FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sapp, JC Hull, SC Duffer, S Zornetzer, S Sutton, E Marteau, TM Biesecker, BB AF Sapp, Julie Chevalier Hull, Sara Chandros Duffer, Shelby Zornetzer, Sarah Sutton, Erica Marteau, Theresa M. Biesecker, Barbara Bowles TI Ambivalence toward undergoing invasive prenatal testing: an exploration of its origins SO PRENATAL DIAGNOSIS LA English DT Article DE informed choice; attitudes; subjective norms; ambivalence; amniocentesis ID INFORMED CHOICE; DIAGNOSIS; ATTITUDES; CONTEXT; WOMEN; AMNIOCENTESIS; DECISIONS; KNOWLEDGE AB Objective This study explores ambivalence toward undergoing amniocentesis among pregnant women with overall positive attitudes. Its novelly lies in the characterization of the type and origins of the ambivalence. Method Thirty-six women between 35 and 44 years of age were recruited from a US prenatal testing center to participate in structured telephone interviews. Results Thirty women chose to undergo testing. Attitudes toward undergoing amniocentesis were generally positive, although all participants simultaneously described feeling ambivalent. The women desired the information that amniocentesis Could provide yet did not want to place their fetus at risk. Participants cited religious, moral, ethical and intellectual Values important in shaping their attitudes toward undergoing amniocentesis. Important referents Such as partners, other pregnant women, family members and physicians influenced their decisions. Conclusion Tensions were evident among the intellectual, moral and spiritual values that contribute to ambivalence toward undergoing amniocentesis. Illuminating and discussing such tensions during the genetic counseling sessions prior to testing may resolve some of this ambivalence and thereby increase the quality of decisions women make. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Sapp, Julie Chevalier] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. [Hull, Sara Chandros] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Duffer, Shelby; Zornetzer, Sarah] Genet & IVF Inst, Fairfax, VA 22039 USA. [Sutton, Erica] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. [Sutton, Erica] Univ Toronto, Joint Ctr Bioeth, Toronto, ON M5S 1A1, Canada. [Marteau, Theresa M.] Kings Coll London, Dept Psychol Guys, Hlth Psychol Sect, Inst Psychiat, London WC2R 2LS, England. [Biesecker, Barbara Bowles] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP Sapp, JC (reprint author), NHGRI, Genet Dis Res Branch, 10 Ctr Dr,Bldg 10,Room 3C710, Bethesda, MD 20892 USA. EM sappj@mail.nih.gov OI Marteau, Theresa/0000-0003-3025-1129 FU Division of Intramural Research in the National Human Genome Research Institute, National Institutes of Health FX The authors wish to thank Dr Harvey Stern and the staff of Genetics & IVF Institute, Fairfax, VA, for their crucial assistance in the design and execution of this project. We are also deeply grateful to all of the women who participated in this study. This work was supported by the Division of Intramural Research in the National Human Genome Research Institute, National Institutes of Health. NR 26 TC 16 Z9 16 U1 0 U2 8 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD JAN PY 2010 VL 30 IS 1 BP 77 EP 82 DI 10.1002/pd.2343 PG 6 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 544WY UT WOS:000273692100012 PM 19924734 ER PT J AU Druss, BG Mays, RA Edwards, VJ Chapman, DP AF Druss, Benjamin G. Mays, Robert A., Jr. Edwards, Valerie J. Chapman, Daniel P. TI Primary Care, Public Health, and Mental Health SO PREVENTING CHRONIC DISEASE LA English DT Editorial Material C1 [Mays, Robert A., Jr.] NIMH, Bethesda, MD 20892 USA. [Edwards, Valerie J.; Chapman, Daniel P.] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Druss, BG (reprint author), Emory Univ, Rollins Sch Publ Hlth, 1518 Clifton Rd NE, Atlanta, GA 30322 USA. EM bdruss@emory.edu NR 6 TC 2 Z9 3 U1 0 U2 1 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD JAN PY 2010 VL 7 IS 1 AR A04 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V20RZ UT WOS:000208158400004 PM 20040219 ER PT J AU Primm, AB Vasquez, MJT Mays, RA Sammons-Posey, D McKnight-Eily, LR Presley-Cantrell, LR McGuire, LC Chapman, DP Perry, GS AF Primm, Annelle B. Vasquez, Melba J. T. Mays, Robert A. Sammons-Posey, Doreleena McKnight-Eily, Lela R. Presley-Cantrell, Letitia R. McGuire, Lisa C. Chapman, Daniel P. Perry, Geraldine S. TI The Role of Public Health in Addressing Racial and Ethnic Disparities in Mental Health and Mental Illness SO PREVENTING CHRONIC DISEASE LA English DT Article AB Racial/ethnic minority populations are underserved in the American mental health care system. Disparity in treatment between whites and African Americans has increased substantially since the 1990s. Racial/ethnic minorities may be disproportionately affected by limited English proficiency, remote geographic settings, stigma, fragmented services, cost, comorbidity of mental illness and chronic diseases, cultural understanding of health care services, and incarceration. We present a model that illustrates how social determinants of health, interventions, and outcomes interact to affect mental health and mental illness. Public health approaches to these concerns include preventive strategies and federal agency collaborations that optimize the resilience of racial/ethnic minorities. We recommend strategies such as enhanced surveillance, research, evidence-based practice, and public policies that set standards for tracking and reducing disparities. C1 [Vasquez, Melba J. T.] Amer Psychol Assoc, Washington, DC 20036 USA. [Mays, Robert A.] NIMH, Bethesda, MD 20892 USA. [Sammons-Posey, Doreleena] Natl Assoc Chron Dis Directors & Directors Hlth P, Trenton, NJ USA. [McKnight-Eily, Lela R.; Presley-Cantrell, Letitia R.; McGuire, Lisa C.; Chapman, Daniel P.; Perry, Geraldine S.] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Primm, AB (reprint author), Amer Psychiat Assoc, 1000 Wilson Blvd,Ste 1825, Arlington, VA 21287 USA. EM aprimm@psych.org NR 30 TC 11 Z9 11 U1 3 U2 6 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD JAN PY 2010 VL 7 IS 1 AR A20 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V20RZ UT WOS:000208158400020 PM 20040235 ER PT J AU Sullivan, HW Rutten, LJF Hesse, BW Moser, RP Rothman, AJ McCaul, KD AF Sullivan, Helen W. Rutten, Lila J. Finney Hesse, Bradford W. Moser, Richard P. Rothman, Alexander J. McCaul, Kevin D. TI Lay Representations of Cancer Prevention and Early Detection: Associations With Prevention Behaviors SO PREVENTING CHRONIC DISEASE LA English DT Article AB Introduction The Common Sense Model of illness representations posits that how people think about an illness affects how they try to prevent the illness. The purpose of this study was to determine whether prevention representations vary by cancer type (colon, lung, and skin cancer) and whether representations are associated with relevant behaviors. Methods We analyzed data from the Health Information National Trends Survey (HINTS 2005), a nationally representative survey of American adults (N = 5,586) conducted by telephone interview. Results Respondents reported that all 3 types of cancer can be prevented through healthy behaviors; however, fewer did so for colon cancer. More respondents reported screening as a prevention strategy for colon cancer than did so for lung or skin cancer. Representations were associated with colon cancer screening, smoking status, and sunscreen use. Conclusion Representations of cancer were associated with relevant health behaviors, providing a target for health messages and interventions. C1 [Sullivan, Helen W.; Rutten, Lila J. Finney; Hesse, Bradford W.; Moser, Richard P.] NIH, Bethesda, MD 20892 USA. [Rothman, Alexander J.] Univ Minnesota, Minneapolis, MN USA. [McCaul, Kevin D.] N Dakota State Univ, Fargo, ND 58105 USA. RP Sullivan, HW (reprint author), 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM helen@aya.yale.edu NR 30 TC 5 Z9 5 U1 1 U2 2 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD JAN PY 2010 VL 7 IS 1 AR A14 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V20RZ UT WOS:000208158400014 PM 20040229 ER PT J AU Guessous, I Dash, C Lapin, P Doroshenk, M Smith, RA Klabunde, CN AF Guessous, Idris Dash, Chiranjeev Lapin, Pauline Doroshenk, Mary Smith, Robert A. Klabunde, Carrie N. CA Natl Colorectal Canc Roundtable Sc TI Colorectal cancer screening barriers and facilitators in older persons SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med DE Colorectal cancer; Screening; Older persons; Barriers; Facilitators ID SERVICES TASK-FORCE; ELDERLY-PATIENTS; UNITED-STATES; COLON-CANCER; RECOMMENDATIONS; PARTICIPATION; DISPARITIES; COLONOSCOPY; AMERICANS; COVERAGE AB Background. This systematic review identifies factors that are most consistently mentioned as either barriers to or facilitators of colorectal cancer (CRC) screening in older persons. Methods. A systematic literature search (1995-2008) was conducted to identify studies that reported barriers to or facilitators of CRC screening uptake, compliance or adherence specifically for older persons (>= 65 years). Information on study characteristics and barriers and facilitators related to subjects; healthcare providers; policies; and screening tests were then abstracted and analyzed. Results. Eighty-three studies met the eligibility criteria. Low level of education, African American race, Hispanic ethnicity, and female gender were the most frequently reported barriers, whereas being married or living with a partner was the most frequently reported facilitator. The most cited barrier related to healthcare providers was lack of screening recommendation by a physician; having a usual source of care was a commonly reported facilitator. Lack of health insurance, and dual coverage with Medicare and Medicaid were the most frequently reported barriers, whereas Medicare's coverage of screening colonoscopy was consistently reported as a facilitator. Conclusions. Barriers to, and facilitators of, CRC screening among older persons are reported. Particular attention should be paid to modifiable factors that could become the focus of interventions aimed at increasing CRC screening participation in older persons. (C) 2009 Elsevier Inc. All rights reserved. C1 [Guessous, Idris; Dash, Chiranjeev] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. [Guessous, Idris] Univ Hosp Geneva, Unit Populat Epidemiol, Div Primary Care Med, Dept Community Med & Primary Care, Geneva, Switzerland. [Lapin, Pauline] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. [Doroshenk, Mary] Amer Canc Soc, Washington, DC USA. [Smith, Robert A.] Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30329 USA. [Klabunde, Carrie N.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA. RP Guessous, I (reprint author), Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. EM iguesso@sph.emory.edu FU NCCDPHP CDC HHS [U50/DP424071] NR 28 TC 71 Z9 71 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD JAN-FEB PY 2010 VL 50 IS 1-2 BP 3 EP 10 DI 10.1016/j.ypmed.2009.12.005 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 565GU UT WOS:000275278700001 PM 20006644 ER PT J AU Anderson, DE Chesney, MA AF Anderson, David E. Chesney, Margaret A. BE Legato, MJ TI Gender Differences in the Role of Stress and Emotion in Cardiovascular Function and Disease SO PRINCIPLES OF GENDER-SPECIFIC MEDICINE, 2ND EDITION LA English DT Article; Book Chapter ID CORONARY-HEART-DISEASE; AMBULATORY BLOOD-PRESSURE; ACUTE MYOCARDIAL-INFARCTION; WESTERN-COLLABORATIVE-GROUP; CARDIAC AUTONOMIC CONTROL; RESERVE CAPACITY MODEL; A-BEHAVIOR PATTERN; MIDDLE-AGED MEN; END-TIDAL CO2; SOCIAL SUPPORT C1 [Anderson, David E.] NIA, NIH, Baltimore, MD 21224 USA. [Chesney, Margaret A.] Univ Maryland Sch Med, Ctr Integrat Med, Baltimore, MD USA. RP Anderson, DE (reprint author), NIA, NIH, Baltimore, MD 21224 USA. NR 204 TC 0 Z9 0 U1 2 U2 3 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND BN 978-0-08-092150-1 PY 2010 BP 186 EP 199 DI 10.1016/B978-0-12-374271-1.00017-4 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA BEO92 UT WOS:000317610700022 ER PT S AU Klein, M Sanders, ME Duong, T Young, HA AF Klein, Marguerite Sanders, Mary Ellen Duong, Tri Young, Howard A. BA Klein, M Sanders, ME Duong, T Young, HA BF Klein, M Sanders, ME Duong, T Young, HA TI Probiotics: From Bench to Market SO PROBIOTICS: FROM BENCH TO MARKET SE Annals of the New York Academy of Sciences LA English DT Article DE probiotics; prebiotics; microbiota; investigational new drug ID IRRITABLE-BOWEL-SYNDROME; INDUCED VISCERAL HYPERSENSITIVITY; ACTIVE ULCERATIVE-COLITIS; DOUBLE-BLIND; DENDRITIC CELLS; CLINICAL-TRIAL; MATERNAL SEPARATION; FECAL MICROBIOTA; PROTECTS MICE; MOUSE MODEL AB "Probiotics: From Bench to Market" was a one-day conference convened by the New York Academy of Sciences on June 11, 2010, with the goal of stimulating discussion of the physiological effects of probiotics on the gastrointestinal, nervous, and immune systems. The program included speakers from academia, industry, and government to give conference participants a full understanding of the state of the field of probiotics. The overall goal of the program was to increase communication and collaboration among these groups to advance probiotic research and probiotic contributions to public health. The conference was divided into three sessions and included both oral and visual presentations as well as panel discussions. C1 [Sanders, Mary Ellen] Dairy & Food Culture Technol, Centennial, CO 80122 USA. [Klein, Marguerite] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Duong, Tri] Texas A&M Univ, Dept Poultry Sci, College Stn, TX 77843 USA. [Young, Howard A.] NCI, NIH, Frederick, MD 21701 USA. RP Sanders, ME (reprint author), Dairy & Food Culture Technol, 7119 S Glencoe Ct, Centennial, CO 80122 USA. EM mes@mesanders.com; mes@mesanders.com RI Duong, Tri/B-5594-2012 OI Duong, Tri/0000-0002-4803-8564 FU Dannon Company Inc.; National Institute of Allergy and Infectious Diseases [1R13AI088836-01] FX Event sponsored by an unrestricted education grant from Dannon Company Inc. Funding for this conference was also made possible in part by 1R13AI088836-01 from the National Institute of Allergy and Infectious Diseases. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government. [Correction added after online publication November 24, 2010: acknowledgement wording amended.] NR 62 TC 13 Z9 14 U1 2 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-756-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1212 IS S1 BP E1 EP E14 DI 10.1111/j.1749-6632.2010.05839.x PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BUA05 UT WOS:000288560400001 PM 21105878 ER PT B AU Xue, SZ Zhu, SR Coble, J Xu, JS Jia, XD Ji, BT Lu, W AF Xue Shou-zheng Zhu Su-rong Coble, Joe Xu Jian-shi Jia Xiao-dong Ji Bu-tian Lu Wei BE Wang, XY Zhang, YR Hong, Q Yu, CY Xin, XP Ding, JY TI Establishment of the JEM for Occupational Hazards, 1953-2000, Shanghai SO PROCEEDINGS OF THE 5TH INTERNATIONAL ACADEMIC CONFERENCE ON ENVIRONMENTAL AND OCCUPATIONAL MEDICINE LA English DT Proceedings Paper CT 5th International Academic Conference on Environmental and Occupational Medicine CY APR 07-10, 2010 CL Dujiangyan, PEOPLES R CHINA SP Shanghai Municipal Ctr Dis Control & Prevent, Shanghai Inst Prevent Med, Journal Env & Occupat Med, US Natl Inst Hlth, China Calif Res Collaborat, US Dis Control & Prevent, Natl Ctr Env Hlth, Shanghai Prevent Med Assoc, Env Hlth Perspect, Dujiangyan Hlth Bur DE occupation health; exposure assessment; job-exposure matrix (JEM); occupational hazards; occupational epidemiology ID JOB-EXPOSURE MATRIX; CANCER AB Establishment of the job exposure matrix (JEM) based upon 704, 504 lines of data from record of occupational hazard monitoring program in Shanghai 1953-2000 is presented. The processes included: data collection, transcription, coding, cleaning-up; eradicating duplicates and unusual extra-large value; logistic check-up; assignment time of period, rating the intensity in various trade and occupation; collapse and condensation of the numbers into groups; multiple-regression with dummy variable and/or weighting in number of samples; predicting and listing the matrix, etc. JEM of thirty occupational hazards was established. Meaning, usefulness, methodology, limitation and perspective of JEM were concisely discussed. Longitudinal trend of the hazard concentration at work place under monitoring showed asharp decline, that indicates remarkable success of the occupation health in this half century. C1 [Xue Shou-zheng] NCI, Bethesda, MD 20892 USA. RP Xue, SZ (reprint author), NCI, Bethesda, MD 20892 USA. EM shouzhengxue@yahoo.com NR 13 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL ENVIRONMENTAL & OCCUPATION MEDICINE-JEOM PI SHANGHAI PA 1380 ZHONGSHAN ROAD W, SHANGHAI, 200336, PEOPLES R CHINA PY 2010 BP 138 EP 140 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BVH53 UT WOS:000291569100092 ER PT S AU Amaruchkul, K Sae-Lim, P AF Amaruchkul, Kannapha Sae-Lim, Patipan BE Zhao, X Zhu, G Flynn, BB TI Airline Overbooking Models with Misspecification SO PROCEEDINGS OF THE FOURTH INTERNATIONAL CONFERENCE ON OPERATIONS AND SUPPLY CHAIN MANAGEMENT (ICOSCM 2010) SE Series of Operations and Supply Chain Management in China LA English DT Proceedings Paper CT 4th International Conference on Operations and Supply Chain Management/15th Annual Meeting of the Asia-Pacific-Decision-Sciences-Institute CY JUL 25-31, 2010 CL Hong Kong, PEOPLES R CHINA SP Hong Kong Sci & Technol Parks, IDS, S China Univ Technol, Res Inst Modern Serv Ind, China Mobile Grp Guangdong Co Ltd, Guangzhou Echom Sci & Technol Co Ltd, Chinese Univ Hong Kong, Li & Fung Inst Supply Chain Management & Logist, Centre Supply Chain Management & Logist, S China Univ Technol, Sch Business Adm, Indiana Univ, Centre Int Business Educ & Res, Asia Pacif Decis Sci Inst DE Revenue Management; Overbooking; Stochastic Model Applications; Operations Research ID REVENUE MANAGEMENT; YIELD MANAGEMENT; TESTS AB Static overbooking models are studied. Suppose that each reservation shows up independently, and that the probability of showing up is identical among all reservations. Then, the random show demand follows the binomial distribution. However, in practice some overbooking modules assume that the show demand is the product of the overbooking level and the random show-up rate. The decision model embedded in a commercial revenue management system is misspecified. In this article, we explore the consequences of the modeling error. Through numerical experiments, we find that the performance of the model with misspecification decreases as the show-up probability decreases. Among our three choices of show-up rate distributions, the beta model performs best. C1 [Amaruchkul, Kannapha; Sae-Lim, Patipan] NIDA, Sch Appl Stat, Bangkok, Thailand. EM kamaruchkul@gmail.com NR 25 TC 0 Z9 0 U1 0 U2 1 PU CHINESE UNIV HONG KONG, ECONOMICS & MANGEMENT SCHOOL, WUHAN UNIV PI WUHAN PA SUPPLY CHAIN MANAGEMENT RESEARCH CENTER, LI & FUNG INST SUPPLY CHAIN MANAGEMENT & LOGISTICS, WUHAN, 00000, PEOPLES R CHINA SN 1993-9078 J9 SER OPER SUPP CH MAN PY 2010 VL 4 BP 282 EP 287 PG 6 WC Business; Management SC Business & Economics GA BWV67 UT WOS:000295080900062 ER PT S AU Amaruchkul, K AF Amaruchkul, Kannapha BE Zhao, X Zhu, G Flynn, BB TI Value of Information in Air-Cargo Revenue Management SO PROCEEDINGS OF THE FOURTH INTERNATIONAL CONFERENCE ON OPERATIONS AND SUPPLY CHAIN MANAGEMENT (ICOSCM 2010) SE Series of Operations and Supply Chain Management in China LA English DT Proceedings Paper CT 4th International Conference on Operations and Supply Chain Management/15th Annual Meeting of the Asia-Pacific-Decision-Sciences-Institute CY JUL 25-31, 2010 CL Hong Kong, PEOPLES R CHINA SP Hong Kong Sci & Technol Parks, IDS, S China Univ Technol, Res Inst Modern Serv Ind, China Mobile Grp Guangdong Co Ltd, Guangzhou Echom Sci & Technol Co Ltd, Chinese Univ Hong Kong, Li & Fung Inst Supply Chain Management & Logist, Centre Supply Chain Management & Logist, S China Univ Technol, Sch Business Adm, Indiana Univ, Centre Int Business Educ & Res, Asia Pacif Decis Sci Inst DE Air-Cargo; Revenue Management; Stochastic Model Applications ID OVERBOOKING; CAPACITY; BOOKING; SPACE AB Air-cargo capacity is random and affected by the number of passengers carried, because both cargo shipments and passenger bags are carried in a belly of a plane. The fewer the passengers carried, the higher the cargo capacity. Current seats sold usually provide some information on the passengers carried, and consequently the cargo capacity. Records of the passengers carried and the seats sold are readily available in a passenger revenue management system. We propose mathematical models to evaluate monetary benefits, if different levels of information in the passenger revenue management system are shared by the cargo revenue management system. At a minimum level, an airline constructs a prior distribution of random cargo capacity from a historical record of passengers carried. At a higher level, the airline updates the distribution of cargo capacity based on the number of seats sold. A numerical example that illustrates the proposed methodology is also provided. C1 [Amaruchkul, Kannapha] NIDA, Sch Appl Stat, Bangkok 10240, Thailand. EM kamaruchkul@gmail.com NR 15 TC 0 Z9 0 U1 0 U2 2 PU CHINESE UNIV HONG KONG, ECONOMICS & MANGEMENT SCHOOL, WUHAN UNIV PI WUHAN PA SUPPLY CHAIN MANAGEMENT RESEARCH CENTER, LI & FUNG INST SUPPLY CHAIN MANAGEMENT & LOGISTICS, WUHAN, 00000, PEOPLES R CHINA SN 1993-9078 J9 SER OPER SUPP CH MAN PY 2010 VL 4 BP 370 EP 374 PG 5 WC Business; Management SC Business & Economics GA BWV67 UT WOS:000295080900080 ER PT J AU O'Rorke, MA Cantwell, MM Abnet, CC Murray, LJ AF O'Rorke, M. A. Cantwell, M. M. Abnet, C. C. Murray, L. J. CA FINBAR Study Grp TI Toenail trace elements and risk of Barrett's oesophagus and oesophageal adenocarcinoma: results from the FINBAR study SO PROCEEDINGS OF THE NUTRITION SOCIETY LA English DT Meeting Abstract C1 [O'Rorke, M. A.; Cantwell, M. M.; Murray, L. J.] Queens Univ Belfast, Ctr Publ Hlth, Canc Epidemiol & Hlth Serv Res Grp, Belfast BT12 6BJ, Antrim, North Ireland. [Abnet, C. C.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0029-6651 EI 1475-2719 J9 P NUTR SOC JI Proc. Nutr. Soc. PY 2010 VL 69 IS OCE5 BP E370 EP E370 DI 10.1017/S0029665110002314 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA V45NH UT WOS:000209822800030 ER PT J AU Erdogan, H Bodenreider, O Erdem, E AF Erdogan, Halit Bodenreider, Olivier Erdem, Esra GP AAAI TI Finding Semantic Inconsistencies in UMLS Using Answer Set Programming SO PROCEEDINGS OF THE TWENTY-FOURTH AAAI CONFERENCE ON ARTIFICIAL INTELLIGENCE (AAAI-10) LA English DT Proceedings Paper CT 24th AAAI Conference on Artificial Intelligence (AAAI) CY JUL 11-15, 2010 CL Atlanta, GA SP Assoc Advancement Artificial Intelligence AB We introduce a new method to find semantic inconsistencies (i.e., concepts with erroneous synonymity) in the Unified Medical Language System (UMLS). The idea is to identify the inconsistencies by comparing the semantic groups of hierarchically-related concepts using Answer Set Programming. With this method, we identified several inconsistent concepts in UMLS and discovered an interesting semantic pattern along hierarchies, which seems associated with wrong synonymy. C1 [Erdogan, Halit; Erdem, Esra] Sabanci Univ, Fac Engn & Nat Sci, Istanbul, Turkey. [Bodenreider, Olivier] NIH, US Natl Lib Med, Bethesda, MD 20892 USA. RP Erdogan, H (reprint author), Sabanci Univ, Fac Engn & Nat Sci, Istanbul, Turkey. FU Intramural Research Program of NIH/NLM; TUBITAK [108E229] FX This research was supported by the Intramural Research Program of NIH/NLM, and TUBITAK Grant 108E229. NR 9 TC 1 Z9 1 U1 0 U2 0 PU ASSOC ADVANCEMENT ARTIFICIAL INTELLIGENCE PI PALO ALTO PA 2275 E BAYSHORE RD, STE 160, PALO ALTO, CA 94303 USA BN 978-1-57735-463-5 PY 2010 BP 1927 EP 1928 PG 2 WC Computer Science, Artificial Intelligence SC Computer Science GA BG7ZA UT WOS:000392059700311 ER PT J AU Greig, NH Becker, RE Yu, Q Holloway, HW Tweedie, D Luo, W Utsuki, T Ingram, DK Maccecchini, ML Rogers, JT Sambamurti, K Lahiri, DK AF Greig, N. H. Becker, R. E. Yu, Q. Holloway, H. W. Tweedie, D. Luo, W. Utsuki, T. Ingram, D. K. Maccecchini, M. L. Rogers, J. T. Sambamurti, K. Lahiri, D. K. TI From natural products to Alzheimer experimental therapeutics, eserine based drugs as symptomatic and disease altering agents SO PROGRESS IN NUTRITION LA English DT Article DE Alzheimer's disease; eserine; physostigmine ID AMYLOID PRECURSOR PROTEIN; BUTYRYLCHOLINESTERASE; PHENSERINE; INFLAMMATION; TRANSLATION; PEPTIDE; TARGET AB Based on the hexahydropyrroloindole backbone of the natural product and alkaloid, (-)-physostigmine (eserine) - a short-acting non-selective reversible cholinesterase inhibitor, three series of compounds were designed and developed to overcome its pharmacokinetic and pharmacodynamic shortfalls to provide experimental therapeutics for Alzheimer's disease (AD) and pharmacological tools to define brain function in health, aging and disease. Posiphen and analogues are amyloid-beta precursor protein (APP) and amyloid-beta peptide (A beta) lowering agents that are cholinergically inert but generate metabolites with anticholinesterase action. (-)-Bisnorcymserine and analogues are potent, centrally active, reversible, selective butyrylcholinesterase inhibitors, whereas (-)-phenserine and analogues are similar but selective acetylcholinesterase inhibitors, and each additionally lowers APP and A beta generation as a secondary action. Defining the clinical value of these agents in AD and related dementias is a key focus of current research. C1 [Greig, N. H.; Becker, R. E.; Yu, Q.; Holloway, H. W.; Tweedie, D.; Luo, W.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Tweedie, D.] MedStar Res Inst, Baltimore, MD USA. [Utsuki, T.; Ingram, D. K.] Pennington Biomed Res Ctr, Lab Nutr Neurosci & Aging, Baton Rouge, LA USA. [Maccecchini, M. L.] QR Pharma, Radnor, PA USA. [Rogers, J. T.] Harvard Univ, Sch Med, Dept Psychiat Neurosci, Charlestown, MA USA. [Sambamurti, K.] Med Univ S Carolina, Dept Neurosci, Ctr Aging, Charleston, SC 29425 USA. [Lahiri, D. K.] Indiana Univ Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN USA. RP Greig, NH (reprint author), NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM greign@mail.nih.gov FU National Institute on Aging, NIH; Medstar Research Institute; NIH [AG023055, AG02081, AG18379, AG18884] FX This work was supported in part by the National Institute on Aging, NIH. DT was supported by the Medstar Research Institute. KS was supported in part by NIH grant AG023055, JTR by grant AG02081, and DKL by grants from NIH (AG18379 and AG18884). NR 20 TC 2 Z9 2 U1 1 U2 5 PU MATTIOLI 1885 PI FIDENZA PA VIA DELLA LODESANA 649-SX, FIDENZA, 43046 PR, ITALY SN 1129-8723 J9 PROG NUTR JI Prog. Nutr. PY 2010 VL 12 IS 1 BP 58 EP 63 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 614KR UT WOS:000279057900011 ER PT J AU Stolk, P Souverein, PC Wilting, I Leufkens, HGM Klein, DF Rapoport, SI Heerdink, ER AF Stolk, Pieter Souverein, Patrick C. Wilting, Ingeborg Leufkens, Hubert G. M. Klein, Donald F. Rapoport, Stanley I. Heerdink, Eibert R. TI Is aspirin useful in patients on lithium? A pharmacoepidemiological study related to bipolar disorder SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE Bipolar disorder; Aspirin; NSAIDs; Glucocorticoids; Lithium; Arachidonic acid; Pharmacoepidemiology ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ARACHIDONIC-ACID CASCADE; CHRONIC DISEASE SCORE; MOOD STABILIZERS; CYCLOOXYGENASE-2 INHIBITORS; INDUCIBLE CYCLOOXYGENASE; FRONTAL-CORTEX; IN-VITRO; DEPRESSION; ANTICONVULSANTS AB Objectives: Administration to rats of mood stabilizers approved for bipolar disorder (BD) down-regulates markers of the brain arachidonic acid (AA 20:4n-6) metabolic cascade, including phospholipase A(2) (PLA(2)) and cyclooxygenase (COX) expression. We hypothesized that other agents that target the brain AA cascade, nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, also would ameliorate BD symptoms. Methods: Medication histories on subjects who had been prescribed lithium were collected from the Netherlands PHARMO Record Linkage System. Data were stratified according to drug classes that inhibit PLA(2) and/or COX enzymes, and duration of use. Incidence density (ID) of medication events (dose increase or substance change) was used as a proxy for clinical worsening. ID ratios in patients with the inhibitors plus lithium were compared to ratios in patients using lithium alone. Results: Low-dose acetylsalicylic acid (aspirin) significantly reduced the ID ratio of medication events, independent of use duration. The ID ratios of NSAIDs and glucocorticoids did not differ significantly from 1.0 if prescribed for >= 180 or >= 90 days, but exceeded 1.0 with shorter use. Selective COX-2 inhibitors had no significant effect and multiagent administration increased the ID ratio above 1.0. Conclusions: Low-dose aspirin produced a statistically significant duration-independent reduction in the relative risk of clinical deterioration in subjects on lithium, whereas other NSAIDs and glucocorticoids did not. These tentative findings could be tested on larger databases containing detailed information about diagnosis and disease course, as well as by controlled clinical trials. Published by Elsevier Ltd. C1 [Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. [Klein, Donald F.] Columbia Univ, Med Ctr, Dept Psychiat, New York, NY 10027 USA. [Wilting, Ingeborg] Univ Med Ctr Utrecht, Dept Clin Pharm, Utrecht, Netherlands. [Stolk, Pieter; Souverein, Patrick C.; Wilting, Ingeborg; Leufkens, Hubert G. M.; Heerdink, Eibert R.] Univ Utrecht, Fac Sci, Utrecht Inst Pharmaceut Sci, Div Pharmacoepidemiol & Pharmacotherapy, Utrecht, Netherlands. RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1 S128,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sir@helix.nih.gov RI Heerdink, Eibert/H-6007-2014; OI Heerdink, Eibert/0000-0002-5946-7209; Souverein, Patrick/0000-0002-7452-0477 FU Dutch Ministry of Health; National Institute on Aging, NIH, Bethesda, MD, USA FX Funding Sources and Conflict of Interest Statement: the work of Pieter Stalk was supported by an unrestricted grant of the Dutch Ministry of Health. Stanley I. Rapoport was supported entirely by the Intramural Program of the National Institute on Aging, NIH, Bethesda, MD, USA. The authors have no other relevant commercial or non-commercial funding sources to disclose. NR 53 TC 32 Z9 32 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD JAN PY 2010 VL 82 IS 1 BP 9 EP 14 DI 10.1016/j.plefa.2009.10.007 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 557XF UT WOS:000274702700002 PM 19939659 ER PT J AU Domecq, C Kireeva, M Archambault, J Kashlev, M Coulombe, B Burton, ZF AF Domecq, Celine Kireeva, Maria Archambault, Jacques Kashlev, Mikhail Coulombe, Benoit Burton, Zachary F. TI Site-directed mutagenesis, purification and assay of Saccharomyces cerevisiae RNA polymerase II SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE RNA polymerase II; Saccharomyces cerevisiae; Site-directed mutagenesis; Fork loop 2 region; Transcription factor IIS ID ELONGATION-FACTOR TFIIS; TRANSCRIPTION ELONGATION; AFFINITY PURIFICATION; STRUCTURAL BASIS; SHUTTLE VECTORS; ACTIVE-CENTER; MUTATIONS; NTP; TRANSLOCATION; BINDING AB In order to analyze the structure-function of multi-subunit RNA polymerases (RNAPs), it is necessary to make site-directed mutations in key residues. Because Saccharomyces cerevisiae RNAP 11 is isolated as a 12 subunit enzyme that has not been amenable to in vitro reconstitution, making site-directed mutations in a particular subunit presents technical issues. In this work, we demonstrate a method to generate and purify site-directed mutants in the second largest (Rpb2) RNAP 11 subunit from yeast, using a tandem affinity purification tag. Mutants are analyzed for growth defects in vivo and for defects in transcriptional elongation in vitro. We show that Rpb2 R512A/C located just C-terminal to fork loop 2 (Rpb2 500-511) has transcriptional defects that are distinct from surrounding fork loop 2 region mutants. Rpb2 E529A/D replacements are faster and E529Q is slower than wild type RNAP 11 in elongation. E529 appears to form an ion pair with K987, an essential active site residue. Mutations are also analyzed within the active site region indicating key residues for catalysis and the importance of a Rpb2 R983-E1028 ion pair. Rpb2 R983Q and E1028Q are defective in escape from a transcriptional stall. (C) 2009 Elsevier Inc. All rights reserved. C1 [Burton, Zachary F.] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. [Domecq, Celine; Archambault, Jacques; Coulombe, Benoit] Inst Rech Clin Montreal, Gene Transcript & Prote Lab, Montreal, PQ H2W 1R7, Canada. [Kireeva, Maria; Kashlev, Mikhail] NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Burton, ZF (reprint author), Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. EM burton@msu.edu OI Archambault, Jacques/0000-0001-8107-3428 FU National Institutes of Health [GM57461]; Michigan State University; Michigan State University Agricultural Experiment Station; Michigan State University College of Osteopathic Medicine FX This work was in part supported by the National Institutes of Health Grant GM57461 (to Z.F.B.). Z.F.B. receives support from Michigan State University, the Michigan State University Agricultural Experiment Station, and the Michigan State University College of Osteopathic Medicine. The contents of this publication do not necessarily reveal the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NR 27 TC 12 Z9 12 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD JAN PY 2010 VL 69 IS 1 BP 83 EP 90 DI 10.1016/j.pep.2009.06.016 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 523VR UT WOS:000272103200013 PM 19567268 ER PT B AU Blumberg, PM Kedei, N Lewin, NE Yang, DZ Tao, JA Telek, A Geczy, T AF Blumberg, Peter M. Kedei, Noemi Lewin, Nancy E. Yang, Dazhi Tao, Juan Telek, Andrea Geczy, Tamas BE Kazanietz, MG TI Phorbol Esters and Diacylglycerol: The PKC Activators SO PROTEIN KINASE C IN CANCER SIGNALING AND THERAPY LA English DT Article; Book Chapter DE C1 domain; Diacylglycerol; Phorbol ester; Protein kinase C ID PROTEIN-KINASE-C; CONFORMATIONALLY CONSTRAINED ANALOGS; SKIN TUMOR PROMOTION; DIFFERENTIAL MEMBRANE-BINDING; SITE-DIRECTED MUTAGENESIS; MOUSE EPIDERMAL-CELLS; CYSTEINE-RICH REGION; DAG-LACTONES; DOWN-REGULATION; BRYOSTATIN 1 AB Protein kinase C (PKC) represents the most prominent of the families of signaling proteins integrating response to the ubiquitous lipophilic second messenger sn-1,2-diacylglycerol and to its ultrapotent analogs, the tumor-promoting phorbol esters. Response is mediated through twin conserved zinc finger structures, the Cl domains. The Cl domains function as hydrophobic switches, for which ligand binding completes a hydrophobic surface on the face of the Cl domain, driving membrane association of PKC and enzymatic activation. Since the lipid bilayer provides critical contacts for ligand binding, along with the C I domain, membrane heterogeneity provides an important mechanism for diversity, as do the differential functions of the twin Cl domains. Consistent with such mechanistic diversity, PKC ligands can differ dramatically in biological consequences. Thus, whereas PKC ligands have provided the paradigm for tumor promoters, some PKC ligands in fact function as inhibitors of tumor promotion. Reflecting the central role of PKC in cellular signaling, PKC has emerged as a promising therapeutic target for cancer with several PKC ligands currently in clinical trials. C1 [Blumberg, Peter M.; Kedei, Noemi; Lewin, Nancy E.; Yang, Dazhi; Tao, Juan; Telek, Andrea; Geczy, Tamas] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. RP Blumberg, PM (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, Room 4048,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. EM blumberp@dc37a.nci.nih.gov NR 135 TC 1 Z9 1 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60761-542-2 PY 2010 BP 25 EP 53 DI 10.1007/978-1-60761-543-9_3 D2 10.1007/978-1-60761-543-9 PG 29 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy GA BPQ27 UT WOS:000279629600003 ER PT S AU Sharma, A Mariappan, M Appathurai, S Hegde, RS AF Sharma, Ajay Mariappan, Malaiyalam Appathurai, Suhila Hegde, Ramanujan S. BE Economou, A TI In Vitro Dissection of Protein Translocation into the Mammalian Endoplasmic Reticulum SO PROTEIN SECRETION: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE in vitro translation; microsomes; membrane proteins; reconstitution; proteoliposomes; protease protection; protein topology ID ER MEMBRANE; TRANSLATION; DEGRADATION; INHIBITOR; INSERTION; COMPLEX AB In eukaryotic cells, roughly one-fourth of all mRNAs code for secretory and membrane proteins. This class of proteins must first be segregated to the endoplasmic reticulum, where they are either translocated into the lumen or inserted into the lipid bilayer. The study of these processes has long relied on their successful reconstitution in cell-free systems. The high manipulability of such in vitro systems has allowed the identification of key machinery, elucidation of their functional roles in translocation, and dissection of their mechanisms of action. Here, we provide the basic methodology for (i) setting up robust mammalian-based in vitro translation and translocation systems, (ii) assays for protein translocation, insertion, and topology, and (iii) methods to solubilize, fractionate, and reconstitute ER membranes. Variations of these methods should be applicable not only to forward protein translocation systems but also for dissecting other poorly understood membrane-associated processes such as retrotranslocation. C1 [Sharma, Ajay; Mariappan, Malaiyalam; Appathurai, Suhila; Hegde, Ramanujan S.] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. RP Sharma, A (reprint author), NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. RI mariappan, malaiyalam/K-9024-2012; OI Hegde, Ramanujan/0000-0001-8338-852X FU Intramural NIH HHS [Z01 HD008752-06] NR 20 TC 23 Z9 23 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-167-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 619 BP 339 EP 363 DI 10.1007/978-1-60327-412-8_20 D2 10.1007/978-1-60327-412-8 PG 25 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BOU44 UT WOS:000277632300020 PM 20419420 ER PT S AU Roy, MJ Francis, J Friedlander, J Banks-Williams, L Lande, RG Taylor, P Blair, J McLellan, J Law, W Tarpley, V Patt, I Yu, H Mallinger, A Difede, J Rizzo, A Rothbaum, B AF Roy, Michael J. Francis, Jennifer Friedlander, Joshua Banks-Williams, Lisa Lande, Raymond G. Taylor, Patricia Blair, James McLellan, Jennifer Law, Wendy Tarpley, Vanita Patt, Ivy Yu, Henry Mallinger, Alan Difede, Joann Rizzo, Albert Rothbaum, Barbara BE Barchas, JD Difede, J TI Improvement in cerebral function with treatment of posttraumatic stress disorder SO PSYCHIATRIC AND NEUROLOGIC ASPECTS OF WAR SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 89th Annual Conference of the Association for Research in Nervous and Mental Disease CY DEC 16, 2009 CL Rockefeller Univ, New York, NY HO Rockefeller Univ DE posttraumatic stress disorder; traumatic brain injury; combat stress; functional magnetic resonance imaging; virtual reality; exposure therapy ID DEPRESSION INVENTORY-II; REALITY EXPOSURE THERAPY; ADMINISTERED PTSD SCALE; TRAUMATIC BRAIN-INJURY; BECK DEPRESSION; NEURAL RESPONSES; PHYSICAL HEALTH; FEARFUL FACES; PRIMARY-CARE; IRAQ AB Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are signature illnesses of the Iraq and Afghanistan wars, but current diagnostic and therapeutic measures for these conditions are suboptimal. In our study, functional magnetic resonance imaging (fMRI) is used to try to differentiate military service members with: PTSD and mTBI, PTSD alone, mTBI alone, and neither PTSD nor mTBI. Those with PTSD are then randomized to virtual reality exposure therapy or imaginal exposure. fMRI is repeated after treatment and along with the Clinician-Administered PTSD Scale (CAPS) and Clinical Global Impression (CGI) scores to compare with baseline. Twenty subjects have completed baseline fMRI scans, including four controls and one mTBI only; of 15 treated for PTSD, eight completed posttreatment scans. Most subjects have been male (93%) and Caucasian (83%), with a mean age of 34. Significant improvements are evident on fMRI scans, and corroborated by CGI scores, but CAPS scores improvements are modest. In conclusion, CGI scores and fMRI scans indicate significant improvement in PTSD in both treatment arms, though CAPS score improvements are less robust. C1 [Roy, Michael J.; Francis, Jennifer; Friedlander, Joshua; Banks-Williams, Lisa; Lande, Raymond G.; Taylor, Patricia; Law, Wendy; Tarpley, Vanita; Patt, Ivy] Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. [Roy, Michael J.; Francis, Jennifer; Friedlander, Joshua; Banks-Williams, Lisa; Lande, Raymond G.; Taylor, Patricia; Law, Wendy; Tarpley, Vanita; Patt, Ivy] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Blair, James; McLellan, Jennifer; Yu, Henry; Mallinger, Alan] NIMH, NIH, Bethesda, MD 20892 USA. [Difede, Joann] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Rizzo, Albert] Univ So Calif, Inst Creat Technol, Los Angeles, CA USA. [Rothbaum, Barbara] Emory Univ, Sch Med, Atlanta, GA USA. RP Roy, MJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, Room A3062,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM mroy@usuhs.mil NR 38 TC 35 Z9 35 U1 4 U2 15 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-804-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1208 BP 142 EP 149 DI 10.1111/j.1749-6632.2010.05689.x PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BSK28 UT WOS:000284742000018 PM 20955336 ER PT J AU Blazer, DG Steffens, DC AF Blazer, Dan G. Steffens, David C. TI THIS ISSUE: Geriatric Psychiatry SO PSYCHIATRIC ANNALS LA English DT Editorial Material C1 [Blazer, Dan G.] Duke Univ, Sch Med, Dept Psychiat, Durham, NC 27706 USA. [Blazer, Dan G.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27515 USA. [Steffens, David C.] Duke Univ, Med Ctr, Div Geriatr Psychiat, Durham, NC 27706 USA. [Steffens, David C.] NIH, Adult Psychopathol & Disorders Aging Study Sect, Ctr Sci Review, Bethesda, MD USA. RP Blazer, DG (reprint author), Duke Univ, Sch Med, Dept Psychiat, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JAN PY 2010 VL 40 IS 1 BP 7 EP + DI 10.3928/00485718-20100105-02 PG 3 WC Psychiatry SC Psychiatry GA 547XI UT WOS:000273922800002 ER PT J AU George, DT Herion, DW Jones, CL Phillips, MJ Hersh, J Hill, D Heilig, M Ramchandani, VA Geyer, C Spero, DE Singley, ED O'Malley, SS Bishai, R Rawlings, RR Kunos, G AF George, David Ted Herion, David W. Jones, Cheryl L. Phillips, Monte J. Hersh, Jacqueline Hill, Debra Heilig, Markus Ramchandani, Vijay A. Geyer, Christopher Spero, David E. Singley, Erick D. O'Malley, Stephanie S. Bishai, Raafat Rawlings, Robert R. Kunos, George TI Rimonabant (SR141716) has no effect on alcohol self-administration or endocrine measures in nontreatment-seeking heavy alcohol drinkers SO PSYCHOPHARMACOLOGY LA English DT Article DE Rimonabant (SR141716); Alcohol; Heavy drinkers; CB(1) receptor antagonist; Alcohol self-administration; Endocannabinoids ID CANNABINOID CB1 RECEPTORS; VOLUNTARY ETHANOL INTAKE; PREFERRING SP RATS; DEPENDENT SUBJECTS; DOPAMINE RELEASE; KNOCKOUT MICE; FOOD-INTAKE; ANTAGONIST; BEHAVIOR; SUCROSE AB There is an extensive literature showing that the CB(1) cannabinoid receptor antagonist rimonabant (SR141716) decreases alcohol consumption in animals, but little is known about its effects in human alcohol drinkers. In this study, 49 nontreatment-seeking heavy alcohol drinkers participated in a 3-week study. After a 1-week baseline, participants received either 20 mg/day of rimonabant or placebo for 2 weeks under double-blind conditions. During these 3 weeks, participants reported their daily alcohol consumption by telephone. Subsequently, they participated in an alcohol self-administration paradigm in which they received a priming dose of alcohol followed by the option of consuming either eight alcohol drinks or receiving $3.00 for each nonconsumed drink. Endocrine measures and self-rating scales were also obtained. Rimonabant did not change alcohol consumption during the 2 weeks of daily call-ins. Similarly, the drug did not change either alcohol self-administration or endocrine measures during the laboratory session. We conclude that the daily administration of 20 mg of rimonabant for 2 weeks has no effect on alcohol consumption in nontreatment-seeking heavy alcohol drinkers. C1 [George, David Ted; Herion, David W.; Jones, Cheryl L.; Phillips, Monte J.; Hersh, Jacqueline; Hill, Debra; Heilig, Markus; Ramchandani, Vijay A.; Singley, Erick D.; Rawlings, Robert R.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. [Geyer, Christopher; Spero, David E.] NIH, Clin Ctr Nursing, Bethesda, MD 20892 USA. [Bishai, Raafat] Sanofi Aventis, Int Clin Dev, Malvern, PA USA. [O'Malley, Stephanie S.] Yale Univ, Sch Med, New Haven, CT USA. [Kunos, George] NIAAA, Rockville, MD 20892 USA. RP George, DT (reprint author), NIAAA, Lab Clin & Translat Studies, 10 Ctr Dr,10 CRC Hatfield Ctr,Rm 1-5330,MSC 1108, Bethesda, MD 20892 USA. EM tedg@mail.nih.gov; gkunos@mail.nih.gov OI Heilig, Markus/0000-0003-2706-2482 FU Intramural NIH HHS [ZIA AA000213-01, ZIA AA000466-04] NR 30 TC 26 Z9 26 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2010 VL 208 IS 1 BP 37 EP 44 DI 10.1007/s00213-009-1704-3 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 531JR UT WOS:000272662200004 PM 19902183 ER PT J AU Schmidt, LS Miller, AD Lester, DB Bay-Richter, C Schulein, C Frikke-Schmidt, H Wess, J Blaha, CD Woldbye, DPD Fink-Jensen, A Wortwein, G AF Schmidt, Lene S. Miller, Anthony D. Lester, Deranda B. Bay-Richter, Cecilie Schulein, Christina Frikke-Schmidt, Henriette Wess, Juergen Blaha, Charles D. Woldbye, David P. D. Fink-Jensen, Anders Wortwein, Gitta TI Increased amphetamine-induced locomotor activity, sensitization, and accumbal dopamine release in M-5 muscarinic receptor knockout mice SO PSYCHOPHARMACOLOGY LA English DT Article DE Muscarinic; M-5; Cocaine; Amphetamine; Sensitization; Dopamine ID VENTRAL TEGMENTAL AREA; INCENTIVE-SENSITIZATION; IN-VIVO; BEHAVIORAL SENSITIZATION; NONLINEAR RELATIONSHIP; PREPULSE INHIBITION; NUCLEUS-ACCUMBENS; SUBSTANTIA-NIGRA; IMPULSE FLOW; ACETYLCHOLINE AB Muscarinic M-5 receptors are the only muscarinic receptor subtype expressed by dopamine-containing neurons of the ventral tegmental area. These cells play an important role for the reinforcing properties of psychostimulants and M-5 receptors modulate their activity. Previous studies showed that M-5 receptor knockout (M (5) (-/-) ) mice are less sensitive to the reinforcing properties of addictive drugs. Here, we investigate the role of M-5 receptors in the effects of amphetamine and cocaine on locomotor activity, locomotor sensitization, and dopamine release using M (5) (-/-) mice backcrossed to the C57BL/6NTac strain. Sensitization of the locomotor response is considered a model for chronic adaptations to repeated substance exposure, which might be related to drug craving and relapse. The effects of amphetamine on locomotor activity and locomotor sensitization were enhanced in M (5) (-/-) mice, while the effects of cocaine were similar in M (5) (-/-) and wild-type mice. Consistent with the behavioral results, amphetamine-, but not cocaine, -elicited dopamine release in nucleus accumbens was enhanced in M (5) (-/-) mice. The different effects of amphetamine and cocaine in M (5) (-/-) mice may be due to the divergent pharmacological profile of the two drugs, where amphetamine, but not cocaine, is able to release intracellular stores of dopamine. In conclusion, we show here for the first time that amphetamine-induced hyperactivity and dopamine release as well as amphetamine sensitization are enhanced in mice lacking the M-5 receptor. These results support the concept that the M-5 receptor modulates effects of addictive drugs. C1 [Schmidt, Lene S.; Bay-Richter, Cecilie; Schulein, Christina; Frikke-Schmidt, Henriette; Woldbye, David P. D.; Fink-Jensen, Anders; Wortwein, Gitta] Rigshosp, Ctr Psychiat, Lab Neuropsychiat, DK-2100 Copenhagen, Denmark. [Miller, Anthony D.; Lester, Deranda B.; Blaha, Charles D.] Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. [Wess, Juergen] NIDDK, Bioorgan Chem Lab, Mol Signaling Sect, NIH, Bethesda, MD 20892 USA. RP Wortwein, G (reprint author), Rigshosp, Ctr Psychiat, Lab Neuropsychiat, O-6102,Blegdamsvej 3, DK-2100 Copenhagen, Denmark. EM gw@rh.dk OI Blaha, Charles/0000-0001-5155-1505; Wortwein, Gitta/0000-0001-6981-7885 FU Lundbeck Foundation; Ivan Nielsen Foundation FX The Lundbeck Foundation and the Ivan Nielsen Foundation supported the present work. We thank Birgit Heine Hansen for expert technical assistance and Morgane Thomsen for critical review of this manuscript. NR 39 TC 18 Z9 18 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2010 VL 207 IS 4 BP 547 EP 558 DI 10.1007/s00213-009-1685-2 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 524WN UT WOS:000272175200004 PM 19820917 ER PT J AU Voon, V Reynolds, B Brezing, C Gallea, C Skaljic, M Ekanayake, V Fernandez, H Potenza, MN Dolan, RJ Hallett, M AF Voon, Valerie Reynolds, Brady Brezing, Christina Gallea, Cecile Skaljic, Meliha Ekanayake, Vindhya Fernandez, Hubert Potenza, Marc N. Dolan, Raymond J. Hallett, Mark TI Impulsive choice and response in dopamine agonist-related impulse control behaviors SO PSYCHOPHARMACOLOGY LA English DT Article DE Dopamine agonist; Gambling; Impulse control; Parkinson's disease; Delay discounting ID REACTION-TIME-TASK; EXPERIENTIAL-DISCOUNTING-TASK; CENTRAL 5-HT DEPLETION; PARKINSON-DISEASE; NUCLEUS-ACCUMBENS; DELAYED REWARDS; ADOLESCENT SMOKERS; CONTROL DISORDERS; DECISION-MAKING; PROBABILISTIC REINFORCEMENT AB Dopaminergic medication-related impulse control disorders (ICDs) such as pathological gambling and compulsive shopping have been reported in Parkinson's disease (PD). We hypothesized that dopamine agonists (DAs) would be associated with greater impulsive choice or greater discounting of delayed rewards in PD patients with ICDs (PDI). Fourteen PDI patients, 14 PD controls without ICDs, and 16 medication-free matched normal controls were tested on the Experiential Discounting Task (EDT), a feedback-based intertemporal choice task, spatial working memory, and attentional set shifting. The EDT was used to assess choice impulsivity (hyperbolic K value), reaction time (RT), and decision conflict RT (the RT difference between high conflict and low conflict choices). PDI patients and PD controls were tested on and off DA. On the EDT, there was a group by medication interaction effect [F(1,26) = 5.62; p = 0.03] with pairwise analyses demonstrating that DA status was associated with increased impulsive choice in PDI patients (p = 0.02) but not in PD controls (p = 0.37). PDI patients also had faster RT compared to PD controls [F(1,26) = 7.51, p = 0.01]. DA status was associated with shorter RT [F(3,24) = 8.39, p = 0.001] and decision conflict RT [F(1,26) = 6.16, p = 0.02] in PDI patients but not in PD controls. There were no correlations between different measures of impulsivity. PDI patients on DA had greater spatial working memory impairments compared to PD controls on DA (t = 2.13, df = 26, p = 0.04). Greater impulsive choice, faster RT, faster decision conflict RT, and executive dysfunction may contribute to ICDs in PD. C1 [Voon, Valerie; Brezing, Christina; Gallea, Cecile; Skaljic, Meliha; Ekanayake, Vindhya; Hallett, Mark] Natl Inst Hlth, Bethesda, MD 20892 USA. [Reynolds, Brady] Ohio State Univ, Columbus, OH 43210 USA. [Fernandez, Hubert] Univ Florida, Gainesville, FL USA. [Potenza, Marc N.] Yale Univ, New Haven, CT USA. [Dolan, Raymond J.] UCL, London, England. RP Voon, V (reprint author), Natl Inst Hlth, 10 Ctr Dr,Bldg 10 Rm 7D37, Bethesda, MD 20892 USA. EM voonv@ninds.nih.gov OI Dolan, Ray/0000-0001-9356-761X FU NINDS [R01 DA019039]; VA VISN1 MIRECC FX This study was supported by intramural NINDS, R01 DA019039, and the VA VISN1 MIRECC. We would like to thank the intramural Parkinson's disease clinic and Dr. Grisel Lopez for assessments and referral of subjects. NR 77 TC 99 Z9 100 U1 4 U2 24 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2010 VL 207 IS 4 BP 645 EP 659 DI 10.1007/s00213-009-1697-y PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 524WN UT WOS:000272175200013 PM 19838863 ER PT J AU Ernst, M Derakshan, N AF Ernst, Monique Derakshan, Nazanin TI FROM PERCEPTION TO ACTION: WHEN, WHERE, AND HOW DOES ANXIETY BREAK THE CHAIN? SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 29-OCT 03, 2010 CL Portland, OR SP Soc Psychophysiol Res C1 [Ernst, Monique] NIMH, Bethesda, MD 20892 USA. [Derakshan, Nazanin] Birkbeck Univ London, London, England. 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 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2010 VL 47 SU 1 BP S5 EP S5 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 635NI UT WOS:000280662000023 ER PT J AU Fowler, KA Blair, JR AF Fowler, Katherine A. Blair, James R. TI YOUTHS WITH CONDUCT DISORDER AND CALLOUS-UNEMOTIONAL TRAITS SHOW DISRUPTED VENTROMEDIAL FRONTAL CORTEX FUNCTION DURING DECISIONS REGARDING ENVIRONMENTAL THREATS AND REWARDS SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting Portland Marriott Downtown Waterfront CY SEP 29-OCT 03, 2010 CL Portland, OR SP Soc Psychophysiolog C1 [Fowler, Katherine A.; Blair, James R.] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2010 VL 47 SU 1 BP S15 EP S15 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 635NI UT WOS:000280662000085 ER PT J AU Mueller, SC Maheu, FS Hardin, MG Korelitz, K Dozier, M Peloso, E Leibenluft, E Pine, DS Ernst, M AF Mueller, Sven C. Maheu, Francoise S. Hardin, Michael G. Korelitz, Katherine Dozier, Mary Peloso, Elizabeth Leibenluft, Ellen Pine, Daniel S. Ernst, Monique TI EARLY LIFE STRESS DUE TO MALTREATMENT IN CHILDHOOD MODULATES INHIBITORY CONTROL AND REWARD PROCESSING: EVIDENCE FROM EYE TRACKING AND FMRI SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 29-OCT 03, 2010 CL Portland, OR SP Soc Psychophysiol Res C1 [Mueller, Sven C.; Hardin, Michael G.; Korelitz, Katherine; Leibenluft, Ellen; Pine, Daniel S.; Ernst, Monique] NIMH, Natl Inst Hlth, Bethesda, MD 20892 USA. [Maheu, Francoise S.] Univ Montreal, Montreal, PQ H3C 3J7, Canada. [Dozier, Mary; Peloso, Elizabeth] Univ Delaware, Newark, DE 19716 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2010 VL 47 SU 1 BP S16 EP S16 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 635NI UT WOS:000280662000093 ER PT J AU Mueller, SC Ernst, M AF Mueller, Sven C. Ernst, Monique TI PSYCHOPHYSIOLOGICAL AND NEUROBIOLOGICAL MARKERS OF EARLY LIFE STRESS THROUGHOUT THE LIFE SPAN SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 29-OCT 03, 2010 CL Portland, OR SP Soc Psychophysiol Res C1 [Mueller, Sven C.; Ernst, Monique] NIMH, Natl Inst Hlth, 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 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2010 VL 47 SU 1 BP S16 EP S16 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 635NI UT WOS:000280662000090 ER PT J AU Schmitz, A Merikangas, KR Swendsen, HC Grillon, C AF Schmitz, Anja Merikangas, Kathleen R. Swendsen, Haruka C. Grillon, Christian TI GIRLS ARE MORE ANXIOUS BUT NOT FEARFUL COMPARED TO BOYS SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting Portland Marriott Downtown Waterfront CY SEP 29-OCT 03, 2010 CL Portland, OR SP Soc Psychophysiolog C1 [Schmitz, Anja; Merikangas, Kathleen R.; Swendsen, Haruka C.; Grillon, Christian] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2010 VL 47 SU 1 BP S103 EP S103 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 635NI UT WOS:000280662000564 ER PT J AU Sanderson, SC Persky, S Michie, S AF Sanderson, S. C. Persky, S. Michie, S. TI Psychological and Behavioral Responses to Genetic Test Results Indicating Increased Risk of Obesity: Does the Causal Pathway from Gene to Obesity Matter? SO PUBLIC HEALTH GENOMICS LA English DT Article DE Genetics and prevention; Genetic testing; Health behavior; Obesity; Prevention of common complex diseases; Psychological impact; Risk; Translational research ID FTO GENE; HEART-DISEASE; FAT MASS; PERCEPTION QUESTIONNAIRE; PARENTAL OBESITY; ADULT OBESITY; WEIGHT; HEALTH; ANALOG; CONSEQUENCES AB Background: Common obesity-associated genetic variants may exert their effects through increasing eating or decreasing metabolism. Such differences might influence individual responses to obesity genetic test results. Methods: This was an experimental analogue study: 191 participants were asked to imagine they had received a genetic test result indicating high eating-based (n = 37) or high metabolism-based (n = 41) risk of obesity, an enzyme test result indicating high eating-based (n = 35) or high metabolism-based (n = 41) risk of obesity, or no risk information (n = 37). Outcomes included perceived risk, self-efficacy (confidence in ability to eat healthily), response-efficacy (confidence that eating healthily will reduce risk), and intention to eat healthily. Results: The groups receiving increased obesity risk information reported greater perceived risk and intention to eat healthily than the no risk information group (both p < 0.01). There were main effects of test type on perceived risk (genetic vs. enzyme: 3.91 vs. 3.55, p = 0.031) and of causal pathway on worry (eating vs. metabolism: 3.33 vs. 2.86, p = 0.049), but no effects of either manipulation on any other outcomes. Conclusion: Personal risk information indicating increased obesity risk may increase motivation to eat healthily, regardless of whether the risk is described as genetic or non-genetic or as acting through an eating-based or metabolism-based causal pathway. Copyright (C) 2009 S. Karger AG, Basel C1 [Sanderson, S. C.] Mt Sinai Sch Med, Dept Genet & Genom Sci, Icahn Med Inst, New York, NY 10029 USA. [Persky, S.] NHGRI, Bethesda, MD 20892 USA. [Michie, S.] UCL, Dept Psychol, London, England. RP Sanderson, SC (reprint author), Mt Sinai Sch Med, Dept Genet & Genom Sci, Icahn Med Inst, Floor 14,1425 Madison Ave, New York, NY 10029 USA. EM saskia.sanderson@mssm.edu RI Michie, Susan/A-1745-2010 OI Michie, Susan/0000-0003-0063-6378 NR 56 TC 18 Z9 18 U1 0 U2 10 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 EI 1662-8063 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2010 VL 13 IS 1 BP 34 EP 47 DI 10.1159/000217794 PG 14 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 497MA UT WOS:000270062400005 PM 19407440 ER PT J AU Adeyemo, A Rotimi, C AF Adeyemo, A. Rotimi, C. TI Genetic Variants Associated with Complex Human Diseases Show Wide Variation across Multiple Populations SO PUBLIC HEALTH GENOMICS LA English DT Article DE Complex disease; Genome wide association studies; Population genetics ID EPIDEMIOLOGY AB Background: The wide use of genome wide association studies (GWAS) has led to the successful identification of multiple genetic susceptibility variants to several complex human diseases. Given the limited amount of data on genetic variation at these loci in populations of non-European origin, we investigated population variation among 11 population groups for loci showing strong and consistent association from GWAS with several complex human diseases. Methods: Data from the International HapMap Project Phase 3, comprising 11 population groups, were used to estimate allele frequencies at loci showing strong and consistent association from GWAS with any of 26 complex human diseases and traits. Allele frequency summary statistics and F(ST) at each locus were used to estimate population differentiation. Results: There is wide variation in allele frequencies and F(ST) across the 11 population groups for susceptibility loci to these complex human diseases and traits. Allele frequencies varied widely across populations, often by as much as 20- to 40-fold. F(ST), as a measure of population differentiation, also varied widely across the loci studied (for example, 0.019 to 0.201 for type 2 diabetes, 0.022 to 0.520 for prostate cancer loci, and 0.006 to 0.520 for serum lipid levels). Conclusions: The public health risk posed by any of these risk alleles is likely to show wide variation across populations simply as a function of its frequency, and this risk difference may be amplified by gene-gene and gene-environment interactions. These analyses offer compelling reasons for including multiple human populations from different parts of the world in the international effort to use genomic tools to understand disease etiology and differential distribution of diseases across ethnic groups. Copyright (C) 2009 S. Karger AG, Basel C1 [Adeyemo, A.; Rotimi, C.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. RP Adeyemo, A (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bldg 12A,Suite 4047,12 South Dr,MSC 5635, Bethesda, MD 20892 USA. EM adeyemoa@mail.nih.gov OI Adeyemo, Adebowale/0000-0002-3105-3231 FU NIH; National Human Genome Research Institute FX This research was supported by the Intramural Research Program of the NIH, National Human Genome Research Institute. AA and CR conceived and designed the study. AA conducted the data acquisition and analysis. Both authors did the interpretation of the data, drafting and approval of the manuscript. NR 15 TC 68 Z9 70 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 J9 PUBLIC HEALTH GENOMI JI Pub. Health Genomics PY 2010 VL 13 IS 2 BP 72 EP 79 DI 10.1159/000218711 PG 8 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 530NB UT WOS:000272598500002 PM 19439916 ER PT J AU Sanderson, SC O'Neill, SC Bastian, LA Bepler, G McBride, CM AF Sanderson, S. C. O'Neill, S. C. Bastian, L. A. Bepler, G. McBride, C. M. TI What Can Interest Tell Us about Uptake of Genetic Testing? Intention and Behavior amongst Smokers Related to Patients with Lung Cancer SO PUBLIC HEALTH GENOMICS LA English DT Article DE Attitudes; Complex diseases; Decision-making; Evaluation of genetic/genomic tools for public health; Genetic testing; Interest; Lung cancer; Uptake ID HEREDITARY PROSTATE-CANCER; ANTICIPATED REACTIONS; UNAFFECTED MEN; SUSCEPTIBILITY; RISK; ATTITUDES; FAMILIES; BREAST; DISEASES; SMOKING AB Background: Much of the research examining psychosocial aspects of genetic testing has used hypothetical scenarios, based on the largely untested assumption that hypothetical genetic testing intentions are good proxies for behavior. We tested whether hypothetical interest predicts uptake of genetic testing and whether factors that predict interest also predict uptake. Methods: Participants (n = 116) were smokers and related to patients with lung cancer, who completed a telephone survey. Interest in genetic testing for lung cancer risk was indicated by responding 'definitely would' to a Likert-style question. Internet-delivered genetic testing for lung cancer risk was then offered. Uptake was indicated by requesting the test and receiving the result. Results: 63% of participants said they ` definitely would' take the genetic test; uptake was 38%. Participants who said they ` definitely would' take the test were more likely than others to take the offered test (45% vs. 26%, p = 0.035). Interest was associated with attitudes towards genetic testing and motivation to quit smoking. Uptake was associated with motivation, prior awareness of genetic testing, and daily Internet use. Conclusion: Hypothetical interest only modestly predicts uptake of genetic testing. Interest in genetic testing likely reflects generally positive attitudes that are not good predictors of the choices individuals subsequently make. Copyright (C) 2009 S. Karger AG, Basel C1 [Sanderson, S. C.] Mt Sinai Sch Med, Dept Genet & Genom Sci, Icahn Med Inst, New York, NY 10029 USA. [O'Neill, S. C.] Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Canc Control Program, Washington, DC USA. [Bastian, L. A.] Duke Univ, Med Ctr, Durham, NC USA. [Bastian, L. A.] Vet Adm Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. [Bepler, G.] H Lee Moffitt Comprehens Canc Ctr, Tampa, FL USA. [McBride, C. M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP Sanderson, SC (reprint author), Mt Sinai Sch Med, Dept Genet & Genom Sci, Icahn Med Inst, Floor 14,1425 Madison Ave, New York, NY 10029 USA. EM saskia.sanderson@mssm.edu FU Intramural NIH HHS [Z01 HG200315-04]; NCI NIH HHS [U01 CA092622, P30 CA051008] NR 27 TC 38 Z9 38 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 J9 PUBLIC HEALTH GENOMI JI Pub. Health Genomics PY 2010 VL 13 IS 2 BP 116 EP 124 DI 10.1159/000226595 PG 9 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 530NB UT WOS:000272598500007 PM 19556750 ER PT J AU Wade, CH McBride, CM Kardia, SLR Brody, LC AF Wade, C. H. McBride, C. M. Kardia, S. L. R. Brody, L. C. TI Considerations for Designing a Prototype Genetic Test for Use in Translational Research SO PUBLIC HEALTH GENOMICS LA English DT Article DE Clinical utility; Common disease; Genetic epidemiology; Genetic testing ID GENOME-WIDE ASSOCIATION; BONE-MINERAL DENSITY; COMMON DISEASE; SMOKING-CESSATION; COMPLEX DISEASES; CANCER SUSCEPTIBILITY; RESEARCH PARTICIPANTS; PSYCHOLOGICAL IMPACT; A986S POLYMORPHISM; COLORECTAL-CANCER AB Background: Translational research is needed to explore how people will respond to personal genetic susceptibility information related to common health conditions. Maximizing the rigor of this research will require that genetic test results be returned to study participants. Currently, there is no established method that guides the selection of genetic variants to be used in research with these objectives. Methods and Results: To address this question, we designed a process to identify gene variants and health conditions to be included in a prototype genetic test for use in a larger research effort, the Multiplex Initiative. The intention of this exploration was to facilitate research that generates individual genetic test results that are returned to study participants. Inclusion criteria were developed as part of a transdisciplinary and iterative process that considered the weight of evidential support for genetic association with common health conditions, the appropriateness of use in human subjects research, and the recommendations of expert peer reviewers. Conclusions: The selection process was designed to identify gene variants for the limited purpose of translational research and, therefore, should not be seen as producing a valid clinical test. However, this example of an applied selection process may provide guidance for researchers who are designing studies to evaluate the implications of genetic susceptibility testing through the return of personalized genetic information. As the rate of genomic discoveries increases, such research will be essential in steering the translation of this information towards the greatest public health benefit. Copyright (C) 2009 S. Karger AG, Basel C1 [Wade, C. H.; Brody, L. C.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Wade, C. H.; McBride, C. M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Kardia, S. L. R.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. RP Brody, LC (reprint author), 50 South Dr,Bldg 50,Room 5306, Bethesda, MD 20892 USA. EM lbrody@helix.nih.gov FU National Human Genome Research Institute, National Institutes of Health FX We would like to thank the members of the external working group, Tanya Agurs-Collins, Holly Peay, Karen Mohlke, and Giovanni Cizza. Additionally, we appreciate the recommendations of our peer reviewers, Muin Khoury, Janet Stanford, Timothy Rebbeck, Alisa Goldstein, and Elaine Ostrander. We also thank Elizabeth Gillanders and other participants in the Multiplex Initiative planning meeting for their useful comments. This research was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 87 TC 17 Z9 17 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 J9 PUBLIC HEALTH GENOMI JI Pub. Health Genomics PY 2010 VL 13 IS 3 BP 155 EP 165 DI 10.1159/000236061 PG 11 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 557TT UT WOS:000274693700004 PM 19729884 ER PT J AU Wade, CH McBride, CM Kardia, SLR Brody, LC AF Wade, C. H. McBride, C. M. Kardia, S. L. R. Brody, L. C. TI A Response to 'Why Realistic Test Scenarios in Translational Research Remain Hypothetical' SO PUBLIC HEALTH GENOMICS LA English DT Article C1 [Wade, C. H.; Brody, L. C.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Wade, C. H.; McBride, C. M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Kardia, S. L. R.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. RP Brody, LC (reprint author), 50 South Dr,Bldg 50,Room 5306, Bethesda, MD 20892 USA. EM lbrody@helix.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 J9 PUBLIC HEALTH GENOMI JI Pub. Health Genomics PY 2010 VL 13 IS 3 BP 169 EP 170 DI 10.1159/000236063 PG 2 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 557TT UT WOS:000274693700006 ER PT J AU Bonham, VL Knerr, S Feero, WG Stevens, N Jenkins, JF McBride, CM AF Bonham, V. L. Knerr, S. Feero, W. G. Stevens, N. Jenkins, J. F. McBride, C. M. TI Patient Physical Characteristics and Primary Care Physician Decision Making in Preconception Genetic Screening SO PUBLIC HEALTH GENOMICS LA English DT Article DE Ancestry; Decision making; Ethnicity; Genetic screening; Guidelines; Physical features; Preconception; Race ID HEALTH-CARE; RACE; RECOMMENDATIONS; POPULATIONS; GENOMICS; OUTCOMES; HISTORY AB Background: There has been growing emphasis on preconception care as a strategy to improve maternal and child health since the 1980s. Increasingly, development of genetic tests will require primary care providers to make decisions about preconception genetic screening. Limited research has been conducted on how primary care providers interpret patients' characteristics and use constructs, such as ethnicity and race, to decide whom to offer preconception genetic screening. Objective: This report assessed the influence of patient characteristics on decisions to offer preconception genetic screening. Methods: A web-based survey of family physicians was conducted. Physicians reviewed a clinical vignette that was accompanied by a picture of either a black or a white patient. Physicians indicated whether they would offer genetic screening, and if yes, what tests they would offer and what factors influenced their decisions. Results: The majority (69.2%) of physicians reported that they would not offer genetic screening. Respondents who reviewed the vignette accompanied by a picture of the black patient were more likely to offer screening (35% vs. 26%, p = 0.0034) and rated race as more important to their decision to offer testing than those who viewed the picture of the white patient (76% vs. 49%, p < 0.0001). Conclusions: Our findings suggest that patient race is important to physicians when making decisions about preconception genetic testing and that decision making is influenced by patients' physical characteristics. The reticence of physicians in this sample to offer preconception screening is an important finding for public health and clinical practice. Copyright (C) 2009 S. Karger AG, Basel C1 [Bonham, V. L.; Knerr, S.; McBride, C. M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Feero, W. G.; Jenkins, J. F.] NHGRI, Genom Healthcare Branch, NIH, Bethesda, MD 20892 USA. [Stevens, N.] Univ Washington, Sch Med, Seattle, WA USA. RP Bonham, VL (reprint author), NHGRI, Social & Behav Res Branch, NIH, 31 Ctr Dr,Bldg 31,Room B1B55, Bethesda, MD 20892 USA. EM bonhamv@mail.nih.gov FU National Human Genome Research Institute, National Institutes of Health FX This research was supported (in part) by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. The content is solely the responsibility of the authors and does not represent the official position of the National Human Genome Research Institute, National Institutes of Health, or the Department of Health and Human Services. We thank Amanda Parsad and Julie Williams for their statistical expertise and Adebola O. Odunlami for her involvement in the study development. We thank the reviewers for their thoughtful comments which improved this article. NR 34 TC 2 Z9 2 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2010 VL 13 IS 6 BP 336 EP 344 DI 10.1159/000262328 PG 9 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 646ED UT WOS:000281518700002 PM 19940457 ER PT J AU Khoury, MJ Reyes, M Gwinn, M Feero, WG AF Khoury, M. J. Reyes, M. Gwinn, M. Feero, W. G. TI A Genetic Test Registry: Bringing Credible and Actionable Data Together SO PUBLIC HEALTH GENOMICS LA English DT Article ID EGAPP WORKING GROUP; GENOMIC APPLICATIONS C1 [Khoury, M. J.; Reyes, M.; Gwinn, M.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA. [Feero, W. G.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Khoury, MJ (reprint author), Ctr Dis Control & Prevent, Off Publ Hlth Genom, 1600 Clifton Rd, Atlanta, GA 30333 USA. EM muk1@cdc.gov NR 6 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2010 VL 13 IS 6 BP 360 EP 361 DI 10.1159/000262327 PG 2 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 646ED UT WOS:000281518700005 PM 19940456 ER PT J AU Wonkam, A Muna, W Ramesar, R Rotimi, CN Newport, MJ AF Wonkam, A. Muna, W. Ramesar, R. Rotimi, C. N. Newport, M. J. TI Capacity-Building in Human Genetics for Developing Countries: Initiatives and Perspectives in Sub-Saharan Africa SO PUBLIC HEALTH GENOMICS LA English DT Article DE Capacity-building; Human genetics; Sub-Saharan Africa ID MEDICAL-STUDENTS; GENOME-PROJECT; CAMEROON; SOCIETY AB Background: Stakeholders who are committed to bridge the gap in genetics services need to be aware of current initiatives in sub-Saharan Africa. Methods: We reviewed selected experiences from African geneticists that led to specific recommendations. Results: The initiation of prenatal diagnosis of sickle cell anaemia founded the first medical genetic service in Cameroon. There remains a need for international collaborative effort to overcome the lack of human, technical and financial resources around the practice of medical genetics in Africa. The African Society of Human Genetics, Wellcome Trust and NIH have recently proposed a model on how to fully engage Africa in genomics. It includes a 'Health and disease' phase I: use of the case-control design to study genetic and epidemiological determinants of 7 important diseases in Africa, and a 'Genetic variation' phase II: comprehensive documentation of genetic variations in 100 carefully selected ethnic groups across Africa. The strategy would require the development of: (1) clinical phenotyping centres, (2) molecular phenotyping centres, (3) genotyping and sequencing capability, (4) data centres, and (5) a bio-repository in Africa. Conclusions: Governments and international health agencies need to recognise that genetics is important to the global medical community. The initiatives of African geneticists need advocacy and encouragement from the international community. Copyright (C) 2010 S. Karger AG, Basel C1 [Wonkam, A.; Ramesar, R.] Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, MRC UCT Human Genet Res Unit,Div Human Genet, ZA-7925 Cape Town, South Africa. [Wonkam, A.; Muna, W.] Univ Yaounde 1, Fac Med & Biomed Sci, Yaounde, Cameroon. [Rotimi, C. N.] NIH, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. [Newport, M. J.] Brighton & Sussex Med Sch, Falmer, England. RP Wonkam, A (reprint author), Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, MRC UCT Human Genet Res Unit,Div Human Genet, Anzio Rd 7925, ZA-7925 Cape Town, South Africa. EM ambroise.wonkam@uct.ac.za RI Ramesar, Raj/I-6941-2015 OI Ramesar, Raj/0000-0001-5688-1634 NR 12 TC 12 Z9 12 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2010 VL 13 IS 7-8 BP 492 EP 494 DI 10.1159/000294171 PG 3 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 690NQ UT WOS:000285011900012 PM 21135570 ER PT J AU Mai, PL Wideroff, L Greene, MH Graubard, BI AF Mai, P. L. Wideroff, L. Greene, M. H. Graubard, B. I. TI Prevalence of Family History of Breast, Colorectal, Prostate, and Lung Cancer in a Population-Based Study SO PUBLIC HEALTH GENOMICS LA English DT Article DE Breast cancer; Colorectal cancer; Family history; Lung cancer; Prevalence; Prostate cancer; Telephone survey ID SOCIOECONOMIC-STATUS; COLON-CANCER; RISK; DISPARITIES; PREVENTION; DATABASE; COHORT; COMMON AB Background: A positive family history is a known risk factor for several cancers; thus, obtaining a thorough family cancer history is essential in cancer risk evaluation and prevention management. Methods: The Family Health Study, a telephone survey in Connecticut, was conducted in 2001. A total of 1,019 participants with demographic information and family cancer history were included in this study. Prevalence of a positive family history of breast, colorectal, prostate, and lung cancer for first-and second-degree relatives was estimated. Logistic regression was used to compare prevalence by demographic factors. Results: A positive family history among first-degree relatives was reported by 10.9% (95% Confidence Interval, CI = 8.8-13.3) of respondents for breast cancer, 5.1% (95% CI = 3.9-6.7) for colorectal cancer, 7.0% (95% CI = 5.2-9.4) for prostate cancer, and 6.4% (95% CI = 4.9-8.3) for lung cancer. The reported prevalence of family history of specific cancers varied by sex, age and race/ethnicity of the respondents. Conclusion: Family history prevalence for 4 of the most common adult solid tumors is substantial and the reported prevalence varied by respondent characteristics. Additional studies are needed to evaluate tools to promote accurate reporting of family history of cancer. Copyright (C) 2010 S. Karger AG, Basel C1 [Mai, P. L.; Greene, M. H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Graubard, B. I.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Wideroff, L.] NIDA, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Mai, PL (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7022, Rockville, MD 20852 USA. EM maip@mail.nih.gov RI Hernandez, Jessica/G-6527-2011 FU National Cancer Institute, National Institutes of Health; Westat, Inc.; [N01-PC-95039] FX This research was funded in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, and supported by contract # N01-PC-95039 with Westat, Inc. The authors have no conflict of interest or financial disclosures to report. NR 35 TC 13 Z9 13 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-4246 J9 PUBLIC HEALTH GENOM JI Pub. Health Genomics PY 2010 VL 13 IS 7-8 BP 495 EP 503 DI 10.1159/000294469 PG 9 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 690NQ UT WOS:000285011900013 PM 20389042 ER PT J AU Nansel, TR Huang, TTK Rovner, AJ Sanders-Butler, Y AF Nansel, Tonja R. Huang, Terry T. K. Rovner, Alisha J. Sanders-Butler, Yvonne TI Association of school performance indicators with implementation of the Healthy Kids, Smart Kids programme: case study SO PUBLIC HEALTH NUTRITION LA English DT Article DE School; Nutrition; Physical activity; Environment ID FOOD-SERVICE INTERVENTION; NUTRIENT CONTENT; US CHILDREN; CHILDHOOD; FRUIT; VEGETABLES; OVERWEIGHT; OBESITY; POLICY; CONSUMPTION AB Objective: The purpose of the present analysis was to examine secular trends in school performance indicators in relationship to the implementation of a programme targeting the school food and physical activity environment. Design: Data on available school performance indicators were obtained; retrospective analyses were conducted to assess trends in indicators in association with programme implementation; each outcome was regressed v. year, beginning with the year prior to programme implementation. Setting: The Healthy Kids, Smart Kids programme, a grass-roots effort to enhance the school food and physical activity environment in the Browns Mill Elementary School in Georgia. Subjects: Data included publicly available school records from the years 1995 to 2006. Results: The number of nurse, counselling and disciplinary referrals per 100 students demonstrated a downward trend, while standardized test scores demonstrated an upward trend beginning in the year of programme implementation. School year was a significant predictor of all indicators. Conclusions: Promoting nutrition and physical activity within the school environment may be a promising approach for enhancing both student health and educational outcomes. C1 [Sanders-Butler, Yvonne] Browns Mill Elementary Sch, Lithonia, GA USA. [Nansel, Tonja R.; Huang, Terry T. K.; Rovner, Alisha J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Sanders-Butler, Y (reprint author), Browns Mill Elementary Sch, Lithonia, GA USA. EM yvonnebnym@aol.com OI Nansel, Tonja/0000-0002-8298-7595 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This project received no external funding. Data analysis and manuscript preparation were supported by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. The contents of this publication do not necessarily represent the views or policies of the National Institutes of Health. None of the authors possesses any conflicts of interest. Y.S.-B. led the development and implementation of the Health Kids, Smart Kids programme and obtained the school data reported. T.R.N., AJ.R. and T.T.K.H. conceptualized the retrospective data analysis. T.R.N. conducted analyses and drafted the manuscript; all author contributed to critical revisions. Y.S.-B. wishes to acknowledge the contribution of the following individuals to the Success of the Healthy Kids, Smart Kids programme. Marilyn Hughes, PhD, RD, LD (nutrition research scientist) assisted with the development of the Healthy Kids, Smart Kids Programme. Lorine Phillips Bizzell (public health nutritionist) analysed recipes and provided technical assistance and resources for the Healthy Kids, Smart Kids Programme. James L. Lawrence (fitness specialist) supported the physical activity format that promoted health and exercise throughout the school clay, NR 32 TC 9 Z9 9 U1 2 U2 5 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 1368-9800 J9 PUBLIC HEALTH NUTR JI Public Health Nutr. PD JAN PY 2010 VL 13 IS 1 BP 116 EP 122 DI 10.1017/S1368980009005898 PG 7 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA 559LZ UT WOS:000274827800014 PM 19454125 ER PT B AU Alexander, MJ McMahon, C AF Alexander, Mary Jane McMahon, Caitlin BE Levin, BL Becker, MA TI Mental Conditions in Adult Women: Epidemiology and Impact SO PUBLIC HEALTH PERSPECTIVE OF WOMEN'S MENTAL HEALTH LA English DT Article; Book Chapter ID NATIONAL-COMORBIDITY-SURVEY; POSTTRAUMATIC-STRESS-DISORDER; SUBSTANCE USE DISORDERS; CHILDHOOD SEXUAL-ABUSE; DSM-IV DISORDERS; QUALITY-OF-LIFE; SURVEY REPLICATION; PSYCHIATRIC-DISORDERS; HOMELESS WOMEN; SOCIAL-CONSEQUENCES C1 [Alexander, Mary Jane] Nathan S Kline Inst Psychiat Res, Ctr Study Recovery Social Contexts Stat, Stat & Hlth Serv Div, Orangeburg, NY 10962 USA. [Alexander, Mary Jane] Nathan S Kline Inst Psychiat Res, Div Res Serv, Orangeburg, NY 10962 USA. [Alexander, Mary Jane] NIMH, Ctr Study Recovery Social Contexts, Bethesda, MD USA. [McMahon, Caitlin] NYU, Sch Med, Dept Psychiat, Div Alcoholism & Drug Abuse, New York, NY 10003 USA. RP Alexander, MJ (reprint author), Nathan S Kline Inst Psychiat Res, Ctr Study Recovery Social Contexts Stat, Stat & Hlth Serv Div, 140 Old Orangeburg Rd, Orangeburg, NY 10962 USA. NR 130 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1525-2 PY 2010 BP 37 EP 63 DI 10.1007/978-1-4419-1526-9_3 D2 10.1007/978-1-4419-1526-9 PG 27 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA BOA83 UT WOS:000276045200003 ER PT B AU DeBate, R Blunt, H Becker, MA AF DeBate, Rita Blunt, Heather Becker, Marion Ann BE Levin, BL Becker, MA TI Eating Disorders SO PUBLIC HEALTH PERSPECTIVE OF WOMEN'S MENTAL HEALTH LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIALS; CANADIAN COMMUNITY SAMPLE; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; ANXIETY DISORDERS; PREVALENCE; COMORBIDITY; POPULATION; EPIDEMIOLOGY; TOPIRAMATE C1 [DeBate, Rita] Univ S Florida, Coll Publ Hlth, Dept Community & Family Hlth, Tampa, FL 33612 USA. [DeBate, Rita] NIH, Bethesda, MD USA. [Becker, Marion Ann] Univ S Florida, Dept Aging & Mental Hlth Dispar, Louis Parte Florida Mental Hlth Inst, Tampa, FL 33612 USA. [Becker, Marion Ann] USF Sch Social Work, Tampa, FL USA. [Becker, Marion Ann] USF Coll Publ Hlth, Tampa, FL USA. [Becker, Marion Ann] USF Coll Nursing, Tampa, FL USA. RP DeBate, R (reprint author), Univ S Florida, Coll Publ Hlth, Dept Community & Family Hlth, 13201 Bruce B Downs Blvd MDC 56, Tampa, FL 33612 USA. NR 58 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1525-2 PY 2010 BP 121 EP 141 DI 10.1007/978-1-4419-1526-9_7 D2 10.1007/978-1-4419-1526-9 PG 21 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA BOA83 UT WOS:000276045200007 ER PT B AU Barry, KL Blow, FC AF Barry, Kristen L. Blow, Frederic C. BE Levin, BL Becker, MA TI Substance Abuse SO PUBLIC HEALTH PERSPECTIVE OF WOMEN'S MENTAL HEALTH LA English DT Article; Book Chapter ID INTIMATE PARTNER VIOLENCE; BRIEF PHYSICIAN ADVICE; POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED TRIAL; GENDER-DIFFERENCES; BRIEF INTERVENTION; DRUG-TREATMENT; PRIMARY-CARE; ALCOHOL-USE; PREGNANT-WOMEN C1 [Barry, Kristen L.; Blow, Frederic C.] Univ Michigan, Dept Psychiat, Sch Med, Mental Hlth Serv Outcomes & Translat Sect, Ann Arbor, MI 48109 USA. [Barry, Kristen L.; Blow, Frederic C.] Natl Serious Mental Illness Treatment Res & Evalu, Dept Vet Affairs, Ann Arbor, MI USA. [Barry, Kristen L.] NIAAA, Bethesda, MD USA. RP Barry, KL (reprint author), Univ Michigan, Dept Psychiat, Sch Med, Mental Hlth Serv Outcomes & Translat Sect, Ann Arbor, MI 48109 USA. NR 113 TC 0 Z9 0 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1525-2 PY 2010 BP 165 EP 184 DI 10.1007/978-1-4419-1526-9_9 D2 10.1007/978-1-4419-1526-9 PG 20 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA BOA83 UT WOS:000276045200009 ER PT B AU Perez, G Dixon, L Kelly, DL AF Perez, Gina Dixon, Lisa Kelly, Deanna L. BE Levin, BL Becker, MA TI Evidence-Based Medicine SO PUBLIC HEALTH PERSPECTIVE OF WOMEN'S MENTAL HEALTH LA English DT Article; Book Chapter ID SEROTONIN REUPTAKE INHIBITORS; PREMENSTRUAL DYSPHORIC DISORDER; NATIONAL-INSTITUTE; MAJOR DEPRESSION; PREGNANCY; THERAPY; POSTPARTUM; SERTRALINE; TRIAL; CARE C1 [Perez, Gina; Dixon, Lisa] Univ Maryland, Sch Med, Div Mental Hlth Serv Res, Baltimore, MD 21201 USA. [Dixon, Lisa] NIMH, Bethesda, MD USA. [Dixon, Lisa] NIDA, Bethesda, MD USA. [Dixon, Lisa] Univ Maryland, Dept Psychiat, Baltimore, MD 21201 USA. [Kelly, Deanna L.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Treatment Res Program, Baltimore, MD 21201 USA. RP Perez, G (reprint author), Univ Maryland, Sch Med, Div Mental Hlth Serv Res, 655 W Baltimore St, Baltimore, MD 21201 USA. NR 33 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1525-2 PY 2010 BP 229 EP 243 DI 10.1007/978-1-4419-1526-9_12 D2 10.1007/978-1-4419-1526-9 PG 15 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA BOA83 UT WOS:000276045200012 ER PT B AU Hogarth, S Barton, D Melzer, D AF Hogarth, Stuart Barton, David Melzer, David BE Kristoffersson, U Schmidtke, J Cassiman, JJ TI The European IVD Directive and Genetic Testing SO QUALITY ISSUES IN CLINICAL GENETIC SERVICES SE Advances in Marine Genomics LA English DT Article; Book Chapter DE Regulation; IVD directive; Clinical validity; Reference materials C1 [Hogarth, Stuart] Kings Coll London, Ctr Biomed & Soc, London WC2R 2LS, England. [Melzer, David] Peninsula Med Sch, Exeter, Devon, England. [Melzer, David] US Natl Inst Aging, Epidemiol Lab, Bethesda, MD USA. [Barton, David] Univ Coll Dublin, Natl Ctr Med Genet, Dublin 2, Ireland. RP Hogarth, S (reprint author), Kings Coll London, Ctr Biomed & Soc, London WC2R 2LS, England. EM stuart.hogarth@kcl.ac.uk; David.Barton@olchc.ie; david.melzer@pms.ac.uk OI Melzer, David/0000-0002-0170-3838 NR 14 TC 2 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-90-481-3918-7 J9 ADV MAR GENOMICS PY 2010 VL 1 BP 49 EP 62 DI 10.1007/978-90-481-3919-4_6 D2 10.1007/978-90-481-3919-4 PG 14 WC Genetics & Heredity; Marine & Freshwater Biology SC Genetics & Heredity; Marine & Freshwater Biology GA BOY76 UT WOS:000278071600006 ER PT J AU Dwyer, DM Dunn, MJ Rhodes, SEV Killcross, AS AF Dwyer, Dominic M. Dunn, Michael J. Rhodes, Sarah E. V. Killcross, A. Simon TI Lesions of the prelimbic prefrontal cortex prevent response conflict produced by action-outcome associations SO QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY LA English DT Article DE Instrumental conditioning; Prelimbic cortex; Biconditional discrimination; Response conflict; Working memory ID CONTEXTUAL CONTROL; RATS; DISRUPT AB Rats with prelimbic (PL) cortex lesions were tested on a discrete-trial discrimination where food rewards were used as both discriminative cues and reinforcing outcomes. On incongruent trials, the discriminative cue food differed from the outcome food; on congruent trials they were the same. When cue and outcome foods differ, a conflict is created between the response directly promoted by the food as a cue (mediated by stimulus-response, S-R, associations) and the response indirectly promoted by the food as an outcome (mediated via action-outcome associations). No conflict is produced when cue and outcome foods are the same. Sham-lesioned rats acquired the discrimination more slowly for incongruent trials than for congruent trials, and incongruent trials were more susceptible to disruption by delay. In contrast there was no difference between congruent and incongruent trial types in PL-lesioned animals during acquisition or delay testing. Delays between cue and response had greater overall effects on lesioned than on sham-lesioned animals. These results are consistent with the behaviour of PL-lesioned animals being controlled by S-R associations with no response conflict due to interference from action-outcome associations. C1 [Dwyer, Dominic M.] Cardiff Univ, Sch Psychol, Cardiff CF10 3YG, S Glam, Wales. [Dunn, Michael J.] Univ Wales Inst, Cardiff Sch Hlth Sci, Ctr Psychol, Cardiff, S Glam, Wales. [Rhodes, Sarah E. V.] NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Killcross, A. Simon] Univ New S Wales, Sydney, NSW, Australia. RP Dwyer, DM (reprint author), Cardiff Univ, Sch Psychol, Cardiff CF10 3YG, S Glam, Wales. EM DwyerDM@cardiff.ac.uk RI Dwyer, Dominic/D-1498-2009; Killcross, Simon/A-4113-2009 FU Medical Research Council [69805345] FX This work was supported by an Medical Research Council Career Establishment Grant ( 69805345) to A. S. K. The authors wish to thank Jo Haddon for her comments on this paper. NR 16 TC 8 Z9 8 U1 0 U2 1 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1747-0218 J9 Q J EXP PSYCHOL JI Q. J. Exp. Psychol. PY 2010 VL 63 IS 3 BP 417 EP 424 AR PII 919582062 DI 10.1080/17470210903411049 PG 8 WC Psychology, Biological; Physiology; Psychology; Psychology, Experimental SC Psychology; Physiology GA 572PL UT WOS:000275845100001 PM 19937507 ER PT J AU Ndlebe, T Panyutin, I Neumann, R AF Ndlebe, Thabisile Panyutin, Igor Neumann, Ronald TI Analysis of the Contribution of Charge Transport in Iodine-125-Induced DNA Damage SO RADIATION RESEARCH LA English DT Article ID TRIPLEX-FORMING OLIGONUCLEOTIDE; MOLECULAR DYNAMIC SIMULATIONS; EXCESS ELECTRON-TRANSFER; STRAND BREAKS; SYNTHETIC OLIGODEOXYNUCLEOTIDE; HOLE TRANSFER; PLASMID DNA; I-125 DECAY; SPIN-RESONANCE; DUPLEX DNA AB Auger electron emitters like (125)I are the radionuclides of choice for gene-targeted radiotherapy. The highly localized damage they induce in DNA is produced by three mechanisms: direct damage by the emitted Auger electrons, indirect damage by diffusible free radicals produced by Auger electrons traveling in water, and charge neutralization of the residual, highly positively charged tellurium daughter atom by stripping electrons from covalent bonds of neighboring residues. The purpose of our work was to determine whether these mechanisms proceed through an intermediate energy transfer step along DNA. It was proposed that this intermediate step proceeds through the charge transport mechanism in DNA. Conventional charge transport has been described as either a hopping mechanism initiated by charge injection into DNA and propagated by charge migration along the DNA or a tunneling mechanism in which charge moves directly from a donor to an acceptor within DNA. Well-known barriers for the hopping mechanism were used to probe the role of charge transport in (125)I-induced DNA damage. We studied their effect. on the distribution of DNA breaks produced by the decay of (125)I in samples frozen at -80 degrees C. We found that these barriers had no measurable effect on the distribution of (125)I-induced breaks. (C) 2010 by Radiation Research Society C1 [Ndlebe, Thabisile; Panyutin, Igor; Neumann, Ronald] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Panyutin, I (reprint author), NIH, Ctr Clin, Bldg 10,Rm 4D45, Bethesda, MD 20892 USA. EM ipanyuting@mail.nih.gov FU NIH Clinical Center FX We thank Dr. Ludwig Feinendegen and Dr. Shubhadeep Purkayastha for their valuable insights on the manuscript. This work was supported by the Intramural Research Program of the NIH Clinical Center. NR 43 TC 2 Z9 2 U1 0 U2 2 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JAN PY 2010 VL 173 IS 1 BP 98 EP 109 DI 10.1667/RR1865.1 PG 12 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 541YA UT WOS:000273456200011 PM 20041764 ER PT J AU Gaedcke, J Grade, M Jung, K Schirmer, M Jo, P Obermeyer, C Wolff, HA Herrmann, MK Beissbarth, T Becker, H Ried, T Ghadimi, M AF Gaedcke, Jochen Grade, Marian Jung, Klaus Schirmer, Markus Jo, Peter Obermeyer, Christoph Wolff, Hendrik A. Herrmann, Markus K. Beissbarth, Tim Becker, Heinz Ried, Thomas Ghadimi, Michael TI KRAS and BRAF mutations in patients with rectal cancer treated with preoperative chemoradiotherapy SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Rectal cancer; Preoperative chemoradiotherapy; KRAS; BRAF; Response ID METASTATIC COLORECTAL-CANCER; K-RAS MUTATIONS; SIGNALING PATHWAY; TUMOR-REGRESSION; MISMATCH-REPAIR; GENE-MUTATIONS; CETUXIMAB; ADENOCARCINOMAS; ACTIVATION; CODON-12 AB Background and purpose: KRAS and BRAF are Mutated in 35% and 10% of colorectal cancers, respectively. However, data specifically for locally advanced rectal cancers are scarce, and the frequency of KRAS mutations in codons 61 and 146 remains to be established. Materials and methods: DNA was isolated from pre-therapeutic biopsies of 94 patients who were treated within two phase-III clinical trials receiving preoperative chemoradiotherapy. Mutation status of KRAS exons 1-3 and BRAF exon 15 was established using the ABI PRISM Big Dye Sequencing Kit and subsequently correlated with clinical parameters. Results: Overall, KRAS was Mutated in 45 patients (48%). Twenty-nine mutations (64%) were located in codon 12, 10 mutations (22%) in codon 13, and 3 mutations (7%) in codons 61 and 146. No V600E BRAF mutation was detected. The presence of KRAS mutations was Correlated neither with tumor response or lymph node Status after preoperative chemoradiotherapy nor with overall Survival or disease-free survival. When KRAS exon I mutations were separated based on the amino-acid exchange, we again failed to detect significant correlations (p = 0.052), However, G12V Mutations appeared to be associated with higher rates Of tumor regression than G13D mutations (p = 0.012). Conclusion: We are the first to report the mutation status of KRAS and BRAF in pre-therapeutic biopsies from locally advanced rectal cancers. The high number of KRAS mutations in codons 61 and 146 emphasizes the importance to expand current mutation analyses, whereas BRAF mutations are not relevant for rectal carcinogenesis. Although the KRAS Mutation Status Was not Correlated with response, the Subtle difference between G12V and G13D mutations warrants analysis of a larger patient population. (C) 2009 Elsevier Ireland Ltd. All rights reserved, Radiotherapy arid Oncology 94 (2010) 76-81 C1 [Ghadimi, Michael] Univ Gottingen, Univ Med Ctr, Dept Gen & Visceral Surg, D-37075 Gottingen, Germany. [Jung, Klaus; Beissbarth, Tim] Univ Med Ctr Gottingen, Dept Med Stat, Gottingen, Germany. [Schirmer, Markus] Univ Med Ctr Gottingen, Dept Pharmacol, Gottingen, Germany. [Wolff, Hendrik A.; Herrmann, Markus K.] Univ Med Ctr Gottingen, Dept Radiat Oncol, Gottingen, Germany. [Ried, Thomas] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ghadimi, M (reprint author), Univ Gottingen, Univ Med Ctr, Dept Gen & Visceral Surg, Robert Koch Str 40, D-37075 Gottingen, Germany. EM mghadim@gwdg.de RI Beissbarth, Tim/B-3129-2013 OI Beissbarth, Tim/0000-0001-6509-2143 FU Deutsche Forschungsgemeinschaft [KFO 179] FX This work was supported by the Deutsche Forschungsgemeinschaft (KFO 179). We are grateful to Dr. Hilka Rothe for histopathological work-Lip, and to Mr. Chan Rong Lai and Mrs. Monika Winkler for technical assistance. NR 36 TC 49 Z9 51 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD JAN PY 2010 VL 94 IS 1 BP 76 EP 81 DI 10.1016/j.radonc.2009.10.001 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 560GK UT WOS:000274889900012 PM 19913317 ER PT S AU Groft, SC de la Paz, MP AF Groft, Stephen C. Posada de la Paz, Manuel BE DelaPaz, MP Groft, SC TI Rare Diseases - Avoiding Misperceptions and Establishing Realities: The Need for Reliable Epidemiological Data SO RARE DISEASES EPIDEMIOLOGY SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Rare diseases; Clinical research networks; Epidemiology; Information systems; Training; Patient organizations AB The rare disease community suffers from the absence of reliable epidemiological data on the prevalence and incidence of rare diseases in the national and global populations. The rare diseases community includes all of the stakeholders involved in the research and development and dissemination of products and information for the diagnosis, prevention or treatment of rare diseases or conditions. To replace many of the perceived myths with realities, several global efforts are required if we are going to sustain and increase the reported progress with the thousands of rare diseases. One is the identification and expansion of worldwide partnerships and collaborations of Patient Advocacy Groups for individual rare diseases. Another requirement is to develop a global research infrastructure of qualified investigators to stimulate and coordinate research efforts by seeking ways to provide access to clinical trials at multi-national research sites with common protocols and multi-disciplinary research teams. Providing ready access to the information about rare diseases, patient advocacy groups, research studies and products in research protocols will continue to improve the lives of patients and their families. Many scientists, public and private sector organizations, patient advocacy groups, foundations, and the pharmaceutical, biotechnology, and medical devices industries are committed to translating research discoveries that will be useful in the care of patients with rare diseases over their lifespan. Evidence from well constructed epidemiological studies will provide the evidence that point to the value of additional clinical studies to increase the understanding of rare diseases. C1 [Groft, Stephen C.] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA. [Posada de la Paz, Manuel] Inst Salud Carlos III, IIER, Madrid, Spain. [Posada de la Paz, Manuel] Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain. RP Groft, SC (reprint author), NIH, Off Rare Dis Res, Bldg 10, Bethesda, MD 20892 USA. EM sg18b@nih.gov; mposada@isciii.es; sg18b@nih.gov NR 6 TC 10 Z9 10 U1 0 U2 7 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-90-481-9484-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2010 VL 686 BP 3 EP 14 DI 10.1007/978-90-481-9485-8_1 PG 12 WC Public, Environmental & Occupational Health; Medicine, Research & Experimental SC Public, Environmental & Occupational Health; Research & Experimental Medicine GA BRC95 UT WOS:000282382800001 PM 20824436 ER PT S AU Cookson, MR AF Cookson, Mark R. BE Bjorklund, A Cenci, MA TI Unravelling the role of defective genes SO RECENT ADVANCES IN PARKINSONS DISEASE: BASIC RESEARCH SE Progress in Brain Research LA English DT Review; Book Chapter DE Genetics; LRRK2; Synuclein; Parkin; PINK1; DJ-1 ID FAMILIAL PARKINSONS-DISEASE; AUTOSOMAL-DOMINANT PARKINSONISM; ALPHA-SYNUCLEIN OLIGOMERS; CYSTEINE-SULFINIC ACID; COMMON LRRK2 MUTATION; MITOCHONDRIAL LOCALIZATION; OXIDATIVE STRESS; KINASE-ACTIVITY; PROTEIN DJ-1; ROC DOMAIN AB Several genes that cause familial forms of Parkinson's disease (PD) or similar disorders have been found in recent years. The aim of this review is to cover two broad aspects of the logic of genetics. The first aspect is the recognition that PD can have a genetic basis, either for Mendelian families where genes can be identified because mutations segregate with disease or in populations where more common variants are associated with disease. There are several causal genes for both dominant and recessive forms of parkinsonism, some of which overlap with sporadic PD and some of which have more complex phenotypes. Several of the dominant loci have also been reliably identified as risk factors for sporadic PD. The second topic is how the study of multiple mutations in any given gene can help understand the role that the protein under investigation plays in PD. Examples will be given of both recessive and dominant genes for parkinsonism, showing how the analysis of multiple gene mutations can be a powerful approach for dissecting out which function(s) are important for the disease process. C1 NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, Bethesda, MD 20892 USA. EM cookson@mail.nih.gov FU Intramural NIH HHS [ZIA AG000939-02] NR 95 TC 4 Z9 4 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53614-3 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2010 VL 183 BP 43 EP 57 DI 10.1016/S0079-6123(10)83003-1 PG 15 WC Medicine, Research & Experimental; Clinical Neurology; Neurosciences SC Research & Experimental Medicine; Neurosciences & Neurology GA BTR42 UT WOS:000287859500003 PM 20696314 ER PT S AU Gladyshev, VN Hatfield, DL AF Gladyshev, Vadim N. Hatfield, Dolph L. BE Atkins, JF Gesteland, RF TI Selenocysteine Biosynthesis, Selenoproteins, and Selenoproteomes SO RECODING: EXPANSION OF DECODING RULES ENRICHES GENE EXPRESSION SE Nucleic Acids and Molecular Biology LA English DT Article; Book Chapter ID TRANSFER-RNA GENE; TARGETING THIOREDOXIN REDUCTASE; PHOSPHOSERINE TRANSFER-RNA; SYNTHETASE 2 SPS2; SELENOPHOSPHATE SYNTHETASE; CANCER-THERAPY; GLUTATHIONE-PEROXIDASE; SELENIUM METABOLISM; ESCHERICHIA-COLI; IN-VIVO AB Selenocysteine (Sec), the 2 1st amino acid in the genetic code, is encoded by UGA. The pathway of Sec biosynthesis in eukaryotes has only recently been discovered. Sec is constructed on its tRNA that is initially aminoacylated with serine and modified to a phosphoseryl-tRNA intermediate with the help of several dedicated enzymes. More than 50 selenoprotein families are now known with most selenoproteins being oxidoreductases. Development of bioinformatics tools led to the identification of entire sets of selenoproteins in organisms, selenoproteomes, which in turn helped explain biological and biomedical effects of dietary selenium and identify new functions of selenium in biology. Roles of selenium and selenoproteins in health have also been addressed through sophisticated transgenic/knockout models that targeted removal or modulation of Sec tRNA expression. C1 [Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. [Gladyshev, Vadim N.] Univ Nebraska, Redox Biol Ctr, Lincoln, NE 68588 USA. [Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM vgladyshev@rics.bwh.harvard.edu NR 110 TC 6 Z9 7 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0933-1891 BN 978-0-387-89381-5 J9 NUCLEIC ACIDS MOL BI JI Nucleic Acids Molec. Biol. PY 2010 VL 24 BP 3 EP 27 DI 10.1007/978-0-387-89382-2_1 D2 10.1007/978-0-387-89382-2 PG 25 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BNC17 UT WOS:000274144100001 ER PT B AU Herold, KE Rasooly, A AF Herold, Keith E. Rasooly, A. BE Zourob, M TI Oligonucleotides as Recognition and Catalytic Elements SO RECOGNITION RECEPTORS IN BIOSENSORS LA English DT Article; Book Chapter DE Oligonucleotides; Recognition; Catalytic; RNA; DNA; Aptamers ID NEAREST-NEIGHBOR THERMODYNAMICS; PEPTIDE NUCLEIC-ACIDS; SMALL INTERFERING RNA; WHOLE-GENOME AMPLIFICATION; SURFACE-PLASMON RESONANCE; DOUBLE-STRANDED-RNA; DOT-T MISMATCHES; POLYMERASE CHAIN-REACTION; RATIONAL SIRNA DESIGN; SHORT HAIRPIN RNAS AB Oligonucleotides function as recognition elements for both nucleic acids and proteins in many ways. starting front their basic function as genetic material recognizing the complementary sequences of RNA or DNA, through their role as genetic regulatory elements in the form of antisense DNA/RNA, interfering RNA (RNAi) as well as enzymatic activities such as trails-cleaving ribozymes. Oligonucleotides call also serve as recognition elements for proteins ill the form of aptamers. All of these functions are derived from the basic primary, secondary, and tertiary structures along with their combinatorial nature, which allows vast variability within even short sequences. For biotechnology, the utility of oligonucleotides goes far beyond their basic function as a carrier of genetic information. Oligonucleotides are widely used as recognition elements for a large number of DNA and protein manipulation technologies. Including numerous Methods for DNA amplification. manipulation (e.g., mutation insertion or repair), and DNA Sequence recognition and analysis They are used for manipulation of gene expression including the use of ribozymes to catalyze RNA digestion, and siRNA and anti-sense RNA/DNA used for gene silencing ill both ill vitro and in vivo lit addition, they serve as ail alternative to antibodies as ligands for protein detection. The term oligonucleotide (or oligo) refers to a short segment of DNA or RNA commonly synthesized today by polymerizing nucleotide precursors using automated synthesizers Although most oligos used in molecular biology arc short ill the range of 20-30 bases (or mer), the term Is used here also to refer to longer sequences (e.g., similar to 200 bases) and to ribozymes, which arc traditionally clot viewed as oligos. In this manuscript. we describe the basic Structure of oligonucleotides relevant to general utility tit molecular biology and biotechnology This utility Includes function as recognition elements, basic utility for DNA amplification, recognition and manipulation, application for the regulation of gene expression and function and utility as protein recognition elements. C1 [Herold, Keith E.] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Rasooly, A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20903 USA. [Rasooly, A.] NCI, NIH, Rockville, MD 20852 USA. RP Herold, KE (reprint author), Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. EM herold@umd.edu; rasoolya@mail.nih.gov NR 205 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0918-3 PY 2010 BP 631 EP 674 DI 10.1007/978-1-4419-0919-0_16 D2 10.1007/978-1-4419-0919-0 PG 44 WC Engineering, Biomedical SC Engineering GA BNU87 UT WOS:000275618200016 ER PT S AU Collins, JR Topol, IA Savitsky, AP Nemukhin, AV AF Collins, Jack R. Topol, Igor A. Savitsky, Alexander P. Nemukhin, Alexander V. BE Achilefu, S Raghavachari, R TI Modeling structure and spectra of red fluorescent proteins SO REPORTERS, MARKERS, DYES, NANOPARTICLES, AND MOLECULAR PROBES FOR BIOMEDICAL APPLICATIONS II SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II CY JAN 25-27, 2010 CL San Francisco, CA SP SPIE DE fluorescent proteins; quantum modeling; DsRed; mFruits ID CHROMOPHORE; GREEN; MFRUITS AB Modern molecular modeling tools are intensively used to gain knowledge of events occurring upon photoexcitation of organic chromophores in the gas-phase, in solution and in protein matrices. We applied quantum mechanical approach to estimate equilibrium geometry configurations as well as positions and intensities of spectral bands for a number of red fluorescent proteins, including the DsRed from Discosoma coral, and its mutants of the so-called mFruits series. As demonstrated in our previous simulations for GFP and blue fluorescent proteins, this strategy was proven to be productive for modeling. The model system is designed as a molecular cluster constructed on the basis of available crystal structures of the related protein. The equilibrium geometry of the cluster is optimized using density functional theory approximations. The vertical excitation energies corresponding to the S(0)-S(1) transitions are computed by using the semiempirical ZINDO technique. Mechanisms of photoexcitation, identification of the functional states of the chromophores, elucidation the role of point mutations in the photoreceptor proteins are considered on the basis of simulations. C1 [Collins, Jack R.; Topol, Igor A.] SAIC Frederick Inc, Adv Biomed Comp Ctr, Informat Syst Program, NCI Frederick, Frederick, MD 21702 USA. RP Collins, JR (reprint author), SAIC Frederick Inc, Adv Biomed Comp Ctr, Informat Syst Program, NCI Frederick, Frederick, MD 21702 USA. EM anemukhin@yahoo.com RI Savitsky, Alexander/O-9799-2015; Nemukhin, Alexander/P-9662-2015 NR 13 TC 0 Z9 0 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7972-3 J9 P SOC PHOTO-OPT INS PY 2010 VL 7576 AR 75760H DI 10.1117/12.840347 PG 5 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Optics SC Engineering; Science & Technology - Other Topics; Optics GA BSS16 UT WOS:000285580600013 ER PT S AU Kosaka, N Ogawa, M Paik, DS Paik, CH Choyke, PL Kobayashi, H AF Kosaka, Nobuyuki Ogawa, Mikako Paik, David S. Paik, Chang H. Choyke, Peter L. Kobayashi, Hisataka BE Achilefu, S Raghavachari, R TI Microdistribution of Fluorescently-labeled Monoclonal Antibody in a Peritoneal Dissemination model of Ovarian Cancer SO REPORTERS, MARKERS, DYES, NANOPARTICLES, AND MOLECULAR PROBES FOR BIOMEDICAL APPLICATIONS II SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II CY JAN 25-27, 2010 CL San Francisco, CA SP SPIE DE peritoneal dissemination; microdistribution; monoclonal antibody; ovarian cancer; fluorescence imaging; semiquantitative analysis ID BINDING-SITE BARRIER; SOLID TUMORS; RADIOIMMUNOTHERAPY; PENETRATION; RESISTANCE; DELIVERY; LYMPHOMA; THERAPY AB The microdistribution of therapeutic monoclonal antibodies within a tumor is important for determining clinical response. Nonuniform microdistribution predicts therapy failure. Herein, we developed a semiquantitative method for measuring microdistribution of an antibody within a tumor using in situ fluorescence microscopy and sought to modulate the microdistribution by altering the route and timing of antibody dosing. The microdistribution of a fluorescently-labeled antibody, trastuzumab (50-mu g and 150-mu g intraperitoneal injection (i.p.), and 100-mu g intravenous injection (i.v.)) was evaluated in a peritoneal dissemination mouse model of ovarian cancer. In addition, we evaluated the microdistribution of concurrently-injected (30-mu g i.p. and 100-mu g i.v.) or serial (two doses of 30-mu g i.p.) trastuzumab using in situ multicolor fluorescence microscopy. After the administration of 50-mu g i.p. and 100-mu g i.v. trastuzumab fluorescence imaging showed no significant difference in the central to peripheral signal ratio (C/P ratio) and demonstrated a peripheral-dominant accumulation, whereas administration of 150-mu g i.p. trastuzumab showed relatively uniform, central dominant accumulation. With concurrent-i.p.-i.v. injections trastuzumab showed slightly higher C/P ratio than concurrently-injected i.p. trastuzumab. Moreover, in the serial injection study, the second injection of trastuzumab distributed more centrally than the first injection, while no difference was observed in the control group. Our results suggest that injection routes do not affect the microdistribution pattern of antibody in small peritoneal disseminations. However, increasing the dose results in a more uniform antibody distribution within peritoneal nodules. Furthermore, the serial i.p. injection of antibody can modify the microdistribution within tumor nodules. This work has implications for the optimal delivery of antibody based cancer therapies. C1 [Kosaka, Nobuyuki; Ogawa, Mikako; Paik, David S.; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kosaka, N (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 15 TC 1 Z9 1 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7972-3 J9 P SOC PHOTO-OPT INS PY 2010 VL 7576 AR 757604 DI 10.1117/12.842090 PG 9 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Optics SC Engineering; Science & Technology - Other Topics; Optics GA BSS16 UT WOS:000285580600003 ER PT S AU Ferrell, RJ Sowers, M AF Ferrell, Rebecca J. Sowers, MaryFran BE Weinstein, M OConnor, K TI Longitudinal, epidemiologic studies of female reproductive aging SO REPRODUCTIVE AGING SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Workshop on Reproductive Aging CY JUN 05-06, 2009 CL Georgetown Univ, Washington, DC HO Georgetown Univ DE ovarian aging; hypothalamic-pituitary axis; menstrual cycle; epidemiologic ID FOLLICLE-STIMULATING-HORMONE; HUMAN MENSTRUAL-CYCLE; EARLY MENOPAUSAL TRANSITION; BONE-MINERAL DENSITY; PROSPECTIVE-STUDY AGGREGATE; PROPOSED BLEEDING CRITERIA; MIDLIFE HEALTH PROJECT; WOMENS HEALTH; PERIMENOPAUSAL WOMEN; INDIVIDUAL CHANGES AB Human female reproductive aging consists of multiple processes and interacts with other physiological systems in unique ways. Here we discuss eight recent longitudinal, epidemiologic studies of female reproductive aging that include endocrine data to highlight their contributions to our understanding of these various aging processes and their interactions. Specifically, we review data on ovarian and nonovarian reproductive aging processes and reproductive staging. We consider these data in the context of longitudinal research design and research goals, identify limitations of the studies but also ways in which existing longitudinal data can further our understanding of aging processes, and make recommendations for future studies of female reproductive aging. C1 [Ferrell, Rebecca J.] NIA, Sci Review Branch, NIH, Bethesda, MD 20892 USA. RP Ferrell, RJ (reprint author), NIA, Sci Review Branch, NIH, 7201 Wisconsin Ave,Room 2C212, Bethesda, MD 20892 USA. EM rebecca.ferrell@nih.gov NR 74 TC 8 Z9 8 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-775-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1204 BP 188 EP 197 DI 10.1111/j.1749-6632.2010.05525.x PG 10 WC Multidisciplinary Sciences; Reproductive Biology SC Science & Technology - Other Topics; Reproductive Biology GA BTN08 UT WOS:000287380800021 PM 20738290 ER PT B AU Bondy, CA AF Bondy, Carolyn A. BE Carrell, DT Peterson, CM TI Turner Syndrome SO REPRODUCTIVE ENDOCRINOLOGY AND INFERTILITY: INTEGRATING MODERN CLINICAL AND LABORATORY PRACTICE LA English DT Article; Book Chapter DE X chromosome; Ovarian failure; Primary amenorrhea; Pubertal induction; Hormone replacement therapy; Osteoporosis ID SEX-CHROMOSOME ABNORMALITIES; PREMATURE OVARIAN FAILURE; HOMEOBOX-CONTAINING GENE; GROWTH-HORMONE THERAPY; FETAL HEART-RATE; PRENATAL-DIAGNOSIS; YOUNG-WOMEN; 45,X KARYOTYPE; SHORT STATURE; X-CHROMOSOME AB Turner syndrome (TS) or monosomy X, is the most common cause of hypergonadotropic hypogonadism in girls and young women. This chapter reviews the prevalence and different presentations of the syndrome and explains its chromosomal origins. The interpretation of chromosomal studies in diagnosis of and prognosis for TS, including prenatal testing, is reviewed. The most recent data on the TS phenotypic spectrum indicate similar to 95% have short stature and similar to 95% have primary ovarian failure, most presenting with primary amenorrhea but a significant number is present with 2 amenorrhea. Recent studies indicate that dysmorphic features are less common than previously described but complex cardiovascular defects and metabolic problems including osteoporosis, thyroid dysfunction, diabetes, and dyslipidemia are more common than previously appreciated. A significant proportion of young girls may have viable ovarian follicles with 15-20% experiencing spontaneous puberty, and 3-5% may achieve natural pregnancy. Spontaneous and assisted pregnancies with donated oocytes are associated with serious maternal complications, including eclampsia, diabetes, and catastrophic aortic dissections in women with TS. Thus, all TS women contemplating pregnancy need thorough medical and especially cardiologic evaluations and counseling as to the risks involved. Protocols for the physiologic induction of puberty and for the maintenance of feminization and prevention of osteoporosis in adults are described. The experience of premature ovarian failure and infertility leads to impaired psychosocial and sexual functioning in many women with TS. More attention focused on the psychological aspects of premature ovarian failure may help them cope with the diagnosis in a more positive manner. C1 NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NIH, CRC 1-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM bondyc@mail.nih.govqa NR 108 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-1435-4 PY 2010 BP 307 EP 324 DI 10.1007/978-1-4419-1436-1_19 D2 10.1007/978-1-4419-1436-1 PG 18 WC Andrology; Obstetrics & Gynecology; Reproductive Biology SC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology GA BOL94 UT WOS:000276968200019 ER PT B AU Signore, C Reddy, UM AF Signore, Caroline Reddy, Uma M. BE Carrell, DT Peterson, CM TI Pregnancy Outcomes in Infertile Couples SO REPRODUCTIVE ENDOCRINOLOGY AND INFERTILITY: INTEGRATING MODERN CLINICAL AND LABORATORY PRACTICE LA English DT Article; Book Chapter DE Assisted reproductive technologies; Infertility; Adverse pregnancy outcomes; Multiple pregnancy; Congenital malformations; Perinatal morbidity ID IN-VITRO FERTILIZATION; ASSISTED REPRODUCTIVE TECHNOLOGY; INTRACYTOPLASMIC SPERM INJECTION; BECKWITH-WIEDEMANN-SYNDROME; SINGLE-EMBRYO-TRANSFER; ORDER MULTIPLE GESTATIONS; MONOZYGOTIC TWINNING RATE; DANISH NATIONAL COHORT; LOW-BIRTH-WEIGHT; CHILDREN BORN AB The use of assisted reproductive technologies (ART) is increasing worldwide. Though most ART pregnancies are uncomplicated and result in the birth of healthy children, it should be noted that some ART pregnancies are at higher risk for adverse maternal and perinatal outcomes as compared to spontaneously conceived pregnancies. For many of these outcomes, it is not clear whether and to what extent observed complications are related to ART procedures themselves vs. the underlying condition(s) impairing fertility. Additional research is needed, keeping in mind specific methodological challenges. It is abundantly clear, however, that complications arising from multiple gestations conceived with ART are the major contributor to the adverse outcomes seen among ART mothers and children. Continued emphasis on reducing morbidity and mortality by reducing the number of embryos transferred per cycle while maintaining reasonable pregnancy rates is imperative. Recent data indicate that even singleton ART pregnancies are at higher risk of perinatal and possibly longer-term child health and developmental problems than naturally conceived singleton pregnancies. Couples seeking infertility treatment and ART should be carefully counseled about these risks. C1 [Signore, Caroline; Reddy, Uma M.] NICHHD, Dept Hlth & Human Serv, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. RP Reddy, UM (reprint author), NICHHD, Dept Hlth & Human Serv, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. EM reddyu@mail.nih.gov NR 112 TC 0 Z9 0 U1 0 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-1435-4 PY 2010 BP 715 EP 725 DI 10.1007/978-1-4419-1436-1_49 D2 10.1007/978-1-4419-1436-1 PG 11 WC Andrology; Obstetrics & Gynecology; Reproductive Biology SC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology GA BOL94 UT WOS:000276968200049 ER PT B AU Peterson, CM Carrell, DT Varner, M Stanford, J Croughan, M Louis, GB AF Peterson, C. Matthew Carrell, Douglas T. Varner, Michael Stanford, Joseph Croughan, Mary Louis, Germaine Buck BE Carrell, DT Peterson, CM TI The Environment and Reproduction: Endocrine Disruption, Reproductive Impairment, and Epigenetics SO REPRODUCTIVE ENDOCRINOLOGY AND INFERTILITY: INTEGRATING MODERN CLINICAL AND LABORATORY PRACTICE LA English DT Article; Book Chapter DE Endocrinedisruptor; Epigenetics; Endometriosis; Environment; Reproductive impairment; Biomarkers; Chemical substance inventory; Chemicals; Contaminants ID DISINFECTION BY-PRODUCTS; MENSTRUAL-CYCLE CHARACTERISTICS; ARYL-HYDROCARBON RECEPTOR; MATRIX-METALLOPROTEINASE EXPRESSION; SERUM DIOXIN CONCENTRATIONS; FEMALE GREENHOUSE WORKERS; PHTHALATE ESTER TOXICITY; ETHYLENE-GLYCOL ETHERS; HUMAN SEMEN PARAMETERS; NATIONAL BIRTH COHORT AB This chapter reviews the evidence that environmental factors have a role in the etiology of reproductive abnormalities. The actions of hormonally active agents, such as endocrine disrupting chemicals, that may alter the synthesis, secretion, transport, binding, or elimination of natural hormones are highlighted. This chapter also highlights the need for and organized collection of data to further analyze the involvemnet of environmental factors in reproductive anomalies. C1 [Peterson, C. Matthew] Univ Utah, Sch Med, Dept Obstet & Gynecol, Utah Ctr Reprod Med, Salt Lake City, UT 84132 USA. [Carrell, Douglas T.] Univ Utah, Sch Med, Dept Urol Surg, Salt Lake City, UT 84132 USA. [Carrell, Douglas T.] Univ Utah, Sch Med, Dept Physiol, Salt Lake City, UT 84132 USA. [Stanford, Joseph] Univ Utah, Hlth Sci Ctr, Dept Family & Prevent Med, Salt Lake City, UT 84132 USA. [Croughan, Mary] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Croughan, Mary] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Louis, Germaine Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, Bethesda, MD USA. RP Peterson, CM (reprint author), Univ Utah, Sch Med, Dept Obstet & Gynecol, Utah Ctr Reprod Med, 30 N Med Dr,2B200, Salt Lake City, UT 84132 USA. EM c.matthew.peterson@hsc.utah.edu; douglas.carrell@hsc.utah.edu RI Varner, Michael/K-9890-2013; OI Varner, Michael/0000-0001-9455-3973; Buck Louis, Germaine/0000-0002-1774-4490 NR 341 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-1435-4 PY 2010 BP 781 EP 803 DI 10.1007/978-1-4419-1436-1_55 D2 10.1007/978-1-4419-1436-1 PG 23 WC Andrology; Obstetrics & Gynecology; Reproductive Biology SC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology GA BOL94 UT WOS:000276968200055 ER PT J AU Jackson, LW Lynch, CD Kostyniak, PJ McGuinness, BM Louis, GMB AF Jackson, Leila W. Lynch, Courtney D. Kostyniak, Paul J. McGuinness, Bridget M. Louis, Germaine M. Buck TI Prenatal and postnatal exposure to polychlorinated biphenyls and child size at 24 months of age SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE Polychlorinated biphenyls; Environmental exposure; Growth and development; Pregnancy; Breast feeding ID IN-UTERO EXPOSURE; DICHLORODIPHENYL DICHLOROETHENE; MATERNAL SERUM; GROWTH; PREGNANCY; MOTHERS; FETAL; MILK; POLLUTANTS; DIOXINS AB Research suggests that exposure to polychlorinated biphenyls (PCBs) may result in decreased child growth, though the critical window(s) are unclear. We investigated the association between PCBs and child size at age 24 months (n = 44). PCBs were measured in first trimester serum, breast milk, and child serum at age 24 months, and dichotomized at the median. Age- and gender-specific z-scores were calculated for anthropometric measures. Using linear regression, we observed no significant changes in z-scores with prenatal or postnatal serum PCB concentrations. PCB-77 in breast milk was associated with a significant decrease in z-score for length. To our knowledge, this study is the first to examine child size in relation to PCBs measured early in pregnancy, as well as quantifying a far greater number of congeners. Further research is needed to clarify critical windows, congener-specific effects, and effect modification by sex in relation to PCBs and child anthropometric measures. (C) 2009 Elsevier Inc. All rights reserved. C1 [Jackson, Leila W.] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Lynch, Courtney D.] Ohio State Univ, Div Epidemiol, Coll Publ Hlth, Columbus, OH 43210 USA. [Kostyniak, Paul J.] SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY 14260 USA. [McGuinness, Bridget M.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Rockville, MD USA. RP Jackson, LW (reprint author), Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, WG37,10900 Euclid Ave, Cleveland, OH 44106 USA. EM leila.jackson@case.edu OI Buck Louis, Germaine/0000-0002-1774-4490 FU Great Lakes Protection Fund [RM 791-3021]; Agency for Toxic Substances and Disease Registry [H75/ATH 298328]; Gerber Foundation; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This research was supported in part by the Great Lakes Protection Fund (RM 791-3021); the Agency for Toxic Substances and Disease Registry (H75/ATH 298328); the Gerber Foundation; and intramural funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 48 TC 6 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD JAN PY 2010 VL 29 IS 1 BP 25 EP 31 DI 10.1016/j.reprotox.2009.09.008 PG 7 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 546HN UT WOS:000273802000003 PM 19819326 ER PT S AU Kim, YA Wuchty, S Przytycka, TM AF Kim, Yoo-Ah Wuchty, Stefan Przytycka, Teresa M. BE Berger, B TI Simultaneous Identification of Causal Genes and Dys-Regulated Pathways in Complex Diseases SO RESEARCH IN COMPUTATIONAL MOLECULAR BIOLOGY, PROCEEDINGS SE Lecture Notes in Bioinformatics LA English DT Proceedings Paper CT 14th Annual International Conference on Research in Computational Molecular Biology CY APR 25-28, 2010 CL Lisbon, PORTUGAL SP INESC-ID, Inst Superior Tecn DE Complex disease; genetic variations; copy number variation; biological pathway; graph theoretic algorithm; glioma ID PROTEIN INTERACTION NETWORK; PHOSPHORYLATION NETWORKS; BREAST-CANCER; EXPRESSION; DISCOVERY; RESOURCE; DATABASE; TUMORS; CLASSIFICATION; ASSOCIATIONS AB In complex diseases different genotypic perturbations of the cellular system often lead to the same phenotype. While characteristic genomic alterations in many cancers exist, other combinations of genomic perturbations potentially lead to the same disease, dysregulating important pathways of the cellular system. In this study, we developed novel computational methods to identify dysregulated pathways and their direct causes in individual patients or patient groups. Specifically, we introduced efficient and powerful graph theoretic algorithms to identify such dysregulated pathways and their causal genes and applied our methods to a large set of glioma specific molecular data. C1 [Kim, Yoo-Ah; Wuchty, Stefan; Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, NLM, Bethesda, MD 20894 USA. RP Kim, YA (reprint author), NIH, Natl Ctr Biotechnol Informat, NLM, 8600 Rockville Pike,Bldg 38A, Bethesda, MD 20894 USA. EM kimy3@ncbi.nlm.nih.gov; wuchtys@ncbi.nlm.nih.gov; przytyck@ncbi.nlm.nih.gov NR 44 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-12682-6 J9 LECT N BIOINFORMAT JI Lect. Notes Bioinforma. PY 2010 VL 6044 BP 263 EP 280 PG 18 WC Biochemical Research Methods; Computer Science, Information Systems; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA BQE27 UT WOS:000280767000017 ER PT S AU Tomasiewicz, HG Liu, XC Tassone, C Thometz, J AF Tomasiewicz, H. G. Liu, X. C. Tassone, C. Thometz, J. BE Aubin, CE Stokes, IAF Labelle, H Moreau, A TI Development of Zebrafish as a Natural Model System for Studying Scoliosis SO RESEARCH INTO SPINAL DEFORMITIES 7 SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 8th Biennial Meeting of the International-Research-Society-of-Spinal-Deformities (IRSSD) CY JUL, 2010 CL Montreal, CANADA SP Int Res Soc Spinal Deformities, Medicorps C1 [Tomasiewicz, H. G.] Univ Wisconsin Milwaukee, NIEHS Childrens Environm Hlth Sci Core Ctr, Milwaukee, WI 53201 USA. [Liu, X. C.; Tassone, C.; Thometz, J.] Childrens Hosp WI, Med Coll WI, Dept Orthopaed Surg, Milwaukee, WI 53201 USA. RP Tomasiewicz, HG (reprint author), Univ Wisconsin Milwaukee, NIEHS Childrens Environm Hlth Sci Core Ctr, Milwaukee, WI 53201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-60750-573-0 J9 STUD HEALTH TECHNOL PY 2010 VL 158 BP 257 EP 257 DI 10.3233/978-1-60750-573-0-257 PG 1 WC Orthopedics SC Orthopedics GA BHJ88 UT WOS:000325662300084 ER PT J AU Eum, SY Lee, YJ Min, JH Kwak, HK Hong, MS Kong, JH Hwang, SH Park, SK LeBlanc, JJ Via, LE Barry, CE Cho, SN AF Eum, Seok-Yong Lee, Ye-Jin Min, Jin-Hong Kwak, Hyun-Kyung Hong, Min-Sun Kong, Ji-Hye Hwang, Soo-Hee Park, Seung-Kyu LeBlanc, Jason J. Via, Laura E. Barry, Clifton E., III Cho, Sang-Nae TI Association of Antigen-Stimulated Release of Tumor Necrosis Factor-Alpha in Whole Blood with Response to Chemotherapy in Patients with Pulmonary Multidrug-Resistant Tuberculosis SO RESPIRATION LA English DT Article DE Chemotherapy; Interferon-gamma; Interleukin-10; Interleukin-12; Multidrug-resistant tuberculosis; Mycobacterial clearance; Tuberculosis; Tumor necrosis factor-alpha ID INTERFERON-GAMMA PRODUCTION; MYCOBACTERIUM-TUBERCULOSIS; MONONUCLEAR-CELLS; CYTOKINE PROFILES; PROTECTIVE IMMUNITY; DISEASE; LYMPHOCYTES; INTERLEUKIN-10; EXPRESSION; INFECTION AB Background: We have previously reported that TNF-alpha levels correlate to total mycobacterial burden in tuberculosis (TB) patients. Objective: To characterize the dynamics of cytokine responses in TB patients during chemotherapy to identify potential surrogate markers for effective treatment. Methods: Following induction by culture filtrate proteins in whole blood, production patterns of TNF-alpha, IL-10, IFN-gamma and IL-12 were measured in 23 non-multidrug-resistant (MDR)-TB and 16 MDR-TB patients and in 31 healthy controls. Rates of mycobacterial clearance from the sputum were then measured and compared. Results: Prior to the initiation of chemotherapy, TNF-alpha and IL-10 levels were significantly higher in TB patients than in healthy controls while IFN-gamma and IL-12 levels were similar. During chemotherapy, the levels of all 4 cytokines increased. We evaluated these responses separately in patients that did and did not clear their sputum culture at 2 and 6 months. At 2 months, decreases in both IFN-gamma and IL-12 correlated strongly with a successful early response, while after 6 months of therapy, when half (7/14) of MDR-TB patients were still sputum culture positive, downregulation of TNF-alpha was uniquely correlated with sputum conversion between the groups. Conclusion: Our findings suggest the possibility that the regulation of TNF-alpha production in whole blood may be a more specific indicator of sputum conversion at 6 months than IFN-gamma, IL-12 or IL-10 in MDR-TB patients. Copyright (C) 2010 S. Karger AG, Basel C1 [Eum, Seok-Yong; Lee, Ye-Jin; Kwak, Hyun-Kyung; Hong, Min-Sun; Kong, Ji-Hye] Int TB Res Ctr, Div Immunopathol & Cellular Immunol, Masan 631320, South Korea. [Eum, Seok-Yong; Lee, Ye-Jin; Kwak, Hyun-Kyung; Hong, Min-Sun; Kong, Ji-Hye] Int TB Res Ctr, Div Mol Microbiol, Masan 631320, South Korea. [Min, Jin-Hong; Hwang, Soo-Hee; Park, Seung-Kyu] Natl Masan TB Hosp, Masan, South Korea. [Cho, Sang-Nae] Yonsei Univ, Coll Med, Dept Microbiol, Seoul, South Korea. [LeBlanc, Jason J.; Via, Laura E.; Barry, Clifton E., III] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA. RP Eum, SY (reprint author), Int TB Res Ctr, Div Immunopathol & Cellular Immunol, 475-1 Gapo, Masan 631320, South Korea. EM syeumkr@gmail.com RI Barry, III, Clifton/H-3839-2012; OI Via, Laura/0000-0001-6074-9521 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md., USA; Yonsei University FX This study was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md., USA, and by a grant from the Brain Korea 21 Project for Medical Sciences in Yonsei University (S.-N.C.). NR 30 TC 8 Z9 8 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0025-7931 J9 RESPIRATION JI Respiration PY 2010 VL 80 IS 4 BP 275 EP 284 DI 10.1159/000283687 PG 10 WC Respiratory System SC Respiratory System GA 642OB UT WOS:000281224000003 PM 20145387 ER PT J AU Vazin, T Freed, WJ AF Vazin, Tandis Freed, William J. TI Human embryonic stem cells: Derivation, culture, and differentiation: A review SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Review DE Human; embryonic; cells; progenitors; differentiation; ectoderm; endoderm; mesoderm; karyotype; feeder-free; synthetic scaffolds; hydrogels; hyaluronic acid; hepatocyte; embryoid bodies; mesenchymal; osteocytes; chondrocytes; stromal; hematopoietic; cardiomyocytes; endothelial; epithelial; neural; neurons; motor neurons; dopaminergic neurons; oligodendrocytes; myelination; degenerative disorders; transplantation ID MIDBRAIN DOPAMINERGIC-NEURONS; LONG-TERM CULTURE; HUMAN ES CELLS; FEEDER LAYERS; DIRECTED DIFFERENTIATION; HUMAN BLASTOCYSTS; IN-VITRO; SELF-RENEWAL; UNDIFFERENTIATED GROWTH; CONDITIONED MEDIUM AB The greatest therapeutic promise of human embryonic stem cells (hESC) is to generate specialized cells to replace damaged tissue in patients suffering from various degenerative diseases. However, the signaling mechanisms involved in lineage restriction of ESC to adopt various cellular phenotypes are still under investigation. Furthermore, for progression of hESC-based therapies towards clinical applications, appropriate culture conditions must be developed to generate genetically stable homogenous populations of cells, to hinder possible adverse effects following transplantation. Other critical challenges that must be addressed for successful cell implantation include problems related to survival and functional efficacy of the grafted cells. This review initially describes the derivation of hESC and focuses on recent advances in generation, characterization, and maintenance of these cells. We also give an overview of original and emerging differentiation strategies used to convert hESC to different cell types. Finally, we will discuss transplantation studies of hESC-derived cells with respect to safety and functional recovery. C1 [Vazin, Tandis; Freed, William J.] Natl Inst Drug Abuse, Dev & Plast Sect, Cellular Neurobiol Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD USA. RP Vazin, T (reprint author), Univ Calif Berkeley, Dept Chem Engn, Dept Bioengn, Berkeley, CA 94720 USA. EM vazint@berkeley.edu FU NIDA, NIH, DHHS FX Research was supported by the IRP of NIDA, NIH, DHHS. NR 123 TC 43 Z9 45 U1 7 U2 42 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 2010 VL 28 IS 4 BP 589 EP 603 DI 10.3233/RNN-2010-0543 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 639KZ UT WOS:000280975000018 PM 20714081 ER PT J AU Yeh, S Forooghian, F Faia, LJ Weichel, ED Wong, WT Sen, HN Chan-Kai, BT Witherspoon, SR Lauer, AK Chew, EY Nussenblatt, RB AF Yeh, Steven Forooghian, Farzin Faia, Lisa J. Weichel, Eric D. Wong, Wai T. Sen, Hatice N. Chan-Kai, Brian T. Witherspoon, Scott R. Lauer, Andreas K. Chew, Emily Y. Nussenblatt, Robert B. TI FUNDUS AUTOFLUORESCENCE CHANGES IN CYTOMEGALOVIRUS RETINITIS SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE fundus autofluorescence; retinal pigment epithelium; retinitis; cytomegalovirus retinitis; human immunodeficiency virus; ophthalmic imaging ID IMMUNODEFICIENCY SYNDROME; EPITHELIAL-CELLS; LIPOFUSCIN; ACCUMULATION; GANCICLOVIR; DIAGNOSIS; UVEITIS; TRIAL AB Purpose: The purpose of this study was to describe fundus autofluorescence imaging features of cytomegalovirus (CMV) retinitis and to correlate fundus autofluorescence features with clinical activity. Methods: A retrospective case series was undertaken to evaluate nine eyes of six patients with active CMV retinitis. Patients were evaluated with a comprehensive ophthalmic examination, fundus autofluorescence imaging, and fundus photography. Oral valganciclovir, intravitreal ganciclovir, intravitreal foscarnet, or an ganciclovir implant was administered as clinically indicated. Results: In all nine eyes with active CMV retinitis, a hyperautofluorescent signal on fundus autofluorescence imaging was correlated spatially with the border of advancing CMV retinitis. Stippled areas of alternating hyperautofluorescence and hypoautofluorescence were observed in regions of retinal pigment epithelium atrophy from prior CMV retinitis. In three eyes with subtle CMV reactivation, a hyperautofluorescent border was helpful in the detection and localization of active CMV retinitis. In another patient, diffuse, punctate hyperautofluorescence after intravitreal ganciclovir and foscarnet was a concern for medication-related toxicity. Conclusion: Fundus autofluorescence imaging was valuable in highlighting areas of active CMV retinitis in all patients in this series, including two patients with subtle clinical features. Fundus autofluorescence may be useful as an adjunctive imaging modality for the detection of CMV activity and aid in our understanding of the structural changes during episodes of CMV retinitis. RETINA 30:42-50,2010 C1 [Yeh, Steven; Forooghian, Farzin; Wong, Wai T.; Sen, Hatice N.; Chew, Emily Y.; Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA. [Faia, Lisa J.; Weichel, Eric D.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Yeh, Steven; Chan-Kai, Brian T.; Witherspoon, Scott R.; Lauer, Andreas K.] Oregon Hlth & Sci Univ, Casey Eye Inst, Retina Serv, Portland, OR 97201 USA. RP Nussenblatt, RB (reprint author), NEI, NIH, Bldg 10,10N-112,10 Ctr Dr, Bethesda, MD 20892 USA. EM DrBob@nei.nih.gov RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 FU National Eye Institute, National Institutes of Health; Heed Ophthalmic Foundation FX Supported by the Intramural Research Program of the National Eye Institute, National Institutes of Health. Dr. Steven Yeh has received support from the Heed Ophthalmic Foundation. NR 24 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD JAN PY 2010 VL 30 IS 1 BP 42 EP 50 DI 10.1097/IAE.0b013e3181bfbdb2 PG 9 WC Ophthalmology SC Ophthalmology GA 607ZX UT WOS:000278547300006 PM 19996825 ER PT J AU Forooghian, F Stetson, PF Meyer, SA Chew, EY Wong, WT Cukras, C Meyerle, CB Ferris, FL AF Forooghian, Farzin Stetson, Paul F. Meyer, Scott A. Chew, Emily Y. Wong, Wai T. Cukras, Catherine Meyerle, Catherine B. Ferris, Frederick L., III TI RELATIONSHIP BETWEEN PHOTORECEPTOR OUTER SEGMENT LENGTH AND VISUAL ACUITY IN DIABETIC MACULAR EDEMA SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE diabetes; diabetic macular edema; optical coherence tomography; visual acuity; outer segments ID OPTICAL COHERENCE TOMOGRAPHY; CENTRAL SEROUS CHORIORETINOPATHY; INTRAVITREAL TRIAMCINOLONE; THICKNESS MEASUREMENT; RETINITIS-PIGMENTOSA; LASER TREATMENT; UNITED-STATES; TIME-DOMAIN; RETINOPATHY; REPRODUCIBILITY AB Purpose: The purpose of this study was to quantify photoreceptor outer segment (PROS) length in 27 consecutive patients (30 eyes) with diabetic macular edema using spectral domain optical coherence tomography and to describe the correlation between PROS length and visual acuity. Methods: Three spectral domain-optical coherence tomography scans were performed on all eyes during each session using Cirrus HD-OCT. A prototype algorithm was developed for quantitative assessment of PROS length. Retinal thicknesses and PROS lengths were calculated for 3 parameters: macular grid (6 x 6 mm), central subfield (1 mm), and center foveal point (0.33 mm). Intrasession repeatability was assessed using coefficient of variation and intraclass correlation coefficient. The association between retinal thickness and PROS length with visual acuity was assessed using linear regression and Pearson correlation analyses. The main outcome measures include intrasession repeatability of macular parameters and correlation of these parameters with visual acuity. Results: Mean retinal thickness and PROS length were 298 mu m to 381 mu m and 30 mu m to 32 mu m, respectively, for macular parameters assessed in this study. Coefficient of variation values were 0.75% to 4.13% for retinal thickness and 1.97% to 14.01% for PROS length. Intraclass correlation coefficient values were 0.96 to 0.99 and 0.73 to 0.98 for retinal thickness and PROS length, respectively. Slopes from linear regression analyses assessing the association of retinal thickness and visual acuity were not significantly different from 0 (P > 0.20), whereas the slopes of PROS length and visual acuity were significantly different from 0 (P < 0.0005). Correlation coefficients for macular thickness and visual acuity ranged from 0.13 to 0.22, whereas coefficients for PROS length and visual acuity ranged from -0.61 to -0.81. Conclusion: Photoreceptor outer segment length can be quantitatively assessed using Cirrus HD-OCT. Although the intrasession repeatability of PROS measurements was less than that of macular thickness measurements, the stronger correlation of PROS length with visual acuity suggests that the PROS measures may be more directly related to visual function. Photoreceptor outer segment length may be a useful physiologic outcome measure, both clinically and as a direct assessment of treatment effects. RETINA 30:63-70,2010 C1 [Forooghian, Farzin; Chew, Emily Y.; Cukras, Catherine; Meyerle, Catherine B.; Ferris, Frederick L., III] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. [Stetson, Paul F.; Meyer, Scott A.] Carl Zeiss Meditec Inc, Dublin, CA USA. [Wong, Wai T.] NEI, Off Sci Director, NIH, Bethesda, MD 20892 USA. RP Forooghian, F (reprint author), Room 10D45,Bldg 10,9000 Rockville Pike, Bethesda, MD USA. EM farzin.forooghian@mssm.edu RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 FU National Eye Institute FX Supported by the National Eye Institute intramural research program. Paul F. Stetson and Scott A. Meyer are both employees of Carl Zeiss Meditec, Inc. NR 30 TC 55 Z9 55 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD JAN PY 2010 VL 30 IS 1 BP 63 EP 70 DI 10.1097/IAE.0b013e3181bd2c5a PG 8 WC Ophthalmology SC Ophthalmology GA 607ZX UT WOS:000278547300008 PM 19952996 ER PT S AU Subramanian, P Notario, PM Becerra, SP AF Subramanian, Preeti Notario, Patricia M. Becerra, S. Patricia BE Anderson, RE LaVail, MM Hollyfield, JG Mandal, MNA TI Pigment Epithelium-derived Factor Receptor (PEDF-R): A Plasma Membrane-linked Phospholipase with PEDF Binding Affinity SO RETINAL DEGENERATIVE DISEASES: LABORATORY AND THERAPEUTIC INVESTIGATIONS SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 13th International Symposium on Retinal Degeneration CY SEP 18-23, 2008 CL Emeishan, PEOPLES R CHINA ID INTERPHOTORECEPTOR MATRIX; EXPRESSION; PATATIN; NEOVASCULARIZATION; IDENTIFICATION; ANGIOGENESIS; DEGENERATION; SECRETION; NEURONS; RETINA AB Pigment epithelium-derived factor (PEDF), a multifunctional protein, acts in retinal differentiation, survival and maintenance by interacting with high affinity receptors on the surface of target cells. We have recently identified PEDF-R, a new member of the patatin-like phospholipase domain-containing 2 (PNPLA2) family with characteristics of a PEDF receptor. The PEDF-R sequence reveals a patatin-like phospholipase domain toward its amino-end, and four transmembrane domains interrupted by two extracellular loops and three intracellular regions along its polypeptide sequence. This newly identified protein is present on the surface of retina and RPE cells, and has the expected transmembrane topology. It has specific and high binding affinity for PEDF, and exhibits a potent phospholipase A(2) activity that liberates fatty acids. Most importantly, PEDF binding stimulates the enzymatic phospholipase A(2) activity of PEDF-R. In summary, PEDF-R is a novel component of the retina that is a phospholipase-linked membrane protein with high affinity for PEDF. The results suggest a molecular pathway by which PEDF ligand/receptor interactions on the cell surface could generate a cellular signal. These conclusions enhance our understanding of the role of PEDF as a neurotrophic survival factor. C1 [Subramanian, Preeti; Becerra, S. Patricia] NEI, NIH, Bethesda, MD 20892 USA. [Notario, Patricia M.] Georgetown Univ, Sch Med, Washington, DC 20007 USA. RP Becerra, SP (reprint author), NEI, NIH, Bldg 6,Room 134,6 Ctr Dr,MSC 0608, Bethesda, MD 20892 USA. EM becerrap@nei.nih.gov FU Intramural NIH HHS [Z01 EY000306-13] NR 29 TC 25 Z9 26 U1 1 U2 6 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-1398-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2010 VL 664 BP 29 EP 37 DI 10.1007/978-1-4419-1399-9_4 PG 9 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA BOU67 UT WOS:000277660900004 PM 20237999 ER PT S AU Murga-Zamalloa, C Swaroop, A Khanna, H AF Murga-Zamalloa, Carlos Swaroop, Anand Khanna, Hemant BE Anderson, RE LaVail, MM Hollyfield, JG Mandal, MNA TI Multiprotein Complexes of Retinitis Pigmentosa GTPase Regulator (RPGR), a Ciliary Protein Mutated in X-Linked Retinitis Pigmentosa (XLRP) SO RETINAL DEGENERATIVE DISEASES: LABORATORY AND THERAPEUTIC INVESTIGATIONS SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 13th International Symposium on Retinal Degeneration CY SEP 18-23, 2008 CL Emeishan, PEOPLES R CHINA ID GUANINE-NUCLEOTIDE-EXCHANGE; NORTH-AMERICAN COHORT; EXON ORF15; INTRAFLAGELLAR TRANSPORT; RETINAL DEGENERATION; RETINITIS-PIGMENTOSA-2 PROTEIN; (RPGR)-INTERACTING PROTEIN; SUBCELLULAR-LOCALIZATION; POSITIONAL CLONING; CONNECTING CILIUM AB Mutations in Retinitis Pigmentosa GTPase Regulator (RPGR) are a frequent cause of X-linked Retinitis Pigmentosa (XLRP). The RPGR gene undergoes extensive alternative splicing and encodes for distinct protein isoforms in the retina. Extensive studies using isoform-specific antibodies and mouse mutants have revealed that RPGR predominantly localizes to the transition zone to primary cilia and associates with selected ciliary and microtubule-associated assemblies in photoreceptors. In this chapter, we have summarized recent advances on understanding the role of RPGR in photoreceptor protein trafficking. We also provide new evidence that suggests the existence of discrete RPGR multiprotein complexes in photoreceptors. Piecing together the RPGR-interactome in different subcellular compartments should provide critical insights into the role of alternative RPGR isoforms in associated orphan and syndromic retinal degenerative diseases. C1 [Murga-Zamalloa, Carlos; Khanna, Hemant] Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. [Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. RP Khanna, H (reprint author), Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. EM hkhanna@med.umich.edu OI Swaroop, Anand/0000-0002-1975-1141 FU National Eye Institute [RO1-EY007961]; Midwest Eye Banks and Transplantation Center; NEI/NIH FX This work is supported by the grants from the National Eye Institute (RO1-EY007961), Midwest Eye Banks and Transplantation Center, and by NEI/NIH intramural program. NR 81 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-1398-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2010 VL 664 BP 105 EP 114 DI 10.1007/978-1-4419-1399-9_13 PG 10 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA BOU67 UT WOS:000277660900013 PM 20238008 ER PT B AU Cukras, C Chan, CC AF Cukras, Catherine Chan, Chi-Chao BE Baert, M Peeters, C TI Diagnosis and Treatment of Retinitis Pigmentosa Based on the Pathology SO RETINITIS PIGMENTOSA: CAUSES, DIAGNOSIS, AND TREATMENT SE Eye and Vision Research Developments LA English DT Article; Book Chapter ID INDEPENDENT PHOTORECEPTOR APOPTOSIS; INHERITED RETINAL DEGENERATION; FIBROBLAST-GROWTH-FACTOR; VIVO GENE-THERAPY; IN-VIVO; RHODOPSIN MUTATION; CELL-DEATH; MACULAR DEGENERATION; RD MOUSE; RCS RAT AB Retinitis pigmentosa (RP) is a group of inherited retinal degenerations, caused by mutations in one of many genes - some already identified, and some still yet to be discovered. While there are many different genes involved and great heterogeneity among these genes, the underlying common source of vision loss is retinal dysfunction related to photoreceptor loss. The sequence of histopathologic changes associated with RP occurs in several stages. The 1st stage is associated with rod photoreceptor dysfunction and ultimate death and the second with cone photoreceptor demise. Following photoreceptor loss, a number of secondary changes occur, with retinal pigment epithelial (RPE) cells detaching from of Bruch's membrane and migrating into the inner retina to ultimately accumulate and surround blood vessels which gives rise to the "bone spicules" observed clinically. Other pathologies include attenuation of blood vessels, retinal gliosis, migration of microglia into the outer retina, optic nerve atrophy and mild vitritis. Current therapies for RP include: genetic replacement of missing/mutated proteins via viral vectors, addition (by injection or surgery) of factors or supplements that may prolong photoreceptor survival, transplantation of photoreceptors and RPE cells and electrical stimulation of remaining neurons, as well as developing therapies targeted at preventing photoreceptor apoptosis. Understanding the histopathologic changes occurring in RP is critical to understanding the rationale for current therapies, as well as to develop future therapies. Mouse models of retinitis pigmentosa, have been instrumental in aiding the study of histopathologic changes that occur in the setting of retinitis pigmentosa and to initiate and study various treatment approaches. Many of the findings of the histopathologic changes and treatment avenues are explored in these models. C1 [Cukras, Catherine; Chan, Chi-Chao] NEI, NIH, Bethesda, MD 20892 USA. RP Cukras, C (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM cukrasc@nei.nih.gov NR 57 TC 0 Z9 0 U1 1 U2 2 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60876-884-4 J9 EYE VIS RES DEV PY 2010 BP 111 EP 125 PG 15 WC Ophthalmology SC Ophthalmology GA BPC65 UT WOS:000278520200004 ER PT B AU Eiden, MV Radke, K Rovnak, J Quackenbush, SL AF Eiden, Maribeth V. Radke, Kathryn Rovnak, Joel Quackenbush, Sandra L. BE Kurth, R Bannert, N TI Non-primate Mammalian and Fish Retroviruses SO RETROVIRUSES: MOLECULAR BIOLOGY, GENOMICS AND PATHOGENESIS LA English DT Article; Book Chapter ID BOVINE LEUKEMIA-VIRUS; WALLEYE DERMAL SARCOMA; CELL-SURFACE RECEPTOR; DISCRETE EPIDERMAL HYPERPLASIA; AMINO-ACID TRANSPORTER; STIZOSTEDION-VITREUM-VITREUM; SALMO-SALAR L; EXPERIMENTAL TRANSMISSION; ENDOGENOUS RETROVIRUS; NUCLEOTIDE-SEQUENCE AB The pioneering phase of the study of retroviruses resulted in the identification of viruses associated with diseases in chickens, mice and cats. Exogenous retroviruses have since been isolated from many vertebrate species, and classified into seven genera that can be grouped into two general categories. Alpharetroviruses, betaretroviruses and gammaretroviruses are genetically simple, encoding only nucleoprotein, matrix, capsid, reverse transcriptase, integrase, protease and envelope proteins. Deltaretroviruses, epsilonretroviruses, lentiviruses and spumaviruses are considered complex because they encode in addition to the proteins listed above, a number of ancillary proteins that often play an important role in gene regulation. In this chapter we review recent findings of representative simple mammalian gammaretroviruses and the complex piscine epsilonretroviruses and bovine leukaemia virus with the intent of illustrating how these viruses have shed light on the mechanisms of viral function, evolution and pathogenesis within the animal kingdom that hosts them. C1 [Eiden, Maribeth V.] NIH, Sect Mol Virol, Lab Cell & Mol Regulat, Bethesda, MD 20892 USA. [Rovnak, Joel; Quackenbush, Sandra L.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. [Radke, Kathryn] Univ Calif Davis, Dept Anim Sci, Davis, CA 95616 USA. RP Eiden, MV (reprint author), NIH, Sect Mol Virol, Lab Cell & Mol Regulat, Bldg 10, Bethesda, MD 20892 USA. EM eidenm@mail.nih.gov; klradke@ucdavis.edu; Joel.Rovnak@colostate.edu; Sandra.Quackenbush@colostate.edu NR 167 TC 0 Z9 0 U1 0 U2 1 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-904455-55-4 PY 2010 BP 371 EP 394 PG 24 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA BND77 UT WOS:000274240500014 ER PT J AU Myslobodsky, M Coppola, R AF Myslobodsky, Michael Coppola, Richard TI Ingestion-Controlling Network: What's Language Got to Do with It? SO REVIEWS IN THE NEUROSCIENCES LA English DT Article DE networks; polysemy; molecular promiscuity; orexigenic and anorexigenic peptides; motifs ID DRUG DEVELOPMENT; LINGUISTIC FEATURES; COMPLEX NETWORKS; ENERGY-BALANCE; MESSENGER-RNA; DNA-SEQUENCES; MAGIC BULLET; LEPTIN; DESIGN; STRESS AB The prevalence of obesity has increased dramatically worldwide, whereas the type s of treatment and their efficacy have not substantially changed over the last two decades. Additionally, drugs used to control weight gain could occasionally create untoward effects in cardiovascular functions, as well as in behaviors, memory, sleep, and emotions because the molecular machinery responsible for ingestion control is interconnected with or shared by the above domains. How each group of drugs preserves the privacy of its message in the mutual network is not fully understood. In the present essay, the graph theory approach was used to explore some aspects of molecular signaling as though they were a 'language'. Its emphasis is on 'molecular polysemy', a term that refers to the ability of biomolecules to be used like words in natural languages more than one-way. This has physiological and clinical implications, in particular when planning drug designs with "specially engineered shotgun loads" that target a combination of biomolecules that assure a better therapeutic outcome without causing deficits in connected but patho-physiologically irrelevant bystanders. C1 [Myslobodsky, Michael; Coppola, Richard] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Myslobodsky, Michael] Howard Univ, Grad Sch, Washington, DC 20059 USA. RP Myslobodsky, M (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA MH002890-05] NR 80 TC 1 Z9 1 U1 2 U2 4 PU FREUND & PETTMAN PUBLISHERS PI EAST YORKSHIRE PA ENHOLMES HALL, PATRINGTON, EAST YORKSHIRE HU12 OPR, ENGLAND SN 0334-1763 J9 REV NEUROSCIENCE JI Rev. Neurosci. PY 2010 VL 21 IS 1 BP 67 EP 81 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 589QS UT WOS:000277168300005 PM 20458888 ER PT S AU Ellis, JC Brown, JW AF Ellis, J. Christopher Brown, James W. BE Liu, F Altman, S TI The Evolution of RNase P and Its RNA SO RIBONUCLEASE P SE Protein Reviews LA English DT Article; Book Chapter ID PYROCOCCUS-HORIKOSHII OT3; BACTERIAL RIBONUCLEASE-P; RIBOZYME-SUBSTRATE COMPLEX; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; NANOARCHAEUM-EQUITANS; BACILLUS-SUBTILIS; PROTEIN-COMPONENT; ARCHAEAL HOMOLOG; CATALYTIC RNA C1 [Ellis, J. Christopher; Brown, James W.] N Carolina State Univ, Dept Microbiol, Raleigh, NC 27695 USA. [Ellis, J. Christopher] Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. RP Brown, JW (reprint author), N Carolina State Univ, Dept Microbiol, Campus Box 7615, Raleigh, NC 27695 USA. EM james_brown@ncsu.edu RI Ellis, Joseph/G-6335-2011 NR 87 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1871-3025 BN 978-1-4419-1141-4 J9 PROTEIN REV JI Protein Rev. PY 2010 VL 10 BP 17 EP 40 DI 10.1007/978-1-4419-1142-1_2 D2 10.1007/978-1-4419-1142-1 PG 24 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BND78 UT WOS:000274240600002 ER PT S AU Lombaert, IMA Hoffman, MP AF Lombaert, Isabelle. M. A. Hoffman, Matthew P. BE Tucker, AS Miletich, I TI Epithelial Stem/Progenitor Cells in the Embryonic Mouse Submandibular Gland SO SALIVARY GLANDS: DEVELOPMENT, ADAPTATIONS AND DISEASE SE Frontiers of Oral Biology LA English DT Article; Book Chapter ID AUTOSOMAL SEX REVERSAL; LABEL-RETAINING CELLS; SRY-RELATED GENE; SALIVARY-GLAND; STEM-CELLS; BRANCHING MORPHOGENESIS; PROGENITOR CELLS; CAMPOMELIC DYSPLASIA; PANCREATIC LINEAGES; MAMMARY-GLAND AB Salivary gland organogenesis involves the specification, maintenance, lineage commitment, and differentiation of epithelial stem/progenitor cells. Identifying how stem/progenitor cells are directed along a series of cell fate decisions to form a functional salivary gland will be necessary for future stem cell regenerative therapy. The identification of stem/progenitor cells within the salivary gland has focused on their role in postnatal glands and little is known about them in embryonic glands. Here, we have reviewed the information available for other developing organ systems and used it to determine whether similar cell populations exist in the mouse submandibular gland. Additionally, using growth factors that influence salivary gland epithelial morphogenesis during development, we have taken a simple experimental approach asking whether any of these growth factors influence early developmental lineages within the salivary epithelium on a transcriptional level. These preliminary findings show that salivary epithelial stem/progenitor populations exist within the gland, and that growth factors that are reported to control epithelial morphogenesis may also impact cell fate decisions. Further investigation of the signaling networks that influence stem/progenitor cell behavior will allow us to hypothesize how we might induce autologous stem cells to regenerate damaged salivary tissue in a therapeutic context. Copyright (C) 2010 S. Karger AG, Basel C1 [Lombaert, Isabelle. M. A.; Hoffman, Matthew P.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Hoffman, MP (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Rm 430,Bldg 30,30 Convent Dr MSC 43780, Bethesda, MD 20892 USA. EM mhoffman@mail.nih.gov FU Intramural NIH HHS [Z01 DE000722-01, ZIA DE000707-07, Z99 DE999999] NR 90 TC 22 Z9 24 U1 0 U2 6 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1420-2433 BN 978-3-8055-9406-6 J9 FRONT ORAL BIOL JI Front. Oral Biol. PY 2010 VL 14 BP 90 EP 106 PG 17 WC Anatomy & Morphology; Dentistry, Oral Surgery & Medicine; Developmental Biology SC Anatomy & Morphology; Dentistry, Oral Surgery & Medicine; Developmental Biology GA BOZ52 UT WOS:000278108000006 PM 20428013 ER PT J AU Stringer, E Read, JS Hoffman, I Valentine, M Aboud, S Goldenberg, RL AF Stringer, Elizabeth Read, Jennifer S. Hoffman, Irving Valentine, Megan Aboud, Said Goldenberg, Robert L. TI Treatment of trichomoniasis in pregnancy in sub-Saharan Africa does not appear to be associated with low birth weight or preterm birth SO SAMJ SOUTH AFRICAN MEDICAL JOURNAL LA English DT Article ID BACTERIAL VAGINOSIS; CLINICAL-TRIAL; METRONIDAZOLE; ANTIBIOTICS; INFECTION; DELIVERY; WOMEN; VAGINALIS; MORTALITY; OUTCOMES AB Objectives. To determine whether treatment of trichomoniasis increases the risk of prematurity Design. Sub-analysis of a randomised trial. Setting We analysed data from HPTN 024, a randomised trial of antenatal and intrapartum antibiotics to reduce chorioamnionitis-related perinatal HIV transmission. Subjects. Pregnant women front four sites in Africa. Outcome measures. Gestational age at the time of delivery or mean birth weight. Results Of 2 428 women-infant pairs included, 428 (18%) had trichomomasis at enrolment. There were no differences in infant age or birth weight between women with or without trichomoniasis By randomisation group, there were no differences in gestational age at birth or birth weight Of the 428 women diagnosed with trichomoniasis, 365 (83%) received antibiotics and 63 (15%) did not In analysis of actual use of antibiotics, women with trichomoniasis who received no treatment were more likely to deliver a preterm infant when the symphysis-fundal height was used to estimate gestational age (36% v. 23%; p=0.03), but not when the Ballard score Was used (16%, v. 21%,; p=0 41). There were no differences in mean birth weight between groups Conclusions In pregnant women in sub-Saharan Africa, most of whom were HIV-infected, neither trichomoniasis nor its treatment appears to influence the risk of preterm birth or a low-birth-weight infant. C1 [Stringer, Elizabeth] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [Stringer, Elizabeth] Ctr Infect Dis Res Zambia, Lusaka, Zambia. [Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Hoffman, Irving] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Valentine, Megan] Family Hlth Int, Durham, NC USA. [Aboud, Said] Muhimbili Univ Hlth & Allied Sci, Dept Microbiol & Immunol, Dar Es Salaam, Tanzania. [Goldenberg, Robert L.] Drexel Univ, Coll Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. RP Stringer, E (reprint author), Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. FU NIAID NIH HHS [N01 AI035173, N01 AI045200, U01 AI047972, U01 AI047972-01, U01 AI048005, U01 AI048005-01, U01 AI048006, U01 AI048006-01, U01-AI-47972] NR 19 TC 14 Z9 15 U1 0 U2 0 PU SA MEDICAL ASSOC PI PRETORIA PA BLOCK F CASTLE WALK CORPORATE PARK, NOSSOB STREET, ERASMUSKLOOF EXT3, PRETORIA, 0002, SOUTH AFRICA SN 0256-9574 EI 2078-5135 J9 SAMJ S AFR MED J JI SAMJ S. Afr. Med. J. PD JAN PY 2010 VL 100 IS 1 BP 58 EP 64 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 550QK UT WOS:000274142800020 PM 20429491 ER PT J AU Mattai, A Chavez, A Greenstein, D Clasen, L Bakalar, J Stidd, R Rapoport, J Gogtay, N AF Mattai, Anand Chavez, Alex Greenstein, Deanna Clasen, Liv Bakalar, Jennifer Stidd, Reva Rapoport, Judith Gogtay, Nitin TI Effects of clozapine and olanzapine on cortical thickness in childhood-onset schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Clozapine; Cortical thickness; Childhood-onset schizophrenia ID AUTOMATED 3-D EXTRACTION; GRAY-MATTER LOSS; ANTIPSYCHOTIC MEDICATIONS; ATYPICAL NEUROLEPTICS; BRAIN-DEVELOPMENT; DOUBLE-BLIND; MRI DATA; VOLUME; PSYCHOSIS; ABNORMALITIES AB Background: Little is known about the effects of antipsychotic medications on gray matter (GM) in schizophrenia. Although clozapine remains the most effective antipsychotic medication in treatment-refractory cases, it is unknown whether it has a differential effect on GM development. Methods: In an exploratory analysis, we used automated cortical thickness measurements and prospectively scanned childhood-onset schizophrenia (COS) patients who were maintained on one medication. Two atypical antipsychotic medications, clozapine (n=12, 37 scans) and olanzapine (n=12, 33 scans) were compared with respect to effects on cortical development, in contrast to GM trajectories of matched controls. Results: There were no significant differences in the trajectories of cortical thickness between the two treatment groups with the exception of a small circumscribed area in the right prefrontal cortex, where the olanzapine group showed thicker cortex As expected, both groups showed thinner GM compared to matched controls. Conclusions: Although these analyses do not rule out effects of antipsychotic medications on GM development in schizophrenia, they show no differential effect between clozapine and olanzapine on GM trajectory. Published by Elsevier B.V. C1 [Mattai, Anand; Chavez, Alex; Greenstein, Deanna; Clasen, Liv; Bakalar, Jennifer; Stidd, Reva; Rapoport, Judith; Gogtay, Nitin] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Mattai, A (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10,3 N202,10 Ctr Dr, Bethesda, MD 20892 USA. EM mattaia@mail.nih.gov RI Gogtay, Nitin/A-3035-2008; OI Chavez, Alexis/0000-0003-1322-4532 FU Intramural Research Program (IRP); National Institute of Mental Health (NIMH) in Bethesda, MD FX The present research was funded by the Intramural Research Program (IRP) at the National Institute of Mental Health (NIMH) in Bethesda, MD. NR 46 TC 27 Z9 27 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2010 VL 116 IS 1 BP 44 EP 48 DI 10.1016/j.schres.2009.10.018 PG 5 WC Psychiatry SC Psychiatry GA 547WR UT WOS:000273920900007 PM 19913390 ER PT J AU Collins, FS AF Collins, Francis S. TI Opportunities for Research and NIH SO SCIENCE LA English DT Editorial Material ID CELLS C1 NIH, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM collinsf@mail.nih.gov NR 7 TC 55 Z9 55 U1 0 U2 11 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 1 PY 2010 VL 327 IS 5961 BP 36 EP 37 DI 10.1126/science.1185055 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 541DZ UT WOS:000273395400018 PM 20044560 ER PT S AU Sahoo, SS Bodenreider, O Hitzler, P Sheth, A Thirunarayan, K AF Sahoo, Satya S. Bodenreider, Olivier Hitzler, Pascal Sheth, Amit Thirunarayan, Krishnaprasad BE Gertz, M Ludascher, B TI Provenance Context Entity (PaCE): Scalable Provenance Tracking for Scientific RDF Data SO SCIENTIFIC AND STATISTICAL DATABASE MANAGEMENT SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 22nd International Conference on Scientific and Statistical Database Management CY JUN 30-JUL 02, 2010 CL Heidelberg, GERMANY SP Heidelberg Univ, Heidelberg Inst Theoret Studies DE Provenance context entity; Biomedical knowledge repository; Context theory; RDF reification; Provenir ontology AB The Resource Description Framework (RDF) format is being used by a large number of scientific applications to store and disseminate their datasets. The provenance information, describing the source or lineage of the datasets, is playing an increasingly significant role in ensuring data quality, computing trust value of the datasets, and ranking query results. Current provenance tracking approaches using the RDF reification vocabulary suffer from a number of known issues, including lack of formal semantics, use of blank nodes, and application-dependent interpretation of reified RDF triples. In this paper, we introduce a new approach called Provenance Context Entity (PaCE) that uses the notion of provenance context to create provenance-aware RDF triples. We also define the formal semantics of PaCE through a simple extension of the existing RDF(S) semantics that ensures compatibility of PaCE with existing Semantic Web tools and implementations. We have implemented the PaCE approach in the Biomedical Knowledge Repository (BKR) project at the US National Library of Medicine. The evaluations demonstrate a minimum of 49% reduction in total number of provenance-specific RDF triples generated using the PaCE approach as compared to RDF reification. In addition, performance for complex queries improves by three orders of magnitude and remains comparable to the RDF reification approach for simpler provenance queries. C1 [Sahoo, Satya S.; Hitzler, Pascal; Sheth, Amit; Thirunarayan, Krishnaprasad] Wright State Univ, Kno E Sis Ctr, Dept Comp Sci & Engn, Dayton, OH 45435 USA. [Bodenreider, Olivier] Natl Lib Med, NIH, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. RP Sahoo, SS (reprint author), Wright State Univ, Kno E Sis Ctr, Dept Comp Sci & Engn, Dayton, OH 45435 USA. EM sahoo.2@wright.edu; obodenreider@mail.nih.gov; pascal.hitzler@wright.edu; amit.sheth@wright.edu; t.k.prasad@wright.edu FU Intramural Research Program of the NIH; U.S. NLM; NIH RO1 [1R01HL087795-01A1] FX This research was supported in part by the Intramural Research Program of the NIH, U.S. NLM and NIH RO1 Grant 1R01HL087795-01A1. The authors would like to thank Tom Rindflesch, Marcelo Fiszman, Genaro Hernandez and Ramez Ghazzaoui for their extensive help. The open source version of the Virtuoso triple store is made available by OpenLink Software NR 13 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-13817-1 J9 LECT NOTES COMPUT SC PY 2010 VL 6187 BP 461 EP + PG 3 WC Computer Science, Information Systems; Computer Science, Theory & Methods SC Computer Science GA BSZ16 UT WOS:000286148800032 ER PT J AU Narva, AS Sequist, TD AF Narva, Andrew S. Sequist, Thomas D. TI Reducing Health Disparities in American Indians With Chronic Kidney Disease SO SEMINARS IN NEPHROLOGY LA English DT Review DE American Indian; health disparities; chronic kidney disease; end-stage renal disease; Native Americans ID STAGE RENAL-DISEASE; PRIMARY-CARE; HEMODIALYSIS; PERFORMANCE; PREVALENCE; OUTCOMES; PROJECT; BURDEN C1 [Narva, Andrew S.] Natl Inst Diabet & Digest Kidney Dis, Natl Kidney Dis Educ Program, Div Kidney Urol & Hematol Dis, NIH,Indian Hlth Serv, Bethesda, MD 20892 USA. [Sequist, Thomas D.] Brigham & Womens Hosp, Dept Med, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Sequist, Thomas D.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Narva, AS (reprint author), Natl Inst Diabet & Digest Kidney Dis, Natl Kidney Dis Educ Program, Div Kidney Urol & Hematol Dis, NIH,Indian Hlth Serv, 2 Democracy Plaza,Room 644,6707 Democracy Blvd,MS, Bethesda, MD 20892 USA. EM narvaa@niddk.nih.gov NR 28 TC 11 Z9 11 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD JAN PY 2010 VL 30 IS 1 BP 19 EP 25 DI 10.1016/j.semnephrol.2009.10.007 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 617CF UT WOS:000279257700005 PM 20116644 ER PT J AU Rubin, P Williams, JP Devesa, SS Travis, LB Constine, LS AF Rubin, Philip Williams, Jacqueline P. Devesa, Susan S. Travis, Lois B. Constine, Louis S. TI Cancer Genesis Across the Age Spectrum: Associations With Tissue Development, Maintenance, and Senescence SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID PREVENTION; IMPACT; CELLS AB Cancer genesis across the age spectrum is a complex, multifactorial process, and parallels changes in site-specific tissue development, maintenance, and senescence. Cancer is not a single disease, and different tumor and stem cells may demonstrate various manifestations of abnormal function. Mutations in DNA, some random and some explained by exogenous insults, accompanied by changes in the tissue microenvironment, generally precede the onset of aberrant replication and apoptosis. Moreover, increasing evidence suggests that genetic programs normally active only during development of human beings may be reactivated during tumorigenesis. The complicated underlying biology of human growth, development, and carcinogenesis is reflected in the highly disparate patterns in site-specific cancer incidence rates across age groups. In childhood, the peak years of an organ system's increase in size correlate with peak years of cancer incidence. Conversely, in most adult-onset cancers, it is exposure to exogenous toxins, the failure of maintenance and repair, and finally, dysfunction(s) in the normal cellular aging process that likely play a role in the development of these malignancies. Additional basic science investigations and epidemiologic studies will assist in our understanding of the mechanisms that underlie the notable difference in site-specific cancer incidence according to age. Semin Radiat Oncol 20:3-11 (C) 2010 Elsevier Inc. All rights reserved. C1 [Constine, Louis S.] Univ Rochester, Med Ctr, Dept Radiat Oncol, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. [Devesa, Susan S.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Constine, Louis S.] Univ Rochester, Med Ctr, Dept Pediat, Rochester, NY 14642 USA. RP Constine, LS (reprint author), Univ Rochester, Med Ctr, Dept Radiat Oncol, James P Wilmot Canc Ctr, 601 Elmwood Ave,Box 647, Rochester, NY 14642 USA. EM louis_constine@urmc.rochester.edu NR 29 TC 13 Z9 13 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 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JAN PY 2010 VL 20 IS 1 BP 3 EP 11 DI 10.1016/j.semradonc.2009.08.001 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 619EM UT WOS:000279412000002 PM 19959026 ER PT J AU Ng, AK Kenney, LB Gilbert, ES Travis, LB AF Ng, Andrea K. Kenney, Lisa B. Gilbert, Ethel S. Travis, Lois B. TI Secondary Malignancies Across the Age Spectrum SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID CHILDHOOD-CANCER SURVIVOR; ACUTE LYMPHOBLASTIC-LEUKEMIA; SURGICAL ADJUVANT BREAST; ACUTE MYELOID-LEUKEMIA; LONG-TERM SURVIVORS; CAUSE-SPECIFIC MORTALITY; STAGE HODGKINS-DISEASE; SOFT-TISSUE SARCOMA; NESTED CASE-CONTROL; EXTENDED FOLLOW-UP AB Development of a second malignancy is one of the most serious late effects in survivors of both childhood and adult-onset cancers. Patterns of second malignancy risk across the age spectrum can differ in terms of the types of second malignancies observed, magnitude of the risks, the latency period, associated risk factors, and modifying influences. Potential explanations for the varying risk patterns by age include differences in susceptibility of individual tissue/organ to carcinogenesis based on stage of development and level of tissue maturity, microenvironment, attained age, and lifestyle factors. A thorough understanding of these differences is essential when considering treatment modifications in newly diagnosed cancer patients who are aimed at reducing the risk of second malignancy and other late effects without compromising cure. Moreover, an understanding of the variations in second cancer risk according to age at treatment is important in customizing patient follow-up. Semin Radiat Oncol 20:67-78 (C) 2010 Elsevier Inc. All rights reserved. C1 [Ng, Andrea K.; Kenney, Lisa B.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Ng, Andrea K.; Kenney, Lisa B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Gilbert, Ethel S.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Travis, Lois B.] Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA. RP Ng, AK (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St,ASBI L2, Boston, MA 02115 USA. EM ang@lroc.harvard.edu FU Intramural NIH HHS [ZIA CP010131-17] NR 120 TC 41 Z9 41 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 EI 1532-9461 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JAN PY 2010 VL 20 IS 1 BP 67 EP 78 DI 10.1016/j.semradonc.2009.09.002 PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 619EM UT WOS:000279412000009 PM 19959033 ER PT S AU Shin, YK Egan, JM AF Shin, Yu-Kyong Egan, Josephine M. BE Meyerhof, W Beisiegel, U Joost, HG TI Roles of Hormones in Taste Signaling SO SENSORY AND METABOLIC CONTROL OF ENERGY BALANCE SE Results and Problems in Cell Differentiation LA English DT Article; Book Chapter ID GLUCAGON-LIKE PEPTIDE-1; VASOACTIVE INTESTINAL POLYPEPTIDE; DIABETIC DB/DB MOUSE; GALANIN RECEPTOR SUBTYPES; NEUROPEPTIDE-Y RECEPTORS; CENTRAL NERVOUS-SYSTEM; CHORDA TYMPANI NERVE; BETA-CELL FUNCTION; LEPTIN RECEPTOR; FOOD-INTAKE AB Proper nutrition, avoidance of ingesting substances that are harmful to the whole organism, and maintenance of energy homeostasis are crucial for living organisms. Additionally, mammals possess a sophisticated system to control the types and content of food that we swallow. Gustation is a vital sensory skill for determining which food stuffs to ingest and which to avoid, and for maintaining metabolic homeostasis. It is becoming apparent that there is a strong link between metabolic control and flavor perception. Although the gustatory system critically influences food preference, food intake, and metabolic homeostasis, the mechanisms for modulating taste sensitivity by metabolic hormones are just now being explored. It is likely that hormones produced in the tongue influence the amounts and types of food that we eat: the hormones that we associate with appetite control, glucose homeostasis and satiety, such as glucagon-like peptide-1, cholecystokinin, and neuropeptide Y are also produced locally in taste buds. In this report, we will provide an overview of the peptidergic endocrine hormone factors that are present or are known to have effects within the gustatory system, and we will discuss their roles, where known, in taste signaling. C1 [Shin, Yu-Kyong; Egan, Josephine M.] NIA, Diabet Sect, NIH, Baltimore, MD 21224 USA. RP Egan, JM (reprint author), NIA, Diabet Sect, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM eganj@grc.nia.nih.gov FU Intramural NIH HHS NR 130 TC 8 Z9 8 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-1844 BN 978-3-642-14425-7 J9 RESULTS PROBL CELL D JI Results Probl. Cell Differ. PY 2010 VL 52 BP 115 EP 137 DI 10.1007/978-3-642-14426-4_10 D2 10.1007/978-3-642-14426-4 PG 23 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BRL23 UT WOS:000283006600010 PM 20865376 ER PT B AU Aravind, L Iyer, LM Anantharaman, V AF Aravind, L. Iyer, Lakshminarayan M. Anantharaman, Vivek BE Spiro, S Dixon, R TI Natural History of Sensor Domains in Bacterial Signalling Systems SO SENSORY MECHANISMS IN BACTERIA: MOLECULAR ASPECTS OF SIGNAL RECOGNITION LA English DT Article; Book Chapter ID C-DI-GMP; PROTEIN-KINASE SUPERFAMILY; COMPLETE GENOME SEQUENCE; SERINE THREONINE KINASE; LIGAND-BINDING DOMAIN; GATED ION-CHANNEL; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; HISTIDINE KINASE; REGULATORY PROTEIN AB Organisms sense stimuli at the molecular level using a relatively small set of protein domains. Computational analysis of protein sequences along with directed experimental studies have played a major role in the characterization of these protein domains. These sensor domains directly or indirectly detect a vast array of sensory inputs such as solutes, gases, redox potential and light. Here, we systematically survey the types of sensor domains found in bacterial signalling proteins. We summarize the key aspects of their structure that are central to their functions and their associations with other signalling domains. Despite the advances several of these domains remain poorly understood in terms of their structure, ligands and functional significance. We accordingly try to highlight the significance of some of the under-appreciated sensor domains. Genomic analysis reveals that the architectural complexity of sensory domains increases with the number of sensor proteins in a genome, with a gradual plateau towards a point where newer combinations of domains do not provide major selective advantage. Syntactical analysis of domain architectures shows several discernable patterns that have functional relevance, especially in terms of the constraints introduced by signal transmission domains such as HAMP and S-helix modules. Across bacteria, the number of signalling proteins shows a positive correlation with respect to proteome size. However, there is a clear distinction in the trends between bacteria that react directly and rapidly to a large number of small molecule signals vis-a-vis those that possess distinct signalling systems related to developmental complexity. Analysis of scaling trends for individual sensor domains shows that lifestyle strategies play a major role in the selection of the type and number of these domains in an organism. From an evolutionary viewpoint, the vast majority of sensory domains appear to have their origins in the bacteria and have been widely transferred to other superkingdoms of life. In particular, most major eukaryotic sensor domains appear to have their antecedents in bacteria. C1 [Aravind, L.; Iyer, Lakshminarayan M.; Anantharaman, Vivek] NIH, Computat Biol Branch, Bethesda, MD 20892 USA. RP Aravind, L (reprint author), NIH, Computat Biol Branch, Bldg 10, Bethesda, MD 20892 USA. EM aravind@mail.nih.gov; lakshmin@mail.nih.gov; ananthar@mail.nih.gov NR 181 TC 11 Z9 11 U1 0 U2 6 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-904455-69-1 PY 2010 BP 1 EP 38 PG 38 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA BRS13 UT WOS:000283520300001 ER PT J AU Wong, C Berkowitz, Z Saraiya, M Wideroff, L Benard, VB AF Wong, Charlene Berkowitz, Zahava Saraiya, Mona Wideroff, Louise Benard, Vicki B. TI US physicians' intentions regarding impact of human papillomavirus vaccine on cervical cancer screening SO SEXUAL HEALTH LA English DT Article DE Pap cytology; prevention ID EARLY-DETECTION PROGRAM; UNITED-STATES; PRACTICE GUIDELINES; NATIONAL BREAST; HPV VACCINATION; HEALTH; WOMEN; ERA AB Background: US cervical cancer screening recommendations have not changed since the human papillomavirus (HPV) vaccine introduction in 2006, but epidemiological and cost-effectiveness studies indicate that recommendations will need to change for fully vaccinated women. We evaluated physician intentions regarding HPV vaccine's impact on future screening. Methods: A nationally representative sample of 1212 primary care physicians was surveyed in 2006-2007 (response rate: 67.5%). Our study included 1114 physicians who provided Pap testing. Questions covered Pap test screening practices and intentions regarding HPV vaccine's impact on screening. Distribution differences were assessed using chi(2) statistics; multivariate analyses were performed. Results: Overall, 40.7% (95% confidence interval (CI): 37.6-43.8%) of physicians agreed that the HPV vaccine will affect screening initiation, and 38.2% (35.0-41.5%) agreed that vaccination will affect screening frequency. Significant differences in responses were found by specialty; internists were more likely to agree that vaccination would impact screening than other specialties. Belief in the effectiveness of new screening technologies was associated with intention to change screening initiation (odds ratio (OR) = 1.66 (1.20-2.31)) and frequency (OR = 1.99 (1.40-2.83)). Adherence to current Pap test screening interval guidelines was associated with intention to change screening frequency (OR = 1.39 (1.01-1.91)). Conclusions: Many providers anticipate adjusting screening for vaccinated women, but a significant group believes nothing will change or are unsure. The present study provides important baseline data on intentions in the period preceding widespread vaccine diffusion and may help explain current and future trends in practice patterns. C1 [Wong, Charlene; Berkowitz, Zahava; Saraiya, Mona; Benard, Vicki B.] Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. [Wideroff, Louise] NCI, Bethesda, MD 20892 USA. RP Wong, C (reprint author), Ctr Dis Control & Prevent, 4770 Buford Highway,Mailstop K-55, Atlanta, GA 30341 USA. EM hrl5@cdc.gov RI Hernandez, Jessica/G-6527-2011 FU National Cancer Institute contract and Interagency Agreements with the Centers for Disease Control and Prevention; Agency for Healthcare Research and Quality; External Medical Affairs; Pfizer Inc. FX Grant support from a National Cancer Institute contract and Interagency Agreements with the Centers for Disease Control and Prevention and the Agency for Healthcare Research and Quality.; Selected data were presented at the 2009 International Papillomavirus Conference. We thank Dr Carrie Klabunde of the National Cancer Institute and Dr Caroline McLeod of WESTAT (Rockville, MD, USA) for survey research work. Charlene Wong completed this project during her 1-year fellowship The CDC Experience, a public/private partnership supported by a grant to the CDC Foundation from External Medical Affairs, Pfizer Inc. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the National Cancer Institute. NR 30 TC 6 Z9 6 U1 0 U2 2 PU CSIRO PUBLISHING PI COLLINGWOOD PA 150 OXFORD ST, PO BOX 1139, COLLINGWOOD, VICTORIA 3066, AUSTRALIA SN 1448-5028 J9 SEX HEALTH JI Sex Health PY 2010 VL 7 IS 3 BP 338 EP 345 DI 10.1071/SH09115 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 640EA UT WOS:000281029900020 PM 20719225 ER PT S AU Schrey, D Walsh, TJ Groll, AH AF Schrey, Dominik Walsh, Thomas J. Groll, Andreas H. BE Aronson, JK TI Antifungal drugs SO SIDE EFFECTS OF DRUGS ANNUAL 32: A WORLDWIDE YEARLY SURVEY OF NEW DATA AND TRENDS IN ADVERSE DRUG REACTIONS AND INTERACTIONS SE Side Effects of Drugs Annual LA English DT Article; Book Chapter ID LIPOSOMAL AMPHOTERICIN-B; INVASIVE FUNGAL-INFECTIONS; STEM-CELL TRANSPLANTATION; AZOLE-REFRACTORY OROPHARYNGEAL; CUTANEOUS LUPUS-ERYTHEMATOSUS; VERSUS-HOST-DISEASE; TORSADES-DE-POINTES; PHARMACOKINETIC INTERACTION; HEALTHY-VOLUNTEERS; HEMATOLOGIC MALIGNANCIES C1 [Schrey, Dominik; Groll, Andreas H.] Univ Childrens Hosp, Infect Dis Res Program, Ctr Bone Marrow Transplantat, D-48129 Munster, Germany. [Schrey, Dominik; Groll, Andreas H.] Univ Childrens Hosp, Dept Hematol Oncol, D-48129 Munster, Germany. [Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Schrey, D (reprint author), Univ Childrens Hosp, Infect Dis Res Program, Ctr Bone Marrow Transplantat, Albert Schweitzer Str 33, D-48129 Munster, Germany. EM Dominik.Schrey@ukmuenster.de; thomaswalshmd@gmail.com; grollan@ukmuenster.de NR 132 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBLISHERS BV BIOMEDICAL DIVISION PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-6080 BN 978-0-44-453551-1 J9 SIDE EFFECT JI Side Eff. Drug Annu. PY 2010 VL 32 BP 491 EP 519 DI 10.1016/S0378-6080(10)32027-7 PG 29 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCX05 UT WOS:000311807800029 ER PT S AU Giubellino, A Arany, PR AF Giubellino, Alessio Arany, Praveen R. BE Wu, WS Hu, CT TI Grb2 and Other Adaptor Proteins in Tumor Metastasis SO SIGNAL TRANSDUCTION IN CANCER METASTASIS SE Cancer Metastasis Biology and Treatment LA English DT Article; Book Chapter DE Adaptor proteins; Grb2; Metastasis; Signaling ID GROWTH-FACTOR RECEPTOR; FOCAL ADHESION KINASE; HUMAN BREAST-CANCER; MELANOMA INHIBITORY-ACTIVITY; CHRONIC MYELOGENOUS LEUKEMIA; DOMAIN-BINDING ANTAGONIST; WISKOTT-ALDRICH SYNDROME; RAS SIGNALING PATHWAY; FACTOR-I RECEPTOR; SH3 DOMAIN AB Metastatic disease is a major source of cancer morbidity and mortality. Understanding the molecular basis of cancer metastasis will have a considerable impact on cancer therapy. We now understand that uncontrolled cell signaling is of great importance in oncogenesis and tumor progression. A major role in the assembly of signaling proteins into biochemical pathways and networks is played by adaptor proteins. In this chapter we describe specifically the role of these proteins in the process of tumor metastasis and the potential for cancer therapy. Historically considered undruggable targets, protein-protein interactions and adaptor proteins are emerging as rational and viable targets, as exemplified by the development of selective antagonist of the adaptor protein Grb2. Targeting adaptor proteins and cellular miswiring is an emerging and exciting, cancer therapeutic opportunity. C1 [Giubellino, Alessio] NCI, NIH, Bethesda, MD 20892 USA. [Arany, Praveen R.] Harvard Univ, Cambridge, MA 02138 USA. RP Giubellino, A (reprint author), NCI, NIH, 10 Ctr Dr,Bldg 10-CRC,Rm 1W-5832, Bethesda, MD 20892 USA. EM giubella@mail.nih.gov; arany@fas.harvard.edu OI Giubellino, Alessio/0000-0002-5352-0662 NR 165 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1568-2102 BN 978-90-481-9521-3 J9 CANCER METAST BIOL T JI Cancer Metastasis-Biol Treat PY 2010 VL 15 BP 77 EP 102 DI 10.1007/978-90-481-9522-0_5 D2 10.1007/978-90-481-9522-0 PG 26 WC Oncology SC Oncology GA BRN65 UT WOS:000283184000005 ER PT B AU Ambudkar, IS Ong, HL Singh, BB AF Ambudkar, Indu S. Ong, Hwei L. Singh, Brij B. BE Sitaramayya, A TI Molecular and Functional Determinants of Ca2+ Signaling Microdomains SO SIGNAL TRANSDUCTION: PATHWAYS, MECHANISMS AND DISEASES LA English DT Article; Book Chapter ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; CAPACITATIVE CALCIUM-ENTRY; PLASMA MEMBRANE JUNCTIONS; STORE-OPERATED CHANNELS; NITRIC-OXIDE SYNTHASE; SALIVARY-GLAND CELLS; LIPID RAFT DOMAINS; ENDOPLASMIC-RETICULUM; TRPC CHANNELS; SMOOTH-MUSCLE C1 [Ambudkar, Indu S.; Ong, Hwei L.] NIDCR, Secretory Physiol Sect, MPTB, NIH, Bethesda, MD 20892 USA. [Singh, Brij B.] Univ N Dakota, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Grand Forks, ND 58201 USA. RP Ambudkar, IS (reprint author), NIDCR, Secretory Physiol Sect, MPTB, NIH, Bethesda, MD 20892 USA. EM indu.ambudkar@nih.gov OI Singh, Brij/0000-0003-0535-5997 NR 111 TC 3 Z9 3 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-3-642-02111-4 PY 2010 BP 237 EP 253 DI 10.1007/978-3-642-02112-1_13 D2 10.1007/978-3-642-02112-1 PG 17 WC Cell Biology SC Cell Biology GA BMV96 UT WOS:000273693600013 ER PT B AU Thorgeirsson, SS Factor, VM AF Thorgeirsson, Snorri S. Factor, Valentina M. BE Dufour, JF Clavien, PA TI The MYC Network and Cancer SO SIGNALING PATHWAYS IN LIVER DISEASES, SECOND EDITION LA English DT Article; Book Chapter ID ARF TUMOR-SUPPRESSOR; C-MYC; CELL-CYCLE; PROTEIN STABILITY; TARGET GENES; IN-VIVO; EXPRESSION; TRANSFORMATION; APOPTOSIS; PATHWAY C1 [Thorgeirsson, Snorri S.; Factor, Valentina M.] 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, 37 Convent Dr, Bethesda, MD 20892 USA. EM thorgeis@mail.nih.gov NR 54 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-3-642-00149-9 PY 2010 BP 359 EP 365 DI 10.1007/978-3-642-00150-5_24 D2 10.1007/978-3-642-00150-5 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BNL44 UT WOS:000274861500024 ER PT S AU Margolis, RN Christakos, S AF Margolis, Ronald N. Christakos, Sylvia BE Zaidi, M TI The nuclear receptor superfamily of steroid hormones and vitamin D gene regulation An update SO SKELETAL BIOLOGY AND MEDICINE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT New York Skeletal Biology and Medicine Conference CY APR 29-MAY 02, 2009 CL Mt Sinai Sch Med, New York, NY HO Mt Sinai Sch Med DE nuclear receptor; steroid hormones; vitamin D ID POTENTIAL VANILLOID TYPE-6; UNION-OF-PHARMACOLOGY; 1,25-DIHYDROXYVITAMIN D-3; SIGNALING ATLAS; BONE-FORMATION; CELLS; HOMEOSTASIS; METABOLISM; EXPRESSION; MICE AB Nuclear receptors bind to chromatin and seed formation of complexes comprising coregulators at the hormone response element. Nuclear receptors and coregulators can mediate chromatin remodeling, epigenetic modification, and ultimately gene expression. Chromatin immunoprecipitation has shown that nuclear receptors bind to chromatin throughout the genome, often at locations distant from the transcription start site. New findings related to the regulation of key vitamin D target genes in intestine and bone as well as nonclassical actions of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], including effects on breast cancer cells and on the immune system, are discussed. These studies will form the basis for future studies examining global networks regulated by the vitamin D receptor. It is becoming increasingly recognized that the actions of 1,25(OH)(2)D(3), similar to those of other steroids, is complex, involving regulation of gene activity at a range of locations. C1 [Margolis, Ronald N.] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. [Christakos, Sylvia] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. RP Margolis, RN (reprint author), NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Democracy 2,Room 693,6707 Democracy Blvd, Bethesda, MD 20892 USA. EM margolisr@mail.nih.gov OI Margolis, Ronald/0000-0002-8956-0455 FU NIDDK NIH HHS [R01 DK038961, R01 DK038961-22] NR 40 TC 24 Z9 25 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-785-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1192 BP 208 EP 214 DI 10.1111/j.1749-6632.2009.05227.x PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BOV34 UT WOS:000277762400029 PM 20392238 ER PT S AU Williams, JP Micoli, K McDonald, JM AF Williams, John P. Micoli, Keith McDonald, Jay M. BE Zaidi, M TI Calmodulin-an often-ignored signal in osteoclasts SO SKELETAL BIOLOGY AND MEDICINE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT New York Skeletal Biology and Medicine Conference CY APR 29-MAY 02, 2009 CL Mt Sinai Sch Med, New York, NY HO Mt Sinai Sch Med DE osteoclasts; calcium; calmodulin; calcineurin; calmodulin kinase II; apoptosis ID OVARIECTOMIZED RAT; BONE-RESORPTION; TAMOXIFEN; DIFFERENTIATION; APOPTOSIS; ACTIVATION; EXPRESSION; ESTROGEN; BINDING; ALPHA AB Calcium signaling plays a key role in bone turnover, regulating both osteoblasts and osteoclasts. Despite this the role of calmodulin, the primary intracellular calcium receptor regulatory protein, has received little attention. In this brief review, the function of Ca(2+)/calmodulin signaling in osteoclast development, function, and apoptosis is reviewed. Considerable evidence supports an important regulatory role for Ca(2+)/calmodulin signaling in each of these processes. The overall role of Ca(2+)/calmodulin in regulating bone turnover is also supported by animal and human studies showing that calmodulin antagonists preserve bone mass. C1 [McDonald, Jay M.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. [Williams, John P.] NIA, Div Aging Biol, Bethesda, MD 20892 USA. [Micoli, Keith] Sackler Inst Grad Biomed Sci, New York, NY USA. [McDonald, Jay M.] Vet Adm Med Ctr, Birmingham, AL USA. RP McDonald, JM (reprint author), Univ Alabama, Dept Pathol, LHRB 509,701 S 19th St, Birmingham, AL 35294 USA. EM mcdonald@uab.edu FU National Institutes of Health [P30 AR046031] FX The author's work was supported by a grant from the National Institutes of Health (P30 AR046031; J.M.M.). NR 24 TC 8 Z9 10 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-785-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1192 BP 358 EP 364 DI 10.1111/j.1749-6632.2009.05242.x PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BOV34 UT WOS:000277762400051 PM 20392260 ER PT J AU Buckley, A Rodriguez, AJ Jennison, K Buckley, J Thurm, A Sato, S Swedo, S AF Buckley, A. Rodriguez, A. J. Jennison, K. Buckley, J. Thurm, A. Sato, S. Swedo, S. TI REM SLEEP DEFICIENCY IN CHILDREN WITH AUTISM COMPARED TO CHILDREN WITH DEVELOPMENTAL DELAY AND TYPICAL DEVELOPMENT SO SLEEP LA English DT Meeting Abstract C1 [Buckley, A.; Jennison, K.; Thurm, A.; Swedo, S.] NIMH, Bethesda, MD 20892 USA. [Buckley, A.] NYU, Child Study Ctr, New York, NY USA. [Buckley, J.] NYU, HMSS, New York, NY USA. [Sato, S.] NINDS, EEG, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2010 VL 33 SU S MA 1010 BP A337 EP A337 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V21LB UT WOS:000208208001493 ER PT J AU Ghofrani, P Lewin, DS Laposky, A Twery, M AF Ghofrani, P. Lewin, D. S. Laposky, A. Twery, M. TI OVERVIEW OF SLEEP RESEARCH GRANTS FUNDED BY THE NATIONAL INSTITUTES OF HEALTH SO SLEEP LA English DT Meeting Abstract C1 [Ghofrani, P.; Lewin, D. S.; Laposky, A.; Twery, M.] NHLBI, Natl Ctr Sleep Disorders Res, Div Lung Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2010 VL 33 SU S MA 1095 BP A366 EP A366 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V21LB UT WOS:000208208001578 ER PT J AU Lamb, A Shockley, KR Raizen, DM AF Lamb, A. Shockley, K. R. Raizen, D. M. TI HOMEOSTASIS OF A C. ELEGANS SLEEP-LIKE STATE SO SLEEP LA English DT Meeting Abstract C1 [Lamb, A.; Raizen, D. M.] U Penn Sch Med, Philadelphia, PA USA. [Shockley, K. R.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2010 VL 33 SU S MA 0170 BP A59 EP A59 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V21LB UT WOS:000208208000172 ER PT J AU Laposky, A Lewin, D Mussolino, M Twery, M Wolz, M AF Laposky, A. Lewin, D. Mussolino, M. Twery, M. Wolz, M. TI PREVALENCE OF SLEEP DISORDERED BREATHING SYMPTOMATOLOGY IN THE US POPULATION SO SLEEP LA English DT Meeting Abstract C1 [Laposky, A.; Lewin, D.; Twery, M.] NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA. [Mussolino, M.; Wolz, M.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2010 VL 33 SU S MA 0363 BP A127 EP A128 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V21LB UT WOS:000208208000366 ER PT J AU Sharkey, KM Carskadon, MA Figueiro, MG Zhu, Y Gordon, HW Crowley, SJ Rea, MS AF Sharkey, K. M. Carskadon, M. A. Figueiro, M. G. Zhu, Y. Gordon, H. W. Crowley, S. J. Rea, M. S. TI THE ROLES OF A MORNING BLUE-LIGHT INTERVENTION AND AN EARLIER SLEEP SCHEDULE IN PHASE ADVANCING DIM LIGHT MELATONIN ONSET (DLMO) OF YOUNG ADULTS SO SLEEP LA English DT Meeting Abstract C1 [Sharkey, K. M.; Carskadon, M. A.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Figueiro, M. G.; Rea, M. S.] Rensselaer Polytech Inst, Lighting Res Ctr, Troy, NY USA. [Zhu, Y.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Gordon, H. W.] Natl Inst Drug Abuse, Div Clin Neurosci & Behav Res, Clin Neurosci Branch, Bethesda, MD USA. [Crowley, S. J.] Rush Univ, Med Ctr, Dept Behav Sci, Biol Rhythms Res Lab, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2010 VL 33 SU S MA 0195 BP A68 EP A68 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V21LB UT WOS:000208208000197 ER PT S AU Kelly, RJ Rixe, O AF Kelly, Ronan Joseph Rixe, Olivier BE Martens, UM TI Axitinib (AG-013736) SO SMALL MOLECULES IN ONCOLOGY SE Recent Results in Cancer Research LA English DT Article; Book Chapter ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; RECEPTOR TYROSINE KINASES; THYROID-CARCINOMA; PHASE-II; TUMOR ANGIOGENESIS; RANDOMIZED-TRIAL; HIGH EXPRESSION; POOR-PROGNOSIS; FACTOR VEGF AB The vascular endothelial growth factor (VEGF)/VEGF receptor tyrosine kinase (RTK) signaling pathway plays a pivotal role in tumor angiogenesis. Neovascularization promotes increased tumor cell proliferation, survival and metasasis. Many antiangiogenic agents including multi-RTK inhibitors are either approved or are undergoing testing in clinical trials. Axitinib is a potent and selective inhibitor of VEGF RTK 1, 2, and 3. This chapter discusses the structure of axitinib as well as its toxicities and drug interactions. Important preclinical and clinical data for axitinib are presented including findings from phase 11 studies in many tumor types including malignant melanoma and renal, pancreatic, thyroid, breast, lung and colorectal carcinomas. Ongoing phase III studies in pancreatic and metastatic renal cell carcinoma will ultimately define the therapeutic role of this targeted agent. C1 [Kelly, Ronan Joseph] NCI, Thorac Oncol Dept, Med Oncol Branch, Bethesda, MD 20892 USA. RP Kelly, RJ (reprint author), NCI, Thorac Oncol Dept, Med Oncol Branch, Bethesda, MD 20892 USA. EM kellyro@mail.nih.gov; olivier.rixe@yahoo.com NR 42 TC 23 Z9 25 U1 1 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 978-3-642-01221-1 J9 RECENT RESULTS CANC JI Rec. Res. Camcer Res. PY 2010 VL 184 BP 33 EP 44 DI 10.1007/978-3-642-01222-8_3 D2 10.1007/978-3-642-01222-8 PG 12 WC Oncology SC Oncology GA BMQ41 UT WOS:000273346300003 PM 20072829 ER PT J AU Adikes, KA Hull, SC Danis, M AF Adikes, Katherin A. Hull, Sara C. Danis, Marion TI The Views of Low-Income Employees Regarding Mandated Comprehensive Employee Benefits for the Sake of Health SO SOCIAL WORK IN PUBLIC HEALTH LA English DT Article DE Public participation; socioeconomic factors; fringe benefits; inequality; insurance benefits; employees ID SOCIAL DETERMINANTS; CARE COSTS; PROMOTION; PROGRAM AB Socioeconomic factors stand in the way of good health for low-income populations. We suggest that employee benefits might serve as a means of improving the health of low-wage earners. We convened groups of low-income earners to design hypothetical employee benefit packages. Qualitative analysis of group discussions regarding state-mandated benefits indicated that participants were interested in a great variety of benefits, beyond health care, that address socioeconomic determinants of health. Long-term financial and educational investments were of particular value. These results may facilitate the design of employee benefits that promote the health of low-income workers. C1 [Adikes, Katherin A.] NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Adikes, KA (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10,Room 1C118,10 Ctr Dr,MSC 1156, Bethesda, MD 20892 USA. EM kadikes@umich.edu FU Intramural NIH HHS [Z01 CL010526-05] NR 32 TC 0 Z9 0 U1 0 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1937-1918 J9 SOC WORK PUBLIC HLTH JI Soc. Work Public Health PY 2010 VL 25 IS 1 BP 102 EP 123 DI 10.1080/19371910903126648 PG 22 WC Public, Environmental & Occupational Health; Social Work SC Public, Environmental & Occupational Health; Social Work GA 837ZU UT WOS:000296255600008 PM 20391255 ER PT J AU Galanis, J Nossal, R Harries, D AF Galanis, Jennifer Nossal, Ralph Harries, Daniel TI Depletion forces drive polymer-like self-assembly in vibrofluidized granular materials SO SOFT MATTER LA English DT Article ID SIZE SEPARATION; SPHERE MIXTURES; ROD; BEHAVIOR; PHASE; MEMBRANES; DYNAMICS; GASES; LONG; THIN AB Ranging from nano-to granular-scales, control of particle assembly can be achieved by limiting the available free space, for example by increasing the concentration of particles (crowding) or through their restriction to 2D environments. It is unclear, however, if self-assembly principles governing thermally equilibrated molecules can also apply to mechanically excited macroscopic particles in non-equilibrium steady-state. Here we show that low densities of vibrofluidized steel rods, when crowded by high densities of spheres and confined to quasi-2D planes, can self-assemble into linear polymer-like structures. Our 2D Monte Carlo simulations show similar finite sized aggregates in thermally equilibrated binary mixtures. Using theory and simulations, we demonstrate how depletion interactions create oriented "binding" forces between rigid rods to form these "living polymers." Unlike rod-sphere mixtures in 3D that can demonstrate well-defined equilibrium phases in coexistence, our mixtures confined to 2D lack these transitions because lower dimensionality favors the formation of linear aggregates, thus suppressing a true phase transition. The qualitative and quantitative agreement between equilibrium and granular patterning for these mixtures suggests that entropy maximization is the determining driving force for bundling. Furthermore, this study uncovers a previously unknown patterning behavior at both the granular and nanoscales, and may provide insights into the role of crowding at interfaces in molecular assembly. C1 [Galanis, Jennifer; Nossal, Ralph] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Galanis, Jennifer; Harries, Daniel] Hebrew Univ Jerusalem, Inst Chem, IL-91904 Jerusalem, Israel. [Galanis, Jennifer; Harries, Daniel] Hebrew Univ Jerusalem, Fritz Haber Ctr, IL-91904 Jerusalem, Israel. RP Galanis, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. EM galanisj@mail.nih.gov; daniel@fh.huji.ac.il RI Harries, Daniel/F-7016-2012 OI Harries, Daniel/0000-0002-3057-9485 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; Israel Science Foundation (ISF) [1011/07, 1012/07]; Minerva Foundation, Munich, Germany FX We thank W. Losert for interesting discussions and D. Lathrop for use of the shaker. This research was supported by intramural funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, Md. (http://biowulf.nih.gov). DH acknowledges financial support from the Israel Science Foundation (ISF Grant No. 1011/07) as well as an allocation for a high-performance computer cluster facility (ISF Grant No. 1012/07). The Fritz Haber research center is supported by the Minerva Foundation, Munich, Germany. NR 42 TC 11 Z9 11 U1 0 U2 15 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1744-683X J9 SOFT MATTER JI Soft Matter PY 2010 VL 6 IS 5 BP 1026 EP 1034 DI 10.1039/b918034f PG 9 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Multidisciplinary; Polymer Science SC Chemistry; Materials Science; Physics; Polymer Science GA 559MW UT WOS:000274830500026 PM 22039392 ER PT J AU Lin, DC Douglas, JF Horkay, F AF Lin, David C. Douglas, Jack F. Horkay, Ferenc TI Development of minimal models of the elastic properties of flexible and stiff polymer networks with permanent and thermoreversible cross-links SO SOFT MATTER LA English DT Article ID SOFT GLASSY MATERIALS; RUBBER ELASTICITY; LOCALIZATION MODEL; MOLECULAR THEORY; SCALING APPROACH; STRAIN BEHAVIOR; ACTIN NETWORKS; STRESS; GELS; THERMODYNAMICS AB We review the elasticity of flexible and stiff polymer networks with permanent cross-links and synthesize these results into a unifying polymer chain network model. This framework is then used to address how the network elasticity becomes modified when the network cross-linking is thermoreversible in nature, changes in the stability of the network with deformation, and the effect of a variable rate of network deformation on the non-linear elastic response. Comparisons are made between this class of simplified network models with elasticity measurements performed on flexible chain and stiff fiber networks, both with permanent and associative cross-links. Although these network models are highly idealized, they are apparently able to capture many aspects of the elastic properties of diverse real networks. C1 [Douglas, Jack F.] NIST, Div Polymers, Gaithersburg, MD 20899 USA. [Lin, David C.; Horkay, Ferenc] Eunice Kennedy Shriver NICHHD, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA. RP Douglas, JF (reprint author), NIST, Div Polymers, Gaithersburg, MD 20899 USA. EM jack.douglas@nist.gov; horkayf@mail.nih.gov FU NIH/NICHD FX This work was supported by the Intramural Research Program of the NIH/NICHD. We greatly acknowledge Kendra Erk and Ken Shull of Northwestern University and Richard Gaylord for their critical reading of our manuscript and constructive advice. We thank Rob Riggleman for providing Fig. 1. NR 81 TC 18 Z9 18 U1 4 U2 21 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1744-683X J9 SOFT MATTER JI Soft Matter PY 2010 VL 6 IS 15 BP 3548 EP 3561 DI 10.1039/b925219n PG 14 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Multidisciplinary; Polymer Science SC Chemistry; Materials Science; Physics; Polymer Science GA 628SH UT WOS:000280140800020 PM 21113355 ER PT J AU Zustiak, SP Boukari, H Leach, JB AF Zustiak, Silviya P. Boukari, Hacene Leach, Jennie B. TI Solute diffusion and interactions in cross-linked poly(ethylene glycol) hydrogels studied by Fluorescence Correlation Spectroscopy SO SOFT MATTER LA English DT Article ID DRUG-DELIVERY; STRUCTURAL-CHANGES; CONTROLLED-RELEASE; LIGHT-SCATTERING; SINGLE-MOLECULE; PEG HYDROGELS; AGAROSE GELS; POLYMER; PROTEIN; TISSUE AB Controlled diffusion and release of soluble molecules is one of the key challenges in developing three-dimensional (3D) scaffolds for tissue engineering and drug delivery applications in part because current methods to measure dynamic transport properties are difficult to perform directly, are strongly affected by the experimental setup, and therefore can be a subject to various artifacts. In this work we present a method for direct measurement of translational diffusion of solutes, namely Fluorescence Correlation Spectroscopy (FCS), by characterizing the diffusion of model proteins through a 3D crosslinked poly(ethylene glycol) (PEG) hydrogel scaffold. We examined both the dynamics of hydrogel structure (e. g., cross-linking and swelling) as well as protein size and their effect on protein diffusivity. For example, we demonstrated that protein diffusivity was closely related to protein size as smaller proteins (e. g., lysozyme) diffused faster than larger proteins (e. g., g-globulin or Ig). We validated the FCS protein diffusivity results by comparison to standard bulk diffusion assays. Additionally, due to the nature of FCS measurements, we were able to probe for hydrogel-protein interactions during cross-linking that may contribute to the obstructed protein diffusion in the 3D scaffold. We determined that such interactions in this system were not covalent (i.e., were independent of the cross-linking chemistry) but may be due to weaker hydrogen bonding or ionic interactions. Also, these interactions were protein specific and contributed up to 25% of the total decrease in protein diffusivity in the hydrogel as compared to diffusivity in water. Though interactions between various proteins and PEG have been reported, this is the first study that has explored these effects in detail in cross-linked PEG hydrogels using FCS; our findings question the assumption that PEG hydrogels are completely inert to protein interactions when applied as drug delivery matrices and tissue engineering scaffolds. C1 [Zustiak, Silviya P.; Leach, Jennie B.] UMBC, Dept Chem & Biochem Engn, Baltimore, MD USA. [Boukari, Hacene] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, Bethesda, MD USA. [Boukari, Hacene] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10467 USA. RP Leach, JB (reprint author), UMBC, Dept Chem & Biochem Engn, Baltimore, MD USA. EM jleach@umbc.edu FU NIH-NINDS [R01NS065205]; Henry Luce Foundation; UMBC FX We thank Drs Ralph Nossal and Dan Sackett for access to the Fluorescence Correlation Spectroscopy equipment and for providing us with EGFP protein. We also thank Dr Douglas Frey for valuable technical discussions. This work was supported by NIH-NINDS (R01NS065205), the Henry Luce Foundation and UMBC. NR 52 TC 38 Z9 38 U1 3 U2 36 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1744-683X J9 SOFT MATTER JI Soft Matter PY 2010 VL 6 IS 15 BP 3609 EP 3618 DI 10.1039/c0sm00111b PG 10 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Multidisciplinary; Polymer Science SC Chemistry; Materials Science; Physics; Polymer Science GA 628SH UT WOS:000280140800027 ER PT J AU Novikov, A AF Novikov, Alexander TI Experimental measurement of work function in doped silicon surfaces SO SOLID-STATE ELECTRONICS LA English DT Article DE Work function; The local work function; Fermi energy; Photovoltage; Doping factor; Potential; Electric field; Injection ratio; Charge carrier; Kelvin probe ID PHOTOVOLTAGE AB Theory and experimental measurement of work function for electrons in doped silicon surfaces are presented in the article. Definitions of work function and of the local work function are given in the introduction. It was shown, that the value of work function defines the position of Fermi energy level. Numerical calculations of surface potential and electric field for theoretical semiconductor surface models show the difference between finite and infinite surfaces. Photovoltage dependence on charge carriers injection ratio for doped silicon surface was numerically calculated as well. Experimentally determined Fermi energies of doped silicon samples show good agreement with theory for low and moderately doped samples only. Appropriate explanations of disagreement between theory and experiment are given in the conclusion. Suggestions for the system improvement are presented in the Appendix. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Novikov, Alexander] Univ Texas Dallas, Dept Phys, Richardson, TX 75080 USA. RP Novikov, A (reprint author), NIH, Bethesda, MD 20892 USA. EM anovikov41@yahoo.com NR 10 TC 24 Z9 24 U1 3 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0038-1101 J9 SOLID STATE ELECTRON JI Solid-State Electron. PD JAN PY 2010 VL 54 IS 1 BP 8 EP 13 DI 10.1016/j.sse.2009.09.005 PG 6 WC Engineering, Electrical & Electronic; Physics, Applied; Physics, Condensed Matter SC Engineering; Physics GA 535LR UT WOS:000272970300003 ER PT S AU Strub, GM Maceyka, M Hait, NC Milstien, S Spiegel, S AF Strub, Graham M. Maceyka, Michael Hait, Nitai C. Milstien, Sheldon Spiegel, Sarah BE Chalfant, C DelPoeta, M TI Extracellular and Intracellular Actions of Sphingosine-1-Phosphate SO SPHINGOLIPIDS AS SIGNALING AND REGULATORY MOLECULES SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID SPHINGOSINE 1-PHOSPHATE RECEPTOR; PROTEIN-COUPLED RECEPTOR; EPIDERMAL-GROWTH-FACTOR; BREAST-CANCER CELLS; SACCHAROMYCES-CEREVISIAE; KINASE TYPE-2; IN-VIVO; ENDOTHELIAL-CELLS; MOLECULAR-CLONING; LYMPHOCYTE EGRESS AB Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator with crucial roles in a wide variety of cellular functions across a broad range of organisms. Though a simple molecule in structure, S1P functions are complex. The formation of S1P is catalyzed by one of two sphingosine kinases that have differential cellular distributions as well as both overlapping and opposing functions and which are activated by many different stimuli. S1P can act on a family of G protein-coupled receptors (S1PRs) that are also differentially expressed in different cell types, which influences the cellular responses to S1P. In addition to acting on receptors located on the plasma membrane, S1P can also function inside the cell, independently of S1PRs. It also appears that both the intracellular location and the isotype of sphingosine kinase involved are major determinants of inside-out signaling of S1P in response to many extracellular stimuli. This chapter is focused on the current literature on extracellular and intracellular actions of S1P. C1 [Strub, Graham M.; Maceyka, Michael; Hait, Nitai C.; Spiegel, Sarah] Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA USA. [Strub, Graham M.; Maceyka, Michael; Hait, Nitai C.; Spiegel, Sarah] Virginia Commonwealth Univ, Sch Med, Dept Mol Biol, Richmond, VA USA. [Milstien, Sheldon] NIMH, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), VCU Sch Med, Dept Biochem & Mol Biol, 1101 E Marshall St,2-011 Sanger Hall, Richmond, VA 23298 USA. EM sspiegel@vcu.edu FU Intramural NIH HHS; NCI NIH HHS [R01 CA061774, R01 CA061774-15, R01CA61774]; NIAID NIH HHS [R01 AI050094, R01 AI050094-06A2, R01AI050094, U19 AI077435, U19 AI077435-010004, U19AI077435-018690]; NIGMS NIH HHS [R37 GM043880, R37 GM043880-18, R37GM043880]; NINDS NIH HHS [F30 NS058008, F30NS058008] NR 138 TC 126 Z9 127 U1 0 U2 13 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-6740-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2010 VL 688 BP 141 EP 155 D2 10.1007/978-1-4419-6741-1 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BQD31 UT WOS:000280732500010 PM 20919652 ER PT B AU Filart, R AF Filart, Rosemarie BE Lin, VW TI The Financial Impact of Spinal Cord Dysfunction SO SPINAL CORD MEDICINE: PRINCIPLES AND PRACTICE, SECOND EDITION LA English DT Article; Book Chapter ID PROSPECTIVE-PAYMENT SYSTEM; ASSISTIVE TECHNOLOGY; MENTAL-HEALTH; UNITED-STATES; INJURY; REHABILITATION; COSTS; TETRAPLEGIA; PREDICTORS; OUTCOMES C1 NIH, Dept Hlth & Human Serv, Rockville, MD USA. RP Filart, R (reprint author), NIH, Dept Hlth & Human Serv, Rockville, MD USA. NR 56 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-19-8 PY 2010 BP 1035 EP 1049 PG 15 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BOJ93 UT WOS:000276871800080 ER PT J AU Lin, J Hong, CZ Russell, J AF Lin, Joseph Hong, Chang-Zern Russell, James BE Chia, M Chiang, J TI A MISUNDERSTOOD MUSCLE PROBLEM IN ATHLETES SO SPORT SCIENCE AND STUDIES IN ASIA: ISSUES, REFLECTIONS AND EMERGENT SOLUTIONS LA English DT Article; Book Chapter ID MYOFASCIAL TRIGGER POINTS; PAIN; FIBROMYALGIA AB Myofascial pain is extremely common in athletes. It is a clinical syndrome caused by myofascial trigger points (MTrPs). MTrP is a highly localized and hyper-irritable spot in a palpable taut band of skeletal muscle Fibre and/or its associated fascia. MTrP is usually caused by or associated with neuromuscular injuries, and can be perpetuated or aggravated by some medical conditions (perpetuating factors). There are certain characteristics of a MTrP; localized spot, tenderness, taut band, referred pain, local twitch response, reduced joint range of motion, symptoms waxed and waned, muscle weakness but without atrophy, and autonomic phenomena. Anybody can have MTrP and any one of the 696 skeletal muscles in the body can have MTrp. MTrPs might not exist in early life, but develop in later life due to soft tissue injuries. MTrP is more likely located at the site of dysfunctional endplates. The pathogenesis of MTrPs is probably related to an integrative mechanism in the spinal cord in response to sensitized sensory nerve fibers (nociceptors) associated with dysfunctional endplates. C1 [Lin, Joseph] Phys Med & Treatment Ctr, Gaithersburg, MD USA. [Hong, Chang-Zern] Univ Calif Irvine, Dept Phys Med & Rehabil, Irvine, CA USA. [Russell, James] NICHHD, NIH, Bethesda, MD 20892 USA. RP Lin, J (reprint author), Phys Med & Treatment Ctr, Gaithersburg, MD USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-4304-08-5 PY 2010 BP 201 EP 210 DI 10.1142/9789814304092_0012 PG 10 WC Sport Sciences SC Sport Sciences GA BOX37 UT WOS:000277917900012 ER PT J AU Kim, KI Roquain, E van de Wiel, MA AF Kim, Kyung In Roquain, Etienne van de Wiel, Mark A. TI Spatial Clustering of Array CGH Features in Combination with Hierarchical Multiple Testing SO STATISTICAL APPLICATIONS IN GENETICS AND MOLECULAR BIOLOGY LA English DT Article DE quadratic exponential model; spatial dependency; array comparative genomic hybridization; FWER; hierarchical testing ID COMPARATIVE GENOMIC HYBRIDIZATION; CANCER; ABERRATIONS AB We propose a new approach for clustering DNA features using array CGH data from multiple tumor samples. We distinguish data-collapsing (joining contiguous DNA clones or probes with extremely similar data into regions) from clustering (joining contiguous, correlated regions based on a maximum likelihood principle). The model-based clustering algorithm accounts for the apparent spatial patterns in the data. We evaluate the randomness of the clustering result by a cluster stability score in combination with cross-validation. Moreover, we argue that the clustering really captures spatial genomic dependency by showing that coincidental clustering of independent regions is very unlikely. Using the region and cluster information, we combine testing of these for association with a clinical variable in a hierarchical multiple testing approach. This allows for interpreting the significance of both regions and clusters while controlling the Family-Wise Error Rate simultaneously. We prove that in the context of permutation tests and permutation-invariant clusters it is allowed to perform clustering and testing on the same data set. Our procedures are illustrated on two cancer data sets. C1 [Kim, Kyung In] NCI, Bethesda, MD 20892 USA. [Roquain, Etienne] Univ Paris 06, F-75252 Paris 05, France. [van de Wiel, Mark A.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. RP Kim, KI (reprint author), NCI, Bethesda, MD 20892 USA. EM kimki2@mail.nih.gov; etienne.roquain@upmc.fr; mark.vdwiel@vumc.nl RI van de Wiel, Mark/F-6759-2013 FU French Agence Nationale de la Recherche (ANR) [ANR-09-JCJC-0027-01, ANR-09-JCJC-0101-01] FX We thank Jelle Goeman and the Associate Editor for discussing the testing procedures with us and Wessel van Wieringen for providing code to create heatmaps. The second author was partly supported by the French Agence Nationale de la Recherche (ANR) (references ANR-PARCIMONIE, ANR-09-JCJC-0027-01, ANR-09-JCJC-0101-01) NR 26 TC 2 Z9 2 U1 0 U2 1 PU BERKELEY ELECTRONIC PRESS PI BERKELEY PA 2809 TELEGRAPH AVENUE, STE 202, BERKELEY, CA 94705 USA SN 1544-6115 J9 STAT APPL GENET MOL JI Stat. Appl. Genet. Mol. Biol. PY 2010 VL 9 IS 1 AR 40 DI 10.2202/1544-6115.1532 PG 25 WC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Mathematics GA 689CS UT WOS:000284905500001 ER PT J AU Wang, CL Szpiech, ZA Degnan, JH Jakobsson, M Pemberton, TJ Hardy, JA Singleton, AB Rosenberg, NA AF Wang, Chaolong Szpiech, Zachary A. Degnan, James H. Jakobsson, Mattias Pemberton, Trevor J. Hardy, John A. Singleton, Andrew B. Rosenberg, Noah A. TI Comparing Spatial Maps of Human Population-Genetic Variation Using Procrustes Analysis SO STATISTICAL APPLICATIONS IN GENETICS AND MOLECULAR BIOLOGY LA English DT Article DE multidimensional scaling; population genetics; principal components analysis; Procrustes analysis ID COPY-NUMBER VARIATION; GENOME-WIDE PATTERNS; HAN CHINESE; SUBSTRUCTURE; ASSOCIATION; SUPERIMPOSITION; MARKERS; EUROPE AB Recent applications of principal components analysis (PCA) and multidimensional scaling (MDS) in human population genetics have found that 'statistical maps' based on the genotypes in population-genetic samples often resemble geographic maps of the underlying sampling locations. To provide formal tests of these qualitative observations, we describe a Procrustes analysis approach for quantitatively assessing the similarity of population-genetic and geographic maps. We confirm in two scenarios, one using single-nucleotide polymorphism (SNP) data from Europe and one using SNP data worldwide, that a measurably high level of concordance exists between statistical maps of population-genetic variation and geographic maps of sampling locations. Two other examples illustrate the versatility of the Procrustes approach in population-genetic applications, verifying the concordance of SNP analyses using PCA and MDS, and showing that statistical maps of worldwide copy-number variants (CNVs) accord with statistical maps of SNP variation, especially when CNV analysis is limited to samples with the highest-quality data. As statistical maps with PCA and MDS have become increasingly common for use in summarizing population relationships, our examples highlight the potential of Procrustes-based quantitative comparisons for interpreting the results in these maps. C1 [Wang, Chaolong; Szpiech, Zachary A.; Pemberton, Trevor J.; Rosenberg, Noah A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Degnan, James H.] Univ Canterbury, Canterbury, New Zealand. [Jakobsson, Mattias] Uppsala Univ, Uppsala, Sweden. [Hardy, John A.] UCL, London WC1E 6BT, England. [Singleton, Andrew B.] NIA, Bethesda, MD 20892 USA. RP Wang, CL (reprint author), Univ Michigan, Ann Arbor, MI 48109 USA. EM chaolong@umich.edu; szpiechz@umich.edu; j.degnan@math.canterbury.ac.nz; mattias.jakobsson@ebc.uu.se; trevorjp@umich.edu; j.hardy@ion.ucl.ac.uk; singleta@mail.nih.gov; rnoah@umich.edu RI Jakobsson, Mattias/A-6116-2011; Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Degnan, James/A-4489-2008 OI Jakobsson, Mattias/0000-0001-7840-7853; FU NIH [R01 GM081441, T32 GM070449]; Burroughs Wellcome Fund Career Award in the Biomedical Sciences; Alfred P. Sloan Research Fellowship; National Institute on Aging, National Institutes of Health, Department of Health and Human Services [Z01-AG000932-02] FX We are grateful to J. Akey and J. Novembre for assistance with the data from their papers. We thank T. Jombart and an anonymous reviewer for comments on the manuscript. This work was supported in part by NIH grants R01 GM081441 and T32 GM070449, by a Burroughs Wellcome Fund Career Award in the Biomedical Sciences, by an Alfred P. Sloan Research Fellowship, and by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services (project number Z01-AG000932-02). NR 37 TC 37 Z9 37 U1 3 U2 13 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 2194-6302 EI 1544-6115 J9 STAT APPL GENET MOL JI Stat. Appl. Genet. Mol. Biol. PY 2010 VL 9 IS 1 AR 13 DI 10.2202/1544-6115.1493 PG 22 WC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Mathematics GA 551HR UT WOS:000274198200007 ER PT J AU Xie, JC Shults, J Peet, J Stambolian, D Cotch, MF AF Xie, Jichun Shults, Justine Peet, Jon Stambolian, Dwight Cotch, Mary Frances TI Quasi-least squares with mixed linear correlation structures SO STATISTICS AND ITS INTERFACE LA English DT Article DE Quasi-least squares; Linear correlation structure; Mixed correlation structure; Familial data ID GENERALIZED ESTIMATING EQUATIONS; LONGITUDINAL DATA; BINARY REGRESSION; MODELS; FAMILY; FRAMEWORK AB Quasi-least squares (QLS) is a two-stage computational approach for estimation of the correlation parameters in the framework of generalized estimating equations. We prove two general results for the class of mixed linear correlation structures: namely, that the stage one QLS estimate of the correlation parameter always exists and is feasible (yields a positive definite estimated correlation matrix) for any correlation structure, while the stage two estimator exists and is unique (and therefore consistent) with probability one, for the class of mixed linear correlation structures. Our general results justify the implementation of QLS for particular members of the class of mixed linear correlation structures that are appropriate for analysis of data from families that may vary in size and composition. We describe the familial structures and implement them in an analysis of optical spherical values in the Old Order Amish (OOA). For the OOA analysis, we show that we would suffer a substantial loss in efficiency, if the familial structures were the true structures, but were misspecified as simpler approximate structures. To help bridge the interface between Statistics and Medicine, we also provide R software so that medical researchers can implement the familial structures in a QLS analysis of their own data. C1 [Xie, Jichun; Shults, Justine] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Peet, Jon; Stambolian, Dwight] Univ Penn, Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. RP Shults, J (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. EM jichun@mail.med.upenn.edu; shults@mail.med.upenn.edu; jonpeet@comcast.net; stamboli@mail.med.upenn.edu; mfc@nei.nih.gov FU Intramural NIH HHS [ZIA EY000405-07, ZIA EY000405-08, Z01 EY000405-05, ZIA EY000405-09, Z01 EY000405-06] NR 25 TC 2 Z9 2 U1 0 U2 1 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 J9 STAT INTERFACE JI Stat. Interface PY 2010 VL 3 IS 2 BP 223 EP 233 PG 11 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA 662UT UT WOS:000282840100009 PM 22518205 ER PT J AU Zheng, HT Zhang, CL Lu, Y Chen, JB AF Zheng, Haitao Zhang, Cuilin Lu, Yun Chen, Jinbo TI Design cost-effective genome-wide and candidate gene association studies of mother-child pairs SO STATISTICS AND ITS INTERFACE LA English DT Article; Proceedings Paper CT 2nd Institute of Mathematical Statistics (IMS) China Conference CY JUL, 2009 CL Weihai, PEOPLES R CHINA DE Mother-child pairs; Maternal genotype effect; Offspring genotype effect; One-stage design; Two-stage design ID HARDY-WEINBERG EQUILIBRIUM; PRETERM DELIVERY; PREECLAMPSIA; PREGNANCY; TESTS; MICE AB A case-control mother-child pair design is popular for genetic association studies of obstetric or neonatal outcomes because it allows assessment of both maternal and offspring genotype effects. But a practical constraint is the high genotyping cost, which may double that for a study with the same number of unrelated cases and controls. This issue is particularly relevant for genome-wide association studies, despite the decreasing genotyping cost. Here, we developed cost-effective genotyping strategies for the case-control mother-child pair design. We assumed that the maternal genome had been genotyped a priori, and that the primary goal was to detect marginal offspring genotype effects. Our results indicated that only offspring of case mothers needed to be genotyped in order to achieve a statistical power similar to that for screening the maternal genome. Our conclusion was based on a novel score statistic for testing offspring genotype effects that has a higher power than the Armitage trend test. C1 [Zheng, Haitao; Lu, Yun; Chen, Jinbo] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Zhang, Cuilin] NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Chen, JB (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. EM htzheng@gmail.com; zhangcu@mail.nih.gov; luyun@mail.med.upenn.edu; jinboche@mail.med.upenn.edu NR 22 TC 0 Z9 0 U1 0 U2 0 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 J9 STAT INTERFACE JI Stat. Interface PY 2010 VL 3 IS 4 BP 543 EP 555 PG 13 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA 700UN UT WOS:000285769900013 ER PT J AU Swistowska, AM da Cruz, AB Han, Y Swistowski, A Liu, Y Shin, S Zhan, M Rao, MS Zeng, XM AF Swistowska, Anna Maria da Cruz, Alexandre Bettencourt Han, Yi Swistowski, Andrzej Liu, Ying Shin, Soojung Zhan, Ming Rao, Mahendra S. Zeng, Xianmin TI Stage-Specific Role for Shh in Dopaminergic Differentiation of Human Embryonic Stem Cells Induced by Stromal Cells SO STEM CELLS AND DEVELOPMENT LA English DT Article ID PARKINSONS-DISEASE; IN-VITRO; SUBSTANTIA-NIGRA; HUMAN BLASTOCYSTS; PROGENITOR CELLS; ES CELLS; NEURONS; MIDBRAIN; TRANSPLANTATION; GENERATION AB Stromal cells have been used to induce dopaminergic differentiation of mouse, primate, and human embryonic stem cells (hESCs), but the mechanism that governs this induction is unknown. In this manuscript, we show that medium conditioned by the stromal cell line PA6 (PA6-CM) can induce dopaminergic differentiation in neural stem cells (NSCs) derived from hESCs but not directly from hESCs, indicating that soluble factors produced by PA6 cells act at the NSC stage to specify a dopaminergic fate. To identify such soluble factors, we analyzed the transcriptomes of PA6 cells, NSCs, and dopaminergic populations induced by PA6-CM from hESC-derived NSCs. We focused our analysis on growth factors expressed by PA6 and receptors expressed by NSCs, and generated a list of growth factors and receptors that are differentially expressed. Some of the growth factor/receptor pairs are categorized into the Shh, Wnt5A, TGF beta, and IGF pathways. The expression of genes activated by these pathways in dopaminergic populations was analyzed to confirm that these signals were likely candidates for specifying dopaminergic fate. Results were verified for Shh by using perturbation agents such as cyclopamine to show that Shh is indeed one of the active agents in PA6-CM, and by showing that Shh and FGF8 can substitute for PA6-CM at the NSC induction stage. We conclude that PA6-CM can induce dopaminergic differentiation in hESCs in a stage-specific manner. Shh is likely an important soluble dopaminergic inducing factor secreted by stromal cells and acts after the neural fate determination. C1 [Swistowska, Anna Maria; da Cruz, Alexandre Bettencourt; Han, Yi; Swistowski, Andrzej; Rao, Mahendra S.; Zeng, Xianmin] Buck Inst Aging Res, Novato, CA 94945 USA. [Liu, Ying; Shin, Soojung; Rao, Mahendra S.] Invitrogen, Carlsbad, CA USA. [Zhan, Ming] NIA, Baltimore, MD 21224 USA. RP Zeng, XM (reprint author), Buck Inst Aging Res, 8001 Redwood Blvd, Novato, CA 94945 USA. EM xzeng@buckinstitute.org FU California Institute for Regenerative Medicine [CL1-00501-1]; Larry L. Hillblom Foundation FX This work was supported by the California Institute for Regenerative Medicine Grant CL1-00501-1 (X.Z.) and the Larry L. Hillblom Foundation. NR 53 TC 30 Z9 33 U1 0 U2 7 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 JAN PY 2010 VL 19 IS 1 BP 71 EP 82 DI 10.1089/scd.2009.0107 PG 12 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 544QZ UT WOS:000273675300009 PM 19788370 ER PT J AU Nicolaides, NC Galata, Z Kino, T Chrousos, GP Charmandari, E AF Nicolaides, Nicolas C. Galata, Zoi Kino, Tomoshige Chrousos, George P. Charmandari, Evangelia TI The human glucocorticoid receptor: Molecular basis of biologic function SO STEROIDS LA English DT Review DE Human glucocorticoid receptor (hGR); Generalized glucocorticoid resistance; Mutations in the hGR gene; Polymorphisms of the hGR gene ID LIGAND-BINDING DOMAIN; UBIQUITIN-PROTEASOME PATHWAY; FRAGMENT-LENGTH-POLYMORPHISM; PRIMARY CORTISOL RESISTANCE; STEROID-HORMONE RECEPTORS; N-TERMINAL KINASE; BODY-MASS INDEX; FACTOR-KAPPA-B; NUCLEAR RECEPTOR; GENE-EXPRESSION AB The characterization of the subfamily of steroid hormone receptors has enhanced our understanding of how a set of hormonally derived lipophilic ligands controls cellular and molecular functions to influence development and help achieve homeostasis. The glucocorticoid receptor (GR), the first member of this subfamily, is a ubiquitously expressed intracellular protein, which functions as a ligand-dependent transcription factor that regulates the expression of glucocorticoid-responsive genes. The effector domains of the GR mediate transcriptional activation by recruiting coregulatory multi-subunit complexes that remodel chromatin, target initiation sites, and stabilize the RNA-polymerase II machinery for repeated rounds of transcription of target genes. This review summarizes the basic aspects of the structure and actions of the human (h) GR, and the molecular basis of its biologic functions. (C) 2009 Elsevier Inc. All rights reserved. C1 [Nicolaides, Nicolas C.; Galata, Zoi; Chrousos, George P.; Charmandari, Evangelia] Acad Athens, Biomed Res Fdn, Clin Res Ctr, Div Endocrinol & Metab, Athens 11527, Greece. [Kino, Tomoshige; Chrousos, George P.; Charmandari, Evangelia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Pediat Endocrinol, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Chrousos, George P.; Charmandari, Evangelia] Univ Athens, Sch Med, Aghia Sophia Childrens Hosp, Div Endocrinol Metab & Diabet,Dept Pediat 1, GR-11527 Athens, Greece. RP Charmandari, E (reprint author), Acad Athens, Biomed Res Fdn, Clin Res Ctr, Div Endocrinol & Metab, 4 Soranou Tou Efessiou St, Athens 11527, Greece. EM evangelia.charmandari@googlemail.com RI Charmandari, Evangelia/B-6701-2011 FU EU-European Social Fund; Greek Ministry of Development-General Secretariat of Research and Technology; National Institutes of Health, Bethesda, Maryland 20892, USA FX Literary work of this article was funded by the EU-European Social Fund, the Greek Ministry of Development-General Secretariat of Research and Technology, and the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. NR 125 TC 157 Z9 164 U1 2 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-128X J9 STEROIDS JI Steroids PD JAN PY 2010 VL 75 IS 1 BP 1 EP 12 DI 10.1016/j.steroids.2009.09.002 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 549VS UT WOS:000274083000001 PM 19818358 ER PT J AU Polak, JF Person, SD Wei, GS Godreau, A Jacobs, DR Harrington, A Sidney, S O'Leary, DH AF Polak, Joseph F. Person, Sharina D. Wei, Gina S. Godreau, Ayleen Jacobs, David R., Jr. Harrington, Anita Sidney, Stephen O'Leary, Daniel H. TI Segment-Specific Associations of Carotid Intima-Media Thickness With Cardiovascular Risk Factors The Coronary Artery Risk Development in Young Adults (CARDIA) Study SO STROKE LA English DT Article DE carotid intimal medial thickness; carotid ultrasound; risk factors ID B-MODE ULTRASOUND; WALL THICKNESS; DISEASE RISK; SHEAR-STRESS; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS RISK; STROKE; PLAQUE; RECRUITMENT; ROTTERDAM AB Background and Purpose-We propose to study possible differences in the associations between risk factors for cardiovascular disease (myocardial infarction and stroke) and carotid intima-media thickness (IMT) measurements made at 3 different levels of the carotid bifurcation. Methods-We conducted a cross-sectional study of a cohort of whites and blacks of both genders with a mean age of 45 years. Traditional cardiovascular risk factors were determined in cohort members. Carotid IMT was measured from high-resolution B-mode ultrasound images at 3 levels: the common carotid artery, the carotid artery bulb (bulb), and the internal carotid artery. Associations with risk factors were evaluated by multivariate linear regression analyses. Results-Of 3258 who underwent carotid IMT measurements, common carotid artery, bulb, and internal carotid artery IMT were measured at all 3 separate levels in 3023 (92.7%). A large proportion of the variability of common carotid artery IMT was explained by cardiovascular risk factors (26.8%) but less so for the bulb (11.2%) and internal carotid artery (8.0%). Carotid IMT was consistently associated with age, low-density lipoprotein cholesterol, smoking, and hypertension in all segments. Associations with fasting glucose and diastolic blood pressure were stronger for common carotid artery than for the other segments. Hypertension, diabetes, and current smoking had qualitatively stronger associations with bulb IMT and low-density lipoprotein cholesterol with internal carotid artery IMT. Conclusion-In our cohort of relatively young white and black men and women, a greater proportion of the variability in common carotid IMT can be explained by traditional cardiovascular risk factors than for the carotid artery bulb and internal carotid arteries. (Stroke. 2010;41:9-15.) C1 [Polak, Joseph F.] Tufts Univ, Sch Med, Dept Radiol, Tufts Med Ctr, Boston, MA 02111 USA. [Person, Sharina D.] Univ Alabama, Div Prevent Med, Birmingham, AL USA. [Wei, Gina S.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Godreau, Ayleen] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. Univ Oslo, Dept Nutr, Oslo, Norway. [Sidney, Stephen] Kaiser Permanente, Epidemiol & Prevent Sect, Div Res, Oakland, CA USA. [O'Leary, Daniel H.] Tufts Univ, Sch Med, Carney Christi Hosp, Boston, MA 02111 USA. RP Polak, JF (reprint author), Tufts Univ, Sch Med, Dept Radiol, Tufts Med Ctr, 299,800 Washington St, Boston, MA 02111 USA. EM jpolak@tuftsmedicalcenter.org FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC95095]; NHLBI [R01 HL069003, HL081352] FX The CARDIA Study is supported by contracts N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, and N01-HC95095 from the National Heart, Lung, and Blood Institute (NHLBI). J. F. P. is partly supported by NHLBI R01 HL069003 and HL081352. NR 31 TC 79 Z9 81 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2010 VL 41 IS 1 BP 9 EP 15 DI 10.1161/STROKEAHA.109.566596 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 537DO UT WOS:000273093400003 PM 19910544 ER PT B AU Mulkidjanian, AY Galperin, MY AF Mulkidjanian, Armen Y. Galperin, Michael Y. BE Frishman, D TI Evolutionary origins of membrane proteins SO STRUCTURAL BIOINFORMATICS OF MEMBRANE PROTEINS LA English DT Article; Book Chapter ID UNIVERSAL COMMON ANCESTOR; VACUOLAR H+-ATPASE; LIPID-BILAYERS; ESCHERICHIA-COLI; CARBON-DIOXIDE; ZINC-SULFIDE; V-ATPASE; F-TYPE; ILYOBACTER-TARTARICUS; POLYPRENYL PHOSPHATES AB Although the genes that encode membrane proteins make about 30% of the sequenced genomes, the evolution of membrane proteins and their origins are still poorly understood. Here we address this topic by taking a closer look at those membrane proteins the ancestors of which were present in the Last Universal Common Ancestor, and in particular, the F/V-type rotating ATPases. Reconstruction of their evolutionary history provides hints for understanding not only the origin of membrane proteins, but also of membranes themselves. We argue that the evolution of biological membranes could occur as a process of co-evolution of lipid bilayers and membrane proteins, where the increase in the ion-tightness of the membrane bilayer may have been accompanied by a transition from amphiphilic, pore-forming membrane proteins to highly hydrophobic integral membrane complexes. C1 [Mulkidjanian, Armen Y.] Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany. [Mulkidjanian, Armen Y.] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow, Russia. [Galperin, Michael Y.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Mulkidjanian, AY (reprint author), Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany. EM amulkid@uos.de RI Mulkidjanian, Armen/J-8086-2013 OI Mulkidjanian, Armen/0000-0001-5844-3064 NR 163 TC 10 Z9 11 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-3-7091-0044-8 PY 2010 BP 1 EP 28 DI 10.1007/978-3-7091-0045-5_1 D2 10.1007/978-3-7091-0045-5 PG 28 WC Chemistry, Applied; Medical Informatics SC Chemistry; Medical Informatics GA BQU36 UT WOS:000281865100001 ER PT J AU Nunez-Smith, M Wolf, E Huang, HM Chen, PG Lee, L Emanuel, EJ Gross, CP AF Nunez-Smith, Marcella Wolf, Elizabeth Huang, Helen Mikiko Chen, Peggy G. Lee, Lana Emanuel, Ezekiel J. Gross, Cary P. TI Media Exposure and Tobacco, Illicit Drugs, and Alcohol Use Among Children and Adolescents: A Systematic Review SO SUBSTANCE ABUSE LA English DT Review DE Adolescents; children; health; media; television ID AMERICAN FEMALE ADOLESCENTS; SMOKING INITIATION; YOUTH SMOKING; PREVENTIVE-SERVICES; VIEWING SMOKING; SUBSTANCE USE; TELEVISION; HEALTH; MOVIES; COHORT AB The authors systematically reviewed 42 quantitative studies on the relationship between media exposure and tobacco, illicit drug, and alcohol use among children and adolescents. Overall, 83% of studies reported that media was associated with increased risk of smoking initiation, use of illicit drugs, and alcohol consumption. Of 30 studies examining media content, 95% found a statistically significant association between increased media exposure and negative outcomes. Similarly, of the 12 studies evaluating the quantity of media exposure, 67% reported an association with a negative outcome. Overall, all 17 of the identified longitudinal studies supported a causal association between media exposure and negative outcomes over time. The evidence was strongest for links between media exposure and tobacco use; it was moderate for illicit drug use and alcohol use. Substantial variability in methodological rigor across studies and expanding definitions of media exposure contribute to persistent gaps in the knowledge base. C1 [Nunez-Smith, Marcella; Wolf, Elizabeth; Gross, Cary P.] Yale Univ, Sch Med, Gen Internal Med Sect, Dept Internal Med, New Haven, CT 06520 USA. [Huang, Helen Mikiko] Calif Pacific Med Ctr, San Francisco, CA USA. [Chen, Peggy G.; Lee, Lana] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. [Chen, Peggy G.; Gross, Cary P.] Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06520 USA. [Emanuel, Ezekiel J.] NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Nunez-Smith, M (reprint author), Yale Univ, Sch Med, Gen Internal Med Sect, Dept Internal Med, IE 61 SHM,POB 208088, New Haven, CT 06520 USA. EM marcella.nunez-smith@yale.edu FU Common Sense Media; Department of Clinical Bioethics, National Institutes of Health FX Financial support for this project was provided by Common Sense Media and The Department of Clinical Bioethics, National Institutes of Health. No form of payment was given to anyone to produce the manuscript. NR 58 TC 19 Z9 21 U1 1 U2 18 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PY 2010 VL 31 IS 3 BP 174 EP 192 DI 10.1080/08897077.2010.495648 PG 19 WC Substance Abuse SC Substance Abuse GA 668XW UT WOS:000283309900006 PM 20687006 ER PT J AU Heinz, AJ Disney, ER Epstein, DH Glezen, LA Clark, PI Preston, KL AF Heinz, Adrienne J. Disney, Elizabeth R. Epstein, David H. Glezen, Louise A. Clark, Pamela I. Preston, Kenzie L. TI A Focus-Group Study on Spirituality and Substance-User Treatment SO SUBSTANCE USE & MISUSE LA English DT Article DE spirituality; religion; focus groups; methadone; substance dependence; recovery ID DRUG-TREATMENT; COCAINE DEPENDENCE; PATIENT ATTITUDES; ABUSE RECOVERY; ADDICTION; RELIGION; PROGRAM; HEALTH; ALCOHOL; INTERVENTION AB Focus groups were conducted in 2005-2006 with 25 urban methadone-maintained outpatients to examine beliefs about the role of spirituality in addiction and its appropriateness informal treatment. Thematic analyses suggested that spirituality and religious practices suffered in complex ways during active addiction, but went "hand in hand" with recovery. Participants agreed that integration of a voluntary spiritual discussion group into formal treatment would be preferable to currently available alternatives. One limitation was that all participants identified as strongly spiritual. Studies of more diverse samples will help guide the development and evaluation of spiritually based interventions informal treatment. C1 [Epstein, David H.] NIDA, IRP, Treatment Sect, Clin Pharmacol & Therapeut Branch, Baltimore, MD 21224 USA. [Disney, Elizabeth R.] Chase Brexton Hlth Serv, Baltimore, MD USA. [Clark, Pamela I.] Battelle Mem Inst, Baltimore, MD USA. RP Epstein, DH (reprint author), NIDA, IRP, Treatment Sect, Clin Pharmacol & Therapeut Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM depstein@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 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 52 TC 4 Z9 4 U1 0 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2010 VL 45 IS 1-2 BP 134 EP 153 DI 10.3109/10826080903035130 PG 20 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 551RM UT WOS:000274226700009 PM 20025443 ER PT S AU Schuck, P Zhao, HY AF Schuck, Peter Zhao, Huaying BE DeMol, NJ Fischer, MJE TI The Role of Mass Transport Limitation and Surface Heterogeneity in the Biophysical Characterization of Macromolecular Binding Processes by SPR Biosensing SO SURFACE PLASMON RESONANCE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Binding kinetics; affinity distribution; thermodynamics; mass transport limitation; surface binding; optical biosensor; Tikhonov regularization ID BIOMOLECULAR INTERACTION ANALYSIS; PLASMON RESONANCE BIOSENSOR; EVANESCENT-WAVE BIOSENSORS; TOTAL INTERNAL-REFLECTION; KINETIC-ANALYSIS; CORRELATION SPECTROSCOPY; OPTICAL BIOSENSORS; DRUG DISCOVERY; PROTEIN; SPECTROMETRY AB This chapter presents an introduction to the kinetic analysis of SPR biosensor data for the determination of affinity and kinetic rate constants of biomolecular interactions between an immobilized and a soluble binding partner. The need to be aware of and critically test the assumptions underlying the analysis models is emphasized and the consequences for the experimental design are discussed. The two most common sources of deviation in SPR surface binding kinetics from the ideal pseudo-first-order binding kinetics of bimolecular reactions are mass transport limitations and the heterogeneity of the surface sites. These problems are intrinsic to the use of a biosensor surface for characterizing interactions. The effect of these factors on the observed binding kinetics, and strategies to account for them are reviewed, both in the context of mathematical data analysis, as well as the design of the experiments and controls. C1 [Schuck, Peter; Zhao, Huaying] NIBIB, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. RP Schuck, P (reprint author), NIBIB, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. RI Zhao, Huaying/F-5716-2012; OI Schuck, Peter/0000-0002-8859-6966 FU Intramural NIH HHS [ZIA EB000049-03] NR 58 TC 48 Z9 48 U1 0 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-669-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 627 BP 15 EP 54 DI 10.1007/978-1-60761-670-2_2 D2 10.1007/978-1-60761-670-2 PG 40 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BOH97 UT WOS:000276684500002 PM 20217612 ER PT B AU Oliveira, J Koroshetz, WJ AF Oliveira-Filho, Jamary Koroshetz, Walter J. BE ODonnell, JM Nacul, FE TI Ischemic Stroke SO SURGICAL INTENSIVE CARE MEDICINE, SECOND EDITION LA English DT Article; Book Chapter ID MIDDLE CEREBRAL-ARTERY; RANDOMIZED CONTROLLED-TRIAL; DIFFUSION-WEIGHTED MRI; FAT-EMBOLISM SYNDROME; BYPASS GRAFT-SURGERY; INTERNAL CAROTID-ARTERY; TRANSCRANIAL DOPPLER; CT ANGIOGRAPHY; BLOOD-PRESSURE; AIR-EMBOLISM C1 [Oliveira-Filho, Jamary] Hosp Espanhol, Neurol Serv, Salvador, BA, Brazil. [Oliveira-Filho, Jamary] Hosp Espanhol, Neurocrit Care Unit, Salvador, BA, Brazil. [Oliveira-Filho, Jamary] Univ Fed Bahia, Salvador, BA, Brazil. [Koroshetz, Walter J.] NINDS, Bethesda, MD 20892 USA. RP Oliveira, J (reprint author), Hosp Espanhol, Neurol Serv, Salvador, BA, Brazil. NR 105 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-0-387-77892-1 PY 2010 BP 149 EP 161 DI 10.1007/978-0-387-77893-8_15 PG 13 WC Surgery SC Surgery GA BMS78 UT WOS:000273499600015 ER PT B AU Oliveira, J Koroshetz, WJ AF Oliveira-Filho, Jamary Koroshetz, Walter J. BE ODonnell, JM Nacul, FE TI Hemorrhagic Stroke SO SURGICAL INTENSIVE CARE MEDICINE, SECOND EDITION LA English DT Article; Book Chapter ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; SPONTANEOUS INTRACEREBRAL HEMORRHAGE; RUPTURED INTRACRANIAL ANEURYSMS; BRAIN NATRIURETIC PEPTIDE; CEREBRAL VASOSPASM; INTRAARTERIAL PAPAVERINE; CEREBELLAR HEMORRHAGE; BLOOD-PRESSURE; INTRAVENTRICULAR HEMORRHAGE; ARTERIAL-HYPERTENSION C1 [Oliveira-Filho, Jamary] Hosp Espanhol, Neurol Serv, Salvador, BA, Brazil. [Oliveira-Filho, Jamary] Hosp Espanhol, Neurocrit Care Unit, Salvador, BA, Brazil. [Oliveira-Filho, Jamary] Univ Fed Bahia, Salvador, BA, Brazil. [Koroshetz, Walter J.] NINDS, Bethesda, MD 20892 USA. RP Oliveira, J (reprint author), Hosp Espanhol, Neurol Serv, Salvador, BA, Brazil. NR 83 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-0-387-77892-1 PY 2010 BP 163 EP 171 DI 10.1007/978-0-387-77893-8_16 PG 9 WC Surgery SC Surgery GA BMS78 UT WOS:000273499600016 ER PT B AU Saltz, LB Duffy, AG AF Saltz, Leonard B. Duffy, Austin G. BE Stubblefield, MD ODell, MW TI Evaluation and Treatment of Colorectal Cancer SO SYNOPSIS OF CLINICAL ONCOLOGY LA English DT Article; Book Chapter ID POSTOPERATIVE ADJUVANT THERAPY; FLUOROURACIL PLUS LEUCOVORIN; GROWTH-FACTOR RECEPTOR; COLON-CANCER; PHASE-III; 1ST-LINE TREATMENT; RANDOMIZED-TRIAL; FOLINIC ACID; IRINOTECAN; OXALIPLATIN C1 [Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, Dept Med, Gastrointestinal Oncol Serv, New York, NY 10021 USA. [Duffy, Austin G.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Saltz, LB (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Gastrointestinal Oncol Serv, 1275 York Ave, New York, NY 10021 USA. NR 36 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-00-0 PY 2010 BP 209 EP 215 PG 7 WC Oncology SC Oncology GA BOK32 UT WOS:000276890200015 ER PT J AU Velazquez, CA Lynn, GM Kumar, V Keefer, LK Malhotra, SV AF Velazquez, Carlos A. Lynn, Geoffrey M. Kumar, Vineet Keefer, Larry K. Malhotra, Sanjay V. TI Arylation of Sensitive 1-(Pyrrolidin-1-yl)-diazen-1-ium-diolate in Ionic Liquids SO SYNTHETIC COMMUNICATIONS LA English DT Article DE Diazeniumdiolate; ionic liquid; nitric oxide donor; nucleophilic displacement ID NUCLEOPHILIC-SUBSTITUTION REACTIONS; NITRIC-OXIDE DONOR; DENSITY-FUNCTIONAL THEORY; IN-VITRO; CHOLINE CHLORIDE/UREA; ANTILEUKEMIC ACTIVITY; ENZYMATIC RESOLUTION; ANTICANCER LEAD; JS-K; DIAZENIUMDIOLATE AB The purpose of this research was to investigate the stability and reactivity of 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (PYRRO/NO) in dimethylformamide (DMF, as the reference solvent) and compare them to those obtained using different ionic liquids. The results of our experiments showed that PYRRO/NO is more stable (based on reactivity) in ionic liquid [EMIM][Ms] (with reaction yields up to 52%) than in DMF, that substitution products can be separated directly and quantitatively from the ionic liquid using a single flash-column separation, and that the ionic liquids can also be recovered and reused in a second iteration of the same reaction to achieve similar yields. C1 [Kumar, Vineet; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick Inc, DTP, Frederick, MD 21702 USA. [Velazquez, Carlos A.; Lynn, Geoffrey M.; Keefer, Larry K.] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Malhotra, SV (reprint author), NCI, Lab Synthet Chem, SAIC Frederick Inc, DTP, 1050 Boyles St, Frederick, MD 21702 USA. EM malhotrasa@mail.nih.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU National Cancer Institute, National Institutes of Health (NIH) [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by federal funds from the National Cancer Institute, National Institutes of Health (NIH) under contract HHSN261200800001E with SAIC-Frederick Inc. as well as by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 32 TC 1 Z9 1 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0039-7911 J9 SYNTHETIC COMMUN JI Synth. Commun. PY 2010 VL 40 IS 9 BP 1322 EP 1332 AR PII 920999795 DI 10.1080/00397910903074079 PG 11 WC Chemistry, Organic SC Chemistry GA 597EE UT WOS:000277738400009 ER PT S AU Zhan, M AF Zhan, Ming BE Choi, S TI Inferring Transcriptional Regulatory Network SO SYSTEMS BIOLOGY FOR SIGNALING NETWORKS SE Systems Biology-Springer LA English DT Article; Book Chapter DE Gene expression; Regulatory network; Transcriptional modules; Transcription factor; Matrix decomposition ID STEM-CELL DIFFERENTIATION; SACCHAROMYCES-CEREVISIAE; COMPONENT ANALYSIS; MICROARRAY DATA; EXPRESSION DATA; MODULES; IDENTIFICATION; DISCOVERY; GENOME; GENES AB Genes are coordinately regulated and expressed as forming various transcriptional modules or networks to carry out complex and condition-specific biological functions in living cells. In this chapter, we describe a series of new methodologies for identifying transcriptional modules and regulatory networks and examining their evolutionarily conserved and divergent patterns from gene expression and transcription factor data. The methods are based on a two-stage matrix decomposition model consisting of a nonlinear independent component analysis followed by a sparse matrix analysis. The methods take into account the nonlinear structure in gene expression data, particularly in the TF-target gene interactions, capable of capturing transcriptional modularity that might result from highly nonlinear interactions among genes. The methods model gene expression as a linear weighted combination of a small number of regulatory prototypes such as transcription factors, underscoring the fact that a small number of regulatory genes have predominant impact to the expression of most of genes and function in a combinatorial manner. The methods allow partitioning genes into mutually nonexclusive transcriptional modules, underlying the fact that one gene may have multiple functions or participate in multiple biological processes. In comparison with other methods, the new methods show a significant improvement in identifying biologically more meaningful transcriptional modules and regulatory network. C1 NIA, Bioinformat Unit, Res Resources Branch, NIH, Baltimore, MD 21224 USA. RP Zhan, M (reprint author), NIA, Bioinformat Unit, Res Resources Branch, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM zhanmi@mail.nih.gov NR 32 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2191-222X BN 978-1-4419-5796-2 J9 SYST BIO JI Syst. Biol. PY 2010 VL 1 BP 235 EP 252 DI 10.1007/978-1-4419-5797-9_9 D2 10.1007/978-1-4419-5797-9 PG 18 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA BQS09 UT WOS:000281687700009 ER PT J AU Doarn, CR Portilla, LM Sayre, MH AF Doarn, Charles R. Portilla, Lili M. Sayre, Michael H. TI NIH Conference on the Future of Telehealth: Essential Tools and Technologies for Clinical Research and Care-A Summary June 25-26, 2009 Bethesda, Maryland SO TELEMEDICINE JOURNAL AND E-HEALTH LA English DT Editorial Material DE NCRR; health information technology; telehealth research and development AB Major government efforts to widen the use of health information technology and speed the translation of biomedical research discoveries into clinical practice are converging with the rapid growth of the Internet to create unprecedented opportunities to use tele-health networks to broaden access to high-quality healthcare and expand the scope and reach of clinical and translational research. Recognizing the dual potential of tele-health networks to improve health outcomes and reduce barriers to participation in research, particularly in medically underserved communities, the National Center for Research Resources (NCRR), part of the National Institutes of Health ( NIH), convened a national conference at the NIH on June 25-26, 2009, titled "Future of Telehealth: Essential Tools and Technologies for Clinical Research and Care,'' in collaboration with experts from the Health Resources and Services Administration, the Indian Health Service, the Department of Veterans Affairs, Internet2, and the NIH National Library of Medicine, National Institute of Biomedical Imaging and Bioengineering, and National Center for Minority Health and Health Disparities. The conference brought together over 400 subject matter experts from government, academia, and industry to discuss a wide range of issues in telehealth research and development. Its primary outcome is a set of short papers reporting on recommendations from thematic breakout sessions and some overarching recommendations that can, taken together, stimulate and help guide further research through new multi-agency, interdisciplinary collaborations. C1 [Doarn, Charles R.] Univ Cincinnati, Dept Publ Hlth Sci, Cincinnati, OH 45267 USA. [Portilla, Lili M.] NIH, Off Director, Natl Ctr Res Resources, Bethesda, MD 20892 USA. [Sayre, Michael H.] NIH, Div Res Infrastruct, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Doarn, CR (reprint author), Univ Cincinnati, Dept Publ Hlth Sci, 260 Stetson,Suite 4200,POB 670840,ML 0840, Cincinnati, OH 45267 USA. EM charles.doarn@uc.edu NR 3 TC 9 Z9 9 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED J E-HEALTH JI Telemed. J. e-Health PD JAN-FEB PY 2010 VL 16 IS 1 BP 89 EP 92 DI 10.1089/tmj.2009.0151 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 551BV UT WOS:000274181600014 PM 20043701 ER PT J AU Ackerman, MJ Filart, R Burgess, LP Lee, I Poropatich, RK AF Ackerman, Michael J. Filart, Rosemarie Burgess, Lawrence P. Lee, Insup Poropatich, Ronald K. TI Developing Next-Generation Telehealth Tools and Technologies: Patients, Systems, and Data Perspectives SO TELEMEDICINE JOURNAL AND E-HEALTH LA English DT Editorial Material DE business administration/economics; telehealth tools; technology; National Institutes of Health ID CLINICAL-DECISION-SUPPORT AB The major goals of telemedicine today are to develop next-generation telehealth tools and technologies to enhance healthcare delivery to medically underserved populations using telecommunication technology, to increase access to medical specialty services while decreasing healthcare costs, and to provide training of healthcare providers, clinical trainees, and students in health-related fields. Key drivers for these tools and technologies are the need and interest to collaborate among telehealth stakeholders, including patients, patient communities, research funders, researchers, healthcare services providers, professional societies, industry, healthcare management/economists, and healthcare policy makers. In the development, marketing, adoption, and implementation of these tools and technologies, communication, training, cultural sensitivity, and end-user customization are critical pieces to the process. Next-generation tools and technologies are vehicles toward personalized medicine, extending the telemedicine model to include cell phones and Internet-based telecommunications tools for remote and home health management with video assessment, remote bedside monitoring, and patient-specific care tools with event logs, patient electronic profile, and physician note-writing capability. Telehealth is ultimately a system of systems in scale and complexity. To cover the full spectrum of dynamic and evolving needs of end-users, we must appreciate system complexity as telehealth moves toward increasing functionality, integration, inter-operability, outreach, and quality of service. Toward that end, our group addressed three overarching questions: (1) What are the high-impact topics? (2) What are the barriers to progress? and (3) What roles can the National Institutes of Health and its various institutes and centers play in fostering the future development of telehealth? C1 [Ackerman, Michael J.] NIH, Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD 20894 USA. [Filart, Rosemarie] NIH, Natl Ctr Res Resources, Bethesda, MD 20894 USA. [Burgess, Lawrence P.] Univ Hawaii, John A Burns Sch Med, Telehlth Res Inst, Honolulu, HI 96822 USA. [Lee, Insup] Univ Penn, Dept Comp & Informat Sci, Philadelphia, PA 19104 USA. [Poropatich, Ronald K.] USA, Med Res & Mat Command, Telemed & Adv Technol Res Ctr, Ft Detrick, MD USA. RP Ackerman, MJ (reprint author), NIH, Natl Lib Med, Off High Performance Comp & Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM mackerman@mail.nih.gov NR 6 TC 38 Z9 39 U1 2 U2 12 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED J E-HEALTH JI Telemed. J. e-Health PD JAN-FEB PY 2010 VL 16 IS 1 BP 93 EP 95 DI 10.1089/tmj.2009.0153 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 551BV UT WOS:000274181600015 PM 20043711 ER PT J AU Puskin, DS Cohen, Z Ferguson, AS Krupinski, E Spaulding, R AF Puskin, Dena S. Cohen, Zohara Ferguson, A. Stewart Krupinski, Elizabeth Spaulding, Ryan TI Implementation and Evaluation of Telehealth Tools and Technologies SO TELEMEDICINE JOURNAL AND E-HEALTH LA English DT Editorial Material AB In June 2009, the National Center for Research Resources (NCRR), National Institutes of Health (NIH), convened a conference of experts to discuss future directions for research in addressing healthcare disparities through the use of telehealth technologies. As part of this conference, a panel was convened to review the status of current efforts to assess, implement, and evaluate telehealth technologies, and to recommend future directions for research. The panel members provided a series of practical recommendations to those who are contemplating establishing a telehealth service, as well as recommendations to the NIH on future funding for telehealth research. The recommendations to the NIH focused on three broad areas of concern: (1) technology assessment, (2) evaluation, and (3) technical assistance, education, and dissemination. The panel members emphasized the need for NIH to support research in areas that have been seriously underfunded in the past, including but not limited to primary care research, multisite collaborative telehealth studies, nonphysician telehealth services, and methodological development to develop a "gold standard" for telehealth studies. C1 [Puskin, Dena S.] US Hlth Resources & Serv Adm, Off Advancement Telehlth, Rockville, MD 20857 USA. [Cohen, Zohara] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Ferguson, A. Stewart] Alaska Fed Hlth Care Access Network, Alaska Native Tribal Hlth Consortium, Anchorage, AK USA. [Krupinski, Elizabeth] Univ Arizona, Dept Radiol Res, Tucson, AZ USA. [Spaulding, Ryan] Univ Kansas, Med Ctr, Ctr Telemed & Telehlth, Kansas City, KS 66103 USA. RP Puskin, DS (reprint author), US Hlth Resources & Serv Adm, Off Advancement Telehlth, Room 7C-26,5600 Fishers Lane, Rockville, MD 20857 USA. EM dpuskin@hrsa.gov OI Spaulding, Ryan/0000-0001-9396-9360 NR 0 TC 12 Z9 12 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED J E-HEALTH JI Telemed. J. e-Health PD JAN-FEB PY 2010 VL 16 IS 1 BP 96 EP 102 DI 10.1089/tmj.2009.0182 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 551BV UT WOS:000274181600016 PM 20067409 ER PT J AU Conde, JG De, S Hall, RW Johansen, E Meglan, D Peng, GCY AF Conde, Jose G. De, Suvranu Hall, Richard W. Johansen, Edward Meglan, Dwight Peng, Grace C. Y. TI Telehealth Innovations in Health Education and Training SO TELEMEDICINE JOURNAL AND E-HEALTH LA English DT Editorial Material DE technology; telecommunications; innovations; teleresearch AB Telehealth applications are increasingly important in many areas of health education and training. In addition, they will play a vital role in biomedical research and research training by facilitating remote collaborations and providing access to expensive/remote instrumentation. In order to fulfill their true potential to leverage education, training, and research activities, innovations in telehealth applications should be fostered across a range of technology fronts, including online, on-demand computational models for simulation; simplified interfaces for software and hardware; software frameworks for simulations; portable telepresence systems; artificial intelligence applications to be applied when simulated human patients are not options; and the development of more simulator applications. This article presents the results of discussion on potential areas of future development, barries to overcome, and suggestions to translate the promise of telehealth applications into a transformed environment of training, education, and research in the health sciences. C1 [Conde, Jose G.] Univ Puerto Rico, RCMI Program, Sch Med, San Juan, PR 00936 USA. [De, Suvranu] Rensselaer Polytech Inst, Dept Mech Aerosp & Nucl Engn, Troy, NY USA. [Hall, Richard W.] Univ Arkansas Med Sci, Coll Med, Little Rock, AR 72205 USA. [Johansen, Edward] Calif Orthoped Res Network, Santa Monica, CA USA. [Meglan, Dwight] SimQuest, Westwood, MA USA. [Peng, Grace C. Y.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. RP Conde, JG (reprint author), Univ Puerto Rico, RCMI Program, Sch Med, Med Sci Campus,Off B621-A,GPO Box 365067, San Juan, PR 00936 USA. EM jose.conde1@upr.edu FU NCRR NIH HHS [G12 RR003051-120002]; NIBIB NIH HHS [R44EB008604] NR 13 TC 6 Z9 6 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED J E-HEALTH JI Telemed. J. e-Health PD JAN-FEB PY 2010 VL 16 IS 1 BP 103 EP 106 DI 10.1089/tmj.2009.0152 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 551BV UT WOS:000274181600017 PM 20155874 ER PT J AU Carroll, M James, JA Lardiere, MR Proser, M Rhee, K Sayre, MH Shore, JH Ternullo, J AF Carroll, Mark James, Judith A. Lardiere, Michael R. Proser, Michelle Rhee, Kyu Sayre, Michael H. Shore, Jay H. Ternullo, Joseph TI Innovation Networks for Improving Access and Quality Across the Healthcare Ecosystem SO TELEMEDICINE JOURNAL AND E-HEALTH LA English DT Editorial Material DE business administration/economics; distance learning; e-health; home health monitoring; policy AB Partnerships between patient communities, healthcare providers, and academic researchers are key to stepping up the pace and public health impact of clinical and translational research supported by the National Institutes of Health. With emphasis shifting toward community engagement and faster translation of research advances into clinical practice, academic researchers have a vital stake in widening the use of health information technology systems and telehealth networks to support collaboration and innovation. However, limited interaction between academic institutions and healthcare providers hinders the ability to form and sustain the integrated networks that are needed to conduct meaningful community-engaged research that improves public health outcomes. Healthcare providers, especially those affiliated with smaller practices, will need sustainable infrastructure and real incentives to utilize such networks, as well as training and additional resources for ongoing technical assistance. C1 [Ternullo, Joseph] Partners HealthCare Syst, Ctr Connected Hlth, Boston, MA 02114 USA. [Carroll, Mark] Indian Hlth Serv, Telehlth Program, Flagstaff, AZ USA. [James, Judith A.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Lardiere, Michael R.; Proser, Michelle] Natl Assoc, Ctr Community Hlth, Policy & Res Div, Bethesda, MD USA. [Rhee, Kyu] US Hlth Resources & Serv Adm, Rockville, MD 20857 USA. [Sayre, Michael H.] NIH, Div Res Infrastruct, Natl Ctr Res Resources, Bethesda, MD 20892 USA. [Shore, Jay H.] Univ Colorado Denver, Ctr Amer Indian, Aurora, CO USA. [Shore, Jay H.] Univ Colorado Denver, Ctr Alaska Native Hlth, Aurora, CO USA. [Shore, Jay H.] Vet Rural Hlth Resource Ctr, Dept Vet Affairs, Off Rural Hlth, Salt Lake City, UT USA. [Ternullo, Joseph] Partners HealthCare Syst, Ctr Connected Hlth, Boston, MA USA. RP Ternullo, J (reprint author), Partners HealthCare Syst, Ctr Connected Hlth, 25 New Chardon St,Suite 400D, Boston, MA 02114 USA. EM jternullo@partners.org FU NIAMS NIH HHS [P30 AR053483] NR 10 TC 7 Z9 7 U1 2 U2 13 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED J E-HEALTH JI Telemed. J. e-Health PD JAN-FEB PY 2010 VL 16 IS 1 BP 107 EP 111 DI 10.1089/tmj.2009.0157 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 551BV UT WOS:000274181600018 PM 20043702 ER PT J AU Alverson, DC Edison, K Flournoy, L Korte, B Magruder, C Miller, C AF Alverson, Dale C. Edison, Karen Flournoy, Larry Korte, Brenda Magruder, Charles Miller, Craig TI Telehealth Tools for Public Health, Emergency, or Disaster Preparedness and Response: A Summary Report SO TELEMEDICINE JOURNAL AND E-HEALTH LA English DT Editorial Material DE distance learning; e-health; extreme environments; telehealth; telemedicine AB Rapid advances in telehealth development and adoption are increasing the spectrum of information and communication technologies that can be applied not only to individual patient care but more broadly to population health as well. Participants in this breakout session were asked to address, from their diverse perspectives, a series of questions relating to the current and potential uses of telehealth applications and networks for public health and emergency/disaster preparedness and response systems. Participants identified several gaps in current understanding and research emphasis. There is a clear need for more and larger outcome studies to assess the impact and cost benefit of telehealth applications in terms of improving public health at the population and community levels. In addition, more research is needed to demonstrate the ability of telehealth tools and technologies to facilitate and extend the reach of major national clinical and public health research initiatives. Perhaps most importantly, the National Institutes of Health should develop and/or strengthen strategic partnerships with other funding agencies with overlapping or complementary interests to accelerate interdisciplinary research in this rapidly evolving but relatively understudied and complex field. C1 [Alverson, Dale C.] Univ New Mexico, Hlth Sci Ctr, Ctr Telehlth & Cybermed Res, Albuquerque, NM 87106 USA. [Edison, Karen] Univ Missouri, Dept Dermatol, Columbia, MO USA. [Flournoy, Larry] Texas A&M Univ, College Stn, TX USA. [Korte, Brenda] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Magruder, Charles] Ctr Dis Control & Prevent, Atlanta, GA USA. [Miller, Craig] US Dept HHS, Fed Hlth Architecture Program, Off Natl Coordinator Hlth Informat Technol, Bethesda, MD USA. RP Alverson, DC (reprint author), Univ New Mexico, Hlth Sci Ctr, Ctr Telehlth & Cybermed Res, 1005 Columbia NE, Albuquerque, NM 87106 USA. EM dalverson@salud.unm.edu NR 4 TC 5 Z9 5 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED J E-HEALTH JI Telemed. J. e-Health PD JAN-FEB PY 2010 VL 16 IS 1 BP 112 EP 114 DI 10.1089/tmj.2009.0149 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 551BV UT WOS:000274181600019 PM 20043703 ER PT J AU Alvarez, A Hoyle, S Valeri, MJ AF Alvarez, Alexandra Hoyle, Susan Josefina Valeri, Maria TI Voices in a love story: Merida letters from the eighteenth century SO TEXT & TALK LA English DT Article DE letters; text; discourse analysis; inequality; marriage; Spanish colonies AB The letter is the written genre, which in the past was nearest to orality, and it was used in the eighteenth century as a very important way of communicating officially and privately. The corpus of 33 letters under study constitutes a dialogue which discusses the issues concerning the marriage of a young mulatto girl with a slave. The corpus introduces 16 subjects-speakers and listeners or readers and writers in different production formats-instantiating the voices in this story. These voices represent conflicting ideologies-social and religious-but also conflicting interests in the development of the action. The study takes the corpus as a single text and interprets the plurality of voices as polyphony in the Bakhtinian sense. C1 [Alvarez, Alexandra] Univ Los Andes, Dept Linguist, Sector Liria, Merida, Venezuela. [Hoyle, Susan] Natl Lib Med, Bethesda, MD 20894 USA. [Josefina Valeri, Maria] Univ Valladolid, E-47002 Valladolid, Spain. RP Alvarez, A (reprint author), Univ Los Andes, Dept Linguist, Sector Liria, Ave Amer,Edificio A, Merida, Venezuela. EM alvarezmuro@gmail.com; susanhoyle@comcast.net; mjvaleri@gmail.com NR 19 TC 0 Z9 0 U1 1 U2 4 PU MOUTON DE GRUYTER PI BERLIN PA GENTHINER STRASSE 13, 10785 BERLIN, GERMANY SN 1860-7330 J9 TEXT TALK JI Text Talk PY 2010 VL 30 IS 4 BP 359 EP 384 DI 10.1515/TEXT.2010.018 PG 26 WC Communication; Linguistics; Language & Linguistics SC Communication; Linguistics GA 649HS UT WOS:000281759700001 ER PT J AU English, BC Baum, CE Adelberg, DE Sissung, TM Kluetz, PG Dahut, WL Price, DK Figg, WD AF English, Bevin C. Baum, Caitlin E. Adelberg, David E. Sissung, Tristan M. Kluetz, Paul G. Dahut, William L. Price, Douglas K. Figg, William D. TI A SNP in CYP2C8 is not associated with the development of bisphosphonate-related osteonecrosis of the jaw in men with castrate-resistant prostate cancer SO THERAPEUTICS AND CLINICAL RISK MANAGEMENT LA English DT Article DE bisphosphonates; ONJ; CYP2C8; polymorphism AB A single nucleotide polymorphism (SNP) in CYP2C8 (rs1934951), was previously identified in a genome-wide association study as a risk factor for the development of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BPs) for multiple myeloma. To determine if the same SNP is also associated with the development of ONJ in men receiving BPs for bone metastases from prostate cancer, we genotyped 100 men with castrate-resistant prostate cancer treated with bisphosphonates for bone metastases, 17 of whom developed ONJ. Important clinical characteristics, including type and duration of bisphosphonate therapy, were consistent among those who developed ONJ and those who did not. We found no significant correlation between the variant allele and the development of ONJ (OR = 0.63, 95% CI: 0.165-2.42, P > 0.47). This intronic SNP in CYP2C8 (rs1934951) does not seem to be a risk factor for the development of bisphosphonate-related ONJ in men with prostate cancer. It is important to note that this is only the second study to investigate the genetics associated with BP-related ONJ and the first to do so in men with prostate cancer. More studies are needed to identify genetic risk factors that may predict the development of this important clinical condition. C1 [English, Bevin C.; Baum, Caitlin E.; Price, Douglas K.; Figg, William D.] NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. [Sissung, Tristan M.; Figg, William D.] NCI, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. [Adelberg, David E.; Kluetz, Paul G.; Dahut, William L.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, 9000 Rockville Pike,Bldg 10,Rm 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Bethesda, MD, USA FX This study was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Bethesda, MD, USA. NR 32 TC 19 Z9 19 U1 0 U2 0 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-6336 J9 THER CLIN RISK MANAG JI Therap. Clin. Risk Manag. PY 2010 VL 6 BP 579 EP 583 DI 10.2147/TCRM.S14303 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA V29BI UT WOS:000208723500063 PM 21151627 ER PT S AU Shineman, DW Salthouse, TA Launer, LJ Hof, PR Bartzokis, G Kleiman, R Luine, V Buccafusco, JJ Small, GW Aisen, PS Lowe, DA Fillit, HM AF Shineman, Diana W. Salthouse, Timothy A. Launer, Lenore J. Hof, Patrick R. Bartzokis, George Kleiman, Robin Luine, Victoria Buccafusco, Jerry J. Small, Gary W. Aisen, Paul S. Lowe, David A. Fillit, Howard M. BA Shineman, DW BF Shineman, DW TI Therapeutics for cognitive aging SO THERAPEUTICS FOR COGNITIVE AGING SE Annals of the New York Academy of Sciences LA English DT Article ID PREFRONTAL CORTEX AREA-9; ALZHEIMERS-DISEASE; PYRAMIDAL NEURONS; MACAQUE MONKEYS; QUANTITATIVE-ANALYSIS; STEREOLOGIC ANALYSIS; RECOGNITION MEMORY; ENTORHINAL CORTEX; VULNERABLE SUBSET; CORTICAL CIRCUITS AB This review summarizes the scientific talks presented at the conference "Therapeutics for Cognitive Aging," hosted by the New York Academy of Sciences and the Alzheimer's Drug Discovery Foundation on May 15, 2009. Attended by scientists from industry and academia, as well as by a number of lay people-approximately 200 in all-the conference specifically tackled the many aspects of developing therapeutic interventions for cognitive impairment. Discussion also focused on how to define cognitive aging and whether it should be considered a treatable, tractable disease. C1 [Shineman, Diana W.; Fillit, Howard M.] Alzheimers Drug Discovery Fdn, New York, NY 10019 USA. [Salthouse, Timothy A.] Univ Virginia, Dept Psychol, Charlottesville, VA 22903 USA. [Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Hof, Patrick R.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Bartzokis, George; Small, Gary W.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Kleiman, Robin] Pfizer Global Res & Dev, Groton, CT USA. [Luine, Victoria] CUNY Hunter Coll, Dept Psychol, New York, NY 10021 USA. [Buccafusco, Jerry J.] Med Coll Georgia, Dept Pharmacol & Toxicol, Augusta, GA 30912 USA. [Aisen, Paul S.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Lowe, David A.] Memory Pharmaceut Corp, Montvale, NJ USA. RP Fillit, HM (reprint author), Alzheimers Drug Discovery Fdn, 1414 Ave Amer,Suite 1502, New York, NY 10019 USA. EM hfillit@alzdiscovery.org RI Bartzokis, George/K-2409-2013 FU NIA NIH HHS [R01 AG027342-03, R01 AG027342-01A2, R01 AG027342-04, R01 AG027342, R01 AG027342-02, R01 AG027342-05] NR 50 TC 5 Z9 5 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-790-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1191 IS S1 BP E1 EP E10 DI 10.1111/j.1749-6632.2010.05532.x PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BUA04 UT WOS:000288559200001 PM 20392284 ER PT B AU Moriwaki, S Kraemer, KH AF Moriwaki, Shinichi Kraemer, Kenneth H. BE Krieg, T Bickers, DR Miyachi, Y TI Disorders of DNA Repair SO THERAPY OF SKIN DISEASES: A WORLDWIDE PERSPECTIVE APPROACHES AND THEIR MOLECULAR BASIS LA English DT Article; Book Chapter ID XERODERMA-PIGMENTOSUM; COCKAYNE-SYNDROME; GENE-THERAPY; SKIN-CANCER; TRICHOTHIODYSTROPHY; CELLS; ABNORMALITIES; PATIENT C1 [Moriwaki, Shinichi] Osaka Med Coll, Dept Dermatol, Osaka 5698686, Japan. [Kraemer, Kenneth H.] NCI, DNA Repair Sect, Basic Res Lab, Bethesda, MD 20892 USA. RP Moriwaki, S (reprint author), Osaka Med Coll, Dept Dermatol, 2-7 Daigaku Cho, Osaka 5698686, Japan. EM der002@poh.osaka-med.ac.jp; Kraemerk@mih.gov NR 27 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-540-78813-3 PY 2010 BP 589 EP 595 DI 10.1007/978-3-540-78814-0_10.4 D2 10.1007/978-3-540-78814-0 PG 7 WC Dermatology SC Dermatology GA BNK93 UT WOS:000274824900052 ER PT J AU Machado-Vieira, R Salvadore, G DiazGranados, N Ibrahim, L Latov, D Wheeler-Castillo, C Baumann, J Henter, ID Zarate, CA AF Machado-Vieira, Rodrigo Salvadore, Giacomo DiazGranados, Nancy Ibrahim, Lobna Latov, David Wheeler-Castillo, Cristina Baumann, Jacqueline Henter, Ioline D. Zarate, Carlos A., Jr. TI New Therapeutic Targets for Mood Disorders SO THESCIENTIFICWORLDJOURNAL LA English DT Review DE bipolar disorder; mania; depression; treatment; mood; trial; therapeutic; target ID PROTEIN-KINASE-C; GLYCOGEN-SYNTHASE KINASE-3; MAJOR DEPRESSIVE DISORDER; BIPOLAR AFFECTIVE-DISORDER; PLACEBO-CONTROLLED TRIAL; HISTONE DEACETYLASE INHIBITORS; URIC-ACID METABOLISM; OPEN-LABEL TRIAL; FORCED SWIM TEST; RECEPTOR ANTAGONIST AB Existing pharmacological treatments for bipolar disorder (BPD) and major depressive disorder (MDD) are often insufficient for many patients. Here we describe a number of targets/compounds that clinical and preclinical studies suggest could result in putative novel treatments for mood disorders. These include: (1) glycogen synthase kinase-3 (GSK-3) and protein kinase C (PKC), (2) the purinergic system, (3) histone deacetylases (HDACs), (4) the melatonergic system, (5) the tachykinin neuropeptides system, (6) the glutamatergic system, and (7) oxidative stress and bioenergetics. The paper reviews data on new compounds that have shown antimanic or antidepressant effects in subjects with mood disorders, or similar effects in preclinical animal models. Overall, an improved understanding of the neurobiological underpinnings of mood disorders is critical in order to develop targeted treatments that are more effective, act more rapidly, and are better tolerated than currently available therapies. C1 [Machado-Vieira, Rodrigo; Salvadore, Giacomo; DiazGranados, Nancy; Ibrahim, Lobna; Latov, David; Wheeler-Castillo, Cristina; Baumann, Jacqueline; Henter, Ioline D.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut Mood & Anxiety Disorders Res Progr, NIH, Bethesda, MD 20892 USA. [Machado-Vieira, Rodrigo] Univ Sao Paulo, Inst & Dept Psychiat, LIM 27, BR-05508 Sao Paulo, Brazil. RP Zarate, CA (reprint author), NIMH, Expt Therapeut Mood & Anxiety Disorders Res Progr, NIH, Bethesda, MD 20892 USA. EM machadovieirar@mail.nih.gov; salvadoreg@mail.nih.gov; dnancy@mail.nih.gov; ibrahiml@mail.nih.gov; latovd@mail.nih.gov; cristina2@mail.nih.gov; baumannj2@mail.nih.gov; ioline.henter@nih.gov; zaratec@mail.nih.gov RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU National Institute of Mental Health (NIMH) FX This research was supported by the Intramural Research Program of the National Institute of Mental Health (NIMH). The authors declare that there are no personal financial holdings that could be perceived as constituting a potential conflict of interest. Dr. Zarate is listed as a coinventor on a patent for the use of ketamine in major depression; he has assigned his patent rights on ketamine to the U.S. Government. NR 129 TC 30 Z9 31 U1 1 U2 3 PU THESCIENTIFICWORLD LTD PI NEWBURY PA 29-34, VENTURE WEST, NEW GREENHAM PARK, NEWBURY, BERKSHIRE RG19 6HX, ENGLAND SN 1537-744X J9 THESCIENTIFICWORLDJO JI TheScientificWorldJOURNAL PY 2010 VL 10 BP 713 EP 726 DI 10.1100/tsw.2010.65 PG 14 WC Environmental Sciences; Multidisciplinary Sciences SC Environmental Sciences & Ecology; Science & Technology - Other Topics GA 585AB UT WOS:000276795500008 PM 20419280 ER PT S AU Philp, D Kleinman, HK AF Philp, Deborah Kleinman, Hynda K. BE Garaci, E Goldstein, AL TI Animal studies with thymosin beta(4), a multifunctional tissue repair and regeneration peptide SO THYMOSINS IN HEALTH AND DISEASE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 2nd International Symposium on Thymosins in Health and Disease CY SEP 30-OCT 02, 2009 CL Catania, ITALY DE thymosin beta(4); wound repair; tissue regeneration; inflammation; apoptosis; re-epithelialization ID CELL-MEDIATED CARDIOPROTECTION; INFLAMMATORY MEDIATORS; ENDOTHELIAL-CELLS; IN-VITRO; BETA-4; MIGRATION; ANGIOGENESIS; METASTASIS; EXPRESSION; SURVIVAL AB Studies in various animal models of disease and repair with thymosin beta(4) (T beta(4)), the major actin-sequestering molecule in mammalian cells, have provided the scientific foundation for the ongoing dermal, corneal, and cardiac wound repair multicenter clinical trials. T beta(4) has of multiple biological activities, which include down-regulation of inflammatory chemokines and cytokines, and promotion of cell migration, blood vessel formation, cell survival, and stem cell maturation. All of these activities contribute to the multiple wound healing properties that have been observed in animal studies. This paper reviews and discusses the topical and systemic uses of T beta(4) in various animal models that demonstrate its potential for clinical use. C1 [Philp, Deborah; Kleinman, Hynda K.] NIDCR, NIH, Bethesda, MD 20892 USA. RP Kleinman, HK (reprint author), NIDCR, NIH, 30 Convent Dr MSC 4370, Bethesda, MD 20892 USA. EM hkleinman@dir.nidcr.nih.gov NR 32 TC 20 Z9 22 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-801-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1194 BP 81 EP 86 DI 10.1111/j.1749-6632.2010.05479.x PG 6 WC Biochemistry & Molecular Biology; Immunology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Immunology; Science & Technology - Other Topics GA BRJ57 UT WOS:000282838000011 PM 20536453 ER PT B AU Luo, SJ Johnson, WE Smith, JLD O'Brien, SJ AF Luo, Shu-Jin Johnson, Warren E. Smith, James L. David O'Brien, Stephen J. BE Tilson, R Nyhus, PJ TI What Is a Tiger? Genetics and Phylogeography SO TIGERS OF THE WORLD: THE SCIENCE, POLITICS, AND CONSERVATION OF PANTHERA TIGRIS, 2ND EDITION LA English DT Article; Book Chapter ID PANTHERA-TIGRIS; CONSERVATION GENETICS; BIOGEOGRAPHIC BARRIER; MITOCHONDRIAL-DNA; VOLCANIC WINTER; SOUTHEAST-ASIA; NUCLEAR GENOME; BIG CAT; ISTHMUS; KRA C1 [Luo, Shu-Jin; Johnson, Warren E.; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21701 USA. [Luo, Shu-Jin; Smith, James L. David] Univ Minnesota, Dept Fisheries Wildlife & Conservat Biol, St Paul, MN 55108 USA. RP Luo, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21701 USA. RI Johnson, Warren/D-4149-2016 OI Johnson, Warren/0000-0002-5954-186X NR 61 TC 4 Z9 5 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-094751-8; 978-0-8155-1570-8 PY 2010 BP 35 EP 51 DI 10.1016/B978-0-8155-1570-8.00003-7 PG 17 WC Biodiversity Conservation; Veterinary Sciences SC Biodiversity & Conservation; Veterinary Sciences GA BES23 UT WOS:000317922600005 ER PT S AU Chen, X Oppenheim, JJ AF Chen, Xin Oppenheim, Joost J. BE Kollias, G Sfikakis, PP TI TNF-alpha: An Activator of CD4+FoxP3+TNFR2+ Regulatory T Cells SO TNF PATHOPHYSIOLOGY: MOLECULAR AND CELLULAR MECHANISMS SE Current Directions in Autoimmunity LA English DT Article; Book Chapter ID TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; PERTUSSIS TOXIN; SYNOVIAL-FLUID; IN-VIVO; AUTOIMMUNE-DISEASES; LUPUS NEPHRITIS; FACTOR RECEPTOR; CUTTING EDGE; NOD MICE AB TNF-alpha (TNF) is a pleiotropic cytokine which can have proinflammatory or immunosuppressive effects, depending on the context, duration of exposure and disease state. The basis for the opposing actions of TNF remains elusive. The growing appreciation of CD4+FoxP3+ regulatory T cells (Tregs), which comprise similar to 10% of peripheral CD4 cells, as pivotal regulators of immune responses has provided a new framework to define the cellular and molecular basis underlying the contrasting action of TNF. TNF by itself can overcome the profound anergic state of T cell receptor-stimulated Tregs. Furthermore, in concert with IL-2, TNF selectively activates Tregs, resulting in proliferation, upregulation of FoxP3 expression and increases in their suppressive activity. Both human and mouse Tregs predominantly express TNFR2, making it possible for TNF to enhance Treg activity, which helps limit the collateral damage caused by excessive immune responses and eventually terminates immune response. TNFR2-expressing CD4+FoxP3+ Tregs comprise similar to 40% of peripheral Tregs in normal mice and present the maximally suppressive subset of Tregs. In this review, studies describing the action of TNF on Treg function will be discussed. The role of Tregs in the autoimmune disorders and cancer as well as the effect of anti-TNF therapy on Tregs, especially in rheumatoid arthritis, will also be considered. Copyright (C) 2010 S. Karger AG, Basel C1 [Chen, Xin] NCI Frederick, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Oppenheim, Joost J.] NCI Frederick, Mol Immunoregulat Lab, CIP, Ctr Canc Res, Frederick, MD 21702 USA. RP Chen, X (reprint author), NCI Frederick, Basic Sci Program, SAIC Frederick Inc, POB B,Bldg 560,Rm 31-19, Frederick, MD 21702 USA. EM chenxin@mail.nih.gov RI Chen, Xin/I-6601-2015 OI Chen, Xin/0000-0002-2628-4027 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 91 TC 50 Z9 50 U1 2 U2 4 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1422-2132 BN 978-3-8055-9383-0 J9 CURR DIR AUTOIMMUN JI Curr. DIr Autoimmun. PY 2010 VL 11 BP 119 EP 134 PG 16 WC Immunology SC Immunology GA BNW18 UT WOS:000275723900007 PM 20173391 ER PT J AU Isomoto, H Moss, J Hirayama, T AF Isomoto, Hajime Moss, Joel Hirayama, Toshiya TI Pleiotropic Actions of Helicobacter pylori Vacuolating Cytotoxin, VacA SO TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Review DE Helicobacter pylori; vacuolating toxin; VacA ID TYROSINE-PHOSPHATASE-BETA; SYNTHASE KINASE 3-BETA; CYTOCHROME-C RELEASE; VIRULENCE FACTORS; T-LYMPHOCYTE; TOXIN VACA; RPTP-BETA; MOLECULAR CHARACTERIZATION; CELLULAR VACUOLATION; SIGNALING PATHWAY AB Helicobacter pylori produces a vacuolating cytotoxin, VacA, and most virulent H. pylori strains secrete VacA. VacA binds to two types of receptor-like protein tyrosine phosphatase (RPTP), RPTP alpha and RPTP beta, on the surface of host cells. VacA bound to RPTP beta, relocates and concentrates in lipid rafts in the plasma membrane. VacA causes vacuolization, membrane anion-selective channel and pore formation, and disruption of endosomal and lysosomal activity in host cells. Secreted VacA is processed into p33 and p55 fragments. The p55 domain not only plays a role in binding to target cells but also in the formation of oligomeric structures and anionic membrane channels. Oral administration of VacA to wild-type mice, but not to RPTP beta knockout mice, resulted in gastric ulcers, in agreement with the clinical effect of VacA. VacA with s1/m1 allele has more potent cytotoxic activity in relation to peptic ulcer disease and appears to be associated with human gastric cancer. VacA activates pro-apoptotic Bcl-2 family proteins, and induces apoptosis via a mitochondria-dependent pathway. VacA can disrupt other signal transduction pathways; VacA activates p38 MAPK, enhancing production of IL-8 and PGE(2), and PI3K/Akt, suppressing GSK-3 beta activity. VacA has immunomodulatory actions on T cells and other immune cells, possibly contributing to the chronic infection seen with this organism. H. pylori virulence factors including VacA and CagA, which is encoded by cytotoxin-associated gene A, along with host genetic and environmental factors, constitute a complex network to regulate chronic gastric injury and inflammation, which is involved in a multistep process leading to gastric carcinogenesis. C1 [Hirayama, Toshiya] Nagasaki Univ, Dept Bacteriol, Inst Trop Med, Nagasaki 8528523, Japan. [Isomoto, Hajime] Nagasaki Univ Hosp, Dept Endoscopy, Nagasaki, Japan. [Moss, Joel] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Hirayama, T (reprint author), Nagasaki Univ, Dept Bacteriol, Inst Trop Med, 1-12-4 Sakamoto, Nagasaki 8528523, Japan. EM hirayama@nagasaki-u.ac.jp NR 77 TC 32 Z9 36 U1 1 U2 7 PU TOHOKU UNIV MEDICAL PRESS PI SENDAI PA 2-1, SEIRYO-MACHI, AOBA-KU, SENDAI, MIYAGI 980-8575, JAPAN SN 0040-8727 EI 1349-3329 J9 TOHOKU J EXP MED JI Tohoku J. Exp. Med. PD JAN PY 2010 VL 220 IS 1 BP 3 EP 14 DI 10.1620/tjem.220.3 PG 12 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 544SN UT WOS:000273679700002 PM 20046046 ER PT J AU French, JE Leblanc, B Long, GG Morton, D Storer, R Leighton, J Swenberg, J Tsuda, H AF French, John E. Leblanc, Bernard Long, Gerald G. Morton, Daniel Storer, Richard Leighton, John Swenberg, James Tsuda, Hiroyuki TI Panel Discussion: Alternative Mouse Models for Carcinogenicity Assessment SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material DE carcinogenesis; animal models; genetically engineered mice; preclinical safety; assessment/risk management AB This article summarizes key points from Dr. Bernard Leblane's presentation European Perpectives on Alternative Mouse Carcinogenicity Models and a distillation of questions and answers from a panel discussion following plesentations on Alternative Mouse Models for Carcinogenicity Assessment at the Society of Toxicologic Pathology's annual symposium on June 23. 2009. in Washington. DC. C1 [French, John E.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Leblanc, Bernard] Pfizer, Amboise, France. [Long, Gerald G.] Eli Lilly & Co, Greenfield, IN USA. [Morton, Daniel] Pfizer Inc, Groton, CT 06340 USA. [Storer, Richard] Merck Res Labs, West Point, PA USA. [Leighton, John] US FDA, Silver Spring, MD USA. [Swenberg, James] Univ N Carolina, Chapel Hill, NC USA. [Tsuda, Hiroyuki] Nagoya City Univ, Sch Med, Nagoya, Aichi 467, Japan. RP Morton, D (reprint author), Pfizer Inc, MS-8274-1345,Eastern Point Rd, Groton, CT 06340 USA. EM dan.g.morton@pfizer.com NR 3 TC 2 Z9 2 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2010 VL 38 IS 1 BP 72 EP 75 DI 10.1177/0192623309352091 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA 559EL UT WOS:000274804800006 PM 19884653 ER PT J AU Bennett, CN Green, JE AF Bennett, Christina N. Green, Jeffrey E. TI Genomic Analyses as a Guide to Target Identification and Preclinical Testing of Mouse Models of Breast Cancer SO TOXICOLOGIC PATHOLOGY LA English DT Article DE genomics; mouse models; mammary cancer; preclinical testing ID MAMMARY-TUMORS; BASAL-LIKE; TRANSGENIC MICE; PARP INHIBITOR; CELL-LINES; STEM-CELLS; IN-VIVO; EXPRESSION; GENE; TUMORIGENESIS AB Cross-species genomic analyses have proven useful for identifying common genomic alterations that occur in human cancers and mouse models designed to recapitulate human tumor development. High-throughput molecular analyses provide a valuable tool for identifying particular animal models that may represent aspects of specific subtypes of human cancers. Corresponding alterations in gene copy number and expression in tumors from mouse and human suggest that these conserved changes may be mechanistically essential for cancer development and progression, and there-fore they may be critical targets for therapeutic intervention. Using a cross-species analysis approach, mouse models in which the functions of p53, Rb, and BRCA1 have been disrupted demonstrate molecular features of human, triple-negative (ER-, PR-, and ERBB2-), basal-type breast cancer. Using mouse tumor models based on the targeted abrogation of p53 and Rb function, we identified a large, integrated genetic network that correlates to poor outcome in several human epithelial cancers. This gene signature is highly enriched for genes involved in DNA replication and repair, chromosome maintenance, cell cycle regulation, and apoptosis. Current studies are determining whether inactivation of specific members within this signature, using drug or siRNA, will identify potentially important new targets to inhibit triple-negative, basal-type breast cancer for which no targeted therapies currently exist. C1 [Bennett, Christina N.; Green, Jeffrey E.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. RP Green, JE (reprint author), NCI, Lab Canc Biol & Genet, 37 Covent Dr, Bethesda, MD 20892 USA. EM jegreen@nih.gov FU Intramural Program; Center for Cancer Research; National Cancer Institute; NIH, Bethesda, MD FX This work was supported by the Intramural Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892. NR 48 TC 9 Z9 10 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2010 VL 38 IS 1 BP 88 EP 95 DI 10.1177/0192623309357074 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 559EL UT WOS:000274804800008 PM 20080934 ER PT J AU Hawes, JJ Reilly, KM AF Hawes, Jessica J. Reilly, Karlyne M. TI Bioluminescent Approaches for Measuring Tumor Growth in a Mouse Model of Neurofibromatosis SO TOXICOLOGIC PATHOLOGY LA English DT Article DE neurofibromatosis; astrocytoma; glioblastoma; malignant peripheral nerve sheath tumor; mouse models of cancer; bioluminescence ID NERVE SHEATH TUMORS; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; GLIOBLASTOMA-MULTIFORME; CELL-PROLIFERATION; IN-VIVO; NF1; TYPE-1; GENE; MICE; GLIOMAS AB Neurofibomatosis (NF1) patients arc susceptible to. multiple tumors of the nervous system including neurofibromas. optic glioma, malignant peripheral nerve sheath tumors(MPNSTs), and astrocytoma. The Nf1+/-; Trp53+/- (NPcis) mouse model of NF1 spontaneously develops astrocytoma and MPNSTs that Eire very similar to human NF1 tumors. To use this model for. testing potential therapeutics, we have developed systems that take advantage of bioluminescent reporters of tumor growth. We have generated E2F1 promoter-driven luciferase (ELUX) reporter mice to detect proliferating tumors in NPcis mice in vivo using bioluminescence. The power of this system is that it enables looking at tumor evolution and detecting spontaneous tumors at early stages of development as they evolve within their natural haploinsufficient microenvironment. This system can be used to identify tumors at different stages of tumorigenesis Mid to examine where spontaneous NF1 tumors initiate. The ability to rapidly screen multiple animals at a time increases the potential for use of this model in preclinical trials. This model will be valuable for the characterization of spontaneous NF1 tumors and will be important for studying the treatment and prevention of NF1 tumors in vivo. C1 [Hawes, Jessica J.; Reilly, Karlyne M.] NCI, Mouse Canc Genet Program, Ft Detrick, MD 21702 USA. RP Reilly, KM (reprint author), NCI, Mouse Canc Genet Program, W 7th St Ft Detrick,POB B,Bldg 560,Rm 32-20, Ft Detrick, MD 21702 USA. EM kreilly@nciferf.gov FU National Institutes of Health; National Cancer Institute; National Institutes of Health [HI-ISN261200800001E] FX This research was Supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HI-ISN261200800001E to SAIC, Inc. This research was performed while. J. J.. H. held a National Research Council Research Associateship Award at the National Cancer Institute. Special thanks to K. Fox and E. Truffer for animal care assistance and A. Leeder for bioimaging assistance. Special thanks to L. Feigenbaum and the Transgenic Mouse Model Laboratory, Laboratory Animal Sciences Program, SAIG Frederick, for generating the ELUX transgenic founder mice. All experiments were conducted in compliance with the Current laws of the United States. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States government. The authors declared that they had no conflicts of interests or financial disclosures with respect to their authorship or the publication of this article. NR 36 TC 7 Z9 7 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2010 VL 38 IS 1 BP 123 EP 130 DI 10.1177/0192623309357075 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 559EL UT WOS:000274804800011 PM 20176786 ER PT J AU Painter, JT Clayton, NP Herbert, RA AF Painter, J. T. Clayton, N. P. Herbert, R. A. TI Useful Immunohistochemical Markers of Tumor Differentiation SO TOXICOLOGIC PATHOLOGY LA English DT Article DE immunohistochemistry; carcinogenesis; rodent pathology ID GASTROINTESTINAL STROMAL TUMORS; CELLS; MICE AB Immunohistochemistry (IHC) has been somewhat underutilized in the practice of toxicological pathology but can be a valuable tool for the evaluation of rodent neoplasma, both in a diagnostic and an investigational role. Determining an exact tumor type using standard hematoxylin and cosin (H&E) staining for formalin-fixed tissues can be challenging, especially with metastatic and/or poorly differentiated tumors. Successful IHC is dependent on many factors, including species and tissue type, type, type and duration of fixation, quality fresh or frozen sectioning, and antibody specificity. The initial approach of most tumor diagnosis IHC applications is distinguishing epithelial from mesenechymal differentiation using vimentin and cytokeration markers, although false-negative and/or false-positive results may occur. Experimentally, IHC can be employed to investigate the earliest changes in transformed tissue, identifying cellular changes not normally visible with H&E. Individual markers for proliferation, apoptosis, and specific tumor proteins can be used to help distinguish hyperplasia from neoplasia and determine specific tumor origin-type. IHC provides a relatively rapid and simple method to better determine the origin of neoplastic tissue or investigate the behavior or progression of a given neoplasm. Several experimental and diagnostic examples will be presented to illustrate the utility of IHC as a supplement to standard staining techniques. C1 [Painter, J. T.] Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. [Clayton, N. P.; Herbert, R. A.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC USA. RP Painter, JT (reprint author), Integrated Lab Syst Inc, POB 13501, Res Triangle Pk, NC 27709 USA. EM tpainter@ils-inc.com FU Intramural NIH HHS [Z99 ES999999, ZIG ES102505-03, ZIG ES102505-02]; NIEHS NIH HHS [1K08-ES-00380, N01ES55548, K08 ES000380] NR 15 TC 13 Z9 14 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2010 VL 38 IS 1 BP 131 EP 141 DI 10.1177/0192623309356449 PG 11 WC Pathology; Toxicology SC Pathology; Toxicology GA 559EL UT WOS:000274804800012 PM 20028992 ER PT J AU King-Herbert, AP Sills, RC Bucher, JR AF King-Herbert, Angela P. Sills, Robert C. Bucher, John R. TI Commentary: Update on Animal Models for NTP Studies SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material DE NTP; animal models; B6C3F1/N mouse; F344/N rat; Wistar Han rat; Sprague Dawley rat ID BIOASSAY AB Based on recommendations of participants at the National Toxicology Program (NTP) workshop "Animal Models for the NTP Cancer Bioassay: Strains and Stocks-Should We Switch?" some modifications to the NTP rodent cancer bioassay were made. The B6C3F1 remains the mouse model Used in the cancer bioassay. The use of multiple strains of mice will be explored through a new branch within the NTP. the Host Susceptibility Branch. Several rat models were evaluated; the Harlan Sprague Dawley rat is currently being used in the NTP studies. C1 [King-Herbert, Angela P.; Sills, Robert C.] NIEHS NTP, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. RP King-Herbert, AP (reprint author), NIEHS NTP, Cellular & Mol Pathol Branch, POB 12233,111 Alexander Dr,Mail Drop B3-06, Res Triangle Pk, NC 27709 USA. EM Kingherl@niehs.nih.gov FU Intramural NIH HHS NR 4 TC 27 Z9 30 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2010 VL 38 IS 1 BP 180 EP 181 DI 10.1177/0192623309356450 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 559EL UT WOS:000274804800018 PM 20019353 ER PT J AU Chandra, SA Nolan, MW Malarkey, DE AF Chandra, Sundeep A. Nolan, Michael W. Malarkey, David E. TI Chemical Carcinogenesis of the Gastrointestinal Tract in Rodents: An Overview with Emphasis on NTP Carcinogenesis Bioassays SO TOXICOLOGIC PATHOLOGY LA English DT Article DE cancer; gastrointestinal tract; forestomach; stomach; intestine; rat; mouse; rodent; carcinoid; papilloma; carcinoma; adenoma; adenocarcinoma; neuroendocrine tumor; colon; colorectal; carcinogens; genotoxic; non-genotoxic; molecular biology; review; p53; animal model; NTP ID RATS SIGMODON-HISPIDUS; O-NITROTOLUENE; NONGENOTOXIC CARCINOGENS; STOMACH CARCINOGENESIS; FORESTOMACH TUMORS; CELL-PROLIFERATION; P-NITROTOLUENE; B6C3F(1) MICE; MOUSE MODELS; COLON-CANCER AB Cancers of the stomach and large intestine (LI) are the second and fourth leading causes of human cancer mortality. A review of the National Toxicology Program (NTP) database and the Carcinogenic Potency Database (CPDB) reveals that chemically induced neoplasma of the gastrointestinal tract (GIT) are relatively common. Within the GIT, epithelial tumors of the forestomach in mice and rats and LI of the rat are most common. Generally, there is a high species concordance for forestomach with at least 26 chemicals inducing tumors in both species. Glandular stomach tumors are rare, and the few reported are usually neuroendocrine tumors (carcinoids) originating from the enterochromaffin-life (ECL) cells. Of 290 carcinogenic agents identified by the NTP, 19 (7%) caused intestinal neoplasia, 14 in the rat and 5 in the mouse. Neoplasms occurred in both males and females, exclusively in the small intestine (SI) of the mouse and in the LI or both SI and LI in the rat. Enteric carcinogens (NTP) frequently induced neoplasms at other alimentary sites (oral cavity, esophagus, and stomach). In conclusion, the most common induced GIT tumors are squamous neoplasms of the forestomach, glandular neoplasms of the stomach are rare, and rats appear more prone to developing LI (colorectal) cancer compared to mice. C1 [Chandra, Sundeep A.] GlaxoSmithKline Inc, Safety Assessment, Pathol, Res Triangle Pk, NC 27709 USA. [Malarkey, David E.] NIEHS, Natl Toxicol Program, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. RP Chandra, SA (reprint author), GlaxoSmithKline Inc, Safety Assessment, Pathol, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS [Z99 ES999999] NR 48 TC 14 Z9 15 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2010 VL 38 IS 1 BP 188 EP 197 DI 10.1177/0192623309356452 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 559EL UT WOS:000274804800020 PM 20019352 ER PT J AU Hines, RN Sargent, D Autrup, H Birnbaum, LS Brent, RL Doerrer, NG Hubal, EAC Juberg, DR Laurent, C Luebke, R Olejniczak, K Portier, CJ Slikker, W AF Hines, Ronald N. Sargent, Dana Autrup, Herman Birnbaum, Linda S. Brent, Robert L. Doerrer, Nancy G. Hubal, Elaine A. Cohen Juberg, Daland R. Laurent, Christian Luebke, Robert Olejniczak, Klaus Portier, Christopher J. Slikker, William TI Approaches for Assessing Risks to Sensitive Populations: Lessons Learned from Evaluating Risks in the Pediatric Population SO TOXICOLOGICAL SCIENCES LA English DT Review DE sensitive populations; pharmacokinetics; pharmacodynamics; genetic variability; pediatric population; risk assessment; exposure assessment ID NMDA RECEPTOR ANTAGONISTS; HUMAN PARAOXONASE PON1; HUMAN-FETAL LIVER; EXPOSURE ASSESSMENT; CHILDRENS HEALTH; ENVIRONMENTAL TOXICANTS; DEVELOPMENTAL-STAGE; IONIZING-RADIATION; NATIONAL CHILDRENS; POLYCHLORINATED-BIPHENYLS AB Assessing the risk profiles of potentially sensitive populations requires a "tool chest" of methodological approaches to adequately characterize and evaluate these populations. At present, there is an extensive body of literature on methodologies that apply to the evaluation of the pediatric population. The Health and Environmental Sciences Institute Subcommittee on Risk Assessment of Sensitive Populations evaluated key references in the area of pediatric risk to identify a spectrum of methodological approaches. These approaches are considered in this article for their potential to be extrapolated for the identification and assessment of other sensitive populations. Recommendations as to future research needs and/or alternate methodological considerations are also made. C1 [Doerrer, Nancy G.] Hlth & Environm Sci Inst, Int Life Sci Inst, Washington, DC 20005 USA. [Hines, Ronald N.] Childrens Hosp & Hlth Syst, Childrens Res Inst, Dept Pediat, Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Sargent, Dana] Bayer CropSci, Res Triangle Pk, NC 27709 USA. [Autrup, Herman] Univ Aarhus, Dept Environm & Occupat Med, DK-8000 Aarhus C, Denmark. [Birnbaum, Linda S.; Portier, Christopher J.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Brent, Robert L.] Alfred I duPont Hosp Children, Wilmington, DE 19899 USA. [Hubal, Elaine A. Cohen; Luebke, Robert] US EPA, Res Triangle Pk, NC 27709 USA. [Juberg, Daland R.] Dow AgroSci, Indianapolis, IN 46268 USA. [Laurent, Christian] European Food Safety Author, I-43100 Parma, Italy. [Olejniczak, Klaus] BfArM, Fed Inst Drugs & Med Devices, D-53175 Bonn, Germany. [Slikker, William] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Doerrer, NG (reprint author), Hlth & Environm Sci Inst, Int Life Sci Inst, 1156 15th St NW,2nd Floor, Washington, DC 20005 USA. EM ndoerrer@hesiglobal.org RI Portier, Christopher/A-3160-2010; OI Portier, Christopher/0000-0002-0954-0279; Hines, Ronald/0000-0002-3094-4200 FU NIGMS NIH HHS [R01 GM081344] NR 143 TC 13 Z9 15 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2010 VL 113 IS 1 BP 4 EP 26 DI 10.1093/toxsci/kfp217 PG 23 WC Toxicology SC Toxicology GA 534ZH UT WOS:000272935700002 PM 19770482 ER PT J AU Bility, MT Zhu, BK Kang, BH Gonzalez, FJ Peters, JM AF Bility, Moses T. Zhu, Bokai Kang, Boo H. Gonzalez, Frank J. Peters, Jeffrey M. TI Ligand Activation of Peroxisome Proliferator-Activated Receptor-beta/delta and Inhibition of Cyclooxygenase-2 Enhances Inhibition of Skin Tumorigenesis SO TOXICOLOGICAL SCIENCES LA English DT Article DE peroxisome proliferator-activated receptor; nonsteroidal anti-inflammatory drugs; cyclooxygenase-2; differentiation ID EPIDERMAL-CELL LINES; PPAR-BETA/DELTA; GENE-EXPRESSION; DIFFERENTIATION; CARCINOGENESIS; GROWTH; KERATINOCYTES; BETA; METABOLISM; MODULATION AB Ligand activation of peroxisome proliferator-activated receptor (PPAR)-beta/delta and inhibition of cyclooxygenase-2 (COX-2) activity by nonsteroidal anti-inflammatory drugs can attenuate skin tumorigenesis. There is also evidence that attenuation of skin tumorigenesis by inhibition of COX-2 activity occurs through PPAR beta/delta-independent mechanisms. The present study examined the hypothesis that combining ligand activation of PPAR beta/delta with inhibition of COX-2 activity will cooperatively inhibit chemically induced skin tumor progression using both in vivo and ex vivo models. A two-stage chemical carcinogenesis bioassay was performed in wild-type and Ppar beta/delta-null mice. After 22 weeks, cohorts of both mouse lines were divided into four experimental groups: (1) control, (2) topical application of the PPAR beta/delta ligand GW0742, (3) dietary administration of the COX-2 inhibitor nimesulide, or (4) both GW0742 and nimesulide. Ligand activation of PPAR beta/delta did not influence skin tumor progression, while a modest decrease in skin tumor multiplicity was observed with dietary nimesulide. Interestingly, the combined treatment of GW0742 and nimesulide increased the efficacy of the decrease in papilloma multiplicity for 6 weeks in wild-type mice, but this effect was not found at later time points and was not found in similarly treated Ppar beta/delta-null mice. Neoplastic keratinocyte lines cultured with GW0742 and nimesulide also exhibited enhanced inhibition of cell proliferation coincident with increased expression of Keratin messenger RNAs. Results from these studies support the hypothesis that combining ligand activation of PPAR beta/delta with inhibition of COX-2 activity can inhibit chemically induced skin tumor progression by modulating differentiation. C1 [Bility, Moses T.; Zhu, Bokai; Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Bility, Moses T.; Zhu, Bokai; Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. [Kang, Boo H.] Preclin Res Ctr, Yongin 449826, Gyeonggi Do, South Korea. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. EM jmp21@psu.edu RI Peters, Jeffrey/D-8847-2011 FU National Institutes of Health [CA124533] FX National Institutes of Health (CA124533 to J. M. P.). NR 35 TC 17 Z9 17 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2010 VL 113 IS 1 BP 27 EP 36 DI 10.1093/toxsci/kfp212 PG 10 WC Toxicology SC Toxicology GA 534ZH UT WOS:000272935700003 PM 19748995 ER PT J AU Wielgus, AR Zhao, B Chignell, CF Hu, DN Roberts, JE AF Wielgus, Albert R. Zhao, Baozhong Chignell, Colin F. Hu, Dan-Ning Roberts, Joan E. TI Phototoxicity and cytotoxicity of fullerol in human retinal pigment epithelial cells SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Nanoparticles; Fullerenes; Fullerol; Ocular toxicology; Ocular phototoxicity; Human retinal pigment epithelial cells; Singlet oxygen; Superoxide; Lipid peroxidation ID ENDOTHELIAL GROWTH-FACTOR; SINGLET OXYGEN GENERATION; WATER-SOLUBLE FULLERENES; GLYCATION END-PRODUCTS; IN-VITRO; PHOTOPHYSICAL PROPERTIES; ASCORBIC-ACID; LIPID-PEROXIDATION; PHOTODYNAMIC THERAPY; OCULAR PHOTOTOXICITY AB The water-soluble nanoparticle hydroxylated fullerene [fullerol, nano-C(60)(OH)(22-26)] has several applications including use as a drug carrier to bypass the blood ocular barriers. We have previously found that fullerol is both cytotoxic and phototoxic to human lens epithelial cells (HLE B-3) and that the endogenous antioxidant lutein blocked some of this phototoxicity. In the present study we have found that fullerol induces cytotoxic and phototoxic damage to human retinal pigment epithelial cells. Accumulation of nano-C(60)(OH)(22-26) in the cells was confirmed spectrophotometrically at 405 nm, and cell viability, cell metabolism and membrane permeability were estimated using trypan blue, MTS and LDH assays, respectively. Fullerol was cytotoxic toward hRPE cells maintained in the dark at concentrations higher than 10 mu M. Exposure to an 8.5 J. cm(-2) dose of visible light in the presence of >5 mu M fullerol induced TBARS formation and early apoptosis, indicating phototoxic damage in the form of lipid peroxidation. Pretreatment with 10 and 20 M lutein offered some protection against fullerol photodamage. Using time resolved photophysical techniques, we have now confirmed that fullerol produces singlet oxygen with a quantum yield of Phi=0.05 in D(2)O and with a range of 0.002-0.439 in various solvents. As our previous studies have shown that fullerol also produces superoxide in the presence of light, retinal phototoxic damage may occur through both type I (free radical) and type II (singlet oxygen) mechanisms. In conclusion, ocular exposure to fullerol, particularly in the presence of sunlight, may lead to retinal damage. (C) Published by Elsevier Inc. C1 [Roberts, Joan E.] Fordham Univ, Dept Nat Sci, Lincoln Ctr, New York, NY 10023 USA. [Wielgus, Albert R.; Zhao, Baozhong; Chignell, Colin F.] Natl Inst Environm Hlth Sci, Pharmacol Lab, Res Triangle Pk, NC 27709 USA. [Hu, Dan-Ning] New York Eye & Ear Infirm, Tissue Culture Ctr, New York, NY 10002 USA. RP Roberts, JE (reprint author), Fordham Univ, Dept Nat Sci, Lincoln Ctr, 113 W 60th St, New York, NY 10023 USA. EM jroberts@fordham.edu RI Zhao, Baozhong/B-5865-2011 FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (NIEHS) FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (NIEHS). We wish to thank the following persons from NIEHS: Dr. Anil Motten for help in preparation of this manuscript, Dr. Carl Bortner and Maria Sifre for their assistance with flow cytometry measurements, Ms. Deloris Sutton for the TEM images, and Dr. Piotr Bilski for his help in setting up the 1O2 detection system. Images of the cells were taken by C. Jeff Tucker at the NIEHS Fluorescence Microscopy and Imaging Center. We also wish to thank Dr. Cynthia Smith of National Toxicology Program, NIEHS for supplying the fullerol, fullerene and fullerene hydride used in these experiments and Drs. William Boyes and Laura Degn of the US Environmental Protection Agency Research (USEPA) for assistance with the Zeta measurements. This manuscript has been reviewed by the National Institutes of Environmental Health Sciences and approved for publication. NR 90 TC 45 Z9 47 U1 3 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JAN 1 PY 2010 VL 242 IS 1 BP 79 EP 90 DI 10.1016/j.taap.2009.09.021 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 528HT UT WOS:000272434800009 PM 19800903 ER PT S AU Bharti, K Debbache, J Wang, X Arnheiter, H AF Bharti, Kapil Debbache, Julien Wang, Xin Arnheiter, Heinz BE Higgins, PJ TI The Basic-Helix-Loop-Helix-Leucine Zipper Gene Mitf: Analysis of Alternative Promoter Choice and Splicing SO TRANSCRIPTION FACTORS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Reverse transcriptase polymerase chain reaction; Real-time PCR; Serine phosphorylation; Knock-in allele ID MOUSE MICROPHTHALMIA LOCUS; SUMOYLATION; MELANOCYTES; MUTATIONS; EYE AB The activity of transcription factors is often regulated by Post-translational modifications. A precondition for such modifications is the presence, in the corresponding mRNAs, of the exons that either directly encode the modifiable residues in question, or encode protein domains that influence their modification indirectly. The inclusion or exclusion of coding exons is regulated predominantly by alternative splicing but can also depend on promoter choice and polyadenylation site selection. Information about exon inclusion and exclusion, both qualitatively and quantitatively, is particularly important for experiments designed to mutate endogenous codons because such mutations can alter splicing patterns. Therefore, we here describe methods employed to quantitate exon inclusion and exclusion, using as example a mouse transcription factor gene, Mitf. C1 [Bharti, Kapil; Debbache, Julien; Wang, Xin; Arnheiter, Heinz] Natl Inst Neurol Disorders & Stroke, Mammalian Dev Sect, NIH, Bethesda, MD USA. RP Bharti, K (reprint author), Natl Inst Neurol Disorders & Stroke, Mammalian Dev Sect, NIH, Bethesda, MD USA. FU Intramural NIH HHS [ZIA NS003021-03] NR 14 TC 3 Z9 3 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-737-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 647 BP 237 EP 250 DI 10.1007/978-1-60761-738-9_14 D2 10.1007/978-1-60761-738-9 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BPS78 UT WOS:000279812300014 PM 20694671 ER PT J AU Mohan, KVK Rao, SS Atreya, CD AF Mohan, Ketha V. K. Rao, Shilpakala Sainath Atreya, Chintamani D. TI Evaluation of antimicrobial peptides as novel bactericidal agents for room temperature-stored platelets SO TRANSFUSION LA English DT Article ID BLOOD COMPONENTS; PATHOGEN-REDUCTION; WHOLE-BLOOD; TRANSFUSION; CONTAMINATION; MECHANISMS; SYSTEMS AB BACKGROUND: A single cost-effective pathogen inactivation approach would help to improve the safety of our nation's blood supply. Several methods and technologies are currently being studied to help reduce bacterial contamination of blood components. There is clearly need for simple and easy-to-use pathogen inactivation techniques specific to plasma, platelets (PLTs), and red blood cells. STUDY DESIGN AND METHODS: In this report, we introduce a novel proof of concept: using known therapeutic antimicrobial peptides (AMPs) as bactericidal agents for room temperature-stored PLT concentrates (PCs). Nine synthetic AMPs, four from PLT microbicidal protein-derived peptides (PD1-4) and five Arg-Trp (RW) repeat peptides containing one to five repeats, were tested for bactericidal activity in plasma and PC samples spiked with Staphylococcus aureus, S. epidermidis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Bacillus cereus. A 3-log reduction of viable bacteria was considered as the bactericidal activity of a given peptide. RESULTS: In both plasma alone and PCs, RW3 peptide demonstrated bactericidal activity against S. aureus, S. epidermidis, E. coli, P. aeruginosa, and K. pneumoniae; PD4 and RW2 against P. aeruginosa; and RW4 against K. pneumoniae. The activity of each of these four peptides against the remaining bacterial species in the test panel resulted in less than a 3-log reduction in the number of viable bacteria and hence considered ineffective. CONCLUSIONS: These findings suggest a new approach to improving the safety of blood components, demonstrating the potential usefulness of screening therapeutic AMPs against selected bacteria to identify suitable bactericidal agents for stored plasma, PCs, and other blood products. C1 [Mohan, Ketha V. K.; Rao, Shilpakala Sainath; Atreya, Chintamani D.] US FDA, Ctr Biol Evaluat & Res, Sect Cell Biol, Lab Cellular Hematol, Bethesda, MD USA. RP Atreya, CD (reprint author), Bldg 29A,Room 2C-11,NIH Campus,8800 Rockville Pik, Bethesda, MD 20892 USA. EM chintamani.atreya@fda.hhs.gov FU Center for Biologics Evaluation and Research (CBER); Oak Ridge Institute for Science and Education (ORISE) FX SSR is a recipient of a postdoctoral fellowship at the Center for Biologics Evaluation and Research (CBER) administered by the Oak Ridge Institute for Science and Education (ORISE) through an intraagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The authors thank M. Kannan and S. Kulkarni, DH, OBRR, CBER, for review of the scientific content of the manuscript and Mitchell Berger, OBRR, CBER, for editorial review. NR 27 TC 10 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 2010 VL 50 IS 1 BP 166 EP 173 DI 10.1111/j.1537-2995.2009.02376.x PG 8 WC Hematology SC Hematology GA 538FX UT WOS:000273171000025 PM 19761549 ER PT J AU Schmid, P von Zabern, I Scharberg, EA Wagner, FF Flegel, WA AF Schmid, Pirmin von Zabern, Inge Scharberg, Erwin A. Wagner, Franz F. Flegel, Willy A. TI Specific amino acid substitutions cause distinct expression of JAL (RH48) and JAHK (RH53) antigens in RhCE and not in RhD SO TRANSFUSION LA English DT Letter ID MOLECULAR-BASIS C1 [Schmid, Pirmin] Univ Hosp Ulm, Inst Transfus Med, Ulm, Germany. [von Zabern, Inge; Scharberg, Erwin A.] German Red Cross DRK Blood Donor Serv, Baden Wurttemberg Hessen, Germany. [von Zabern, Inge; Scharberg, Erwin A.] German Red Cross DRK Blood Donor Serv, Ulm, Germany. [von Zabern, Inge; Scharberg, Erwin A.] German Red Cross DRK Blood Donor Serv, Baden Baden, Germany. [Wagner, Franz F.] German Red Cross DRK Blood Donor Serv NSTOB, Springe, Germany. [Flegel, Willy A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Schmid, P (reprint author), Univ Hosp Ulm, Inst Transfus Med, Ulm, Germany. EM flegelwa@cc.nih.gov RI Schmid, Pirmin/A-1457-2009 FU Intramural NIH HHS [Z99 CL999999] NR 8 TC 2 Z9 3 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 2010 VL 50 IS 1 BP 267 EP 269 PG 3 WC Hematology SC Hematology GA 538FX UT WOS:000273171000040 PM 20233350 ER PT J AU Op de Beeck, HP Baker, CI AF Op de Beeck, Hans P. Baker, Chris I. TI The neural basis of visual object learning SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID INFERIOR TEMPORAL CORTEX; MONKEY INFEROTEMPORAL CORTEX; HUMAN EXTRASTRIATE CORTEX; LONG-TERM-MEMORY; SHAPE SELECTIVITY; FACE RECOGNITION; RESPONSE PROPERTIES; NATURAL STATISTICS; ADULT MONKEYS; HUMAN BRAIN AB Object vision in human and nonhuman primates is often cited as a primary example of adult plasticity in neural information processing. It has been hypothesized that visual experience leads to single neurons in the monkey brain with strong selectivity for complex objects, and to regions in the human brain with a preference for particular categories of highly familiar objects. This view suggests that adult visual experience causes dramatic local changes in the response properties of high-level visual cortex. Here, we review the current neurophysiological and neuroimaging evidence and find that the available data support a different conclusion: adult visual experience introduces moderate, relatively distributed effects that modulate a pre-existing, rich and flexible set of neural object representations. C1 [Op de Beeck, Hans P.] Univ Leuven KU Leuven, Lab Biol Psychol, B-3000 Louvain, Belgium. [Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Op de Beeck, HP (reprint author), Univ Leuven KU Leuven, Lab Biol Psychol, Tiensestr 102, B-3000 Louvain, Belgium. EM hans.opdebeeck@psy.kuleuven.be; bakerchris@mail.nih.gov OI Baker, Chris/0000-0001-6861-8964 FU Human Frontier Science Program [CDA 0040/2008]; Fund for Scientific Research - Flanders [1.5.022.08]; NIH FX We thank Annie Chan, Assaf Harel, Dwight Kravitz, Sue-Hyun Lee and Rufin Vogels for comments on the manuscript, and Wouter De Baene, James DiCarlo, Chou Hung, Xiong Jiang, Nuo Li, Christopher Moore, Charan Ranganath, Maximilian Riesenhuber and Rufin Vogels for providing stimuli and data values. Support was provided by the Human Frontier Science Program (grant CDA 0040/2008 to H.O.d.B.), the Fund for Scientific Research - Flanders (grant 1.5.022.08 to H.O.d.B.), and the NIH Intramural Research Program at NIMH. NR 103 TC 31 Z9 31 U1 1 U2 25 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD JAN PY 2010 VL 14 IS 1 BP 22 EP 30 DI 10.1016/j.tics.2009.11.002 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 548OR UT WOS:000273974700007 PM 19945336 ER PT J AU Biddie, SC John, S Hager, GL AF Biddie, Simon C. John, Sam Hager, Gordon L. TI Genome-wide mechanisms of nuclear receptor action SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID RNA-POLYMERASE-II; PROTEIN-DNA INTERACTIONS; IN-VIVO; GLUCOCORTICOID-RECEPTOR; ESTROGEN-RECEPTOR; GENE-EXPRESSION; BINDING-SITES; BREAST-CANCER; TRANSCRIPTIONAL NETWORK; CHROMATIN-STRUCTURE AB Nuclear receptors are involved in a myriad of physiological processes, responding to ligands and binding to DNA at sequence-specific cis-regulatory elements. This binding occurs in the context of chromatin, a critical factor in regulating eukaryotic transcription. Recent high-throughput assays have examined nuclear receptor action genome-wide, advancing our understanding of receptor binding to regulatory elements. Here, we discuss current knowledge of genome-wide response element occupancy by receptors and the function of transcription factor networks in regulating nuclear receptor action. We highlight emerging roles for the epigenome, chromatin remodeling, histone modification, histone variants and long-range chromosomal interactions in nuclear receptor binding and receptor-dependent gene regulation. These mechanisms contribute importantly to the action of nuclear receptors in health and disease. C1 [Biddie, Simon C.; John, Sam; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. [Biddie, Simon C.] Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, Bristol BS1 3NY, Avon, England. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,Room B602,41 Lib Dr, Bethesda, MD 20892 USA. OI Biddie, Simon/0000-0002-8253-0253 FU Intramural Research Program of the National Institutes of Health; National Cancer Institute; Center for Cancer Research; Needham Cooper Postgraduate Medicine Scholarship; Faculty of Medicine, University of Bristol FX This research was supported, in part, by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research S C B was supported, in part, by The Needham Cooper Postgraduate Medicine Scholarship held by Stafford L Lightman and the Faculty of Medicine, University of Bristol The authors would like to thank Karen J Meaburn and Ofir Hakim for helpful comments NR 59 TC 55 Z9 55 U1 1 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD JAN PY 2010 VL 21 IS 1 BP 3 EP 9 DI 10.1016/j.tem.2009.08.006 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 554JC UT WOS:000274430300001 PM 19800253 ER PT J AU Kristensen, DM Mushegian, AR Dolja, VV Koonin, EV AF Kristensen, David M. Mushegian, Arcady R. Dolja, Valerian V. Koonin, Eugene V. TI New dimensions of the virus world discovered through metagenomics SO TRENDS IN MICROBIOLOGY LA English DT Review ID STRANDED RNA VIRUSES; TRANSFER AGENT GENES; LARGE DNA VIRUSES; EVOLUTIONARY GENOMICS; VIRAL METAGENOMICS; MARINE VIRUSES; SARGASSO SEA; MIMIVIRUS; SEQUENCES; COMMUNITIES AB Metagenomic analysis of viruses suggests novel patterns of evolution, changes the existing ideas of the composition of the virus world and reveals novel groups of viruses and virus-like agents. The gene composition of the marine DNA virome is dramatically different from that of known bacteriophages. The virome is dominated by rare genes, many of which might be contained within virus-like entities such as gene transfer agents. Analysis of marine metagenomes thought to consist mostly of bacterial genes revealed a variety of sequences homologous to conserved genes of eukaryotic nucleocytoplasmic large DNA viruses, resulting in the discovery of diverse members of previously undersampled groups and suggesting the existence of new classes of virus-like agents. Unexpectedly, metagenomics of marine RNA viruses showed that representatives of only one superfamily of eukaryotic viruses, the picorna-like viruses, dominate the RNA virome. C1 [Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Kristensen, David M.; Mushegian, Arcady R.] Stowers Inst Med Res, Kansas City, MO 64110 USA. [Mushegian, Arcady R.] Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66160 USA. [Dolja, Valerian V.] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA. [Dolja, Valerian V.] Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov OI Mushegian, Arcady/0000-0002-6809-9225 FU Intramural NIH HHS [ZIA LM000073-16] NR 67 TC 140 Z9 145 U1 3 U2 56 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD JAN PY 2010 VL 18 IS 1 BP 11 EP 19 DI 10.1016/j.tim.2009.11.003 PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 562VV UT WOS:000275084300002 PM 19942437 ER PT J AU Holmes, A Quirk, GJ AF Holmes, Andrew Quirk, Gregory J. TI Pharmacological facilitation of fear extinction and the search for adjunct treatments for anxiety disorders - the case of yohimbine SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; FREELY-MOVING RATS; CONDITIONED FEAR; SEROTONIN TRANSPORTER; FRONTAL-CORTEX; INFRALIMBIC CORTEX; INDUCED INCREASES; 5-HT1A RECEPTORS; D-CYCLOSERINE; MICE AB There is current interest in identifying drugs that facilitate fear extinction, as this form of learning is the basis of certain cognitive therapies for anxiety disorders. Following an initial report several years ago that the alpha 2-adrenoreceptor antagonist yohimbine facilitated extinction in mice, more recent studies have shown mixed effects or even impairment. It has become clear that the effect of yohimbine on extinction depends on a number of factors, including genetic background, contextual variables and the presence of competing behaviors. To what extent theses effects of yohimbine are mediated through the alpha 2-adrenoreceptor, as opposed to other sites of action, is also uncertain. More work is needed before this drug can be approved as a pharmacological adjunct for extinction-based therapies. More generally, the case of yohimbine may serve as a model for the development of other extinction facilitators. C1 [Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Bethesda, MD 20852 USA. [Quirk, Gregory J.] Univ Puerto Rico, Sch Med, Dept Psychiat, San Juan, PR 00936 USA. [Quirk, Gregory J.] Univ Puerto Rico, Sch Med, Dept Anat & Neurobiol, San Juan, PR 00936 USA. RP Holmes, A (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Bethesda, MD 20852 USA. EM holmesan@mail.nih.gov FU NIAAA; NIH [MH058883, MH081975] FX AH is supported by the NIAAA intramural research program. GJQ is supported by NIH grants MH058883 and MH081975. NR 70 TC 51 Z9 53 U1 2 U2 11 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD JAN PY 2010 VL 31 IS 1 BP 2 EP 7 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 553OW UT WOS:000274377700002 PM 20036429 ER PT B AU Rapisarda, A Melillo, G AF Rapisarda, Annamaria Melillo, Giovanni BE Bagley, RG TI Combination Strategies Targeting Hypoxia Inducible Factor 1 (HIF-1) for Cancer Therapy SO TUMOR MICROENVIRONMENT SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter ID ENDOTHELIAL-GROWTH-FACTOR; HISTONE DEACETYLASE INHIBITORS; SMALL-MOLECULE INHIBITORS; FACTOR-I INHIBITION; TUMOR-CELL DEATH; FACTOR 1-ALPHA; MAMMALIAN TARGET; BREAST-CANCER; UNFAVORABLE PROGNOSIS; FACTOR EXPRESSION AB Solid tumors often present regions of decreased oxygen levels (hypoxia) due to an imbalance between increased oxygen consumption and insufficient oxygen delivery from the aberrant tumor vasculature. Intratumor hypoxia is associated with altered cellular metabolism, an invasive and metastatic phenotype, as well as resistance to radiation and chemotherapy. The discovery of Hypoxia Inducible Factor-1 (HIF-1), a transcription factor critically involved in cellular responses to hypoxia and tumor progression, has provided evidence of a potential molecular target of intratumor hypoxia that could be exploited for the development of novel cancer therapeutics. A growing number of small molecule inhibitors of HIF-1, which act by distinct molecular mechanisms, have been described so far. However, HIF-1 expression in human cancers is focal and heterogeneous, consistent with the possibility that single agent HIF-1 inhibitors may have limited clinical activity. It is then plausible that combination strategies aimed at maximizing the clinical potential of HIF-1 inhibition may be more effective. We will discuss current approaches used for targeting HIF-1, emphasizing in particular opportunities for rationally designed combination strategies aimed at exploiting vulnerable features of the tumor microenvironment. C1 [Rapisarda, Annamaria; Melillo, Giovanni] NCI, SAIC Frederick Inc, DTP Tumor Hypoxia Lab, Dev Therapeut Program, Frederick, MD 21702 USA. RP Melillo, G (reprint author), NCI, SAIC Frederick Inc, DTP Tumor Hypoxia Lab, Dev Therapeut Program, Bldg 432,Room 218, Frederick, MD 21702 USA. EM melillog@mail.nih.gov NR 117 TC 1 Z9 2 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4419-6614-8 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2010 BP 3 EP 21 DI 10.1007/978-1-4419-6615-5_1 D2 10.1007/978-1-4419-6615-5 PG 19 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BQY41 UT WOS:000282104500001 ER PT B AU Jakowlew, SB AF Jakowlew, Sonia B. BE Bagley, RG TI Transforming Growth Factor-beta in Lung Cancer, Carcinogenesis, and Metastasis SO TUMOR MICROENVIRONMENT SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter ID EPITHELIAL-MESENCHYMAL TRANSITION; RECEPTOR-TYPE-I; MESSENGER-RNA EXPRESSION; HUMAN-CHROMOSOME 18Q21.1; HUMAN PROSTATE-CANCER; CD8(+) T-CELLS; TGF-BETA; BREAST-CANCER; TUMOR-METASTASIS; EXTRACELLULAR-MATRIX AB Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory polypeptide that is the prototypical member of a large family of cytokines that controls many aspects of cellular function, including cellular proliferation, differentiation, migration, apoptosis, adhesion, angiogenesis, immune surveillance, and survival. Contrary to the initial concept that these proteins may be down-regulated in cancer cells to promote their growth, a marked increase in the expression of TGF-beta has often been found in human cancers in vivo, including cancer of the lung. Moreover, in lung cancer, increased expression of TGF-beta correlates with more advanced stages of malignancy and metastasis and with decreased survival. Increased expression of TGF-beta is usually accompanied by a loss in the growth inhibitory response to TGF-beta. Indeed, some lung cancer cells in culture demonstrate a progressive loss of the growth inhibitory response to TGF-beta that varies directly with the malignant stage of the original tumor. The study of the molecular events associated with the escape of cancer cells from growth regulation by TGF-beta has provided insight into mechanisms underlying carcinogenesis. Specific defects in TGF-beta receptors, TGF-beta-related signal transduction/gene activation, and TGF-beta-regulated cell cycle proteins, have been implicated in the oncogenesis of human lung cancer and metastasis. This review provides background information on TGF-beta and updates the status of our knowledge of the role of TGF-beta in lung cancer, carcinogenesis, and metastasis. C1 NCI, Ctr Canc Training, Canc Training Branch, Bethesda, MD 20892 USA. RP Jakowlew, SB (reprint author), NCI, Ctr Canc Training, Canc Training Branch, Bethesda, MD 20892 USA. EM jakowles@mail.nih.gov NR 156 TC 3 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4419-6614-8 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2010 BP 633 EP 671 DI 10.1007/978-1-4419-6615-5_28 D2 10.1007/978-1-4419-6615-5 PG 39 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BQY41 UT WOS:000282104500028 ER PT J AU Lee, W Espinoza, J Cutlers, N Bronsteen, RA Yeo, L Romero, R AF Lee, W. Espinoza, J. Cutlers, N. Bronsteen, R. A. Yeo, L. Romero, R. TI The 'starfish' sign: a novel sonographic finding with B-flow imaging and spatiotemporal image correlation in a fetus with total anomalous pulmonary venous return SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Editorial Material ID CONNECTION; DIAGNOSIS C1 [Lee, W.; Espinoza, J.; Bronsteen, R. A.] William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI 48073 USA. [Cutlers, N.] William Beaumont Hosp, Div Pediat Cardiol, Dept Pediat, Royal Oak, MI 48073 USA. [Lee, W.; Yeo, L.; Romero, R.] Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI USA. [Lee, W.; Yeo, L.; Romero, R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH DHHS, Bethesda, MD USA. RP Lee, W (reprint author), William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, 3601 W 13 Mile Rd, Royal Oak, MI 48073 USA. EM wlee@beaumont.edu FU Intramural NIH HHS [ZIA HD002401-17] NR 4 TC 3 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD JAN PY 2010 VL 35 IS 1 BP 124 EP 125 DI 10.1002/uog.7503 PG 2 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 544SO UT WOS:000273679800023 PM 20033997 ER PT S AU Gonzales, PA Zhou, H Pisitkun, T Wang, NS Star, RA Knepper, MA Yuen, PST AF Gonzales, Patricia A. Zhou, Hua Pisitkun, Trairak Wang, Nam Sun Star, Robert A. Knepper, Mark A. Yuen, Peter S. T. BE Rai, AJ TI Isolation and Purification of Exosomes in Urine SO URINARY PROTEOME: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Exosomes; Endocytosis; Biomarker; Proteomics; Uromodulin/Tamm-Horsfall protein; Podocyte; Ultracentrifugation ID BIOMARKERS; DISCOVERY AB Exosomes represent an important and readily isolated subset of the urinary proteome that has the potential to shed much insight on the health status of the kidney. Each segment of the nephron sheds exosomes into the urine. Exosomes are rich in potential biomarkers, especially membrane proteins such as transporters and receptors that may be up- or downregulated during disease states. Two differential centrifugation methods are available for simple purification of exosomes: one uses ultracentrifugation, and the other uses a nanomembrane concentrator. Validation methods include western blots of pan-exosome markers and segment-specific exosome markers, and negative staining electron microscopy. C1 [Gonzales, Patricia A.; Pisitkun, Trairak; Knepper, Mark A.] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. [Zhou, Hua; Star, Robert A.; Yuen, Peter S. T.] NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD USA. [Wang, Nam Sun] Univ Maryland, Dept Chem & Bimol Engn, College Pk, MD 20742 USA. RP Gonzales, PA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RI Yuen, Peter/B-1954-2008; OI Yuen, Peter/0000-0001-9557-3909; Pisitkun, Trairak/0000-0001-6677-2271 NR 5 TC 39 Z9 41 U1 1 U2 11 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-710-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 641 BP 89 EP 99 DI 10.1007/978-1-60761-711-2_6 D2 10.1007/978-1-60761-711-2 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BOU38 UT WOS:000277627500006 PM 20407943 ER PT J AU Lerner, SP Bochner, B Linehan, WM Klein, E Cookson, M AF Lerner, Seth P. Bochner, Bernard Linehan, W. Marston Klein, Eric Cookson, Michael TI Overview of SUO Winter 2008 proceedings Seminar section introduction SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Editorial Material C1 [Lerner, Seth P.] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [Bochner, Bernard] Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10021 USA. [Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Klein, Eric] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA. [Cookson, Michael] Vanderbilt Univ, Med Ctr, Dept Urol, Nashville, TN USA. RP Lerner, SP (reprint author), Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JAN-FEB PY 2010 VL 28 IS 1 BP 67 EP 68 DI 10.1016/j.urolonc.2009.11.022 PG 2 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 613AP UT WOS:000278948500010 PM 20123350 ER PT J AU Tennstedt, SL Chiu, GR Link, CL Litman, HJ Kusek, JW McKinlay, JB AF Tennstedt, Sharon L. Chiu, Gretchen R. Link, Carol L. Litman, Heather J. Kusek, John W. McKinlay, John B. TI The Effects of Severity of Urine Leakage on Quality of Life in Hispanic, White, and Black Men and Women: The Boston Community Health Survey SO UROLOGY LA English DT Article ID EPIDEMIOLOGIC SURVEY; DIVERSE POPULATION; OLDER-ADULTS; INCONTINENCE; PREVALENCE; SEEKING; IMPACT; STRESS; CARE AB OBJECTIVES To investigate the relationship between the severity of urine leakage and quality of life (QOL) in men and women of different race/ethnicity. METHODS An epidemiologic survey was conducted with a population-based random sample of 3202 women and 2301 men (1767 black, 1877 Hispanic, 1859 white) aged 30-79 years in Boston, MA. Severity of leakage was based on frequency and amount by the Sandvik Severity Scale. QOL was measured with physical and mental component summaries of Medical Outcomes Study Short Form-12. Covariates included race/ethnicity, age, socioeconomic status, urinary incontinence risk factors, and comorbidities. Analysis included multivariate linear regression modeling by gender. RESULTS Urine leakage, most of which was mild or moderate, was reported in 30% of women and 18% of men. Women (5.1%) were more likely than men (0.9%) to report severe leakage. In multivariate analysis, as severity of leakage increased, both components of QOL declined, with decreases in scores of 7-8 points for men (P <=.001 for each) and 4-6 points (P <.05 and P = .001, respectively) for women. Severe leakage was associated with a greater decline in QOL than that observed for most other comorbidities considered. The effect of urine leakage on QOL was similar among racial and ethnic groups. CONCLUSIONS Urine leakage impairs QOL for both men and women, with no evidence of different effects by racial/ethnic group. Leakage has clinically significant effects on physical health-related QOL for men and on mental health QOL for both men and women. UROLOGY 75: 27-33, 2010. (C) 2010 Elsevier Inc. C1 [McKinlay, John B.] New England Res Inst, Watertown, MA 02111 USA. NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA. RP McKinlay, JB (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02111 USA. EM jmckinlay@neriscience.com FU National Institute of Diabetes and Digestive and Kidney Diseases [DK56842] FX This research was funded by grant DK56842 from the National Institute of Diabetes and Digestive and Kidney Diseases. NR 28 TC 11 Z9 11 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JAN PY 2010 VL 75 IS 1 BP 27 EP 33 DI 10.1016/j.urology.2009.08.019 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 553UV UT WOS:000274393200010 PM 19854479 ER PT S AU Cohen, JI AF Cohen, Jeffrey I. BE Abendroth, A Arvin, AM Moffat, JF TI The Varicella-Zoster Virus Genome SO VARICELLA-ZOSTER VIRUS SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID REPLICATION IN-VITRO; BACTERIAL ARTIFICIAL CHROMOSOME; LATENCY-ASSOCIATED PROTEIN; OPEN READING FRAME-62; TO-CELL SPREAD; SCID-HU MOUSE; INSULIN DEGRADING ENZYME; VIRAL REPLICATION; MUTATIONAL ANALYSIS; GLYCOPROTEIN I AB The varicella-zoster virus (VZV) genome contains at least 70 genes, and all but six have homologs in herpes simplex virus (HSV). Cosmids and BACs corresponding to the VZV parental Oka and vaccine Oka viruses have been used to "knockout" 34 VZV genes. Seven VZV genes (ORF4, 5, 9, 21, 29,62, and 68) have been shown to be required for growth in vitro. Recombinant viruses expressing several markers (e.g., beta-galactosidase, green fluorescence protein, luciferase) and several foreign viral genes (from herpes simplex, Epstein Barr virus, hepatitis B, mumps, HIV, and simian immunodeficiency virus) have been constructed. Further studies of the VZV genome, using recombinant viruses, may facilitate the development of safer and more effective VZV vaccines. Furthermore, VZV might be useful as a vaccine vector to immunize against both VZV and other viruses. C1 NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIH, Lab Clin Infect Dis, Bldg 10,Room 11N234,10 Ctr Dr, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov FU Intramural NIH HHS [ZIA AI000430-27] NR 65 TC 21 Z9 24 U1 1 U2 7 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-12727-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2010 VL 342 BP 1 EP 14 DI 10.1007/82_2010_10 D2 10.1007/978-3-642-12728-1 PG 14 WC Immunology; Microbiology SC Immunology; Microbiology GA BQY44 UT WOS:000282104800001 PM 20225013 ER PT S AU Cohen, JI AF Cohen, Jeffrey I. BE Abendroth, A Arvin, AM Moffat, JF TI Rodent Models of Varicella-Zoster Virus Neurotropism SO VARICELLA-ZOSTER VIRUS SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID LATENCY-ASSOCIATED PROTEIN; REPLICATION IN-VITRO; DORSAL-ROOT GANGLIA; SCID-HU MOUSE; HUMAN T-CELLS; VIRAL REPLICATION; GENE-EXPRESSION; RAT MODEL; INFECTION; ESTABLISHMENT AB Inoculation of rodents with varicella-zoster virus (VZV) results in a latent infection in dorsal root ganglia with expression of at least five of the six VZV transcripts and one of the viral proteins that are reported to be expressed during latency in human ganglia. Rats develop allodynia and hyperalgesia in the limb distal to the site of injection and the resulting exaggerated withdrawal response to stimuli is reduced by treatment with gabapentin and amitryptyline, but not by antiviral therapy. Inoculation of rats with VZV mutants show that most viral genes are dispensable for latency, but that some genes (e.g., ORF4, 29, and ORF63) that are expressed during latency are important for the establishment of latency in rodents, but not for infection of rodent ganglia. The rodent model for VZV latency allows one to study ganglia removed immediately after death, avoiding the possibility of reactivation, and helps to identify VZV genes required for latency. C1 NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIH, Lab Clin Infect Dis, Bldg 10,Room 11N234,10 Ctr Dr, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov FU Intramural NIH HHS [ZIA AI000430-27] NR 53 TC 8 Z9 9 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-12727-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2010 VL 342 BP 277 EP 289 DI 10.1007/82_2010_11 D2 10.1007/978-3-642-12728-1 PG 13 WC Immunology; Microbiology SC Immunology; Microbiology GA BQY44 UT WOS:000282104800017 PM 20225012 ER PT J AU Starost, MF Tsang, K Zerfas, PM Stratakis, CA AF Starost, M. F. Tsang, K. Zerfas, P. M. Stratakis, C. A. TI A Rhabdomyoma Within a Multilocular Thymic Cyst in a p53-Null Mouse SO VETERINARY PATHOLOGY LA English DT Article DE genetically engineered mouse; multilocular cyst; myoid cell; p53 gene; thymus; ultrastructure ID MYOID CELLS; THYMOMA; HYPERPLASIA; CARCINOMA; TUMOR; CATS; MICE; DOG AB A 9-month-old p53-null female mouse was found dead in its cage. At necropsy, a large thymic mass encompassed the heart. Microscopically, the mass was composed of numerous varying-sized cysts lined with simple squamous epithelial cells to columnar ciliated cells. Also present within this mass was a large aggregate of loosely arranged fusiform-shaped cells. These cells also were found in smaller numbers in the connective tissue surrounding the cysts. The larger aggregate of fusiform cells was positive for desmin and S-100 and negative for smooth muscle actin. Electron microscopy revealed well-formed Z lines and I bands of skeletal muscle phenotype. A diagnosis of rhabdomyoma within a congenital multilocular thymic cyst was made. The thymus contains a small population of myoid cells, which should be taken in consideration when evaluating thymic tumors. C1 [Starost, M. F.; Zerfas, P. M.] NIH, Div Vet Resources, Bethesda, MD 20892 USA. [Tsang, K.; Stratakis, C. A.] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Starost, MF (reprint author), NIH, Div Vet Resources, Bldg 28A,Room 115,9000 Rockville Pike, Bethesda, MD 20892 USA. EM starostm@mail.nih.gov FU National Institutes of Health, Office of Research Services; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health intramural project [Z01-HD-000642-04] FX We Would like to thank Jorge Chavez and Annie Merriweather for technical assistance. This work was Supported in part by the Intramural Research Program of the National Institutes of Health, Office or Research Services (MFS), and in part by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health intramural project Z01-HD-000642-04 (CAS). NR 34 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0300-9858 EI 1544-2217 J9 VET PATHOL JI Vet. Pathol. PD JAN PY 2010 VL 47 IS 1 SI SI BP 132 EP 136 DI 10.1177/0300985809353175 PG 5 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 551OJ UT WOS:000274218600018 PM 20080493 ER PT J AU Jacobson, S AF Jacobson, Steven TI The NK Cell as a new player in the pathogenesis of HTLV-I associated neurologic disease SO VIRULENCE LA English DT Editorial Material DE HTLV-I; HAM/TSP; NK cells; virus-host interactions ID VIRUS TYPE-I; SPONTANEOUS LYMPHOPROLIFERATION; SPASTIC PARAPARESIS; T-CELLS; MYELOPATHY C1 NIH, Viral Immunol Sect, Bethesda, MD 20892 USA. RP Jacobson, S (reprint author), NIH, Viral Immunol Sect, Bldg 10, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov NR 14 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 J9 VIRULENCE JI Virulence PD JAN-FEB PY 2010 VL 1 IS 1 BP 8 EP 9 DI 10.4161/viru.1.1.10327 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 788TQ UT WOS:000292467700005 PM 21178408 ER PT J AU Otto, M AF Otto, Michael TI Mobile genetic element-encoded cytolysin connects virulence to methicillin resistance in MRSA SO VIRULENCE LA English DT Article DE Staphylococcus aureus; Staphylococcus epidermidis; MRSA; MRSE; toxin; antibiotic resistance; mobile genetic element; methicillin ID CASSETTE CHROMOSOME MEC; COMMUNITY-ASSOCIATED MRSA; STAPHYLOCOCCUS-AUREUS; IDENTIFICATION; DETERMINANTS; EPIDERMIDIS; EVOLUTION; STRAINS AB Virulence and antibiotic resistance of the dangerous human pathogen Staphylococcus aureus are to large extent determined by the acquisition of mobile genetic elements (MGEs). Up to now, these elements were known to comprise either resistance or virulence determinants, but not a mixture of the two. Queck et al. now found a cytolysin gene of the phenol-soluble modulin (PSM) family within SCCmec elements, which contain methicillin resistance genes and are largely responsible for the spread of methicillin-resistant S. aureus (MRSA). The novel gene, called psm-mec, had a significant impact on virulence in MRSA strains that do not produce high levels of genome-encoded PSMs. This first example of a combination of toxin and resistance genes on one staphylococcal MGE shows that such bundling is possible and may lead to an even faster acquisition of toxin and resistance genes by S. aureus and other staphylococcal pathogens. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Otto, M (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 FU Intramural NIH HHS NR 19 TC 13 Z9 15 U1 1 U2 12 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 J9 VIRULENCE JI Virulence PD JAN-FEB PY 2010 VL 1 IS 1 BP 49 EP 51 DI 10.4161/viru.1.1.10453 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 788TQ UT WOS:000292467700012 PM 21178414 ER PT B AU Motulsky, AG Dean, M AF Motulsky, Arno G. Dean, Michael BE Speicher, MR Antonarakis, SE Motulsky, AG TI Linkage Analysis for Monogenic Traits SO VOGEL AND MOTULSKY'S HUMAN GENETICS, FOURTH EDITION: PROBLEMS AND APPROACHES LA English DT Article; Book Chapter ID GENETICALLY COMPLEX TRAITS; HUMAN Y-CHROMOSOME; FRAGMENT LENGTH POLYMORPHISMS; AFFECTED RELATIVE PAIRS; SEX-DETERMINING REGION; HUMAN GENOME; CYSTIC-FIBROSIS; MENDELIAN DISORDERS; CROSSING-OVER; DNA MARKERS AB Linkage analysis, that is the observation of cosegregation of adjacent,genetic markers or traits, is the principal means of constructing genetic maps, and locating genes that cause disease, or genetic traits. Although these methods have been partially supplanted by newer methods such as whole genorne sequencing, linkage analysis still has considerable utility. The history of the method and the mathematical basis of linkage analysis are presented as well as specific applications to human genetics. Gene clusters consist of groups of adjacent genes that exist largely though mechanisms of gene duplication. In addition there exist Clusters of genes that have related function, the best studied of which is the Major Histocompatibility Complex. The structure and evolutionary history of these clusters provides insight into the history of mammalian genomes. C1 [Dean, Michael] NCI, Frederick, MD 21702 USA. [Motulsky, Arno G.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [Motulsky, Arno G.] Univ Washington, Sch Med, Dept Med, Div Med Genet, Seattle, WA 98195 USA. RP Dean, M (reprint author), NCI, Frederick, MD 21702 USA. EM agmot@u.washington.edu; deanm@mail.nih.gov; agmot@u.washington.edu NR 114 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-540-37653-8 PY 2010 BP 211 EP 241 DI 10.1007/978-3-540-37654-5_6 D2 10.1007/978-3-540-37654-5 PG 31 WC Genetics & Heredity SC Genetics & Heredity GA BNM20 UT WOS:000274935100007 ER PT B AU Wang, SS Beaty, TH Khoury, MJ AF Wang, Sophia S. Beaty, Terri H. Khoury, Muin J. BE Speicher, MR Antonarakis, SE Motulsky, AG TI Genetic Epidemiology SO VOGEL AND MOTULSKY'S HUMAN GENETICS, FOURTH EDITION: PROBLEMS AND APPROACHES LA English DT Article; Book Chapter ID GENOME-WIDE ASSOCIATION; ENVIRONMENT INTERACTIONS; QUANTITATIVE-TRAIT; LINKAGE ANALYSIS; BREAST-CANCER; SOCIAL IMPLICATIONS; COMMON DISEASES; POPULATION; MEDICINE; HEALTH AB In this chapter, we describe both the historical and contemporary teminologies that reflect the evolving field of genetic epidemiology. We discuss the conduct of family-based studies to identify high-penetrance disease genes, along with traditional genetic analyses of human pedigrees to assess Mendelian transmission (segregation analysis) or to locate causal genes (linkage analysis/gene mapping). We also describe epidemiologic approaches used to study gene-disease associations (including genome-wide association studies) plus gene-gene and gene-environment interactions. We review analytic and methodologic issues applicable to each of these studies and emerging, nontraditional epidemiologic methods that can be used as all adjunct to traditional approaches, particularly for the simultaneous study of hundreds of thousands of data points per person. We further discuss the challenging nature of analysis, synthesis, and dissemination of these genetic data, and the value of systematic reviews, meta-analyses and consortia in evaluating large bodies of scientific evidence. Finally, we describe the need for follow-up of these results to identify causal variants and the need for translational research efforts to apply these gene discoveries to personalized medicine, such as evaluation of genetic testing in clinical practice (in terms of analytic validity, clinical validity, clinical utility), and to population health including determining the disease risk and burden in populations (e.g., absolute and attributable risks). We also consider the ethical, legal, and social implications of these discoveries. C1 [Wang, Sophia S.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Wang, Sophia S.] City Hope Natl Med Ctr, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA. [Beaty, Terri H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Natl Off Publ Hlth Genom, Atlanta, GA 30333 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA. RP Wang, SS (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 5104, Rockville, MD 20852 USA. EM wangso@mail.nih.gov; tbeaty@jhsph.edu; muk1@cdc.gov NR 79 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-540-37653-8 PY 2010 BP 617 EP 634 DI 10.1007/978-3-540-37654-5_21 D2 10.1007/978-3-540-37654-5 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA BNM20 UT WOS:000274935100023 ER PT B AU Goldman, D Ducci, F AF Goldman, David Ducci, Francesca BE Speicher, MR Antonarakis, SE Motulsky, AG TI The Genetics of Alcoholism and Other Addictive Disorders SO VOGEL AND MOTULSKY'S HUMAN GENETICS, FOURTH EDITION: PROBLEMS AND APPROACHES LA English DT Article; Book Chapter ID CATECHOL-O-METHYLTRANSFERASE; POPULATION-BASED SAMPLE; SUBSTANCE USE DISORDERS; NATIONAL EPIDEMIOLOGIC SURVEY; SEROTONIN TRANSPORTER GENE; ENVIRONMENTAL RISK-FACTORS; CHILDHOOD SEXUAL-ABUSE; DOPAMINE-RECEPTOR GENE; AMERICAN-INDIAN TRIBE; MONOAMINE-OXIDASE-A AB Addictions are common, complex disorders that are to some extent tied together by shared genetic and environmental etiological factors. They are frequently chronic, with a relapsing/remitting course. Addictive disorders, which are in part volitional, in part inborn, and in part determined by environmental experiences, pose the full range of medical, genetic, policy, and moral challenges. Genetic factors account for 40-70% of the variance in addiction liability. There is little evidence for large influences on overall population vulnerability from any single gene. Instead, multiple genetic loci are likely to be involved, each with a small attributable risk. Gene discovery is being facilitated by a variety of powerful approaches and tools, but is in its infancy Susceptibility loci for addictions include both drug-specific genes (e.g., alcohol-metabolizing genes) and loci moderating neuronal pathways, such as reward, behavioral control, and stress resiliency, that are involved in several psychiatric diseases (e.g., MAOA and COMT). In recent years, major progress has been made in identification of genes using intermediate phenotypes such as task-related brain activation that confer the opportunity of exploring the neuronal mechanisms through which genetic variation is translated into behavior. Fundamental to the detection of gene effects are also the understanding of the interplay between genes and of genes/environment interactions. The identification of genes altering the liability to addiction and treatment response (e.g., OPRMI) could provide new therapeutic targets and an ability to individualize treatment. Although the genetic bases of addiction remain largely unknown, there are reasons to think that more genes will be C1 [Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. [Ducci, Francesca] Inst Psychiat, SGDP Ctr, Div Psychol Med, London SE5 8AF, England. RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, NIH, 5625 Fishers Lane,Room 3S32,MSC 9412, Rockville, MD 20852 USA. EM davidgoldman@mail.nih.gov; Francesca.Ducci@iop.kcl.ac.uk NR 155 TC 0 Z9 0 U1 3 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-540-37653-8 PY 2010 BP 715 EP 741 DI 10.1007/978-3-540-37654-5_23.5 D2 10.1007/978-3-540-37654-5 PG 27 WC Genetics & Heredity SC Genetics & Heredity GA BNM20 UT WOS:000274935100030 ER PT B AU Parker, HG Ostrander, EA AF Parker, Heidi G. Ostrander, Elaine A. BE Speicher, MR Antonarakis, SE Motulsky, AG TI Human Genetics and the Canine System SO VOGEL AND MOTULSKY'S HUMAN GENETICS, FOURTH EDITION: PROBLEMS AND APPROACHES LA English DT Article; Book Chapter ID QUANTITATIVE TRAIT LOCI; PROGRESSIVE RETINAL ATROPHY; ROD CGMP-PHOSPHODIESTERASE; DYSPLASIA TYPE-2 RCD2; DOMESTIC DOG BREEDS; GERMAN-SHEPHERD DOG; HOGG-DUBE-SYNDROME; LINKAGE DISEQUILIBRIUM; RADIATION-HYBRID; TRINUCLEOTIDE REPEATS AB With constant advances in canine genomics, the dog has found a permanent position as a Source of genetic information for the inheritance of morphologic traits and disease susceptibility. The modern domestic dog is not a typical model organism. They share our environment, our life-styles and often our food. In addition, they experience many of the same diseases that people do and are diagnosed and treated using the same medical procedures and pharmaceuticals. However, unlike humans, the purebred dog maintains a highly structured population organization that, if used correctly, can simplify the genetics of complex traits and disorders. In this chapter, we will discuss the history of canine genomics along with recent advances in resource development. Specific examples will be provided to demonstrate strategies for using population stratification to the best advantage in mapping traits both simple and complex. Together, these data highlight the utility of the canine system for mapping traits and finding mutations important in both human and companion animal science. C1 [Parker, Heidi G.; Ostrander, Elaine A.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Ostrander, EA (reprint author), NHGRI, NIH, 50 S Dr,MSC 8000,Bldg 50,Room 5334, Bethesda, MD 20892 USA. EM hgparker@mail.nih.gov; eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 NR 79 TC 0 Z9 0 U1 1 U2 6 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-540-37653-8 PY 2010 BP 813 EP 826 DI 10.1007/978-3-540-37654-5_24.4 D2 10.1007/978-3-540-37654-5 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA BNM20 UT WOS:000274935100037 ER PT B AU Pagon, RA Hamosh, A den Dunnen, J Firth, HV Maglott, DR Sherry, ST Feolo, M Cooper, D Stenson, P AF Pagon, Roberta A. Hamosh, Ada den Dunnen, Johan Firth, Helen V. Maglott, Donna R. Sherry, Stephen T. Feolo, Michael Cooper, David Stenson, Peter BE Speicher, MR Antonarakis, SE Motulsky, AG TI Databases in Human and Medical Genetics SO VOGEL AND MOTULSKY'S HUMAN GENETICS, FOURTH EDITION: PROBLEMS AND APPROACHES LA English DT Article; Book Chapter ID MUTATION DATABASE; GENOME; EVOLUTIONARY; INFORMATION; SEQUENCE; INSIGHTS; DISEASE AB This chapter provides an introduction to the major, freely available, Internet-accessible databases in human and medical genetics used by healthcare providers in the diagnosis, management, and genetic Counseling of persons with inherited disorders and their families, as well as by researchers for gene discovery, recording allelic variants, and cataloging genotype-phenotype relationships. Databases discussed include: GeneTests (view: www.genetests.org); Online Mendelian Inheritance in Man (view: www.ncbi.nlm.nih.gov/Omim); locus specific databases (LSDBs) identified at the Human Genome Variation Society (HGVS) web site (http://www.HGVS.org/dblist.html); DatabasE of Chromosome Imbalance and Phenotype in Humans using Ensembl Resources (view: http://decipher.sanger.ac.uk); Entrez Gene (view: ncbi.nlm.nih.gov/gene); dbGap: Database of Genotype and Phenotype (view: ncbi.nlm.nih.gov/dbgap); and the Human Gene Mutation Database HGMD (R) (view: http://www.hgmd.org). C1 [Pagon, Roberta A.] Univ Washington, Seattle, WA 98115 USA. [Hamosh, Ada] Johns Hopkins Univ, Inst Med Genet, Sch Med, Baltimore, MD 21287 USA. [den Dunnen, Johan] Leiden Univ, Med Ctr, NL-2333 RC Leiden, Netherlands. [Firth, Helen V.] Addenbrookes Hosp, Cambridge CB2 2QQ, England. [Maglott, Donna R.] Natl Ctr Biotechnol Info, Bethesda, MD 20892 USA. [Sherry, Stephen T.; Feolo, Michael] Natl Lib Med, Bethesda, MD 20892 USA. [Cooper, David; Stenson, Peter] Cardiff Univ, Sch Med, Inst Med Genet, Cardiff CF14 4XN, S Glam, Wales. RP Pagon, RA (reprint author), Univ Washington, Suite 602,9725 3rd Ave NE, Seattle, WA 98115 USA. EM bpagon@u.washington.edu; ahamosh@mail.jhmi.edu; ddunnen@HumGen.nl; helen.firth@addenbrookes.nhs.uk; maglott@ncbi.nlm.nih.gov; sherry@ncbi.nlm.nih.gov; feolo@ncbi.nlm.nih.gov; cooperdn@cardiff.ac.uk; stensonpd@cardiff.ac.uk OI Cooper, David N./0000-0002-8943-8484 NR 21 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-540-37653-8 PY 2010 BP 941 EP 960 DI 10.1007/978-3-540-37654-5_29.3 D2 10.1007/978-3-540-37654-5 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA BNM20 UT WOS:000274935100046 ER PT J AU Wang, JK Klein, HG AF Wang, J. K. Klein, H. G. TI Red blood cell transfusion in the treatment and management of anaemia: the search for the elusive transfusion trigger SO VOX SANGUINIS LA English DT Review ID CRITICALLY-ILL PATIENTS; ACUTE ISOVOLEMIC HEMODILUTION; ACUTE NORMOVOLEMIC HEMODILUTION; CRITICAL OXYGEN DELIVERY; INTENSIVE-CARE-UNIT; ACUTE CORONARY SYNDROMES; ERYTHROPOIETIN RESPONSE; MYOCARDIAL-INFARCTION; COGNITIVE FUNCTION; CLINICAL-OUTCOMES AB Therapeutic red blood cell (RBC) transfusion is widely utilized in the management of anaemia. Critically ill intensive care unit (ICU) patients in particular, as well as medical and haematology-oncology patients, are among the largest groups of users of RBC products. While anaemia is common in these patients, its treatment and management, including appropriate thresholds for RBC transfusion, remain controversial. We review here the function of RBCs in oxygen transport and physiology, with a view to their role in supporting and maintaining systemic tissue oxygenation. Adaptive and physiological compensatory mechanisms in the setting of anaemia are discussed, along with the limits of compensation. Finally, data from clinical studies will be examined in search of evidence for, or against, a clinically relevant transfusion trigger. C1 [Wang, J. K.; Klein, H. G.] NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Klein, HG (reprint author), NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Room 1C711,Bldg 10 MSC 1184,10 Ctr Dr, Bethesda, MD 20892 USA. EM wangjean@cc.nih.gov NR 81 TC 39 Z9 40 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 2010 VL 98 IS 1 BP 2 EP 11 DI 10.1111/j.1423-0410.2009.01223.x PG 10 WC Hematology SC Hematology GA 531JZ UT WOS:000272663200002 PM 19682346 ER PT J AU Belcher, A Sinnott-Armstrong, W AF Belcher, Annabelle Sinnott-Armstrong, Walter TI Neurolaw SO WILEY INTERDISCIPLINARY REVIEWS-COGNITIVE SCIENCE LA English DT Editorial Material ID LIE DETECTION; FMRI AB Less than three decades ago, the fields of cognitive psychology and neuroscience joined forces to form cognitive neuroscience. More recently, neuroscience has combined with social psychology and with economics to produce social neuroscience and neuroeconomics. Each of these amalgamations has been revolutionary in its own way. Neurolaw extends this trend. (C) 2009 John Wiley & Sons, Ltd. WIREs Cogn Sci 2010 1 18-22 C1 [Sinnott-Armstrong, Walter] Duke Univ, Kenan Inst Eth, Durham, NC 27708 USA. [Sinnott-Armstrong, Walter] Duke Univ, Dept Philosophy, Durham, NC 27708 USA. [Belcher, Annabelle] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA. RP Sinnott-Armstrong, W (reprint author), Duke Univ, Kenan Inst Eth, Durham, NC 27708 USA. EM Walter.P.Sinnott-Armstrong@dartmouth.edu NR 20 TC 6 Z9 7 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-5078 EI 1939-5086 J9 WIRES COGN SCI JI Wiley Interdiscip. Rev.-Cogn. Sci. PD JAN-FEB PY 2010 VL 1 IS 1 BP 18 EP 22 DI 10.1002/wcs.8 PG 5 WC Psychology, Experimental SC Psychology GA 863NM UT WOS:000298171200004 PM 26272834 ER PT J AU Kang, HG Tokumasu, F Clarke, M Zhou, ZP Tang, JY Nguyen, T Hwang, J AF Kang, Hyeong-Gon Tokumasu, Fuyuki Clarke, Matthew Zhou, Zhenping Tang, Jianyong Nguyen, Tinh Hwang, Jeeseong TI Probing dynamic fluorescence properties of single and clustered quantum dots toward quantitative biomedical imaging of cells SO WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY LA English DT Review ID RESONANCE ENERGY-TRANSFER; WALLED CARBON NANOTUBE; PHOTOLUMINESCENCE; INTERMITTENCY; ERYTHROCYTES; BLINKING; APTAMER; GROWTH; LAYER; SHIFT AB We present results on the dynamic fluorescence properties of bioconjugated nanocrystals or quantum dots (QDs) in different chemical and physical environments. A variety of QD samples was prepared and compared: isolated individual QDs, QD aggregates, and QDs conjugated to other nanoscale materials, such as single-wall carbon nanotubes (SWCNTs) and human erythrocyte plasma membrane proteins. We discuss plausible scenarios to explain the results obtained for the fluorescence characteristics of QDs in these samples, especially for the excitation time-dependent fluorescence emission from clustered QDs. We also qualitatively demonstrate enhanced fluorescence emission signals from clustered QDs and deduce that the band 3 membrane proteins in erythrocytes are clustered. This approach is promising for the development of QD-based quantitative molecular imaging techniques for biomedical studies involving biomolecule clustering. (C) 2009 John Wiley & Sons, Inc. WIREs Nanomed Nanobiotechnol 2010 2 48-58 C1 [Kang, Hyeong-Gon; Clarke, Matthew; Zhou, Zhenping; Tang, Jianyong; Nguyen, Tinh; Hwang, Jeeseong] NIST, Gaithersburg, MD 20899 USA. [Tokumasu, Fuyuki] NIAID, Bethesda, MD 20892 USA. RP Hwang, J (reprint author), NIST, 100 Bur Dr, Gaithersburg, MD 20899 USA. EM jch@nist.gov OI Tokumasu, Fuyuki/0000-0003-2790-1071 FU NIST; NIAID/NIH FX The authors give special thanks to the late Dr James A. Dvorak for his scientific dedication to malaria research at National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH). The authors thank Dr Jeffrey Fagan for kindly providing DNA-wrapped SWCNTs and Dr Thomas E. Wellems at NIAID/NIH, Georgeta Crivat, Grace S. Chou, John Woodward, Garnett Bryant, and Paul De Rose at National Institute of Standards and Technology (NIST), and Dr Anil Patri at the Nanotechnology Characterization Laboratory (NCL) at SAIC-Frederick/NCI-Frederick for useful discussions. JH was supported by the NIST Advanced Technology Program. FT was supported by the Intramural Research Program of the NIAID/NIH. Official contribution of the NIST; not subject to copyright in the Unites States. Certain commercial equipment, instruments, or materials are identified in this article to foster understanding and does not imply recommendation or endorsement by NIST, it does not imply that the materials or equipment identified are necessarily the best available for the purpose. NR 38 TC 9 Z9 9 U1 2 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1939-5116 J9 WIRES NANOMED NANOBI JI Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol. PD JAN-FEB PY 2010 VL 2 IS 1 BP 48 EP 58 DI 10.1002/wnan.62 PG 11 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 585PY UT WOS:000276840100005 PM 20049830 ER PT J AU Adiseshaiah, PP Hall, JB McNeil, SE AF Adiseshaiah, Pavan P. Hall, Jennifer B. McNeil, Scott E. TI Nanomaterial standards for efficacy and toxicity assessment SO WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY LA English DT Review ID STERICALLY STABILIZED LIPOSOMES; INTRAVENOUSLY INJECTED MICROSPHERES; IRON-OXIDE NANOPARTICLES; HUMAN TUMOR XENOGRAFT; IN-VIVO; PARTICLE-SIZE; ENCAPSULATED DOXORUBICIN; VASCULAR-PERMEABILITY; THERAPEUTIC-EFFICACY; TRANSFERRIN RECEPTOR AB Decreased toxicity via selective delivery of cancer therapeutics to tumors has become a hallmark achievement of nanotechnology. In order to be optimally efficacious, a systemically administered nanomedicine must reach cancer cells in sufficient quantities to elicit a response and assume its active form within the tumor microenvironment (e.g., be taken up by cancer cells and release a toxic component once within the cytosol or nuclei). Most nanomedicines achieve selective tumor accumulation via the enhanced permeability and retention (EPR) effect or a combination of the EPR effect and active targeting to cellular receptors. Here, we review how the fundamental physicochemical properties of a nanomedicine (its size, charge, hydrophobicity, etc.) can dramatically affect its distribution to cancerous tissue, transport across vascular walls, and retention in tumors. We also discuss how nanoparticle characteristics such as stability in the blood and tumor, cleavability of covalently bound components, cancer cell uptake, and cytotoxicity contribute to efficacy once the nanoparticle has reached the tumor's interstitial space. We elaborate on how tumor vascularization and receptor expression vary depending on cancer type, stage of disease, site of implantation, and host species, and review studies which have demonstrated that these variations affect tumor response to nanomedicines. Finally, we show how knowledge of these properties (both of the nanoparticle and the cancer/tumor under study) can be used to design meaningful in vivo tests to evaluate nanoparticle efficacy. (C) 2009 John Wiley & Sons, Inc. WIREs Nanomed Nanobiotechnol 2010 2 99-112 C1 [Adiseshaiah, Pavan P.; Hall, Jennifer B.; McNeil, Scott E.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick, Frederick, MD 21702 USA. RP Adiseshaiah, PP (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick, Frederick, MD 21702 USA. EM adiseshaiahp@mail.nih.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 70 TC 103 Z9 104 U1 9 U2 69 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1939-5116 J9 WIRES NANOMED NANOBI JI Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol. PD JAN-FEB PY 2010 VL 2 IS 1 BP 99 EP 112 DI 10.1002/wnan.66 PG 14 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 585PY UT WOS:000276840100009 PM 20049834 ER PT J AU Panuncialman, J Hammerman, S Carson, P Falanga, V AF Panuncialman, Jaymie Hammerman, Scott Carson, Polly Falanga, Vincent TI Wound edge biopsy sites in chronic wounds heal rapidly and do not result in delayed overall healing of the wounds SO WOUND REPAIR AND REGENERATION LA English DT Article ID BASAL-CELL CARCINOMA; CHRONIC LEG ULCERS; VENOUS ULCERS; FIBROBLASTS; DIFFERENTIATION; PROLIFERATION; GUIDELINES; EXPRESSION; MARKERS; TISSUE AB Wound biopsies are an essential diagnostic component in the management of chronic wounds. First, the possibility of malignancy or infection in the wound often requires sampling of the wound edge and its bed. Secondly, several practice guidelines recommend biopsying wounds that have not responded to treatment after 2-6 weeks. However, there has always been a concern that the biopsy may worsen the wound and delay overall healing. In this report, we investigated the safety and effects of wound biopsies on overall chronic wound healing rates (advance of the wound edge per week toward the center) before and after the biopsy was performed. In a cohort of 14 consecutive patients with chronic wounds of the lower extremity, we found that postbiopsy chronic wound healing rates (0.99 +/- 1.18 mm/week; mean +/- SD) were not decreased and were actually higher than prebiopsy chronic wound healing rates (0.49 +/- 0.85 mm/week; mean +/- SD, p < 0.05). In addition, we documented that healing of the biopsy sites up to the original wound edge occurred within 6 weeks in 11 of the 14 subjects. Therefore, we conclude that chronic wounds do not worsen after being biopsied and that wound biopsies are a safe procedure that does not delay overall healing of the chronic wound. C1 [Panuncialman, Jaymie; Hammerman, Scott; Carson, Polly; Falanga, Vincent] Roger Williams Canc Med Ctr, Dept Dermatol & Skin Surg, Providence, RI 02908 USA. [Hammerman, Scott; Carson, Polly; Falanga, Vincent] NIH, Ctr Biomed Res Excellence, Roger Williams Med Ctr, Providence, RI USA. [Falanga, Vincent] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. [Falanga, Vincent] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. RP Falanga, V (reprint author), Roger Williams Canc Med Ctr, Dept Dermatol & Skin Surg, 50 Maude St, Providence, RI 02908 USA. EM vfalanga@bu.edu FU NIH [P20RR018757] FX This work was supported by NIH Grant P20RR018757 and its Imaging Core. We thank Dr. Yajni Warnapala for assistance in the statistical analysis and the determination of overall chronic wound healing rates. NR 24 TC 15 Z9 15 U1 2 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD JAN-FEB PY 2010 VL 18 IS 1 BP 21 EP 25 DI 10.1111/j.1524-475X.2009.00559.x PG 5 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 542FQ UT WOS:000273478800005 PM 20082677 ER PT S AU Schultz, ZD Levin, IW AF Schultz, Zachary D. Levin, Ira W. BE Champion, PM Ziegler, LD TI Higher-Order Optical Modes and Nanostructures for Detection and Imaging Applications SO XXII INTERNATIONAL CONFERENCE ON RAMAN SPECTROSCOPY SE AIP Conference Proceedings LA English DT Proceedings Paper CT 22nd International Conference on Raman Spectroscopy CY AUG 08-13, 2010 CL Boston, MA SP NE Univ, Boston Univ & Photon Ctr, Horiba Sci, Thermo Sci, Bruker Opt ID ENHANCED RAMAN-SPECTROSCOPY AB Raman spectroscopy offers a label-free, chemically specific, method of detecting molecules; however, the low cross-section attendant to this scattering process has hampered trace detection. The realization that scattering is enhanced at a metallic surface has enabled new techniques for spectroscopic and imaging analysis.(1-3) [GRAPHICS] . C1 [Schultz, Zachary D.] Univ Notre Dame, Dept Chem & Biochem, 251 Nieuwland Sci Hall, Notre Dame, IN 46556 USA. [Levin, Ira W.] Natl Inst Hlth, Natl Inst Diabetes & Digest & Kidney Diseases, Bethesda, MD 20892 USA. RP Schultz, ZD (reprint author), Univ Notre Dame, Dept Chem & Biochem, 251 Nieuwland Sci Hall, Notre Dame, IN 46556 USA. RI Schultz, Zachary/L-5724-2013 OI Schultz, Zachary/0000-0003-1741-8801 FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health; NIH [4R00RR024367-02] FX The Authors acknowledge support from the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. ZDS acknowledges funding from NIH 4R00RR024367-02. The authors thank Stephan Stranick for his helpful discussions and input into these projects. NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0818-0 J9 AIP CONF PROC PY 2010 VL 1267 BP 242 EP + DI 10.1063/1.3482491 PG 2 WC Physics, Applied SC Physics GA BQK65 UT WOS:000281210900133 ER PT S AU Crampton, SR Voynova, E Bolland, S AF Crampton, Steve R. Voynova, Elisaveta Bolland, Silvia BE Rose, NR TI Innate pathways to B-cell activation and tolerance SO YEAR IN IMMUNOLOGY 2 SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE B cells; Toll-like receptors; TLRs; autoimmunity; autoreactive; tolerance; innate; SLE; Lupus; BAFF; IFN-I ID TOLL-LIKE-RECEPTOR; SYSTEMIC-LUPUS-ERYTHEMATOSUS; PLASMACYTOID DENDRITIC CELLS; SELF-TOLERANCE; I INTERFERON; IMMUNE-RESPONSES; MURINE LUPUS; T-CELLS; LYMPHOCYTE STIMULATOR; RHEUMATOID-ARTHRITIS AB B cells represent an important link between the adaptive and innate immune systems as they express both antigen-specific B-cell receptors (BCRs) as well as various Toll-like receptors (TLRs). Several checkpoints in B-cell development ensure that self-specific cells are eliminated from the mature B-cell repertoire to avoid harmful autoreactive responses. These checkpoints are controlled by BCR-mediated events but are also influenced by TLR-dependent signals from the innate immune system. Additionally, B-cell-intrinsic and extrinsic TLR signaling are critical for inflammatory events required for the clearance of microbial infections. Factors secreted by TLR-activated macrophages or dendritic cells directly influence the fate of protective and autoreactive B cells. Additionally, naive and memory B cells respond differentially to TLR ligands, as do different B-cell subsets. We review here recent literature describing intrinsic and extrinsic effects of TLR stimulation on the fate of B cells, with particular attention to autoimmune diseases. C1 [Crampton, Steve R.; Voynova, Elisaveta; Bolland, Silvia] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Bolland, S (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklawn Dr,Twinbrook 2,Room 217, Rockville, MD 20852 USA. EM sbolland@niaid.nih.gov FU Intramural NIH HHS [ZIA AI000912-09] NR 107 TC 32 Z9 33 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-779-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1183 BP 58 EP 68 PG 11 WC Immunology SC Immunology GA BNG71 UT WOS:000274519000005 PM 20146708 ER PT S AU Steward-Tharp, SM Song, YJ Siegel, RM O'Shea, JJ AF Steward-Tharp, Scott M. Song, Yun-jeong Siegel, Richard M. O'Shea, John J. BE Rose, NR TI New insights into T cell biology and T cell-directed therapy for autoimmunity, inflammation, and immunosuppression SO YEAR IN IMMUNOLOGY 2 SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE CD4(+) T helper; autoimmune; immunosuppression; monoclonal antibody; therapy ID PLACEBO-CONTROLLED TRIAL; GROWTH-FACTOR-BETA; INTERLEUKIN-12/23 MONOCLONAL-ANTIBODY; SEVERE PLAQUE PSORIASIS; ACTIVE CROHNS-DISEASE; HYPER-IGE SYNDROME; ROR-GAMMA-T; INTERCELLULAR-ADHESION MOLECULE-1; RELAPSING MULTIPLE-SCLEROSIS; RANDOMIZED CONTROLLED-TRIAL AB T cell-directed therapies have become mainstays in the management of various autoimmune diseases and organ transplantation. The understanding of T cell biology has expanded greatly since the development of most agents currently in use. Here we discuss important recent discoveries pertaining to T helper cell differentiation, lineage commitment, and function. Within this context, we examine existing T cell-directed therapies, including new agents being evaluated in clinical and preclinical studies. We also use recent findings to speculate on novel targets. C1 [Steward-Tharp, Scott M.; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Steward-Tharp, Scott M.] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. [Song, Yun-jeong; Siegel, Richard M.] NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Steward-Tharp, SM (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, 10 Ctr Dr,RM 13C103, Bethesda, MD 20892 USA. EM stewardtharpsm@mail.nih.gov OI Siegel, Richard/0000-0001-5953-9893 FU Intramural NIH HHS [Z99 AR999999] NR 250 TC 25 Z9 27 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-779-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1183 BP 123 EP 148 PG 26 WC Immunology SC Immunology GA BNG71 UT WOS:000274519000009 PM 20146712 ER PT S AU Damsker, JM Hansen, AM Caspi, RR AF Damsker, Jesse M. Hansen, Anna M. Caspi, Rachel R. BE Rose, NR TI Th1 and Th17 cells Adversaries and collaborators SO YEAR IN IMMUNOLOGY 2 SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE autoimmune disease; inflammation; Th1; Th17 ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; COLLAGEN-INDUCED ARTHRITIS; GAMMA-DEFICIENT MICE; REGULATORY T-CELLS; IFN-GAMMA; MULTIPLE-SCLEROSIS; MYCOBACTERIUM-TUBERCULOSIS; INTERLEUKIN-17 FAMILY AB Autoreactive effector CD4(+) T cells have been associated with the pathogenesis of autoimmune disorders. Early studies implicated the interferon (IFN)-gamma-producing T helper (Th)1 subset of CD4(+) cells as the causal agents in the pathogenesis of autoimmunity. However, further studies have suggested a more complex story. In models thought to be driven by Th1 cells, mice lacking the hallmark Th1 cytokine IFN-gamma were not protected but tended to have enhanced susceptibility to disease. Identification of the IL-17-producing CD4(+) effector cell lineage (Th17) has helped shed light on this issue. Th17 effector cells are induced in parallel to Th1, and, like Th1, polarized Th17 cells have the capacity to cause inflammation and autoimmune disease. This, together with the finding that deficiency of the Th17-related cytokine IL-23 but not the Th I-related cytokine IL-12 causes resistance, led to the notion that Th17 cells are the chief contributors to autoimmune tissue inflammation. Nevertheless, mice lacking IL-17 are not protected from disease and display elevated numbers of IFN-gamma-producing CD4(+) T cells, and, in some cases, lack of IFN-gamma does confer resistance. Recent studies report overlapping as well as differential roles of these cells in tissue inflammation, which suggests the existence of a more complex relationship between these two effector T-cell Subsets than has hitherto been suspected. This review will attempt to bring together current information regarding interaction, balance, and collaborative potential between the Th1 and Th17 effector lineages. C1 [Damsker, Jesse M.; Hansen, Anna M.; Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 10N222, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov FU Intramural NIH HHS [Z99 EY999999, ZIA EY000184-27, ZIC EY000457-02] NR 87 TC 140 Z9 156 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-779-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1183 BP 211 EP 221 PG 11 WC Immunology SC Immunology GA BNG71 UT WOS:000274519000014 PM 20146717 ER PT S AU Kamei, M Isogai, S Pan, WP Weinstein, BM AF Kamei, Makoto Isogai, Sumio Pan, Weijun Weinstein, Brant M. BE Detrich, HW Westerfield, M Zon, LI TI Imaging Blood Vessels in the Zebrafish SO ZEBRAFISH: CELLULAR AND DEVELOPMENTAL BIOLOGY, PT A, THIRD EDITION SE Methods in Cell Biology LA English DT Review; Book Chapter ID EMBRYONIC VASCULAR DEVELOPMENT; IN-VIVO; TRANSGENIC ZEBRAFISH; EXPRESSION; GENE; TRANSPLANTATION; VASCULOGENESIS; ANGIOGENESIS; ENDOTHELIUM; VERTEBRATE AB Understanding on the mechanisms of vascular branching morphogenesis has become a subject of enormous scientific and clinical interest. Zebrafish, which have small, accessible, transparent embryos and larvae, provides a unique living animal model to facilitating high-resolution imaging on ubiquitous and deep localization of vessels within embryo development and also in adult tissues. In this chapter, we have summarized various methods for vessel imaging in zebrafish, including in situ hybridization for vascular-specific genes, resin injection- or dye injection-based vessel visualization, and alkaline phosphatase staining. We also described detail protocols for live imaging of vessels by microangiography or using various transgenic zebrafish lines. C1 [Kamei, Makoto; Pan, Weijun; Weinstein, Brant M.] NICHHD, Program Genom Differentiat, Bethesda, MD 20892 USA. [Isogai, Sumio] Iwate Med Univ, Sch Med, Dept Anat, Morioka, Iwate 020, Japan. [Kamei, Makoto] Univ S Australia, Sch Pharm & Med Sci, Sansom Inst Hlth Res, Cell Biol Dis Grp, Adelaide, SA 5001, Australia. RP Kamei, M (reprint author), NICHHD, Program Genom Differentiat, Bethesda, MD 20892 USA. OI Kamei, Makoto/0000-0002-1438-0783 NR 43 TC 20 Z9 20 U1 2 U2 16 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-384892-5 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2010 VL 100 BP 27 EP 54 DI 10.1016/B978-0-12-384892-5.00002-5 PG 28 WC Cell Biology SC Cell Biology GA BSR05 UT WOS:000285524800002 PM 21111213 ER PT J AU Lissek, S Grillon, C AF Lissek, Shmuel Grillon, Christian TI Overgeneralization of Conditioned Fear in the Anxiety Disorders Putative Memorial Mechanisms SO ZEITSCHRIFT FUR PSYCHOLOGIE-JOURNAL OF PSYCHOLOGY LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER; POTENTIATED STARTLE; D-CYCLOSERINE; PANIC DISORDER; HUMANS; CORTEX C1 [Lissek, Shmuel; Grillon, Christian] Natl Inst Mental Hlth, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Lissek, S (reprint author), Natl Inst Mental Hlth, Mood & Anxiety Disorders Program, Bldg 15K, MSC 2670, Bethesda, MD 20892 USA. EM lisseks@intra.nimh.nih.gov NR 22 TC 12 Z9 12 U1 2 U2 9 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0044-3409 J9 Z PSYCHOL JI Z. Psychol.-J. Psychol. PY 2010 VL 218 IS 2 BP 146 EP 148 DI 10.1027/0044-3409/a000022 PG 3 WC Psychology, Multidisciplinary SC Psychology GA 651FT UT WOS:000281912700011 ER EF