countries place no limits on the risks that these participants face. In this essay, I argue that there should be some limits on the risks for biomedical research involving healthy volunteers. Limits on risk are necessary to protect human participants, institutions, and the scientific community from harm. With the exception of self-experimentation, limits on research risks faced by healthy volunteers constitute a type of soft, impure paternalism because participants usually do not fully understand the risks they are taking. I consider some approaches to limiting research risks and propose that healthy volunteers in biomedical research should not be exposed to greater than a 1% chance of serious harm, such as death, permanent disability, or severe illness or injury. While this guideline would restrict research risks, the limits would not be so low that they would prevent investigators from conducting valuable research. They would, however, set a clear upper boundary for investigators and signal to the scientific community and the public that there are limits on the risks that healthy participants may face in research. This standard provides guidance for decisions made by oversight bodies, but it is not an absolute rule. Investigators can enroll healthy volunteers in studies involving a greater than 1% chance of serious harm if they show that the research addresses a compelling public health or social problem and that the risk of serious harm is only slightly more than 1%. The committee reviewing the research should use outside experts to assess these risks. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Box 12233,Mail Drop CU 03, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU Intramural NIH HHS [ZIA ES102646-03] NR 46 TC 9 Z9 9 U1 0 U2 17 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1386-7415 J9 THEOR MED BIOETH JI Theor. Med. Bioeth. PD APR PY 2012 VL 33 IS 2 BP 137 EP 149 DI 10.1007/s11017-011-9201-1 PG 13 WC Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Social Issues; Biomedical Social Sciences GA 913MP UT WOS:000301882400003 PM 22198413 ER PT J AU Lock, EF Abdo, N Huang, RL Xia, MH Kosyk, O O'Shea, SH Zhou, YH Sedykh, A Tropsha, A Austin, CP Tice, RR Wright, FA Rusyn, I AF Lock, Eric F. Abdo, Nour Huang, Ruili Xia, Menghang Kosyk, Oksana O'Shea, Shannon H. Zhou, Yi-Hui Sedykh, Alexander Tropsha, Alexander Austin, Christopher P. Tice, Raymond R. Wright, Fred A. Rusyn, Ivan TI Quantitative High-Throughput Screening for Chemical Toxicity in a Population-Based In Vitro Model SO TOXICOLOGICAL SCIENCES LA English DT Article DE chemical cytotoxicity; apoptosis; HapMap; lymphoblasts; qHTS ID HUMAN BREAST-CANCER; NF-KAPPA-B; GENE-EXPRESSION; ENVIRONMENTAL CHEMICALS; RISK-ASSESSMENT; HUMAN GENOME; CYTOTOXICITY; ASSOCIATION; CELLS; THIOREDOXIN AB A shift in toxicity testing from in vivo to in vitro may efficiently prioritize compounds, reveal new mechanisms, and enable predictive modeling. Quantitative high-throughput screening (qHTS) is a major source of data for computational toxicology, and our goal in this study was to aid in the development of predictive in vitro models of chemical-induced toxicity, anchored on interindividual genetic variability. Eighty-one human lymphoblast cell lines from 27 Centre d'Etude du Polymorphisme Humain trios were exposed to 240 chemical substances (12 concentrations, 0.26nM-46.0 mu M) and evaluated for cytotoxicity and apoptosis. qHTS screening in the genetically defined population produced robust and reproducible results, which allowed for cross-compound, cross-assay, and cross-individual comparisons. Some compounds were cytotoxic to all cell types at similar concentrations, whereas others exhibited interindividual differences in cytotoxicity. Specifically, the qHTS in a population-based human in vitro model system has several unique aspects that are of utility for toxicity testing, chemical prioritization, and high-throughput risk assessment. First, standardized and high-quality concentration-response profiling, with reproducibility confirmed by comparison with previous experiments, enables prioritization of chemicals for variability in interindividual range in cytotoxicity. Second, genome-wide association analysis of cytotoxicity phenotypes allows exploration of the potential genetic determinants of interindividual variability in toxicity. Furthermore, highly significant associations identified through the analysis of population-level correlations between basal gene expression variability and chemical-induced toxicity suggest plausible mode of action hypotheses for follow-up analyses. We conclude that as the improved resolution of genetic profiling can now be matched with high-quality in vitro screening data, the evaluation of the toxicity pathways and the effects of genetic diversity are now feasible through the use of human lymphoblast cell lines. C1 [Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Huang, Ruili; Xia, Menghang; Austin, Christopher P.] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. [Tice, Raymond R.] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27711 USA. RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. EM iir@unc.edu RI Tropsha, Alexander/G-6245-2014; Rusyn, Ivan/S-2426-2016 FU National Institute of Environmental Health Sciences interagency [Y2-ES-7020-01]; National Institutes of Health (NIH) [R01 ES015241]; U.S. Environmental Protection Agency (U.S. EPA) [RD83382501] FX This research was supported, in part, by the Intramural Research Programs of the National Toxicology Program, National Institute of Environmental Health Sciences interagency agreement Y2-ES-7020-01 and by grants from the National Institutes of Health (NIH) (R01 ES015241) and U.S. Environmental Protection Agency (U.S. EPA) (RD83382501). NR 47 TC 21 Z9 22 U1 2 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD APR PY 2012 VL 126 IS 2 BP 578 EP 588 DI 10.1093/toxsci/kfs023 PG 11 WC Toxicology SC Toxicology GA 915FD UT WOS:000302008600028 PM 22268004 ER PT J AU Zou, SM Stramer, SL Dodd, RY AF Zou, Shimian Stramer, Susan L. Dodd, Roger Y. TI Donor Testing and Risk: Current Prevalence, Incidence, and Residual Risk of Transfusion-Transmissible Agents in US Allogeneic Donations SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; WEST-NILE-VIRUS; CROSS BLOOD SERVICES; TRANSMITTED VIRAL-INFECTIONS; NUCLEIC-ACID-AMPLIFICATION; UNSAFE INJECTION PRACTICES; UNITED-STATES; HEPATITIS-B; BORNE INFECTIONS; SEROLOGIC TEST AB Over the past 20 years, there has been a major increase in the safety of the blood supply, as demonstrated by declining rates of posttransfusion infection and reductions in estimated residual risk for such infections. Reliable estimates of residual risk have been possible within the American Red Cross system because of the availability of a large amount of reliable and consistent data on donations and infectious disease testing results. Among allogeneic blood donations, the prevalence rates of infection markers for hepatitis C virus (HCV) and hepatitis B virus have decreased over time, although rates for markers of human immunodeficiency virus (HIV) and human T-cell lymphotropic virus did not. The incidence (/100 000 person-years) of HIV and HCV among repeat donors showed apparent increases from 1.55 and 1.89 in 2000 through 2001 to 2.16 and 2.98 in 2007 through 2008. These observed fluctuations confirm the need for continuous monitoring and evaluation. The residual risk of HIV. HCV, and human T-cell lymphotropic virus among all allogeneic donations is currently below 1 per 1 million donations, and that of hepatitis B surface antigen is close to 1 per 300 000 donations. (C) 2012 Elsevier Inc. All rights reserved. C1 [Zou, Shimian] NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA. Amer Red Cross, Biomed Serv, Sci Support Off, Gaithersburg, MD USA. Amer Red Cross, Holland Lab, Gaithersburg, MD USA. RP Zou, SM (reprint author), NHLBI, Natl Inst Hlth, Rockledge 2,6701 Rockledge Dr, Bethesda, MD 20892 USA. EM shimian.zou@nih.gov NR 63 TC 54 Z9 57 U1 3 U2 15 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD APR PY 2012 VL 26 IS 2 BP 119 EP 128 DI 10.1016/j.tmrv.2011.07.007 PG 10 WC Hematology SC Hematology GA 916OI UT WOS:000302112700002 PM 21871776 ER PT J AU Saslow, D Solomon, D Lawson, HW Killackey, M Kulasingam, SL Cain, J Garcia, FAR Moriarty, AT Waxman, AG Wilbur, DC Wentzensen, N Downs, LS Spitzer, M Moscicki, AB Franco, EL Stoler, MH Schiffman, M Castle, PE Myers, ER AF Saslow, Debbie Solomon, Diane Lawson, Herschel W. Killackey, Maureen Kulasingam, Shalini L. Cain, Joanna Garcia, Francisco A. R. Moriarty, Ann T. Waxman, Alan G. Wilbur, David C. Wentzensen, Nicolas Downs, Levi S., Jr. Spitzer, Mark Moscicki, Anna-Barbara Franco, Eduardo L. Stoler, Mark H. Schiffman, Mark Castle, Philip E. Myers, Evan R. TI American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology Screening Guidelines for the Prevention and Early Detection of Cervical Cancer SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article ID HUMAN-PAPILLOMAVIRUS DNA; RANDOMIZED CONTROLLED-TRIAL; ATYPICAL SQUAMOUS-CELLS; INTRAEPITHELIAL NEOPLASIA GRADE-2; INTERNATIONAL INCIDENCE RATES; ADENOCARCINOMA IN-SITU; LIQUID-BASED CYTOLOGY; LONG-TERM RISK; WOMEN 30 YEARS; COST-EFFECTIVENESS AB An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HP V) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HP VI 6 and HPV18 infections. C1 [Saslow, Debbie] Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30303 USA. [Solomon, Diane] NCI, Canc Prevent Div, NIH, Rockville, MD USA. [Lawson, Herschel W.] Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA USA. [Killackey, Maureen] Mem Sloan Kettering Canc Ctr, Dept Surg, Mem Sloan Kettering Canc Ctr Reg Network, Gynecol Serv, New York, NY 10021 USA. [Kulasingam, Shalini L.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Cain, Joanna] Univ Massachusetts, Sch Med, Dept Obstet & Gynecol, Worcester, MA USA. [Garcia, Francisco A. R.] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Ctr Excellence Womens Hlth, Tucson, AZ USA. [Moriarty, Ann T.] AmeriPath Indiana, Dept Esoter Testing, Indianapolis, IN USA. [Waxman, Alan G.] Univ New Mexico, Sch Med, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. [Wilbur, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Downs, Levi S., Jr.] Univ Minnesota, Sch Med, Dept Obstet Gynecol & Womens Hlth, Div Gynecol Oncol,Masonic Canc Ctr, Minneapolis, MN 55455 USA. [Spitzer, Mark] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Moscicki, Anna-Barbara] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Franco, Eduardo L.] McGill Univ, Dept Oncol, Montreal, PQ, Canada. [Franco, Eduardo L.] McGill Univ, Dept Epidemiol, Montreal, PQ, Canada. [Stoler, Mark H.] Univ Virginia Hlth Syst, Dept Pathol, Charlottesville, VA USA. [Schiffman, Mark] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Castle, Philip E.] Amer Soc Clin Pathol Inst, Washington, DC USA. [Myers, Evan R.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. RP Saslow, D (reprint author), Amer Canc Soc, Canc Control Sci Dept, 250 Williams St NW,Suite 600, Atlanta, GA 30303 USA. EM debbie.saslow@cancer.org RI perumal, murugiah/D-1565-2012; Colgan, Terence/J-2339-2016; OI Franco, Eduardo/0000-0002-4409-8084 FU Merck and Company; Roche Pharmaceutical/Roche Molecular; Hologic; Third Wave Technologies; MTM Laboratories; Qiagen; Becton, Dickson and Company (BD); MediSpectra/LUMA; Roche; Gen-Probe, Inc; Abbott Laboratories; Roche Molecular Systems; Merck, Inc; GlaxoSmithKline (GSK), Inc.; Merck Research Laboratories; Ventana Medical Systems, Inc; BD Diagnostics; National Institute of Allergy and Infectious Diseases FX P. Castle receives payment for service on the Data Monitoring and Safety Board for Merck Sharp & Dohme and has received free or discounted human papillomavirus tests for research from Qiagen and Roche. C. Cohen serves as a speaker for Merck, Inc, and receives honoraria. M. Edelson's spouse is employed by and receives a salary from Merck and Company. F. Garcia is employed by the University of Arizona, which holds contracts for the performance of research with Roche Pharmaceutical/Roche Molecular; Hologic; Third Wave Technologies; MTM Laboratories; Qiagen; Becton, Dickson and Company (BD); and MediSpectra/LUMA. He also serves on the Speakers' Bureau for Qiagen and receives honoraria. J. Cuzick serves on advisory boards and as an ad hoc consultant for Qiagen; Roche; Gen-Probe, Inc; BD; and Abbott Laboratories, with research funds provided to his institution from Qiagen; Roche; Gen-Probe, Inc; BD; and Abbott Laboratories. P. Gravitt has acted as a member of the Women's Health Advisory Board for Qiagen Corporation and has received research funding from Roche Molecular Systems and Merck, Inc, within the last 5 years. E. Myers received research support for investigations for Gen-Probe, Inc, and from GlaxoSmithKline (GSK), Inc. He served as a speaker for and received honoraria from Gen-Probe, Inc, and has served as a consultant for and received honoraria from Gen-Probe, Inc; Merck and Company; and GSK. M Schiffman holds a research agreement to serve as a medical monitor in the National Cancer Institute (NCI) vaccine trial through GSK; he also receives research support from Qiagen for careHPV research in Nigeria. D. Solomon serves as a medical monitor for the NCI's Costa Rica HPV Vaccine Trial; the trial receives vaccine from GSK. M Stoler received fees for serving as a consultant to Merck Research Laboratories; Roche; Ventana Medical Systems, Inc; BD; Hologic; MTM Laboratories; and Gen-Probe, Inc. D. Mody conducted lectures and workshops for the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Cytopathology (ASC), for which she received honoraria and/or travel expenses. G. Birdsong 's employer receives funding for contracted research performed by him for BD Diagnostics. C. Wheeler is an employee of University of New Mexico, which is contracted by GSK for its vaccine trials and receives equipment/reagents from Roche Molecular Systems, Inc, for human papillomavirus genotyping. D. Wilbur serves on the scientific advisory board for Corista, LLC. T Darragh received ThinPrep supplies for research from Hologic. She also serves on an advisory board for OncoHealth Corporation and has received stock options as payment and serves on the advisory board of Arbor Vita Corporation. E. Mayeaux serves on the speakers' advisory board for both Merck, Inc, and PharmaDerm and receives honoraria from both companies for his service. M Spitzer serves as a speaker for both Merck, Inc, and Qiagen and receives honoraria. K. Ault received clinical research grants from the National Institute of Allergy and Infectious Diseases; Gen-Probe, Inc; Merck, Inc; and Roche and served as a site principal investigator for the research. All grants were provided to his employer, Emory University. E.; Franco received honorarium as a Study Steering Committee member for GSK; he also serves on the advisory boards of Merck, Inc; Roche; and Gen-Probe, Inc, from which he receives honoraria and has acted as an ad hoc consultant for Merck, Inc; Roche; Gen-Probe, Inc; and Qiagen, for which honoraria were paid to compensate for time away and work performed. M Gold received honorarium for serving as a speaker and consultant for Hologic. W. Huh serves as a consultant to Roche; Qiagen; Merck, Inc; and Inovio Pharmaceuticals, Inc, and receives honoraria from all 4 companies. A-B. Moscicki received honorarium for serving as a consultant to an advisory board for Merck, Inc. M Einstein has advised or participated in educational speaking activities, but does not receive an honorarium from any companies. His employer, Montefiore Medical Center, has received payment for his time spent on activities for Merck, Inc; GSK; Roche; Bristol-Myers Squibb; Hologic; Advaxis, Inc; Aura Biosciences, Inc; Inovio Pharmaceuticals, Inc; Photocure ASA; NeoDiagnostix, Inc; and PDS Biotechnology Corporation. Montefiore has received grant funding for research related to the costs of those Merck, GSK, Roche, Advaxis, and Hologic clinical trials for which Dr Einstein served as the Montefiore principal investigator. A. Moriarty received honorarium as a speaker for ASC. R. Guido has acted as the local principal investigator for a multicenter study (contracted research) for IKONOsys. A. Waxman receives honoraria and expenses for teaching related to the subject matter in this article from nonprofit professional organizations and governmental agencies and contractors. He is on the executive committee of the board of directors of the American Society for Colposcopy and Cervical Pathology; he lectures for them and codirects some of their courses and receives honoraria and expenses for these functions. He also lectures and directs courses for the American College/Congress of Obstetricians and Gynecologists on subjects related to this article and receives honoraria from them. Both organizations are nonprofit professional organizations. He has also received honoraria and expenses from the State of Alaska Department of Health and Social Services and several Alaska Native corporations (Southcentral Foundation, SouthEast Alaska Regional Health Corporation, Arctic Slope Regional Corporation, and Yukon-Kuskokwim Health Corporation) and the Breast Cancer Detection Center of Alaska for lecturing on material related to this article. He also received honoraria from the Center for Health Training, a contractor to Title X agencies for lecturing for the Texas Department of State Health Services. He also received a $200 honorarium from Quadrant HealthCom, Inc, for writing an article related to cervical cancer screening for the journal OBG Management. NR 159 TC 277 Z9 299 U1 5 U2 19 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 APR PY 2012 VL 137 IS 4 BP 516 EP 542 DI 10.1309/AJCPTGD94EVRSJCG PG 27 WC Pathology SC Pathology GA 912BJ UT WOS:000301768400002 PM 22431528 ER PT J AU Khrutchinsky, A Drozdovitch, V Kutsen, S Minenko, V Khrouch, V Luckyanov, N Voilleque, P Bouville, A AF Khrutchinsky, Arkady Drozdovitch, Vladimir Kutsen, Semion Minenko, Victor Khrouch, Valeri Luckyanov, Nickolas Voilleque, Paul Bouville, Andre TI Mathematical modeling of a survey-meter used to measure radioactivity in human thyroids: Monte Carlo calculations of the device response and uncertainties SO APPLIED RADIATION AND ISOTOPES LA English DT Article DE Chernobyl; Thyroid; Measurement; Survey meter; Monte Carlo ID CHERNOBYL ACCIDENT; I-131; BYELARUS; INHABITANTS; SIMULATION; PHANTOM; AREAS; MASS AB This paper presents results of Monte Carlo modeling of the SRP-68-01 survey meter used to measure exposure rates near the thyroid glands of persons exposed to radioactivity following the Chernobyl accident. This device was not designed to measure radioactivity in humans. To estimate the uncertainty associated with the measurement results, a mathematical model of the SRP-68-01 survey meter was developed and verified. A Monte Carlo method of numerical simulation of radiation transport has been used to calculate the calibration factor for the device and evaluate its uncertainty. The SRP-68-01 survey meter scale coefficient, an important characteristic of the device, was also estimated in this study. The calibration factors of the survey meter were calculated for I-131, I-132, I-133, and I-135 content in the thyroid gland for six age groups of population: newborns; children aged 1 yr, 5 yr, 10 yr, 15 yr; and adults. A realistic scenario of direct thyroid measurements with an "extended" neck was used to calculate the calibration factors for newborns and one-year-olds. Uncertainties in the device calibration factors due to variability of the device scale coefficient, variability in thyroid mass and statistical uncertainty of Monte Carlo method were evaluated. Relative uncertainties in the calibration factor estimates were found to be from 0.06 for children aged 1 yr to 0.1 for 10-yr and 15-yr children. The positioning errors of the detector during measurements deviate mainly in one direction from the estimated calibration factors. Deviations of the device position from the proper geometry of measurements were found to lead to overestimation of the calibration factor by up to 24 percent for adults and up to 60 percent for 1-yr children. The results of this study improve the estimates of I-131 thyroidal content and, consequently, thyroid dose estimates that are derived from direct thyroid measurements performed in Belarus shortly after the Chernobyl accident. (c) 2012 Published by Elsevier Ltd. C1 [Drozdovitch, Vladimir; Luckyanov, Nickolas; Bouville, Andre] NCI, DHHS, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Khrutchinsky, Arkady; Kutsen, Semion] Res Inst Nucl Problems, Minsk 220030, Byelarus. [Minenko, Victor] Belarusian Med Acad Postgrad Educ, Minsk 220714, Byelarus. [Khrouch, Valeri] Burnasyan Fed Med Biophys Ctr, Moscow 123182, Russia. [Voilleque, Paul] MJP Risk Assessment Inc, Denver, CO 80220 USA. RP Drozdovitch, V (reprint author), NCI, DHHS, NIH, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7100, Bethesda, MD 20892 USA. EM drozdovv@mail.nih.gov RI Kuten, Semen/F-6699-2016 OI Kuten, Semen/0000-0003-0827-8421 FU National Institutes of Health, National Cancer Institute (USA) [N02-CP-45506]; ISTC [B-488P]; National Institute of Allergy and Infectious Diseases (USA); National Cancer Institute; NIAID [Y2-AI-5077]; NCI [Y3-CO-5117] FX This work was supported by the National Institutes of Health, National Cancer Institute (USA) within the framework of Belarus-U.S. Study of Thyroid Cancer and Other Disease following the Chernobyl Accident [N02-CP-45506] and the ISTC Project B-488P; and by the Intra-Agency Agreement between the National Institute of Allergy and Infectious Diseases (USA) and the National Cancer Institute, NIAID agreement #Y2-AI-5077 and NCI agreement #Y3-CO-5117. The authors are grateful to Vladimir Guzov, Georgy Shulgovich (deceased), and Valeri Kozhemiakin (Atomtex, Minsk, Belarus) for performing measurements of the exposure rate and fruitful discussion of measurements results. Special thanks are to Nikolay Bakovets and Valeri Milevsky (Belstandard, Minsk, Belarus), who provided useful information on calibration of the SRP-68-01 device. The authors would like to thank the reviewer for constructive comments and suggestions that help improve the manuscript. NR 18 TC 4 Z9 4 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD APR PY 2012 VL 70 IS 4 BP 743 EP 751 DI 10.1016/j.apradiso.2011.12.032 PG 9 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 913YW UT WOS:000301914300030 PM 22245289 ER PT J AU Hasko, G Pacher, P AF Hasko, Gyorgy Pacher, Pal TI Regulation of Macrophage Function by Adenosine SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE cytokines; G proteins; immune system; immunosuppressive therapy; macrophages ID ENDOTHELIAL GROWTH-FACTOR; A(2A) RECEPTOR AGONISTS; NECROSIS-FACTOR-ALPHA; ALTERNATIVELY ACTIVATED MACROPHAGES; SYNERGISTIC UP-REGULATION; TNF-ALPHA; MURINE MACROPHAGES; VASCULAR INJURY; HUMAN MONOCYTES; A2A RECEPTOR AB Following its release into the extracellular space in response to metabolic disturbances, the endogenous nucleoside adenosine exerts a range of immunomodulatory effects and cells of the mononuclear phagocyte system are among its major targets. Adenosine governs mononuclear phagocyte functions via 4 G-protein-coupled cell membrane receptors, which are denoted A(1), A(2A), A(2B), and A(3) receptors. Adenosine promotes osteoclast differentiation via A(1) receptors and alters monocyte to dendritic cell differentiation through A(2B) receptors. Adenosine downregulates classical macrophage activation mainly through A(2A) receptors. In contrast A(2B) receptor activation upregulates alternative macrophage activation. Adenosine promotes angiogenesis, which is mediated by inducing the production of vascular endothelial growth factor by mononuclear phagocytes through A(2A), A(2B), and A(3) receptors. By regulating mononuclear phagocyte function adenosine dictates the course of inflammatory and vascular diseases and cancer. (Arterioscler Thromb Vasc Biol. 2012;32:865-869.) C1 [Hasko, Gyorgy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. [Hasko, Gyorgy] Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Immun & Inflammat, Newark, NJ 07103 USA. [Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA. RP Hasko, G (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, 185 S Orange Ave, Newark, NJ 07103 USA. EM haskoge@umdnj.edu RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU National Institutes of Health [R01GM66189]; USAMRMC [09065004, W81XWH-10-1-1015]; NIH/NIAAA FX This work was supported by National Institutes of Health Grant R01GM66189 (to G.H.), USAMRMC grant log #09065004 (Contract W81XWH-10-1-1015) (to G.H.), and Intramural Research Program of NIH/NIAAA (to P.P.). NR 59 TC 48 Z9 49 U1 0 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 2012 VL 32 IS 4 BP 865 EP 869 DI 10.1161/ATVBAHA.111.226852 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 910VV UT WOS:000301672300009 PM 22423038 ER PT J AU Kim, YC Hummer, G AF Kim, Young C. Hummer, Gerhard TI Proton-pumping mechanism of cytochrome c oxidase: A kinetic master-equation approach SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Review DE Proton pumping; Cytochrome c oxidase; Respiratory chain; Energy transduction; Molecular machine; Kinetic master equation ID HEME-COPPER OXIDASES; NONEQUILIBRIUM STEADY-STATE; ELECTRON-TRANSFER; PARACOCCUS-DENITRIFICANS; MOLECULAR MOTORS; CATALYTIC CYCLE; RHODOBACTER-SPHAEROIDES; OXYGEN ACTIVATION; TRANSLOCATION; WATER AB Cytochrome c oxidase is an efficient energy transducer that reduces oxygen to water and converts the released chemical energy into an electrochemical membrane potential. As a true proton pump, cytochrome c oxidase translocates protons across the membrane against this potential. Based on a wealth of experiments and calculations, an increasingly detailed picture of the reaction intermediates in the redox cycle has emerged. However, the fundamental mechanism of proton pumping coupled to redox chemistry remains largely unresolved. Here we examine and extend a kinetic master-equation approach to gain insight into redox-coupled proton pumping in cytochrome c oxidase. Basic principles of the cytochrome c oxidase proton pump emerge from an analysis of the simplest kinetic models that retain essential elements of the experimentally determined structure, energetics, and kinetics, and that satisfy fundamental physical principles. The master-equation models allow us to address the question of how pumping can be achieved in a system in which all reaction steps are reversible. Whereas proton pumping does not require the direct modulation of microscopic reaction barriers, such kinetic gating greatly increases the pumping efficiency. Further efficiency gains can be achieved by partially decoupling the proton uptake pathway from the active-site region. Such a mechanism is consistent with the proposed Glu valve, in which the side chain of a key glutamic acid shuttles between the D channel and the active-site region. We also show that the models predict only small proton leaks even in the absence of turnover. The design principles identified here for cytochrome c oxidase provide a blueprint for novel biology-inspired fuel cells, and the master-equation formulation should prove useful also for other molecular machines. This article is part of a Special Issue entitled: Respiratory Oxidases. Published by Elsevier B.V. C1 [Kim, Young C.] USN, Res Lab, Ctr Computat Mat Sci, Washington, DC 20375 USA. [Hummer, Gerhard] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Kim, YC (reprint author), USN, Res Lab, Ctr Computat Mat Sci, Washington, DC 20375 USA. EM youngchan.kim@nrl.navy.mil; gerhard.hummer@nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX We thank Prof. Marten Wikstrom and Dr. Ville Kaila for many insightful and stimulating discussions. G.H. is supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 80 TC 19 Z9 19 U1 2 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 EI 0006-3002 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD APR PY 2012 VL 1817 IS 4 SI SI BP 526 EP 536 DI 10.1016/j.bbabio.2011.09.004 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 913NV UT WOS:000301885600008 PM 21946020 ER PT J AU Harlow, SD Gass, M Hall, JE Lobo, R Maki, P Rebar, RW Sherman, S Sluss, PM de Villiers, TJ AF Harlow, Sioban D. Gass, Margery Hall, Janet E. Lobo, Roger Maki, Pauline Rebar, Robert W. Sherman, Sherry Sluss, Patrick M. de Villiers, Tobie J. CA STRAW 10 Collaborative Grp TI Executive summary of the Stages of Reproductive Aging Workshop+10: addressing the unfinished agenda of staging reproductive aging SO CLIMACTERIC LA English DT Article DE REPRODUCTIVE AGING; OVARIAN AGING; MENOPAUSE; FOLLICLE-STIMULATING HORMONE; ANTIMULLERIAN HORMONE; ANTRAL FOLLICLE COUNT; INHIBIN-B ID FOLLICLE-STIMULATING-HORMONE; ANTI-MULLERIAN HORMONE; EARLY MENOPAUSAL TRANSITION; POLYCYSTIC-OVARY-SYNDROME; MIDDLE-AGED WOMEN; REGULAR MENSTRUAL CYCLES; INHIBIN-B; ANTIMULLERIAN HORMONE; LONGITUDINAL CHANGES; DEPRESSIVE SYMPTOMS AB Objective The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period. Methods Scientists from five countries and multiple disciplines evaluated data from cohort studi